21 results on '"Ara M"'
Search Results
2. The prospect of spray pyrolyzed pure, Mn-doped, and Zn-doped nickel oxide thin films as TCO material
- Author
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Begum, M. Esmotara, Islam, M. Bodiul, Ara, M. Hosne, Doris, Anannya, Kaiyum, M. Abdul, and Rasadujjaman, Md.
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- 2024
- Full Text
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3. Incorporation of Multiple β2-Hydroxy Acids into a Protein In Vivo Using an Orthogonal Aminoacyl-tRNA Synthetase
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Hamlish, Noah X., primary, Abramyan, Ara M., additional, Shah, Bhavana, additional, Zhang, Zhongqi, additional, and Schepartz, Alanna, additional
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- 2024
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4. Arsenic pollution and its impact on agricultural production, including the ecosystem services delivered by biodiversity
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Hoque, M. M., primary, Rahman, S., additional, Hoque, M. E., additional, Ara, M. J., additional, and Jamal, M. R., additional
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- 2024
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5. Incorporation of Multiple β2‑Hydroxy Acids into a Protein In Vivo Using an Orthogonal Aminoacyl-tRNA Synthetase.
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Hamlish, Noah X., Abramyan, Ara M., Shah, Bhavana, Zhang, Zhongqi, and Schepartz, Alanna
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- 2024
- Full Text
- View/download PDF
6. Incorporation of Multiple β2-Hydroxy Acids into a Protein In VivoUsing an Orthogonal Aminoacyl-tRNA Synthetase
- Author
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Hamlish, Noah X., Abramyan, Ara M., Shah, Bhavana, Zhang, Zhongqi, and Schepartz, Alanna
- Abstract
The programmed synthesis of sequence-defined biomaterials whose monomer backbones diverge from those of canonical α-amino acids represents the next frontier in protein and biomaterial evolution. Such next-generation molecules provide otherwise nonexistent opportunities to develop improved biologic therapies, bioremediation tools, and biodegradable plastic-like materials. One monomer family of particular interest for biomaterials includes β-hydroxy acids. Many natural products contain isolated β-hydroxy acid monomers, and polymers of β-hydroxy acids (β-esters) are found in polyhydroxyalkanoate (PHA) polyesters under development as bioplastics and drug encapsulation/delivery systems. Here we report that β2-hydroxy acids possessing both (R) and (S) absolute configuration are substrates for pyrrolysyl-tRNA synthetase (PylRS) enzymes in vitroand that (S)-β2-hydroxy acids are substrates in cellulo. Using the orthogonal MaPylRS/MatRNAPylsynthetase/tRNA pair, in conjunction with wild-type E. coliribosomes and EF-Tu, we report the cellular synthesis of model proteins containing two (S)-β2-hydroxy acid residues at internal positions. Metadynamics simulations provide a rationale for the observed preference for the (S)-β2-hydroxy acid and provide mechanistic insights that inform future engineering efforts. As far as we know, this finding represents the first example of an orthogonal synthetase that acylates tRNA with a β2-hydroxy acid substrate and the first example of a protein hetero-oligomer containing multiple expanded-backbone monomers produced in cellulo.
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- 2024
- Full Text
- View/download PDF
7. An annotated checklist of the mammals of the Chimanimani National Park, Mozambique
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Mnqobi L. Mamba, Ana Gledis da Conceição, Piotr Naskrecki, Antonio Ngovene, Desiré Lee Dalton, Isa-Rita M. Russo, Fleur Visser, and Ara Monadjem
- Subjects
Afromontane ,biodiversity ,cytochrome b ,Eutheria ,Biology (General) ,QH301-705.5 - Abstract
The Chimanimani Mountains of Mozambique and Zimbabwe harbour diverse and unique flora and fauna. Because of these unique floral characteristics, this region has received considerable attention by botanists. In contrast, the vertebrates occurring here have received little attention. The aim of this paper was to synthesise data collected on multiple recent surveys into the first annotated checklist of the mammals of the Mozambican side of the Chimanimani Mountains. We identified medium-sized and large mammals by exterior appearance, mostly as captured on camera traps. We combined morphological and molecular methods to identify small mammals, and we report on echolocation calls of some of the poorly known bat species. In total, we recorded 69 species, including 23 species of bats (Chiroptera), 15 species of rodents (Rodentia), 11 species of carnivores (Carnivora), nine species of ungulates (Cetartiodactyla), and the rest comprising Primates, Eulipotyphla, Lagomorpha, Proboscidea, and Pholidota. Of these, five species are listed as threatened, demonstrating the importance of the Chimanimani Mountains for mammalian biodiversity conservation in South Eastern Africa.
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- 2024
- Full Text
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8. Dopamine release plateau and outcome signals in dorsal striatum contrast with classic reinforcement learning formulations
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Min Jung Kim, Daniel J. Gibson, Dan Hu, Tomoko Yoshida, Emily Hueske, Ayano Matsushima, Ara Mahar, Cynthia J. Schofield, Patlapa Sompolpong, Kathy T. Tran, Lin Tian, and Ann M. Graybiel
- Subjects
Science - Abstract
Abstract We recorded dopamine release signals in centromedial and centrolateral sectors of the striatum as mice learned consecutive versions of visual cue-outcome conditioning tasks. Dopamine release responses differed for the centromedial and centrolateral sites. In neither sector could these be accounted for by classic reinforcement learning alone as classically applied to the activity of nigral dopamine-containing neurons. Medially, cue responses ranged from initial sharp peaks to modulated plateau responses; outcome (reward) responses during cue conditioning were minimal or, initially, negative. At centrolateral sites, by contrast, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. At most sites, we found no evidence for a transition from outcome signaling to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopaminergic neuronal activity. These findings delineate a reshaping of striatal dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.
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- 2024
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9. A genomic basis of vocal rhythm in birds
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Matteo Sebastianelli, Sifiso M. Lukhele, Simona Secomandi, Stacey G. de Souza, Bettina Haase, Michaella Moysi, Christos Nikiforou, Alexander Hutfluss, Jacquelyn Mountcastle, Jennifer Balacco, Sarah Pelan, William Chow, Olivier Fedrigo, Colleen T. Downs, Ara Monadjem, Niels J. Dingemanse, Erich D. Jarvis, Alan Brelsford, Bridgett M. vonHoldt, and Alexander N. G. Kirschel
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Science - Abstract
Abstract Vocal rhythm plays a fundamental role in sexual selection and species recognition in birds, but little is known of its genetic basis due to the confounding effect of vocal learning in model systems. Uncovering its genetic basis could facilitate identifying genes potentially important in speciation. Here we investigate the genomic underpinnings of rhythm in vocal non-learning Pogoniulus tinkerbirds using 135 individual whole genomes distributed across a southern African hybrid zone. We find rhythm speed is associated with two genes that are also known to affect human speech, Neurexin-1 and Coenzyme Q8A. Models leveraging ancestry reveal these candidate loci also impact rhythmic stability, a trait linked with motor performance which is an indicator of quality. Character displacement in rhythmic stability suggests possible reinforcement against hybridization, supported by evidence of asymmetric assortative mating in the species producing faster, more stable rhythms. Because rhythm is omnipresent in animal communication, candidate genes identified here may shape vocal rhythm across birds and other vertebrates.
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- 2024
- Full Text
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10. A biogeographical appraisal of the threatened South East Africa Montane Archipelago ecoregion
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Julian Bayliss, Gabriela B. Bittencourt-Silva, William R. Branch, Carl Bruessow, Steve Collins, T. Colin E. Congdon, Werner Conradie, Michael Curran, Savel R. Daniels, Iain Darbyshire, Harith Farooq, Lincoln Fishpool, Geoffrey Grantham, Zacharia Magombo, Hermenegildo Matimele, Ara Monadjem, Jose Monteiro, Jo Osborne, Justin Saunders, Paul Smith, Claire N. Spottiswoode, Peter J. Taylor, Jonathan Timberlake, Krystal A. Tolley, Érica Tovela, and Philip J. Platts
- Subjects
Medicine ,Science - Abstract
Abstract Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the ‘South East Africa Montane Archipelago’ (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains’ great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)—one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.
- Published
- 2024
- Full Text
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11. Diet components associated with specific bacterial taxa shape overall gut community compositions in omnivorous African viverrids
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Malou B. Storm, Emilia M. R. Arfaoui, Phumlile Simelane, Jason Denlinger, Celine Alfredo Dias, Ana Gledis daConceição, Ara Monadjem, Kristine Bohmann, Michael Poulsen, and Kasun H. Bodawatta
- Subjects
Civettictis ,Genetta ,gut microbiome ,metabarcoding ,omnivores ,southern Africa ,Ecology ,QH540-549.5 - Abstract
Abstract Gut bacterial communities provide flexibility to hosts during dietary changes. Despite the increasing number of studies exploring the associations between broader dietary guilds of mammalian hosts and their gut bacteria, it is generally unclear how diversity and variability in consumed diets link to gut bacterial taxa in wild non‐primate mammals, particularly in omnivores. Here, we contribute to filling this gap by exploring consumed diets and gut bacterial community compositions with metabarcoding of faecal samples for two African mammals, Civettictis civetta and Genetta spp., from the family Viverridae. For each individual sample, we characterised bacterial communities and identified dietary taxa by sequencing vertebrate, invertebrate and plant markers. This led us to establish diet compositions that diverged from what has previously been found from visual identification methods. Specifically, while the two genera have been categorised into the same dietary guild, we detected more animal dietary items than plant items in C. civetta, while in Genetta spp., we observed the opposite. We further found that individuals with similar diets have similar gut bacterial communities within both genera. This association tended to be driven by specific links between dietary items and gut bacterial genera, rather than communities as a whole, implying diet‐driven selection for specific gut microbes in individual wild hosts. Our findings underline the importance of molecular tools for improving characterisations of omnivorous mammalian diets and highlight the opportunities for simultaneously disentangling links between diets and gut symbionts. Such insights can inform robustness and flexibility in host‐microbe symbioses to dietary change associated with seasonal and habitat changes.
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- 2024
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12. The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses
- Author
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Hayley S. Clements, Emmanuel Do Linh San, Gareth Hempson, Birthe Linden, Bryan Maritz, Ara Monadjem, Chevonne Reynolds, Frances Siebert, Nicola Stevens, Reinette Biggs, Alta De Vos, Ryan Blanchard, Matthew Child, Karen J. Esler, Maike Hamann, Ty Loft, Belinda Reyers, Odirilwe Selomane, Andrew L. Skowno, Tshegofatso Tshoke, Diarrassouba Abdoulaye, Thierry Aebischer, Jesús Aguirre-Gutiérrez, Graham J. Alexander, Abdullahi H. Ali, David G. Allan, Esther E. Amoako, Samuel Angedakin, Edward Aruna, Nico L. Avenant, Gabriel Badjedjea, Adama Bakayoko, Abraham Bamba-kaya, Michael F. Bates, Paul J. J. Bates, Steven R. Belmain, Emily Bennitt, James Bradley, Chris A. Brewster, Michael B. Brown, Michelle Brown, Josef Bryja, Thomas M. Butynski, Filipe Carvalho, Alan Channing, Colin A. Chapman, Callan Cohen, Marina Cords, Jennifer D. Cramer, Nadine Cronk, Pamela M. K. Cunneyworth, Fredrik Dalerum, Emmanuel Danquah, Harriet T. Davies-Mostert, Andrew D. de Blocq, Yvonne A. De Jong, Terrence C. Demos, Christiane Denys, Chabi A. M. S. Djagoun, Thomas M. Doherty-Bone, Marine Drouilly, Johan T. du Toit, David A. Ehlers Smith, Yvette C. Ehlers Smith, Seth J. Eiseb, Peter J. Fashing, Adam W. Ferguson, José M. Fernández-García, Manfred Finckh, Claude Fischer, Edson Gandiwa, Philippe Gaubert, Jerome Y. Gaugris, Dalton J. Gibbs, Jason S. Gilchrist, Jose M. Gil-Sánchez, Anthony N. Githitho, Peter S. Goodman, Laurent Granjon, J. Paul Grobler, Bonginkosi C. Gumbi, Vaclav Gvozdik, James Harvey, Morgan Hauptfleisch, Firas Hayder, Emmanuel M. Hema, Marna Herbst, Mariano Houngbédji, Brian J. Huntley, Rainer Hutterer, Samuel T. Ivande, Kate Jackson, Gregory F. M. Jongsma, Javier Juste, Blaise Kadjo, Prince K. Kaleme, Edwin Kamugisha, Beth A. Kaplin, Humphrey N. Kato, Christian Kiffner, Duncan M. Kimuyu, Robert M. Kityo, N’goran G. Kouamé, Marcel Kouete T, Aliza le Roux, Alan T. K. Lee, Mervyn C. Lötter, Anne Mette Lykke, Duncan N. MacFadyen, Gacheru P. Macharia, Zimkitha J. K. Madikiza, Themb’alilahlwa A. M. Mahlaba, David Mallon, Mnqobi L. Mamba, Claude Mande, Rob A. Marchant, Robin A. Maritz, Wanda Markotter, Trevor McIntyre, John Measey, Addisu Mekonnen, Paulina Meller, Haemish I. Melville, Kevin Z. Mganga, Michael G. L. Mills, Liaan Minnie, Alain Didier Missoup, Abubakr Mohammad, Nancy N. Moinde, Bakwo Fils E. Moise, Pedro Monterroso, Jennifer F. Moore, Simon Musila, Sedjro Gilles A. Nago, Maganizo W. Namoto, Fatimata Niang, Violaine Nicolas, Jerry B. Nkenku, Evans E. Nkrumah, Gonwouo L. Nono, Mulavwa M. Norbert, Katarzyna Nowak, Benneth C. Obitte, Arnold D. Okoni-Williams, Jonathan Onongo, M. Justin O’Riain, Samuel T. Osinubi, Daniel M. Parker, Francesca Parrini, Mike J. S. Peel, Johannes Penner, Darren W. Pietersen, Andrew J. Plumptre, Damian W. Ponsonby, Stefan Porembski, R. John Power, Frans G. T. Radloff, Ramugondo V. Rambau, Tharmalingam Ramesh, Leigh R. Richards, Mark-Oliver Rödel, Dominic P. Rollinson, Francesco Rovero, Mostafa A. Saleh, Ute Schmiedel, M. Corrie Schoeman, Paul Scholte, Thomas L. Serfass, Julie Teresa Shapiro, Sidney Shema, Stefan J. Siebert, Jasper A. Slingsby, Alexander Sliwa, Hanneline A. Smit-Robinson, Etotepe A. Sogbohossou, Michael J. Somers, Stephen Spawls, Jarryd P. Streicher, Lourens Swanepoel, Iroro Tanshi, Peter J. Taylor, William A. Taylor, Mariska te Beest, Paul T. Telfer, Dave I. Thompson, Elie Tobi, Krystal A. Tolley, Andrew A. Turner, Wayne Twine, Victor Van Cakenberghe, Frederik Van de Perre, Helga van der Merwe, Chris J. G. van Niekerk, Pieter C. V. van Wyk, Jan A. Venter, Luke Verburgt, Geraldine Veron, Susanne Vetter, Maria S. Vorontsova, Thomas C. Wagner, Paul W. Webala, Natalie Weber, Sina M. Weier, Paula A. White, Melissa A. Whitecross, Benjamin J. Wigley, Frank J. Willems, Christiaan W. Winterbach, and Galena M. Woodhouse
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Science - Abstract
Abstract Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.
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- 2024
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13. IUCN Red List Training and Assessment Workshop for Africa's bats, Namibia
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Simon Mickleburgh, David L. Waldien, Ara Monadjem, and Rachael Cooper-Bohannon
- Subjects
General. Including nature conservation, geographical distribution ,QH1-199.5 - Published
- 2024
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14. Structure–Activity Relationship Studies on a Series of 3α-[Bis(4-fluorophenyl)methoxy]tropanes and 3α-[Bis(4-fluorophenyl)methylamino]tropanes As Novel Atypical Dopamine Transporter (DAT) Inhibitors for the Treatment of Cocaine Use Disorders
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Zou, Mu-Fa, Cao, Jianjing, Abramyan, Ara M., Kopajtic, Theresa, Zanettini, Claudio, Guthrie, Daryl A., Rais, Rana, Slusher, Barbara S., Shi, Lei, Loland, Claus J., and Newman, Amy Hauck
- Abstract
The development of medications to treat cocaine use disorders has thus far defied success, leaving this patient population without pharmacotherapeutic options. As the dopamine transporter (DAT) plays a prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and based on its pharmacological profile, the lead compound 10awas evaluated in phase I metabolic stability studies in mouse liver microsomes and compared to cocaine in locomotor activity and drug discrimination paradigms in mice. A molecular dynamic simulation study supported the hypothesis that atypical DAT inhibitors have similar binding poses at DAT in a conformation that differs from that of cocaine. Such differences may ultimately contribute to their unique behavioral profiles and potential for development as cocaine use disorder therapeutics.
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- 2024
- Full Text
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15. Large-scale analysis of the integration of enhancer-enhancer signals by promoters.
- Author
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Martinez-Ara M, Comoglio F, and van Steensel B
- Subjects
- Animals, Mice, Mouse Embryonic Stem Cells metabolism, Genes, Reporter, Gene Expression Regulation, Promoter Regions, Genetic, Enhancer Elements, Genetic genetics
- Abstract
Genes are often regulated by multiple enhancers. It is poorly understood how the individual enhancer activities are combined to control promoter activity. Anecdotal evidence has shown that enhancers can combine sub-additively, additively, synergistically, or redundantly. However, it is not clear which of these modes are more frequent in mammalian genomes. Here, we systematically tested how pairs of enhancers activate promoters using a three-way combinatorial reporter assay in mouse embryonic stem cells. By assaying about 69,000 enhancer-enhancer-promoter combinations we found that enhancer pairs generally combine near-additively. This behaviour was conserved across seven developmental promoters tested. Surprisingly, these promoters scale the enhancer signals in a non-linear manner that depends on promoter strength. A housekeeping promoter showed an overall different response to enhancer pairs, and a smaller dynamic range. Thus, our data indicate that enhancers mostly act additively, but promoters transform their collective effect non-linearly., Competing Interests: MM, Bv No competing interests declared, FC co-founder of enGene Statistics GmbH, (© 2023, Martinez-Ara et al.)
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- 2024
- Full Text
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16. Unusual rapid development of portopulmonary hypertension after shunt closure for congenital portosystemic shunt.
- Author
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Honda S, Kawakita I, Okumura K, Ara M, Goto R, Takeda A, Shimamura T, Kawahara I, and Taketomi A
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- Humans, Hypertension, Portal etiology, Hypertension, Portal surgery, Portasystemic Shunt, Surgical methods, Male, Female, Postoperative Complications etiology, Infant, Hypertension, Pulmonary etiology
- Published
- 2024
- Full Text
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17. Design and preparation of a novel Mg-Al LDH@EDTA-Melamine nanocomposite for effective adsorptive removal of methylene blue and rhodamine B dyes from water.
- Author
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Ara M and Ghafuri H
- Abstract
This paper deals with the preparation of a novel nanocomposite consisted of magnesium-aluminum layered double hydroxide (Mg-Al LDH) and ethylenediaminetetraacetic acid (EDTA) as well as melamine (MA) as an adsorbent. This nanocomposite was utilized to adsorb different dyes such as rhodamine B (RhB) and methylene blue (MB) from water. The prepared adsorbent was characterized using FT-IR, EDS, XRD, TGA, and FE-SEM analyses. The effects of various parameters such as concentration, time, adsorbent dosage, temperature, and pH were tested to investigate their influence on adsorption conditions. Both methylene blue and rhodamine B dyes showed pseudo-second-order adsorption kinetics, and their adsorption followed the Langmuir isotherm. Moreover, the maximum adsorption capacities for methylene blue and rhodamine B were found to be 1111.103 mg/g at 45 °C and 232.558 mg/g at 60 °C, respectively. Additionally, the adsorption processes were found to be spontaneous (ΔG°< 0, for both dyes) and exothermic (ΔH° = -12.42 kJ/mol for methylene blue and ΔH° = -25.84 kJ/mol for rhodamine B) for both dyes. Hydrogen bonding and electrostatic forces are responsible for the interactions occur between the nanocomposite and the functional groups in the dyes. The experimental findings demonstrated a greater adsorption rate of MB than RhB, suggesting the adsorbent's stronger affinity for MB. This preference is likely due to MB's size, specific functional groups, and smaller molecule size, enabling stronger interactions and more efficient access to adsorption sites compared to RhB. Even after recycling 4 times, the dye adsorption percentages of the adsorbent for MB and RhB dyes were 90 % and 87 %, but the desorption percentages of the adsorbate dyes were 85 % and 80 %, respectively. The prepared adsorbent boasts several unique properties, such as the swift and effortless adsorption of MB and RhB dyes, straightforward synthesis, mild adsorption conditions, remarkable efficiency, and the ability to be recycled up to 4 times without a significant decrease in activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
18. Incorporation of Multiple β 2 -Hydroxy Acids into a Protein In Vivo Using an Orthogonal Aminoacyl-tRNA Synthetase.
- Author
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Hamlish NX, Abramyan AM, Shah B, Zhang Z, and Schepartz A
- Abstract
The programmed synthesis of sequence-defined biomaterials whose monomer backbones diverge from those of canonical α-amino acids represents the next frontier in protein and biomaterial evolution. Such next-generation molecules provide otherwise nonexistent opportunities to develop improved biologic therapies, bioremediation tools, and biodegradable plastic-like materials. One monomer family of particular interest for biomaterials includes β-hydroxy acids. Many natural products contain isolated β-hydroxy acid monomers, and polymers of β-hydroxy acids (β-esters) are found in polyhydroxyalkanoate (PHA) polyesters under development as bioplastics and drug encapsulation/delivery systems. Here we report that β
2 -hydroxy acids possessing both ( R ) and ( S ) absolute configuration are substrates for pyrrolysyl-tRNA synthetase (PylRS) enzymes in vitro and that ( S )-β2 -hydroxy acids are substrates in cellulo . Using the orthogonal Ma PylRS/ Ma tRNAPyl synthetase/tRNA pair, in conjunction with wild-type E. coli ribosomes and EF-Tu, we report the cellular synthesis of model proteins containing two ( S )-β2 -hydroxy acid residues at internal positions. Metadynamics simulations provide a rationale for the observed preference for the ( S )-β2 -hydroxy acid and provide mechanistic insights that inform future engineering efforts. As far as we know, this finding represents the first example of an orthogonal synthetase that acylates tRNA with a β2 -hydroxy acid substrate and the first example of a protein hetero-oligomer containing multiple expanded-backbone monomers produced in cellulo ., Competing Interests: The authors declare the following competing financial interest(s): N.X.H. and A.S. are coinventors on an international patent application that incorporates methods outlined in this manuscript., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
- Full Text
- View/download PDF
19. SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma.
- Author
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Fujiyoshi S, Honda S, Ara M, Kondo T, Kobayashi N, and Taketomi A
- Abstract
Background: Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based chemotherapy; however, 22.3% of patients develop cisplatin resistance and thus face a poor prognosis. We hypothesized that glucose transporters are associated with acquiring cisplatin resistance with increasing sugar intake inhibiting glucose transporters could reduce cisplatin resistance in hepatoblastoma patients., Methods: We established cisplatin-resistant HepG2 and HuH6 cells by continuous treatment with cisplatin. We evaluated the relationship between cisplatin resistance and glucose uptake. We used an expression array to select cisplatin-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo., Results: We found a strong relationship between cisplatin resistance and glucose uptake. Additionally, SGLT2 was upregulated in resistant cells after cisplatin treatment. After dapagliflozin treatment, glucose uptake and cisplatin resistance decreased in resistant cells., Conclusions: Cisplatin-resistant hepatoblastoma cells exhibited upregulated SGLT2 expression and activated glucose uptake to survive under cisplatin stress. SGLT2 inhibition decreased cellular resistance to cisplatin. SGLT2 inhibition with cisplatin therapy could be a novel therapeutic strategy for cisplatin-resistant hepatoblastoma patients., (© 2023 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)
- Published
- 2024
- Full Text
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20. Subcutaneous injection of lidocaine around ischemic ankle provides safe and effective foot analgesia in patients with critical limb ischemia.
- Author
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Kanai A, Ara M, Saito R, Mishima T, and Takahashi Y
- Abstract
Objective: It is often difficult to alleviate foot pain associated with critical limb ischemia (CLI) using common analgesics. Neuraxial block is contraindicated in anticoagulant therapy. This study was designed to determine the response to subcutaneous injection of lidocaine around the network of peripheral nerves around the ankle in patients with CLI pain on anticoagulants and antiplatelets., Methods: Sixteen patients with CLI pain in the foot were enrolled in this double-blind placebo-controlled crossover study. Patients were randomized to receive either 2% lidocaine or saline via catheters inserted into the subcutaneous area around the ankle. After recurrence of pain, the patients were crossed over to receive the alternative treatment. Pain was assessed with a numerical rating scale (NRS) before and 15 min after injection. Patients used a descriptive scale to grade pain control and were asked to determine the duration of analgesia in each arm of the study., Results: No serious complications including protracted bleeding occurred. Lidocaine significantly decreased the NRS on movement from 10 (6, 10) [median (range)] to 2 (0, 10) ( p < .001), and the differences in the Δ change in NRS between lidocaine and placebo were significant ( p = .009). Of the 16 patients, 14 patients were very satisfied after lidocaine but only one described the same after saline. The effect of lidocaine and placebo lasted 11 (0, 28) and 1 (0, 22) h, respectively., Conclusion: Subcutaneous injection of lidocaine around the ischemic ankle affectively alleviated pain in patients with CLI without serious adverse effects under anticoagulant therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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21. Asenapine versus olanzapine for the treatment of nausea and vomiting in patients with cancer: A retrospective study.
- Author
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Kimura T, Kanai A, Muraoka H, Takahashi Y, Ara M, and Inada K
- Subjects
- Humans, Olanzapine, Retrospective Studies, Vomiting chemically induced, Vomiting drug therapy, Nausea chemically induced, Nausea drug therapy, Antiemetics adverse effects, Neoplasms chemically induced, Dibenzocycloheptenes
- Abstract
Aim: Patients with cancer often experience nausea and vomiting (N/V), but may have difficulty using olanzapine (OLZ), a common antiemetic. Asenapine (ASE) is a multi-acting receptor-targeted antipsychotic like OLZ, although there is little evidence that ASE serves as an antiemetic. The aim of this study was to evaluate the efficacy and tolerability of ASE compared to those of OLZ for the treatment of N/V in patients with cancer., Methods: This retrospective study involved patients who received 5 mg ASE, 5 mg OLZ, or 2.5 mg OLZ for 2 days. Daily worst N/V was rated on a scale of 0 (none) to 3 (very much). The primary endpoint was the proportion of patients who had a response, defined as any reduction in N/V score. A complete response (CR) was defined as a score reduction to 0. Secondary endpoints included the proportion of patients with CR and adverse events., Results: Between April 2017 and March 2023, 212 patients were enrolled to receive treatment: 5 mg ASE (n = 34), 5 mg OLZ (n = 102), or 2.5 mg OLZ (n = 76). No significant differences in response rates (52.9% vs. 58.8% vs. 52.6%, p = 0.671) or secondary endpoints were observed between the groups. Patients receiving ASE were more likely to experience oral hypoesthesia (p = 0.004)., Conclusion: This preliminary study suggests that ASE may be effective for N/V. Further studies are required to confirm these findings., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)
- Published
- 2024
- Full Text
- View/download PDF
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