Article added to library!
x
Pubchase is a service of protocols.io - free, open access, crowdsourced protocols repository. Explore protocols.
Sign in
Reset password
or connect with
Facebook
By signing in you are agreeing to our
Terms Of Service and Privacy Policy
Microbiology
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Feb 24, 2017   The Journal Of Experimental Medicine
Öhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS,   . . . . . .   , Fearon DT, Crawford JM, Clevers H, Park Y, Tuveson DA
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Feb 24, 2017
The Journal Of Experimental Medicine
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated αSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.© 2017 Öhlund et al.
Inhibition of Virulence-promoting Disulfide Bond Formation Enzyme DsbB is blocked by Mutating Residues in two distinct regions
Feb 24, 2017   The Journal Of Biological Chemistry
Landeta C, Meehan BM, McPartland L, Ingendahl L, Hatahet F, Tran NQ, Boyd D, Beckwith J
Inhibition of Virulence-promoting Disulfide Bond Formation Enzyme DsbB is blocked by Mutating Residues in two distinct regions
Feb 24, 2017
The Journal Of Biological Chemistry
Disulfide bonds contribute to protein stability, activity and folding in a variety of proteins including many involved in bacterial virulence such as, toxins, adhesins, flagella and pili among others. Therefore, inhibitors of disulfide bond formation enzymes could have profound effects on pathogen virulence. In the Escherichia coli disulfide bond formation pathway, the periplasmic protein DsbA introduces disulfide bonds into substrates and then the cytoplasmic membrane protein DsbB reoxidizes DsbAs cysteines regenerating its activity. Thus, DsbB generates a protein disulfide bond de novo by transferring electrons to the quinone pool. We previously identified an effective pyridazinone-related inhibitor of DsbB enzymes from several gram-negative bacteria. In order to map the protein residues that are important for the interaction with this inhibitor, we randomly mutagenized by error-prone PCR the E. coli dsbB gene and selected dsbB mutants that confer resistance to this drug using two approaches. We characterized in vivo and in vitro some of these mutants that map to two areas in the structure of DsbB, one located between the two first transmembrane segments where the quinone ring binds and the other located in the second periplasmic loop of DsbB, which interacts with DsbA. In addition, we show that a mutant version of a protein involved in lipopolysaccharide assembly, lptD4213, is synthetically lethal with the deletion of dsbB as well as with DsbB inhibitors. This finding suggests that drugs decreasing LptD assembly may be synthetically lethal with inhibitors of the Dsb pathway, potentiating antibiotic effects.Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
Genome Sequences of
Feb 24, 2017   Genome Announcements
Kamali M, Heydarnejad J, Pouramini N, Masumi H, Farkas K, Kraberger S, Varsani A
Genome Sequences of
Feb 24, 2017
Genome Announcements
Implementation of a vector-enabled metagenomics approach resulted in the identification of various geminiviruses. We identified the genome sequences of Copyright © 2017 Kamali et al.
Draft Genome Sequences of
Feb 24, 2017   Genome Announcements
Klein BA, Lemon KP, Gajare P, Jospin G, Eisen JA, Coil DA
Draft Genome Sequences of
Feb 24, 2017
Genome Announcements
We present here the draft genome sequences of Copyright © 2017 Klein et al.
Epitopes and Mechanism of Action of the Clostridium Difficile Toxin A-Neutralizing Antibody Actoxumab
Feb 24, 2017   Journal Of Molecular Biology
Hernandez LD, Kroh HK, Hsieh E, Yang X, Beaumont M,   . . . . . .   , Fischer P, Sher X, Gupta P, Lacy DB, Therien AG
Epitopes and Mechanism of Action of the Clostridium Difficile Toxin A-Neutralizing Antibody Actoxumab
Feb 24, 2017
Journal Of Molecular Biology
The exotoxins TcdA and TcdB are produced by the bacterial pathogen Clostridium difficile and are responsible for the pathology associated with C. difficile infection (CDI). The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively. Bezlotoxumab was recently approved by the FDA for reducing the recurrence of CDI. We have previously shown that a single molecule of bezlotoxumab binds to two distinct epitopes within the TcdB CROP domain preventing toxin binding to host cells. In this study we characterize the binding of actoxumab to TcdA and examine its mechanism of toxin neutralization. Using a combination of approaches including a number of biophysical techniques, we show there are 2 distinct actoxumab binding sites within the CROP domain of TcdA centered around identical amino acid sequences at residues 2162-2189 and 2410-2437. Actoxumab binding caused aggregation of TcdA especially at higher antibody:toxin concentration ratios. Actoxumab prevented association of TcdA with target cells demonstrating that actoxumab neutralizes toxin activity by inhibiting the first step of the intoxication cascade. This mechanism of neutralization is similar to that observed with bezlotoxumab and TcdB. Comparisons of the putative TcdA epitope sequences across several C. difficile ribotypes and homologous repeat sequences within TcdA suggest a structural basis for observed differences in actoxumab binding and/or neutralization potency. These data provide a mechanistic basis for the protective effects of the antibody in vitro and in vivo, including in various preclinical models of CDI.Copyright © 2017. Published by Elsevier Ltd.
Within-Host Sampling of a Natural Population Shows Signs of Selection on Pde1 during Bacterial Meningitis
Feb 24, 2017   Infection And Immunity
Lees JA, Brouwer M, van der Ende A, Parkhill J, van de Beek D, Bentley SD
Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer
Feb 24, 2017   Molecular Imaging And Biology : MIB : The Official Publication Of The Academy Of Molecular Imaging
He H, Chiu AC, Kanada M, Schaar BT, Krishnan V, Contag CH, Dorigo O
Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer
Feb 24, 2017
Molecular Imaging And Biology : MIB : The Official Publication Of The Academy Of Molecular Imaging
PURPOSE: Tumor-associated macrophages (TAMs) are often associated with a poor prognosis in cancer. To gain a better understanding of cellular recruitment and dynamics of TAM biology during cancer progression, we established a novel transgenic mouse model for in vivo imaging of luciferase-expressing macrophages. PROCEDURES: B6.129P2-Lyz2 RESULTS: In vivo imaging of LysM-LG mice showed luciferase activity was generated by macrophages. Clodronate liposome-mediated depletion of macrophages lowered overall bioluminescence while lipopolysaccharide injection increased macrophage bioluminescence in both the B16 and ID8 models. Tracking macrophages weekly in tumor-bearing animals after intraperitoneal (i.p.) or intraovarian (i.o.) injection resulted in distinct, dynamic patterns of macrophage activity. Animals with metastatic ovarian cancer after i.p. injection exhibited significantly higher peritoneal macrophage activity compared to animals after i.o. injection. CONCLUSION: The LysM-LG model allows tracking of macrophage recruitment and activation during disease initiation and progression in a noninvasive manner. This model provides a tool to visualize and monitor the benefit of pharmacological interventions targeting macrophages in preclinical models.
Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
Feb 24, 2017   Scientific Reports
Ch'ng JH, Sirel M, Zandian A, Del Pilar Quintana M, Chun Leung Chan S, Moll K, Tellgren-Roth A, Nilsson I, Nilsson P, Qundos U, Wahlgren M
Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
Feb 24, 2017
Scientific Reports
Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents. In this study, we assess the specificities of three promising polyclonal anti-RIFIN antibodies that were IgG-purified from sera of immunized animals. Their epitope regions were mapped using a 175,000-peptide microarray holding overlapping peptides of the P. falciparum variable surface antigens. Through immunoblotting and immunofluorescence imaging, we show that different antibodies give varying results in different applications/assays. Finally, we authenticate the antibody-based detection of RIFINs in two previously uncharacterized non-rosetting parasite lines by identifying the dominant rif transcripts using RNA sequencing.
Inhibition of Cronobacter sakazakii Virulence Factors by Citral
Feb 24, 2017   Scientific Reports
Shi C, Sun Y, Liu Z, Guo D, Sun H, Sun Z, Chen S, Zhang W, Wen Q, Peng X, Xia X
Inhibition of Cronobacter sakazakii Virulence Factors by Citral
Feb 24, 2017
Scientific Reports
Cronobacter sakazakii is a foodborne pathogen associated with fatal forms of necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The aim of this study was to determine whether citral, a major component of lemongrass oil, could suppress putative virulence factors of C. sakazakii that contribute to infection. Sub-inhibitory concentrations of citral significantly decreased motility, quorum sensing, biofilm formation and endotoxin production. Citral substantially reduced the adhesion and invasion of C. sakazakii to Caco-2 cells and decreased bacterial survival and replication within the RAW 264.7 macrophage cells. Citral also repressed the expression of eighteen genes involved in the virulence. These findings suggest that citral has potential to be developed as an alternative or supplemental agent to mitigate the infections caused by C. sakazakii.
Transcriptomic and virulence factors analyses of Cryptococcus neoformans hypoxia response
Feb 24, 2017   APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
Kong Q, Yang R, Wang Z, Zhou W, Du X, Huang S, Jiang Y, Liu W, Sang H
Transcriptomic and virulence factors analyses of Cryptococcus neoformans hypoxia response
Feb 24, 2017
APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
Cryptococcus neoformans is an environmental pathogen requiring atmospheric levels of oxygen for optimal growth. Upon inhalation, C. neoformans disseminates to the brain and causes meningoencephalitis. However, the mechanisms by which the pathogen adapts to the low-oxygen environment in the brain have not been investigated. We isolated a C. neoformans strain with a small capsule from a host tissue, although this strain produces large capsules in normoxic conditions. We hypothesize that this difference in capsule size is attributed to hypoxia caused by chronic inflammatory response. This study investigated the effect of hypoxia on virulence factors (including capsule, melanin, urease, and phospholipase) of C. neoformans and conducted transcriptomic analyses of the virulence-associated genes. We found that C. neoformans grew under hypoxic condition, albeit slowly, and that hypoxia may have inhibited the capsule size, melanin production, and phospholipase and urease activities in C. neoformans.© 2017 APMIS. Published by John Wiley & Sons Ltd.
Novel Cardiac Intracrine Mechanisms Based on Ang-(1-12)/Chymase Axis Require a Revision of Therapeutic Approaches in Human Heart Disease
Feb 24, 2017   Current Hypertension Reports
Reyes S, Varagic J, Ahmad S, VonCannon J, Kon ND, Wang H, Groban L, Cheng CP, Dell'Italia LJ, Ferrario CM
Novel Cardiac Intracrine Mechanisms Based on Ang-(1-12)/Chymase Axis Require a Revision of Therapeutic Approaches in Human Heart Disease
Feb 24, 2017
Current Hypertension Reports
PURPOSE OF THE REVIEW: Drugs targeting the renin-angiotensin system (RAS), namely angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are the most commonly prescribed drugs for patients with or at risk for cardiovascular events. However, new treatment strategies aimed at mitigating the rise of the heart failure pandemic are warranted because clinical trials show that RAS blockers have limited benefits in halting disease progression. The main goal of this review is to put forward the concept of an intracrine RAS signaling through the novel angiotensin-(1-12)/chymase axis as the main source of deleterious angiotensin II (Ang II) in cardiac maladaptive remodeling leading to heart failure (HF). RECENT FINDINGS: Expanding traditional knowledge, Ang II can be produced in tissues independently from the circulatory renin-angiotensin system. In the heart, angiotensin-(1-12) [Ang-(1-12)], a recently discovered derivative of angiotensinogen, is a precursor of Ang II, and chymase rather than ACE is the main enzyme contributing to the direct production of Ang II from Ang-(1-12). The Ang-(1-12)/chymase axis is an independent intracrine pathway accounting for the trophic, contractile, and pro-arrhythmic Ang II actions in the human heart. Ang-(1-12) expression and chymase activity have been found elevated in the left atrial appendage of heart disease subjects, suggesting a pivotal role of this axis in the progression of HF. Recent meta-analysis of large clinical trials on the use of ACE inhibitors and angiotensin receptor blockers in cardiovascular disease has demonstrated an imbalance between patients that significantly benefit from these therapeutic agents and those that remain at risk for heart disease progression. Looking to find an explanation, detailed investigation on the RAS has unveiled a previously unrecognized complexity of substrates and enzymes in tissues ultimately associated with the production of Ang II that may explain the shortcomings of ACE inhibition and angiotensin receptor blockade. Discovery of the Ang-(1-12)/chymase axis in human hearts, capable of producing Ang II independently from the circulatory RAS, has led to the notion that a tissue-delimited RAS signaling in an intracrine fashion may account for the deleterious effects of Ang II in the heart, contributing to the transition from maladaptive cardiac remodeling to heart failure. Targeting intracellular RAS signaling may improve current therapies aimed at reducing the burden of heart failure.
World TB Day 2017: Advances, Challenges and Opportunities in the "End-TB" Era
Feb 24, 2017   International Journal Of Infectious Diseases : IJID : Official Publication Of The International Society For Infectious Diseases
Petersen E, Maeurer M, Marais B, Migliori GB, Mwaba P, Ntoumi F, Vilaplana C, Kim K, Schito M, Zumla A
World TB Day 2017: Advances, Challenges and Opportunities in the "End-TB" Era
Feb 24, 2017
International Journal Of Infectious Diseases : IJID : Official Publication Of The International Society For Infectious Diseases
Sensitive detection of respiratory syncytial virus based on a dual signal amplified plasmonic enzyme-linked immunosorbent assay
Feb 24, 2017   Analytica Chimica Acta
Zhan L, Wu WB, Yang L, Huang CZ
Sensitive detection of respiratory syncytial virus based on a dual signal amplified plasmonic enzyme-linked immunosorbent assay
Feb 24, 2017
Analytica Chimica Acta
The timely detection of infectious pathogen is critical in clinical early diagnosis and treatment of infectious diseases. Plasmonic enzyme-linked immunosorbent assay (ELISA), by means of enzyme-mediated growth or aggregation of AuNPs, has received considerable attention because it allows a naked-eye detection of target in very low numbers. In this work, a dual-signal amplified plasmonic ELISA combined the high loading capacity of magnetic beads with the establishing stimulation effect of zinc ion has been developed to detect RSV as a model pathogen based on alkaline phosphatase-triggered dispersion of aggregated AuNPs. In ideal conditions, the proposed immunoassay can conveniently distinguish the concentration of RSV in a range of 0.1-30 pg/mL. In addition, the limit of detection of RSV of this immunoassay exceeds that of conventional ELISA by about 50 times. The high sensitivity makes this approach a good alternative to existing colorimetric immunoassays for pathogen detection.Copyright © 2017 Elsevier B.V. All rights reserved.
Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology
Feb 23, 2017   International Journal Of Molecular Sciences
Ni Z, Chen Y, Ong E, He Y
Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology
Feb 23, 2017
International Journal Of Molecular Sciences
As one of the most influential and troublesome human pathogens,
PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model
Feb 23, 2017   Viruses
Wu W, Liu Y, Lin Y, Pan D, Yang D, Lu M, Xu Y
PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model
Feb 23, 2017
Viruses
In the hydrodynamic injection (HI) BALB/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (WHV) could persist for a prolonged period of time (up to 45 weeks), while hepatitis B virus (HBV) was mostly cleared at week four. In this study, we constructed a series of chimeric genomes based on HBV and WHV, in which the individual sequences of a 1.3-fold overlength HBV genome in pBS-HBV1.3 were replaced by their counterparts from WHV. After HI with the WHV-HBV chimeric constructs in BALB/c mice, serum viral antigen, viral DNA (vDNA), and intrahepatic viral antigen expression were analyzed to evaluate the persistence of the chimeric genomes. Interestingly, we found that HI with three chimeric WHV-HBV genomes resulted in persistent antigenemia in mice. All of the persistent chimeric genomes contained the preC region and the part of the C region encoding the N-terminal 1-145 amino acids of the WHV genome. These results indicated that the preC region and the N-terminal part of the C region of the WHV genome may play a role in the persistent antigenemia. The chimeric WHV-HBV genomes were able to stably express viral antigens in the liver and could be further used to express hepadnaviral antigens to study their pathogenic potential.
Stabilized HIV-1 envelope glycoprotein trimers for vaccine use
Feb 23, 2017   Current Opinion In HIV And AIDS
Medina-Ramírez M, Sanders RW, Sattentau QJ
Stabilized HIV-1 envelope glycoprotein trimers for vaccine use
Feb 23, 2017
Current Opinion In HIV And AIDS
PURPOSE OF REVIEW: To provide an update on the latest developments in the field of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env trimer immunogens has moved the field of antibody-based vaccine design forward dramatically over the past few years with refinement of various stabilizing approaches. However, despite this progress, significant challenges remain. Firstly, although trimers are relatively stable in solution, they nevertheless sample different conformational states, some of which may be less relevant to binding and induction of broadly neutralizing antibodies (bNAbs). Secondly, these trimers expose unwanted immunodominant surfaces that may distract the adaptive immune response from recognizing more immunorecessive but conserved neutralization-relevant surfaces on the trimer. The availability of atomic-resolution structural information has allowed guided design of mutations that have further stabilized trimers and allowed reduced exposure of unwanted epitopes. Moreover, chemical cross-linking approaches that do not require structural information have also contributed to trimer stabilization and selection of particular conformational forms. However, current knowledge suggests that strategies additional to trimer stabilization will be required to elicit bNAb, including targeting naïve B cell receptors with specific immunogens, and guiding B cell lineages toward recognizing conserved surfaces on Env with high affinity. SUMMARY: This review will give a perspective on these challenges, and summarize current approaches to overcoming them with the aim of developing immunogens to elicit bNAb responses in humans by active vaccination.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.
Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015
Feb 23, 2017   Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin
Fonteneau L, Jourdan Da Silva N, Fabre L, Ashton P, Torpdahl M,   . . . . . .   , Weill FX, Gossner CM, Bertrand S, Dallman T, Le Hello S
Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015
Feb 23, 2017
Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin
Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonella enterica serotype Chester cases with travel to Morocco occurring in six European countries. Epidemiological and microbiological investigations were conducted. In addition to gathering information on the characteristics of cases from the different countries in 2014, the epidemiological investigation comprised a matched case-case study involving French patients with salmonellosis who travelled to Morocco that year. A univariate conditional logistic regression was performed to quantify associations. The microbiological study included a whole genome sequencing (WGS) analysis of clinical and non-human isolates of S. Chester of varied place and year of isolation. A total of 162 cases, mostly from France, followed by Belgium, the Netherlands, Spain, Denmark and Sweden were reported, including 86 (53%) women. The median age per country ranged from 3 to 38 years. Cases of S. Chester were more likely to have eaten in a restaurant and visited the coast of Morocco. The results of WGS showed five multilocus sequence types (ST), with 96 of 153 isolates analysed clustering into a tight group that corresponded to a novel ST, ST1954. Of these 96 isolates, 46 (48%) were derived from food or patients returning from Morocco and carried two types of plasmids containing either qnrS1 or qnrB19 genes. This European-wide outbreak associated with travel to Morocco was likely a multi-source outbreak with several food vehicles contaminated by multidrug-resistant S. Chester strains.This article is copyright of The Authors, 2017.
Unravelling the metabolic impact of SBS-associated microbial dysbiosis: Insights from the piglet short bowel syndrome model
Feb 23, 2017   Scientific Reports
Pereira-Fantini PM, Byars SG, Pitt J, Lapthorne S, Fouhy F, Cotter PD, Bines JE
Unravelling the metabolic impact of SBS-associated microbial dysbiosis: Insights from the piglet short bowel syndrome model
Feb 23, 2017
Scientific Reports
Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD. Multi-variate analyses were performed to elucidate contributing SBS-ALD microbe and metabolite panels and to identify microbe-metabolite interactions. A unique SBS-ALD microbe panel was clearest at the genus level, with discriminating bacteria predominantly from the Firmicutes and Bacteroidetes phyla. The SBS-ALD metabolome included important alterations in the microbial metabolism of amino acids and the mitochondrial metabolism of branched chain amino acids. Correlation analysis defined microbe-metabolite clustering patterns unique to SBS-ALD and identified a metabolite panel that correlates with dysbiosis of the gut microbiome in SBS.
Genome Sequence of Rhodoferax antarcticus ANT.BR
Feb 23, 2017   Microorganisms
Baker JM, Riester CJ, Skinner BM, Newell AW, Swingley WD,   . . . . . .   , Tang JK, Blankenship RE, Zhao T, Touchman JW, Sattley WM
A mouse model of paralytic myelitis caused by enterovirus D68
Feb 23, 2017   PLoS Pathogens
Hixon AM, Yu G, Leser JS, Yagi S, Clarke P, Chiu CY, Tyler KL
A mouse model of paralytic myelitis caused by enterovirus D68
Feb 23, 2017
PLoS Pathogens
In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM) cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68) respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF) from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested) produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.
A novel redox regulator, MnTnBuOE-2-PyP
Feb 23, 2017   Redox Biology
Zhao Y, Carroll DW, You Y, Chaiswing L, Wen R, Batinic-Haberle I, Bondada S, Liang Y, St Clair DK
A novel redox regulator, MnTnBuOE-2-PyP
Feb 23, 2017
Redox Biology
The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyPCopyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Co-occurrence and hybridization of anther-smut pathogens specialized on Dianthus hosts
Feb 23, 2017   Molecular Ecology
Petit E, Silver C, Cornille A, Gladieux P, Rosenthal L, Bruns E, Yee S, Antonovics J, Giraud T, Hood ME
Co-occurrence and hybridization of anther-smut pathogens specialized on Dianthus hosts
Feb 23, 2017
Molecular Ecology
Host specialization has important consequences for the diversification and ecological interactions of obligate pathogens. The anther-smut disease of natural plant populations, caused by Microbotryum fungi, has been characterized by specialized host-pathogen interactions, which contribute in part to the isolation among these numerous fungal species. This study investigated the molecular variation of Microbotryum pathogens within the geographic and host-specific distributions on wild Dianthus species in southern European Alps. In contrast to prior studies on this pathogen genus, a range of overlapping host specificities was observed for four delineated Microbotryum lineages on Dianthus hosts, and their frequent co-occurrence within single-host populations was quantified at local and regional scales. In addition to potential consequences for direct pathogen competition, the sympatry of Microbotryum lineages led to hybridization between them in many populations, and these admixed genotypes suffered significant meiotic sterility. Therefore, this investigation of the anther-smut fungi reveals how variation in the degrees of host specificity can have major implications for ecological interactions and genetic integrity of differentiated pathogen lineages. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas
Feb 23, 2017   PLoS Genetics
Thorell K, Yahara K, Berthenet E, Lawson DJ, Mikhail J, Kato I, Mendez A, Rizzato C, Bravo MM, Suzuki R, Yamaoka Y, Torres J, Sheppard SK, Falush D
Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas
Feb 23, 2017
PLoS Genetics
For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.
Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae
Feb 23, 2017   PLoS Genetics
Rollins M, Huard S, Morettin A, Takuski J, Pham TT, Fullerton MD, Côté J, Baetz K
Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae
Feb 23, 2017
PLoS Genetics
Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules.
Alteration of N-glycan expression profile and glycan pattern of glycoproteins in human hepatoma cells after HCV infection
Feb 23, 2017   Biochimica Et Biophysica Acta
Xiang T, Yang G, Liu X, Zhou Y, Fu Z, Lu F, Gu J, Taniguchi N, Tan Z, Chen X, Xie Y, Guan F, Zhang XL
Alteration of N-glycan expression profile and glycan pattern of glycoproteins in human hepatoma cells after HCV infection
Feb 23, 2017
Biochimica Et Biophysica Acta
BACKGROUND: Hepatitis C virus (HCV) infection causes chronic liver diseases, liver fibrosis and even hepatocellular carcinoma (HCC). However little is known about any information of N-glycan pattern in human liver cell after HCV infection. METHODS: The altered profile of N-glycans in HCV-infected Huh7.5.1 cell were analyzed by using mass spectrometry. Then, lectin microarray, lectin pull-down assay, reverse transcription-quantitative real time PCR (RT-qPCR) and western-blotting were used to identify the altered N-glycosylated proteins and glycosyltransferases. RESULTS: Compared to uninfected cells, significantly elevated levels of fucosylated, sialylated and complex N-glycans were found in HCV infected cells. Furthermore, Lens culinaris agglutinin (LCA)-binding glycoconjugates were increased most. Then, the LCA-agarose was used to precipitate the specific glycosylated proteins and identify that fucosylated modified annexin A2 (ANXA2) and heat shock protein 90 beta family member 1 (HSP90B1) was greatly increased in HCV-infected cells. However, the total ANXA2 and HSP90B1 protein levels remained unchanged. Additionally, we screened the mRNA expressions of 47 types of different glycosyltransferases and found that α1,6-fucosyltransferase 8 (FUT8) was the most up-regulated and contributed to strengthen the LCA binding capability to fucosylated modified ANXA2 and HSP90B1 after HCV infection. CONCLUSIONS: HCV infection caused the altered N-glycans profiles, increased expressions of FUT8, fucosylated ANXA2 and HSP90B1 as well as enhanced LCA binding to Huh7.5.1. GENERAL SIGNIFICANCE: Our results may lay the foundation for clarifying the role of N-glycans and facilitate the development of novel diagnostic biomarkers and therapeutic targets based on the increased FUT8, fucosylated ANXA2 and HSP90B1 after HCV infection. Copyright © 2017. Published by Elsevier B.V.

The link you entered does not seem to be valid

Please make sure the link points to nature.com contains a valid shared_access_token

Downloading PDF to your library...

Uploading PDF...

PDF uploading

Delete tag: