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https://www.readbyqxmd.com/read/28646754/free-energy-analysis-of-cell-spreading
#1
Eóin McEvoy, Vikram S Deshpande, Patrick McGarry
In this study we present a steady-state adaptation of the thermodynamically motivated stress fiber (SF) model of Vigliotti et al. (2015). We implement this steady-state formulation in a non-local finite element setting where we also consider global conservation of the total number of cytoskeletal proteins within the cell, global conservation of the number of binding integrins on the cell membrane, and adhesion limiting ligand density on the substrate surface. We present a number of simulations of cell spreading in which we consider a limited subset of the possible deformed spread-states assumed by the cell in order to examine the hypothesis that free energy minimization drives the process of cell spreading...
June 7, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28646721/biochemical-immunological-hybrid-biosensor-based-on-two-dimensional-chromatography-for-on-site-sepsis-diagnosis
#2
Seung-Wan Kim, Il-Hoon Cho, Guei-Sam Lim, Gi-Na Park, Se-Hwan Paek
A hybrid-biosensor system that can simultaneously fulfill the immunoassay for protein markers (e.g., C-reactive protein (CRP) and procalcitonin (PCT)) and the enzyme assay for metabolic substances (e.g., lactate) in the same sepsis-based sample has been devised. Such a challenge was pursued through the installation of an enzyme-reaction zone on the signal pad of the typical immuno-strip for the rapid two-dimensional (2-D)-chromatography test. To minimize the mutual interference in the hybrid assays, a pre-determined membrane site was etched in a pattern and mounted with a biochemical-reaction pad, thereby allowing a loaded sample to enter and then stay in the pad for a colored-signal production over the course of an immunoassay...
June 16, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28646657/-half-sandwich-schiff-base-ir-iii-complexes-as-anticancer-agents
#3
Ze-Dong Mou, Ning Deng, Feng Zhang, Jiaying Zhang, Juan Cen, Xia Zhang
A series of "half-sandwich" Schiff-base Ir(III) complexes were synthesized and investigated for their in vitro activities against the leukemia K562 cell line. These compounds demonstrated antiproliferative activities against K562 cells with IC50 values of 0.26-4.77 μM. In particular, compound 10c showed cytotoxicity against five cancer cell lines/sublines and stronger activities than cisplatin in K562, K562/A02, MCF-7, MCF-7/ADM, and A549 cells. Mechanism studies illustrated that compound 10c increased the level of reactive oxygen species and induced apoptosis of K562 cells...
June 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646653/cryo-em-beyond-the-microscope
#4
REVIEW
Lesley A Earl, Veronica Falconieri, Jacqueline Ls Milne, Sriram Subramaniam
The pace at which cryo-EM is being adopted as a mainstream tool in structural biology has continued unabated over the past year. Initial successes in obtaining near-atomic resolution structures with cryo-EM were enabled to a large extent by advances in microscope and detector technology. Here, we review some of the complementary technical improvements that are helping sustain the cryo-EM revolution. We highlight advances in image processing that permit high resolution structure determination even in the presence of structural and conformational heterogeneity...
June 21, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28646649/two-single-mutations-in-the-fusion-protein-of-newcastle-disease-virus-confer-hemagglutinin-neuraminidase-independent-fusion-promotion-and-attenuate-the-pathogenicity-in-chickens
#5
Yanhong Ji, Tao Liu, Yane Jia, Bin Liu, Qingzhong Yu, Xiaole Cui, Fengfeng Guo, Huiyun Chang, Qiyun Zhu
The fusion (F) protein of Newcastle disease virus (NDV) affects viral infection and pathogenicity through mediating membrane fusion. Previously, we found NDV with increased fusogenic activity in which contained T458D or G459D mutation in the F protein. Here, we investigated the effects of these two mutations on viral infection, fusogenicity and pathogenicity. Syncytium formation assays indicated that T458D or G459D increased the F protein cleavage activity and enhanced cell fusion with or without the presence of HN protein...
June 21, 2017: Virology
https://www.readbyqxmd.com/read/28646547/a-dual-fluorescence-reporter-in-the-eomes-locus-for-live-imaging-and-medium-term-lineage-tracing
#6
Simone Probst, Ray A Daza, Natalie Bader, Jonas F Hummel, Matthias Weiß, Yakup Tanriver, Robert F Hevner, Sebastian J Arnold
The T-box transcription factor Eomes (also known as Tbr2) shows short-lived expression in various localized domains of the embryo, including epiblast cells during gastrulation and intermediate progenitor cells in the cerebral cortex. In these tissues Eomes fulfills crucial roles for lineage specification of progenitors. To directly observe Eomes-dependent cell lineages in the living embryo, we generated a novel dual-fluorescence reporter allele that expresses a membrane-bound tdTomato protein for investigation of cell morphology and a nuclear GFP for cell tracing...
June 24, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28646452/dosage-effects-of-zp2-and-zp3-heterozygous-mutations-cause-human-infertility
#7
Wenqiang Liu, Kunming Li, Dandan Bai, Jiqing Yin, Yuanyuan Tang, Fengli Chi, Linfeng Zhang, Yu Wang, Jiaping Pan, Shanshan Liang, Yi Guo, Jingling Ruan, Xiaochen Kou, Yanhong Zhao, Hong Wang, Jiayu Chen, Xiaoming Teng, Shaorong Gao
The zona pellucida (ZP) is an extracellular matrix universally surrounding mammalian eggs, which is essential for oogenesis, fertilization, and pre-implantation embryo development. Here, we identified two novel heritable mutations of ZP2 and ZP3, both occurring in an infertile female patient with ZP-abnormal eggs. Mouse models with the same mutations were generated by CRISPR/Cas9 gene editing system, and oocytes obtained from female mice with either single heterozygous mutation showed approximately half of the normal ZP thickness compared to wild-type oocytes...
June 24, 2017: Human Genetics
https://www.readbyqxmd.com/read/28646429/decoupled-side-chain-and-backbone-dynamics-for-proton-translocation-m2-of-influenza-a
#8
Monoj Mon Kalita, Wolfgang B Fischer
The 97 amino acid bitopic membrane protein M2 of influenza A forms a tetrameric bundle in which two of the monomers are covalently linked via a cysteine bridge. In its tetrameric assembly the protein conducts protons across the viral envelope and within intracellular compartments during the infectivity cycle of the virus. A key residue in the translocation of the protons is His-37 which forms a planar tetrad in the configuration of the bundle accepting and translocating the incoming protons from the N terminal side, exterior of the virus, to the C terminal side, inside the virus...
July 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28646414/dynamic-meso-scale-anchorage-of-gpi-anchored-receptors-in-the-plasma-membrane-prion-protein-vs-thy1
#9
Yuri L Nemoto, Roger J Morris, Hiroko Hijikata, Taka A Tsunoyama, Akihiro C E Shibata, Rinshi S Kasai, Akihiro Kusumi, Takahiro K Fujiwara
The central mechanism for the transmission of the prion protein misfolding is the structural conversion of the normal cellular prion protein to the pathogenic misfolded prion protein, by the interaction with misfolded prion protein. This process might be enhanced due to the homo-dimerization/oligomerization of normal prion protein. However, the behaviors of normal prion protein in the plasma membrane have remained largely unknown. Here, using single fluorescent-molecule imaging, we found that both prion protein and Thy1, a control glycosylphosphatidylinositol-anchored protein, exhibited very similar intermittent transient immobilizations lasting for a few seconds within an area of 24...
June 24, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28646266/pericytes-promote-abnormal-tumor-angiogenesis-in-a-rat-rg2-glioma-model
#10
Junji Hosono, Shunichi Morikawa, Taichi Ezaki, Takakazu Kawamata, Yoshikazu Okada
In glioma angiogenesis, tumor vessels cause morphological and functional abnormalities associated with malignancy and tumor progression. We hypothesized that certain structural changes or scantiness of functional pericytes may be involved in the formation of dysfunctional blood vessels in gliomas. In this study, we performed morphological examinations to elucidate the possible involvement of pericytes in brain tumor vessel abnormalities using a rat RG2 glioma model. After implantation of RG2 glioma cells in the syngeneic rat brain, gliomas were formed as early as day 7...
June 23, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28646173/transmembrane-interactions-of-full-length-mammalian-bitopic-cytochrome-p450-cytochrome-b5-complex-in-lipid-bilayers-revealed-by-sensitivity-enhanced-dynamic-nuclear-polarization-solid-state-nmr-spectroscopy
#11
Kazutoshi Yamamoto, Marc A Caporini, Sang-Choul Im, Lucy Waskell, Ayyalusamy Ramamoorthy
The dynamic protein-protein and protein-ligand interactions of integral bitopic membrane proteins with a single membrane-spanning helix play a plethora of vital roles in the cellular processes associated with human health and diseases, including signaling and enzymatic catalysis. While an increasing number of high-resolution structural studies of membrane proteins have successfully manifested an in-depth understanding of their biological functions, intact membrane-bound bitopic protein-protein complexes pose tremendous challenges for structural studies by crystallography or solution NMR spectroscopy...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646165/selective-inhibition-of-sterolo-acyltransferase-1-isozyme-by-beauveriolide-iii-in-intact-cells
#12
Taichi Ohshiro, Keisuke Kobayashi, Mio Ohba, Daisuke Matsuda, Lawrence L Rudel, Takashi Takahashi, Takayuki Doi, Hiroshi Tomoda
Beauveriolide III (BeauIII) inhibited sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT2), which are endoplasmic reticulum (ER) membrane proteins, in an enzyme-based assay, and selectively inhibited SOAT1 in a cell-based assay using SOAT1-/SOAT2-CHO cells. This discrepancy in SOAT inhibition by BeauIII was investigated. In the enzyme-based assay, BeauIII inhibited SOAT1 and SOAT2 to a similar extent using microsomes prepared from cells disrupted under the strongest sonication condition. In semi-intact SOAT1-/SOAT2-CHO cells prepared by a treatment with digitonin (plasma membrane permeabilized), BeauIII selectively inhibited SOAT1 (IC50; 5...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646141/human-sialidase-neu3-is-s-acylated-and-behaves-like-an-integral-membrane-protein
#13
Macarena Rodriguez-Walker, Jose L Daniotti
Membrane-bound sialidase Neu3 is involved in the catabolism of glycoconjugates, and plays crucial roles in numerous biological processes. Since the mechanism of its association with membranes is still not completely understood, the aim of this work was to provide further information regarding this aspect. Human Neu3 was found to be associated with the plasma membrane and endomembranes, and it was not released from the lipid bilayer under conditions that typically release peripheral membrane proteins. By different experimental approaches, we demonstrated that its C-terminus is exposed to the cytosol while another portion of the protein is exposed to the extracellular space, suggesting that Neu3 possesses the features of a transmembrane protein...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646128/%C3%AE-copi-mediates-the-retention-of-kae1-g701d-protein-in-golgi-apparatus-a-mechanistic-explanation-of-drta-associated-g701d-mutation
#14
Natapol Duangtum, Mutita Junking, Suratchanee Phadngam, Nunghathai Sawasdee, Andrea Castiglioni, Komgrid Charngkaew, Thawornchai Limjindaporn, Ciro Isidoro, Pa-Thai Yenchitsomanus
Mutations of solute carrier family 4 member 1 ( SLC4A1 ) gene encoding kidney anion (chloride/bicarbonate ion) exchanger 1 (kAE1) can cause genetic distal renal tubular acidosis (dRTA). Different SLC4A1 mutations give rise to mutant kAE1 proteins with distinct defects in protein trafficking. The mutant kAE1 protein may be retained in endoplasmic reticulum (ER), Golgi apparatus, or mis-targeted to the apical membrane, failing to display its function at the baso-lateral membrane. The ER-retained mutant kAE1 interacts with calnexin chaperone protein; disruption of this interaction permits the mutant kAE1 to reach the cell surface and display anion exchange activity...
June 23, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28646126/how-a-helix-imposes-palmitoylation-of-a-membrane-protein-what-one-can-learn-from-ncx
#15
Daniel Khananshvili
Palmitoylation is a critical post-translational modification that anchors proteins to, and regulates transport across, the lipid bilayer. Palmitoylation enzymes have been assumed to select their substrates based on a protein's primary sequence, but a consensus sequence has been slow to emerge. A study of the sodium/calcium exchanger now suggests that secondary structure may hold the key to understanding the determinants of this modification.
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28646092/deletion-analysis-of-agd1-reveals-domains-crucial-for-its-plasma-membrane-recruitment-and-function-in-root-hair-polarity
#16
Cheol-Min Yoo, Satoshi Naramoto, J Alan Sparks, Bibi Rafeiza Khan, Jin Nakashima, Hiroo Fukuda, Elison B Blancaflor
AGD1, a plant ACAP-type ADP-ribosylation factor-GTPase activating protein (ARF-GAP), functions in specifying root hair polarity in Arabidopsis thaliana To better understand how AGD1 modulates root hair growth, we generated full length and domain-deleted AGD1-green fluorescent protein (GFP) constructs, and followed their localization during root hair development. AGD1-GFP localized to the cytoplasm and was recruited to specific regions of the root hair plasma membrane (PM). Distinct PM AGD1-GFP signal was first detected along the site of root hair bulge formation...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28646090/cellular-functions-of-wasp-family-proteins-at-a-glance
#17
REVIEW
Olga Alekhina, Ezra Burstein, Daniel D Billadeau
Proteins of the Wiskott-Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#18
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28646018/the-amyloid-precursor-protein-modulates-%C3%AE-2a-adrenergic-receptor-endocytosis-and-signaling-through-disrupting-arrestin-3-recruitment
#19
Fang Zhang, Mary Gannon, Yunjia Chen, Lufang Zhou, Kai Jiao, Qin Wang
The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28645896/nucleotide-dependent-farnesyl-switch-orchestrates-polymerization-and-membrane-binding-of-human-guanylate-binding-protein-1
#20
Sergii Shydlovskyi, Anke Y Zienert, Semra Ince, Christine Dovengerds, Annika Hohendahl, Julia M Dargazanli, Ailisa Blum, Saskia D Günther, Nikolay Kladt, Michael Stürzl, Astrid C Schauss, Miriam Kutsch, Aurélien Roux, Gerrit J K Praefcke, Christian Herrmann
Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction...
June 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
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