Search results for "MR"
showing 10 items of 3001 documents
Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy
2018
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory p…
Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2
2016
We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …
Structural and functional insights into lysostaphin–substrate interaction
2018
Lysostaphin from Staphylococcus simulans and its family enzymes rapidly acquire prominence as the next generation agents in treatment of S. aureus infections. The specificity of lysostaphin is promoted by its C-terminal cell wall targeting domain selectivity towards pentaglycine bridges in S. aureus cell wall. Scission of these cross-links is carried out by its N-terminal catalytic domain, a zinc-dependent endopeptidase. Understanding the determinants affecting the efficiency of catalysis and strength and specificity of interactions lies at the heart of all lysostaphin family enzyme applications. To this end, we have used NMR, SAXS and molecular dynamics simulations to characterize lysostap…
Transcriptional Upregulation of DNA Damage Response Genes in Bank Voles (Myodes glareolus) Inhabiting the Chernobyl Exclusion Zone
2018
Exposure to ionizing radiation (IR) from radionuclides released into the environment can damage DNA. An expected response to exposure to environmental radionuclides, therefore, is initiation of DNA damage response (DDR) pathways. Increased DNA damage is a characteristic of many organisms exposed to radionuclides but expression of DDR genes of wildlife inhabiting an area contaminated by radionuclides is poorly understood. We quantified expression of five central DDR genes Atm, Mre11, p53, Brca1, and p21 in the livers of the bank vole Myodes glareolus that inhabited areas within the Chernobyl Exclusion Zone (CEZ) that differed in levels of ambient radioactivity, and also from control areas ou…
Development of a Sensitive Detection Method for Alphaviruses and Its Use as a Virus Neutralization Assay
2021
Alphaviruses have a single-stranded, positive-sense RNA genome that contains two open reading frames encoding either the non-structural or the structural genes. Upon infection, the genomic RNA is translated into the non-structural proteins (nsPs). NsPs are required for viral RNA replication and transcription driven from the subgenomic promoter (sgP). Transfection of an RNA encoding the luciferase gene under the control of the sgP into cells enabled the detection of replication-competent chikungunya virus (CHIKV) or Mayaro virus (MAYV) with high sensitivity as a function of the induced luciferase activity. This assay principle was additionally used to analyze virus-neutralizing antibodies in…
ICTV Virus Taxonomy Profile: Solinviviridae
2019
Solinviviridae is a family of picorna/calici-like viruses with non-segmented, linear, positive-sense RNA genomes of approximately 10-11 kb. Unusually, their capsid proteins are encoded towards the 3'-end of the genome where they can be expressed both from a subgenomic RNA and as an extension of the replication (picorna-like helicase-protease-polymerase) polyprotein. Members of two species within the family infect ants, but related unclassified virus sequences derive from a large variety of insects and other arthropods. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the Solinviviridae, which is available at www.ictv.global/report/solinviviridae.
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
2017
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensiti…
Dispersion from Cα or NH: 4D experiments for backbone resonance assignment of intrinsically disordered proteins
2020
AbstractResonance assignment of intrinsically disordered proteins is remarkably challenging due to scant chemical shift dispersion arising from conformational heterogeneity. The challenge is even greater if repeating segments are present in the amino acid sequence. To forward unambiguous resonance assignment of intrinsically disordered proteins, we present iHACANCO, HACACON and (HACA)CONCAHA, three Hα-detected 4D experiments with Cα as an additional dimension. In addition, we present (HACA)CON(CA)NH and (HACA)N(CA)CONH, new 4D Hα-start, HN-detect experiments which have two NH dimensions to enhance peak dispersion in a sequential walk through C′, NH and HN, and provide more accurate NH/HN ch…
Reduced firing rates of pyramidal cells in frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam
2019
AbstractIn recent years aberrant neural oscillations in various cortical areas have emerged as a common physiological hallmark across mouse models of amyloid pathology and patients with Alzheimer’s disease. However, much less is known about the underlying effect of amyloid pathology on single cell activity. Here, we used high density silicon probe recordings from frontal cortex area of 9 months old APP/PS1 mice to show that resting state Local Field Potential (LFP) power in the theta and beta band is increased in transgenic animals, while single cell firing rates, specifically of putative pyramidal cells, are significantly reduced. At the same time, these sparsely firing pyramidal cells pha…
1H, 13C, and 15N NMR chemical shift assignment of the complex formed by the first EPEC EspF repeat and N-WASP GTPase binding domain
2021
AbstractLEE-encoded effector EspF (EspF) is an effector protein part of enteropathogenic Escherichia coli’s (EPEC’s) arsenal for intestinal infection. This intrinsically disordered protein contains three highly conserved repeats which together compose over half of the protein’s complete amino acid sequence. EPEC uses EspF to hijack host proteins in order to promote infection. In the attack EspF is translocated, together with other effector proteins, to host cell via type III secretion system. Inside host EspF stimulates actin polymerization by interacting with Neural Wiskott-Aldrich syndrome protein (N-WASP), a regulator in actin polymerization machinery. It is presumed that EspF acts by di…