Medicine and Health Sciences Commons^™

Gantenerumab: An Anti-Amyloid Monoclonal Antibody With Potential Disease-Modifying Effects In Early Alzheimer's Disease, Randall J Bateman, Jeffrey Cummings, Scott Schobel, Stephen Salloway, Bruno Vellas, Mercè Boada, Sandra E Black, Kaj Blennow, Paulo Fontoura, Gregory Klein, Sheila Seleri Assunção, Janice Smith, Rachelle S Doody

2020-Current year OA Pubs

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal …

Fgfr2b Signalling Restricts Lineage-Flexible Alveolar Progenitors During Mouse Lung Development And Converges In Mature Alveolar Type 2 Cells, Matthew R Jones, Arun Lingampally, Negah Ahmadvand, Lei Chong, Jin Wu, Jochen Wilhem, Ana Ivonne Vazquez-Armendariz, Meshal Ansari, Susanne Herold, David M Ornitz, Herbert B Schiller, Cho-Ming Chao, Jin-San Zhang, Gianni Carraro, Saverio Bellusci

2020-Current year OA Pubs

The specification, characterization, and fate of alveolar type 1 and type 2 (AT1 and AT2) progenitors during embryonic lung development are poorly defined. Current models of distal epithelial lineage formation fail to capture the heterogeneity and dynamic contribution of progenitor pools present during early development. Furthermore, few studies explore the pathways involved in alveolar progenitor specification and fate. In this paper, we build upon our previously published work on the regulation of airway epithelial progenitors by fibroblast growth factor receptor 2b (FGFR2b) signalling during early (E12.5) and mid (E14.5) pseudoglandular stage lung development. Our results suggest that a significant proportion …

Non-Standard Viral Genome-Derived Rna Activates Tlr3 And Type I Ifn Signaling To Induce Cdc1-Dependent Cd8+ T-Cell Responses During Vaccination In Mice, Devin G Fisher, Victoria Gnazzo, David J Holthausen, Carolina B López

2020-Current year OA Pubs

There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node …

Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al.

2020-Current year OA Pubs

CONTEXT: Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

OBJECTIVE: We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

METHODS: We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

RESULTS: We identified causative variants in CLPB, encoding a mitochondrial …

Stakeholder Engagement In Eight Comparative Effectiveness Trials In African Americans And Latinos With Asthma, Tiffany Dy, Winifred J Hamilton, C Bradley Kramer, Andrea Apter, Jerry A Krishnan, James W Stout, Stephen J Teach, Alex Federman, John Elder, Tyra Bryant-Stephens, Rebecca J Bruhl, Shawni Jackson, Kaharu Sumino

2020-Current year OA Pubs

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies.

METHODS: Using the method content analysis of cases, we identified themes regarding the …

Multilevel Correlates Of Domain-Specific Physical Activity Among Rural Adults - A Cross-Sectional Study, Alan M Beck, Natalicio H Serrano, Audrey Toler, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Increasing physical activity (PA) in rural communities is a vital prevention tactic in multiple chronic diseases; however, little is known on the multilevel correlates of PA rural areas. A better understanding of domain-specific PA adds context for promoting PA in rural communities. The current study sought to determine factors associated with domain-specific and overall moderate-vigorous physical activity (MVPA) in rural communities.

METHODS: Surveys were conducted across 14 rural mid-Western communities, with the final analytical sample including 1241 adults (ages 19-96, M = 57.0 [SD = 16.7], 67.8% female, 83.8% white). Generalized linear models with negative binomial distributions examined the …

Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled

2020-Current year OA Pubs

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the …

De Novo Serine Biosynthesis From Glucose Predicts Sex-Specific Response To Antifolates In Non-Small Cell Lung Cancer Cell Lines, Jasmin Sponagel, Siddhartha Devarakonda, Joshua B Rubin, Jingqin Luo, Joseph E Ippolito

2020-Current year OA Pubs

Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to the antifolate pemetrexed in male and female NSCLC cell lines. Using [

Collegiate Wrestler With A Bicuspid Aortic Valve And Aortic Dilation, Rahul Chhana, Christopher Rymer, Mahesh Vidula, Kristopher Fayock, Helene Glassberg, Chris Kusmiesz, Mustafa Husaini, Sanjay Sivalokanathan, Neel Chokshi, Sheela Krishnan

2020-Current year OA Pubs

Bicuspid aortic valve and aortopathy are generally considered contraindications to isometric exercise. For athletes with mild disease at low risk of adverse events, a shared decision-making approach for continued sports participation is reasonable. We present a case of a collegiate wrestler with bicuspid aortic valve and aortopathy to illustrate shared decision making. (

Economic Evaluation Of Implementation Science Outcomes In Low- And Middle-Income Countries: A Scoping Review, Akash Malhotra, Abigail Barker, Victor G Davila-Roman, William Effah, Et Al.

2020-Current year OA Pubs

BACKGROUND: Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in …

Β-Amyloid Pet Harmonisation Across Longitudinal Studies: Application To Aibl, Adni And Oasis3, Pierrick Bourgeat, Manu Goyal, Pamela Lamontagne, John C Morris, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Centiloid scale was developed to harmonise the quantification of β-amyloid (Aβ) PET images across tracers, scanners, and processing pipelines. However, several groups have reported differences across tracers and scanners even after centiloid conversion. In this study, we aim to evaluate the impact of different pre and post-processing harmonisation steps on the robustness of longitudinal Centiloid data across three large international cohort studies.

METHODS: All Aβ PET data in AIBL (N = 3315), ADNI (N = 3442) and OASIS3 (N = 1398) were quantified using the MRI-based Centiloid standard SPM pipeline and the PET-only pipeline CapAIBL. SUVR were converted …

Sex Differences In Brain Tumor Glutamine Metabolism Reveal Sex-Specific Vulnerabilities To Treatment, Jasmin Sponagel, Jill K Jones, Cheryl Frankfater, Shanshan Zhang, Olivia Tung, Kevin Cho, Kelsey L Tinkum, Hannah Gass, Elena Nunez, Gary J Patti, Jingqin Luo, Joshua B Rubin, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue.

METHODS: Using positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity.

FINDINGS: We found that male glioblastoma …

Liquefied Petroleum Gas Or Biomass For Cooking And Effects On Birth Weight, Thomas F Clasen, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear.

METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 μm [PM

RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate …

Persistence Of Onchocerciasis In Villages In Enugu And Ogun States In Nigeria Following Many Rounds Of Mass Distribution Of Ivermectin, Uwem F Ekpo, Obiora A Eneanya, Edith N Nwankwo, Islamiat Y Soneye, Gary J Weil, Peter U Fischer, Obioma C Nwaorgu

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis is endemic in most local government areas (LGAs) in Enugu and Ogun states. Most meso- and hyper-endemic LGAs have received many rounds of ivermectin mass drug administration (MDA). This study aimed to determine the current prevalence of onchocerciasis in villages in Enugu and Ogun states that were formerly highly endemic and to assess progress toward elimination of the infection in areas believed to be at high risk for persistence.

METHODS: Cross-sectional community surveys were conducted 8 to 12 months after the last round of MDA in 16 villages (6 in Enugu state and 10 in Ogun state) in …

Tuft-Cell-Intrinsic And -Extrinsic Mediators Of Norovirus Tropism Regulate Viral Immunity, Madison S Strine, Mia Madel Alfajaro, Vincent R Graziano, Jaewon Song, Leon L Hsieh, Ryan Hill, Jun Guo, Kelli L Vandussen, Robert C Orchard, Megan T Baldridge, Sanghyun Lee, Craig B Wilen

2020-Current year OA Pubs

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoV

Bi-Allelic Camsap1 Variants Cause A Clinically Recognizable Neuronal Migration Disorder, Reham Khalaf-Nazzal, Jennifer L Griffith, Joseph R Walsh, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T Curiel, Et Al.

2020-Current year OA Pubs

Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and …

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …

Importance Of First Pass Reperfusion In Endovascular Stroke Care - Insights From Thrombectomy And Aneurysm Registry (Star), Ilko L Maier, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mechanical thrombectomy has become the first-line treatment strategy for patients with large-vessel occlusion strokes. Often >1 thrombectomy maneuver is necessary to achieve reperfusion. A first-pass (FP) effect with improved functional outcomes after mechanical thrombectomy has been described. Aim of the present study is to investigate the FP effect in a large, international, multicenter stroke database.

METHODS: Patients who underwent mechanical thrombectomy for large-vessel occlusion stroke in the anterior cerebral circulation between January 2014 and January 2021 and achieved complete reperfusion were identified from the STAR (Stroke Thrombectomy and Aneurysm Registry). We compared functional outcomes of patients with FP (defined …

Distinct Stimulus-Dependent Neutrophil Dynamics Revealed By Real-Time Imaging Of Intestinal Mucosa After Acute Injury, Veronica Azcutia, Matthias Kelm, Seonyoung Kim, Anny-Claude Luissint, Sven Flemming, Lisa Abernathy-Close, Vincent B Young, Asma Nusrat, Mark J Miller, Charles A Parkos

2020-Current year OA Pubs

Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds. Similar numbers of PMNs infiltrated colonic mucosa after wounding in germ-free mice, suggesting microbiota-independent mechanisms. By contrast, acute mucosal injury secondary to either a treatment of mice with dextran sodium sulfate or …

Quantification Of Sulcal Emergence Timing And Its Variability In Early Fetal Life: Hemispheric Asymmetry And Sex Difference, Hyuk Jin Yun, Hyun Ju Lee, Joo Young Lee, Tomo Tarui, Caitlin K. Rollins, Cynthia M. Ortinau, Henry A. Feldman, P. Ellen Grant, Kiho Im

2020-Current year OA Pubs

Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logistic curve to presence or absence of sulcus. We found that the sulcal emergence started from the central to the temporo-parieto-occipital lobes and frontal lobe, and the temporal variability of emergence in most of the sulci was similar between 1 and 2 weeks. Small variability (< 1 week) was found in the left central and postcentral sulci and larger variability (>2 weeks) was shown in …

A Preclinical And Phase Ib Study Of Palbociclib Plus Nab-Paclitaxel In Patients With Metastatic Adenocarcinoma Of The Pancreas, Manuel Hidalgo, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

PURPOSE: To assess the preclinical efficacy, clinical safety and efficacy, and MTD of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

EXPERIMENTAL DESIGN: Preclinical activity was tested in patient-derived xenograft (PDX) models of PDAC. In the open-label, phase I clinical study, the dose-escalation cohort received oral palbociclib initially at 75 mg/day (range, 50‒125 mg/day; modified 3+3 design; 3/1 schedule); intravenous nab-paclitaxel was administered weekly for 3 weeks/28-day cycle at 100‒125 mg/m

RESULTS: Palbociclib plus nab-paclitaxel was more effective than gemcitabine plus nab-paclitaxel in three of four PDX models tested; the combination was not inferior to paclitaxel plus …

Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright

2020-Current year OA Pubs

IMPORTANCE: Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures.

OBJECTIVE: To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in …

Durable Melanoma Control Following Disseminated Talimogene Laherparepvec Herpetic Infection, Leonid Shmuylovich, Aubriana M Mcevoy, Ryan C Fields, Leonel Hernandez-Aya, George Ansstas, David Y Chen

2020-Current year OA Pubs

No abstract provided.

Acute-Onset, Painful, Acral Granuloma Annulare In A 52-Year-Old Female, Faisal S Ahmad, Michael R Vittori, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.

The Serotonin Receptor 3e Variant Is A Risk Factor For Female Ibs-D, Nikola Fritz, Gregory Sayuk, Et Al.

2020-Current year OA Pubs

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT

Risk-Adjusted Safety Analysis Of The Oral Jak2/Irak1 Inhibitor Pacritinib In Patients With Myelofibrosis, Naveen Pemmaraju, Claire Harrison, Vikas Gupta, Srdan Verstovsek, Bart Scott, Stephen T Oh, Francesca Palandri, Haifa Kathrin Al-Ali, Marta Sobas, Mary Frances Mcmullin, Ruben Mesa, Sarah Buckley, Karisse Roman-Torres, Alessandro Vannucchi, Abdulraheem Yacoub

2020-Current year OA Pubs

The safety profile of the novel oral JAK2/IRAK1 inhibitor pacritinib in patients with cytopenic myelofibrosis was described in the Phase 2 PAC203 and Phase 3 PERSIST-2 studies. To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia.

Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions.

OBJECTIVE: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms.

METHODS: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to …

Inositol Phosphorylceramide Synthase Null Leishmania Are Viable And Virulent In Animal Infections Where Salvage Of Host Sphingomyelin Predominates, F Matthew Kuhlmann, Phillip N Key, Suzanne M Hickerson, John Turk, Fong-Fu Hsu, Stephen M Beverley

2020-Current year OA Pubs

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt2

The Programmed Death-1 Signaling Axis Modulates Inflammation And Lv Structure/Function In A Stress-Induced Cardiomyopathy Model, Tomohiro Hayashi, Sajal K Tiwary, Kory J Lavine, Sandeep Acharya, Michael Brent, Luigi Adamo, Attila Kovacs, Douglas L Mann

2020-Current year OA Pubs

The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling …

Peroxisomal Regulation Of Energy Homeostasis: Effect On Obesity And Related Metabolic Disorders, Brian Kleiboeker, Irfan J Lodhi

2020-Current year OA Pubs

BACKGROUND: Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well beyond reactive oxygen species (ROS) metabolism and include fatty acid oxidation of unique substrates that cannot be catabolized in mitochondria, and synthesis of ether lipids and bile acids. Metabolic functions of peroxisomes involve crosstalk with other organelles, including mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. Emerging studies suggest that peroxisomes are important regulators of energy homeostasis and that disruption of peroxisomal functions influences the risk for obesity and the associated metabolic disorders, including type 2 diabetes and hepatic …