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https://www.readbyqxmd.com/read/28255536/central-role-of-pi3k-syk-interaction-in-fibrinogen-induced-lamellipodia-and-filopodia-formation-in-platelets
#1
Raghvendra Singh
The WAVE complex-1, a complex of WAVE, Abi1, NAP1, PIR121, HSPC300, RacGTP and Arp2/3 proteins, and WASP complex-1, a complex of WASP, Cdc42, PIP2, and Arp2/3 proteins, are involved in lamellipodia and filopodia formation, respectively. It is known that the two complexes have opposite dynamics. Furthermore, Rac has two guanine nucleotide exchange factors, Vav and Sos, whose role in activating Rac is not well understood. In this work, by the construction of signaling network, analysis, and mathematical modeling, I show that Sos generates a pulse of WAVE complex-1, decreasing the response time of WAVE complex-1 formation upon the stimulation of platelets by fibrinogen...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28138017/the-histone-chaperone-nrp1-interacts-with-werewolf-to-activate-glabra2-in-arabidopsis-root-hair-development
#2
Yan Zhu, Liang Rong, Qiang Luo, Baihui Wang, Nana Zhou, Yue Yang, Chi Zhang, Haiyang Feng, Lina Zheng, Wen-Hui Shen, Jinbiao Ma, Aiwu Dong
NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss of function of the Arabidopsis thaliana NAP1 family genes NAP1-RELATED PROTEIN1 (NRP1) and NRP2 causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the GLABRA2 (GL2) promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix...
February 2017: Plant Cell
https://www.readbyqxmd.com/read/28128545/single-molecule-investigations-on-histone-h2a-h2b-dynamics-in-the-nucleosome
#3
Jaehyoun Lee, Tae-Hee Lee
Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28125650/development-of-a-novel-vaccine-containing-binary-toxin-for-the-prevention-of-clostridium-difficile-disease-with-enhanced-efficacy-against-nap1-strains
#4
Susan Secore, Su Wang, Julie Doughtry, Jinfu Xie, Matt Miezeiewski, Richard R Rustandi, Melanie Horton, Rachel Xoconostle, Bei Wang, Catherine Lancaster, Adam Kristopeit, Sheng-Ching Wang, Sianny Christanti, Salvatore Vitelli, Marie-Pierre Gentile, Aaron Goerke, Julie Skinner, Erica Strable, David S Thiriot, Jean-Luc Bodmer, Jon H Heinrichs
Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality...
2017: PloS One
https://www.readbyqxmd.com/read/28122580/identification-of-small-molecule-modulators-of-hiv-1-tat-and-rev-protein-accumulation
#5
Ahalya Balachandran, Raymond Wong, Peter Stoilov, Sandy Pan, Benjamin Blencowe, Peter Cheung, P Richard Harrigan, Alan Cochrane
BACKGROUND: HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of specific HIV-1 RNAs and the levels of Tat and Rev proteins. RESULTS: The screen for small molecules modulators of HIV-1 gene expression at the post-transcriptional level identified three (a pyrimidin-7-amine, biphenylcarboxamide, and benzohydrazide, designated 791, 833, and 892, respectively) that not only reduce expression of HIV-1 Gag and Env and alter the accumulation of viral RNAs, but also dramatically decrease Tat and Rev levels...
January 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#6
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27974641/proper-cytoskeletal-architecture-beneath-the-plasma-membrane-of-red-blood-cells-requires-ttll4
#7
Faryal Ijaz, Yasue Hatanaka, Takahiro Hatanaka, Koji Tsutsumi, Takayuki Iwaki, Kazuo Umemura, Koji Ikegami, Mitsutoshi Setou
Mammalian red blood cells (RBCs) circulate through blood vessels, including capillaries, for tens of days under high mechanical stress. RBCs tolerate this mechanical stress while maintaining their shape because of their elastic membrane skeleton. This membrane skeleton consists of spectrin-actin lattices arranged as quasi-hexagonal units beneath the plasma membrane. In this study, we found that the organization of the RBC cytoskeleton requires tubulin tyrosine ligase-like 4 (Ttll4). RBCs from Ttll4-knockout mice showed larger average diameters in smear test...
February 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27897206/the-incidence-and-drug-resistance-of-clostridium-difficile-infection-in-mainland-china-a-systematic-review-and-meta-analysis
#8
Chenjie Tang, Lunbiao Cui, Yuqiao Xu, Le Xie, Pengfei Sun, Chengcheng Liu, Wenying Xia, Genyan Liu
It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains of C. difficile in Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenic C. difficile among patients with diarrhoea was 14% (95% CI = 12-16%)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876241/recycling-of-typical-difficult-to-treat-e-waste-synthesize-zeolites-from-waste-cathode-ray-tube-funnel-glass
#9
Zhitong Yao, Daidai Wu, Jie Liu, Weihong Wu, Hongting Zhao, Junhong Tang
The disposal of waste cathode ray-tubes (CRTs) from old televisions and discarded computer monitors has become a major environmental concern worldwide. In this work, an open-loop recycling method was developed to synthesize zeolites using CRT funnel glass as the raw material. The effects of hydrothermal temperatures and pressure, n(SiO2/Al2O3) molar ratios and hydrothermal time on the resulting products were investigated. The results indicated that hydrothermal temperatures and pressure played critical roles in zeolite synthesis...
February 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27818179/spatial-control-of-primary-ciliogenesis-by-subdistal-appendages-alters-sensation-associated-properties-of-cilia
#10
Gregory Mazo, Nadine Soplop, Won-Jing Wang, Kunihiro Uryu, Meng-Fu Bryan Tsou
Vertebrate cells can initiate ciliogenesis from centrioles at the cell center, near the Golgi, forming primary cilia confined or submerged in a deep narrow pit created by membrane invagination. How or why cells maintain submerged cilia is unclear. Here, by characterizing centriole subdistal appendages (sDAP) in cells exclusively growing submerged cilia, we found that a group of sDAP components localize to the centriole proximal end through the cohesion factor C-Nap1 and that sDAP function redundantly with C-Nap1 for submerged cilia maintenance...
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27648685/purification-and-characterization-of-a-novel-alginate-lyase-from-the-marine-bacterium-cobetia-sp-nap1-isolated-from-brown-algae
#11
Hisashi Yagi, Asako Fujise, Narumi Itabashi, Takashi Ohshiro
The application of marine resources, instead of fossil fuels, for biomass production is important for building a sustainable society. Seaweed is valuable as a source of marine biomass for producing biofuels such as ethanol, and can be used in various fields. Alginate is an anionic polysaccharide that forms the main component of brown algae. Various alginate lyases (e.g. exo- and endo-types and oligoalginate lyase) are generally used to degrade alginate. We herein describe a novel alginate lyase, AlgC-PL7, which belongs to the polysaccharide lyase 7 family...
December 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27633064/reprofiled-anthelmintics-abate-hypervirulent-stationary-phase-clostridium-difficile
#12
Major Gooyit, Kim D Janda
Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27620379/structural-insights-into-the-interaction-and-disease-mechanism-of-neurodegenerative-disease-associated-optineurin-and-tbk1-proteins
#13
Faxiang Li, Xingqiao Xie, Yingli Wang, Jianping Liu, Xiaofang Cheng, Yujiao Guo, Yukang Gong, Shichen Hu, Lifeng Pan
Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins...
2016: Nature Communications
https://www.readbyqxmd.com/read/27614757/thrombocytopenia-in-hospitalized-patients-with-severe-clostridium-difficile-infection
#14
Eric M Fountain, Maggie C Moses, Lawrence P Park, Christopher W Woods, Gowthami M Arepally
Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization...
September 10, 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27588452/bi-allelic-truncating-mutations-in-cep78-encoding-centrosomal-protein-78-cause-cone-rod-degeneration-with-sensorineural-hearing-loss
#15
Prasanthi Namburi, Rinki Ratnapriya, Samer Khateb, Csilla H Lazar, Yael Kinarty, Alexey Obolensky, Inbar Erdinest, Devorah Marks-Ohana, Eran Pras, Tamar Ben-Yosef, Hadas Newman, Menachem Gross, Anand Swaroop, Eyal Banin, Dror Sharon
Inherited retinal diseases (IRDs) are a diverse group of genetically and clinically heterogeneous retinal abnormalities. The present study was designed to identify genetic defects in individuals with an uncommon combination of autosomal recessive progressive cone-rod degeneration accompanied by sensorineural hearing loss (arCRD-SNHL). Homozygosity mapping followed by whole-exome sequencing (WES) and founder mutation screening revealed two truncating rare variants (c.893-1G>A and c.534delT) in CEP78, which encodes centrosomal protein 78, in six individuals of Jewish ancestry with CRD and SNHL...
September 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27521427/drosophila-kette-coordinates-myoblast-junction-dissolution-and-the-ratio-of-scar-to-wasp-during-myoblast-fusion
#16
Julia Hamp, Andreas Löwer, Christine Dottermusch-Heidel, Lothar Beck, Bernard Moussian, Matthias Flötenmeyer, Susanne-Filiz Önel
The fusion of founder cells and fusion-competent myoblasts (FCMs) is crucial for muscle formation in Drosophila Characteristic events of myoblast fusion include the recognition and adhesion of myoblasts, and the formation of branched F-actin by the Arp2/3 complex at the site of cell-cell contact. At the ultrastructural level, these events are reflected by the appearance of finger-like protrusions and electron-dense plaques that appear prior to fusion. Severe defects in myoblast fusion are caused by the loss of Kette (a homolog of Nap1 and Hem-2, also known as NCKAP1 and NCKAP1L, respectively), a member of the regulatory complex formed by Scar or WAVE proteins (represented by the single protein, Scar, in flies)...
September 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27486244/dishevelled-is-a-nek2-kinase-substrate-controlling-dynamics-of-centrosomal-linker-proteins
#17
Igor Cervenka, Jana Valnohova, Ondrej Bernatik, Jakub Harnos, Matej Radsetoulal, Katerina Sedova, Katerina Hanakova, David Potesil, Miroslava Sedlackova, Alena Salasova, Zachary Steinhart, Stephane Angers, Gunnar Schulte, Ales Hampl, Zbynek Zdrahal, Vitezslav Bryja
Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt signaling pathways. Here, we present conclusive evidence that DVL regulates the centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but not DIX domain-mediated multimerization, is essential for DVL's centrosomal localization. DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at a multitude of residues, as detected by a set of novel phospho-specific antibodies...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27451899/arabidopsis-nap1-regulates-the-formation-of-autophagosomes
#18
Pengwei Wang, Christine Richardson, Chris Hawes, Patrick J Hussey
The SCAR/WAVE complex is required for ARP2/3-mediated actin nucleation, and these complexes are highly conserved in plants and animals [1, 2]. Proteins from the SCAR/WAVE complex have been found to be membrane associated in plants [3]. Using fluorescent protein fusions, we have found that NAP1 [4], a component of the SCAR/WAVE complex, locates to vesicles or puncta that appear upon applied pressure. These NAP1 vesicles can be endoplasmic reticulum (ER)-associated, can co-align with the cytoskeleton, and fuse to each other homotypically...
August 8, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27433848/brca2-mediates-centrosome-cohesion-via-an-interaction-with-cytoplasmic-dynein
#19
Sadiya Malik, Hiroko Saito, Miho Takaoka, Yoshio Miki, Akira Nakanishi
BRCA2 is responsible for familial breast and ovarian cancer and has been linked to DNA repair and centrosome duplication. Here we analyzed the mechanism by which the centrosomal localization signal (CLS) of BRCA2 interacts with cytoplasmic dynein 1 to localize BRCA2 to the centrosome. In vitro pull-down assays demonstrated that BRCA2 directly binds to the cytoplasmic dynein 1 light intermediate chain 2. A dominant-negative HA-CLS-DsRed fusion protein, the depletion of dynein by siRNA, and the inactivation of dynein by EHNA, inhibited the localization of BRCA2 at centrosomes and caused the separation of centrosome pairs during the S-phase...
August 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27427464/induction-of-antitoxin-responses-in-clostridium-difficile-infected-patients-compared-to-healthy-blood-donors
#20
Alice von Eichel-Streiber, Wonbeom Paik, Katherine Knight, Karina Gisch, Karolina Nadjafi, Christine Decker, Oliver Bosnjak, Adam Cheknis, Stuart Johnson, Christoph von Eichel-Streiber
According to the literature Clostridium difficile antitoxins are present in up to 66% of humans. In a survey of ∼400 plasma samples from healthy blood donors we found that less than 6% were positive for anti-TcdA or anti-TcdB antitoxins. Using the same standard immunoassay protocol, we looked for IgG and IgA antitoxins in the blood and stool samples from 25 patients with C. difficile infection (CDI). Some patients with CDI had no antitoxin detected at all, while others had high levels of specific IgG- and IgA-antitoxins against both TcdA and TcdB in blood and IgA-anti-TcdA and -anti-TcdB antibodies in stool...
October 2016: Anaerobe
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