Author: "Chua, BY" / Topic: biology - Searchworks@Jio Institute Digital Library Search Results

3,455 results on '"Chua, BY"'

1. Representation of NOS Aspects across Chapters in Singapore Grade 9 and 10 Biology Textbooks: Insights for Improving NOS Representation

Author: Chua, Jia Xun, Tan, Aik-Ling, and Ramnarain, Umesh
Abstract: Background: Nature of Science (NOS) is defined to be the epistemology of science, and comprised of distinctive defining aspects. The representation of these NOS aspects in school science textbooks is likely to affect how students understand NOS. Representation of NOS aspects can differ between topics even within the same textbook and these topical differences may shed light on the different improvements required for a progressive and more balanced representation of NOS aspects. Purpose: This study aims to (1) analyse the representations of NOS aspects in Singapore biology textbooks; (2) identify and discuss topical differences in the representation of NOS aspects; and (3) suggest some ways to improve NOS representation in textbooks. Method: Three Singapore secondary school biology textbooks were analysed for their representations of 11 key NOS aspects using a document analysis approach. Textual material was coded into discrete categories in a topic-by-topic manner independently by two coders. Results: Informed statements regarding NOS aspects were predominantly implicit in nature. High scores for eight NOS aspects were obtained in one textbook incorporating experimental work in many chapters to support and illustrate scientific concepts. High scores for the creative NOS and the nature for scientific theories were scored in another textbook that was found to utilise History of Science to provide a context for presenting scientific information. Topics with consistently low NOS representations were predominantly presented in a descriptive, factual manner, while topics with consistently high scores generally approached the topics by discussing the historical development of knowledge. Conclusions: Using experimental work to present scientific knowledge and discussions of the historical development of scientific knowledge are both effective approaches to represent many NOS aspects well in a textbook. These two approaches can be used in combination in a textbook in order to further improve NOS representation and overcome the individual limitations of each approach.
Published: 2019
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2. The Role of Motivation and Perceptions about Science Laboratory Environment on Lower Secondary Students' Attitude towards Science

Author: Chua, Kah-Eng and Karpudewan, Mageswary
Abstract: Attitude towards learning science is a well-researched domain for more than four decades. Globally, studies on attitude still stay relevant following the decline in enrollment in science-related studies across many levels. Particularly, emergent of new sciences in this century calls for a shift in the content included in school science, to be more contemporary. Hence, there is a need to inculcate an appropriate attitude to learn the new content. Many factors contribute to the development of attitude, in particular, motivation in learning the subject and the environment constitute learning the subject are imperative. In school science, investigating science laboratory environment is essential. Following this claim, in this study, an attempt was made to articulate the relationship between lower secondary school students' perceptions about laboratory environment, attitude, and motivation towards learning. For this purpose, in this quantitative survey, a total of 1003 lower secondary students between 13-15 years old from different schools in the Northern Region of Malaysia have participated. The result shows that motivation and perceptions of the learning environment are two factors that predict attitude towards learning science. These findings suggest that in designing teaching strategies, teachers need to consider how the teaching can affect the motivation and learning environment. Subsequently, the teaching strategies anticipated to influence students' attitude towards learning science.
Published: 2017

3. A Survey of First-Year Biology Student Opinions Regarding Live Lectures and Recorded Lectures as Learning Tools

Author: Simcock, D. C., Chua, W. H., Hekman, M., Levin, M. T., and Brown, S.
Abstract: A cohort of first-year biology students was surveyed regarding their opinions and viewing habits for live and recorded lectures. Most respondents (87%) attended live lectures as a rule (attenders), with 66% attending more than two-thirds of the lectures. In contrast, only 52% accessed recordings and only 13% viewed more than two-thirds of the available recordings. Respondents regarded lectures as efficient for information delivery (75%), and 89% enjoyed live lectures because they were useful for learning (89%), understanding coursework (94%), and keeping up with the subject (93%). Lecture enjoyment was driven less by entertainment (34%) or interaction with the lecturers (47%), although most students preferred an entertaining lecturer to a factual expert (72%). Exam marks were positively correlated with the number of lectures attended (P < 0.001) and negatively correlated with the number of recordings viewed (P < 0.05), although marks were similar for lecture attenders and nonattenders (P > 0.05). Lecture attenders mostly missed lectures to complete assessments during the same week (68%), whereas nonattenders were more likely to miss lectures due to outside commitments or preference for study from books or recorded lectures (P < 0.001). Recordings were used to replace missed lectures (64%), rather than for revision, and were viewed mostly alone (96%) in one sitting (65%). Only 22% of respondents agreed that some lectures could be replaced by recordings, but 59% agreed with having some videoconference lectures from experts on another campus. Overall, this cohort showed a clear preference for live lectures over recordings, with limited support for synchronous videoconference lectures.
Published: 2017
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4. The Protein Homeostasis Network Promotes Hematopoietic Stem Cell Fitness

Author: Chua, Bernadette Anne
Subjects: Biology
Abstract: Hematopoietic stem cells (HSCs) are multipotent stem cells that give rise to all blood lineages and persist throughout life to constantly replenish blood cells. To preserve their health and longevity, HSCs are particularly dependent on maintaining protein homeostasis (proteostasis). The proteostasis network oversees protein quality and quantity within a cell, and can be divided into nodes that coordinately oversee protein synthesis, folding, and degradation, as well as respond to proteotoxic stress. HSCs maintain proteostasis partly by sustaining low protein synthesis rates that limit the biogenesis of misfolded proteins. Nevertheless, HSCs ultimately accumulate misfolded proteins that must be eliminated to preserve stem cell fitness. This work aims to address two open questions in the field: what mechanisms HSCs employ to attenuate translation and how HSCs purge misfolded proteins. Here, I investigate the hypothesis that a tRNA code may exist to tune protein synthesis and self-renewal of stem cells. Furthermore, I show that HSCs depend on aggrephagy, a selective form of autophagy, to clear misfolded proteins and maintain proteostasis in vivo. Overall, these studies demonstrate that the proteostasis network is uniquely configured in HSCs to preserve proteostasis and fitness.
Published: 2022

5. National audit of a hereditary and acquired angioedema cohort in New Zealand

Author: Ignatius Chua, Karen Lindsay, Anthony Jordan, and Simone Stephens
Subjects: Pediatrics, medicine.medical_specialty, biology, business.industry, Audit, medicine.disease, C1-inhibitor, Long-term care, Quality of life, Cohort, Hereditary angioedema, Health care, Internal Medicine, biology.protein, Medicine, business, Tranexamic acid, medicine.drug
Abstract: Background HAE leads to significant morbidity and mortality from unpredictable intermittent peripheral, abdominal and laryngeal swelling. Access to appropriate healthcare and effective therapies which can prevent and treat attacks, reduce the suffering and greatly improve quality of life. Although treatments such as C1 inhibitor (Berinert®), and Icatibant® are available in New Zealand (Aotearoa), there is no published data available on their use. Aims This study presents a national audit of Hereditary Angioedema (HAE) and Acquired Angioedema (AAE) in 2019. Results The total number of known adult (48) and children (3) HAE and Acquired Angioedema (3) patients is 54. Of these, 41/ 54 (75%) of HAE and AAE patients were recruited to the audit. Icatibant® has been available for treatment of acute HAE attacks since 2016, and is now used in 73% of HAE patients. Icatibant® is also used by patients for laryngeal attacks in the community, who may not then present to hospital. Androgens are used in half of the patients as prophylaxis but 33% of the latter were identified as not having regular liver ultrasound screening. Tranexamic acid is used as prophylaxis in one fifth of patients. Participants have had 40 children, half of whom may be affected. Three have been diagnosed with HAE, suggesting that the majority have not yet been tested. Conclusions Corrective actions arising from this audit will improve our capacity to provide long term care for HAE patients and their families. This article is protected by copyright. All rights reserved.
Published: 2022
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6. Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production

Author: Kim, Mi Jung, Jin, Jingjing, Zheng, Junshi, Wong, Limsoon, Chua, Nam-Hai, and Jang, In-Cheol
Published: 2015

7. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, Begun, Jakob, Behrends, Christian, Behrens, Georg, Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno, Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin, Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri, Besteiro, Sebastien, Betin, Virginie, Beyaert, Rudi, Bezbradica, Jelena, Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor, Bijian, Krikor, Billes, Viktor, Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa, Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice, Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan, Boone, Brian, Bootman, Martin, Bordi, Matteo, Borner, Christoph, Bornhauser, Beat, Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, botana, luis, Botas, Juan, Boulanger, Chantal, Boulton, Michael, Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig, Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter, Bozi, Luiz, Bozkurt, Tolga, Brackney, Doug, Brandts, Christian, Braun, Ralf, Braus, Gerhard, Bravo-Sagua, Roberto, Bravo-San Pedro, José, Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V Courtney, Brodersen, Peter, Brodsky, Jeffrey, Brody, Steven, Bronson, Paola, Bronstein, Jeff, Brown, Carolyn, Brown, Rhoderick, Brum, Patricia, Brumell, John, Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert, Bucci, Cecilia, Buchrieser, Carmen, Bueno, Marta, Buitrago-Molina, Laura Elisa, Buraschi, Simone, Buch, Shilpa, Buchan, J Ross, Buckingham, Erin, Budak, Hikmet, Budini, Mauricio, Bultynck, Geert, Burada, Florin, Burgoyne, Joseph, Burón, M Isabel, Bustos, Victor, Büttner, Sabrina, Butturini, Elena, Byrd, Aaron, Cabas, Isabel, Cabrera-Benitez, Sandra, Cadwell, Ken, Cai, Jingjing, Cai, Lu, Cai, Qian, Cairó, Montserrat, Calbet, Jose, Caldwell, Guy, Caldwell, Kim, Call, Jarrod, Calvani, Riccardo, Calvo, Ana, Calvo-Rubio Barrera, Miguel, Camara, Niels OS, Camonis, Jacques, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Edward, Campbell-Valois, François-Xavier, Campello, Silvia, Campesi, Ilaria, Campos, Juliane, Camuzard, Olivier, Cancino, Jorge, Candido de Almeida, Danilo, Canesi, Laura, Caniggia, Isabella, Canonico, Barbara, Cantí, Carles, Cao, Bin, Caraglia, Michele, Caramés, Beatriz, Carchman, Evie, Cardenal-Muñoz, Elena, Cardenas, Cesar, Cardenas, Luis, Cardoso, Sandra, Carew, Jennifer, Carle, Georges, Carleton, Gillian, Carloni, Silvia, Carmona-Gutierrez, Didac, Carneiro, Leticia, Carnevali, Oliana, Carosi, Julian, Carra, Serena, Carrier, Alice, Carrier, Lucie, Carroll, Bernadette, Carter, A Brent, Carvalho, Andreia Neves, Casanova, Magali, Casas, Caty, Casas, Josefina, Cassioli, Chiara, Castillo, Eliseo, Castillo, Karen, Castillo-Lluva, Sonia, Castoldi, Francesca, Castori, Marco, Castro, Ariel, Castro-Caldas, Margarida, Castro-Hernandez, Javier, Castro-Obregon, Susana, Catz, Sergio, Cavadas, Claudia, Cavaliere, Federica, Cavallini, Gabriella, Cavinato, Maria, Cayuela, Maria, Cebollada Rica, Paula, Cecarini, Valentina, Cecconi, Francesco, Cechowska-Pasko, Marzanna, Cenci, Simone, Ceperuelo-Mallafré, Victòria, Cerqueira, João, Cerutti, Janete, Cervia, Davide, Cetintas, Vildan Bozok, Cetrullo, Silvia, Chae, Han-Jung, Chagin, Andrei, Chai, Chee-Yin, Chakrabarti, Gopal, Chakrabarti, Oishee, Chakraborty, Tapas, Chakraborty, Trinad, Chami, mounia, Chamilos, Georgios, Chan, David, Chan, Edmond, Chan, Edward, Chan, H.Y. Edwin, Chan, Helen, Chan, Hung, Chan, Matthew, Chan, Yau Sang, Chandra, Partha, Chang, Chih-Peng, Chang, Chunmei, Chang, Hao-Chun, Chang, Kai, Chao, Jie, Chapman, Tracey, Charlet-Berguerand, Nicolas, Chatterjee, Samrat, Chaube, Shail, Chaudhary, Anu, Chauhan, Santosh, Chaum, Edward, Checler, Frédéric, Cheetham, Michael, Chen, Chang-Shi, Chen, Guang-Chao, Chen, Jian-Fu, Chen, Liam, Chen, Leilei, Chen, Lin, Chen, Mingliang, Chen, Mu-Kuan, Chen, Ning, Chen, Quan, Chen, Ruey-Hwa, Chen, Shi, Chen, Wei, Chen, Weiqiang, Chen, Xin-Ming, Chen, Xiong-Wen, Chen, Xu, Chen, Yan, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Zhefan Stephen, Chen, Zhi, Chen, Zhi-Hua, Chen, Zhijian, Chen, Zhixiang, Cheng, Hanhua, Cheng, Jun, Cheng, Shi-Yuan, Cheng, Wei, Cheng, Xiaodong, Cheng, Xiu-Tang, Cheng, Yiyun, Cheng, Zhiyong, Chen, Zhong, Cheong, Heesun, Cheong, Jit Kong, Chernyak, Boris, Cherry, Sara, Cheung, Chi Fai Randy, Cheung, Chun Hei Antonio, Cheung, King-Ho, Chevet, Eric, Chi, Richard, Chiang, Alan Kwok Shing, Chiaradonna, Ferdinando, Chiarelli, Roberto, Chiariello, Mario, Chica, Nathalia, Chiocca, Susanna, Chiong, Mario, Chiou, Shih-Hwa, Chiramel, Abhilash, Chiurchiù, Valerio, Cho, Dong-Hyung, Choe, Seong-Kyu, Choi, Augustine, Choi, Mary, Choudhury, Kamalika Roy, Chow, Norman, Chu, Charleen, Chua, Jason, Chua, John Jia En, Chung, Hyewon, Chung, Kin Pan, Chung, Seockhoon, Chung, So-Hyang, Chung, Yuen-Li, Cianfanelli, Valentina, Ciechomska, Iwona, Cifuentes, Mariana, Cinque, Laura, Cirak, Sebahattin, Cirone, Mara, Clague, Michael, Clarke, Robert, Clementi, Emilio, Coccia, Eliana, Codogno, Patrice, Cohen, Ehud, Cohen, Mickael, Colasanti, Tania, Colasuonno, Fiorella, Colbert, Robert, Colell, Anna, Čolić, Miodrag, Coll, Nuria, Collins, Mark, Colombo, María, Colón-Ramos, Daniel, Combaret, Lydie, Comincini, Sergio, Cominetti, Márcia, Consiglio, Antonella, Conte, Andrea, Conti, Fabrizio, Contu, Viorica Raluca, Cookson, Mark, Coombs, Kevin, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale, Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter, Crespo, Jose, Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea, Cybulsky, Andrey, Czaja, Mark, Czuczwar, Stanislaw, D'Adamo, Stefania, D'Amelio, Marcello, D'Arcangelo, Daniela, D'Lugos, Andrew, D'Orazi, Gabriella, da Silva, James, Dafsari, Hormos Salimi, Dagda, Ruben, Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico, Darling, April, Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh, Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian, Davies, Jeffrey, Dávila, Valeria, Davis, Roger, Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara, De Meyer, Guido, De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian, Decuypere, Jean-Paul, Deehan, Mark, Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe, Delbridge, Lea, Delorme-Axford, Elizabeth, Delpino, M Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas, Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin, Der, Channing, Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni, Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, Federica, Diallinas, George, Diao, Jiajie, Diaz-Araya, Guillermo, Díaz-Laviada, Inés, Dickinson, Jared, Diederich, Marc, Dieudé, Mélanie, Dikic, Ivan, Ding, Shiping, Ding, Wen-Xing, Dini, Luciana, Dinić, Jelena, Dinic, Miroslav, Dinkova-Kostova, Albena, Dionne, Marc, Distler, Jörg, Diwan, Abhinav, Dixon, Ian, Djavaheri-Mergny, Mojgan, Dobrinski, Ina, Dobrovinskaya, Oxana, Dobrowolski, Radek, Dobson, Renwick, Đokić, Jelena, Dokmeci Emre, Serap, Donadelli, Massimo, Dong, Bo, Dong, Xiaonan, Dong, Zhiwu, Dorn Ii, Gerald, Dotsch, Volker, Dou, Huan, Dou, Juan, Dowaidar, Moataz, Dridi, Sami, Drucker, Liat, Du, Ailian, Du, Caigan, Du, Guangwei, Du, Hai-Ning, Du, Li-Lin, du Toit, André, Duan, Shao-Bin, Duan, Xiaoqiong, Duarte, Sónia, Dubrovska, Anna, Dunlop, Elaine, Dupont, Nicolas, Durán, Raúl, Dwarakanath, Bilikere, Dyshlovoy, Sergey, Ebrahimi-Fakhari, Darius, Eckhart, Leopold, Edelstein, Charles, Efferth, Thomas, Eftekharpour, Eftekhar, Eichinger, Ludwig, Eid, Nabil, Eisenberg, Tobias, Eissa, N Tony, Eissa, Sanaa, Ejarque, Miriam, El Andaloussi, Abdeljabar, El-Hage, Nazira, El-Naggar, Shahenda, Eleuteri, Anna Maria, El-Shafey, Eman, Elgendy, Mohamed, Eliopoulos, Aristides, Elizalde, María, Elks, Philip, Elsasser, Hans-Peter, Elsherbiny, Eslam, Emerling, Brooke, Emre, N., Eng, Christina, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelsen, Agnete, Enserink, Jorrit, Escalante, Ricardo, Esclatine, Audrey, Escobar-Henriques, Mafalda, Eskelinen, Eeva-Liisa, Espert, Lucile, Eusebio, Makandjou-Ola, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Facchiano, Francesco, Fadeel, Bengt, Fader, Claudio, Faesen, Alex, Fairlie, W Douglas, Falcó, Alberto, Falkenburger, Bjorn, Fan, Daping, Fan, Jie, Fan, Yanbo, Fang, Evandro, Fang, Yanshan, Fang, Yognqi, Fanto, Manolis, Farfel-Becker, Tamar, Faure, Mathias, Fazeli, Gholamreza, Fedele, Anthony, Feldman, Arthur, Feng, Du, Feng, Jiachun, Feng, Lifeng, Feng, Yibin, Feng, Yuchen, Feng, Wei, Fenz Araujo, Thais, Ferguson, Thomas, Fernández, Álvaro, Fernandez-Checa, Jose, Fernández-Veledo, Sonia, Fernie, Alisdair, Ferrante, Anthony, Ferraresi, Alessandra, Ferrari, Merari, Ferreira, Julio, Ferro-Novick, Susan, Figueras, Antonio, Filadi, Riccardo, Filigheddu, Nicoletta, Filippi-Chiela, Eduardo, Filomeni, Giuseppe, Fimia, Gian Maria, Fineschi, Vittorio, Finetti, Francesca, Finkbeiner, Steven, Fisher, Edward, Fisher, Paul, Flamigni, Flavio, Fliesler, Steven, Flo, Trude, Florance, Ida, Florey, Oliver, Florio, Tullio, Fodor, Erika, Follo, Carlo, Fon, Edward, Forlino, Antonella, Fornai, Francesco, Fortini, Paola, Fracassi, Anna, Fraldi, Alessandro, Franco, Brunella, Franco, Rodrigo, Franconi, Flavia, Frankel, Lisa, Friedman, Scott, Fröhlich, Leopold, Frühbeck, Gema, Fuentes, Jose, Fujiki, Yukio, Fujita, Naonobu, Fujiwara, Yuuki, Fukuda, Mitsunori, Fulda, Simone, Furic, Luc, Furuya, Norihiko, Fusco, Carmela, Gack, Michaela, Gaffke, Lidia, Galadari, Sehamuddin, Galasso, Alessia, Galindo, Maria, Gallolu Kankanamalage, Sachith, Galluzzi, Lorenzo, Galy, Vincent, Gammoh, Noor, Gan, Boyi, Ganley, Ian, Gao, Feng, Gao, Hui, Gao, Minghui, Gao, Ping, Gao, Shou-Jiang, Gao, Wentao, Gao, Xiaobo, Garcera, Ana, Garcia, Maria Noé, Garcia, Verónica, García-del Portillo, Francisco, Garcia-Escudero, Vega, Garcia-Garcia, Aracely, Garcia-Macia, Marina, García-Moreno, Diana, Garcia-Ruiz, Carmen, García-Sanz, Patricia, Garg, Abhishek, Gargini, Ricardo, Garofalo, Tina, Garry, Robert, Gassen, Nils, Gatica, Damian, Ge, Liang, Ge, Wanzhong, Geiss-Friedlander, Ruth, Gelfi, Cecilia, Genschik, Pascal, Gentle, Ian, Gerbino, Valeria, Gerhardt, Christoph, Germain, Kyla, Germain, Marc, Gewirtz, David, Ghasemipour Afshar, Elham, Ghavami, Saeid, Ghigo, Alessandra, Ghosh, Manosij, Giamas, Georgios, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibson, Gary, Gibson, Spencer, Ginet, Vanessa, Giniger, Edward, Giorgi, Carlotta, Girao, Henrique, Girardin, Stephen, Giridharan, Mridhula, Giuliano, Sandy, Giulivi, Cecilia, Giuriato, 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Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, 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Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. 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T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. 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K., Shutt, T. E., Sica, V., Siddiqui, A., Sierra, A., Sierra-Torre, V., Signorelli, S., Sil, P., Silva, B. J. D. A., Silva, J. D., Silva-Pavez, E., Silvente-Poirot, S., Simmonds, R. E., Simon, A. K., Simon, H. -U., Simons, M., Singh, A., Singh, L. P., Singh, R., Singh, S. V., Singh, S. K., Singh, S. B., Singh, S., Singh, S. P., Sinha, D., Sinha, R. A., Sinha, S., Sirko, A., Sirohi, K., Sivridis, E. L., Skendros, P., Skirycz, A., Slaninova, I., Smaili, S. S., Smertenko, A., Smith, M. D., Soenen, S. J., Sohn, E. J., Sok, S. P. M., Solaini, G., Soldati, T., Soleimanpour, S. A., Soler, R. M., Solovchenko, A., Somarelli, J. A., Sonawane, A., Song, F., Song, H. K., Song, J. -X., Song, K., Song, Z., Soria, L. R., Sorice, M., Soukas, A. A., Soukup, S. -F., Sousa, D., Sousa, N., Spagnuolo, P. A., Spector, S. A., Srinivas Bharath, M. M., S, t. Clair D., Stagni, V., Staiano, L., Stalnecker, C. A., Stankov, M. V., Stathopulos, P. B., Stefan, K., Stefan, S. M., Stefanis, L., Steffan, J. S., Steinkasserer, A., Stenmark, H., Sterneckert, J., Stevens, C., Stoka, V., Storch, S., Stork, B., Strappazzon, F., Strohecker, A. M., Stupack, D. G., Su, H., Su, L. -Y., Su, L., Suarez-Fontes, A. M., Subauste, C. S., Subbian, S., Subirada, P. V., Sudhandiran, G., Sue, C. M., Sui, X., Summers, C., Sun, G., Sun, J., Sun, K., Sun, M. -X., Sun, Q., Sun, Y., Sun, Z., Sunahara, K. K. S., Sundberg, E., Susztak, K., Sutovsky, P., Suzuki, H., Sweeney, G., Symons, J. D., Sze, S. C. W., Szewczyk, N. J., Tabecka-Lonczynska, A., Tabolacci, C., Tacke, F., Taegtmeyer, H., Tafani, M., Tagaya, M., Tai, H., Tait, S. W. G., Takahashi, Y., Takats, S., Talwar, P., Tam, C., Tam, S. Y., Tampellini, D., Tamura, A., Tan, C. T., Tan, E. -K., Tan, Y. -Q., Tanaka, M., Tang, D., Tang, J., Tang, T. -S., Tanida, I., Tao, Z., Taouis, M., Tatenhorst, L., Tavernarakis, N., Taylor, A., Taylor, G. A., Taylor, J. M., Tchetina, E., Tee, A. R., Tegeder, I., Teis, D., Teixeira, N., Teixeira-Clerc, F., Tekirdag, K. A., Tencomnao, T., Tenreiro, S., Tepikin, A. V., Testillano, P. S., Tettamanti, G., Tharaux, P. -L., Thedieck, K., Thekkinghat, A. A., Thellung, S., Thinwa, J. W., Thirumalaikumar, V. P., Thomas, S. M., Thomes, P. G., Thorburn, A., Thukral, L., Thum, T., Thumm, M., Tian, L., Tichy, A., Till, A., Timmerman, V., Titorenko, V. I., Todi, S. V., Todorova, K., Toivonen, J. M., Tomaipitinca, L., Tomar, D., Tomas-Zapico, C., Tomic, S., Tong, B. C. -K., Tong, C., Tong, X., Tooze, S. A., Torgersen, M. L., Torii, S., Torres-Lopez, L., Torriglia, A., Towers, C. G., Towns, R., Toyokuni, S., Trajkovic, V., Tramontano, D., Tran, Q. -G., Travassos, L. H., Trelford, C. B., Tremel, S., Trougakos, I. P., Tsao, B. P., Tschan, M. P., Tse, H. -F., Tse, T. F., Tsugawa, H., Tsvetkov, A. S., Tumbarello, D. A., Tumtas, Y., Tunon, M. J., Turcotte, S., Turk, B., Turk, V., Turner, B. J., Tuxworth, R. I., Tyler, J. K., Tyutereva, E. V., Uchiyama, Y., Ugun-Klusek, A., Uhlig, H. H., Ulamek-Koziol, M., Ulasov, I. V., Umekawa, M., Ungermann, C., Unno, R., Urbe, S., Uribe-Carretero, E., Ustun, S., Uversky, V. N., Vaccari, T., Vaccaro, M. I., Vahsen, B. F., Vakifahmetoglu-Norberg, H., Valdor, R., Valente, M. J., Valko, A., Vallee, R. B., Valverde, A. M., Van den Berghe, G., van der Veen, S., Van Kaer, L., van Loosdregt, J., van Wijk, S. J. L., Vandenberghe, W., Vanhorebeek, I., Vannier-Santos, M. A., Vannini, N., Vanrell, M. C., Vantaggiato, C., Varano, G., Varela-Nieto, I., Varga, M., Vasconcelos, M. H., Vats, S., Vavvas, D. G., Vega-Naredo, I., Vega-Rubin-de-Celis, S., Velasco, G., Velazquez, A. P., Vellai, T., Vellenga, E., Velotti, F., Verdier, M., Verginis, P., Vergne, I., Verkade, P., Verma, M., Verstreken, P., Vervliet, T., Vervoorts, J., Vessoni, A. T., Victor, V. M., Vidal, M., Vidoni, C., Vieira, O. V., Vierstra, R. D., Vigano, S., Vihinen, H., Vijayan, V., Vila, M., Vilar, M., Villalba, J. M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021
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8. Identification of Phytochemicals from the Water Extract of Eurycoma longifolia Roots using Solid-Liquid and Liquid-Liquid Extraction Based Fractionation Techniques

Author: Abirame Segaran, Lee Suan Chua, and Hoi Jin Wong
Subjects: Liquid-Liquid Extraction, Phytochemicals, Ethyl acetate, Fractionation, Plant Roots, chemistry.chemical_compound, Tandem Mass Spectrometry, Liquid–liquid extraction, saponins, eurycomanone, Acetone, Solid phase extraction, Eurycoma, QD1-999, Chromatography, High Pressure Liquid, General Environmental Science, Chromatography, Quassins, biology, Plant Extracts, Butanol, Extraction (chemistry), solid phase extraction, Water, quassinoids, biology.organism_classification, solvent partition, Chemistry, chemistry, Solvents, eurycoma longifolia, General Earth and Planetary Sciences, Eurycoma longifolia
Abstract: Phytochemicals in the water extract of Eurycoma longofolia roots were identified using both solid-liquid and liquid-liquid extraction based fractionation techniques. A reversed phase C18 solid phase extraction (SPE) was used as solid-liquid extraction, whereas solvent partition was applied as liquid-liquid extraction. Total saponin was increased after fractionation. A few known quassinoids; eurycomanone, 13α(21)-epoxyeurycomanone, pasakbumin D, 13β,18-dihydroeurycomanol and 13β,21-dihydroxyeurycomanol were identified from the 40% and 60% methanol fractions of SPE. Solvent partition extract using ethyl acetate was found to have the highest saponin content compared to butanol and chloroform fractions. Subsequent acetone precipitation of the organic fractions recovered a formylated hexose trimer and other saccharide-containing compounds. Ethyl acetate effectively recovered saponins from E. longofolia water extract using liquid-liquid extraction followed by acetone precipitation.
Published: 2021

9. Diagnostic Accuracy of COVID-19 Antibody Tests Authorized by FDA Philippines: A Systematic Review and Meta-Analysis

Author: Karla Veronica H. Escasa, Esther Delle E. de los Santos, Sherill D. Tesalona, Sabrina Audrey E. Ortega, Richmond Louis G. Estolas, Carlo Ledesma, Carmel Reina R. Chua, Jan Ebrian D. Leonin, and Junnealyn Feliciano
Subjects: medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), chemiluminescence immunoassay (clia), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Diagnostic accuracy, enzyme-linked immunosorbent assay (elisa), Confidence interval, Serology, covid-19, antibody test, Internal medicine, Meta-analysis, biology.protein, Medicine, lateral flow immunoassay (lfia), Antibody, Public aspects of medicine, RA1-1270, business, RC254-282, Lateral flow immunoassay
Abstract: Introduction : Coronavirus Disease (COVID-19) is a highly infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has infected many people all over the world. One of the best ways to lessen its spread is through early detection and diagnosis. Various serological tests are now being used as a surveillance tool in the detection of antibodies as a response to SARS-CoV-2. The aim of this study is to evaluate the diagnostic accuracy and performance of the available COVID-19 antibody tests authorized by the Food and Drug Administration (FDA) Philippines that make use of Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescence Immunoassay (CLIA) and Lateral Flow Immunoassay (LFIA). Method : Complete published journal articles relevant to the diagnostic accuracy of the three antibody tests were collected using trusted medical journal search engines. The quality of journals was assessed using QUADAS-2 to determine the risk of bias and assess the applicability judgments of diagnostic accuracy studies. Forest plots were used to summarize the performance of LFIA, ELISA and CLIA according to their specificity and sensitivity in detecting various antibodies. Pooled sensitivity and specificity were also done using bivariate random-effects models with its log-likelihood, a corresponding chi-square test statistic, and area under the summary Receiver-Operating Characteristic curve to see the potential heterogeneity in the data and to assess the diagnostic accuracy of the COVID-19 antibody tests. Results : Bivariate random-effects model and areas under the sROC curve were used to evaluate the diagnostic accuracy of COVID-19 antibody tests. The pooled sensitivity in detecting IgG based on CLIA, ELISA, and LFIA were 81.7%, 58.7%, and 74.3% respectively, with an overall of 72.0%. For IgM detection, LFIA has a higher pooled sensitivity of 69.6% than CLIA with 61.0%. Overall, the pooled sensitivity is 68.5%. In IgA detection, only ELISA based test was included with a pooled sensitivity of 84.8%. Lastly, pooled sensitivities for combined antibodies based on ELISA and LFIA were 89.0% and 81.6% respectively, with an overall of 82.5%. On the other hand, all tests excluding ELISA-IgA displayed high pooled specificities with a range of 94.0% to 100.0%. Diagnostic accuracies of the test in detecting IgG, IgM, and combined antibodies were found out to be almost perfect based on the computed area under the sROC with values of 0.973, 0.953, and 0.966, respectively. Conclusion : In this systematic review and meta-analysis, existing evidence on the diagnostic accuracy of antibody tests for COVID-19 were found to be characterized by high risks of bias, consistency in the heterogeneity of sensitivities, and consistency in the homogeneity of high specificities except in IgA detection using ELISA. The bivariate random-effects models showed that there are no significant differences in terms of sensitivity among CLIA, ELISA and LFIA in detecting IgG, IgM, and combined antibodies at a 95% confidence interval. Nonetheless, CLIA, ELISA and LFIA were found to have excellent diagnostic accuracies in the detection of IgG, IgM and combined antibodies as reflected by their AUC values. Doi: 10.28991/SciMedJ-2021-0304-1 Full Text: PDF
Published: 2021

10. Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis

Author: Xu-jie Zhou, Yuta Kochi, Guru P. Maiti, Joel M. Guthridge, Sang Cheol Bae, Mehdi Fazel-Najafabadi, Kek Heng Chua, Judith A. James, Loren L. Looger, Yukinori Okada, Swapan K. Nath, Chikashi Terao, Bhupinder Singh, Celi Sun, Hong Zhang, Matthew T. Weirauch, John B. Harley, and Gaurav K. Varshney
Subjects: 1.1 Normal biological development and functioning, Immunology, Lupus, Apoptosis, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Autoimmune Disease, Article, Promoter Regions, Genetic, Rheumatology, Underpinning research, Genetics, Lupus Erythematosus, Systemic, Humans, 2.1 Biological and endogenous factors, Immunology and Allergy, Genetic Predisposition to Disease, Epigenetics, Polymorphism, Aetiology, Promoter Regions, Genetic, Enhancer, Transcription factor, Alleles, Cell Proliferation, Lupus Erythematosus, Inflammatory and immune system, Systemic, Human Genome, Computational Biology, Promoter, Single Nucleotide, Chromatin, CTCF, H3K4me3, Generic health relevance, Cyclin-Dependent Kinase Inhibitor p27, Genome-Wide Association Study, Biotechnology
Abstract: ObjectiveIn a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.MethodsWe performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.ResultsWe replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.ConclusionCollectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.
Published: 2021
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11. Concordance of Cytological Specimens with Histological Tissue for Detection of Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer: A Systematic Review

Author: Tzy Harn Chua and Khoon Leong Chuah
Subjects: Mutation, Pathology, medicine.medical_specialty, Histology, biology, medicine.diagnostic_test, business.industry, Concordance, General Medicine, medicine.disease_cause, medicine.disease, Pathology and Forensic Medicine, Liquid-based cytology, Cytology, Biopsy, biology.protein, medicine, Epidermal growth factor receptor, Non small cell, business, Lung cancer
Abstract: Introduction: There is increasing need for more testing in non-small cell lung cancer given the introduction of newer targeted therapies. Cytological specimens including conventional smears (CS), cell blocks (CB), and liquid-based cytology (LBC) are an alternative to histologic tissue (HT) specimens in detecting EGFR mutations, but the concordance of these 2 specimens is yet to be determined. The aim of the present systematic review is to determine the concordance rates between different cytologic specimens with HT in detecting EGFR mutations. Methods: PubMed, Cochrane Library, and Google Scholar were utilized in the primary search, along with reference lists of electronically retrieved full-text articles. Concordance rates were pooled together if 2 or more studies reporting the same type of cytologic specimen were available. Results: Overall, 15 studies were included in this review, with 13 studies included in the pooled analysis. There was an overall concordance rate of 92.8% in 593 paired cytologic and HT specimens, with LBC having the highest concordance rate of 96.0%, followed by CS and CB, each with a concordance rate of 95.8%, although the concordance rate of CS and/or CB was lower at 90.6% with a larger pool of studies. LBC was found to have a significantly higher concordance rate than CS and/or CB. Conclusion: Cytological specimens have a high concordance rate in detecting EGFR mutations, when compared to HT. LBC has shown superior concordance rates compared to CS and CB. Cytological specimens should be considered as an additional and alternative source of diagnostic material for EGFR testing.
Published: 2021
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12. Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells

Author: Gitta Anne Heinz, Josefine Radke, Sophie Mc Ewen, V. Moos, Jobst Roehmel, Tilmann Kallinich, Pawel Durek, Daniela Niemeyer, Leif G. Hanitsch, Florian Kurth, Thordis Hohnstein, Uwe Kölsch, Mario Witkowski, Philipp Nawrath, Marcus A. Mall, Frederik Heinrich, Leif E. Sander, Stefan Frischbutter, Mir-Farzin Mashreghi, Tom Aschman, Emanuela Marcenaro, Victor M. Corman, Edoardo Viviano, Sascha Treskatsch, Andreas Diefenbach, Marta Ferreira-Gomes, Marcus Maurer, Christian Meisel, Caroline Tizian, Robert Lorenz Chua, Claudia U. Duerr, Stefan Angermair, Andrey Kruglov, Helena Radbruch, Birgit Sawitzki, Silvia Zocche, Christian Conrad, Andreas Radbruch, Irene Mattiola, Joseph A. Trapani, Thomas Schneider, Christian Drosten, Terry Jones, and Kristina Allers
Subjects: Multidisciplinary, Innate immune system, Effector, medicine.medical_treatment, Cell, Innate lymphoid cell, Biology, Virus, Cell biology, medicine.anatomical_structure, Cytokine, Viral replication, medicine, Cytotoxic T cell
Abstract: SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and ‘adaptive’ phenotype3,4. Here we show that viral load decline in COVID-19 correlates with NK cell status and that NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19, NK cells show remarkable defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA-sequencing (scRNA-seq) of NK cells along the time course of the entire COVID-19 disease spectrum reveals a unique gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant TGFβ response signature with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGFβ peak during the first 2 weeks of infection, and serum obtained from these patients profoundly inhibits NK cell function in a TGFβ-dependent manner. Our data reveal that untimely production of TGFβ is a hallmark of severe COVID-19 and may inhibit NK cell function and early virus control.
Published: 2021
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13. Fission yeast RNA‐binding proteins Puf2 and Puf4 are involved in repression of ferrireductase Frp1 expression in response to iron

Author: Eric Massé, François Bachand, Darren Henry, Vincent Normant, Simon Labbé, Gordon Chua, Jude Beaudoin, and Ariane Brault
Subjects: Untranslated region, FMN Reductase, Iron, RNA-binding protein, Biology, Microbiology, Gene Expression Regulation, Fungal, Schizosaccharomyces, RNA, Messenger, RNA Processing, Post-Transcriptional, DNA, Fungal, Promoter Regions, Genetic, 3' Untranslated Regions, Molecular Biology, Psychological repression, chemistry.chemical_classification, Messenger RNA, Reporter gene, RNA-Binding Proteins, biology.organism_classification, Reverse transcriptase, Cell biology, Enzyme, chemistry, Mutation, Schizosaccharomyces pombe, Schizosaccharomyces pombe Proteins
Abstract: This study identifies a post-transcriptional mechanism of iron uptake regulation by Puf2 and Puf4 of the Pumilio and FBF (Puf) family of RNA-binding proteins in Schizosaccharomyces pombe. Cells expressing Puf2 and Puf4 stimulate decay of the frp1+ mRNA encoding a key enzyme of the reductive iron uptake pathway. Results consistently showed that frp1+ mRNA is stabilized in puf2Δ puf4Δ mutant cells under iron-replete conditions. As a result, puf2Δ puf4Δ cells exhibit an increased sensitivity to iron accompanied by enhanced ferrireductase activity. A pool of GFP-frp1+ 3'UTR RNAs was generated using a reporter gene containing the 3' untranslated region (UTR) of frp1+ that was under the control of a regulatable promoter. Results showed that Puf2 and Puf4 accelerate the destabilization of mRNAs containing the frp1+ 3'UTR which harbors two Pumilio response elements (PREs). Binding studies revealed that the PUM-homology RNA-binding domain of Puf2 and Puf4 expressed in Escherichia coli specifically interacts with PREs in the frp1+ 3'UTR. Using RNA immunoprecipitation in combination with reverse transcription qPCR assays, results showed that Puf2 and Puf4 interact preferentially with frp1+ mRNA under basal and iron-replete conditions, thereby contributing to inhibit Frp1 production and protecting cells against toxic levels of iron.
Published: 2021
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14. Effects of Hawley, Essix, and Vivera® retainers on salivary properties, oral hygiene, and Streptococcus mutans levels: A prospective clinical pilot study

Author: Mimi Yow, Chua Sheng Da Jason, Chaminda Jayampath Seneviratne, and Hung Chew Wong
Subjects: Saliva, biology, business.industry, Dentistry, Orthodontics, biology.organism_classification, Control subjects, Streptococcus mutans, Oral hygiene, Oral Hygiene Index, In vitro study, Medicine, Orthodontic retainer, business, Retainer
Abstract: Objectives: The objectives of the study were to investigate the in vitro and in vivo effects of various removable orthodontic retainer materials on clinical and microbiological parameters, specifically on saliva characteristics, oral hygiene, and salivary levels of Streptococcus mutans (S. mutans). Materials and Methods: This study consists of two parts: An in vitro study and in vivo prospective clinical pilot study. The in vitro study measures surface roughness and S. mutans adhesion of three orthodontic retainer materials: Polymethylmethacrylate (PMMA) used in traditional Hawley removable retainers, polypropylene (PP), and polyurethane (PU) used in vacuum-formed retainers. In the clinical pilot study, 20 subjects, on completion of orthodontic treatment were randomized into three groups to receive PMMA, PP, or PU removable orthodontic retainers. They were compared with control subjects with no orthodontic treatment and retainers. Quantitative analysis of salivary S. mutans using real-time polymerase chain reaction was performed to screen for differences during retainer issue (T0) and 8–15 weeks later (T1). Salivary flow rate, pH, buffering capacity, and plaque scores were also recorded at these two periods for comparison. Results: PMMA had significantly greater surface roughness and S. mutans adhesion than PP and PU (P = 0.027). The PMMA group displayed significantly greater amounts of salivary S. mutans count when compared to the PP (0.001) and PU (P = 0.011) groups. Conclusion: PMMA retainers showed increased S. mutans adhesion and intra-oral colonization of S. mutans compared to PP and PU retainers. The results validate further clinical testing for a relationship between caries risk and type of retainer prescribed.
Published: 2021
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15. Parasite community structure in sympatric Bornean primates

Author: Andrew J. J. MacIntosh, Hideo Hasegawa, Tock H. Chua, Symphorosa Sipangkui, Danica J. Stark, Liesbeth Frias, Benoit Goossens, Kenneth Keuk, Munehiro Okamoto, Milena Salgado-Lynn, and Asian School of the Environment
Subjects: Primates, 0301 basic medicine, 030231 tropical medicine, Wildlife, Biodiversity, Zoology, Biology, 03 medical and health sciences, 0302 clinical medicine, Biological sciences::Ecology [Science], Helminths, Animals, Parasite hosting, Parasites, Ecosystem, Phylogeny, Trophic level, Community structure, Southeast Asia, 030104 developmental biology, Infectious Diseases, Habitat, Sympatric speciation, Wildlife parasites, Parasitology, Anthropogenic landscapes, Host-parasite interactions
Abstract: Parasites are important components of ecosystems, influencing trophic networks, competitive interactions and biodiversity patterns. Nonetheless, we are not nearly close to disentangling their complex roles in natural systems. Southeast Asia falls within global areas targeted as most likely to source parasites with zoonotic potential, where high rates of land conversion and fragmentation have altered the circulation of wildlife species and their parasites, potentially resulting in altered host-parasite systems. Although the overall biodiversity in the region predicts equally high, or even higher, parasite diversity, we know surprisingly little about wild primate parasites, even though this constitutes the first step towards a more comprehensive understanding of parasite transmission processes. Here, we characterise the gastrointestinal helminth parasite assemblages of a community of Bornean primates living along the Kinabatangan floodplain in Sabah (Malaysian Borneo), including two species endemic to the island. Through parasitological analyses, and by using several measures of parasite infection as proxies for parasite diversity and distribution, we show that (i) most parasite taxonomic groups are not limited to a single host, suggesting a greater flexibility for habitat disturbance, (ii) parasite infracommunities of nocturnal primates differ from their diurnal counterparts, reflecting both phylogenetic and ecological constraints, and (iii) soil-transmitted helminths such as whipworm, threadworm and nodule worm are widespread across the primate community. This study also provides new parasite records for southern pig-tailed macaques (Macaca nemestrina), silvered langurs (Trachypithecus cristatus) and Western tarsiers (Cephalopachus bancanus) in the wild, while adding to the limited records for the other primate species in the community. Given the information gap regarding primate-parasite associations in the region, the information presented here should prove relevant for future studies of parasite biodiversity and infectious disease ecology in Asia and elsewhere. Published version This study was financially supported by grants from Kyoto University, Japan through its Step-Up program (AM) and by the Japan Society for the Promotion of Science (#24770232 and #16H06181 to AM, and #15H04283 to MO). LF was supported by the Japan Ministry of Education, Culture, Sports, Science and Technology (MEXT) through a Monbukagakusho schol- arship (#140411), by the Japan Society for the Promotion of Science through a JSPS-DC2 fellowship and Grant-in-Aid (#446), and by the Leading Graduate Program in Primatology and Wildlife Science (PWS) of Kyoto University (JSPS-U04).
Published: 2021
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16. Poster Presentations

Author: N. Sutamam, Florent Ginhoux, Barnaby Edward Young, Akshamal M. Gamage, Karen Donceras Nadua, Pavanish Kumar, Chee Fu Yung, Natalie Woon Hui Tan, Amanda Jin Mei Lim, D. Guo, Cheng Tung Chong, K. S. Yeo, Su Li Poh, Jiahui Li, Jing Yao Leong, Randy Foo, Katherine Nay Yaung, Xiao Qian Ng, Joo Guan Yeo, David C. Lye, Camillus Chua, Sharifah Nur Hazirah, Martin Qui, Jerry Kok Yen Chan, Martin Wasser, Lin-Fa Wang, Thaschawee Arkachaisri, Kai Qian Kam, Koh Cheng Thoon, Danielle E. Anderson, Salvatore Albani, L. Ramakrishna, and Shi Huan Tay
Subjects: biology, business.industry, FOXP3, Human leukocyte antigen, CXCR3, Immune system, Rheumatology, TIGIT, Immunology, biology.protein, Medicine, IL-2 receptor, Antibody, business, CD8
Abstract: Background/Purpose: The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in significant mortality, social disorder and economic hardships. We set out to understand why certain individuals could resolve the disease successfully without serious complications by immune profiling of PBMCs from convalescent COVID-19 patients (n = 14) with mild disease trajectory. Methods: We designed 7 peptides targeting the receptor binding region (RBD) of the spike protein of SARS-CoV-2, that encompass broad HLA class I / II alleles, with the aid of the Immune Epitope Database and Analysis Resource (IEDB) website. The RBD site was chosen as it was shown to be protective when neutralising antibodies against this region could negate binding of viral spike protein to host cell ACE-2 receptor. Convalescent COVID-19 patients enrolled in this study were screened and selected for positive antibody titre against the RBD region. PBMCs from convalescent COVID-19 patients were stimulated with/without the peptides for 72hrs and immune profiled (n = 70 markers across two panels) with the high dimensional single cell mass cytometry platform (CyToF). Results: Convalescent COVID-19 patients elicited a robust recall memory T follicular helper response (CD3 + CD4 + CD45RO + CXCR5 + Tigit + ;∗∗∗∗ p < 0.0001) demonstrating peptide efficacy. Unsupervised clustering (FlowSOM) of the CD4 T cell immune landscape reaffirmed increase in memory T follicular subsets and additionally CD4 + CD45RO + CXCR5 -subsets. Further gating of antigen specific memory cells (CD45RO + CD69 + ) revealed an increase in Tbet + CXCR3 + T effectors in both CD4 and CD8 compartments. Strikingly we detected a parallel increase in CD4 + Treg (CD25 + FoxP3 + ) CXCR3 + Tbet + CD45RO + CD152 + Tigit + expression. Conclusions: COVID-19 patients that successfully resolve the viral infection not only mount a robust T effector and follicular response but also in tandem a similar T regulatory profile.
Published: 2021
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17. Novel Mouse Models of Bladder Cancer Identify a Prognostic Signature Associated with Risk of Disease Progression

Author: Cory Abate-Shen, Amir Lankarani, Matteo Di Bernardo, Michael M. Shen, Rivka L. Shoulson, Soonbum Park, Lijie Rong, Tomasz Owczarek, Talal Syed, Hikmat Al-Ahmadie, David B. Solit, James M. McKiernan, Chee-Wai Chua, Prithi Chakrapani, and Jaime Y. Kim
Subjects: Male, Cancer Research, urologic and male genital diseases, medicine.disease_cause, Article, Bladder Urothelium, Mice, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Animals, Humans, PTEN, Neoplasm Invasiveness, RNA-Seq, Urothelium, Mice, Knockout, Bladder cancer, biology, business.industry, PTEN Phosphohydrolase, Cancer, Gene signature, Prognosis, medicine.disease, female genital diseases and pregnancy complications, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Survival Rate, Disease Models, Animal, Urinary Bladder Neoplasms, Oncology, Disease Progression, biology.protein, Cancer research, Female, Tumor Suppressor Protein p53, business, Carcinogenesis, Tamoxifen, medicine.drug
Abstract: To study the progression of bladder cancer from non–muscle-invasive to muscle-invasive disease, we have developed a novel toolkit that uses complementary approaches to achieve gene recombination in specific cell populations in the bladder urothelium in vivo, thereby allowing us to generate a new series of genetically engineered mouse models (GEMM) of bladder cancer. One method is based on the delivery of adenoviruses that express Cre recombinase in selected cell types in the urothelium, and a second uses transgenic drivers in which activation of inducible Cre alleles can be limited to the bladder urothelium by intravesicular delivery of tamoxifen. Using both approaches, targeted deletion of the Pten and p53 tumor suppressor genes specifically in basal urothelial cells gave rise to muscle-invasive bladder tumors. Furthermore, preinvasive lesions arising in basal cells displayed upregulation of molecular pathways related to bladder tumorigenesis, including proinflammatory pathways. Cross-species analyses comparing a mouse gene signature of early bladder cancer with a human signature of bladder cancer progression identified a conserved 28-gene signature of early bladder cancer that is associated with poor prognosis for human bladder cancer and that outperforms comparable gene signatures. These findings demonstrate the relevance of these GEMMs for studying the biology of human bladder cancer and introduce a prognostic gene signature that may help to stratify patients at risk for progression to potentially lethal muscle-invasive disease. Significance: Analyses of bladder cancer progression in a new series of genetically engineered mouse models has identified a gene signature of poor prognosis in human bladder cancer.
Published: 2021
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18. Absence of BapA type III effector protein affects Burkholderia pseudomallei intracellular lifecycle in human host cells

Author: Kumutha Malar Vellasamy, Vanitha Mariappan, Eng Guan Chua, Guang Han Ong, Kum Thong Wong, Micheal J. Wise, Leang Chung Choh, Asif M. Khan, Jamuna Vadivelu, and KHAN, MOHAMMAD ASİF
Subjects: 0106 biological sciences, 0303 health sciences, biology, Burkholderia pseudomallei, Effector, Mutant, Virulence, Bioengineering, biology.organism_classification, 01 natural sciences, Applied Microbiology and Biotechnology, Biochemistry, Cell biology, 03 medical and health sciences, 010608 biotechnology, Secretion, Choh L., Ong G., Chua E., Vellasamy K. M. , Mariappan V., Khan A. M. , Wise M. J. , Wong K., Vadivelu J., -Absence of BapA type III effector protein affects Burkholderia pseudomallei intracellular lifecycle in human host cells-, PROCESS BIOCHEMISTRY, cilt.108, ss.48-59, 2021, Caenorhabditis elegans, Gene knockout, Intracellular, 030304 developmental biology
Abstract: The etiological agent of melioidosis, Burkholderia pseudomallei, utilises a type III secretion system cluster 3 (T3SS3) to deliver proteins termed type III effectors (T3SEs) into the host cytoplasm in order to establish an intracellular lifecycle in phagocytic and non-phagocytic cells, thus playing an important role in pathogenesis. To gain insight into possible functional roles for BapA, a putative T3SE with unknown function, in the intracellular lifecycle of B.pseudomallei, bapA gene knockout mutant was constructed. The effect of the knockout on virulence to the otherwise isogenic parental strain, K96243, was studied by cellular infection assays and Caenorhabditis elegans killing assay. The attachment and subsequent entry into A549 cells was significantly (P < 0.05) attenuated in the Delta bapA compared to K96243. However, intracellular replication was not affected. Furthermore, the cell-to-cell spreading capacity of Delta bapA was impaired although the mutant exhibited no evident defect in its actin tail formation. Additionally, phagocytosis and intracellular replication rates of Delta bapA in U937 macrophage cells were significantly reduced relative to K96243 without phagosomal escape being affected. Based on these observations, we conclude that the BapA T3SE could play an important role in B.pseudomallei intracellular lifecycle, especially, in the early stages of attachment and entry into the host cell.
Published: 2021
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19. Complete mitochondrial genome of Dacus vijaysegarani and phylogenetic relationships with congeners and other tephritid fruit flies (Insecta: Diptera)

Author: Hoi-Sen Yong, Yvonne Jing Mei Liew, Kah-Ooi Chua, Sze-Looi Song, Kok-Gan Chan, and Praphathip Eamsobhana
Subjects: Subfamily Dacinae, Mitochondrial DNA, Tephritoidea, Insecta, Lineage (evolution), Biology, DNA, Mitochondrial, Monophyly, Phylogenetics, Systematics, Genetics, Animals, Bactrocera, Molecular Biology, Phylogeny, Base Composition, Base Sequence, Phylogenetic tree, Diptera, Tephritidae, High-Throughput Nucleotide Sequencing, Subclade, Tribe Dacini, Sequence Analysis, DNA, General Medicine, biology.organism_classification, Mitogenome, Dacus, Evolutionary biology, Genome, Mitochondrial, Original Article
Abstract: Background Tephritid fruit flies of the genus Dacus are members of the tribe Dacini, subfamily Dacinae. There are some 274 species worldwide, distributed in Africa and the Asia-Pacific. To date, only five complete mitochondrial genomes (mitogenomes) of Dacus fruit flies have been published and are available in the GenBank. Methods and results In view of the lack of study on their mitogenome, we sequenced (by next generation sequencing) and annotated the complete mitogenome of D. vijaysegarani from Malaysia to determine its features and phylogenetic relationship. The whole mitogenome of D. vijaysegarani has identical gene order with the published mitogenomes of the genus Dacus, with 13 protein-coding genes, two rRNA genes, 22 tRNAs, a non-coding A + T rich control region, and intergenic spacer and overlap sequences. Phylogenetic analysis based on 15 mitochondrial genes (13 PCGs and two rRNA genes), reveals Dacus, Zeugodacus and Bactrocera forming a distinct clade. The genus Dacus forms a monophyletic group in the subclade containing also the Zeugodacus group; this Dacus-Zeugodacus subclade is distinct from the Bactrocera subclade. D. (Mellesis) vijaysegarani forms a lineage with D. (Mellesis) trimacula in the subcluster containing also the lineage of D. (Mellesis) conopsoides and D. (Callantra) longicornis. D. (Dacus) bivittatus and D. (Didacus) ciliatus form a distinct subcluster. Based on cox1 sequences, the Malaysia and Vietnam taxa of D. vijaysegarani may not be conspecific. Conclusions Overall, the mitochondrial genome of D. vijaysegarani provided essential molecular data that could be useful for further studies for species diagnosis, evolution and phylogeny research of other tephritid fruit flies in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-021-06608-2.
Published: 2021
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20. Phytochemical Profile of Orthosiphon aristatusSamples Prepared by Acetone Precipitation

Author: Lee Suan Chua
Subjects: chemistry.chemical_compound, Orthosiphon, Chromatography, Complementary and alternative medicine, biology, Phytochemical, Chemistry, Precipitation (chemistry), Drug Discovery, Acetone, biology.organism_classification
Abstract: Background: Orthosiphon aristatus is a popular medicinal herb because of its pharmacological significance. Therefore, a lot of products formulated from the plant extract are available in the market. However, many phytochemicals in the plant extract are still remained to be unknown. Objective: The objective of this study was to profile phytochemicals from the plant extracts prepared using water and ethanol in a reflux system for comparison. Method: The commonly used analytical techniques of acetone precipitation (gravimetry) and vanillin assay (colorimetry) were used to estimate total saponin in the plant extracts. The low dielectric constant of acetone (20.7) was used to precipitate saponins. The phytochemicals in the plant extracts and their respective precipitates were then identified by LC-MS/MS. Results: Higher amount of precipitate was formed from ethanol extract than water extract. The results of LC-MS/MS revealed that not only saponins, but other phytochemicals, such as phenolic acids, flavonoids, terpenoids and aliphatic acids were also detected in the precipitates. In particular, ethanol extract and its precipitate were found to have higher flavonoids. Acetone precipitation could significantly increase the content of sagerinic acid and rosmarinic acid, as well as polyhydroxylated and polymethoxylated flavones from the water extract. Conclusion: Acetone precipitation is not specific for saponin, but also any phytochemicals which have lower solubility due to the lack of hydrogen bonding in high dipole moment medium of acetone. Gravimetric acetone precipitation had successfully profiled the phytochemicals in both highly complex water and ethanol based crude extracts.
Published: 2021
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21. Bioinformatics characterization of Plasmodium knowlesi apical membrane antigen 1 (PkAMA1) for multi-epitope vaccine design

Author: Ping Chin Lee, Yvonne A. L. Lim, Kek Heng Chua, F N Haron, Ching Hoong Chew, and A Azazi
Subjects: biology, Malaria vaccine, Protozoan Proteins, Anopheles, Computational Biology, Epitopes, T-Lymphocyte, Membrane Proteins, Antigens, Protozoan, biology.organism_classification, medicine.disease, Major histocompatibility complex, Bioinformatics, Epitope, Malaria, Vaccinology, Antigen, Plasmodium knowlesi, Malaria Vaccines, parasitic diseases, medicine, biology.protein, Humans, Apical membrane antigen 1
Abstract: Malaria caused by Plasmodium knowlesi species has become a public health concern, especially in Malaysia. Plasmodium knowlesi parasite which originates from the macaque species, infects human through the bite of the Anopheles mosquitoes. Research on malaria vaccine has been a continuous effort to eradicate the malaria infection, yet there is no vaccine against P. knowlesi malaria to date. Apical membrane antigen 1 (AMA1) is a unique surface protein of all apicomplexan parasites that plays a crucial role in parasite-host cell invasion and thus has been a long-standing malaria vaccine candidate. The selection of protective epitopes in silico has led to significant advances in the design of the vaccine. The present study aimed to employ bioinformatics tools to predict the potential immunogenic B- and T-cell epitopes in designing malaria vaccine targeting P. knowlesi AMA1 (PkAMA1). B-cell epitopes were predicted using four bioinformatics tools, i.e., BepiPred, ABCpred, BcePred, and IEDB servers whereas T-cell epitopes were predicted using two bioinformatics servers, i.e., NetMHCpan4.1 and NetMHCIIpan-4.0 targeting human major histocompatibility complex (MHC) class I and class II molecules, respectively. The antigenicity of the selected epitopes computed by both B- and T-cell predictors were further analyzed using the VaxiJen server. The results demonstrated that PkAMA1 protein encompasses multi antigenic regions that have the potential for the development of multi-epitope vaccine. Two B- and T-cell epitopes consensus regions, i.e., NSGIRIDLGEDAEVGNSKYRIPAGKCP (codons 28-54) and KTHAASFVIAEDQNTSY RHPAVYDEKNKT (codons 122-150) at domain I (DI) of PkAMA1 were reported. Advancement of bioinformatics in characterization of the target protein may facilitate vaccine development especially in vaccine design which is costly and cumbersome process. Thus, comprehensive B-cell and T-cell epitope prediction of PkAMA1 offers a promising pipeline for the development and design of multi-epitope vaccine against P. knowlesi.
Published: 2021
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22. Characterisation and isolation of bioactive compounds of anti-oomycete bacterial isolates inhibiting the growth of Phytophthora capsici

Author: Sharifah Farhana Syed-Ab-Rahman, Peer M. Schenk, and Elvis T. Chua
Subjects: Oomycete, chemistry.chemical_classification, biology, fungi, food and beverages, Plant Science, biology.organism_classification, Antimicrobial, Isolation (microbiology), Microbiology, Crop, Phytophthora capsici, Enzyme, chemistry, Pathogen, Bacteria
Abstract: Some bacteria can antagonize and competitively exclude pathogens by producing antimicrobial substances in their immediate environment. These antimicrobial agents can be grouped into enzymes, protein such as polypeptides and non-protein compounds. Of the various crop pests and pathogens that devastate harvests, oomycetes and fungi are the most broadly distributed groups causing global issues in food security and environmental damage in natural ecosystems. In this study, three bacterial isolates, Bacillus amyloliquefaciens (UQ154), Bacillus velezensis (UQ156) and Acinetobacter sp. (UQ202), previously shown to promote plant growth and anti-oomycete properties against Phytophthora spp., were selected for further investigation. These isolates were subjected to extractions with dichloromethane. The crude extracts were fractionated by preparative silica gel thin-layer chromatography and tested for their anti-oomycete activities against Phytophthora capsici. The results show that nine out of 16 fractions exhibited high (> 50%) P. capsici growth inhibition, comparable to the application of the live bacterial isolates. Using GCMS analyses, the compounds identified from the bacterial fractions were pyrrolopyrazine and various phenolic compounds, including the previously identified diketopiperazine compounds (DKPs) from the crude bacterial extracts. The ability of these bacterial isolates and their bioactive compounds to inhibit plant pathogen growth deserves further investigations, offering a potential roadmap for the development of bio-pesticides.
Published: 2021
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23. Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells

Author: Fumihito Muro, Tomoyoshi Sobue, Yasushi Itoh, Yuya Mori, Naoki Nomura, Yoichiro Kino, Chimuka Handabile, Hiroki Kitayama, Ryotarou Mitsumata, Hironori Hatanaka, Kazuhiko Kimachi, Ryosuke Omori, Tomohiro Nishimura, Misako Nakayama, Kazumasa Ogasawara, Brendon Y. Chua, Cong Thanh Nguyen, Marumi Ohno, David C. Jackson, Katherine Kedzierska, Masafumi Endo, Toshiki Sekiya, Marios Koutsakos, Yuki Ohara, Saori Suzuki, Masashi Shingai, Lorena E. Brown, Tomio Ikeda, Daisuke Fujikura, Hirohito Ishigaki, and Hiroshi Kida
Subjects: 030231 tropical medicine, Orthomyxoviridae, Inactivated whole influenza virus particle, Antigen-Presenting Cells, Biology, Antibodies, Viral, Virus, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Orthomyxoviridae Infections, Interferon, vaccine, Seasonal and pandemic influenza, medicine, Animals, 030212 general & internal medicine, Innate immune system, General Veterinary, General Immunology and Microbiology, RIG-I, Immunogenicity, Public Health, Environmental and Occupational Health, Virion, RNA, biology.organism_classification, Virology, Infectious Diseases, Vaccines, Inactivated, Influenza Vaccines, Molecular Medicine, RNA, Viral, medicine.drug
Abstract: Current detergent or ether-disrupted split vaccines (SVs) for influenza do not always induce adequate immune responses, especially in young children. This contrasts with the whole virus particle vaccines (WPVs) originally used against influenza that were immunogenic in both adults and children but were replaced by SV in the 1970s due to concerns with reactogenicity. In this study, we re-evaluated the immunogenicity of WPV and SV, prepared from the same batch of purified influenza virus, in cynomolgus macaques and confirmed that WPV is superior to SV in priming potency. In addition, we compared the ability of WPV and SV to induce innate immune responses, including the maturation of dendritic cells (DCs) in vitro. WPV stimulated greater production of inflammatory cytokines and type-I interferon in immune cells from mice and macaques compared to SV. Since these innate responses are likely triggered by the activation of pattern recognition receptors (PRRs) by viral RNA, the quantity and quality of viral RNA in each vaccine were assessed. Although the quantity of viral RNA was similar in the two vaccines, the amount of viral RNA of a length that can be recognized by PRRs was over 100-fold greater in WPV than in SV. More importantly, 1000-fold more viral RNA was delivered to DCs by WPV than by SV when exposed to preparations containing the same amount of HA protein. Furthermore, WPV induced up regulation of the DC maturation marker CD86 on murine DCs, while SV did not. The present results suggest that the activation of antigen-presenting DCs, by PRR-recognizable viral RNA contained in WPV is responsible for the effective priming potency of WPV observed in naive mice and macaques. WPV is thus recommended as an alternative option for seasonal influenza vaccines, especially for children. (c) 2021 Elsevier Ltd. All rights reserved.
Published: 2021

24. The outcome of intra-cytoplasmic sperm injection (ICSI): do the sperm concentration and motility matter?

Author: Mohd Faizal Ahmad, Muhammad Azrai Abu, Ai Chen Chua, Albert Chao Chiet Tan, and Abdul Kadir Abdul Karim
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Embryonic Development, Fertilization in Vitro, Biology, Intracytoplasmic sperm injection, Andrology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Human fertilization, Pregnancy, medicine, Humans, Sperm Injections, Intracytoplasmic, Molecular Biology, Infertility, Male, Sperm motility, 030219 obstetrics & reproductive medicine, In vitro fertilisation, Sperm Count, Malaysia, Pregnancy Outcome, Embryo, General Medicine, medicine.disease, Sperm, 030104 developmental biology, Sperm Motility, Female, Embryo quality
Abstract: Objectives The male-factor subfertility was reported to be 30% globally; thus, the intracytoplasmic sperm injection (ICSI) procedure was implemented to improve the overall in vitro fertilization (IVF) rates. Nevertheless, at least 10% of fertilization failure still occurs. Concerning this issue, we explored the association of sperm concentration and motility with the quality of embryo development and pregnancy outcome in IVF-ICSI cycles. Methods Retrospective analysis of 109 couples with male factor were done over 14 months in a tertiary university hospital in Malaysia. The data were divided into four groups; Group I: normal sperm parameters, Group II: normal sperm concentration but reduced total sperm motility, Group III: reduced sperm concentration and motility, Group IV: reduced sperm concentration but normal sperm motility. Only fresh semen samples and fresh embryo transfers were included. The fertilization, cleavage rate, embryo quality and pregnancy outcome were assessed. Results Overall, group I had the highest oocytes yield and ICSI attempted; (10.12 + 6.50), whereas the lowest was in group IV; (7.00 + 2.82). Group II revealed the highest fertilization and cleavage rates; (54.14 + 25.36), (55.16 + 26.06), thus not surprisingly resulting in the highest number of good embryos and highest clinical pregnancy rates. The lowest cleavage and pregnancy rates were seen in group IV. However, all the outcomes were not statically significant (p>0.05). Conclusions Similar fertilization rate and comparable pregnancy outcome was seen among couples with normal and reduced sperm concentration and motility.
Published: 2021
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25. In vitroAnti-colorectal Cancer Potential of the Medicinal MushroomGanoderma neo-japonicumImazeki in Hyperglycemic Condition: Impact on Oxidative Stress, Cell Cycle and Apoptosis

Author: Kek Heng Chua, Meng-Fei Lau, Umah Rani Kuppusamy, and Vikineswary Sabaratnam
Subjects: 0301 basic medicine, Cancer Research, 030109 nutrition & dietetics, Nutrition and Dietetics, Cell cycle checkpoint, biology, Ganoderma, Medicine (miscellaneous), Glutathione, Cell cycle, Pharmacology, medicine.disease_cause, biology.organism_classification, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, medicine, Viability assay, Cytotoxicity, Oxidative stress
Abstract: Clinical efficacy of chemotherapy is often compromised by diabetogenic glucose on colorectal cancer (CRC). High glucose has been shown to diminish the cytotoxicity of anticancer drugs. The issue can potentially be addressed with natural products. Recently, we revealed that Ganoderma neo-japonicum exhibits inhibitory activities against human colonic carcinoma cells. In this study, the impacts of hexane fraction (Hex, sterol-enriched) and chloroform fraction (Chl, terpenoid-enriched) were further elucidated. The cellular responses, including oxidative stress, cell cycle, and apoptosis were compared between the presence of normal glucose (NG, 5.5 mM) and high glucose (HG, 25 mM). HG promoted cell viability with concomitant elevation of GSH level. Both Hex and Chl fractions stimulated NO production, in addition, induced cell cycle arrest. The apoptotic effect of Hex fraction was glucose-dependent, but Chl fraction triggered apoptosis with an equivalent extent in NG and HG conditions. Overall, the active fractions from G. neo-japonicum show therapeutic potential in managing hyperglycemia-associated CRC.
Published: 2021
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26. Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial

Author: Lydiah Mutumbi, Guido Ferrari, Jennifer Schwartz, Charles E. L. B. Davis, Kelli Greene, Robin Flinko, Monica W. Gerber, Jennifer Husson, Raphael Gottardo, Amy Nelson, Joel V Chua, Celia Mahoney, Bruce L. Gilliam, Ka Wing J. Lam, George K. Lewis, Robert C. Gallo, Ilia Prado, Hongmei Gao, Georgia D. Tomaras, Dan Dong, William Fulp, Timothy R. Fouts, Nicole L. Yates, Mohammad M. Sajadi, Anthony L. DeVico, Bryan T. Mayer, and David C. Montefiori
Subjects: Adult, medicine.medical_treatment, 030231 tropical medicine, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Article, Epitope, Chimeric subunit vaccine, 03 medical and health sciences, Immunogenicity, Vaccine, 0302 clinical medicine, medicine, Animals, Humans, 030212 general & internal medicine, HIV vaccine, Adverse effect, AIDS Vaccines, General Veterinary, General Immunology and Microbiology, biology, business.industry, Immunogenicity, Public Health, Environmental and Occupational Health, HIV, CD4i, Vaccination, Infectious Diseases, Immunization, CD4 Antigens, Vaccines, Subunit, Immunology, HIV-1, biology.protein, Molecular Medicine, Antibody, business, Vaccine, Adjuvant, Full-length single chain (FLSC)
Abstract: A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult volunteers in this first-in-human phase 1a randomized, double-blind, placebo-controlled study with three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. The overall incidence of adverse events (AEs) was not significantly different between vaccinees and controls. The majority (89%) of vaccine-related AE were mild. The most common vaccine-related adverse event was injection site pain. There were no vaccine-related serious AE, discontinuation due to AE, intercurrent HIV infection, or significant decreases in CD4 count. By the final vaccination, all vaccine recipients developed antibodies against IHV01 and demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 vaccine was safe, well tolerated, and immunogenic at all doses tested. The vaccine raised broadly reactive humoral responses against conserved CD4i epitopes on gp120 that mediates antiviral functions.
Published: 2021
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27. Autophagy and ALS: mechanistic insights and therapeutic implications

Author: Edor Kabashi, Jason P. Chua, Sami J. Barmada, and Hortense de Calbiac
Subjects: 0301 basic medicine, 030102 biochemistry & molecular biology, Amyotrophic Lateral Sclerosis, Neurodegeneration, Autophagy, PINK1, Cell Biology, Charged multivesicular body protein 2B, Biology, medicine.disease, Cell biology, 03 medical and health sciences, 030104 developmental biology, TANK-binding kinase 1, Frontotemporal Dementia, Mitophagy, Proteostasis, Unfolded Protein Response, medicine, biology.protein, Humans, TFEB, Molecular Biology, Mechanistic target of rapamycin
Abstract: Mechanisms of protein homeostasis are crucial for overseeing the clearance of misfolded and toxic proteins over the lifetime of an organism, thereby ensuring the health of neurons and other cells of the central nervous system. The highly conserved pathway of autophagy is particularly necessary for preventing and counteracting pathogenic insults that may lead to neurodegeneration. In line with this, mutations in genes that encode essential autophagy factors result in impaired autophagy and lead to neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). However, the mechanistic details underlying the neuroprotective role of autophagy, neuronal resistance to autophagy induction, and the neuron-specific effects of autophagy-impairing mutations remain incompletely defined. Further, the manner and extent to which non-cell autonomous effects of autophagy dysfunction contribute to ALS pathogenesis are not fully understood. Here, we review the current understanding of the interplay between autophagy and ALS pathogenesis by providing an overview of critical steps in the autophagy pathway, with special focus on pivotal factors impaired by ALS-causing mutations, their physiologic effects on autophagy in disease models, and the cell type-specific mechanisms regulating autophagy in non-neuronal cells which, when impaired, can contribute to neurodegeneration. This review thereby provides a framework not only to guide further investigations of neuronal autophagy but also to refine therapeutic strategies for ALS and related neurodegenerative diseases.Abbreviations: ALS: amyotrophic lateral sclerosis; Atg: autophagy-related; CHMP2B: charged multivesicular body protein 2B; DPR: dipeptide repeat; FTD: frontotemporal dementia; iPSC: induced pluripotent stem cell; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PINK1: PTEN induced kinase 1; RNP: ribonuclear protein; sALS: sporadic ALS; SPHK1: sphingosine kinase 1; TARDBP/TDP-43: TAR DNA binding protein; TBK1: TANK-binding kinase 1; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase; UPR: unfolded protein response; UPS: ubiquitin-proteasome system; VCP: valosin containing protein.
Published: 2021
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28. Metagenomics: A viable tool for reconstructing herbivore diet

Author: Physilia Ying Shi Chua, Inger Greve Alsos, Kristine Bohmann, Youri Lammers, Sanne Boessenkool, and Alex Crampton-Platt
Subjects: 0106 biological sciences, 0301 basic medicine, In silico, Computational biology, Biology, shotgun sequencing, 010603 evolutionary biology, 01 natural sciences, Plant identification, 03 medical and health sciences, VDP::Mathematics and natural science: 400::Zoology and botany: 480, Genetics, DNA Barcoding, Taxonomic, Environmental DNA, Resource Article, Herbivory, Ecology, Evolution, Behavior and Systematics, 2. Zero hunger, Herbivore, plants, Shotgun sequencing, Environmental DNA, Faeces, Grouse, Plants, Shotgun sequencing, RESOURCE ARTICLES, Significant difference, Molecular and Statistical Advance, environmental DNA, Diet, 030104 developmental biology, Metagenomics, Metagenome, grouse, Identification (biology), faeces, VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480, Biotechnology
Abstract: Metagenomics can generate data on the diet of herbivores, without the need for primer selection and PCR enrichment steps as is necessary in metabarcoding. Metagenomic approaches to diet analysis have remained relatively unexplored, requiring validation of bioinformatic steps. Currently, no metagenomic herbivore diet studies have utilized both chloroplast and nuclear markers as reference sequences for plant identification, which would increase the number of reads that could be taxonomically informative. Here, we explore how in silico simulation of metagenomic data sets resembling sequences obtained from faecal samples can be used to validate taxonomic assignment. Using a known list of sequences to create simulated data sets, we derived reliable identification parameters for taxonomic assignments of sequences. We applied these parameters to characterize the diet of western capercaillies (Tetrao urogallus) located in Norway, and compared the results with metabarcoding trnL P6 loop data generated from the same samples. Both methods performed similarly in the number of plant taxa identified (metagenomics 42 taxa, metabarcoding 43 taxa), with no significant difference in species resolution (metagenomics 24%, metabarcoding 23%). We further observed that while metagenomics was strongly affected by the age of faecal samples, with fresh samples outperforming old samples, metabarcoding was not affected by sample age. On the other hand, metagenomics allowed us to simultaneously obtain the mitochondrial genome of the western capercaillies, thereby providing additional ecological information. Our study demonstrates the potential of utilizing metagenomics for diet reconstruction but also highlights key considerations as compared to metabarcoding for future utilization of this technique.
Published: 2021
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29. Drying Kinetics and Optimization of Quercetrin Extraction from Melastoma malabathricum Leaves

Author: Mohd Azrie Awang, Lee Suan Chua, Kar Yong Pin, and Luqman Chuah Abdullah
Subjects: Melastoma malabathricum, Chromatography, biology, Chemistry, General Chemical Engineering, Extraction (chemistry), Kinetics, General Chemistry, Response surface methodology, biology.organism_classification, Industrial and Manufacturing Engineering
Published: 2021
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30. Assessing diatom-mediated fatty acids in intertidal biofilm: a new conservation concern

Author: Jessica E. Ollinik, Pamela Brunswick, Marcus Kim, Mark C. Drever, Robert W. Elner, Oxana Blajkevitch, Candice C. Chua, Graham van Aggelen, and Dayue Shang
Subjects: 0106 biological sciences, Intertidal zone, Mass spectrometry, 01 natural sciences, Environmental technology. Sanitary engineering, chemistry.chemical_compound, Nutrient, Climate change, GE1-350, Fatty acids, Derivatization, Mudflats, TD1-1066, chemistry.chemical_classification, Diatoms, biology, 010604 marine biology & hydrobiology, Aquatic ecosystem, Biofilm, 010401 analytical chemistry, Fatty acid, biology.organism_classification, 0104 chemical sciences, Environmental sciences, Diatom, Migratory shorebirds, chemistry, Environmental chemistry
Abstract: Biofilm communities on intertidal mudflats are recognized as major producers of nutrients, especially fatty acids. The rising threats posed by both climatic and anthropogenic stressors increase the necessity of understanding and conserving these communities. Shorebirds provide a proxy for studying the complex ecology of biofilm communities because of their heavy reliance on fatty acids from diatomaceous biofilm for successful long-distance migration. Herein, we review biofilm feeding patterns by migratory shorebirds, experimental design considerations for sampling and studying the fatty acid content of biofilm, and the literature describing established and emerging analytical methodology. Techniques for fatty acid analysis include the commonly employed gas chromatography–flame ionization detection (GC/FID) and gas chromatography–mass spectrometry (GC/MS) with derivatization. Liquid chromatography–mass spectrometry (LC/MS) and liquid chromatography–quadrupole time of flight (LC/QTOF) are newly emerging techniques that enable derivatization to be eliminated. In addition, Fourier transform infrared spectroscopy (FT/IR), a common instrument in chemistry laboratories, has applications in fatty acid research, specifically for screening. Using a combination of sampling and analytical methods is necessary for improved understanding of intertidal biofilm, both as a source of essential fatty acids in aquatic systems and a critical food for shorebirds.
Published: 2021

31. INFLUENCE OF ULTRASOUND-ASSISTED OSMOTIC DEHYDRATION PRE-TREATMENT ON TOTAL PHENOLIC CONTENT, ANTIOXIDANT CAPACITY AND P-CYMENE CONTENT OF EUCALYPTUS DEGLUPTA

Author: Ameena Ali, H Ravikumar, YC Khor, and Bee Lin Chua
Subjects: Pre treatment, Antioxidant capacity, chemistry.chemical_compound, Eucalyptus deglupta, p-Cymene, biology, Chemistry, Forestry, Food science, Ultrasound assisted, biology.organism_classification, Osmotic dehydration
Published: 2021
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32. Biochemical Characterization of Orthosiphon Aristatus and Evaluation of Pharmacological Activities

Author: Siti Pauliena Mohd Bohari, Hafedh Almoalemi, Nadia Adrus, Zaidah Rahmat, and Lee Suan Chua
Subjects: Pharmacology, Orthosiphon aristatus, biology, 010405 organic chemistry, Rosmarinic acid, Transketolase, biology.organism_classification, 01 natural sciences, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Cellulose fiber, chemistry.chemical_compound, Complementary and alternative medicine, Biochemistry, chemistry, Cellulose, Cytotoxicity
Abstract: This study investigated the phytochemicals, protein and cellulose profiles, and the antiradical, antibacterial and cytotoxicity activities of Orthosiphon aristatus. The cellulose profile of the her...
Published: 2021
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33. Systems serology detects functionally distinct coronavirus antibody features in children and elderly

Author: Allen C. Cheng, Francesca L Mordant, Katherine Kedzierska, Keith J. Chappell, Daniel Watterson, Brendon Y. Chua, Hannah G. Kelly, Suzanne K. Shoffner, Jane Crowe, Carolien E. van de Sandt, Melissa M. Lemke, Naphak Modhiran, Bruce D. Wines, Fatima Amanat, Thi H. O. Nguyen, Adam K. Wheatley, Marios Koutsakos, Wen Shi Lee, Hyon-Xhi Tan, Luca Hensen, Kelly B. Arnold, David C. Jackson, Paul R. Young, Amy W. Chung, Paul V. Licciardi, Katie L. Flanagan, Shidan Tosif, Samantha K Davis, Louise C. Rowntree, Chinn Yi Wong, Jennifer A Juno, Stephen J. Kent, Nigel W Crawford, P. Mark Hogarth, Philip Sutton, Melanie R Neeland, Robyn Esterbauer, Kevin J. Selva, Florian Krammer, Denise L. Doolan, Christina Lee, and Landsteiner Laboratory
Subjects: 0301 basic medicine, Immunoglobulin A, Antibody Formation/immunology, viruses, Antibodies, SARS-CoV-2, COVID-19, Infection, Viral infection, General Physics and Astronomy, Antibodies, Viral, medicine.disease_cause, Viral/blood, Immunoglobulin G, Serology, Antibodies, Viral/blood, 0302 clinical medicine, Immunoglobulin A/blood, Receptors, 80 and over, Medicine, Child, skin and connective tissue diseases, Coronavirus, Aged, 80 and over, Multidisciplinary, biology, virus diseases, Middle Aged, Spike Glycoprotein, 3. Good health, Vaccination, COVID-19/immunology, Child, Preschool, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Antibody, Adult, COVID-19 Vaccines, Adolescent, Science, Cross Reactions, Article, General Biochemistry, Genetics and Molecular Biology, SARS-CoV-2/immunology, 03 medical and health sciences, Young Adult, Humans, Preschool, Aged, business.industry, Receptors, IgG, fungi, Coronavirus/immunology, General Chemistry, biochemical phenomena, metabolism, and nutrition, Receptors, IgG/immunology, Immunoglobulin M/blood, body regions, 030104 developmental biology, Immunoglobulin M, Immunoglobulin G/blood, Antibody Formation, Humoral immunity, Immunology, biology.protein, IgG/immunology, Spike Glycoprotein, Coronavirus/immunology, COVID-19 Vaccines/immunology, Cross Reactions/immunology, business
Abstract: The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics., Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.
Published: 2021

34. Aryltetralin-type Lignan of Podophyllum: A Comprehensive Review

Author: Wen Gan Pei, Chyi Liew Jeou, Kumar Dharmendra, R. Mogana, Lee Yong-Xin, Wei Chong Chua, and Akyirem Akowuah Gabriel
Subjects: Lignan, chemistry.chemical_compound, Complementary and alternative medicine, biology, Traditional medicine, chemistry, Drug Discovery, Podophyllum, biology.organism_classification
Abstract: Podophyllotoxin is a nonalkaloid toxin aryltetralin lactone lignan, occurring naturally and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives have been shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic and antiviral properties. Podophyllotoxin serves as a potential anticancer agent and also the precursor for the chemical synthesis of some clinically important anticancer agents. The chemical modification and pharmacological investigation of podophyllotoxin derivatives have become a concern nowadays. Research interest has been stimulated towards the innovation of podophyllotoxin derivatives as the semi-synthetic anticancer agents, especially etoposide and teniposide. Podophyllotoxin and its derivatives are available in several formulations and also found to be effective in combination therapy. This review article aims to provide an overview of the role of podophyllotoxin, its mechanism of action, pharmacological activities, pharmacokinetics, available formulations, and its effects in combination therapy. This article also reviews the biosynthesis, structure and modifications of podophyllotoxin and its derivatives as an anticancer agent.
Published: 2022
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35. Lin28a rejuvenates muscle stem cells via mitochondrial optimization

Author: Chunwei Li, Kang Yu, Wenhua Cao, Yan-Jiang Benjamin Chua, Min-Wen Jason Chua, Peng Wang, Bin Tean Teh, Jiali Su, Lanfang Luo, Yu Chen, Shilin Ma, Ruirui Liu, Lan Jiang, Zongming Jiang, Shuqing Liu, Xupeng Liu, Ng Shyh-Chang, Yuefan Wang, Taoyan Liu, Liping Zhang, Lu Guang, Yun Li, Luyao Guo, Wenwu Ma, Ziyue Yao, Na Ai, Ruiqi Rachel Wang, Tan J, Hefan Miao, and Kun Liang
Subjects: Somatic cell, PAX3, Myocyte, Stem cell factor, Biology, Stem cell, Reprogramming, Embryonic stem cell, Tissue homeostasis, Cell biology
Abstract: The well-conserved correlation between juvenility and tissue regeneration was first discussed by Charles Darwin. Ectopic Lin28 is known to play an important role in somatic reprogramming and tissue regeneration, but endogenous Lin28’s role in tissue homeostasis and juvenility had remained unclear. Through lineage tracing, we found that a rare subset of muscle stem cells (MuSCs) expressing Lin28a can respond to acute injury by proliferating as Pax3+ or Pax7+ MuSCs, and contribute to all types of myofibers during muscle regeneration. Compared with conventional Pax7+ MuSCs, Lin28a+ MuSCs express more Pax3 and show enhanced myogenicity in vitro. In terms of the epigenetic clock, adult Lin28a+ MuSCs lie between adult Pax7+ MuSCs and embryonic Pax7+ myoblasts according to their DNA methylation profiles. We found that Lin28a+ MuSCs upregulate several embryonic limb bud mesoderm transcription factors and could maintain a juvenile state with enhanced stem cell self-renewal and stress-responsiveness in vitro and in vivo. When combined with telomerase and TP53 inhibition to biomimic mouse Lin28a+ MuSCs, we found that Lin28a can rejuvenate and dedifferentiate aged human primary myoblasts into engraftable, self-renewing MuSCs. Mechanistic studies revealed that Lin28a activated the HIF1A pathway by optimizing mitochondrial ROS (mtROS), thereby rejuvenating MuSC self-renewal and muscle regeneration. Our findings connect the stem cell factor Lin28, mtROS metabolism and stress response pathways to the process of stem cell rejuvenation and tissue regeneration.
Published: 2021
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36. Risk factors of post-anaesthesia care unit delirium in patients undergoing non-cardiac surgery in Singapore

Author: Vanessa Chua, Lian Kah Ti, Ne Hooi Will Loh, Nelson Chua, Edwin Seet, Vera Lim, Beatrice Lim, Wan Yi Wong, Jinbin Zhang, Yuhe Ke, and Sophia Tsong Huey Chew
Subjects: Geriatrics, medicine.medical_specialty, education.field_of_study, biology, business.industry, Incidence (epidemiology), Population, General Medicine, biology.organism_classification, Logistic regression, Malignancy, medicine.disease, behavioral disciplines and activities, nervous system diseases, Pacu, Informed consent, mental disorders, Emergency medicine, Medicine, Delirium, medicine.symptom, business, education
Abstract: Introduction: Post-anaesthesia care unit (PACU) delirium affects 5%–45% of patients after surgery and is associated with postoperative delirium and increased mortality. Up to 40% of PACU delirium is preventable but it remains under-recognised due to a lack of awareness for its diagnosis. Nursing Delirium Screening Scale (Nu-DESC) has been validated in diagnosing PACU delirium but is not routine locally. This study aim was to use the Nu-DESC to establish the incidence and risk factors of PACU delirium in patients undergoing non-cardiac surgery in the surgical population. Methods: With IRB approval and informed consent, we conducted an audit of eligible patients undergoing major surgery in three major public hospitals in Singapore over one week. Patients were assessed for delirium 30–60 minutes following their arrival in the PACU using the Nu-DESC with a score of ≥ 2 as indicative of delirium. Results: A total of 478 patients were assessed. The overall incidence rate of PACU delirium was 18/478 (3.8%) and 9/146 (6.2%) in patients over 65 years old. PACU delirium was more common in females, patients with malignancy and those who underwent longer operations. Logistic Regression analysis showed that the use of BIS (p < 0.001) and the presence of malignancy (p
Published: 2021

37. Vandetanib sensitizes head and neck squamous cell carcinoma to photodynamic therapy through modulation of EGFR-dependent DNA repair and the tumour microenvironment

Author: Eugenia Li Ling Yeo, Melvin L.K. Chua, Zhong-Guo Liang, Pek Lim Chu, Dennis J.J. Poon, Khee Chee Soo, Waseem Ahamed Shihabuddeen, Kevin L.M. Chua, Wen Long Nei, Kar Perng Low, Bhuvaneswari Ramaswamy, and Patricia S. P. Thong
Subjects: Porphyrins, Cell Survival, DNA repair, DNA damage, medicine.medical_treatment, Biophysics, Down-Regulation, Mice, Nude, Photodynamic therapy, DNA-Activated Protein Kinase, Dermatology, Vandetanib, Mice, chemistry.chemical_compound, Piperidines, Cell Line, Tumor, Tumor Microenvironment, medicine, Animals, Humans, Pharmacology (medical), Viability assay, Epidermal growth factor receptor, Cell Proliferation, Photosensitizing Agents, Chlorophyllides, biology, Squamous Cell Carcinoma of Head and Neck, business.industry, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Head and neck squamous-cell carcinoma, ErbB Receptors, Vascular endothelial growth factor, Photochemotherapy, Oncology, chemistry, Head and Neck Neoplasms, Quinazolines, Cancer research, biology.protein, Drug Therapy, Combination, business, DNA Damage, medicine.drug
Abstract: Background Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT). Purpose We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT. Methods We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues. Results First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction. Conclusion Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.
Published: 2019
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38. Characterization of the relationship between polar and lateral flagellar genes in clinical Aeromonas dhakensis: phenotypic, genetic and biochemical analyses

Author: S. D. Puthucheary, Jin-Ai Mary Anne Tan, Tien-Tien Vicky Lau, Kek Heng Chua, and Suat Moi Puah
Subjects: 0303 health sciences, biology, 030306 microbiology, Swarming (honey bee), Motility, Swarming motility, Bacterial, Fungal and Virus Molecular Biology - Research Paper, biology.organism_classification, Microbiology, Phenotype, Virulence factor, 03 medical and health sciences, Aeromonas, Flagella, Genotype, Media Technology, Humans, Gram-Negative Bacterial Infections, Gene, Flagellin, 030304 developmental biology
Abstract: Flagellar-mediated motility is a crucial virulence factor in many bacterial species. A dual flagellar system has been described in aeromonads; however, there is no flagella-related study in the emergent human pathogen Aeromonas dhakensis. Using 46 clinical A. dhakensis, phenotypic motility, genotypic characteristics (flagellar genes and sequence types), biochemical properties and their relationship were investigated in this study. All 46 strains showed swimming motility at 30 °C in 0.3% Bacto agar and carried the most prevalent 6 polar flagellar genes cheA, flgE, flgG, flgH, flgL, and flgN. On the contrary, only 18 strains (39%) demonstrated swarming motility on 0.5% Eiken agar at 30 °C and they harbored 11 lateral flagellar genes lafB, lafK, lafS, lafT, lafU, flgCL, flgGL, flgNL, fliEL, fliFL, and fliGL. No association was found between biochemical properties and motility phenotypes. Interestingly, a significant association between swarming and strains isolated from pus was observed (p = 0.0171). Three strains 187, 277, and 289 isolated from pus belonged to novel sequence types (ST522 and ST524) exhibited fast swimming and swarming profiles, and they harbored > 90% of the flagellar genes tested. Our findings provide a fundamental understanding of flagellar-mediated motility in A. dhakensis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-021-00457-8.
Published: 2021
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39. Sago palm (Metroxylon sagu) starch yield, influencing factors and estimation from morphological traits

Author: S. N. David Chua, M. H. Hussain, S. F. Lim, and E. P. Kho
Subjects: Materials science, biology, Starch, fungi, food and beverages, Sago palm, biology.organism_classification, Industrial and Manufacturing Engineering, Crop, Horticulture, chemistry.chemical_compound, chemistry, Mechanics of Materials, Yield (wine), Sago starch, Metroxylon sagu, General Materials Science, human activities
Abstract: Sago palm (Metroxylon sagu) has been a promising crop with its exceptionally high starch content compared to other starch-producing crops. Sago starch has diverse applications in both food and non-...
Published: 2021
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40. Phytochemical Analysis of Three Common Medicinal Plants (Gliricidia sepium, Melothria pendula, and Pithecellobium dulce) in the Philippines

Author: Jinky Marie T. Chua, Ramachandran Rahul, Sruthi Sadeesh Poonangadu, Julius T. Capili, Toms Prakash, Siranjeevi Senthil Kumar, Renjith Raju, and Prasanth Sonaimuthu
Subjects: Phytochemical, Traditional medicine, General Medicine, Biology, Melothria pendula, Medicinal plants, biology.organism_classification, Pithecellobium dulce, Gliricidia sepium
Published: 2021
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41. Deodorizing the king of fruits: Durian stalk deodorizes the aroma of durian

Author: Chun Kiang Chua, Zhi Kheng Lim, Ke Qi Tan, Yunbo Lv, Carmen Sze Min Pui, Hua Jun Zhang, and Esther Zi Hui Fang
Subjects: biology, Stalk, Chemistry, Biomass feedstock, General Chemistry, Food science, Gas chromatography–mass spectrometry, biology.organism_classification, Aroma
Published: 2021
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42. Evaluation of the Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Expression in Osteosarcoma and Its Association with the Clinicopathological Data

Author: Sharifah Emilia Tuan Sharif, Muhamad Syahrul Fitri Zawawi, Hui Heng Chua, Wan Faisham Numan Wan Ismail, and Sarimah Abdullah
Subjects: Adult, Male, musculoskeletal diseases, 0301 basic medicine, Oncology, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Bone Neoplasms, Kaplan-Meier Estimate, Letter to Editor, Amputation, Surgical, Disease-Free Survival, Bone remodeling, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Child, Receptor, Survival analysis, Aged, Osteosarcoma, biology, business.industry, RANK Ligand, General Medicine, Middle Aged, Limb Salvage, Prognosis, medicine.disease, Immunohistochemistry, 030104 developmental biology, Amputation, RANKL, Child, Preschool, 030220 oncology & carcinogenesis, biology.protein, Female, Sarcoma, business
Abstract: Background The receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key regulators of bone remodelling in bone oncology, including osteosarcoma. We assessed RANKL immunohistochemical expression in osteosarcoma, its association, and disease-free survival with the patients' clinicopathological characteristics. Methods One hundred osteosarcoma cases from 2003 to 2018 in Hospital Universiti Sains Malaysia were retrieved. The tissue samples were stained for RANKL, and the association with the clinicopathological characteristics was evaluated. Staining was interpreted in a semiquantitative scoring system and classified into negative and positive expressions. Results: Eighty-two cases had a positive expression of RANKL in which 56 and 26 patients were classified as low expression and high expression, respectively. The positive expression of RANKL did not show a significant association with clinicopathological characteristics. However, Kaplan Meier survival analysis showed a significant improvement in the disease-free survival patients who underwent limb salvage surgery (LSS) than amputated patients (p-value 0.002), whereas poorer survival was observed among conventional osteosarcomas compared to non-conventional osteosarcoma (p-value 0.01). Conclusion Limb salvage surgery had proven to improve osteosarcoma patients' survival compared to amputation, which could improve overall quality of life in osteosarcoma patients. However, our data did not show a significant association between positive RANKL immunohistochemistry with any of the clinicopathological characteristics and patients' final survival. Further studies may be acquired to understand the suitability of using RANKL immunohistochemistry as prognostication in the management of osteosarcoma patients.
Published: 2021
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43. Prognostic significance of phosphoglycerate dehydrogenase in breast cancer

Author: Aye Aye Thike, Puay Hoon Tan, Pei Jou Chua, Ruby Yun-Ju Huang, George W. Yip, Umamaheswari Muniasamy, Cheng Teng Ng, Boon-Huat Bay, and Muthukrishnan Chandrika
Subjects: 0301 basic medicine, Cancer Research, Cell, Breast Neoplasms, Biology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cell Line, Tumor, Serine, medicine, Humans, Phosphoglycerate dehydrogenase, skin and connective tissue diseases, Lymph node, Phosphoglycerate Dehydrogenase, Cell Proliferation, Tissue microarray, Cell growth, Cancer, Cell cycle, Prognosis, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female
Abstract: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation. Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay. Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced. The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.
Published: 2021
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44. Concentrating rosmarinic acid from Orthosiphon aristatus extract for high antioxidative candies

Author: Lee Suan Chua and Jin Ru Lim
Subjects: Orthosiphon aristatus, Antioxidant, biology, medicine.medical_treatment, Rosmarinic acid, Extraction (chemistry), Fractionation, biology.organism_classification, Industrial and Manufacturing Engineering, chemistry.chemical_compound, Ingredient, Column chromatography, chemistry, Polyphenol, medicine, Food science, Food Science
Abstract: Extraction and fractionation were carried out to concentrate the rosmarinic acid from Orthosiphon aristatus in order to increase the value of herbal candy formulated using polyphenolic rich extract. The herb was extracted and fractionated in column chromatography, and then analyzed by LC-MS/MS. The collected plant fractions with similar chromatographic profiles were combined and determined for antioxidant capacities expressed in radical scavenging activity. The results showed that the antioxidant capacity was in good agreement with the concentration of rosmarinic acid in the combined fractions. The combined fraction II showed the highest rosmarinic acid content, 3.8%w/w and the highest antioxidant capacity (IC50=14.922 ppm). The incorporation of rosmarinic acid rich extract into candy formulation did not statistically affect the antioxidant capacity. Hence, the rosmarinic acid rich extract could be another choice of ingredient to enhance the beneficial property of candies. Candy is another form of carrier to deliver herbal ingredient for health promotion.
Published: 2021
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45. The complete mitochondrial genome of the Indian leafwing butterfly Kallima paralekta (insecta: Lepidoptera: Nymphalidae)

Author: Hannah M. Buhr, Heeeun Yang, Parneet K. Ateliey, Ruth Marte, Sean M. Robertson, Jaime C. McNicholl, Rayeil J. Chua, Carly Gair, Claudia Pfeifer, Brendan Dennehy, Ryan M. Aikens, Shamsa Ricci, Jennifer Watt, David Laudato, Jillian Roziere, Clémence Kokolo, Soomin Huh, Danilo Shevkoplyas, Fariba Ishrar, Connor S. McIntyre, McKay Lowry, Charanpreet F. Kaur, Luc J. Posillipo, Imane Marrakchi, Brady R. Gordon, Katrina Lanyon, Elizabeth B. Jonson, Prerna Sharma, Heather N. Deane, Gabrielle B. Nowlin, Jenelle M. Williams, Jeffrey M. Marcus, Tri Q. Le, Arizona G. Wilkinson, Michael G. Castro, Cassidy P. Aguila, Chenyi Wang, Jessica L. Fay, Holly J. Stokes, Rebecca E. Twilley, Nishtha Dayal, Michael D. Wood, and Meerim Esenbekova
Subjects: 0106 biological sciences, 0301 basic medicine, Mitochondrial DNA, biology, Kallima paralekta, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Nymphalidae, Genome, Lepidoptera genitalia, 03 medical and health sciences, 030104 developmental biology, Evolutionary biology, Butterfly, Genetics, Molecular Biology, Illumina dye sequencing
Abstract: The Indian leafwing butterfly Kallima paralekta (Horsfield, 1829) (Nymphalidae) is an Asian forest-dwelling, leaf-mimic. Genome skimming by Illumina sequencing permitted assembly of a complete circ...
Published: 2021
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46. Widely heterogeneous humoral and cellular immunity after mild SARS-CoV-2 infection in a homogeneous population of healthy young men

Author: Aven Ng, Louisa Sun, Kamini Kunasegaran, Jinyan Fang, Iain Beehuat Tan, Fong Sin Lee, Clarence C. Tam, Hannah E. Clapham, Siew Kim Ong, Doreen Soek Chin Tan, Shawn Vasoo, Lin-Fa Wang, Shiow Pin Tan, Alex R. Cook, Tar Choon Aw, Li Yang Hsu, Nicole Tan, Antonio Bertoletti, Mao Sheng Lee, Adeline Chia, Enan Jun-Kang Goh, Wei Yee Wan, Monica Socheata Suor Peou, Julian Xiao-Li Ang, Alvin Kuo Jing Teo, Wan Ni Chia, Samuel Zeng-Rong Chong, Mohammad Yazid Abdad, Jingxiang Huang, Nina Le Bert, Feng Zhu, Qin Xuan Chua, and Biauw Chi Ong
Subjects: education.field_of_study, Cellular immunity, South asia, Coronavirus disease 2019 (COVID-19), biology, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Population, General Medicine, Acquired immune system, Microbiology, Virology, Infectious Diseases, Homogeneous, Drug Discovery, biology.protein, Parasitology, Antibody, education
Abstract: Background: We studied humoral and cellular responses against SARS-CoV-2 longitudinally in a homogeneous population of healthy young/middle-aged men of South Asian ethnicity with mild COVID-19. Met...
Published: 2021
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47. Loss of FEZ1, a gene deleted in Jacobsen syndrome, causes locomotion defects and early mortality by impairing motor neuron development

Author: Venetia Kok Jing Tong, Sylvester Wong Shu Ming, Kah-Leong Lim, Ziyin Wang, Rafhanah Banu Bte Abdul Razar, Saravanan Gunaseelan, Sumitra Srimasorn, Wei-Yi Ong, and John Jia En Chua
Subjects: 0301 basic medicine, Neurite, Neurogenesis, Central nervous system, Nerve Tissue Proteins, Biology, Axonal Transport, Neuromuscular junction, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Animals, Autophagy-Related Protein-1 Homolog, Drosophila Proteins, Humans, Jacobsen Distal 11q Deletion Syndrome, Jacobsen syndrome, Axon, Molecular Biology, Gait Disorders, Neurologic, Genetics (clinical), Adaptor Proteins, Signal Transducing, Motor Neurons, Brain, General Medicine, Motor neuron, medicine.disease, Rats, Cytoskeletal Proteins, 030104 developmental biology, medicine.anatomical_structure, Peripheral nervous system, Axoplasmic transport, Neuroscience, Locomotion, 030217 neurology & neurosurgery
Abstract: FEZ1-mediated axonal transport plays important roles in central nervous system development but its involvement in the peripheral nervous system is not well-characterized. FEZ1 is deleted in Jacobsen syndrome (JS), an 11q terminal deletion developmental disorder. JS patients display impaired psychomotor skills, including gross and fine motor delay, suggesting that FEZ1 deletion may be responsible for these phenotypes, given its association with the development of motor-related circuits. Supporting this hypothesis, our data show that FEZ1 is selectively expressed in the rat brain and spinal cord. Its levels progressively increase over the developmental course of human motor neurons (MN) derived from embryonic stem cells. Deletion of FEZ1 strongly impaired axon and dendrite development, and significantly delayed the transport of synaptic proteins into developing neurites. Concurring with these observations, Drosophila unc-76 mutants showed severe locomotion impairments, accompanied by a strong reduction of synaptic boutons at neuromuscular junctions. These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin. Collectively, the results highlight a role for FEZ1 in MN development and implicate its deletion as an underlying cause of motor impairments in JS patients.
Published: 2021
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48. Amelioration of high-fat diet-induced obesity and its associated complications by a myricetin derivative-rich fraction from Syzygium malaccense in C57BL/6J mice

Author: Cindy Shuan Ju Teh, Devi Nallappan, Kien Chai Ong, Umah Rani Kuppusamy, Chun Wie Chong, Kek Heng Chua, and Uma Devi Palanisamy
Subjects: 0301 basic medicine, medicine.medical_specialty, Normal diet, Trolox equivalent antioxidant capacity, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, biology, business.industry, Akkermansia, General Medicine, medicine.disease, biology.organism_classification, 030104 developmental biology, Endocrinology, chemistry, Myricetin, Steatosis, business, Thermogenesis, Dyslipidemia, Food Science
Abstract: Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1 metformin (positive control) and normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant weight reduction without appetite suppression and amelioration of insulin resistance, steatosis and dyslipidemia. Besides, MD significantly reduced lipid hydroperoxides and protein carbonyls in tissue homogenates and urine and elevated Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) and thus, alleviated oxidative stress. The weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of obesity and its associated metabolic disorders.
Published: 2021
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49. Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage

Author: Ruklanthi de Alwis, John E. Connolly, Danielle E. Anderson, Damien Marlier, Veronika von Messling, October M. Sessions, Raphaël M. Zellweger, Lin-Fa Wang, Edmond Chua, and Tanu Chawla
Subjects: 0301 basic medicine, Epidemiology, Viral pathogenesis, Disease, Virus Replication, Systemic inflammation, Monocytes, Zika virus, Pathogenesis, flavivirus, Drug Discovery, innate immunity, Interleukin-15, Virulence, biology, Zika Virus Infection, General Medicine, Flavivirus, Infectious Diseases, medicine.symptom, Brazil, Research Article, Adult, Asia, 030106 microbiology, Immunology, NHP, Microbiology, Arbovirus, 03 medical and health sciences, Species Specificity, Virology, medicine, Animals, Humans, Tumor Necrosis Factor-alpha, Virusinfektion, inflammation, arbovirus, business.industry, Outbreak, Dendritic Cells, Zika Virus, biology.organism_classification, medicine.disease, Immunity, Innate, Disease Models, Animal, Macaca fascicularis, 030104 developmental biology, Parasitology, business
Abstract: Zika virus (ZIKV) is an emerging arbovirus with recent global expansion. Historically, ZIKV infections with Asian lineages have been associated with mild disease such as rash and fever. However, recent Asian sub-lineages have caused outbreaks in the South Pacific and Latin America with increased prevalence of neurological disorders in infants and adults. Asian sub-lineage differences may partially explain the range of disease severity observed. However, the effect of Asian sub-lineage differences on pathogenesis remains poorly characterized. Current study conducts a head-to-head comparison of three Asian sub-lineages that are representative of the circulating ancestral mild Asian strain (ZIKV-SG), the 2007 epidemic French Polynesian strain (ZIKV-FP), and the 2013 epidemic Brazil strain (ZIKV-Brazil) in adult Cynomolgus macaques. Animals infected intervenously or subcutaneously with either of the three clinical isolates showed sub-lineage-specific differences in viral pathogenesis, early innate immune responses and systemic inflammation. Despite the lack of neurological symptoms in infected animals, the epidemiologically neurotropic ZIKV sub-lineages (ZIKV-Brazil and/or ZIKV-FP) were associated with more sustained viral replication, higher systemic inflammation (i.e. higher levels of TNFα, MCP-1, IL15 and G-CSF) and greater percentage of CD14+ monocytes and dendritic cells in blood. Multidimensional analysis showed clustering of ZIKV-SG away from ZIKV-Brazil and ZIKV-FP, further confirming sub-lineage differences in the measured parameters. These findings highlight greater systemic inflammation and monocyte recruitment as possible risk factors of adult ZIKV disease observed during the 2007 FP and 2013 Brazil epidemics. Future studies should explore the use of anti-inflammatory therapeutics as early treatment to prevent ZIKV-associated disease in adults.
Published: 2021
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50. Plasmodium berghei Hsp90 contains a natural immunogenic I-Ab-restricted antigen common to rodent and human Plasmodium species

Author: Ganchimeg Bayarsaikhan, William R. Heath, Lynette Beattie, Rose May, Zhengyu Ge, Vanessa Mollard, Peck Szee Tan, Daniel Fernandez-Ruiz, Anton Cozijnsen, Mireille H. Lahoud, Yu Cheng Chua, Ralf B. Schittenhelm, Matthias H. Enders, Anthony W. Purcell, Katsuyuki Yui, Maria N. de Menezes, Irina Caminschi, Sonia Ghilas, and Geoffrey I. McFadden
Subjects: MHC class II, Adoptive cell transfer, biology, Vaccination, Immunology, Specialties of internal medicine, Plasmodium epitope, T cell memory, Parasitemia, CD4 T cell subsets, medicine.disease, biology.organism_classification, Virology, Epitope, RC581-951, Antigen, Immunity, Malaria immunity, Heat shock protein, Experimental cerebral malaria, parasitic diseases, medicine, biology.protein, Plasmodium berghei
Abstract: Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of Plasmodium-derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4+ T cells specific for an MHC class II (I-Ab)-restricted Plasmodium epitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. berghei heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. berghei blood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naive repertoire. Adoptive transfer of in vitro activated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. berghei parasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria.
Published: 2021
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