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https://www.readbyqxmd.com/read/28823106/mitochondrial-outer-membrane-permeabilization-a-focus-on-the-role-of-mitochondrial-membrane-structural-organization
#1
REVIEW
Siti Haji Suhaili, Hamed Karimian, Matthew Stellato, Tzong-Hsien Lee, Marie-Isabel Aguilar
Apoptosis is important in regulating cell death turnover and is mediated by the intrinsic and death receptor-based extrinsic pathways which converge at the mitochondrial outer membrane (MOM) leading to mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of apoptotic proteins that further activate the downstream pathway of apoptosis. Thus, tight regulation of MOMP is crucial in controlling apoptosis, and a lack of control may lead to tissue and organ malformation and the development of cancers...
August 19, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28823097/epitope-mapping-of-histo-blood-group-antigens-bound-to-norovirus-vlps-using-std-nmr-experiments-reveals-fine-details-of-molecular-recognition
#2
Brigitte Fiege, Mila Leuthold, Francisco Parra, Kevin P Dalton, Peter J Meloncelli, Todd L Lowary, Thomas Peters
Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be critical for the infection process. Therefore, we have determined binding epitopes of synthetic type 1 to 6 blood group A- and B-tetrasaccharides binding to GII.4 human Norovirus virus like particles (VLPs) using STD NMR experiments. So far, little information is available from crystal structure analysis studies on the interactions of the reducing-end sugars with the protruding domain (P-domain) of the viral coat protein VP1...
August 19, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28822801/microarray-gene-expression-study-in-fibroblast-and-lymphoblastoid-cell-lines-from-antipsychotic-na%C3%A3-ve-first-episode-schizophrenia-patients
#3
Patricia Gassó, Sergi Mas, Natalia Rodríguez, Daniel Boloc, Susana García-Cerro, Miquel Bernardo, Amalia Lafuente, Eduard Parellada
Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls...
August 5, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28822783/the-expression-induction-and-pharmacological-activity-of-cyp1a2-are-post-transcriptionally-regulated-by-microrna-hsa-mir-132-5p
#4
Yinting Chen, Linjuan Zeng, Yong Wang, William H Tolleson, Bridgett Knox, Si Chen, Zhen Ren, Lei Guo, Nan Mei, Feng Qian, Kaihong Huang, David Liu, Weida Tong, Dianke Yu, Baitang Ning
Cytochrome P450 1A2 (CYP1A2) is one of the most abundant and important drug metabolizing enzymes in human liver. However, little is known about the post-transcriptional regulation of CYP1A2, especially the mechanisms involving microRNAs (miRNAs). This study applied a systematic approach to investigate the post-transcriptional regulation of CYP1A2 by miRNAs. Candidate miRNAs targeting the 3'-untranslated region (3'-UTR) of CYP1A2 were screened in silico, resulting in the selection of sixty-two potential miRNAs for further analysis...
August 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28822454/-effects-of-up-regulation-of-cathepsin-s-by-hbx-gene-on-hepg2-cell
#5
Z Zhang, P Guo, X Sun, Y Xiao, J Xu, Z S Fang, S Y Wu, H Huang
Objective: To explore the expression of cathepsin S (Cat S) and Hepatitis B virus X protein (HBx) in HBeAg(-) and HBeAg(+ ) hepatocellular carcinoma (HCC), and discuss the effects of Cat S and HBx interaction on HepG2 cell. Methods: Seventy HCC tissue specimens were collected from the surgical resection which were confirmed by pathology in the Fifth Affiliated Hospital of Guangxi Medical University. The tissue samples were separated into two groups: HBeAg(-) group and HBeAg(+ ) group according to the serology of HBeAg...
August 8, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28822126/dimethyl-labeling-based-quantification-of-the-lysine-acetylome-and-proteome-of-plants
#6
Ines Lassowskat, Markus Hartl, Fabian Hosp, Paul J Boersema, Matthias Mann, Iris Finkemeier
Photorespiratory enzymes in different cellular compartments have been reported to be posttranslational modified by phosphorylation, disulfide formation, S-nitrosylation, glutathionylation, and lysine acetylation. However, not much is known yet about the function of these modifications to regulate the activities, localizations, or interactions of the proteins in this metabolic pathway. Hence, it will be of great importance to study these modifications and their temporal and conditional occurrence in more detail...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822116/interactions-between-variation-in-candidate-genes-and-environmental-factors-in-the-etiology-of-schizophrenia-and-bipolar-disorder-a-systematic-review
#7
REVIEW
Błażej Misiak, Filip Stramecki, Łukasz Gawęda, Katarzyna Prochwicz, Maria M Sąsiadek, Ahmed A Moustafa, Dorota Frydecka
Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28822103/current-progress-in-innovative-engineered-antibodies
#8
REVIEW
William R Strohl
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year...
August 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28822076/studies-of-the-benzopyran-class-of-selective-cox-2-inhibitors-using-3d-qsar-and-molecular-docking
#9
Dharmendra K Yadav, Saloni, Praveen Sharma, Sanjeev Misra, Harpreet Singh, Ricardo L Mancera, Kang Kim, Cheongyun Jang, Mi-Hyun Kim, Horacio Pérez-Sánchez, Eun Ha Choi, Surendra Kumar
The Gaussian-based 3D-QSAR studies for 58 selective COX-2 (cyclooxygenase-2) inhibitors belonging to benzopyran chemical class were performed. Partial least squares analysis produced statistically significant model with (R training(2)  = 0.866) and predictability (Q training(2)  = 0.66, Q test(2)  = 0.846). The 3D-QSAR model includes steric, electrostatic, hydrophobic, and hydrogen bond acceptor field indicators, whereas the potential field contributions indicate that the steric and hydrophobic features of the molecules play an important role in governing their biological activity...
August 18, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#10
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28821952/genome-wide-association-study-and-gene-set-analysis-for-understanding-candidate-genes-involved-in-salt-tolerance-at-the-rice-seedling-stage
#11
Jie Yu, Weiguo Zao, Qiang He, Tae-Sung Kim, Yong-Jin Park
Salt is the major factor limiting crop productivity in saline soils and is controlled by various genes. The development of salt-tolerant rice through molecular breeding methods is important to meet the needs of rice breeding. We used 295 accessions to perform a genome-wide association study (GWAS) of salt tolerance-related phenotypes in rice at the seedling stage and obtained 93 candidate genes with high association peaks across six phenotypes. We constructed a protein interaction network using the candidate genes identified here, and 33 genes were associated...
August 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28821864/nanomechanics-of-multidomain-neuronal-cell-adhesion-protein-contactin-revealed-by-single-molecule-afm-and-smd
#12
K Mikulska-Ruminska, A J Kulik, C Benadiba, I Bahar, G Dietler, W Nowak
Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821863/the-heat-shock-response-and-humoral-immune-response-are-mutually-antagonistic-in-honey-bees
#13
Mia McKinstry, Charlie Chung, Henry Truong, Brittany A Johnston, Jonathan W Snow
The honey bee is of paramount importance to humans in both agricultural and ecological settings. Honey bee colonies have suffered from increased attrition in recent years, stemming from complex interacting stresses. Defining common cellular stress responses elicited by these stressors represents a key step in understanding potential synergies. The proteostasis network is a highly conserved network of cellular stress responses involved in maintaining the homeostasis of protein production and function. Here, we have characterized the Heat Shock Response (HSR), one branch of this network, and found that its core components are conserved...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821854/dynamics-of-hydration-water-plays-a-key-role-in-determining-the-binding-thermodynamics-of-protein-complexes
#14
Song-Ho Chong, Sihyun Ham
Interfacial waters are considered to play a crucial role in protein-protein interactions, but in what sense and why are they important? Here, using molecular dynamics simulations and statistical thermodynamic analyses, we demonstrate distinctive dynamic characteristics of the interfacial water and investigate their implications for the binding thermodynamics. We identify the presence of extraordinarily slow (~1,000 times slower than in bulk water) hydrogen-bond rearrangements in interfacial water. We rationalize the slow rearrangements by introducing the "trapping" free energies, characterizing how strongly individual hydration waters are captured by the biomolecular surface, whose magnitude is then traced back to the number of water-protein hydrogen bonds and the strong electrostatic field produced at the binding interface...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821836/porv-is-an-outer-membrane-shuttle-protein-for-the-type-ix-secretion-system
#15
Michelle D Glew, Paul D Veith, Dina Chen, Dhana G Gorasia, Ben Peng, Eric C Reynolds
Porphyromonas gingivalis is a keystone pathogen associated with chronic periodontitis. Major virulence factors named gingipains (cysteine proteinases, RgpA, RgpB and Kgp) are secreted via the Type IX Secretion System (T9SS). These, together with approximately 30 other proteins, are secreted to the cell surface and anchored to the outer membrane by covalent modification to anionic lipopolysaccharide (A-LPS) via the novel Gram negative sortase, PorU. PorU is localised on the cell surface and cleaves the C-terminal domain signal (CTD) of T9SS substrates and conjugates their new C-termini to A-LPS...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821821/the-inhibitory-mechanism-of-hal3-on-the-yeast-ppz1-phosphatase-a-mutagenesis-analysis
#16
Cristina Molero, Carlos Casado, Joaquín Ariño
The Ser/Thr protein phosphatase (PPase) Ppz1 is an enzyme related to the ubiquitous type-1 PPases (PP1c) but found only in fungi. It is regulated by an inhibitory subunit, Hal3, which binds to its catalytic domain. Overexpression of Ppz1 is highly toxic for yeast cells, so its de-regulation has been proposed as a target for novel antifungal therapies. While modulation of PP1c by its many regulatory subunits has been extensively characterized, the manner by which Hal3 controls Ppz1 remains unknown. We have used error-prone PCR mutagenesis to construct a library of Ppz1 variants and developed a functional assay to identify mutations affecting the binding or/and the inhibitory capacity of Hal3...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821809/impact-of-varying-social-experiences-during-life-history-on-behaviour-gene-expression-and-vasopressin-receptor-gene-methylation-in-mice
#17
Carina Bodden, Daniel van den Hove, Klaus-Peter Lesch, Norbert Sachser
Both negative and positive social experiences during sensitive life phases profoundly shape brain and behaviour. Current research is therefore increasingly focusing on mechanisms mediating the interaction between varying life experiences and the epigenome. Here, male mice grew up under either adverse or beneficial conditions until adulthood, when they were subdivided into groups exposed to situations that either matched or mismatched previous conditions. It was investigated whether the resulting four life histories were associated with changes in anxiety-like behaviour, gene expression of selected genes involved in anxiety and stress circuits, and arginine vasopressin receptor 1a (Avpr1a) gene methylation...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821780/selective-inhibition-mechanism-of-rvx-208-to-the-second-bromodomain-of-bromo-and-extraterminal-proteins-insight-from-microsecond-molecular-dynamics-simulations
#18
Qianqian Wang, Ying Li, Jiahui Xu, Yuwei Wang, Elaine Lai-Han Leung, Liang Liu, Xiaojun Yao
RVX-208 is a recently reported inhibitor of bromo and extraterminal (BET) family proteins (including BRD2-4 and BRDT) with selectivity for the second bromodomain (BD2), currently in phase III clinical trials. Despite of its promising antitumor activity, due to the conserved folds of the first and second bromodomains (BD1 and BD2), the detailed selectivity mechanism of RVX-208 towards BD2 over BD1 is still unknown. To elucidate selective inhibition mechanism of RVX-208 to BD2, microsecond molecular dynamics simulations were performed in this study for BRD2-BD1, BRD2-BD2 and BRD4-BD1 with and without RVX-208, respectively...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821763/activation-of-an-anti-bacterial-toxin-by-the-biosynthetic-enzyme-cysk-mechanism-of-binding-interaction-specificity-and-competition-with-cysteine-synthase
#19
Roberto Benoni, Christina M Beck, Fernando Garza-Sánchez, Stefano Bettati, Andrea Mozzarelli, Christopher S Hayes, Barbara Campanini
Contact-dependent growth inhibition (CDI) is a wide-spread mechanism of inter-bacterial competition. CDI(+) bacteria deliver CdiA-CT toxins into neighboring bacteria and produce specific immunity proteins that protect against self-intoxication. The CdiA-CT toxin from uropathogenic Escherichia coli 536 is a latent tRNase that is only active when bound to the cysteine biosynthetic enzyme CysK. Remarkably, the CysK:CdiA-CT binding interaction mimics the 'cysteine synthase' complex of CysK:CysE. The C-terminal tails of CysE and CdiA-CT each insert into the CysK active-site cleft to anchor the respective complexes...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821747/the-integration-of-g%C3%AE-and-mapk-signaling-cascade-in-zygote-development
#20
Guo-Liang Yuan, Hong-Ju Li, Wei-Cai Yang
Cells respond to many signals with a limited number of signaling components. Heterotrimeric G proteins and MAPK cascades are universally used by eukaryotic cells to transduce signals in various developmental processes or stress responses by activating different effectors. MAPK cascade is integrated with G proteins by scaffold protein during plant immunity. However, the molecular relationship between G proteins and MAPK modules in plant development is still unclear. In this study, we demonstrate that Arabidopsis Gβ protein AGB1 interacts with MPK3 and 6, MKK4 and 5, as well as the regulatory domains of YODA (YDA), the upstream MEKK of MKK4/5...
August 18, 2017: Scientific Reports
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