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https://www.readbyqxmd.com/read/28449558/in-silicomodel-driven-assessment-of-the-effects-of-brain-derived-neurotrophic-factor-deficiency-on-glutamate-and-gamma-aminobutyric-acid-implications-for-understanding-schizophrenia-pathophysiology
#1
Rimjhim Agrawal, Sunil Vasu Kalmady, Ganesan Venkatasubramanian
Objective: Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Methods: Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA...
May 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-kappa-opioid-receptors
#2
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
Synaptic plasticity in striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (Dopamine D1 Receptor containing; D1R) - spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic kappa opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#3
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28449119/mutations-in-thap11-cause-an-inborn-error-of-cobalamin-metabolism-and-developmental-abnormalities
#4
Anita M Quintana, Hung-Chun Yu, Alison Brebner, Mihaela Pupavac, Elizabeth A Geiger, Abigail Watson, Victoria L Castro, Warren Cheung, Shu-Huang Chen, David Watkins, Tomi Pastinen, Flemming Skovby, Bruce Appel, David S Rosenblatt, Tamim H Shaikh
CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28449081/the-coxiella-burnetii-type-ivb-secretion-system-t4bss-component-dota-is-released-secreted-during-infection-of-host-cells-and-during-in-vitro-growth-in-a-t4bss-dependent-manner
#5
Brandon E Luedtke, Saugata Mahapatra, Erika I Lutter, Edward I Shaw
Coxiella burnetii is a Gram-negative intracellular pathogen and is the causative agent of the zoonotic disease Q-fever. To cause disease, C. burnetii requires a functional type IVB secretion system (T4BSS) to transfer effector proteins required for the establishment and maintenance of a membrane bound parasitophorous vacuole (PV) and further modulation of host cell process. However, it is not clear how the T4BSS interacts with the PV membrane since neither a secretion pilus nor an extracellular pore forming apparatus has not been described...
April 25, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28449072/functions-of-galectins-as-self-non-self-recognition-and-effector-factors
#6
Gerardo R Vasta, Chiguang Feng, Nuria González-Montalbán, Justin Mancini, Lishi Yang, Kelsey Abernathy, Graeme Frost, Cheyenne Palm
Carbohydrate structures on the cell surface encode complex information that through specific recognition by carbohydrate-binding proteins (lectins), modulates interactions between cells, cells and the extracellular matrix, or mediates recognition of potential microbial pathogens. Galectins are a family of ß-galactoside-binding lectins, which are evolutionary conserved and have been identified in most organisms, from fungi to invertebrates and vertebrates, including mammals. Since their discovery in the 1970s, their biological roles, initially understood as limited to recognition of endogenous carbohydrate ligands in embryogenesis and development, have expanded in recent years by the discovery of their roles in tissue repair and regulation of immune homeostasis...
April 25, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28449070/in-situ-screening-for-postsynaptic-cell-adhesion-molecules-during-synapse-formation
#7
Takeshi Uemura, Tomoko Shiroshima, Asami Maeda, Misato Yasumura, Takashi Shimada, Yuko Fukata, Masaki Fukata, Tomoyuki Yoshida
Neuronal synapse formation is regulated by pre- and postsynaptic cell adhesion molecules. Presynaptic neurexins (NRXNs) and receptor protein tyrosine phosphatases (RPTPs; PTPδ, PTPσ, and LAR in mammals) can induce postsynaptic differentiation through the interaction with various postsynaptic cell adhesion molecules. Here, we developed a novel in situ screening method to identify postsynaptic membranous proteins involved in synaptogenesis. Magnetic beads coated with the extracellular domains of NRXN1β(-S4) and PTPδ-A6 variants preferentially induced excitatory postsynaptic differentiation on the beads' surface when co-cultured with cortical neurons...
April 25, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28449065/a-homozygous-missense-mutation-in-eral1-encoding-a-mitochondrial-rrna-chaperone-causes-perrault-syndrome
#8
Iliana A Chatzispyrou, Marielle Alders, Sergio Guerrero-Castillo, Ruben Zapata Perez, Martin A Haagmans, Laurent Mouchiroud, Janet Koster, Rob Ofman, Frank Baas, Hans R Waterham, Johannes N Spelbrink, Johan Auwerx, Marcel M Mannens, Riekelt H Houtkooper, Astrid S Plomp
Perrault syndrome (PS) is a rare recessive disorder characterized by ovarian dysgenesis and sensorineural deafness. It is clinically and genetically heterogeneous, and previously mutations have been described in different genes, mostly related to mitochondrial proteostasis. We diagnosed three unrelated females with PS and set out to identify the underlying genetic cause using exome sequencing. We excluded mutations in the known PS genes, but identified a single homozygous mutation in the ERAL1 gene (c.707A>T; p...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28449056/plant-hexokinases-are-multifaceted-proteins
#9
Giovanna P Aguilera-Alvarado, Sobeida Sánchez-Nieto
Sugars are the main carbon and energy source in cells, but they can also act as signaling molecules that affect the whole plant life cycle. Certain tissues can produce sugars and supply them to others, and this plant tissue heterogeneity makes sugar signaling a highly complex process that requires elements capable of perceiving changes in sugar concentrations among different tissues, cell compartments and developmental stages. In plants, the regulatory effects of Glucose (Glc) have been the most studied to date...
April 25, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28448995/cytoprotective-effect-of-heat-shock-protein-27-against-lipopolysaccharide-induced-apoptosis-of-renal-epithelial-hk-2-cells
#10
Chunmei Li, Jiang Wu, Yuan Li, Guangqun Xing
BACKGROUND: In response to various stimuli, heat shock protein 27 (Hsp27) functions as an anti-apoptotic or/and anti-inflammatory factor which confers a survival advantage to cells. This study was aimed to explore whether Hsp27 also has a cytoprotective role in human renal tubular epithelial cells, and to evaluate its potential in treating septic acute kidney injury (septic AKI). METHODS: HK-2 cells were subjected to different concentrations (0-10 µg/mL) of lipopolysaccharide (LPS) for various times (0-24 h) to establish a septic AKI model in vitro...
April 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28448993/the-long-non-coding-rna-xist-controls-non-small-cell-lung-cancer-proliferation-and-invasion-by-modulating-mir-186-5p
#11
Haoyou Wang, Qiming Shen, Xin Zhang, Chunlu Yang, Su Cui, Yanbin Sun, Liming Wang, Xiaoxi Fan, Shun Xu
BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are key players in the development and progression of human cancers. The lncRNA XIST (X-inactive specific transcript) has been shown to be upregulated in human non-small cell lung cancer (NSCLC); however, its role and molecular mechanisms in NSCLC cell progression remain unclear. METHODS: qRT-PCR was conducted to assess the expression of XIST and miR-186. Cell proliferation was detected using MTT assay. Cell invasion and migration were evaluated using transwell assay...
April 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28448979/combination-of-correctors-rescues-cftr-transmembrane-domain-mutants-by-mitigating-their-interactions-with-proteostasis
#12
Miquéias Lopes-Pacheco, Clément Boinot, Inna Sabirzhanova, Daniele Rapino, Liudmila Cebotaru
BACKGROUND/AIMS: Premature degradation of mutated cystic fibrosis transmembrane conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest Mendelian disease in Caucasians. Despite recent advances in precision medicines for CF patients, many CFTR mutants have not been characterized and the effects of these new therapeutic approaches are still unclear for those mutants. METHODS: Cells transfected or stably expressing four CFTR transmembrane-domain mutants (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants according to their protein expression, thermal sensitivity, and degradation pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore the effects of correctors on CFTR interactions with proteostasis components...
April 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28448874/regulation-and-roles-of-cd26-dppiv-in-hematopoiesis-and-diseases
#13
REVIEW
Zeynab Aliyari Serej, Abbas Ebrahimi Kalan, Ahmad Mehdipour, Hojjatollah Nozad Charoudeh
Dipeptidyl peptidase IV (DPPIV),(1) on the surface of certain cells, where it is also referred to as CD26, is involved in a vast majority of biological and pathological processes. CD26/DPPIV function contributes to cancer and tumor metastasis as well as inhibition of its expression which alters the expression of immune response-related genes. CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448794/principles-of-systems-biology-no-16
#14
(no author information available yet)
This month: how T cells signal in binary (Vale), advances in interaction mapping (Greenleaf/Sabatini/Ahroni/Bodenmiller), single-cell RNA-seq (Suvà/Ramanathan/Marioni), and more (Hilvert/Wong/Chisholm).
April 26, 2017: Cell Systems
https://www.readbyqxmd.com/read/28448737/involvement-of-arhgef10-gef-for-rhoa-in-rab6-rab8-mediating-membrane-traffic
#15
Satoshi Shibata, Yui Teshima, Kenta Niimi, Shinobu Inagaki
Small GTPases play crucial roles in the maintenance of a homeostatic environment and appropriate movements of the cell. In these processes, the direct or indirect interaction between distinct small GTPases could be required for regulating mutual signaling pathways. In our recent study, ARHGEF10, known as a guanine nucleotide exchange factor (GEF) for RhoA, was indicated to interact with Rab6A and Rab8A, which are known to function in the exocytotic pathway, and colocalized with these Rabs at exocytotic vesicles...
April 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28448610/characterization-and-expression-analysis-of-galnts-in-developing-strongylocentrotus-purpuratus-embryos
#16
Amber L Famiglietti, Zheng Wei, Thomas M Beres, Adina L Milac, Duy T Tran, Divya Patel, Robert C Angerer, Lynne M Angerer, Lawrence A Tabak
Mucin-type O-glycosylation is a ubiquitous posttranslational modification in which N-Acetylgalactosamine (GalNAc) is added to the hydroxyl group of select serine or threonine residues of a protein by the family of UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferases (GalNAc-Ts; EC 2.4.1.41). Previous studies demonstrate that O-glycosylation plays essential roles in protein function, cell-cell interactions, cell polarity and differentiation in developing mouse and Drosophila embryos. Although this type of protein modification is highly conserved among higher eukaryotes, little is known about this family of enzymes in echinoderms, basal deuterostome relatives of the chordates...
2017: PloS One
https://www.readbyqxmd.com/read/28448599/simulation-of-the-dynamics-of-primary-immunodeficiencies-in-cd4-t-cells
#17
Gabriel N Teku, Mauno Vihinen
Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes...
2017: PloS One
https://www.readbyqxmd.com/read/28448559/hexa-is-a-versatile-regulator-involved-in-the-control-of-phenotypic-heterogeneity-of-photorhabdus-luminescens
#18
Angela Langer, Adriana Moldovan, Christian Harmath, Susan A Joyce, David J Clarke, Ralf Heermann
Phenotypic heterogeneity in microbial communities enables genetically identical organisms to behave differently even under the same environmental conditions. Photorhabdus luminescens, a bioluminescent Gram-negative bacterium, contains a complex life cycle, which involves a symbiotic interaction with nematodes as well as a pathogenic association with insect larvae. P. luminescens exists in two distinct phenotypic cell types, designated as the primary (1°) and secondary (2°) cells. The 1° cells are bioluminescent, pigmented and can support nematode growth and development...
2017: PloS One
https://www.readbyqxmd.com/read/28448443/the-effect-of-thermal-fluctuation-on-the-receptor-mediated-adhesion-of-a-cell-membrane-to-an-elastic-substrate
#19
Bahador Marzban, Hongyan Yuan
Mechanics of the bilayer membrane play an important role in many biological and bioengineering problems such as cell-substrate and cell-nanomaterial interactions. In this work, we study the effect of thermal fluctuation and the substrate elasticity on the cell membrane-substrate adhesion. We model the adhesion of a fluctuating membrane on an elastic substrate as a two-step reaction comprised of the out-of-plane membrane fluctuation and the receptor-ligand binding. The equilibrium closed bond ratio as a function of substrate rigidity was computed by developing a coupled Fourier space Brownian dynamics and Monte Carlo method...
April 27, 2017: Membranes
https://www.readbyqxmd.com/read/28448066/structural-basis-of-crispr-spycas9-inhibition-by-an-anti-crispr-protein
#20
De Dong, Minghui Guo, Sihan Wang, Yuwei Zhu, Shuo Wang, Zhi Xiong, Jianzheng Yang, Zengliang Xu, Zhiwei Huang
The CRISPR-Cas9 systems are bacterial encoded adaptive immune systems to defend against phages infection, through RNA-guided endonuclease activity of Cas9 to degrade double-stranded DNA bearing a protospacer adjacent motif (PAM) and complementary sequences to the guide RNA1,2,3,4,5. Recently, two anti-CRISPR proteins AcrIIA2 and AcrIIA4 from Listeria monocytogenes (Lmo) prophages have been identified, both of which potently inhibit Streptococcus pyogenes Cas9 (SpyCas9) and LmoCas9 activity in bacteria and human cells6...
April 27, 2017: Nature
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