8,122 results match your criteria activation altering

Activation of VTA GABA Neurons Disrupts Reward Seeking by Altering Temporal Processing.

Behav Brain Res 2021 Apr 6:113292. Epub 2021 Apr 6.

Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, 14214, United States; Clinical Research Institute on Addictions, University at Buffalo, State University of New York, Buffalo, NY, 14203, United States. Electronic address:

The role of ventral tegmental area (VTA) dopamine in reward, cue processing, and interval timing is well characterized. Using a combinatorial viral approach to target activating DREADDs (Designer Receptors Exclusively Activated by Designer Drugs, hM3D) to GABAergic neurons in the VTA of male rats, we previously showed that activation disrupts responding to reward-predictive cues. Here we explored how VTA GABA neurons influence the perception of time in two fixed interval (FI) tasks, one where the reward or interval is not paired with predictive cues (Non-Cued FI), and another where the start of the FI is signaled by a constant tone that continues until the rewarded response is emitted (Cued FI). Read More

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IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia.

Neurochem Res 2021 Apr 9. Epub 2021 Apr 9.

Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, Pécs, 7624, Hungary.

The hormone hepcidin plays a central role in controlling iron homeostasis. Iron-mediated hepcidin synthesis is triggered via the BMP/SMAD pathway. At inflammation, mainly IL-6 pro-inflammatory cytokine mediates the regulation of hepcidin via the JAK/STAT signalling pathway. Read More

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Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4 T cell perturbations.

Nat Immunol 2021 Apr 8. Epub 2021 Apr 8.

Department of Immunology, Harvard Medical School, Boston, MA, USA.

FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T) cells. CD4 T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T-like cells, some very similar to normal T cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4 T cells. Read More

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Structural variant evolution after telomere crisis.

Nat Commun 2021 04 7;12(1):2093. Epub 2021 Apr 7.

Department of Pathology and Laboratory Medicine, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Telomere crisis contributes to cancer genome evolution, yet only a subset of cancers display breakage-fusion-bridge (BFB) cycles and chromothripsis, hallmarks of experimental telomere crisis identified in previous studies. We examine the spectrum of structural variants (SVs) instigated by natural telomere crisis. Eight spontaneous post-crisis clones did not show prominent patterns of BFB cycles or chromothripsis. Read More

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Differential in vitro effect of endogenous and exogenous nitric oxide on replication of the persistent respiratory syncytial virus genome.

Acta Virol 2021 ;65(1):49-57

Synthesis of nitric oxide (NO) is induced as an early response to viral challenges. Here, we studied effects of endogenous and exogenous NO on respiratory syncytial virus (RSV) genome replication, using a persistently RSV infected macrophage-like cell line. NO was evaluated indirectly by nitrites accumulation and it was increased in infected macrophages with respect to non-infected cells. Read More

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January 2021

Altered Actin Dynamics in Cell Migration of GNE Mutant Cells.

Front Cell Dev Biol 2021 18;9:603742. Epub 2021 Mar 18.

School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.

Cell migration is an essential cellular process that requires coordination of cytoskeletal dynamics, reorganization, and signal transduction. The actin cytoskeleton is central in maintaining the cellular structure as well as regulating the mechanisms of cell motility. Glycosylation, particularly sialylation of cell surface proteins like integrins, regulates signal transduction from the extracellular matrix to the cytoskeletal network. Read More

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Spectral Resting-State EEG (rsEEG) in Chronic Aphasia Is Reliable, Sensitive, and Correlates With Functional Behavior.

Front Hum Neurosci 2021 17;15:624660. Epub 2021 Mar 17.

Department of Speech and Hearing Sciences, University of New Mexico, Albuquerque, NM, United States.

We investigated spectral resting-state EEG in persons with chronic stroke-induced aphasia to determine its reliability, sensitivity, and relationship to functional behaviors. Resting-state EEG has not yet been characterized in this population and was selected given the demonstrated potential of resting-state investigations using other neuroimaging techniques to guide clinical decision-making. Controls and persons with chronic stroke-induced aphasia completed two EEG recording sessions, separated by approximately 1 month, as well as behavioral assessments of language, sensorimotor, and cognitive domains. Read More

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Clustering of adenosine A receptors with ectonucleotidases in caveolin-rich lipid rafts underlies immunomodulation by Leishmania amazonensis.

FASEB J 2021 May;35(5):e21509

Laboratório de Imunoparasitologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.

Extracellular adenosine plays important roles in modulating the immune responses. We have previously demonstrated that infection of dendritic cells (DC) by Leishmania amazonensis leads to increased expression of CD39 and CD73 and to the selective activation of the low affinity A receptors (A R), which contributes to DC inhibition, without involvement of the high affinity A R. To understand this apparent paradox, we now characterized the alterations of both adenosine receptors in infected cells. Read More

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The Mediator complex kinase module is necessary for fructose regulation of liver glycogen levels through induction of glucose-6-phosphatase catalytic subunit (G6pc).

Mol Metab 2021 Mar 31:101227. Epub 2021 Mar 31.

Departments of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461 USA; Developmental and Molecular Biology, and Albert Einstein College of Medicine, Bronx, NY 10461 USA; Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY 10461 USA.

Objective: Liver glycogen levels are dynamic and highly regulated by nutrient availability as the levels decrease during fasting and are restored during the feeding cycle. However, feeding in the presence of fructose in water suppressed glycogen accumulation in the liver by up-regulating the expression of glucose-6-phosphatase catalytic subunit (G6pc) gene although the exact mechanism is unknown. We generated liver specific knockout of MED13 mice that lack the transcriptional Mediator complex kinase module to examine its effect on transcriptional activation of inducible target gene expression, such as the ChREBP- and FOXO1-dependent control of the G6pc gene promoter. Read More

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Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia.

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

Department of Veterinary Medicine and Animal Production, Unit of Pathology, University of Naples "Federico II", 80137 Naples, Italy.

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Read More

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In Vitro Antiviral Activities of Salinomycin on Porcine Epidemic Diarrhea Virus.

Viruses 2021 03 30;13(4). Epub 2021 Mar 30.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. Owing to the lack of effective vaccines and specific therapeutic options for PEDV, it is pertinent to develop new and available antivirals. This study identified, for the first time, a salinomycin that actively inhibited PEDV replication in Vero cells in a dose-dependent manner. Read More

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Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice.

Cells 2021 Mar 4;10(3). Epub 2021 Mar 4.

Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA.

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by "active" cardiac fibroblasts (i.e. Read More

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The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's Disease.

Genes (Basel) 2021 Mar 20;12(3). Epub 2021 Mar 20.

UK Dementia Research Institute at Cardiff University, School of Medicine, Cardiff, CF24 4HQ, UK.

Late-onset Alzheimer's disease (LOAD), the most common cause of dementia, and a huge global health challenge, is a neurodegenerative disease of uncertain aetiology. To deliver effective diagnostics and therapeutics, understanding the molecular basis of the disease is essential. Contemporary large genome-wide association studies (GWAS) have identified over seventy novel genetic susceptibility loci for LOAD. Read More

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Eicosapentaenoic Acid Inhibits Mutant Pancreatic Cancer Cell Growth by Suppressing Hepassocin Expression and STAT3 Phosphorylation.

Biomolecules 2021 Mar 2;11(3). Epub 2021 Mar 2.

Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 11031, Taiwan.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog () mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear.

Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a -wild-type PDAC cell line (BxPC-3), and -mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. Read More

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Brassinosteroid homeostasis is critical for the functionality of the Medicago truncatula pulvinus.

Plant Physiol 2021 Jan 26. Epub 2021 Jan 26.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao, 266237, China.

Many plant species open their leaves during the daytime and close them at night as if sleeping. This leaf movement is known as nyctinasty, a unique and intriguing phenomenon that been of great interest to scientists for centuries. Nyctinastic leaf movement occurs widely in leguminous plants, and is generated by a specialized motor organ, the pulvinus. Read More

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January 2021

Tetherin/BST2, a physiologically and therapeutically relevant regulator of platelet receptor signalling.

Blood Adv 2021 Apr;5(7):1884-1898

School of Physiology, Pharmacology, and Neuroscience, and.

The reactivity of platelets, which play a key role in the pathogenesis of atherothrombosis, is tightly regulated. The integral membrane protein tetherin/bone marrow stromal antigen-2 (BST-2) regulates membrane organization, altering both lipid and protein distribution within the plasma membrane. Because membrane microdomains have an established role in platelet receptor biology, we sought to characterize the physiological relevance of tetherin/BST-2 in those cells. Read More

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Are cysteine residues of human phospholipid scramblase 1 essential for Pb and Hg binding-induced scrambling of phospholipids?

Eur Biophys J 2021 Mar 31. Epub 2021 Mar 31.

Applied and Industrial Microbiology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600 036, India.

Lead and mercury being common environmental pollutants are often associated with erythrocytes, where phosphatidylserine (PS) exposure-mediated procoagulant activation is induced. Human phospholipid scramblase 1 (hPLSCR1) identified in the erythrocyte membrane is a type II transmembrane protein involved in Ca-dependent bidirectional scrambling of phospholipids (PL) during blood coagulation, cell activation, and apoptosis. The prominent role of hPLSCR1 in Pb and Hg poisoning was demonstrated by a biochemical assay, where recombinant hPLSCR1 induced PL scrambling across bilayer with a higher binding affinity (K) towards Hg (4. Read More

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Sleep disturbance induces depressive behaviors and neuroinflammation by altering the circadian oscillations of clock genes in rats.

Neurosci Res 2021 Mar 27. Epub 2021 Mar 27.

Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing, 100850, China. Electronic address:

Sleep loss leads to a spectrum of mood disorders such as anxiety disorders, bipolar disorder and depression in many individuals. However, the underlying mechanisms are largely unknown. In this study, sleep-disturbed animals were tested for anxiety and depressive behaviors. Read More

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New insights into cytotoxic mechanisms of bozepinib against glioblastoma.

Eur J Pharm Sci 2021 Mar 27;162:105823. Epub 2021 Mar 27.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address:

Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults and the current treatments only have a modest effect on patient survival. Recent studies show that bozepinib (BZP), a purine derivative, has potential applications in cancer treatment. The aim of this study was to evaluate the effect of BZP against GBM cells, specially concerning the purinergic system. Read More

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Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation.

Front Immunol 2021 10;12:625165. Epub 2021 Mar 10.

Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. Read More

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Rhubarb extract relieves constipation by stimulating mucus production in the colon and altering the intestinal flora.

Biomed Pharmacother 2021 Mar 25;138:111479. Epub 2021 Mar 25.

Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing 100069, China. Electronic address:

Background: Constipation, mainly characterized by the difficulty in defecation, is a clinical symptom caused by a variety of factors. It can be manifested as normal or slow colonic transport abnormalities, which can occur alone or concurrently with defecation disorders. As there is not uniform definition and assessment standard, no clear plan could be used for the treatment of constipation. Read More

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P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression.

Nat Commun 2021 03 26;12(1):1912. Epub 2021 Mar 26.

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Glioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. Read More

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Adipocyte and steroidogenic cell cross-talk in polycystic ovary syndrome.

Hum Reprod Update 2021 Mar 25. Epub 2021 Mar 25.

Robinson Research Institute Adelaide Medical School, Adelaide, South Australia, Australia.

Background: Metabolic and endocrine alterations in women with polycystic ovary syndrome (PCOS) affect adipose tissue mass and distribution. PCOS is characterised by hyperandrogenism, obesity and adipocyte dysfunction. Hyperandrogenism in PCOS drives dysfunctional adipocyte secretion of potentially harmful adipocytokines. Read More

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Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.

Cardiovasc Res 2021 Mar 23. Epub 2021 Mar 23.

Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.

Aims: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Read More

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Exopolysaccharide anchoring creates an extreme resistance to sedimentation.

J Bacteriol 2021 Mar 22. Epub 2021 Mar 22.

Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA

By evolving strains of that hyper-resist sedimentation, we discovered an uncharacterized mechanism that bacteria can use to remain in suspension indefinitely without expending energy. This unusual phenotype was traced to the anchoring of long colanic acid polymers (CAP) that project from the cell surface. Although each characterized mutant activated this same mechanism, the genes responsible and the strengths of the phenotypes varied. Read More

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Aggregation-induced emission (AIE) nanoparticles labeled human embryonic stem cells (hESCs)-derived neurons for transplantation.

Biomaterials 2021 Mar 9;271:120747. Epub 2021 Mar 9.

Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, 308433, Singapore; Neuroscience & Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore, 169857, Singapore; Lee Kong Chian School of Medicine, Nanyang Technology University, Novena Campus, 11 Mandalay Road, 308232, Singapore. Electronic address:

Transplantation of differentiated neurons derived from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) is an emerging therapeutic strategy for various neurodegenerative diseases. One important aspect of transplantation is the accessibility to track and control the activity of the stem cells-derived neurons post-transplantation. Recently, the characteristics of organic nanoparticles (NPs) with aggregation-induced emission (AIE) have emerged as efficient cell labeling reagents, where positive outcomes were observed in long-term cancer cell tracing in vivo. Read More

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Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle.

J Gen Physiol 2021 Jul;153(7)

Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD.

Microtubules tune cytoskeletal stiffness, which affects cytoskeletal mechanics and mechanotransduction of striated muscle. While recent evidence suggests that microtubules enriched in detyrosinated α-tubulin regulate these processes in healthy muscle and increase them in disease, the possible contribution from several other α-tubulin modifications has not been investigated. Here, we used genetic and pharmacologic strategies in isolated cardiomyocytes and skeletal myofibers to increase the level of acetylated α-tubulin without altering the level of detyrosinated α-tubulin. Read More

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Intrauterine Lethality in Tfpi Gene Disrupted Mice is Differentially Suppressed during Mid- and Late-Gestation by Platelet TFPIα Overexpression.

J Thromb Haemost 2021 Mar 17. Epub 2021 Mar 17.

Versiti Blood Research Institute, Milwaukee, WI, 53226, USA.

Background: Tissue Factor Pathway Inhibitor (TFPI) is an anticoagulant protein required for murine embryonic development. Intrauterine lethality of Tfpi mice occurs at mid- and late-gestation, the latter of which is associated with severe cerebrovascular defects. Megakaryocytes produce only the TFPIα isoform which is stored within platelets and released upon activation. Read More

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Attendance, activation and health profiles of participants, a prospective study on a regional cardiometabolic disease self-management program in Laval, Canada.

BMC Public Health 2021 Mar 12;21(1):497. Epub 2021 Mar 12.

CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Montreal, Canada.

Background: Chronic diseases are responsible for over 70% of all deaths globally. While some self-management programs have been shown to be efficacious in preventing or altering trajectories for some chronic conditions, scaling-up and sustaining such programs beyond tightly-controlled study conditions remain a major challenge. CISSS-Laval partnered with the Cardiovascular Health Awareness Program team to co-develop Cible-santé/prévention and evaluate the first cohort of participants enrolled in the program, in order to better understand the program's implementation and scope. Read More

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Network-based gene deletion analysis identifies candidate genes and molecular mechanism involved in clear cell renal cell carcinoma.

J Genet 2021 ;100

Bioinformatics Programming Lab, Department of Biotechnology, School of Bio Sciences and Technology, VIT, Vellore 632 014, India.

Human clear cell renal cell carcinoma (ccRCC) is the most common and frequently occurring histological subtype of RCC. Unlike other carcinomas, candidate predictive biomarkers for this type are in need to explore the molecular mechanism of ccRCC and identify candidate target genes for improving disease management. For this, we chose case-control-based studies from the Gene Expression Omnibus and subjected the gene expression microarray data to combined effect size meta-analysis for identifying shared genes signature. Read More

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January 2021