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The Basic Structure In Malaysia: Less Than Meets The Eye, Benjamin Joshua Ong

Research Collection Yong Pung How School Of Law

At first glance, studying the basic structure doctrine in Malaysia can be frustrating due to its inconsistent judicial treatment. While early cases such as Loh Kooi Choon and Phang Chin Hock rejected the doctrine, it was later accepted in landmark decisions like Sivarasa Rasiah, Semenyih Jaya, and Indira Gandhi. In 2020, scholars such as Jaclyn Neo and Yvonne Tew suggested a judicial embrace of the doctrine and its global trend toward constitutional unamendability. However, the Federal Court’s 2021 decision in Maria Chin Abdullah appeared to reject it once more, illustrating the doctrine’s precarious status. The resurgence seen in Dhinesh a/l …

The Answer To Perimenstrual Distress Is Not Automatically Prescription: Review Of Allopathic And Integrative Approaches To Mental Health Care For Pms & Pmdd Symptoms, Grace Oja

University Honors Theses

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) affect a notable percentage of people who menstruate. PMS/PMDD have a wide range of symptoms that negatively impact mental well-being and quality of life. This review is the culmination of a database search to review current allopathic treatments for PMS/PMDD, which often include oral contraceptives and antidepressants, and explore evidence-based methods for integrative and alternative treatments to address some of the limitations of standard allopathic care, including limitations on which symptoms they address and side effects. This paper aims to examine how integrative medicine may expand existing treatments for PMS and PMDD …

Persistent Imbalance: Women’S Representation In North American Pediatric Cardiology Leadership Roles.Persistent Imbalance: Women’S Representation In North American Pediatric Cardiology Leadership Roles, Alaina K. Kipps, Audrey C. Marshall, Neha Bansal, Holly Bauser-Heaton, Nadine Choueiter, Devyani Chowdhury, Aarti Dalal, Molly Ehrlich, Lindsay R. Freud, Supriya S. Jain, Pei-Ni Jone, Kristin Laraja, Dalia Lopez-Colon, Sonal T. Owens, Christina Ronai, Ritu Sachdeva, Corey Stiver, Nicole Sutton, Terrie Vasilopoulos, Jennifer Co-Vu

Department of Pediatrics Faculty Papers

BACKGROUND: Despite recent gender parity of physicians entering pediatric cardiology, representation of women leaders lags their male colleagues.

OBJECTIVES: We sought to better understand the variation in women in leadership roles in pediatric cardiology.

METHODS: The gender of physicians in 16 prespecified leadership positions was collected by survey between July 2022 and January 2023 from pediatric cardiology programs with >5 cardiologists in North America. We analyzed the association of women leaders with center size (based on surgical volume), geographic region, presence of categorical fellowship program, and gender of division chief and department chair.

RESULTS: Across 99 centers, a median of …

Behavioral Responses Of The California Two-Spot Octopus Octopus Bimaculoides To Changes In Color And Sound, Sofia I. Ramirez, Nathalie Reyns

McNair Summer Research Program

Recreational and commercial boat activity, military and construction operations, and seismic surveys among other human activities produce excessive sound that is classified as anthropogenic noise. Because the intensity and frequency of anthropogenic noise is often higher than that of natural underwater acoustic stimuli, marine animals may experience physiological damage to their sound-detecting organs which in turn, affects their communication and orientation abilities. In our study, we aimed to analyze the differences in behaviors exhibited by the California two-spot octopus (Octopus bimaculoides) when exposed to various volumes of noise at 54 Hz. To further investigate behavioral changes under varying conditions, we …

The Role Of Insularity: Plants Have Few Ornithophilous Traits But Are Visited By Morphologically More Distinct Hummingbirds In The Caribbean Islands, Maximillian G.R. Vollstädt, Rasmus D. Jensen, Pietro K. Maruyama, Matthias Schleuning, Francielle P. Araújo-Hoffmann, Marlies Sazima, Jesper Sonne, Taia S.O. Schrøder, Fredrik Møller-Stranges, Stefan Abrahamczyk, Mónica B. Ramírez-Burbano, Marcelo Ferreira De Vasconcelos, Boris A. Tinoco, María A. Maglianesi, Ruth Partida-Lara, José Raúl Vázquez-Pérez, Paula L. Enríquez, André Rodrigo Rech, Aline G. Coelho, Fernando Gonçalves, Edvaldo Nunes Da Silva Neto, Manoel Martins Dias Filho, Matheus Reis, Oscar H. Marín-Gómez, Juan Francisco Ornelas, Peter A. Cotton, Paulo Eugenio Oliveira, Adriana Oliveira Machado, Jeferson Vizentin-Bugoni, Pedro Joaquim Bergamo

School of Biological and Marine Sciences

Functional traits determine interactions between plants and pollinators, and to increase pollination efficiency, many plants have evolved traits to attract specific pollinator groups. However, biogeographical setting may influence trait evolution and biotic interactions. For instance, plants pollinated by hummingbirds often have ornithophilous traits, that is, flowers with elongated corollas, dilute nectar and red colours, but—due to colonization history, depauperate biotas and unstable environmental conditions—it might be disadvantageous for species to rely on mutualistic partners with specific functional traits on oceanic islands. Hummingbird-visited plants on islands are thus expected to have fewer ornithophilous traits and be functionally less diverse in their …

Emergence Of Cellular Nematic Order Is A Conserved Feature Of Gastrulation In Animal Embryos, Xin Li, Robert J Huebner, Margot L K Williams, Jessica Sawyer, Mark Peifer, John B Wallingford, D Thirumalai

Faculty, Staff and Students Publications

Cells undergo dramatic morphological changes during embryogenesis, yet how these changes affect the formation of ordered tissues remains elusive. Here, we show that a phase transition leading to the formation of a nematic liquid crystal state during gastrulation in the development of embryos of fish, frogs, and fruit flies occurs by a common mechanism despite substantial differences between these evolutionarily distant animals. Importantly, nematic order forms early before any discernible changes in the shapes of cells. All three species exhibit similar propagation of the nematic phase, reminiscent of nucleation and growth mechanisms. The spatial correlations in the nematic phase in …

Outcomes Of Specialist Physiotherapy For Functional Motor Disorder: The Physio4fmd Rct, Physio4fmd Study Group, Glenn Nielsen, Louise Marston, Rachael Maree Hunter, Alan Carson, Laura H. Goldstein, Kate Holt, Teresa C. Lee, Marie Le Novere, Jonathan Marsden, Irwin Nazareth, Hayley Noble, Markus Reuber, Jon Stone, Ann Marie Strudwick, Beatriz Santana Suarez, Mark J. Edwards

School of Health Professions

Background: Functional motor disorder often causes persistent disabling symptoms that are associated with high healthcare costs. In recent years, specialist physiotherapy, informed by an understanding of functional motor disorder, has emerged as a promising treatment, but there is an absence of evidence of its effectiveness from large randomised controlled trials. Methods: We conducted a pragmatic, multicentre, randomised controlled trial, comparing specialist physiotherapy for functional motor disorder to treatment as usual, which was defined as community neurological physiotherapy. The primary outcome was the Short Form questionnaire-36 items Physical Functioning domain at 12 months (scale range 0–100, with 100 indicating optimum health). …

Fgf21 Promotes Longevity In Diet-Induced Obesity Through Metabolic Benefits Independent Of Growth Suppression, Christy M Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao, Yi Zhu, Clifford J Rosen, Tamas L Horvath, Vishwa Deep Dixit, Philipp E Scherer

Faculty, Staff and Students Publications

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence …

Role Of Kctd13 In Modulating Ar And Sox9 Expression In Different Penile Cell Populations, Carolina J Jorgez, Ahmed Chahdi, Hunter Flores, Marisol O'Neill, Abhishek Seth

Faculty, Staff and Students Publications

Objective: Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. Kctd13-knockout (Kctd13-KO) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the Kctd13-KO penis could help us to understand the mechanism of action of these signaling pathways on penile development.

Methods: We generated transgenic mice lacking Kctd13 and conditionally expressing AR in the urethral mesenchyme after Cre activation with Twist2cre (Kctd13-KO; AR-CMV; Twist2cre; herein called AR+), and Sox9 in the urethral …

Mechanisms Of Change In Exposure Therapy For Anxiety And Related Disorders: A Research Agenda, Kristen Benito, Andre Pittig, Jonathan Abramowitz, Joanna J Arch, Denise Chavira, Rianne De Kleine, Alessandro S De Nadai, Dirk Hermans, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, Katharina Kircanski, Peter M Mcevoy, Heidi Meyer, Marie-H Monfils, Santiago Papini, Winfried Rief, David Rosenfield, Eric A Storch, Michael J Telch, Michael W Otto, Jasper A J Smits

Faculty, Staff and Students Publications

Anxiety and related disorders are a significant public health burden with rising prevalence in the wake of the COVID-19 pandemic. As demand for effective anxiety treatment increases, so too does the need for strategies to bolster treatment outcomes. Research on the mechanisms of exposure therapy, the frontline behavioral treatment, will be critically important for optimizing clinical outcomes. We outline an initial agenda for future research on the mechanisms of change of exposure therapy, developed in collaboration with a large international team of researchers through the Exposure Therapy Consortium (ETC). Key questions and recommendations for future research focus on five priority …

Evaluation Of The Incremental Effect Of Fasting Length On Ph, Select Cecal Microbial Groups, Cecal Volatile Fatty Acid Concentrations, And Secretory Iga Excretion In Roosters, B.W. Parsons, M.R. Bedford, C.L. Wyatt

Poultry Science Faculty Publications and Presentations

Two experiments were conducted to evaluate the effect of incremental fasting time on the gastrointestinal tract in chickens. Adult White Leghorn roosters with intact ceca were provided a nutrient-adequate corn-soybean meal diet ad libitum for 3 weeks. Prior to initiation of the experimental phase, ad libitum feed intake was recorded for 8 h and immediately after the fasting period commenced. In Experiment 1, roosters were fasted for either 0, 3, 6, 9, 12, 16, or 24 h. At each time point birds were euthanized and pH in the crop, gizzard, and ceca were recorded and cecal contents were collected to …

Identification Of Distinct Biological Groups Of Patients With Cryptogenic Norse Via Inflammatory Profiling, Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin

Faculty, Staff and Students Publications

Background and objectives: Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms. The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.

Methods: Sixty-two patients with c-NORSE were included. A comprehensive panel …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

The East Palestine Train Derailment: A Complex Environmental Disaster, Lynn T. Singer, Fredrick R. Schumacher, Timothy Ciesielski

Faculty Scholarship

This symposium, The East Palestine Train Derailment: A Complex Environmental Disaster, brought together scientists whose research represented initial scientific responses to the community health impacts of the chemical exposures incurred from a disastrous train derailment and subsequent combustion in East Palestine, Ohio in February, 2023. This derailment and burn led to multiple complex toxic exposures to air, soil and water, including vinyl chloride and butyl acrylate. Presenters described the multi-university consortium formed to assist with developing and communicating data-informed summaries to the affected community. Presenters also reported on the immediate health sequelae experienced by the community and the stress and …

The Effect Of Integrating Augmented Reality (Ar) Technology In Science Education Teaching On Improving The Biological Concepts Learning Among Kindergarten Children, Kawthar Habeeb

Journal of Educational and Psychological Studies

This quasi-experimental study explored the impact of AR on acquiring biological concepts among kindergarteners. The sample comprised 30 second-level kindergarteners from a school in Farwaniya Educational Directorate, Kuwait. Participants were randomly divided into an experimental group (n = 15), taught using AR, and a control group (n = 15), taught traditionally. Results revealed statistically significant di erences in biological concept understanding, favoring the experimental group. Additionally, the experimental group demonstrated significant improvement from pre-test to post-test stages. These findings highlight the potential of AR to enhance learning outcomes in kindergarten biology education. The study emphasizes the importance of integrating AR …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

Distinguishing Pex2 And Pex16 Gene Variant Severity For Mild, Severe And Atypical Peroxisome Biogenesis Disorders, Vanessa A Gomez, Oguz Kanca, Sharayu V Jangam, Saurabh Srivastav, Jonathan C Andrews, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Peroxisomal biogenesis disorders (PBD) are autosomal recessive diseases caused by mutations in specific PEX genes that impair peroxisome formation, leading to multi-systemic failure. Symptoms vary, even in patients with variants in the same PEX gene. Our goal is to select PEX mutations and use Drosophila to model a severity spectrum based on genotype-phenotype correlations. Utilizing KozakGAL4 (KZ) cassettes, we replaced the coding sequence of Pex with a GAL4 driver, ideal for making 'humanized' flies in which human PEX can replace the fly loss. We generated Pex2KZ and Pex16KZ lines and assessed them in various behavior assays, confirming their severe phenotypes. …

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Gut Virome Profile In New Onset Treatment Naïve Saudi Children With Ulcerative Colitis, Mohammad El Mouzan, Tor C Savidge, Ahmed Al Sarkhy, Shyam Badu, Badr Alsaleem, Mohammad Al Mofarreh, Abdullah Almasood, Asaad Assiri

Faculty, Staff and Students Publications

Background: Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.

Methods: Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-naïve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal …

A Lysosomal Surveillance Response To Stress Extends Healthspan, Terytty Yang Li, Arwen W Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J Liu, Rachel N Arey, Kimberly Morales, Raya B Liu, Wenzheng Wang, Ang Zhou, Tong-Jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H Houtkooper, Johan Auwerx

Faculty, Staff and Students Publications

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H+-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

A Hypomorphic Model Of Cps1 Deficiency For Investigating The Effects Of Hyperammonemia On The Developing Nervous System, Stuti Bakshi, Taryn Diep, Brandon J Willis, Rachel Reyes, Grace F Wu, Georgios Makris, Martin Poms, Isabel Day, Qin Sun, Irina Zhuravka, Lindsay Lueptow, Michelle Tang, Gareth A Cromie, Aimée M Dudley, Johannes Häberle, Gerald S Lipshutz

Faculty, Staff and Students Publications

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare metabolic disorder that, in neonatal onset, is typically characterized by severe life-threatening and neurologically injuring hyperammonemic episodes with high unmet patient need. Patients that retain limited enzyme activity may present later in life with less severe hyperammonemia. CPS1 drives the first step in the urea cycle, the pathway terrestrial mammals utilize to metabolize nitrogen. In order to probe the effect of hyperammonemia on the developing nervous system and explore new therapies, a murine Cps1 exon 3-4 mutant was previously generated. However, these mice die within 24 h of birth, limiting study …

Formation Of An Expanding Memory Representation In The Hippocampus, Sachin P Vaidya, Guanchun Li, Raymond A Chitwood, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with …

A Survey Study Of Roadblocks In Translational Science, Fasiha Kanwal, Christopher I Amos, Katherine H Sippel, Claudia Neuhauser, Ariel Harrison, Mary E Dickinson, Charles Minard, Bettina M Beech

Faculty, Staff and Students Publications

Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks …

Cardiovascular-Kidney-Metabolic Effects: Steroidal And Nonsteroidal Mineralocorticoid Receptor Antagonists, Biykem Bozkurt, James L Januzzi, Shweta Bansal

Faculty, Staff and Students Publications

Cardiovascular (CV)-kidney-metabolic (CKM) syndrome is a complex disorder characterized by the co-occurrence of CV risk factors, including chronic kidney disease (CKD), hypertension, and metabolic dysfunction, which creates a vicious cycle where one factor negatively impacts the others, ultimately leading to poor overall CV and kidney outcomes. Overactivation of the mineralocorticoid receptor, through binding with aldosterone and ligand-independent mechanisms, is implicated in the pathogenesis of CKM; mineralocorticoid receptor antagonists (MRAs) can block this interaction. Steroidal MRAs are currently recommended for people with heart failure (HF) with reduced ejection fraction and hypertension; however, the role of nonsteroidal MRAs in CKM is evolving. …

Dichotomous Roles Of Acbd3 In Nsclc Growth And Metastasis, Xiaochao Tan, Chao Wu, Priyam Banerjee, Shike Wang, Derrick L Cardin, Yuting Xu, Chad J Creighton, William K Russell

Faculty, Staff and Students Publications

Lung cancer continues to be the leading cause of cancer-related deaths globally. Unraveling the regulators behind lung cancer growth and its metastatic spread, along with understanding the underlying mechanisms, is crucial for developing novel and effective therapeutic strategies. While much research has focused on identifying potential oncogenes or tumor suppressors, the roles of certain genes can vary depending on the context and may even exhibit contradictory effects. In this study, we demonstrate that acyl-CoA binding domain containing 3 (ACBD3), a Golgi resident protein, promotes primary lung cancer growth by recruiting phosphatidylinositol (PI)-4-kinase IIIβ (PI4KB) to the Golgi, thereby enhancing oncogenic …

High Prevalence Of Strongyloides Stercoralis In People Living With Hiv: A Critical Health Challenge In The Peruvian Amazon Basin, Silvia Otero-Rodriguez, Martin Casapia-Morales, Viviana Pinedo-Cancino, Seyer Mego-Campos, Victoria-Ysabel Villacorta-Pezo, Jorge Parráguez-De-La-Cruz, Eva H Clark, Esperanza Merino, Jose-Manuel Ramos-Rincon

Faculty, Staff and Students Publications

Introduction: Strongyloidiasis is an important but underdiagnosed soil-transmitted helminthiasis, particularly in tropical areas and some vulnerable groups.

Objectives: To assess the parasitological prevalence, seroprevalence and sociodemographic factors of Strongyloides stercoralis infection in patients living with human immunodeficiency virus (PLWH) in an endemic area.

Materials and methods: We performed a cross-sectional study of strongyloidiasis in 537 PLWH in two hospitals in Iquitos, Peru, from 20 Oct 2023 to 20 May 2024. We tested patient sera using Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) and stool via the modified Baermann technique and/or charcoal fecal culture as highly sensitive parasitological techniques. We used multivariable …

Glioblastoma-Instructed Astrocytes Suppress Tumour-Specific T Cell Immunity, Camilo Faust Akl, Brian M Andersen, Zhaorong Li, Federico Giovannoni, Martin Diebold, Liliana M Sanmarco, Michael Kilian, Luca Fehrenbacher, Florian Pernin, Joseph M Rone, Hong-Gyun Lee, Gavin Piester, Jessica E Kenison, Joon-Hyuk Lee, Tomer Illouz, Carolina M Polonio, Léna Srun, Jazmin Martinez, Elizabeth N Chung, Anton Schüle, Agustin Plasencia, Lucinda Li, Kylynne Ferrara, Mercedes Lewandrowski, Craig A Strathdee, Lorena Lerner, Christophe Quéva, Iain C Clark, Benjamin Deneen, Judy Lieberman, David H Sherr, Jack P Antel, Michael A Wheeler, Keith L Ligon, E Antonio Chiocca, Marco Prinz, David A Reardon, Francisco J Quintana

Faculty, Staff and Students Publications

Glioblastoma is the most common and aggressive primary brain cancer and shows minimal response to therapies. The immunosuppressive tumour microenvironment in glioblastoma contributes to the limited therapeutic response. Astrocytes are abundant in the central nervous system and have important immunoregulatory roles. However, little is known about their role in the immune response to glioblastoma1. Here we used single-cell and bulk RNA sequencing of clinical glioblastoma samples and samples from preclinical models, multiplexed immunofluorescence, in vivo CRISPR-based cell-specific genetic perturbations and in vitro mouse and human experimental systems to address this gap in knowledge. We identified an astrocyte subset …