Digital Commons Network^™

Eligibility For Anti-Amyloid Treatment In A Multiethnic Community-Based Study, Lydia Trudel, Joseph Therriault, Arthur C Macedo, Karin L Meeker, Meredith N Braskie, Arthur W Toga, Serge Gauthier, Paolo Vitali, Suzanne E Schindler, Sid E O'Bryant, Pedro Rosa-Neto

2020-Current year OA Pubs

INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Cutibacterium Adaptation To Life On Humans Provides A Potential C Acnes Infection Biomarker, Md Shafiuddin, Wen-Chi Huang, Gabriel William Prather, Jeffrey Ryan Anton, Andrew Lawrence Martin, Sydney Brianna Sillart, Jonathan Z Tang, Michael R Vittori, Michael J Prinsen, Jessica Jane Ninneman, Chandrashekhara Manithody, Jeffrey P Henderson, Alexander W Aleem, Ma Xenia Garcia Ilagan, William H Mccoy 4th

2020-Current year OA Pubs

Propionibacteriaceae appear to have adapted to life on humans during the domestication of cattle. These microbial immigrants formed the genus Cutibacterium, and a descendent of those microbial trailblazers (C acnes) now dominates 25% of human skin. C acnes colonization of human skin requires the protein RoxP. Although all Cutibacteria encode this adaptation to life on humans, nothing like RoxP has been found in any other organism. In this study, we report an extensive assessment of 21 RoxP orthologs, which identified conserved molecular surfaces linked to heme-dependent oligomerization and low pH stability. Our investigation suggests how RoxP helps C acnes dominate …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

Dysregulated Lactate Metabolism Synergizes With Als Genetic Risk Factors To Accelerate Motor Decline, Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Neurons rely on glial 'lactate shuttling' for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional …

Oculomics And Ai: The Eye As A Biomarker For Health Span, Joy Le Yi Wong, Rajendra S Apte, Et Al.

2020-Current year OA Pubs

As the world's population ages, the focus of healthcare is shifting from extending life span to promoting health span. There is an unmet need to identify sensitive and reliable markers of health span through more cost-effective and non-invasive methods, to enable early and effective intervention on modifiable aging factors. The eye offers a unique window into systemic health, providing direct visualization of the body's vascular and neural health. This review presents an overview of how various ocular structures can serve as biomarkers of health span-drawing on insights from ocular imaging, metabolomics, and proteomics, with evidence from basic science, animal models, …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

A Microenvironment-Driven Hla-Ii-Associated Insulin Neoantigen Elicits Persistent Memory T Cell Activation In Diabetes, Neetu Srivastava, Anthony N Vomund, Rongzhen Yu, Orion J Peterson, Yuqing Yang, David P Turicek, Omar Abousaway, Tiandao Li, Pamela Stone, Aisha Ansar, Rima Melhem, Bo Zhang, Chang Liu, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Emil R Unanue, Ana Maria Arbelaez, Cheryl F Lichti, Xiaoxiao Wan, Et Al.

2020-Current year OA Pubs

The antigenic landscape of autoimmune diabetes reflects a failure to preserve self-tolerance, yet how novel neoantigens emerge in humans remains incompletely understood. Here we designed an immunopeptidomics-based approach to probe HLA-II-bound, islet-derived neoepitopes in patients with type 1 diabetes. We uncovered a Cys→Ser transformation, conserved between mice and humans, that reshapes autoreactivity to insulin at the single-residue level. This transformation, which we call C19S, arises from oxidative remodeling of insulin in stressed pancreatic islets and also occurs in cytokine-activated antigen-presenting cells, contributing to a feed-forward loop of neoepitope formation and presentation. Despite involving just one amino acid, C19S is recognized …

Infant Sensory Gating And A Developmental Cascade To Autistic Traits And Anxiety, Rebecca F Schwarzlose

2020-Current year OA Pubs

Disruptions to the infant sensory environment can have lasting effects on neural response properties and behavior in both humans and animals. Recent work has begun to highlight an additional factor in infant sensory experience: differences in inhibitory signaling and sensory gating. Converging work from human and animal studies has begun to implicate a developmental cascade by which impaired sensory gating during a sensitive period of neonatal neurodevelopment promotes a phenotype of sensory over-responsivity, autistic traits, anxiety, and other psychiatric challenges. In this Review, I propose a model for this developmental cascade and highlight how differences in infant sensory responsivity represent …

Eata Mediated Degradation Of Intestinal Mucus Is Species-Specific And Driven By Muc2 Structural Features, Sergio Trillo-Muyo, Brendan Dolan, Frida Svensson, Tim J Vickers, Liisa Arike, Maria-Jose García-Bonete, Jenny K Gustafsson, Mathias I Nielsen, Hans H Wandall, James M Fleckenstein, Gunnar C Hansson, Sjoerd Van Der Post

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) infections are a leading cause of diarrheal illness, responsible for an estimated 100,000 deaths annually. ETEC pathogenesis is driven by various virulence factors, including toxins, adhesins, and noncanonical factors such as the protease EatA. The first line of host defense against intestinal pathogenic bacterial infections is the protective intestinal mucus layer. Here, we demonstrate the mechanism by which EatA degrades the core mucus component MUC2, thereby facilitating access to the epithelial cell surface and promoting infection. We identify the specific cleavage site region localized at the C-terminal of MUC2. EatA's protease activity depends on the interaction …

Chemotherapy-Induced Adipo-Lineage Cell Senescence Drives Bone Loss, Ganesh Kumar Raut, Taylor Malachowski, Anupama Melam, Renata Ramalho-Oliveira, Taylor Holt, Xianmin Luo, Zhangting Yao, Douglas V Faget, Qihao Ren, David G Denardo, Sheila A Stewart

2020-Current year OA Pubs

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to significant bone loss. Notably, we find that inhibition of the p38MAPK-MK2 pathway suppresses the senescence-associated secretory phenotype (SASP), including RANKL production abrogating bone loss. Furthermore, treatment with the senolytic combination dasatinib and quercetin (D + Q) selectively eliminates …

Exploring Cellular Heterogeneity: Single-Cell And Spatial Transcriptomics Of Alzheimer's Disease Brains And Ipsc-Derived Microglia, Anjali Garg, Sheeny Vo, Iara D De Souza, Ayslan Castro Brant, Logan Brase, Ekaterina Aladyeva, Ricardo D 'O Albanus, Aasritha Nallapu, Hongjun Fu, Oscar Harari

2020-Current year OA Pubs

BACKGROUND: Microglia, the brain’s resident immune cells, play a pivotal role in Alzheimer’s disease (AD) pathogenesis. These cells exhibit diverse transcriptional states in response to neuroinflammatory stimuli, and characterizing these states is essential for understanding AD mechanisms. METHODS: We integrated single-cell and spatial transcriptomic datasets from multiple cohorts and brain regions, encompassing both experimental models and human tissues. Findings were validated through immunostaining of human brain samples. RESULTS: Our comprehensive atlas revealed pronounced heterogeneity among microglial states, with disease-associated microglia (DAM) significantly enriched in AD brains compared to controls. Spatial transcriptomics and immunohistochemistry demonstrated that DAM predominantly localize to external …

Distinct Populations Of Lung Capillary Endothelial Cells And Their Functional Significance, Joel James, Dan Yi, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

The role of the lung's microcirculation and capillary endothelial cells in normal physiology and the pathobiology of pulmonary diseases is obviously vital. The recent discovery of molecularly distinct aerocytes and general capillary (gCaps) endothelial cells by single-cell transcriptomics (scRNAseq) advanced the field in understanding microcirculatory milieu and cellular communications. However, increasing evidence from different groups indicated the possibility of a more heterogeneous nature of lung capillaries. Therefore, we investigated enriched lung endothelial cells by scRNAseq and identified five novel populations of gCaps with distinct molecular signatures and roles. Our analysis suggests that two major populations of gCaps that express Scn7a(Na

Phospholipid Scramblase 1 (Plscr1) Regulates Interferon-Lambda Receptor 1 (Ifn-Λr1) And Ifn-Λ Signaling In Influenza A Virus (Iav) Infection, Alina Xiaoyu Yang, Lisa Ramos-Rodriguez, Parand Sorkhdini, Dongqin Yang, Carmelissa Norbrun, Sonoor Majid, Sanghyun Lee, Yong Zhang, Michael Holtzman, David F Boyd, Yang Zhou

2020-Current year OA Pubs

Phospholipid scramblase 1 (PLSCR1) is an interferon-stimulated gene (ISG) that has several known anti-influenza functions. However, the mechanisms in relation to its expression compartment and enzymatic activity have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections. Our results showed that influenza A virus (IAV)-infected

Ribosomal Protein Control Of Hematopoietic Stem Cell Transformation Through Regulation Of Metabolism, Bryan Harris, Stephen Sykes, Et Al.

2020-Current year OA Pubs

We report here that expression of the ribosomal protein RPL22 is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), and reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from altered metabolism, including increased fatty acid oxidation (FAO) and a striking induction of the stemness factor Lin28b in the resulting leukemia. Lin28b promotes a substantial increase in lipid …

Current Controversies On Adequate Circulating Vitamin D Levels In Ckd, Adriana S Dusso, Daniela J Porta, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) has evolved dramatically over the past five decades, driven by discoveries that have fundamentally reshaped our understanding of the vitamin D endocrine system and its role in disease progression. This review synthesizes the key pathophysiological insights and clinical evidence underlying three critical paradigm shifts. The first shift moved beyond simple calcitriol replacement with the development of selective vitamin D receptor activators (VDRAs) designed to minimize hypercalcemia while maximizing PTH suppression. Crucially, these analogs revealed unexpected survival benefits, suggesting protective VDR actions extending beyond mineral metabolism. The second shift recognized the …

A Protein Complex In The Extreme Distal Tip Of Vertebrate Motile Cilia Controls Their Organization, Length, And Function, Juyeon Hong, Jiehong Pan, Amjad Horani, Steven L Brody, Et Al.

2020-Current year OA Pubs

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization …

A Proteogenomic Gene Signature Defines Prognostic Subgroups Highlighting Pi3k/Akt/Mtor Signaling Pathway As A Therapeutic Vulnerability In Myeloid Malignancies, Fan He, Shuyang Lin, Bei Gao, Varun Ramesh, Alexander B Kim, Tim Kong, Daniel A C Fisher, Christopher T Letson, Molly Brakhane, Mary Fulbright, Yanbo Yu, Marco Sardiello, Jorge Di Paola, Stephen M Sykes, Stephen T Oh

2020-Current year OA Pubs

INTRODUCTION: Myeloid malignancies, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), exhibit overlapping pathophysiology. Chronic MPNs can transform into secondary AML (sAML), which is associated with poor prognosis and limited treatment options. However, the process and prognostic significance of leukemic transformation remain incompletely understood.

METHOD: Through a two-sample bidirectional Mendelian randomization (MR) analysis, we showed that genetic liability to MPN significantly predicts the risk of developing AML, establishing MPN as the precursor to leukemia. To identify mediators of this risk, we integrated population-level plasma proteomics data, identifying 55 proteins associated with MPN. Upon integrative analysis with the BEAT-AML cohort, …

The Inferred Functional Connectome Underlying Circadian Synchronization In The Mouse Suprachiasmatic Nucleus, K L Nikhil, Bharat Singhal, Daniel Granados-Fuentes, Jr-Shin Li, István Z Kiss, Erik D Herzog

2020-Current year OA Pubs

Circadian rhythms in mammals arise from the spatiotemporal synchronization of ~20,000 neuronal clocks in the suprachiasmatic nucleus (SCN). Although anatomical, molecular, and genetic approaches have revealed diverse SCN cell types, how network-level wiring enables their synchronization remains unclear. To overcome the challenges of inferring functional connectivity from fixed tissue, we developed Mutual Information & Transfer Entropy (MITE), an information-theoretic framework to infer directed cell-cell connections with high fidelity from long-term live-cell imaging. Recording and analyzing 3,290 h of clock gene expression from 8,261 SCN neurons across 17 mice, we uncovered a highly conserved, sparse SCN network organized into two asymmetrically …

Wdfy4-Dependent Cross-Presentation Proceeds Via A Vacuolar Antigen-Processing Route, J Luke Postoak, Alyssa Koch, Sicong Shan, Ray A Ohara, Suin Jo, Jing Chen, Pritesh Desai, Feiya Ou, Magdalena Kraft, Michael S Diamond, Sunkyung Kim, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

The intracellular processing route used by type I conventional dendritic cells (cDC1) for cross-presentation of viral- or tumor-associated antigens remains controversial. One model proposes that captured antigens exit from damaged phagolysosomes and enter the cytosol, where they are processed for presentation by MHC class I molecules (MHC-I). This model relies on proteasomal degradation and TAP-dependent peptide transport into the endoplasmic reticulum (ER) for loading by the peptide loading complex (PLC). An alternative model proposes a vesicular route in which captured antigens are retained and processed within an endocytic compartment. A compelling argument favoring the cytosolic model is the dramatic loss …

Intracellular Acinetobacter Baumannii Acts As A Transient Reservoir In Lung Infection Via A "Persist And Resist" Strategy, Manon Janet-Maitre, Gisela Di Venanzio, Clay D Jackson-Litteken, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Although considered primarily extracellular,

Intracranial Injection Of Genetically Modified, Mosquito Non-Transmissible Zika Virus: Safety In Primates And Ramifications For Brain Tumor Therapy, Alec J Hirsch, Amanda De Andrade Costa, Emilie Russler-Germain, Ashwani Kesarwani, Yuping Li, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the …

Loss Of Mfap5 And Its Effect On Skin Homeostasis And Wound Healing, Chen Han, Heidi Yuan, Timothy J Koh, Lin Chen, Robert P Mecham, Luisa A Dipietro

2020-Current year OA Pubs

MFAP5, also known as microfibrillar-associated glycoprotein-2 (MAGP2), may influence parameters of skin wound healing related to scar formation. To further elucidate its role in skin wound healing, we assessed skin wound repair in Mfap5

Biophysical Simulation Enables Segmentation And Nervous System Atlas Mapping For Image First Spatial Omics, Lina Mohammed Ali, Aldrin Kay Yuen Yim, Emanuel Gerbi, Thien Nguyen, Nicholas Tu, Faith Ikede, Remi Sampaleanu, Diana Grigore, Jason Waligorski, Colin Kremitzki, Liya Yuan, Wendy Dong, Robi Mitra, Jeffrey Milbrandt, William Buchser

2020-Current year OA Pubs

Spatial omics (SO) produces high-definition mapping of subcellular molecules within tissue samples. Mapping transcripts to anatomical regions requires segmentation, but this remains challenging in tissue cross-sections with tubular structures like axons in peripheral nerve or spinal cord. Neural networks could address misidentification but are hindered by the need for extensive human annotations. We present SiDoLa-NS (Simulate, Don't Label-Nervous System), an image-driven (top-down) approach to SO analysis in the nervous system. We utilize biophysical properties of tissue architectures to design synthetic images of tissue samples, eliminating reliance on manual annotation and enabling scalable training data generation. With synthetic samples, we trained …

In The Mouth Or In The Gut? Innovation Through Implementing Oral And Gastrointestinal Health Science In Chronic Pain Management, Jo Nijs, Burel R Goodin, Et Al.

2020-Current year OA Pubs

Recent scientific advances point towards an important role for oral and gastrointestinal health in people with chronic pain. Poor oral health (e.g., periodontitis, tooth loss) is observed in subgroups of the chronic pain population, including abdominal pain, low back pain, fibromyalgia, and rheumatoid arthritis. In addition to poor oral health, studies have also revealed altered intestinal microbiota compositions in various types of chronic pain, including people with chronic low back pain, knee osteoarthritis, visceral pain, fibromyalgia, tinnitus, and migraine. While overweight/obesity contributes to the likelihood of gut dysbiosis, normal-weight individuals with chronic pain also more often present with poor gut …

Conservation Of Cis-Regulatory Codes Over Half A Billion Years Of Evolution, Yohey Ogawa, Yu Liu, Connie A Myers, Ala Morshedian, Gordon L Fain, Alapakkam P Sampath, Joseph C Corbo

2020-Current year OA Pubs

Identifying homologous cell types across species is essential for understanding cell type evolution. The retina is ideal for comparative analysis because its six major cell classes have persisted since the origin of vertebrates more than half a billion years ago. Here, we show that the retina's conserved cellular architecture is mirrored by deep conservation of the cis-regulatory codes that govern gene expression. Through single-cell chromatin accessibility analysis of lamprey, fish, bird, and mammalian retinas, we demonstrate cross-species conservation of cis-regulatory codes in all retinal cell classes despite extensive turnover of cis-regulatory regions. Conservation manifests as clustering of high-affinity transcription factor …

Evolutionarily Convergent Mechanism Of Formin Regulation Coordinates Actin Polymerization In Apicomplexan Parasites, Pengge Qian, Yong Fu, Jianwei Zeng, Michael J Naldrett, Rui Zhang, L David Sibley

2020-Current year OA Pubs

Apicomplexan parasites rely on actin-based motility for host cell invasion and for their dissemination. Although previous studies implicate formin 1 (FRM1) in governing this process in

Glycoside Hydrolase-Mediated Glucomannan Catabolism In Segatella Copri, A Target Of Microbiota-Directed Foods For Malnourished Children, Cyrus Zhou, Matthew C Hibberd, Evan M Lee, Suzanne Henrissat, Marie A Crane, Jiye Cheng, Michael J Barratt, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of

Myocardial Lipin1 Protects The Heart Against Ischemic Injury By Preserving Lipid Homeostasis, Jiaxi Guo, Brian N. Finck, Et Al.

2020-Current year OA Pubs

Impaired cardiac lipid metabolism has been reported to cause heart failure. Lipin1, a multifunctional protein, is a phosphatidate phosphatase that generates diacylglycerol from phosphatidic acid and a transcriptional cofactor that regulates lipid metabolism-related gene expression. Here, we investigated the roles of lipin1 in cardiac remodeling after myocardial infarction (MI). The expression levels of lipin1 significantly decreased in cardiomyocytes of the human failing heart and murine ischemic myocardium. Cardiomyocyte-specific Lpin1 knockout (cKO) mice showed left ventricle enlargement and reduced fractional shortening after MI, compared with control mice. This was accompanied by elevated cardiac fibrosis, accumulation of reactive oxygen species, and increased …