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1. Two gates mediate NMDA receptor activity and are under subunit-specific regulation

Author

Johansen B. Amin, Miaomiao He, Ramesh Prasad, Xiaoling Leng, Huan-Xiang Zhou, and Lonnie P. Wollmuth

Subjects
Science
Abstract

NMDA receptors are glutamate-gated ion channels that regulate fast signaling in the brain. Here, the authors show that the opening and closing patterns of the channel derive from the action of two gates that are regulated by distinct subunits.

Published
2023
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2. Anti-Inflammatory and Antiviral Osmotic Polymeric Film to Treat Covid-19 Early-Stage Infection

Author

Shrivastava R, Johansen B, and Allain T

Subjects
filmogen glycerol, antiviral, anti-cytokines, anti-inflammatory, covid-19, s1, rbd, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Ravi Shrivastava,1 Remi Shrivastava,1 Bianca Johansen,1 Thibault Allain2,3 1VITROBIO Research Institute, Issoire, 63500, France; 2Laboratoire SANABEL, Paris, 75011, France; 3UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, Toulouse, FranceCorrespondence: Ravi Shrivastava Email rs@vitrobio.comBackground: Covid-19 infection starts in the nasal cavity when viral S1 and RBD proteins bind to the host cell ACE2 receptors, the virus multiplies, causes cell lysis, and enters the circulation. This triggers a strong cytokine release and inflammation of the nasal mucosa. A multitarget approach of cleaning the nasal mucosa and suppressing chances of nasal and systemic inflammation should minimize severe respiratory consequences. Unfortunately, no such treatments are yet available.Methods: We describe the conception of an osmotic polymeric film using an in vitro nasal mucosa mimicking model, containing polymers to neutralize Covid-19 specific viral S1, RBD proteins and selected proinflammatory cytokines.Results: The filmogen barrier forms a stable and osmotic film on the nasal mucosa. Hypotonic liquid exudation from the nasal surface detaches and drains the inflammatory cytokines and other contaminants towards the film where selected polymers bind and neutralize SARS-CoV-2 spike S1 and RBD protein as well as Covid-19 disease-specific key pro-inflammatory IL-6, TNF-α, IL-10, IL-13, and GM-CSF cytokines.Conclusion: Minimizing the nasal surface concentration of pro-inflammatory cytokines and viruses should help nasal mucosa repair and avoid immune stress. This nearly instant, simple, scientific, safe, and logical approach should help attenuate Covid-19 induced systemic inflammation at an early stage without being affected by viral S1 spike protein mutations.Keywords: filmogen glycerol, antiviral, anti-cytokines, anti-inflammatory, Covid-19, S1, RBD

Published
2021

3. A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high Ca2+ permeability

Author

Johansen B. Amin, Xiaoling Leng, Aaron Gochman, Huan-Xiang Zhou, and Lonnie P. Wollmuth

Subjects
Science
Abstract

Little is known about the impact of de novo and inherited missense mutations in the NMDA receptor M4 transmembrane helices. In this study, the authors use functional and computational approaches to demonstrate how mutations to conserved glycine sites within this region cause structural rearrangement, altered receptor deactivation and calcium permeability.

Published
2018
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4. A Swiss army knife for targeting receptors

Author

Johansen B Amin and Lonnie P Wollmuth

Subjects
NMDA receptor, allosteric modulator, pharmacology, neurotransmitter, glutamate, Medicine, Science, Biology (General), QH301-705.5
Abstract

A compound can change the activity of NMDA receptors in some regions of a synapse without affecting those in other regions.

Published
2018
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6. Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate collagen-induced arthritis

Author

Feuerherm, AJ, Dennis, EA, and Johansen, B

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Arthritis, Autoimmune Disease, Aetiology, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Inflammatory and immune system, Animals, Antirheumatic Agents, Arachidonic Acid, Arthritis, Experimental, Cell Line, Tumor, Dinoprostone, Etanercept, Fatty Acids, Omega-3, Group IV Phospholipases A2, Humans, Male, Methotrexate, Mice, Inbred DBA, Molecular Structure, Synovial Membrane, cPLA2 alpha, Disease-modifying, Anti-rheumatic, Small molecule inhibitors, cPLA2α, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

BackgroundCytosolic phospholipase A2 group IVA (cPLA2α)-deficient mice are resistant to collagen-induced arthritis, suggesting that cPLA2α is an important therapeutic target. Here, the anti-inflammatory effects of the AVX001 and AVX002 cPLA2α inhibitors were investigated.MethodsIn vitro enzyme activity was assessed by a modified Dole assay. Effects on inhibiting IL-1β-induced release of arachidonic acid (AA) and prostaglandin E2 (PGE2) were measured using SW982 synoviocyte cells. In vivo effects were studied in prophylactic and therapetic murine collagen-induced arthritis models and compared to methotrexate (MTX) and Enbrel, commonly used anti-rheumatic drugs. The in vivo response to treatment was evaluated in terms of the arthritis index (AI), histopathology scores and by plasma levels of PGE2 following 14 and 21 days of treatment.ResultsBoth cPLA2α inhibitors are potent inhibitors of cPLA2α in vitro. In synoviocytes, AVX001 and AVX002 reduce, but do not block, release of AA or PGE2 synthesis. In both CIA models, the AI and progression of arthritis were significantly lower in the mice treated with AVX001, AVX002, Enbrel and MTX than in non- treated mice. Several histopathology parameters of joint damage were found to be significantly reduced by AVX001 and AVX002 in both prophylactic and therapeutic study modes; namely articular cavity and peripheral tissue inflammatory cell infiltration; capillary and synovial hyperplasia; articular cartilage surface damage; and periostal and endochondral ossification. In comparison, MTX did not significantly improve any histopathology parameters and Enbrel only improved ossification. Finally, as a biomarker of inflammation and as an indication that AVX001 and AVX002 blocked the cPLA2α target, we determined that plasma levels of PGE2 were significantly reduced in response to the AVX inhibitors and MTX, but not Enbrel.ConclusionsAVX001 and AVX002 display potent anti-inflammatory activity and disease-modifying properties in cellular and in vivo models. The in vivo effects of AVX001 and AVX002 were comparable to, or superior, to those of MTX and Enbrel. Taken together, this study suggests that cPLA2α inhibitors AVX001 and AVX002 are promising small molecule disease-modifying anti-rheumatic therapies.

Published
2019

14. Parenting Styles and Influences of Millennial Parents in the Development of Values System of Grade 7 Learners in Negros Occidental: A Case Study.

Author

Alsagon Jr., Carlito A., Ganancial, Kareen C., Taparan, Janeth G., and Caluza, Las Johansen B.

Subjects
PARENTAL influences, AUTHORITATIVE parenting, SYSTEMS development, CHILD development, VALUES (Ethics), SELF-control, PARENTING, RESPECT
Abstract

This qualitative research determined the parenting styles and influences of millennial parents in the values development system of Grade 7 learners in Negros Occidental: A case study. Diana Baumrind describes three parenting styles that affect the values development of children (Santrock, 2017) but in Nancy Darling (1999) cited by Situmorang (2021) in his study perceived parenting styles urges that parenting styles focus on four typologies; authoritative, authoritarian, indulgent and uninvolved. Influences of millennial parents in terms of character and religious aspects of millennial parents (Moriss, 2022) may have a role in the values development system for their children. A case study approach was used to gather primary data through in- depth interviews with our ten (10) millennial participants in Negros Occidental. Thematic analysis was used to analyze the classifications and present themes or patterns that relate to the data with the following steps: finalizing data, assigning preliminary code, searching for themes, reviewing themes, defining and naming themes, and producing reports (Braun & Clarke, 2006). The findings revealed that the majority of the study concluded that the authoritative parenting style is the parenting style of millennial parents prefer to employ, which affects or influence the values development system of their children positively. The study shows that the love, respect, open communication, and self-discipline of millennial parents influence the opportunities to improve their children's family significantly in helping their children build and refine their positive values development system. The study was organized into five parts. First, the introduction. Second, the theoretical framework. Third part is the review of the related literature about parenting styles, values development system, and influences of millennial parents. Fourth part is the purpose of the study and the research questions. The fifth part is the Research methodology which includes research design and research procedure and sampling. The sixth part is the results and discussion. Lastly, are the conclusion and recommendations of the research. [ABSTRACT FROM AUTHOR]

Published
2023
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15. From bedside‐to‐bench: What disease‐associated variants are teaching us about the NMDA receptor

Author

Lonnie P. Wollmuth, Johansen B. Amin, and Gabrielle Moody

Subjects
0301 basic medicine, biology, Physiology, business.industry, Glutamic Acid, GRIN1, Drug design, Gating, Receptors, N-Methyl-D-Aspartate, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, nervous system, biology.protein, Humans, GRIN2A, GRIN2B, Personalized medicine, Receptor, business, Neuroscience, 030217 neurology & neurosurgery, Function (biology), Signal Transduction
Abstract

NMDA receptors (NMDARs) are glutamate-gated ion channels that contribute to nearly all brain processes. Not surprisingly then, genetic variations in the genes encoding NMDAR subunits can be associated with neurodevelopmental, neurological and psychiatric disorders. These disease-associated variants (DAVs) present challenges, such as defining how DAV-induced alterations in receptor function contribute to disease progression and how to treat the affected individual clinically. As a starting point to overcome these challenges, we need to refine our understanding of the complexity of NMDAR structure function. In this regard, DAVs have expanded our knowledge of NMDARs because they do not just target well-known structure-function motifs, but rather give an unbiased view of structural elements that are important to the biology of NMDARs. Indeed, established NMDAR structure-function motifs have been validated by the appearance of disorders in patients where these motifs have been altered, and DAVs have identified novel structural features in NMDARs such as gating triads and hinges in the gating machinery. Still, the majority of DAVs remain unexplored and occur at sites in the protein with unidentified function or alter receptor properties in multiple and unanticipated ways. Detailed mechanistic and structural investigations are required of both established and novel motifs to develop a highly refined pathomechanistic model that accounts for the complex machinery that regulates NMDARs. Such a model would provide a template for rational drug design and a starting point for personalized medicine.

Published
2020
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20. A topic modeling analysis on the early phase of COVID-19 response in the Philippines

Author

Las Johansen B. Caluza, Joshua Francisco Vibar Neo, and Ginbert Permejo Cuaton

Subjects
Topic model, Economic growth, 010504 meteorology & atmospheric sciences, Philippines, 0211 other engineering and technologies, Globe, 02 engineering and technology, 01 natural sciences, Article, Political science, Pandemic, Machine learning, medicine, 0105 earth and related environmental sciences, Militarization, 021110 strategic, defence & security studies, Government, COVID-19, Geology, Building and Construction, Government response, Geotechnical Engineering and Engineering Geology, Livelihood, medicine.anatomical_structure, Securitization, Safety Research, Administration (government)
Abstract

Like many others across the globe, Filipinos continue to suffer from the COVID-19 pandemic. To shed light on how the Philippines initially managed the disease, our paper analyzed the early phase of the government's pandemic response. Using machine learning, we compiled the official press releases issued by the Department of Health from early January to mid-April 2020 where a total of 283,560 datasets amounting to 2.5 megabytes (Mb) were analyzed using the Latent Dirichlet Allocation (LDA) algorithm. Our results revealed five latent themes: the highest effort (40%) centered on "Nationwide Reporting of COVID-19 Status", while "Contact Tracing of Suspected and Infected Individuals" had the least focus at only 11.68%- indicating a lack of priority in this area. Our findings suggest that while the government was ill-prepared in the early phase of the pandemic, it exerted efforts in rearranging its fiscal and operational priorities toward the management of the disease. However, we emphasize that this article should be read and understood with caution. More than a year has already passed since the outbreak in the country and many (in)actions and challenges have adversely impacted its response. These include the Duterte administration's securitization and militarization of pandemic response and its apparent failure to find a balance between the lives and livelihoods of Filipinos, to name a few. We strongly recommend that other scholars study the various aspects of the government's response, i.e., economic, peace and security, agriculture, and business, to assess better how the country responded and continually responds to the pandemic.

Published
2021

22. Needs Assessment of Grade 8 Instructional Materials in Teaching Filipino: A Phenomenology

Author

Las Johansen B. Caluza, Mary Anne C. Sedanza, and Camille N. Dumpang

Subjects
Phenomenology (philosophy), Nonprobability sampling, Medical education, Instructional design, Process (engineering), Needs assessment, ComputingMilieux_COMPUTERSANDEDUCATION, Face (sociological concept), Achievement test, Subject (documents), Psychology, Education, Needs Assessment, Instructional Materials, Qualitative Single Case Study, Leyte, Philippines
Abstract

Instructional materials are the tools used to educate learners and help the teaching-learning process be more effective and meaningful. However, teachers face problems regarding sources of information or materials to be used in instruction especially those teaching in public schools. Using a qualitative single-case study design, this study aims to determine the available instructional materials used by the Filipino Subject Teacher in a National High School which was identified by the City Division to be one of the low performing schools in the city based on the National Achievement Test 2016. This study will use purposive sampling and the use of semi-structured interviews as it links to Instructional Design Theory that worries how the student is going to learn and not more than what the student is going to learn. Results of this study could provide necessary assistance or school intervention for teachers teaching Filipino subject.

Published
2021

23. Evaluating the Kindergarten Instructional Materials: Inputs for Materials Production

Author

Majean R. Placigo, Las Johansen B. Caluza, and Ma. Rebecca A. Abayan

Subjects
Nonprobability sampling, Resource (project management), Meaningful learning, Process (engineering), ComputingMilieux_COMPUTERSANDEDUCATION, Mathematics education, Production (economics), Psychology, Experiential learning, Effective teaching, Qualitative research
Abstract

Instructional materials are tools necessary in making the teaching-learning process effective and meaningful for the learners. They help enhance instruction thereby uplifting the students’ knowledge, skills and abilities. However, teachers experience problems pertaining to lack of appropriate and rich resource of instructional materials, thereby limiting their capacity to provide meaningful learning opportunities. This is a qualitative research which aimed to find out the availability of teaching materials in the Kindergarten classes of a public elementary school. It is grounded on the experiential learning theory in using instructional materials through concrete experience. Employing the single-case study design, it further tried to determine the challenges experienced by the teachers in the production of instructional materials. The purposive sampling technique was employed to select the participants, who are all Kindergarten teachers. The findings revealed that the Kindergarten classrooms lacked developmentally appropriate materials necessary for effective teaching and learning, and teachers are burdened in the production of teaching materials due to some factors. Results of this study will provide inputs in the production of instructional materials for Kindergarten.

Published
2021
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24. Needs-Based Assessment of Instructional Materials in the Kindergarten Level: A Husserlian Phenomenology Study

Author

Las Johansen B. Caluza, MA.Ed . Ma. Christina A. Gallaza, and Lpt . Kathy N. Garcia

Subjects
Phenomenology (philosophy), Nonprobability sampling, Process (engineering), Instructional design, ComputingMilieux_COMPUTERSANDEDUCATION, Learning theory, Mathematics education, Psychology, Phenomenological method
Abstract

Instructional materials come in many shapes and sizes but they have one thing in common, the ability to support the students’ learning. The prevailing purpose of this study is to seek the insights of the classroom teachers on the available instructional materials used in teaching Kindergarten in a certain public elementary school in Tacloban City Division and the participants will be selected through purposive sampling. This study is supported by the Meaningful Reception Learning Theory of David Ausubel which states that teachers or instructional designers can best arrange the conditions that facilitate learning for students. This study utilized the Husserlian phenomenological design using Colaizzi's descriptive phenomenological method of data analysis through semi-structured interviews. The result of this study could provide insights on the available instructional materials in a Kindergarten classroom and what other materials could be produced to aid in the teaching process.

Published
2021
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25. Fuzzy Unordered Rule Induction Algorithm Application Basic Programming Language Competence: A Rule-Based Model

Author

Las Johansen B. Caluza

Subjects
Data processing, Multidisciplinary, Data collection, business.industry, Computer science, Information technology, Rule-based system, 02 engineering and technology, Machine learning, computer.software_genre, Fuzzy logic, 030507 speech-language pathology & audiology, 03 medical and health sciences, Cohen's kappa, Cronbach's alpha, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, Artificial intelligence, 0305 other medical science, business, Competence (human resources), computer
Abstract

Objective: A rule-based model using Fuzzy Unordered Rule Induction Algorithm (FURIA) aimed to be developed in this study. Methods/Statistical Analysis: This study utilized a Machine-Learning algorithm called FURIA in developing the model. Graduates of the K to 12 programs in the Philippines who enrolled in the Bachelor of Science in Information Technology in a State University were the respondents of this study. Respondents were assessed using a self-made questionnaire in basic programming using Java programming language and validated both face validation and the internal reliability test with a Cronbach alpha value of 83. Furthermore, the steps performed in this study were the variable definition and data collection, data processing and cleaning, machine-learning algorithm application, verifying and interpreting the model, and reporting the model and synthesizing. Findings: This study revealed seven (7) rule-based models with a substantial rating in Kappa statistics and a very high accuracy rating in predicting the competencies by class. Applications/ Improvements: The researcher believed the need to unveil the competence of the Senior High School graduates in the K to 12 programs of the Department of Education in the Philippines in basic programming, which aimed to retool the type of teaching strategies to fit the competencies of the student. Keywords: Basic Programming, Competence, Data Mining, Fuzzy Algorithm, Fuzzy Unordered Rule Induction Algorithm (FURIA), Machine Learning, Rule Model

Published
2019
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26. NMDA receptors require multiple pre-opening gating steps for efficient synaptic activity

Author

Johansen B. Amin, Noele Certain, Miaomiao He, Lonnie P. Wollmuth, and Aaron Gochman

Subjects
Models, Molecular, 0301 basic medicine, Nervous system, Agonist, medicine.drug_class, Glutamic Acid, Gating, Neurotransmission, Receptors, N-Methyl-D-Aspartate, Synaptic Transmission, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Ion channel, Chemistry, General Neuroscience, Glutamate receptor, Transmembrane protein, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, Synapses, Helix, Biophysics, NMDA receptor, Ion Channel Gating, Neuroscience, 030217 neurology & neurosurgery
Abstract

NMDA receptors (NMDAR) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission in the nervous system. A central feature of NMDAR physiology is the opening of the ion channel driven by presynaptically-released glutamate. Using glutamate applications to outside-out patches containing a single NMDAR in the continuous presence of the co-agonist glycine, we find that agonist-bound receptors transition to the open state via two conformations, an ‘unconstrained pre-active’ state that can rapidly transition to the open state and contributes to synaptic events, and a ‘constrained pre-active’ state that requires more energy and hence time to open and does not contribute to fast signaling. To define how agonist binding might drive these conformations, we decoupled the ligand-binding domains from specific transmembrane segments for the GluN1 and GluN2A subunits. Displacements of the central pore-forming M3 segments define the energy of fast channel opening. However, to enter the unconstrained conformation and contribute to fast signaling, a peripheral helix, the GluN2 pre-M1, must be displaced before the M3 segments move. This pre-M1 displacement is facilitated by the flexibility of another nearby peripheral element, the GluN1 and GluN2A S2-M4. We conclude that peripheral structural elements – pre-M1 and S2-M4 – work in concert to remove constraints and prime the channel for rapid opening, thus facilitating fast synaptic transmission.

Published
2020
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32. Predicting Teachers� ICT Competence in a Philippine University Using J48 Algorithm

Author

Las Johansen B. Caluza

Subjects
Multidisciplinary, Computer science, business.industry, 05 social sciences, Decision tree, 050301 education, Information technology, 02 engineering and technology, Decision rule, Blended learning, C4.5 algorithm, Information and Communications Technology, 020204 information systems, ComputingMilieux_COMPUTERSANDEDUCATION, 0202 electrical engineering, electronic engineering, information engineering, business, 0503 education, Competence (human resources), Algorithm
Abstract

Objectives: The advent of information technology causes a significant impact on pedagogy and using ICT technologies in school-related activities. With this argument, determining the teacher’s ICT competence is expected to yield a better or positive impact on the learners and the performance of the teachers itself, however, no model was developed in predicting teachers ICT competence. In line with this, it is empirical to study and develop a model that will help the university in predicting teacher’s ICT competence. Methods: Data mining approach utilizing J48 algorithm was applied in this paper to create a model suitable for the actual teachers’ characteristics in the University. Moreover, Cross-validation technique was used to validate the dataset to have an optimum and acceptable model and generating the Receiving Operating Characteristics Curve (ROC) Area under ROC Curve technique. Findings: Decision tree model and decision rule for classification were created. Additionally, there were 92.78% correctly classified with an AUC weighted mean of 92.4%. Also, the model has very high acceptability and accuracy in predicting Teacher’s ICT Competence. However, it also revealed that many teachers still need more exposure in utilizing ICT technologies in pedagogy and any school-related activities. Application/Improvements: The result of this study can be a basis for developing software that will automatically categorize or classify the Teacher’s ICT competence. For more improvement of this paper and the model, it is suggested to add additional parameters to have more factors involved in predicting Teacher’s ICT competence. Keywords: Blended Learning, Decision Tree, ICT Competency, ICT Domain, ICT Pedagogy, J48 Algorithm, Machine Learning

Published
2018
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33. Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors

Author

Lonnie P. Wollmuth, Mark E. Bowen, Catherine L. Salussolia, Hiro Furukawa, Michael C. Regan, Jian Dai, Johansen B. Amin, Kelvin Chan, and Huan-Xiang Zhou

Subjects
0301 basic medicine, Physiology, Protein subunit, Gating, AMPA receptor, Biology, Receptors, N-Methyl-D-Aspartate, Evolution, Molecular, 03 medical and health sciences, Protein Domains, Animals, Humans, Receptors, AMPA, Receptor, Research Articles, Ion channel, musculoskeletal, neural, and ocular physiology, Rats, Cell biology, Transmembrane domain, HEK293 Cells, 030104 developmental biology, nervous system, NMDA receptor, Protein Multimerization, Ion Channel Gating, Neuroscience, Research Article, Ionotropic effect
Abstract

AMPA and NMDA receptors are ionotropic glutamate receptors that make fundamental contributions to synaptic activity in the brain in different ways. Amin et al. show that their respective M4 segments, located on the periphery of their pore domains, contribute to their functional diversity., Ionotropic glutamate receptors (iGluRs), including AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subtypes, are ligand-gated ion channels that mediate signaling at the majority of excitatory synapses in the nervous system. The iGluR pore domain is structurally and evolutionarily related to an inverted two-transmembrane K+ channel. Peripheral to the pore domain in eukaryotic iGluRs is an additional transmembrane helix, the M4 segment, which interacts with the pore domain of a neighboring subunit. In AMPARs, the integrity of the alignment of a specific face of M4 with the adjacent pore domain is essential for receptor oligomerization. In contrast to AMPARs, NMDARs are obligate heterotetramers composed of two GluN1 and typically two GluN2 subunits. Here, to address the function of the M4 segments in NMDARs, we carry out a tryptophan scan of M4 in GluN1 and GluN2A subunits. Unlike AMPARs, the M4 segments in NMDAR subunits makes only a limited contribution to their biogenesis. However, the M4 segments in both NMDAR subunits are critical for receptor activation, with mutations at some positions, most notably at the extreme extracellular end, completely halting the gating process. Furthermore, although the AMPAR M4 makes a minimal contribution to receptor desensitization, the NMDAR M4 segments have robust and subunit-specific effects on desensitization. These findings reveal that the functional roles of the M4 segments in AMPARs and NMDARs have diverged in the course of their evolution and that the M4 segments in NMDARs may act as a transduction pathway for receptor modulation at synapses.

Published
2017
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35. Defining the role of common variation in the genomic and biological architecture of adult human height

Author

Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, 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Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.

Subjects
Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, Medizin, Genome-wide association study, Adult, Analysis of Variance, Body Height/genetics, European Continental Ancestry Group/genetics, Genetic Variation/genetics, Genetics, Population, Genome-Wide Association Study/methods, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide/genetics, heritability, 0302 clinical medicine, Genome-wide, SNPS, snps, Genetics & Heredity, ddc:616, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, variants, GENETIC-VARIATION, Biological Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], body height, genetic-variation, Life Sciences & Biomedicine, Single Nucleotide/genetics, Human, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, NO, complex traits, 03 medical and health sciences, Genetic variation, heritability, adult, height, Polymorphism, Human height, PAGEGE Consortium, education, Gene, VLAG, 030304 developmental biology, Global Nutrition, Wereldvoeding, genome-wide association study, Science & Technology, Whites, Oligonucleotide Array Sequence Analysi, MUTATIONS, COMPLEX TRAITS, ta1184, Klinisk medicin, population genetics, Genetic Variation, Heritability, ta3121, mutations, Genetic architecture, Body Height, genetic variation, MIGen Consortium, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Clinical Medicine, 030217 neurology & neurosurgery, height, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract

Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Published
2014
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38. An Assessment of ICT Competencies of Public School Teachers: Basis for Community Extension Program

Author

Rommel L. Verecio, Mark Lester P. Laurente, Micheline A. Gotardo, Devine Grace D. Funcion, Lowell A. Quisumbin, Jeffrey C. Cinco, Las Johansen B. Caluza, and Vanessa Marmita

Subjects
School teachers, 0508 media and communications, Extension (metaphysics), Information and Communications Technology, 05 social sciences, Pedagogy, Mathematics education, 050301 education, 050801 communication & media studies, Psychology, 0503 education
Published
2017
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42. De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases

Author

Scott J. Myers, Ruth K. Mizu, Sharon A. Swanger, Stephanie Keller, Weiting Tang, William R. Wilcox, Yuchen Xu, Chun Hu, Slavé Petrovski, Jia Li, Wenjuan Chen, Varun Kannan, Johansen B. Amin, Lonnie P. Wollmuth, Stephen F. Traynelis, Wenshu XiangWei, Hirofumi Kusumoto, Johannes R. Lemke, Hongjie Yuan, and Jin Zhang

Subjects
Agonist, Male, Models, Molecular, medicine.drug_class, Protein Conformation, Mutation, Missense, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Article, 03 medical and health sciences, Xenopus laevis, Genetics, medicine, Missense mutation, Animals, Humans, Receptor, Child, Genetics (clinical), 030304 developmental biology, 0303 health sciences, biology, 030305 genetics & heredity, Glutamate receptor, GRIN1, Cell biology, Disease Models, Animal, HEK293 Cells, Phenotype, biology.protein, Excitatory postsynaptic potential, GRIN2A, GRIN2B, Female, Nervous System Diseases
Abstract

N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role in neuronal development and brain function. Rare genetic variants in the GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize the clinical presentations for 18 patients harboring 12 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M2 re-entrant loop, a region that lines the pore and is intolerant to missense variation. These de novo variants were identified in children with a set of neurological and neuropsychiatric conditions. Evaluation of the receptor cell surface expression, pharmacological properties, and biophysical characteristics show that these variants can have modest changes in agonist potency, proton inhibition, and surface expression. However, voltage-dependent magnesium inhibition is significantly reduced in all variants. The NMDARs hosting a single copy of a mutant subunit showed a dominant reduction in magnesium inhibition for some variants. These variant NMDARs also show reduced calcium permeability and single-channel conductance, as well as altered open probability. The data suggest that M2 missense variants increase NMDAR charge transfer in addition to varied and complex influences on NMDAR functional properties, which may underlie the patients' phenotypes.

Published
2019

44. Stories Unfold of Grade 7 Science Teachers on Instructional Materials: An Assessment

Author

Tan, Maria Lourdes G., Espina, Vinella F., and Caluza, Las Johansen B.

Subjects
K to 12 curriculum, ComputingMilieux_COMPUTERSANDEDUCATION
Abstract

Common sentiments of teachers in the field with the implementation of the K to 12 Curriculum are limited instructional materials. One of the responses to face these challenges is to use localized and contextualized materials for teaching based on the needs of students and teachers. This descriptive single case study anchored on Kolb’s theory of experiential learning highlights the role of instructional materials in student’s retention of knowledge. An in-depth, focused group discussion was used to assess the needs of Grade 7 science teachers of Northern Tacloban City National High School purposely selected as participants. Findings revealed that teachers need multimedia in the form of animated video with corresponding worksheets where they can answer questions based on the video seen, this helped for a more in-depth understanding of concepts, skills, and processes of the subject. The result of the study paves the way to develop an instructional kit in making learning more interactive and enjoyable to students.

Published
2018
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45. A Swiss army knife for targeting receptors

Author

Lonnie P. Wollmuth and Johansen B. Amin

Subjects
0301 basic medicine, Structural Biology and Molecular Biophysics, Xenopus, Synapse, chemistry.chemical_compound, 0302 clinical medicine, Biology (General), Receptor, Neurotransmitter, skin and connective tissue diseases, Cells, Cultured, Neurotransmitter Agents, Chemistry, General Neuroscience, Glutamate receptor, food and beverages, allosteric modulator, General Medicine, NMDA receptor, Medicine, Insight, neurotransmitter, Allosteric modulator, QH301-705.5, Science, glutamate, Receptors, N-Methyl-D-Aspartate, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Allosteric Regulation, None, Animals, Humans, Binding Sites, General Immunology and Microbiology, Molecular biophysics, fungi, Epithelial Cells, 030104 developmental biology, Structural biology, nervous system, Oocytes, sense organs, pharmacology, Neuroscience, 030217 neurology & neurosurgery
Abstract

N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations. Modest changes to the chemical structure interconvert negative and positive modulation. All modulators share the ability to enhance agonist potency and are use-dependent, requiring the binding of both agonists before modulators act with high potency. Data suggest that these modulators, including both enantiomers, bind to the same site on the receptor and share structural determinants of action. Due to the modulator properties, submaximal negative modulators in this series may spare NMDAR at the synapse, while augmenting the response of NMDAR in extrasynaptic spaces. These modulators could serve as useful tools to probe the role of extrasynaptic NMDARs.

Published
2018

46. De novoGRINvariants in NMDA receptor M2 channel pore‐forming loop are associated with neurological diseases

Author

Li, Jia, primary, Zhang, Jin, additional, Tang, Weiting, additional, Mizu, Ruth K., additional, Kusumoto, Hirofumi, additional, XiangWei, Wenshu, additional, Xu, Yuchen, additional, Chen, Wenjuan, additional, Amin, Johansen B., additional, Hu, Chun, additional, Kannan, Varun, additional, Keller, Stephanie R., additional, Wilcox, William R., additional, Lemke, Johannes R., additional, Myers, Scott J., additional, Swanger, Sharon A., additional, Wollmuth, Lonnie P., additional, Petrovski, Slavé, additional, Traynelis, Stephen F., additional, and Yuan, Hongjie, additional

Published
2019
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