3,495 results match your criteria wild-type counterparts


Sestrin proteins protect against lipotoxicity-induced oxidative stress in the liver via suppression of c-Jun N-terminal kinases: Short title: Sestrins ameliorate hepatic lipotoxicity.

Cell Mol Gastroenterol Hepatol 2021 May 4. Epub 2021 May 4.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:

Background & Aims: Sestrin 1/2/3 (Sesn1/2/3) belong to a small family of proteins that have been implicated in the regulation of metabolic homeostasis and oxidative stress. However, the underlying mechanisms remain incompletely understood. The aim of this work was to illustrate the collective function of Sesn1/2/3 in the protection against hepatic lipotoxicity. Read More

View Article and Full-Text PDF

Ammonium transporter AcAmt mutagenesis uncovers reproductive and physiological defects without impacting olfactory responses to ammonia in the malaria vector mosquito Anopheles coluzzii.

Insect Biochem Mol Biol 2021 Apr 30;134:103578. Epub 2021 Apr 30.

Department of Biological Sciences, Vanderbilt University, Nashville, TN, 37235, USA. Electronic address:

Anopheline mosquitoes are the sole vectors of malaria and rely on olfactory cues for host seeking in which ammonia derived from human sweat plays an essential role. To investigate the function of the Anopheles coluzzii ammonium transporter (AcAmt) in the mosquito olfactory system, we generated an AcAmt null mutant line using CRISPR/Cas9. AcAmt mutants displayed a series of novel phenotypes compared with wild-type mosquitoes including significantly lower insemination rates during mating and increased mortality during eclosion. Read More

View Article and Full-Text PDF

Influence of TRAIL Deficiency on Th17 Cells and Colonic Microbiota in Experimental Colitis Mouse Model.

Am J Med Sci 2021 Apr 28. Epub 2021 Apr 28.

Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address:

Background: The abnormalities of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are implicated in various autoimmune disorders and tumors. This study investigated the influence of TRAIL deficiency on Th17 cells and colonic microbiota in experimental colitis mouse model.

Methods: Mice were randomly divided into 4 groups: wild-type, TRAIL gene knock-out (TRAIL), wild-type colitis and TRAIL colitis groups. Read More

View Article and Full-Text PDF

Age-Dependent Dysregulation of Muscle Vasculature and Blood Flow Recovery after Hindlimb Ischemia in the Model of Duchenne Muscular Dystrophy.

Biomedicines 2021 Apr 27;9(5). Epub 2021 Apr 27.

Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.

Duchenne muscular dystrophy (DMD), caused by a lack of functional dystrophin, is characterized by progressive muscle degeneration. Interestingly, dystrophin is also expressed in endothelial cells (ECs), and insufficient angiogenesis has already been hypothesized to contribute to DMD pathology, however, its status in mice, a model of DMD, is still not fully clear. Our study aimed to reveal angiogenesis-related alterations in skeletal muscles of mice compared to wild-type (WT) counterparts. Read More

View Article and Full-Text PDF

Aim2 and Nlrp3 Are Dispensable For Vaccine-Induced Immunity Against Live Vaccine Strain.

Infect Immun 2021 Apr 19. Epub 2021 Apr 19.

Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USA

() is a facultative intracellular, Gram-negative bacterium that causes a fatal disease known as tularemia. Due to its extremely high virulence, ease of spread by aerosolization, and the potential to be used as a bioterror agent, is classified by the CDC as a Tier 1 Category A Select Agent. Previous studies have demonstrated the roles of inflammasome sensors; absent in melanoma 2 (AIM2) and NLRP3, in the generation of innate immune responses to infection. Read More

View Article and Full-Text PDF

Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice.

Toxicology 2021 Apr 16;456:152785. Epub 2021 Apr 16.

Department of Occupational and Environmental Health, Tokyo University of Science, Noda, Japan. Electronic address:

Acrylamide (ACR), a recognized neurotoxicant in humans and experimental animals, is widely used in industry and in food generated through Maillard reaction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular defense system and activates antioxidants and cytoprotective genes. The exact roles of Nrf2 in environmental electrophile-induced neurotoxicity is poorly understood. Read More

View Article and Full-Text PDF

Enhancement of Pharmaceutical Urate Oxidase Thermostability by Rational Design of Disulfide Bridge.

Iran J Biotechnol 2020 Jul 1;18(3):e2662. Epub 2020 Jul 1.

Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background And Purpose: As a therapeutic enzyme, urate oxidase is utilized in the reduction of uric acid in various conditions such as gout or tumor syndrome lysis. However, even bearing kinetical advantage over other counterparts, it suffers from structural instability most likely due to its subcellular and fungal origin.

Objectives: In this research, by using rational design and introduction of disulfide bridge in urate oxidase structure, we designed and created a thermostable urate oxidase for the first time. Read More

View Article and Full-Text PDF

Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden;

The gut epithelium serves to maximize the surface for nutrient and fluid uptake, but at the same time must provide a tight barrier to pathogens and remove damaged intestinal epithelial cells (IECs) without jeopardizing barrier integrity. How the epithelium coordinates these tasks remains a question of significant interest. We used imaging and an optical flow analysis pipeline to study the dynamicity of untransformed murine and human intestinal epithelia, cultured atop flexible hydrogel supports. Read More

View Article and Full-Text PDF

Impaired contextual fear conditioning in RasGRF2 mutant mice is likely Ras-ERK-dependent.

Neurobiol Learn Mem 2021 Apr 6;181:107435. Epub 2021 Apr 6.

Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. Electronic address:

Ras/Raf/MEK/ERK (Ras-ERK) signaling has been shown to play an important role in fear acquisition. However, little information is known regarding the mechanisms that contribute to the regulation of this pathway in terms of the learning of conditioned fears. Ras Guanine Nucleotide Releasing Factor 2 (RasGRF2) is one of two guanine nucleotide exchange factors (GEF) that regulates the Ras-ERK signaling pathway in a Ca-dependent manner via control of the cycling of Ras isoforms between an inactive and active state. Read More

View Article and Full-Text PDF

Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss.

Front Cell Neurosci 2021 22;15:658990. Epub 2021 Mar 22.

Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, France.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. Read More

View Article and Full-Text PDF

Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders.

eNeuro 2021 Mar-Apr;8(2). Epub 2021 Apr 16.

Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada

Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been largely overlooked. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. Genetically engineered mouse models are widely used to gain insight into the biology of human NDDs, but research focus has been on behavioral and neurophysiological abnormalities. Read More

View Article and Full-Text PDF

Auranofin Resistance in Decreases the Accumulation of Reactive Oxygen Species but Does Not Target Parasite Thioredoxin Reductase.

Front Cell Infect Microbiol 2021 19;11:618994. Epub 2021 Mar 19.

Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, United States.

Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including . We generated auranofin resistant lines through chemical mutagenesis to identify the molecular target of this drug. Read More

View Article and Full-Text PDF

The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis.

Front Cell Infect Microbiol 2021 18;11:618265. Epub 2021 Mar 18.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: Aging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.

Objective: To explore the underlying mechanism of how aging aggravates AS advancement.

Methods: A young (five-week-old, YM) and aged group (32-week-old, OM) male apoE mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. Read More

View Article and Full-Text PDF

Perspectives on New Vaccines against Arboviruses Using Insect-Specific Viruses as Platforms.

Vaccines (Basel) 2021 Mar 16;9(3). Epub 2021 Mar 16.

Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, 1945 SW 16th Ave, Gainesville, FL 32608, USA.

Arthropod-borne viruses (arboviruses) are global pathogens circulating endemically with local explosive outbreaks and constant encroachment into new locations. Few vaccines against arboviruses exist; most for humans are in development or clinical trials. Insect-specific viruses (ISVs) offer a unique platform for expression of arbovirus proteins, through the creation of ISV/arbovirus chimeras. Read More

View Article and Full-Text PDF

Poly(ADP-Ribose) Polymerase 1 Promotes Inflammation and Fibrosis in a Mouse Model of Chronic Pancreatitis.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by ductal obstructions, tissue fibrosis, atrophy and exocrine and endocrine pancreatic insufficiency. However, our understanding is very limited concerning the disease's progression from a single acute inflammation, via recurrent acute pancreatitis (AP) and early CP, to the late stage CP. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage. Read More

View Article and Full-Text PDF

Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice.

Nutrients 2021 Mar 24;13(4). Epub 2021 Mar 24.

Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.

Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor's (GHS-R; a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models. Read More

View Article and Full-Text PDF

Voluntary Wheel Running Did Not Alter Gene Expression in 5xfad Mice, but in Wild-Type Animals Exclusively after One-Day of Physical Activity.

Cells 2021 Mar 20;10(3). Epub 2021 Mar 20.

Working Group Healthy Aging and Neurodegeneration, Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.

Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer's disease (AD). However, the positive effect of therapeutic administration of physical activity has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different routines of physical activity in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute) and 30-day (chronic) voluntary wheel running and compared them with age-matched sedentary controls. Read More

View Article and Full-Text PDF

Regulation of -Butyl Hydroperoxide Resistance by Chromosomal OhrR in ATCC 19606.

Microorganisms 2021 Mar 18;9(3). Epub 2021 Mar 18.

Master Program in Microbiology and Immunology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.

In this study, we show that ATCC 19606 harbors two sets of genes, respectively encoded in chromosomal DNA and a pMAC plasmid. We found no significant difference in organic hydroperoxide (OHP) resistance between strains with or without pMAC. However, a disk diffusion assay conducted by exposing wild-type, , represented gene on chromosome, or single mutants, or -- double mutants to -butyl hydroperoxide (BHP) found that the genes, represented genes on pMAC plasmid, may be able to complement the function of their chromosomal counterparts. Read More

View Article and Full-Text PDF

Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle.

Membranes (Basel) 2021 Mar 3;11(3). Epub 2021 Mar 3.

Center of Physiology and Pharmacology, Institute of Pharmacology and the Gaston H. Glock Research Laboratories for Exploratory Drug Development, Medical University of Vienna, 1090 Vienna, Austria.

Plasmalemmal solute carriers (SLC) gauge and control solute abundance across cellular membranes. By virtue of this action, they play an important role in numerous physiological processes. Mutations in genes encoding the SLCs alter amino acid sequence that often leads to impaired protein function and onset of monogenic disorders. Read More

View Article and Full-Text PDF

An SNX10-dependent mechanism down-regulates fusion between mature osteoclasts.

J Cell Sci 2021 04 1. Epub 2021 Apr 1.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel

Homozygosity for the R51Q mutation in sorting nexin 10 (SNX10) inactivates osteoclasts (OCLs) and induces autosomal recessive osteopetrosis in humans and in mice. We show here that fusion of wild-type murine monocytes to form OCLs is highly regulated, and that its extent is limited by blocking fusion between mature OCLs. In contrast, monocytes from homozygous R51Q SNX10 mice fuse uncontrollably, forming giant dysfunctional OCLs that can become 10-100 fold larger than their wild-type counterparts. Read More

View Article and Full-Text PDF

MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs.

Elife 2021 03 31;10. Epub 2021 Mar 31.

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Read More

View Article and Full-Text PDF

RNA-sequencing and behavioral testing reveals inherited physical inactivity co-selects for anxiogenic behavior without altering depressive-like behavior in Wistar rats.

Neurosci Lett 2021 05 27;753:135854. Epub 2021 Mar 27.

Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA.

Physical inactivity is positively associated with anxiety and depression. Considering physical inactivity, anxiety, and depression each have a genetic basis for inheritance, our lab used artificial selectively bred low-voluntary running (LVR) and wild type (WT) female Wistar rats to test if physical inactivity genes selected over multiple generations would lead to an anxiety or depressive-like phenotype. We performed next generation RNA sequencing and immunoblotting on the dentate gyrus to reveal key biological functions from heritable physical inactivity. Read More

View Article and Full-Text PDF

Characterization of an algal phosphomannose isomerase gene and its application as a selectable marker for genetic manipulation of tomato.

Plant Divers 2021 Feb 15;43(1):63-70. Epub 2020 Jun 15.

Key Laboratory of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.

Establishing a transgenic plant largely relies on a selectable marker gene that can confer antibiotic or herbicide resistance to plant cells. The existence of such selectable marker genes in genetically modified foods has long been criticized. Plant cells generally exhibit too low an activity of phosphomannose isomerase (PMI) to grow with mannose as a sole carbon source. Read More

View Article and Full-Text PDF
February 2021

Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice.

Front Endocrinol (Lausanne) 2021 5;12:619696. Epub 2021 Mar 5.

Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.

Prolactin (PRL) levels are reduced in the circulation of rats with diabetes or obesity, and lower circulating levels of PRL correlate with increased prevalence of diabetes and a higher risk of metabolic alterations in the clinic. Furthermore, PRL stimulates β-cell proliferation, survival, and insulin production and pregnant mice lacking PRL receptors in β-cells develop gestational diabetes. To investigate the protective effect of endogenous PRL against diabetes outside pregnancy, we compared the number of cases and severity of streptozotocin (STZ)-induced hyperglycemia between C57BL/6 mice null for the PRL receptor gene ( ) and wild-type mice ( ). Read More

View Article and Full-Text PDF

ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1.

Allergy Asthma Immunol Res 2021 May;13(3):479-497

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.

Purpose: Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. Read More

View Article and Full-Text PDF

Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling.

J Cell Mol Med 2021 Mar 17. Epub 2021 Mar 17.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

Under steady-state conditions, the pool size of peripheral CD8 T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8 T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). Read More

View Article and Full-Text PDF

Ectopic expression of GmHP08 enhances resistance of transgenic Arabidopsis toward drought stress.

Plant Cell Rep 2021 May 16;40(5):819-834. Epub 2021 Mar 16.

Applied Biotechnology for Crop Development Research Unit, School of Biotechnology, International University, Quarter 6, Linh Trung Ward, Thu Duc, Ho Chi Minh, 700000, Vietnam.

Key Message: Ectopic expression of Glycine max two-component system member GmHP08 in Arabidopsis enhanced drought tolerance of transgenic plants, possibly via ABA-dependent pathways. Phosphorelay by two-component system (TCS) is a signal transduction mechanism which has been evolutionarily conserved in both prokaryotic and eukaryotic organisms. Previous studies have provided lines of evidence on the involvement of TCS genes in plant perception and responses to environmental stimuli. Read More

View Article and Full-Text PDF

The effect of aging and chronic microglia activation on the morphology and numbers of the cerebellar Purkinje cells.

Neurosci Lett 2021 04 8;751:135807. Epub 2021 Mar 8.

Department of Pharmacology, School of Medicine, Western Sydney University, Penrith, New South Wales, Australia. Electronic address:

Reduced cerebellar volume and motor dysfunction have previously been observed in the GFAP-IL6 murine model of chronic neuroinflammation. This study aims to extend these findings by investigating the effect of microglial activation and ageing on the total number of Purkinje cells and the morphology of their dendritic arborization. Through comparison of transgenic GFAP-IL6 mice and their wild-type counterparts at the ages of 12 and 24-months, we were able to investigate the effects of ageing and chronic microglial activation on Purkinje cells. Read More

View Article and Full-Text PDF

IL-17 deficiency aggravates the streptozotocin-induced diabetic nephropathy through the reduction of autophagosome formation in mice.

Mol Med 2021 03 10;27(1):25. Epub 2021 Mar 10.

Department of Veterinary Medicine, Institute of Veterinary Science, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.

Background: Diabetic nephropathy (DN) is one of the most important medical complications of diabetes mellitus. Autophagy is an important mediator of pathological response and plays a critical role in inflammation during the progression of diabetic nephropathy. Interleukin (IL)-17A favorably modulates inflammatory disorders including DN. Read More

View Article and Full-Text PDF

Fungal -Intrinsic Protein Aquaporin from : Structural and Functional Considerations.

Biomolecules 2021 02 23;11(2). Epub 2021 Feb 23.

Université Clermont Auvergne, INRAE, PIAF, 63000 Clermont-Ferrand, France.

The major intrinsic protein (MIP) superfamily is a key part of the fungal transmembrane transport network. It facilitates the transport of water and low molecular weight solutes across biomembranes. The fungal uncharacterized X-Intrinsic Protein (XIP) subfamily includes the full protein diversity of MIP. Read More

View Article and Full-Text PDF
February 2021