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https://www.readbyqxmd.com/read/28893366/fidaxomicin-reduces-early-toxin-a-and-b-production-and-sporulation-in-clostridium-difficilein-vitro
#1
Michael J Aldape, Aaron E Packham, Dustin D Heeney, Savannah N Rice, Amy E Bryant, Dennis L Stevens
PURPOSE: Fidaxomicin, a macrocyclic antibiotic, has been approved for the treatment of Clostridium difficile infection (CDI). Previous work by our group has demonstrated that some antibiotics at sub-inhibitory concentrations stimulate early toxin production and sporulation by C. difficile. Prior studies revealed that fidaxomicin, when added to late stationary-phase organisms, reduced exotoxin production and spore formation by C. difficile. However, the ability of fidaxomicin to trigger early virulence factor production and spore formation has never been investigated...
September 12, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28883625/redundant-functions-for-nap1-and-chz1-in-h2a-z-deposition
#2
Raghuvar Dronamraju, Srinivas Ramachandran, Deepak K Jha, Alexander T Adams, Julia V DiFiore, Michael A Parra, Nikolay V Dokholyan, Brian D Strahl
H2A.Z is a histone H2A variant that contributes to transcriptional regulation, DNA damage response and limits heterochromatin spreading. In Saccharomyces cerevisiae, H2A.Z is deposited by the SWR-C complex, which relies on several histone chaperones including Nap1 and Chz1 to deliver H2A.Z-H2B dimers to SWR-C. However, the mechanisms by which Nap1 and Chz1 cooperate to bind H2A.Z and their contribution to H2A.Z deposition in chromatin is not well understood. Using structural modeling and molecular dynamics simulations, we identify a series of H2A...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733522/abi3-a-component-of-the-wave2-complex-is-potentially-regulated-by-pi3k-akt-pathway
#3
Lais Moraes, Nilson I T Zanchin, Janete M Cerutti
We previously reported that ABI3 expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth in vivo. The mechanistic basis by which ABI3 exerts its tumor suppressive effects is not fully understood. In this study, we show that ABI3 is a phosphoprotein. Using proteomic array analysis, we showed that ABI3 modulated distinct cancer-related pathways in thyroid cancer cells. The KEA analysis found that PI3K substrates were enriched and forced expression of ABI3 markedly decreased the phosphorylation of AKT and the downstream-targeted protein pGSK3β...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729205/antimicrobial-susceptibility-of-clostridium-difficile-isolates-in-israel
#4
Linda Tkhawkho, Orna Nitzan, Nina Pastukh, Diana Brodsky, Karen Jackson, Avi Peretz
OBJECTIVES: An increase of Clostridium difficile isolates with reduced susceptibility to various antimicrobial agents has been observed, including isolates that are non-susceptible to antibiotics that are routinely used for treatment of C. difficile, such as vancomycin and metronidazole. We determined the susceptibility rates of C. difficile isolates from hospitals in northern Israel to various antibiotics including tigecycline, which was not previously reported from Israel. METHODS: A total of 81 stool samples were collected from three hospitals in northern Israel from patients with C...
September 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28708379/chemical-genomics-structure-elucidation-and-in-vivo-studies-of-the-marine-derived-anticlostridial-ecteinamycin
#5
Thomas P Wyche, René F Ramos Alvarenga, Jeff S Piotrowski, Megan N Duster, Simone R Warrack, Gabriel Cornilescu, Travis J De Wolfe, Yanpeng Hou, Doug R Braun, Gregory A Ellis, Scott W Simpkins, Justin Nelson, Chad L Myers, James Steele, Hirotada Mori, Nasia Safdar, John L Markley, Scott R Rajski, Tim S Bugni
A polyether antibiotic, ecteinamycin (1), was isolated from a marine Actinomadura sp., cultivated from the ascidian Ecteinascidia turbinata. (13)C enrichment, high resolution NMR spectroscopy, and molecular modeling enabled elucidation of the structure of 1, which was validated on the basis of comparisons with its recently reported crystal structure. Importantly, ecteinamycin demonstrated potent activity against the toxigenic strain of Clostridium difficile NAP1/B1/027 (MIC = 59 ng/μL), as well as other toxigenic and nontoxigenic C...
September 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28692454/phosphorylation-of-cyfip2-a-component-of-the-wave-regulatory-complex-regulates-dendritic-spine-density-and-neurite-outgrowth-in-cultured-hippocampal-neurons-potentially-by-affecting-the-complex-assembly
#6
Yeunkum Lee, Doyoun Kim, Jae Ryun Ryu, Yinhua Zhang, Shinhyun Kim, Yoonhee Kim, Bokyoung Lee, Woong Sun, Kihoon Han
Actin dynamics is a critical mechanism underlying many cellular processes in neurons. The heteropentameric WAVE-regulatory complex (WRC), consisting of WAVE, CYFIP1/2, Nap, Abi, and HSPC300, is a key regulator of actin dynamics that activates the Arp2/3 complex to initiate actin polymerization and branching. The WRC is basally inactive because of intermolecular interactions among the components, which can be modulated by bindings of phospholipids and Rac1, and phosphorylations of WAVE and Abi. However, the phosphorylation of other components of WRC and their functional significance remain largely unknown...
August 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28687276/nap1l1-regulates-nf-%C3%AE%C2%BAb-signaling-pathway-acting-on-anti-apoptotic-mcl-1-gene-expression
#7
Toshiaki Tanaka, Yasukazu Hozumi, Mitsuyoshi Iino, Kaoru Goto
Nuclear factor-κB (NF-κB) participates in apoptosis signaling pathway under various pathophysiological conditions. It exerts transcriptional control on the anti-apoptotic Bcl-2 family, such as Bcl-2, Bcl-xl, and Mcl-1, which act on the mitochondrial outer membrane. Previously, we described that NF-κB is negatively regulated by diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates a lipid second messenger diacylglycerol. DGKζ downregulation enhances inhibitors of NF-κB α (IκBα) degradation and p65 subunit phosphorylation, leading to enhanced NF-κB transcriptional activity...
July 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28669616/clostridium-difficile-chimeric-toxin-receptor-binding-domain-vaccine-induced-protection-against-different-strains-in-active-and-passive-challenge-models
#8
Jing-Hui Tian, Gregory Glenn, David Flyer, Bin Zhou, Ye Liu, Eddie Sullivan, Hua Wu, James F Cummings, Larry Elllingsworth, Gale Smith
Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C. difficile (B1/NAP1/027) have emerged and are linked to an increase in morbidity and mortality. Increased virulence is attributed to multiple factors including: increased production of A- and B-toxins; production of binary toxin (CDT); and the emergence of more toxic TcdB variants (TcdB(027))...
July 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28645479/impact-of-the-nap-1-strain-on-disease-severity-mortality-and-recurrence-of-healthcare-associated-clostridium-difficile-infection
#9
Karri A Bauer, Jessica E W Johnston, Eric Wenzler, Debra A Goff, Charles H Cook, Joan-Miquel Balada-Llasat, Preeti Pancholi, Julie E Mangino
OBJECTIVES: Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. METHODS: Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence...
June 21, 2017: Anaerobe
https://www.readbyqxmd.com/read/28641088/application-of-zeolite-hydrous-zirconia-composite-as-a-novel-sediment-capping-material-to-immobilize-phosphorus
#10
Yi Fan, Yiwen Li, Deyi Wu, Chunjie Li, Hainan Kong
A unique sediment-capping agent consisting of a zeolite/hydrous zirconia composite (ZHZ) was developed and tested for P-immobilization in the overlying water and sediment cores from a freshwater pond. In the ZHZ, NaP1 zeolite was covered with hydrous zirconia, which existed as an amorphous phase. Experimental results in pond water indicated that ZHZ could efficiently remove soluble reactive phosphorus. The 28-day sediment incubation experiments showed that capping sediment with ZHZ resulted in a more efficient, rapid and sustained decrease in P concentration when compared with the traditional alum treatment method...
June 12, 2017: Water Research
https://www.readbyqxmd.com/read/28625250/-fulminant-clostridium-difficile-colitis-new-challenges-in-critical-care-medicine
#11
Bin Liu
Fulminant Clostridium difficile colitis (FCDC) means severe Clostridium difficile colitis (CDC), which often manifested with severe diarrhea, fever, abdominal distention, electrolyte disorder, hypoalbuminemia, and it can lead to pseudo membrane colonitis, toxic megacolon, bowel perforation, septic shock, and multiple organ dysfunction. Now Clostridium difficile (CD) becomes one of the most important medical institutions related infectious pathogens. In particular, the recently discovered mutant CD strain NAP1/BI/ribotype 027 has high pathogenicity in the global epidemic and its outbreak...
June 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28501926/an-outbreak-of-clostridium-difficile-pcr-ribotype-027-in-spain-risk-factors-for-recurrence-and-a-novel-treatment-strategy
#12
E Bouza, L Alcalá, M Marín, M Valerio, E Reigadas, P Muñoz, M González-Del Vecchio, V de Egea
An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027...
May 13, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28482300/recovery-of-nutrients-n-p-k-from-potassium-rich-sludge-anaerobic-digestion-side-streams-by-integration-of-a-hybrid-sorption-membrane-ultrafiltration-process-use-of-powder-reactive-sorbents-as-nutrient-carriers
#13
Mehrez Hermassi, Cèsar Valderrama, Oriol Gibert, Natalia Moreno, Xavier Querol, Narjès Harrouch Batis, Jose Luis Cortina
Here, an alternative nutrient (N-P-K) recovery route from potassium-rich sludge anaerobic digestion side-streams using powder reactive sorbents (PRSs) is presented. In the first step, the optimum PRS system was determined in batch experiments with mixtures of: a) a sodium zeolite (NaP1) to facilitate the NH4(+) and K(+) sorption; b) a Ca-zeolite (CaP1) to facilitate the removal of P by formation of Ca-phosphates (e.g., CaHPO4(s)), and c) caustic magnesia containing mixtures of MgO to facilitate the formation of Mg/NH4/PO4 minerals (e...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28402634/synthesis-and-biological-evaluation-of-bile-acid-analogues-inhibitory-to-clostridium-difficile-spore-germination
#14
Kristen L Stoltz, Raymond Erickson, Christopher Staley, Alexa R Weingarden, Erin Romens, Clifford J Steer, Alexander Khoruts, Michael J Sadowsky, Peter I Dosa
Standard antibiotic-based strategies for the treatment of Clostridium difficile infections disrupt indigenous microbiota and commonly fail to eradicate bacterial spores, two key factors that allow recurrence of infection. As an alternative approach to controlling C. difficile infection, a series of bile acid derivatives have been prepared that inhibit taurocholate-induced spore germination. These analogues have been evaluated in a highly virulent NAP1 strain using optical density and phase-contrast microscopy assays...
April 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28369616/nap1l1-accelerates-activation-and-decreases-pausing-to-enhance-nucleosome-remodeling-by-csb
#15
Ju Yeon Lee, Robert J Lake, Jaewon Kirk, Vilhelm A Bohr, Hua-Ying Fan, Sungchul Hohng
Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. While chromatin remodeling by CSB and NAP1-like proteins is crucial for efficient transcription-coupled DNA repair, the mechanism by which NAP1-like proteins enhance chromatin remodeling by CSB remains unknown...
May 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28351991/the-composition-of-the-arabidopsis-rna-polymerase-ii-transcript-elongation-complex-reveals-the-interplay-between-elongation-and-mrna-processing-factors
#16
Wojciech Antosz, Alexander Pfab, Hans F Ehrnsberger, Philipp Holzinger, Karin Köllen, Simon A Mortensen, Astrid Bruckmann, Thomas Schubert, Gernot Längst, Joachim Griesenbeck, Veit Schubert, Marion Grasser, Klaus D Grasser
Transcript elongation factors (TEFs) are a heterogeneous group of proteins that control the efficiency of transcript elongation of subsets of genes by RNA polymerase II (RNAPII) in the chromatin context. Using reciprocal tagging in combination with affinity purification and mass spectrometry, we demonstrate that in Arabidopsis thaliana, the TEFs SPT4/SPT5, SPT6, FACT, PAF1-C, and TFIIS copurified with each other and with elongating RNAPII, while P-TEFb was not among the interactors. Additionally, NAP1 histone chaperones, ATP-dependent chromatin remodeling factors, and some histone-modifying enzymes including Elongator were repeatedly found associated with TEFs...
April 2017: Plant Cell
https://www.readbyqxmd.com/read/28255536/central-role-of-pi3k-syk-interaction-in-fibrinogen-induced-lamellipodia-and-filopodia-formation-in-platelets
#17
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
#18
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
#19
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 21, 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
#20
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
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