52,375 results match your criteria model wild-type


GPR120 inhibits colitis through regulation of CD4T cell IL-10 production.

Gastroenterology 2021 Sep 15. Epub 2021 Sep 15.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA; Department of Pathology, The University of Texas Medical Branch, Galveston, TX, 77555, USA. Electronic address:

Background & Aims: G protein-coupled receptor (GPR) 120 has been implicated in regulating metabolic syndromes with anti-inflammatory function. However, the role of GPR120 in intestinal inflammation is unknown. Here, we investigated whether and how GPR120 regulates CD4T cell function to inhibit colitis development. Read More

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September 2021

Overexpression of miR-132-3p contributes to neuronal protection in in vitro and in vivo models of Alzheimer's disease.

Behav Brain Res 2021 Sep 15:113584. Epub 2021 Sep 15.

Central Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong, 528300, China; Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address:

One of the neuropathological hallmarks of Alzheimer's disease (AD) is accumulation and deposition of amyloid-beta (Aβ) plaques in the hippocampus. Recently, microRNAs (miRNAs), have been demonstrated to play an essential role in AD. We have previously demonstrated that miR-132-3p exerts neuroprotection via regulating histone deacetylase 3 (HDAC3) in a mouse model of AD. Read More

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September 2021

IQSEC2 mutation associated with epilepsy, intellectual disability, and autism results in hyperexcitability of patient-derived neurons and deficient synaptic transmission.

Mol Psychiatry 2021 Sep 17. Epub 2021 Sep 17.

Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.

Mutations in the IQSEC2 gene are associated with drug-resistant, multifocal infantile and childhood epilepsy; autism; and severe intellectual disability (ID). We used induced pluripotent stem cell (iPSC) technology to obtain hippocampal neurons to investigate the neuropathology of IQSEC2-mediated disease. The neurons were characterized at three-time points during differentiation to assess developmental progression. Read More

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September 2021

Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity.

Nat Commun 2021 Sep 17;12(1):5520. Epub 2021 Sep 17.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

PTEN promoter hypermethylation is nearly universal and PTEN copy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we show Pten deletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. Read More

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September 2021

Regulatory effect of NLRP3 on airway inflammatory response and pyroptosis in mice with asthma.

Authors:
Chao Hui Xin Liu

Zhongguo Dang Dai Er Ke Za Zhi 2021 Sept 15;23(9):959-964

Clinical Laboratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China (Liu X, Email: com).

Objectives: To study the regulatory effect of the NOD-like receptor, pyrin domain-containing 3 (NLRP3) on airway inflammatory response and pyroptosis in mice with asthma.

Methods: The wild-type (WT) C57BL/6J mice were divided into two groups: -WT control and -WT asthma. The mice with knockout (KO) were divided into two groups: -KO control and -KO asthma (=10 each). Read More

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September 2021

Dopaminergic but not Cholinergic Neurodegeneration is Correlated with Gait Disturbances in PINK1 Knockout Rats.

Behav Brain Res 2021 Sep 14:113575. Epub 2021 Sep 14.

Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030. Electronic address:

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by gait dysfunction in later stages of the disease. PD hallmarks include a decrease in stride length, run speed, and swing time; an increase in stride time, stance time, and base of support; dopaminergic degeneration in the basal ganglia; and cholinergic degeneration in the pedunculopontine nucleus (PPN). A progressive animal model of PD is needed to identify treatments for gait dysfunction. Read More

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September 2021

High salt diet-induced proximal tubular phenotypic changes and sodium-glucose cotransporter-2 expression are coordinated by cold shock Y-box binding protein-1.

FASEB J 2021 Oct;35(10):e21912

Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

High salt diet (HSD) is a hallmark of blood pressure elevations, weight gain and diabetes onset in the metabolic syndrome. In kidney, compensatory mechanisms are activated to balance salt turnover and maintain homeostasis. Data on the long-term effects of HSD with respect to tubular cell functions and kidney architecture that exclude confounding indirect blood pressure effects are scarce. Read More

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October 2021

Mitochondrial ROS Induced Lysosomal Dysfunction and Autophagy Impairment in an Animal Model of Congenital Hereditary Endothelial Dystrophy.

Invest Ophthalmol Vis Sci 2021 Sep;62(12):15

Vision Science Program, School of Optometry, Indiana University, Bloomington, Indiana, United States.

Purpose: The Slc4a11 knock out (KO) mouse model recapitulates the human disease phenotype associated with congenital hereditary endothelial dystrophy (CHED). Increased mitochondrial reactive oxygen species (ROS) in the Slc4a11 KO mouse model is a major cause of edema and endothelial cell loss. Here, we asked if autophagy was activated by ROS in the KO mice. Read More

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September 2021

Modeling human glucose-6-phosphate dehydrogenase mutations using GSPD-1.

MicroPubl Biol 2021 10;2021. Epub 2021 Sep 10.

Division of Natural Sciences, New College of Florida, Sarasota, FL, USA.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked, recessive condition that causes intermittent jaundice or hemolytic anemia because of low NADPH levels in red blood cells. We performed steady-state enzyme kinetics with the recombinant ortholog of human G6PD, GSPD-1, and two mutants containing amino acid changes found in human patients. The values for glucose-6-phosphate were 100 ± 27 µM, 80 ± 22 µM, and 1000 ± 300 µM for the wild-type, D60N, and R252L GSPD-1 enzymes, respectively. Read More

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September 2021

Adiponectin alleviated renal cell apoptosis and inflammation via inactivation of JAK2/STAT3 signal pathway in an acute pyelonephritis mouse model.

Authors:
Guoyu Dai Yao He

Ann Transl Med 2021 Aug;9(16):1311

Department of Urology, Xiangya Hospital, Central South University, Changsha, China.

Background: Acute pyelonephritis (APN), an acute and severe kidney infection, is usually treated with antibiotics. However, APN treatment has become increasingly challenging because of bacterial resistance. Adiponectin, an adipokine, has recently been reported to exhibit profound anti-inflammatory and anti-apoptotic effects. Read More

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Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration.

Front Pharmacol 2021 31;12:711590. Epub 2021 Aug 31.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY, United States.

Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. Read More

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Estrogen Receptor β as a Candidate Regulator of Sex Differences in the Maternal Immune Activation Model of ASD.

Front Mol Neurosci 2021 31;14:717411. Epub 2021 Aug 31.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States.

Interestingly, more males are diagnosed with autism spectrum disorder (ASD) than females, yet the mechanism behind this difference is unclear. Genes on the sex chromosomes and differential regulation by sex steroid hormones and their receptors are both candidate mechanisms to explain this sex-dependent phenotype. Nuclear receptors (NRs) are a large family of transcription factors, including sex hormone receptors, that mediate ligand-dependent transcription and may play key roles in sex-specific regulation of immunity and brain development. Read More

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Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii.

Sci Rep 2021 Sep 16;11(1):18414. Epub 2021 Sep 16.

Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, 800 N State College Blvd, Fullerton, CA, 92831, USA.

In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. Read More

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September 2021

The hepatic senescence-associated secretory phenotype promotes hepatocarcinogenesis through Bcl3-dependent activation of macrophages.

Cell Biosci 2021 Sep 16;11(1):173. Epub 2021 Sep 16.

Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian, 350004, People's Republic of China.

Background: Liver cancer is one of the most common malignancies in the world with a poor prognosis. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer, accounting for 80-90% of cases. The initiation and progression of HCC are closely associated with chronic liver inflammation. Read More

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September 2021

Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes.

Parasit Vectors 2021 Sep 16;14(1):480. Epub 2021 Sep 16.

CSIRO Data61, Hobart, Australia.

Background: Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains.

Methods: In this study, we: (i) describe a diffusion-advection-reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains.

Results: If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location. Read More

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September 2021

Endosomal traffic and glutamate synapse activity are increased in VPS35 D620N mutant knock-in mouse neurons, and resistant to LRRK2 kinase inhibition.

Mol Brain 2021 Sep 16;14(1):143. Epub 2021 Sep 16.

Graduate Program in Neuroscience and Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.

Vacuolar protein sorting 35 (VPS35) regulates neurotransmitter receptor recycling from endosomes. A missense mutation (D620N) in VPS35 leads to autosomal-dominant, late-onset Parkinson's disease. Here, we study the basic neurobiology of VPS35 and Parkinson's disease mutation effects in the D620N knock-in mouse and the effect of leucine-rich repeat kinase 2 (LRRK2) inhibition on synaptic phenotypes. Read More

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September 2021

Arg Deficiency Does not Influence the Course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced Experimental Autoimmune Encephalomyelitis.

J Clin Cell Immunol 2016 23;7(3). Epub 2016 May 23.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has been extensively studied in immune activation, roles for Arg are incompletely characterized. Read More

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Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease.

Parkinsonism Relat Disord 2021 Sep 11;91:59-65. Epub 2021 Sep 11.

Laboratory for Translational Neurodegeneration Research, Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Austria. Electronic address:

The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). Read More

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September 2021

Sex and dose-dependent antinociceptive effects of the JNK (c-Jun N-terminal kinase) inhibitor SU 3327 are mediated by CB receptors in female, and CB/CB receptors in male mice in an inflammatory pain model.

Brain Res Bull 2021 Sep 13. Epub 2021 Sep 13.

Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, 79430; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, 79430. Electronic address:

Activation of c-Jun N-terminal kinases (JNKs) has been implicated in the development and persistence of inflammatory and neuropathic pain in animal models. Moreover, JNKs have been involved in the maintenance of chronic pain, as well as development of tolerance to antinociceptive agents in the opioid and cannabinoid class of compounds. In this study, we evaluated the antinociceptive effects of the JNK inhibitor SU 3327 (0. Read More

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September 2021

Cost-minimization analysis of biweekly dosing of cetuximab and FOLFIRI compared with panitumumab and FOLFOX for first-line treatment of patients with KRAS wild type metastatic colorectal cancer in the United States.

J Med Econ 2021 Sep 16. Epub 2021 Sep 16.

Eli Lilly and Company, Indianapolis, IN, United States.

Aim: To compare the cost of biweekly regimens of first-line (1L) treatments of cetuximab-FOLFIRI versus panitumumab-FOLFOX in patients with Kirsten's rat sarcoma wild type (KRAS WT) metastatic colorectal cancer (mCRC) in the US, across varying weights and body surface areas (BSAs).

Materials And Methods: Cost-minimization analysis (CMA) was performed to estimate per-patient cost differences of cetuximab-FOLFIRI versus panitumumab-FOLFOX. The CMA estimated the costs of rat sarcoma (RAS) testing, premedication, drug acquisition, treating infusion reactions (IRs), supportive therapy, and biweekly administration of chemotherapy, cetuximab (500 mg/m), and panitumumab (6 mg/kg) over 43 weeks (median progression-free survival). Read More

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September 2021

Whole-organism 3D quantitative characterization of zebrafish melanin by silver deposition micro-CT.

Elife 2021 09 16;10. Epub 2021 Sep 16.

Division of Experimental Pathology, Department of Pathology, Pennsylvania State University College of Medicine, Hershey, United States.

We previously described X-ray histotomography, a high-resolution, non-destructive form of X-ray microtomography (micro-CT) imaging customized for three-dimensional (3D), digital histology, allowing quantitative, volumetric tissue and organismal phenotyping (Ding et al., 2019). Here, we have combined micro-CT with a novel application of ionic silver staining to characterize melanin distribution in whole zebrafish larvae. Read More

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September 2021

Endothelial Poldip2 regulates sepsis-induced lung injury via Rho pathway activation.

Cardiovasc Res 2021 Sep 16. Epub 2021 Sep 16.

Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA.

Aims: Sepsis-induced lung injury is associated with significant morbidity and mortality. Previously, we showed that heterozygous deletion of polymerase δ-interacting protein 2 (Poldip2) was protective against sepsis-induced lung injury. Since endothelial barrier disruption is thought to be the main mechanism of sepsis-induced lung injury, we sought to determine if the observed protection was specifically due to the effect of reduced endothelial Poldip2. Read More

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September 2021

A Dual Role for Death Receptor 5 in Regulating Cardiac Fibroblast Function.

Front Cardiovasc Med 2021 30;8:699102. Epub 2021 Aug 30.

Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, United States.

The fibrotic response is involved in nearly all forms of heart failure and dysregulated responses can lead to enhanced cardiac dysfunction. TNF-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor (DR) 5, are associated with multiple forms of heart failure, but their role in the heart is poorly defined. Our previous study identified DR5 expression on cardiac fibroblasts however, the impact of DR5 on fibroblast function remains unexplored. Read More

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Efficient Correction of a Hypertrophic Cardiomyopathy Mutation by ABEmax-NG.

Circ Res 2021 Sep 16. Epub 2021 Sep 16.

Anzhen Hospital, Capital Medical University, CHINA.

Genetic editing has shown great potential for the treatment of human hereditary disorders via the elimination of mutations in embryos. However, the efficiency and safety of germline gene editing are not well understood. We aimed to examine the preclinical efficacy/safety of embryonic base editing in a mouse model of hypertrophic cardiomyopathy (HCM) using a novel adenine base editor (ABE) platform. Read More

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September 2021

Role of cellular prion protein in splenic CD4 T cell differentiation in cerebral ischaemic/reperfusion.

Ann Clin Transl Neurol 2021 Sep 15. Epub 2021 Sep 15.

Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China.

Objective: Cellular prion protein (PrP ), the primary form of prion diseases pathogen, has received increasing attention for its protective effect against ischaemic stroke. Little is known about its role in peripheral immune responses after cerebral ischaemia/reperfusion (I/R) injury. This study is to detect the variation of splenic CD4 T lymphocytes differentiation and the concentration of inflammatory cytokines after murine cerebral I/R injury in the context of PRNP expression as well as its influence on the ischaemic neuronal apoptosis. Read More

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September 2021

Gene expression profiles in the brain of phenylketonuria mouse model reversed by the low phenylalanine diet therapy.

Metab Brain Dis 2021 Sep 15. Epub 2021 Sep 15.

Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Kongjiang Road 1665#, Shanghai, 200092, China.

To gain insight into the potential protective mechanisms of low phenylalanine diet (LPD) in phenylketonuria (PKU), gene expression profiles were studied in the cerebral cortex and hippocampus of a PKU mouse model (BTBR-Pah). PKU mice were fed with low Phe diet (LPD-PKU group) and normal diet (PKU group). Wild-type mice were treated with normal diet (WT group) as control. Read More

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September 2021

Master regulator NtrC controls the utilization of alternative nitrogen sources in Pseudomonas stutzeri A1501.

World J Microbiol Biotechnol 2021 Sep 15;37(10):177. Epub 2021 Sep 15.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.

Pseudomonas stutzeri A1501 is a model strain used to study associative nitrogen fixation, and it possesses the nitrogen regulatory NtrC protein in the core genome. Nitrogen sources represent one of the important factors affecting the efficiency of biological nitrogen fixation in the natural environment. However, the regulation of NtrC during nitrogen metabolism in P. Read More

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September 2021

A natural variant in ANP32B impairs influenza virus replication in human cells.

J Gen Virol 2021 Sep;102(9)

Department of Infectious Disease, Faculty of Medicine, Imperial College London, UK.

Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human and genes. Read More

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September 2021

Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging.

Microbiol Spectr 2021 Sep 15:e0049821. Epub 2021 Sep 15.

Juniata Collegegrid.258264.f, Huntingdon, Pennsylvania, USA.

Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans () and three long-lived mutants (, , and ) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. Read More

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September 2021

Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

J Virol 2021 Sep 15:JVI0097421. Epub 2021 Sep 15.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Read More

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September 2021