bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Incidence and Endemic Spread of NDM-1-Positive Enterobacteriaceae in Henan Province, China
Authors: Qin Shangshang , Fu Ying , Zhang Qijing , Qi Hui , Wen Jian Guo , Xu Hui , Xu Lijuan , Zeng Li , Tian Hao , Rong Lijuan , Li Yonghong , Shan Lihong , Xu Hongde , Yu Yunsong , Feng Xianju , Liu Hong-Min 
Published: April 2014

ABSTRACT

The emergence and spread of New Delhi metallo-β-lactamase 1 (NDM-1)-producing carbapenem-resistant
Enterobacteriaceae
(CRE) present an urgent threat to human health. In China, the
bla
NDM-1
gene has been reported mostly in
Acinetobacter
spp. but is rarely found in
Enterobacteriaceae
. Here, we report a high incidence and endemic spread of NDM-1-producing CRE in Henan Province in China. Sixteen (33.3%) of the 48 CRE isolates obtained from patients during June 2011 to July 2012 were positive for
bla
NDM-1
, and the gene was found to be carried on plasmids of various sizes (∼55 to ∼360 kb). These plasmids were readily transferrable to recipient
Escherichia coli
by conjugation, conferred resistance to multiple antibiotics, and belonged to multiple replicon types. The
bla
NDM-1
-positive CRE isolates were genetically diverse, and six new multilocus sequence typing (MLST) sequence types were linked to the carriage of NDM-1. Five of the isolates were classified as extensively drug-resistant (XDR) isolates, four of which also carried the
fosA3
gene conferring resistance to fosfomycin, an alternative drug for treating infections by CRE. In each
bla
NDM-1
-positive CRE isolate, the
bla
NDM-1
gene was downstream of an intact IS
Aba125
element and upstream of the
ble
MBL
gene. Furthermore, gene environment analysis suggested the possible transmission of
bla
NDM-1
-containing sequences from
Acinetobacter
spp. to
Klebsiella pneumoniae
and
Klebsiella oxytoca
. These findings reveal the emergence and active transmission of NDM-1-positive CRE in China and underscore the need for heightened measures to control their further spread.
SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion
Authors: Gallotta Marilena , Gancitano Giovanni , Pietrocola Giampiero , Mora Marirosa , Pezzicoli Alfredo , Tuscano Giovanna , Chiarot Emiliano , Nardi-Dei Vincenzo , Taddei Anna Rita , Rindi Simonetta , Speziale Pietro , Soriani Marco , Grandi Guido , Margarit Immaculada , Bensi Giuliano 
Published: April 2014

ABSTRACT

Group A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of the
spy0269
gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interact
in vitro
with the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cells
in vitro
and that
Lactococcus lactis
expressing Spy0269 on its cell surface could adhere to mammalian cells
in vitro
and to mice nasal mucosa
in vivo
. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (

S
treptococcus
py
ogenes

A
dhesion and
D
ivision protein).
FTT0831c/FTL_0325 Contributes to Francisella tularensis Cell Division, Maintenance of Cell Shape, and Structural Integrity
Authors: Robertson Gregory T. , Case Elizabeth Di Russo , Dobbs Nicole , Ingle Christine , Balaban Murat , Celli Jean , Norgard Michael V. 
Published: April 2014

ABSTRACT

The
Francisella
FTT0831c/FTL_0325 gene encodes amino acid motifs to suggest it is a lipoprotein and that it may interact with the bacterial cell wall as a member of the OmpA-like protein family. Previous studies have suggested that FTT0831c is surface exposed and required for virulence of
Francisella tularensis
by subverting the host innate immune response (M. Mahawar et al., J. Biol. Chem. 287:25216–25229, 2012). We also found that FTT0831c is required for murine pathogenesis and intramacrophage growth of Schu S4, but we propose a different model to account for the proinflammatory nature of the resultant mutants. First, inactivation of FTL_0325 from live vaccine strain (LVS) or FTT0831c from Schu S4 resulted in temperature-dependent defects in cell viability and morphology. Loss of FTT0831c was also associated with an unusual defect in lipopolysaccharide O-antigen synthesis, but loss of FTL_0325 was not. Full restoration of these properties was observed in complemented strains expressing FTT0831c
in trans
, but not in strains lacking the OmpA motif, suggesting that cell wall contact is required. Finally, growth of the LVS FTL_0325 mutant in Mueller-Hinton broth at 37°C resulted in the appearance of membrane blebs at the poles and midpoint, prior to the formation of enlarged round cells that showed evidence of compromised cellular membranes. Taken together, these data are more consistent with the known structural role of OmpA-like proteins in linking the OM to the cell wall and, as such, maintenance of structural integrity preventing altered surface exposure or release of Toll-like receptor 2 agonists during rapid growth of
Francisella
in vitro
and
in vivo
.
The Salmonella Effector SteA Contributes to the Control of Membrane Dynamics of Salmonella-Containing Vacuoles
Authors: Domingues Lia , Holden David W. , Mota Luís Jaime 
Published: April 2014

ABSTRACT

Salmonella enterica
serovar Typhimurium is a bacterial pathogen causing gastroenteritis in humans and a typhoid-like systemic disease in mice.
S
. Typhimurium virulence is related to its capacity to multiply intracellularly within a membrane-bound compartment, the
Salmonella
-containing vacuole (SCV), and depends on type III secretion systems that deliver bacterial effector proteins into host cells. Here, we analyzed the cellular function of the
Salmonella
effector SteA. We show that, compared to cells infected by wild-type
S
. Typhimurium, cells infected by Δ
steA
mutant bacteria displayed fewer
Salmonella
-induced filaments (SIFs), an increased clustering of SCVs, and morphologically abnormal vacuoles containing more than one bacterium. The increased clustering of SCVs and the appearance of vacuoles containing more than one bacterium were suppressed by inhibition of the activity of the microtubule motor dynein or kinesin-1. Clustering and positioning of SCVs are controlled by the effectors SseF and SseG, possibly by helping to maintain a balanced activity of microtubule motors on the bacterial vacuoles. Deletion of
steA
in
S
. Typhimurium Δ
sseF
or Δ
sseG
mutants revealed that SteA contributes to the characteristic scattered distribution of Δ
sseF
or Δ
sseG
mutant SCVs in infected cells. Overall, this shows that SteA participates in the control of SCV membrane dynamics. Moreover, it indicates that SteA is functionally linked to SseF and SseG and suggests that it might contribute directly or indirectly to the regulation of microtubule motors on the bacterial vacuoles.
Chemokines and Antimicrobial Peptides Have a
cag
-Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells
Authors: Mustapha Pascale , Paris Isabelle , Garcia Magali , Tran Cong Tri , Cremniter Julie , Garnier Martine , Faure Jean-Pierre , Barthes Thierry , Boneca Ivo G. , Morel Franck , Lecron Jean-Claude , Burucoa Christophe , Bodet Charles 
Published: April 2014

ABSTRACT

Helicobacter pylori
infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The
cag
pathogenicity island (
cag
PAI) of
H. pylori
allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to
H. pylori
, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with
H. pylori
B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with
H. pylori
B128ΔcagM, a
cag
PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with
H. pylori
, inflammatory-mediator production was largely due to
cag
PAI substrate-independent virulence factors. Thus,
H. pylori
cag
PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during
H. pylori
infection.
Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury
Authors: Rao Roshni , Nagarkatti Prakash , Nagarkatti Mitzi 
Published: April 2014

ABSTRACTStaphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155−/−mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-γ). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-γ, was identified as a potential target of miR-155. While miR-155−/−mice displayed increased expression ofSocs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-γ levels. Additionally, the inhibition of miR-155 resulted in restoredSocs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs throughSocs1suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury.
Structural Conservation, Variability, and Immunogenicity of the T6 Backbone Pilin of Serotype M6 Streptococcus pyogenes
Authors: Young Paul G. , Moreland Nicole J. , Loh Jacelyn M. , Bell Anita , Atatoa Carr Polly , Proft Thomas , Baker Edward N. 
Published: April 2014

ABSTRACT

Group A streptococcus (GAS;
Streptococcus pyogenes
) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection
in vivo
. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine.
The future of population registers: linking routine health datasets to assess a population's current glycaemic status for quality improvement
Authors: Chan Wing Cheuk , Jackson Gary , Wright Craig Shawe , Orr-Walker Brandon , Drury Paul L , Boswell D Ross , Lee Mildred Ai Wei , Papa Dean , Jackson Rod 
Published: April 2014

ObjectivesTo determine the diabetes screening levels and known glycaemic status of all individuals by age, gender and ethnicity within a defined geographic location in a timely and consistent way to potentially facilitate systematic disease prevention and management.DesignRetrospective observational study.SettingAuckland region of New Zealand.Participants1 475 347 people who had utilised publicly funded health service in New Zealand and domicile in the Auckland region of New Zealand in 2010. The health service utilisation population was individually linked to a comprehensive regional laboratory repository dating back to 2004.Outcome measuresThe two outcomes measures were glycaemia-related blood testing coverage (glycated haemoglobin (HbA1c), fasting and random glucose and glucose tolerance tests), and the proportions and number of people with known dysglycaemia in 2010 using modified American Diabetes Association (ADA) and WHO criteria.ResultsWithin the health service utilisation population, 792 560 people had had at least one glucose or HbA1c blood test in the previous 5.5 years. Overall, 81% of males (n=198 086) and 87% of females (n=128 982) in the recommended age groups for diabetes screening had a blood test to assess their glycaemic status. The estimated age-standardised prevalence of dysglycaemia was highest in people of Pacific Island ethnicity at 11.4% (95% CI 11.2% to 11.5%) for males and 11.6% (11.4% to 11.8%) for females, followed closely by people of Indian ethnicity at 10.8% (10.6% to 11.1%) and 9.3% (9.1% to 9.6%), respectively. Among the indigenous Maori population, the prevalence was 8.2% (7.9% to 8.4%) and 7% (6.8% to 7.2%), while for ‘Others’ (mainly Europeans) it was 3% (3% to 3.1%) and 2.2% (2.1% to 2.2%), respectively.ConclusionsWe have demonstrated that the data linkage between a laboratory repository and national administrative datasets has the potential to provide a systematic and consistent individual level clinical information that is relevant to medical auditing for a large geographically defined population.
Acupuncture for the treatment of chronic obstructive pulmonary disease: a protocol of a systematic review
Authors: Choi Tae-Young , Jun Ji Hee , Choi Jun-Young , Kim Jong-In , Lee Myeong Soo , Ernst Edzard 
Published: April 2014

IntroductionThis review aims to evaluate the efficacy of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD).Methods and analysis14 databases will be searched from their inception. These include PubMed, AMED, EMBASE, the Cochrane Library, seven Korean medical databases (Korean Studies Information Service System, DBPIA, Oriental Medicine Advanced Searching Integrated System, Research Information Service System, KoreaMed, The Town Society of Science Technology and the Korean National Assembly Library), three Chinese Databases (China National Knowledge Infrastructure Database (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and the Wanfang Database). Only randomised clinical trials (RCTs) using acupuncture for COPD will be considered. The selection of the studies, data abstraction and validation will be performed independently by two researchers. Methodological quality will be assessed with the Cochrane risk of bias.DisseminationThe systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. Updates of the review will be conducted to inform and guide the healthcare practice and policy.Trial registration numberPROSPERO 2013: CRD42013004824.
Falling mortality when adjusted for comorbidity in upper gastrointestinal bleeding: relevance of multi-disciplinary care
Authors: Taha Ali S , Saffouri Eliana , McCloskey Caroline , Craigen Theresa , Angerson Wilson J 
Published: April 2014

ObjectivesThe understanding of changes in comorbidity might improve the management of upper gastrointestinal bleeding (UGIB); such changes might not be detectable in short-term studies. We aimed to study UGIB mortality as adjusted for comorbidity and the trends in risk scores over a 14-year period.MethodsPatients presenting with UGIB to a single institution, 1996–2010, were assessed. Those with multiple comorbidities were managed in a multi-disciplinary care unit since 2000. Trends with time were assessed using logistic regression, including those for Charlson comorbidity score, the complete Rockall score and 30-day mortality.Results2669 patients were included. The Charlson comorbidity score increased significantly with time: the odds of a high (3+) score increasing at a relative rate of 4.4% a year (OR 1.044; p<0.001). The overall 30-day mortality was 4.9% and inpatient mortality was 7.1%; these showed no relationship with time. When adjusted for the increasing comorbidity, the odds of death decreased significantly at a relative rate of 4.5% per year (p=0.038). After the introduction of multi-disciplinary care, the raw mortality OR was 0.680 (p=0.08), and adjusted for comorbidity it was 0.566 (p=0.013).Conclusions30-day mortality decreased when adjusted for the rising comorbidity in UGIB; whether this is related to the introduction of multi-disciplinary care needs to be considered.
Too heavy, too late: investigating perinatal health outcomes in immigrants residing in Spain. A cross-sectional study (2009–2011)
Authors: Juárez Sol P , Revuelta-Eugercios Bárbara A 
Published: April 2014

BackgroundStudies have shown that immigrants residing in Spain have lower risks of delivering low birthweight (LBW) and preterm babies despite their socioeconomic disadvantages (the healthy migrant paradox). However, less is known about other important perinatal outcomes derived from birth weight and gestational age such as macrosomia and post-term birth. This paper aims to compare the main indicators related to birth weight and gestational age (LBW, macrosomia, preterm and post-term) for immigrants and Spaniards.MethodsCross-sectional study based on the Spanish vital statistics for years 2009–2011. Multinomial regression models were performed to obtain crude and adjusted ORs and their 95% CIs.ResultsAfter adjusting for known confounders, compared with Spaniards, most immigrant groups show lower or not significantly different risks of delivering LBW (OR between 0.65 and 0.87) or, more exceptionally, preterm babies (between 0.75 and 0.93). However, most of them also show higher risks of delivering macrosomic (OR between 1.21 and 2.58) and post-term babies (OR between 1.11 and 1.50). Mothers from sub-Saharan Africa show a higher risk in all perinatal outcomes studied.ConclusionsThe immigrant health paradox should be carefully assessed in comprehensive terms. Together with a predominantly lower risk of LBW, most immigrants have a higher risk of macrosomia, post-term and preterm births. These results have policy-making implications since studying the right tail of the birth weight and gestational age distributions implies considering a different set of risk factors.
Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis in Male Mice through Activation of the Wnt/β-Catenin Signaling Pathway
Authors: Mercer Kelly E. , Hennings Leah , Sharma Neha , Lai Keith , Cleves Mario A. , Wynne Rebecca A. , Badger Thomas M. , Ronis Martin J.J. 
Published: April 2014

Abstract
Although alcohol effects within the liver have been extensively studied, the complex mechanisms by which alcohol causes liver cancer are not well understood. It has been suggested that ethanol (EtOH) metabolism promotes tumor growth by increasing hepatocyte proliferation. In this study, we developed a mouse model of tumor promotion by chronic EtOH consumption in which EtOH feeding began 46 days after injection of the chemical carcinogen diethylnitrosamine (DEN) and continued for 16 weeks. With a final EtOH concentration of 28% of total calories, we observed a significant increase in the total number of preneoplastic foci and liver tumors per mouse in the EtOH+DEN group compared with corresponding pair-fed (PF)+DEN and chow+DEN control groups. We also observed a 4-fold increase in hepatocyte proliferation (P &lt; 0.05) and increased cytoplasmic staining of active-β-catenin in nontumor liver sections from EtOH+DEN mice compared with PF+DEN controls. In a rat model of alcohol-induced liver disease, we found increased hepatocyte proliferation (P &lt; 0.05); depletion of retinol and retinoic acid stores (P &lt; 0.05); increased expression of cytosolic and nuclear expression of β-catenin (P &lt; 0.05) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β), P &lt; 0.05; significant upregulation in Wnt7a mRNA expression; and increased expression of several β-catenin targets, including, glutamine synthetase (GS), cyclin D1, Wnt1 inducible signaling pathways protein (WISP1), and matrix metalloproteinase-7(MMP7), P &lt; 0.05. These data suggest that chronic EtOH consumption activates the Wnt/β-catenin signaling pathways to increase hepatocyte proliferation, thus promoting tumorigenesis following an initiating insult to the liver. Cancer Prev Res; 7(7); 675–85. ©2014 AACR.