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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
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
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
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
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
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
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
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
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
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...
July 14, 2016: Anaerobe
Hongbing Jia, Pengcheng Du, Hui Yang, Yuanyuan Zhang, Jing Wang, Wen Zhang, Guiling Han, Na Han, Zhiyuan Yao, Haiyin Wang, Jing Zhang, Zhen Wang, Qingming Ding, Yujun Qiang, Frédéric Barbut, George F Gao, Yongtong Cao, Ying Cheng, Chen Chen
BACKGROUND: The rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. However, C. difficile 027 infections have been rarely reported in Asia, particularly in China. RESULTS: In this study, we identified a rare C. difficile bloodstream infection (BSI) from three isolates of a patient during repeated hospital admission. This finding triggered a retrospective epidemiological study to scan all cases and strains emerged from this ward during the past three years...
2016: BMC Genomics
Agatha N Jassem, Natalie Prystajecky, Fawziah Marra, Pamela Kibsey, Kennard Tan, Patricia Umlandt, Loretta Janz, Sylvie Champagne, Bruce Gamage, George R Golding, Michael R Mulvey, Bonnie Henry, Linda M N Hoang
Background. Clostridium difficile is a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressor tcdC, and a binary toxin. Objectives. To determine the molecular epidemiology of C. difficile in British Columbia and compare between two time points in one region. Methods. C. difficile isolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession, tcdC genotype, and antimicrobial susceptibility...
2016: Canadian Journal of Infectious Diseases & Medical Microbiology
Wangbin Zhou, Juan Gao, Jing Ma, Lin Cao, Chi Zhang, Yan Zhu, Aiwu Dong, Wen-Hui Shen
Nuclear DNA homologous recombination (HR) occurs within the context of a highly complex chromatin structure. In spite of extensive studies of HR in diverse organisms, mechanisms regulating HR within chromatin context remain poorly elucidated. Here we investigate the role and interplay of the histone chaperones NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) and NAP1-RELATED PROTEIN (NRP) and the ATP-dependent chromatin-remodeling factor INOSITOL AUXOTROPHY80 (INO80) in regulating somatic HR in Arabidopsis thaliana. We show that simultaneous knockout of the four AtNAP1 genes and the two NRP genes in the sextuple mutant m123456-1 barely affects normal plant growth and development...
June 29, 2016: Plant Journal: for Cell and Molecular Biology
Imad Kansau, Amira Barketi-Klai, Marc Monot, Sandra Hoys, Bruno Dupuy, Claire Janoir, Anne Collignon
Clostridium difficile is responsible for a wide spectrum of infection from asymptomatic carriage to severe, relapsing colitis. Since 2003, C. difficile infections have increased with a higher morbidity and mortality due to the emergence of epidemic and hypervirulent C. difficile strains such as those of the epidemic lineage 027/BI/NAP1. To decipher the hypervirulence and epidemicity of 027 strains, we analyzed gene expression profiles of the R20291 027 strain using a monoxenic mouse model during the first 38h of infection...
2016: PloS One
Braden M Roth, Kristen M Varney, Richard R Rustandi, David J Weber
Once considered a relatively harmless bacterium, Clostridium difficile has become a major concern for healthcare facilities, now the most commonly reported hospital-acquired pathogen. C. difficile infection (CDI) is usually contracted when the normal gut microbiome is compromised by antibiotic therapy, allowing the opportunistic pathogen to grow and produce its toxins. The severity of infection ranges from watery diarrhea and abdominal cramping to pseudomembranous colitis, sepsis, or death. The past decade has seen a marked increase in the frequency and severity of CDI among industrialized nations owing directly to the emergence of a highly virulent C...
October 2016: Biomolecular NMR Assignments
Jae Hyun Shin, Esteban Chaves-Olarte, Cirle A Warren
Clostridium difficile is an anaerobic, Gram-positive, spore-forming, toxin-secreting bacillus that has long been recognized to be the most common etiologic pathogen of antibiotic-associated diarrhea. C. difficile infection (CDI) is now the most common cause of health care-associated infections in the United States and accounts for 12% of these infections (Magill SS et al., N Engl J Med370:1198-1208, 2014). Among emerging pathogens of public health importance in the United States, CDI has the highest population-based incidence, estimated at 147 per 100,000 (Lessa FC et al...
June 2016: Microbiology Spectrum
Cecília Leite Costa, Diana López-Ureña, Thiago de Oliveira Assis, Ronaldo A Ribeiro, Rodrigo Otávio Silveira Silva, Maja Rupnik, Mark H Wilcox, Alex Fiorini de Carvalho, Anderson Oliveira do Carmo, Adriana Abalen Martins Dias, Cibele Barreto Mano de Carvalho, Esteban Chaves-Olarte, César Rodríguez, Carlos Quesada-Gómez, Gerly Anne de Castro Brito
The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA(+), tcdB(+) and ctdB(+)) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype...
August 2016: Anaerobe
Benjamin W Campbell, Anna N Hofstad, Suma Sreekanta, Fengli Fu, Thomas J Y Kono, Jamie A O'Rourke, Carroll P Vance, Gary J Muehlbauer, Robert M Stupar
Three adjacent and distinct sequence rearrangements were identified at a NAP1 locus in a soybean mutant. Genetic dissection and validation revealed the function of this gene in soybean trichome development. A soybean (Glycine max (L.) Merr.) gnarled trichome mutant, exhibiting stunted trichomes compared to wild-type, was identified in a fast neutron mutant population. Genetic mapping using whole genome sequencing-based bulked segregant analysis identified a 26.6 megabase interval on chromosome 20 that co-segregated with the phenotype...
September 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Rashmi Prasad, Sheena D'Arcy, Arjan Hada, Karolin Luger, Blaine Bartholomew
The SWI/SNF and RSC family of ATP-dependent chromatin remodelers disassembles nucleosomes by moving nucleosomes into the vicinity of adjoining nucleosomes. We found that the histone chaperone Nap1 efficiently promotes disassembly of adjacent nucleosomes with which RSC collides and not the disassembly of nucleosomes mobilized by RSC. Nap1 is specific to RSC, as it does not target SWI/SNF, its paralog in Saccharomyces cerevisiae Extensive mutational analysis of Nap1 has revealed that Nap1 affinity for histones H2A-H2B and H3-H4 and its ability to displace histones from DNA are required for Nap1 to enhance RSC-mediated disassembly...
September 1, 2016: Molecular and Cellular Biology
Larry K Kociolek, Dale N Gerding, James R Osmolski, Sameer J Patel, David R Snydman, Laura A McDermott, David W Hecht
The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital...
August 2016: Antimicrobial Agents and Chemotherapy
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