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PSYCHIATRY AND NEUROLOGY (833 journals)                  1 2 3 4 5 | Last

Showing 1 - 200 of 833 Journals sorted alphabetically
Academic Psychiatry     Full-text available via subscription   (Followers: 32)
Academic Psychiatry and Psychology Journal : APPJ     Open Access   (Followers: 13)
ACS Chemical Neuroscience     Hybrid Journal   (Followers: 24)
Acta Neurochirurgica     Hybrid Journal   (Followers: 7)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 3)
Acta Neurológica Colombiana     Open Access   (Followers: 2)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 6)
Acta Neuropathologica     Hybrid Journal   (Followers: 6)
Acta Neuropathologica Communications     Open Access   (Followers: 1)
Acta Neuropsychiatrica     Hybrid Journal   (Followers: 6)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 44)
Actas Españolas de Psiquiatría     Free   (Followers: 2)
Activitas Nervosa Superior     Hybrid Journal  
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 28)
ADHD Report The     Full-text available via subscription   (Followers: 12)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 20)
Adolescent Psychiatry     Hybrid Journal   (Followers: 12)
Adolescent Research Review     Hybrid Journal   (Followers: 3)
Advances in Alzheimer's Disease     Open Access   (Followers: 16)
Advances in Clinical Neuroscience and Rehabilitation     Free   (Followers: 31)
Advances in Eating Disorders : Theory, Research and Practice     Hybrid Journal   (Followers: 18)
Advances in Mental Health     Hybrid Journal   (Followers: 91)
Advances in Parkinson's Disease     Open Access   (Followers: 1)
Advances in School Mental Health Promotion     Partially Free   (Followers: 12)
African Journal of Neurological Sciences     Open Access  
African Journal of Psychiatry     Full-text available via subscription   (Followers: 3)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 487)
Aggressive Behavior     Hybrid Journal   (Followers: 22)
Aging & Mental Health     Hybrid Journal   (Followers: 37)
Aging, Neuropsychology, and Cognition     Hybrid Journal   (Followers: 50)
AJOB Neuroscience     Hybrid Journal   (Followers: 5)
Aktuelle Neurologie     Hybrid Journal   (Followers: 9)
Alzheimer Disease & Associated Disorders     Hybrid Journal   (Followers: 20)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 60)
Alzheimer's Research & Therapy     Open Access   (Followers: 4)
American Journal of Alzheimer's Disease and Other Dementias     Hybrid Journal   (Followers: 19)
American Journal of Clinical Hypnosis     Hybrid Journal   (Followers: 6)
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4)
American Journal of Neuroprotection and Neuroregeneration     Full-text available via subscription   (Followers: 2)
American Journal of Psychiatric Rehabilitation     Hybrid Journal   (Followers: 13)
American Journal of Psychiatry     Full-text available via subscription   (Followers: 242)
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration     Hybrid Journal   (Followers: 2)
Analitika : Jurnal Magister Psikologi Uma     Open Access  
Annales Médico-psychologiques, revue psychiatrique     Full-text available via subscription   (Followers: 5)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 15)
Annals of Child Neurology     Open Access   (Followers: 1)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Clinical Psychiatry : The official Journal of the American Academy of Clinical Psychiatrists     Hybrid Journal   (Followers: 28)
Annals of General Psychiatry     Open Access   (Followers: 28)
Annals of Indian Academy of Neurology     Open Access   (Followers: 3)
Annals of Indian Psychiatry     Open Access  
Annals of Neurology     Hybrid Journal   (Followers: 61)
Annals of Neurosciences     Open Access   (Followers: 4)
Annals of Psychiatry and Treatment     Open Access   (Followers: 2)
Annual Review of Neuroscience     Full-text available via subscription   (Followers: 57)
Anxiety, Stress & Coping: An International Journal     Hybrid Journal   (Followers: 27)
Aphasiology     Hybrid Journal   (Followers: 55)
Applied Neuropsychology : Adult     Hybrid Journal   (Followers: 45)
Applied Neuropsychology : Child     Hybrid Journal   (Followers: 28)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 32)
Archives of Neuroscience     Open Access   (Followers: 6)
Archives of Psychiatric Nursing     Hybrid Journal   (Followers: 29)
Archives of Suicide Research     Hybrid Journal   (Followers: 9)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 18)
Archivos de Neurociencias     Open Access   (Followers: 3)
Arquivos Brasileiros de Neurocirurgia : Brazilian Neurosurgery     Open Access  
Arquivos de Neuro-Psiquiatria     Open Access  
Art Therapy Online     Open Access   (Followers: 4)
Asia Pacific Journal of Counselling and Psychotherapy     Hybrid Journal   (Followers: 11)
Asian Journal of Psychiatry     Hybrid Journal   (Followers: 2)
ASN Neuro     Open Access   (Followers: 2)
Assessment     Hybrid Journal   (Followers: 17)
Assessment and Treatment of Child Psychopathology and Developmental Disabilities     Full-text available via subscription   (Followers: 4)
Atherosclerosis     Hybrid Journal   (Followers: 13)
Atherosclerosis Supplements     Hybrid Journal   (Followers: 1)
Audiology and Neurotology     Full-text available via subscription   (Followers: 9)
Audiology and Neurotology Extra     Open Access   (Followers: 1)
Australasian Journal of Neuroscience     Open Access   (Followers: 2)
Australasian Psychiatry     Hybrid Journal   (Followers: 18)
Australian & New Zealand Journal of Psychiatry     Hybrid Journal   (Followers: 29)
Autism & Developmental Language Impairments     Open Access   (Followers: 12)
Autism and Developmental Disorders     Open Access   (Followers: 9)
Autism Research     Hybrid Journal   (Followers: 52)
Autism Research and Treatment     Open Access   (Followers: 34)
Autism's Own     Open Access   (Followers: 6)
Autism-Open Access     Open Access   (Followers: 8)
Autonomic Neuroscience     Hybrid Journal   (Followers: 10)
Autonomy, the Critical Journal of Interdisciplinary Autism Studies     Open Access   (Followers: 5)
Avicenna Journal of Neuro Psycho Physiology     Open Access  
Basal Ganglia     Hybrid Journal  
Basic and Clinical Neuroscience     Open Access   (Followers: 9)
Behavior Therapy     Hybrid Journal   (Followers: 54)
Behavioral and Brain Functions     Open Access   (Followers: 3)
Behavioral and Brain Sciences     Hybrid Journal   (Followers: 38)
Behavioral and Cognitive Neuroscience Reviews     Hybrid Journal   (Followers: 26)
Behavioral Healthcare     Full-text available via subscription   (Followers: 8)
Behavioral Medicine     Hybrid Journal   (Followers: 9)
Behavioral Sciences     Open Access   (Followers: 4)
Behavioral Sleep Medicine     Hybrid Journal   (Followers: 15)
Behavioural Brain Research     Hybrid Journal   (Followers: 19)
Behavioural Neurology     Open Access   (Followers: 9)
Behavioural Processes     Hybrid Journal   (Followers: 9)
Biological Psychiatry     Hybrid Journal   (Followers: 53)
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging     Hybrid Journal   (Followers: 11)
Biologically Inspired Cognitive Architectures     Hybrid Journal   (Followers: 2)
Biology of Mood & Anxiety Disorders     Open Access   (Followers: 6)
Biomarkers in Neuropsychiatry     Open Access   (Followers: 1)
BioMolecular Concepts     Open Access   (Followers: 2)
Bipolar Disorders     Hybrid Journal   (Followers: 11)
BJPsych Advances     Full-text available via subscription   (Followers: 57)
BJPsych Bulletin     Full-text available via subscription   (Followers: 19)
BJPsych International     Open Access   (Followers: 2)
BJPsych Open     Open Access   (Followers: 3)
Blue Books of Neurology     Full-text available via subscription   (Followers: 1)
BMC Neurology     Open Access   (Followers: 22)
BMC Neuroscience     Open Access   (Followers: 17)
BMC Psychiatry     Open Access   (Followers: 38)
Borderline Personality Disorder and Emotion Dysregulation     Open Access   (Followers: 10)
Brain     Hybrid Journal   (Followers: 78)
Brain & Life     Full-text available via subscription   (Followers: 3)
Brain and Behavior     Open Access   (Followers: 15)
Brain and Cognition     Hybrid Journal   (Followers: 38)
Brain and Development     Full-text available via subscription   (Followers: 5)
Brain and Language     Hybrid Journal   (Followers: 68)
Brain and Mind     Hybrid Journal   (Followers: 6)
Brain and Neuroscience Advances     Open Access  
Brain Behavior and Evolution     Full-text available via subscription   (Followers: 9)
Brain Communications     Open Access   (Followers: 3)
Brain Disorders & Therapy     Open Access   (Followers: 1)
Brain Hemorrhages     Open Access   (Followers: 1)
Brain Imaging and Behavior     Hybrid Journal   (Followers: 9)
Brain Impairment     Full-text available via subscription   (Followers: 2)
Brain Informatics     Open Access   (Followers: 1)
Brain Injury     Hybrid Journal   (Followers: 31)
Brain Pathology     Hybrid Journal   (Followers: 5)
Brain Research     Hybrid Journal   (Followers: 26)
Brain Research Bulletin     Hybrid Journal   (Followers: 5)
Brain Sciences     Open Access   (Followers: 5)
Brain Stimulation     Hybrid Journal   (Followers: 8)
Brain Structure and Function     Partially Free   (Followers: 9)
Brain Topography     Hybrid Journal   (Followers: 2)
Brain, Behavior, and Immunity     Hybrid Journal   (Followers: 11)
Brazilian Journal of Pain (BrJP)     Open Access  
British Journal of Mental Health Nursing     Full-text available via subscription   (Followers: 23)
British Journal of Music Therapy     Hybrid Journal   (Followers: 8)
British Journal of Pain     Hybrid Journal   (Followers: 28)
British Journal of Psychiatry     Hybrid Journal   (Followers: 247)
British Journal of Social Psychology     Full-text available via subscription   (Followers: 41)
Canadian Journal of Behavioural Science     Full-text available via subscription   (Followers: 7)
Canadian Journal of Counselling and Psychotherapy / Revue canadienne de counseling et de psychothérapie     Hybrid Journal   (Followers: 10)
Canadian Journal of Neurological Sciences     Full-text available via subscription  
Canadian Journal of Psychiatry     Hybrid Journal   (Followers: 27)
Cannabis and Cannabinoid Research     Hybrid Journal   (Followers: 2)
Case Reports in Neurological Medicine     Open Access   (Followers: 1)
Case Reports in Neurology     Open Access   (Followers: 5)
Case Reports in Psychiatry     Open Access   (Followers: 17)
Cellular and Molecular Life Sciences (CMLS)     Hybrid Journal   (Followers: 5)
Central Nervous System Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 1)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cerebellum & Ataxias     Open Access   (Followers: 1)
Cerebral Cortex     Hybrid Journal   (Followers: 56)
Cerebrovascular Diseases     Full-text available via subscription   (Followers: 3)
Cerebrovascular Diseases Extra     Open Access  
Child and Adolescent Psychiatry and Mental Health     Open Access   (Followers: 28)
Child Neurology Open     Open Access   (Followers: 5)
Child Psychiatry & Human Development     Hybrid Journal   (Followers: 12)
Chinese Neurosurgical Journal     Open Access  
Chronic Stress     Open Access  
Ciencia Cognitiva     Open Access   (Followers: 3)
Clínica e Investigación en Arteriosclerosis     Full-text available via subscription  
Clinical and Experimental Neuroimmunology     Hybrid Journal   (Followers: 1)
Clinical and Translational Neuroscience     Open Access  
Clinical EEG and Neuroscience     Hybrid Journal   (Followers: 6)
Clinical Journal of Pain     Hybrid Journal   (Followers: 19)
Clinical Medicine Insights : Psychiatry     Open Access   (Followers: 10)
Clinical Neurology and Neurosurgery     Hybrid Journal   (Followers: 16)
Clinical Neuropathology     Full-text available via subscription   (Followers: 1)
Clinical Neuropharmacology     Hybrid Journal   (Followers: 4)
Clinical Neurophysiology     Full-text available via subscription   (Followers: 13)
Clinical Neurophysiology Practice     Open Access  
Clinical Neuropsychiatry     Open Access   (Followers: 2)
Clinical Practice & Epidemiology in Mental Health     Open Access   (Followers: 1)
Clinical Psychological Science     Hybrid Journal   (Followers: 12)
CNS & Neurological Disorders - Drug Targets     Hybrid Journal   (Followers: 3)
CNS Spectrums     Hybrid Journal   (Followers: 3)
Cognition     Hybrid Journal   (Followers: 231)
Cognitive and Behavioral Neurology     Hybrid Journal   (Followers: 10)
Cognitive and Behavioral Practice     Hybrid Journal   (Followers: 13)
Cognitive Neurodynamics     Hybrid Journal   (Followers: 2)
Cognitive Neuropsychiatry     Hybrid Journal   (Followers: 1)
Cognitive Neuropsychology     Hybrid Journal   (Followers: 40)
Cognitive Neuroscience     Hybrid Journal   (Followers: 29)
Cognitive Therapy and Research     Hybrid Journal   (Followers: 7)
Cognitive, Affective, & Behavioral Neuroscience     Full-text available via subscription   (Followers: 24)
Community Mental Health Journal     Hybrid Journal   (Followers: 18)
Comprehensive Psychiatry     Open Access   (Followers: 13)
Computational Brain & Behavior     Hybrid Journal  
Computational Psychiatry     Open Access   (Followers: 2)
Consciousness and Cognition     Hybrid Journal   (Followers: 39)
Contemporary Neurosurgery     Full-text available via subscription   (Followers: 4)

        1 2 3 4 5 | Last

Similar Journals
Journal Cover
Cellular and Molecular Life Sciences (CMLS)
Journal Prestige (SJR): 3.388
Citation Impact (citeScore): 6
Number of Followers: 5  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1420-682X - ISSN (Online) 1420-9071
Published by Springer-Verlag Homepage  [2626 journals]
  • miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts
           cardiac development and electrical activity in zebrafish
    • Abstract: Abstract To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5lox/+and Tbx5del/+ mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. MiR-182-5p, the most highly expressed miRNA of this family, was functionally analyzed in zebrafish. Transient overexpression of miR-182-5p affected heart morphology, calcium handling and the onset of arrhythmias as detected by ECG tracings. Accordingly, several calcium channel proteins identified as putative miR-182-5p targets were downregulated in miR-182-5p overexpressing hearts. In stable zebrafish transgenic lines, we demonstrated that selective miRNA-182-5p upregulation contributes to arrhythmias. Moreover, cardiac-specific down-regulation of miR-182-5p rescued cardiac defects in a zebrafish model of Holt–Oram syndrome. In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development.
      PubDate: 2020-08-01
       
  • Why and how to investigate the role of protein phosphorylation in ZIP and
           ZnT zinc transporter activity and regulation
    • Abstract: Abstract Zinc is required for the regulation of proliferation, metabolism, and cell signaling. It is an intracellular second messenger, and the cellular level of ionic, mobile zinc is strictly controlled by zinc transporters. In mammals, zinc homeostasis is primarily regulated by ZIP and ZnT zinc transporters. The importance of these transporters is underscored by the list of diseases resulting from changes in transporter expression and activity. However, despite numerous structural studies of the transporters revealing both zinc binding sites and motifs important for transporter function, the exact molecular mechanisms regulating ZIP and ZnT activities are still not clear. For example, protein phosphorylation was found to regulate ZIP7 activity resulting in the release of Zn2+ from intracellular stores leading to phosphorylation of tyrosine kinases and activation of signaling pathways. In addition, sequence analyses predict all 24 human zinc transporters to be phosphorylated suggesting that protein phosphorylation is important for regulation of transporter function. This review describes how zinc transporters are implicated in a number of important human diseases. It summarizes the current knowledge regarding ZIP and ZnT transporter structures and points to how protein phosphorylation seems to be important for the regulation of zinc transporter activity. The review addresses the need to investigate the role of protein phosphorylation in zinc transporter function and regulation, and argues for a pressing need to introduce quantitative phosphoproteomics to specifically target zinc transporters and proteins involved in zinc signaling. Finally, different quantitative phosphoproteomic strategies are suggested.
      PubDate: 2020-08-01
       
  • Functional mosaic organization of neuroligins in neuronal circuits
    • Abstract: Abstract Complex brain circuitry with feedforward and feedback systems regulates neuronal activity, enabling neural networks to process and drive the entire spectrum of cognitive, behavioral, sensory, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits is underpinned by hundreds of synaptic adhesion molecules that span synaptic junctions. Dysfunction of a single molecule or molecular interaction at synapses can lead to disrupted circuit activity and brain disorders. Neuroligins, a family of cell adhesion molecules, were first identified as postsynaptic-binding partners of presynaptic neurexins and are essential for synapse specification and maturation. Here, we review recent advances in our understanding of how this family of adhesion molecules controls neuronal circuit assembly by acting in a synapse-specific manner.
      PubDate: 2020-08-01
       
  • Exocytosis of large-diameter lysosomes mediates interferon γ-induced
           relocation of MHC class II molecules toward the surface of astrocytes
    • Abstract: Abstract Astrocytes are the key homeostatic cells in the central nervous system; initiation of reactive astrogliosis contributes to neuroinflammation. Pro-inflammatory cytokine interferon γ (IFNγ) induces the expression of the major histocompatibility complex class II (MHCII) molecules, involved in antigen presentation in reactive astrocytes. The pathway for MHCII delivery to the astrocyte plasma membrane, where MHCII present antigens, is unknown. Rat astrocytes in culture and in organotypic slices were exposed to IFNγ to induce reactive astrogliosis. Astrocytes were probed with optophysiologic tools to investigate subcellular localization of immunolabeled MHCII, and with electrophysiology to characterize interactions of single vesicles with the plasmalemma. In culture and in organotypic slices, IFNγ augmented the astrocytic expression of MHCII, which prominently co-localized with lysosomal marker LAMP1-EGFP, modestly co-localized with Rab7, and did not co-localize with endosomal markers Rab4A, EEA1, and TPC1. MHCII lysosomal localization was corroborated by treatment with the lysosomolytic agent glycyl-l-phenylalanine-β-naphthylamide, which reduced the number of MHCII-positive vesicles. The surface presence of MHCII was revealed by immunolabeling of live non-permeabilized cells. In IFNγ-treated astrocytes, an increased fraction of large-diameter exocytotic vesicles (lysosome-like vesicles) with prolonged fusion pore dwell time and larger pore conductance was recorded, whereas the rate of endocytosis was decreased. Stimulation with ATP, which triggers cytosolic calcium signaling, increased the frequency of exocytotic events, whereas the frequency of full endocytosis was further reduced. In IFNγ-treated astrocytes, MHCII-linked antigen surface presentation is mediated by increased lysosomal exocytosis, whereas surface retention of antigens is prolonged by concomitant inhibition of endocytosis.
      PubDate: 2020-08-01
       
  • The RNA–RNA base pairing potential of human Dicer and Ago2 proteins
    • Abstract: Abstract The ribonuclease Dicer produces microRNAs (miRNAs) and small interfering RNAs that are handed over to Ago proteins to control gene expression by targeting complementary sequences within transcripts. Interestingly, a growing number of reports have demonstrated that the activity of Dicer may extend beyond the biogenesis of small regulatory RNAs. Among them, a report from our latest studies revealed that human Dicer facilitates base pairing of complementary sequences present in two nucleic acids, thus acting as a nucleic acid annealer. Accordingly, in this manuscript, we address how RNA structure influences the annealing activity of human Dicer. We show that Dicer supports hybridization between a small RNA and a complementary sequence of a longer RNA in vitro, even when both complementary sequences are trapped within secondary structures. Moreover, we show that under applied conditions, human Ago2, a core component of RNA-induced silencing complex, displays very limited annealing activity. Based on the available data from new-generation sequencing experiments regarding the RNA pool bound to Dicer in vivo, we show that multiple Dicer-binding sites within mRNAs also contain miRNA targets. Subsequently, we demonstrate in vitro that Dicer but not Ago2 can anneal miRNA to its target present within mRNA. We hypothesize that not all miRNA duplexes are handed over to Ago proteins. Instead, miRNA-Dicer complexes could target specific sequences within transcripts and either compete or cooperate for binding sites with miRNA-Ago complexes. Thus, not only Ago but also Dicer might be directly involved in the posttranscriptional control of gene expression.
      PubDate: 2020-08-01
       
  • Targets for protection and mitigation of radiation injury
    • Abstract: Abstract Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to an old dogma in radiation biology; a major amount of reactive oxygen species (ROS) production and cell toxicity occur during some hours to years after exposure to ionizing radiation. This can be attributed to upregulation of inflammatory and fibrosis mediators, epigenetic changes and disruption of the normal metabolism of oxygen. In the current review, we explain the cellular and molecular changes following exposure of normal tissues to ionizing radiation. Furthermore, we review potential targets that can be proposed for protection and mitigation of radiation toxicity.
      PubDate: 2020-08-01
       
  • Cellular uptake of collagens and implications for immune cell regulation
           in disease
    • Abstract: Abstract As the dominant constituent of the extracellular matrix (ECM), collagens of different types are critical for the structural properties of tissues and make up scaffolds for cellular adhesion and migration. Importantly, collagens also directly modulate the phenotypic state of cells by transmitting signals that influence proliferation, differentiation, polarization, survival, and more, to cells of mesenchymal, epithelial, or endothelial origin. Recently, the potential of collagens to provide immune regulatory signals has also been demonstrated, and it is believed that pathological changes in the ECM shape immune cell phenotype. Collagens are themselves heavily regulated by a multitude of structural modulations or by catabolic pathways. One of these pathways involves a cellular uptake of collagens or soluble collagen-like defense collagens of the innate immune system mediated by endocytic collagen receptors. This cellular uptake is followed by the degradation of collagens in lysosomes. The potential of this pathway to regulate collagens in pathological conditions is evident from the increased extracellular accumulation of both collagens and collagen-like defense collagens following endocytic collagen receptor ablation. Here, we review how endocytic collagen receptors regulate collagen turnover during physiological conditions and in pathological conditions, such as fibrosis and cancer. Furthermore, we highlight the potential of collagens to regulate immune cells and discuss how endocytic collagen receptors can directly regulate immune cell activity in pathological conditions or do it indirectly by altering the extracellular milieu. Finally, we discuss the potential collagen receptors utilized by immune cells to directly detect ECM-related changes in the tissues which they encounter.
      PubDate: 2020-08-01
       
  • Genetic deletion of a short fragment of glucokinase in rabbit by
           CRISPR/Cas9 leading to hyperglycemia and other typical features seen in
           MODY-2
    • Abstract: Abstract Glucokinase (GCK) is a key enzyme in glucose sensing and glycemic regulation. In humans, mutations in the GCK gene cause maturity-onset diabetes of the young 2 (MODY-2), a disease that is characterized by an early-onset and persistent hyperglycemia. It is known that Gck knockout (KO) is lethal in mice with Gck KO mice dying within 2 weeks after birth. Therefore, Gck KO mice are not suitable for preclinical study and have limited suitability to study the pathophysiological role of glucokinase in vivo. Here, we report the generation of a novel rabbit with a non-frameshift mutation of GCK gene (GCK-NFS) by cytoplasm microinjection of Cas9 mRNA and gRNA. These GCK-NFS rabbits showed typical features of MODY-2 including hyperglycemia and glucose intolerance with similar survival rate and weight compared to wild-type (WT) rabbits. The diabetic phenotype including pancreatic and renal dysfunction was also found in the F1-generation rabbits, indicating that the genetic modification is germline transmissible. Treatment of GCK-NFS rabbit with glimepiride successfully reduced the fasting blood glucose drastically and improved its islet function. In conclusion, this novel GCK mutant rabbit generated with the CRISPR/Cas9 system mimics most, if not all, histopathological and functional defects seen in MODY-2 patients such as hyperglycemia and will be a valuable rabbit model for preclinical studies and drug screening for diabetes as well as for studying the pathophysiological role of glucokinase.
      PubDate: 2020-08-01
       
  • Deletion of Voltage-Dependent Anion Channel 1 knocks mitochondria down
           triggering metabolic rewiring in yeast
    • Abstract: Abstract The Voltage-Dependent Anion-selective Channel (VDAC) is the pore-forming protein of mitochondrial outer membrane, allowing metabolites and ions exchanges. In Saccharomyces cerevisiae, inactivation of POR1, encoding VDAC1, produces defective growth in the presence of non-fermentable carbon source. Here, we characterized the whole-genome expression pattern of a VDAC1-null strain (Δpor1) by microarray analysis, discovering that the expression of mitochondrial genes was completely abolished, as consequence of the dramatic reduction of mtDNA. To overcome organelle dysfunction, Δpor1 cells do not activate the rescue signaling retrograde response, as ρ0 cells, and rather carry out complete metabolic rewiring. The TCA cycle works in a “branched” fashion, shunting intermediates towards mitochondrial pyruvate generation via malic enzyme, and the glycolysis-derived pyruvate is pushed towards cytosolic utilization by PDH bypass rather than the canonical mitochondrial uptake. Overall, Δpor1 cells enhance phospholipid biosynthesis, accumulate lipid droplets, increase vacuoles and cell size, overproduce and excrete inositol. Such unexpected re-arrangement of whole metabolism suggests a regulatory role of VDAC1 in cell bioenergetics.
      PubDate: 2020-08-01
       
  • Revisiting cellular immune response to oncogenic Marek’s disease virus:
           the rising of avian T-cell immunity
    • Abstract: Abstract Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. Although Marek’s disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding of molecular and cellular immunity to MDV and its immunopathogenesis has significantly improved, but those findings about cellular immunity to MDV are largely out-of-date, hampering the development of more effective vaccines against MD. T-cell-mediated cellular immunity was thought to be of paramount importance against MDV. However, MDV also infects macrophages, B cells and T cells, leading to immunosuppression and T-cell lymphoma. Additionally, there is limited information about how uninfected immune cells respond to MDV infection or vaccination, specifically, the mechanisms by which T cells are activated and recognize MDV antigens and how the function and properties of activated T cells correlate with immune protection against MDV or MD tumor. The current review revisits the roles of each immune cell subset and its effector mechanisms in the host immune response to MDV infection or vaccination from the point of view of comparative immunology. We particularly emphasize areas of research requiring further investigation and provide useful information for rational design and development of novel MDV vaccines.
      PubDate: 2020-08-01
       
  • Physiological functions of SPP/SPPL intramembrane proteases
    • Abstract: Abstract Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still growing spectrum of biological functions and also promoted the substrate discovery of these proteases. In this review, we will summarise the current hypotheses how phenotypes of these mouse models are linked to the molecular function of the enzymes. At the cellular level, SPP/SPPL-mediated cleavage events rather provide specific regulatory switches than unspecific bulk proteolysis. By this means, a plethora of different cell biological pathways is influenced including signal transduction, membrane trafficking and protein glycosylation.
      PubDate: 2020-08-01
       
  • Nitric oxide and peroxynitrite trigger and enhance release of neutrophil
           extracellular traps
    • Abstract: Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently induced NETs release and potentiated NETs-inducing properties of platelet activating factor and lipopolysaccharide. RNS-induced NETs formation was independent of autophagy and histone citrullination, but dependent on the activity of phosphoinositide 3-kinases (PI3K) and myeloperoxidase, as well as selective degradation of histones H2A and H2B by neutrophil elastase. Additionally, NADPH oxidase activity was required to release NETs upon stimulation with NO, as shown in NADPH-deficient neutrophils isolated from patients with chronic granulomatous disease. The role of RNS was further supported by increased RNS synthesis upon stimulation of NETs release with phorbol 12-myristate 13-acetate and calcium ionophore A23187. Scavenging or inhibition of RNS formation diminished NETs release triggered by these stimuli while scavenging of peroxynitrite inhibited NO-induced NETs formation. Our data suggest that RNS may act as mediators and inducers of NETs release. These processes are PI3K-dependent and ROS-dependent. Since inflammatory reactions are often accompanied by nitrosative stress and NETs formation, our studies shed a new light on possible mechanisms engaged in various immune-mediated conditions.
      PubDate: 2020-08-01
       
  • Adenosine-to-inosine RNA editing in the immune system: friend or foe'
    • Abstract: Abstract Our body expresses sensors to detect pathogens through the recognition of expressed molecules, including nucleic acids, lipids, and proteins, while immune tolerance prevents an overreaction with self and the development of autoimmune disease. Adenosine (A)-to-inosine (I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a post-transcriptional modification that can potentially occur at over 100 million sites in the human genome, mainly in Alu repetitive elements that preferentially form a double-stranded RNA (dsRNA) structure. A-to-I conversion within dsRNA, which may induce a structural change, is required to escape from the host immune system, given that endogenous dsRNAs transcribed from Alu repetitive elements are potentially recognized by melanoma differentiation-associated protein 5 (MDA5) as non-self. Of note, loss-of-function mutations in the ADAR1 gene cause Aicardi–Goutières syndrome, a congenital autoimmune disease characterized by encephalopathy and a type I interferon (IFN) signature. However, the loss of ADAR1 in cancer cells with an IFN signature induces lethality via the activation of protein kinase R in addition to MDA5. This makes cells more sensitive to immunotherapy, highlighting the opposing immune status of autoimmune diseases (overreaction) and cancer (tolerance). In this review, we provide an overview of insights into two opposing aspects of RNA editing that functions as a modulator of the immune system in autoimmune diseases and cancer.
      PubDate: 2020-08-01
       
  • Apelin/APJ system: an emerging therapeutic target for respiratory diseases
    • Abstract: Abstract Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells’ proliferation and migration via triggering ERK1/2–cyclin D1 and PAK1–cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.
      PubDate: 2020-08-01
       
  • CFP1-dependent histone H3K4 trimethylation in murine oocytes facilitates
           
    • Abstract: Abstract CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles. CFP1-dependent H3K4 trimethylation in oocytes was necessary to maintain the expression of key paracrine factors and to facilitate the communication between an oocyte and the surrounding granulosa cells. The distinct gene expression patterns in cumulus cells within preovulatory follicles were disrupted by the Cxxc1 deletion in oocytes. Both follicle growth and ovulation were compromised after CFP1 deletion, because Cxxc1 deletion in oocytes indirectly impaired essential signaling pathways in granulosa cells that mediate the functions of follicle-stimulating hormone and luteinizing hormone. Therefore, CFP1-regulated epigenetic modification of the oocyte genome influences the responses of ovarian follicles to gonadotropin in a cell-nonautonomous manner.
      PubDate: 2020-08-01
       
  • Founder cells for hepatocytes during liver regeneration: from
           identification to application
    • Abstract: Abstract Liver regeneration (LR) capacity in vertebrates developed through natural selection over a hundred million years of evolution. To maintain homeostasis or recover from various injuries, liver cells must regenerate; this process includes the renewal of parenchymal and nonparenchymal cells as well as the formation of liver structures. The cellular origin of newly grown tissue is one of the critical questions in this area and has been a subject of prolonged debate. The regenerative tissue may derive from either hepatocyte self-duplication or liver stem/progenitor cells (LSPCs). Recently, hepatocyte subpopulations and cholangiocytes were also described as important founder cells. The niche that triggers the proliferation of hepatocytes and the differentiation of LSPCs has been extensively studied. Meanwhile, in vitro culture systems for liver founder cells and organoids have been developed rapidly for mechanistic studies and potential therapeutic purposes. This review summarizes the cellular sources and niches that give rise to renewed hepatocytes during LR, and it also describes in vitro culture studies of those founder cells for future applications, as well as current reports for stem cell-based therapies for liver diseases.
      PubDate: 2020-08-01
       
  • Abnormal X chromosome inactivation and tumor development
    • Abstract: Abstract During embryonic development, one of the two X chromosomes of a mammalian female cell is randomly inactivated by the X chromosome inactivation mechanism, which is mainly dependent on the regulation of the non-coding RNA X-inactive specific transcript at the X chromosome inactivation center. There are three proteins that are essential for X-inactive specific transcript to function properly: scaffold attachment factor-A, lamin B receptor, and SMRT- and HDAC-associated repressor protein. In addition, the absence of X-inactive specific transcript expression promotes tumor development. During the process of chromosome inactivation, some tumor suppressor genes escape inactivation of the X chromosome and thereby continue to play a role in tumor suppression. A well-functioning tumor suppressor gene on the idle X chromosome in women is one of the reasons they have a lower propensity to develop cancer than men, women thereby benefit from this enhanced tumor suppression. This review will explore the mechanism of X chromosome inactivation, discuss the relationship between X chromosome inactivation and tumorigenesis, and consider the consequent sex differences in cancer.
      PubDate: 2020-08-01
       
  • Running and swimming prevent the deregulation of the BDNF/TrkB
           neurotrophic signalling at the neuromuscular junction in mice with
           amyotrophic lateral sclerosis
    • Abstract: Abstract Nerve-induced muscle contraction regulates the BDNF/TrkB neurotrophic signalling to retrogradely modulate neurotransmission and protect the neuromuscular junctions and motoneurons. In muscles with amyotrophic lateral sclerosis, this pathway is strongly misbalanced and neuromuscular junctions are destabilized, which may directly cause the motoneuron degeneration and muscular atrophy observed in this disease. Here, we sought to demonstrate (1) that physical exercise, whose recommendation has been controversial in amyotrophic lateral sclerosis, would be a good option for its therapy, because it normalizes and improves the altered neurotrophin pathway and (2) a plausible molecular mechanism underlying its positive effect. SOD1-G93A mice were trained following either running or swimming-based protocols since the beginning of the symptomatic phase (day 70 of age) until day 115. Next, the full BDNF pathway, including receptors, downstream kinases and proteins related with neurotransmission, was characterized and motoneuron survival was analysed. The results establish that amyotrophic lateral sclerosis-induced damaging molecular changes in the BDNF/TrkB pathway are reduced, prevented or even overcompensated by precisely defined exercise protocols that modulate TrkB isoforms and neurotransmission regulatory proteins and reduce motoneuron death. Altogether, the maintenance of the BDNF/TrkB signalling and the downstream pathway, particularly after the swimming protocol, adds new molecular evidence of the benefits of physical exercise to reduce the impact of amyotrophic lateral sclerosis. These results are encouraging since they reveal an improvement even starting the therapy after the onset of the disease.
      PubDate: 2020-08-01
       
  • Dynamics of kinetochore structure and its regulations during mitotic
           progression
    • Abstract: Abstract Faithful chromosome segregation during mitosis in eukaryotes requires attachment of the kinetochore, a large protein complex assembled on the centromere of each chromosome, to the spindle microtubules. The kinetochore is a structural interface for the microtubule attachment and provides molecular surveillance mechanisms that monitor and ensure the precise microtubule attachment as well, including error correction and spindle assembly checkpoint. During mitotic progression, the kinetochore undergoes dynamic morphological changes that are observable through electron microscopy as well as through fluorescence microscopy. These structural changes might be associated with the kinetochore function. In this review, we summarize how the dynamics of kinetochore morphology are associated with its functions and discuss recent findings on the switching of protein interaction networks in the kinetochore during cell cycle progression.
      PubDate: 2020-08-01
       
  • Homotrimeric MMP-9 is an active hitchhiker on alpha-2-macroglobulin
           partially escaping protease inhibition and internalization through LRP-1
    • Abstract: Abstract Proteolysis is a crucial process in life, tightly controlled by numerous natural protease inhibitors. In human blood, alpha-2-macroglobulin is an emergency protease inhibitor preventing coagulation and damage to endothelia and leukocytes. With the use of a unique protease trapping mechanism, alpha-2-macroglobulin lures active proteases into its snap-trap, shields these from potential substrates and ‘flags’ their complex for elimination by receptor-mediated endocytosis. Matrix metalloprotease-9/gelatinase B is a secreted protease increased in blood of patients with inflammations, vascular disorders and cancers. Matrix metalloprotease-9 occurs as monomers and stable homotrimers, but the reason for their co-existence remains obscure. We discovered that matrix metalloprotease-9 homotrimers undergo reduced anti-proteolytic regulation by alpha-2-macroglobulin and are able to travel as a proteolytically active hitchhiker on alpha-2-macroglobulin. As a comparison, we revealed that monomeric active matrix metalloprotease-9 is efficiently trapped by human plasma alpha-2-macroglobulin and this masks the detection of activated matrix metalloprotease-9 with standard analysis techniques. In addition, we show that alpha-2-macroglobulin/trimer complexes escape clearance through the receptor low-density lipoprotein receptor-related protein 1, also known as the alpha-2-macroglobulin receptor. Thus, the biochemistry and biology of matrix metalloprotease-9 monomers and trimers are completely different as multimerization enables active matrix metalloprotease-9 to partially avoid alpha-2-macroglobulin regulation both by direct protease inhibition and by removal from the extracellular space by receptor-mediated endocytosis. Finally, for the biomarker field, the analysis of alpha-2-macroglobulin/protease complexes with upgraded technology is advocated as a quotum for protease activation in human plasma samples.
      PubDate: 2020-08-01
       
 
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