bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Polymorphisms in the Pf
mdr6
Gene and
Ex Vivo
Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal
Authors: Gendrot Mathieu , Diawara Silman , Madamet Marylin , Kounta Mame Bou , Briolant Sébastien , Wade Khalifa Ababacar , Fall Mansour , Benoit Nicolas , Nakoulima Aminata , Amalvict Rémy , Diémé Yaya , Fall Bécaye , Wade Boubacar , Diatta Bakary , Pradines Bruno 
Published: January 2017

ABSTRACT

Polymorphisms and the overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese
Plasmodium falciparum
isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of the
Plasmodium falciparum
multidrug resistance 6 gene (Pf
mdr6
) and the
ex vivo
susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine.
Plasmids of Distinct IncK Lineages Show Compatible Phenotypes
Authors: Rozwandowicz Marta , Brouwer Michael S. M. , Zomer Aldert L. , Bossers Alex , Harders Frank , Mevius Dik J. , Wagenaar Jaap A. , Hordijk Joost 
Published: January 2017

ABSTRACT

IncK plasmids are some of the main carriers of
bla
CTX-M-14
and
bla
CMY-2
genes and show high similarity to other plasmids belonging to the I complex, including IncB/O plasmids. Here, we studied the phylogenetic relationship of 37 newly sequenced IncK and IncB/O plasmids. We show that IncK plasmids can be divided into two compatible lineages named IncK1 and IncK2.
Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae
Authors: Łaniewski Paweł , Gomez Adriana , Hire Geoffrey , So Magdalene , Herbst-Kralovetz Melissa M. 
Published: January 2017

ABSTRACT

Colonization of the endometrium by pathogenic bacteria ascending from the lower female reproductive tract (FRT) is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions
in vitro
, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and the rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue, including cell differentiation, the presence of junctional complexes/desmosomes and microvilli, and the production of membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with poly(I·C) and flagellin but not with synthetic lipoprotein (fibroblast-stimulating lipoprotein 1 [FSL-1]) or lipopolysaccharide (LPS) significantly induced proinflammatory mediators in a dose-dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria:
Lactobacillus crispatus
,
Gardnerella vaginalis
, and
Neisseria gonorrhoeae
. All vaginal microbiota and
N. gonorrhoeae
efficiently colonized the 3-D surface, localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic
N. gonorrhoeae
and not infection with the other bacteria tested significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells. The latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of the 3-D EEC model for the study of the pathogenesis of
N. gonorrhoeae
using a well-characterized Δ
pilT
mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.
Molecular Epidemiology of Clostridium difficile Infection in Hospitalized Patients in Eastern China
Authors: Jin Dazhi , Luo Yun , Huang Chen , Cai Jian , Ye Julian , Zheng Yi , Wang Liqian , Zhao Peng , Liu Anbing , Fang Weijia , Wang Xianjun , Xia Shichang , Jiang Jianmin , Tang Yi-Wei 
Published: January 2017

ABSTRACT

Few studies on risk factors for and transmission of
Clostridium difficile
infection (CDI) in China have been reported. A cross-sectional study was conducted for 3 years in eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for
C. difficile. C. difficile
isolates from these patients then were analyzed for toxin genes, genotypes, and antimicrobial resistance. A severity score for the CDI in each patient was determined by a blinded review of the medical record, and these scores ranged from 1 to 6. A total of 397 out of 3,953 patients (10.0%) with diarrhea were found to have CDI. Severity of CDI was mild to moderate, and the average (± standard deviation) severity score was 2.61 ± 1.01.
C. difficile
was isolated from stool specimens in 432 (10.9%) of all the patients who had diarrhea.
C. difficile
genotypes were determined by multilocus sequence analysis and PCR ribotyping; sequence type 37 (ST37)/ribotype 017 (RT017) (
n
= 68, 16.5%) was the dominant genotype. Eleven patients (16.2%) with this genotype had a CDI severity score of 5. Overall, three RTs and four STs were predominant; these genotypes were associated with significantly different antimicrobial resistance patterns in comparison to all genotypes (χ
2
= 79.56 to 97.76;
P
< 0.001). Independent risk factors associated with CDI included age greater than 55 years (odds ratio [95% confidence interval], 26.80 [18.76 to 38.29]), previous hospitalization (12.42 [8.85 to 17.43]), previous antimicrobial treatment within 8 weeks (150.56 [73.11 to 310.06]), hospital stay more than 3 days before sampling (2.34 [1.71 to 3.22]), undergoing chemotherapy (3.31 [2.22 to 4.92]), and undergoing abdominal surgery (4.82 [3.54 to 6.55]). CDI is clearly a problem in eastern China and has a prevalence of 10.0% in hospitalized patients. Among risk factors for CDI, the advanced age threshold was younger for Chinese patients than that reported for patients in developed countries.
Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov
Authors: Siqueira J. P. Z. , Sutton D. A. , Gené J. , García D. , Wiederhold N. , Peterson S. W. , Guarro J. 
Published: January 2017

ABSTRACT

A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from
Aspergillus
section
Circumdati
from the United States and to determine their
in vitro
antifungal susceptibility against eight antifungal drugs. The genetic markers used were the internal transcribed spacer (ITS) region, and fragments of the beta-tubulin (
BenA
), calmodulin (
CaM
), and RNA polymerase II second largest subunit (
RPB2
) genes. The drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was
A. westerdijkiae
(29.4%), followed by a novel species, which was described here as
A. pseudosclerotiorum
(23.5%). Other species identified were
A. sclerotiorum
(17.6%),
A. ochraceus
(8.8%),
A. subramanianii
(8.8%), and
A. insulicola
and
A. ochraceopetaliformis
, with two isolates (5.9%) of each. The drugs that showed the most potent activity were caspofungin, micafungin, and terbinafine, while amphotericin B showed the least activity.
Singleton Sequence Type 382, an Emerging Clonal Group of Listeria monocytogenes Associated with Three Multistate Outbreaks Linked to Contaminated Stone Fruit, Caramel Apples, and Leafy Green Salad
Authors: Chen Yi , Luo Yan , Pettengill James , Timme Ruth , Melka David , Doyle Matthew , Jackson Alikeh , Parish Mickey , Hammack Thomas S. , Allard Marc W. , Brown Eric W. , Strain Errol A. 
Published: January 2017

ABSTRACT

Three multistate outbreaks between 2014 and 2016, involving case patients in and outside the United States, were linked to stone fruit, caramel apples, and packaged leafy green salad contaminated with
Listeria monocytogenes
singleton sequence type 382 (ST382), a serotype IVb-v1 clone with limited genomic divergence. Isolates from these outbreaks and other ST382 isolates not associated with these outbreaks were analyzed by whole-genome sequencing (WGS) analysis. The primary differences among ST382 strains were single nucleotide polymorphisms (SNPs). WGS analysis differentiated ST382 from a clonal complex 1 outbreak strain co-contaminating the caramel apples. WGS clustered food, environmental, and clinical isolates within each outbreak, and also differentiated among the three outbreak strains and epidemiologically unrelated ST382 isolates, which were indistinguishable by pulsed-field gel electrophoresis. ST382 appeared to be an emerging clone that began to diverge from its ancestor approximately 32 years before 2016. We estimated that there was 1.29 nucleotide substitution per genome (2.94 Mbp) per year for this clone.
Nosocomial Outbreak of Drug-Resistant Streptococcus pneumoniae Serotype 9V in an Adult Respiratory Medicine Ward
Authors: Jauneikaite Elita , Khan-Orakzai Zareena , Kapatai Georgia , Bloch Susannah , Singleton Julie , Atkin Sara , Shah Victoria , Hatcher James , Samarasinghe Dunisha , Sheppard Carmen , Fry Norman K. , Satta Giovanni , Sriskandan Shiranee 
Published: January 2017

ABSTRACT

Streptococcus pneumoniae
infections arising in hospitalized patients are often assumed to be sporadic and linked to community acquisition. Here, whole-genome sequencing was used to demonstrate nosocomial acquisition of antimicrobial-resistant sequence type 156 (ST156) serotype 9V
S. pneumoniae
in 3 respiratory patients that resulted in two bacteremias and one lower respiratory tract infection. Two of the cases arose in patients who had recently been discharged from the hospital and were readmitted from the community. Nosocomial spread was suspected solely because of the highly unusual resistance pattern and case presentations within 24 h of one another. The outbreak highlights the potential for rapid transmission and the short incubation period in the respiratory ward setting.
The Viral Bcl-2 Homologs of Kaposi's Sarcoma-Associated Herpesvirus and Rhesus Rhadinovirus Share an Essential Role for Viral Replication
Authors: Gallo Antonio , Lampe Melanie , Günther Thomas , Brune Wolfram 
Published: January 2017

ABSTRACT

KS-Bcl-2 is a Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral Bcl-2 (vBcl-2) homolog which has apoptosis- and autophagy-inhibiting activity when expressed in transfected cells. However, little is known about its function during viral infection. As KS-Bcl-2 is expressed during the lytic replication cycle, we used constitutively lytic and inducibly lytic KSHV mutants to investigate the role of KS-Bcl-2 during the lytic cycle. We show that KSHV cannot complete the lytic replication cycle and produce infectious progeny in the absence of KS-Bcl-2, indicating that the protein is essential for KSHV replication. Replacement of the KS-Bcl-2 coding sequence, ORF16, by sequences encoding a potent cellular apoptosis and autophagy inhibitor, Bcl-XL, or the cytomegalovirus mitochondrial inhibitor of apoptosis, vMIA, did not rescue KSHV replication, suggesting that KS-Bcl-2 has a function that goes beyond apoptosis and autophagy inhibition. Strikingly, the vBcl-2 proteins of the related γ
2
-herpesviruses murine herpesvirus 68 and herpesvirus saimiri did not rescue the replication of a KS-Bcl-2 deletion mutant, but rhesus rhadinovirus (RRV) vBcl-2 did. Deletion of ORF16 from the RRV genome abrogated viral replication, but its replacement by KSHV ORF16 rescued RRV replication, indicating that the essential vBcl-2 function is conserved between these two primate rhadinoviruses. We further show that the KSHV and RRV Bcl-2 homologs localize to the mitochondria and nuclei of infected cells. Deletion of 17 amino acids from the N terminus of KS-Bcl-2 abrogates nuclear localization and KSHV replication, suggesting that KS-Bcl-2 might execute its essential function in the nuclei of infected cells.

IMPORTANCE
Several viruses express proteins homologous to cellular Bcl-2. Viral Bcl-2 proteins have functions similar to those of cellular Bcl-2: they can inhibit apoptosis, a form of programmed cell death, and autophagy, a self-degradative process for the disposal of dysfunctional or unwanted components. This study shows that the vBcl-2 proteins of KSHV and RRV differ from other vBcl-2 proteins in that they are essential for viral replication. The essential function is separate from the apoptosis- and autophagy-inhibiting activity but correlates with an unusual localization within the cell nucleus, suggesting that these proteins exert a novel function in the nucleus.
Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Upregulates Glucose Transporter 1 Transcription via the mTORC1/NF-κB Signaling Pathways
Authors: Zhang Jun , Jia Lin , Lin Weitao , Yip Yim Ling , Lo Kwok Wai , Lau Victoria Ming Yi , Zhu Dandan , Tsang Chi Man , Zhou Yuan , Deng Wen , Lung Hong Lok , Lung Maria Li , Cheung Lai Man , Tsao Sai Wah 
Published: January 2017

ABSTRACT

Accumulating evidence indicates that oncogenic viral protein plays a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a transmembrane protein with potent cell signaling properties and has tumorigenic transformation property. Activation of NF-κB is a major signaling pathway mediating many downstream transformation properties of LMP1. Here we report that activation of mTORC1 by LMP1 is a key modulator for activation of NF-κB signaling to mediate aerobic glycolysis. NF-κB activation is involved in the LMP1-induced upregulation of glucose transporter 1 (Glut-1) transcription and growth of nasopharyngeal carcinoma (NPC) cells. Blocking the activity of mTORC1 signaling effectively suppressed LMP1-induced NF-κB activation and Glut-1 transcription. Interfering NF-κB signaling had no effect on mTORC1 activity but effectively altered Glut-1 transcription. Luciferase promoter assay of Glut-1 also confirmed that the Glut-1 gene is a direct target gene of NF-κB signaling. Furthermore, we demonstrated that C-terminal activating region 2 (CTAR2) of LMP1 is the key domain involved in mTORC1 activation, mainly through IKKβ-mediated phosphorylation of TSC2 at Ser
939
. Depletion of Glut-1 effectively led to suppression of aerobic glycolysis, inhibition of cell proliferation, colony formation, and attenuation of tumorigenic growth property of LMP1-expressing nasopharyngeal epithelial (NPE) cells. These findings suggest that targeting the signaling axis of mTORC1/NF-κB/Glut-1 represents a novel therapeutic target against NPC.

IMPORTANCE
Aerobic glycolysis is one of the hallmarks of cancer, including NPC. Recent studies suggest a role for LMP1 in mediating aerobic glycolysis. LMP1 expression is common in NPC. The delineation of essential signaling pathways induced by LMP1 in aerobic glycolysis contributes to the understanding of NPC pathogenesis. This study provides evidence that LMP1 upregulates Glut-1 transcription to control aerobic glycolysis and tumorigenic growth of NPC cells through mTORC1/NF-κB signaling. Our results reveal novel therapeutic targets against the mTORC1/NF-κB/Glut-1 signaling axis in the treatment of EBV-infected NPC.
Urinary C peptide creatinine ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion
Authors: Markoska Ankica , Valaiyapathi Rajalakshmi , Thorn Chloe , Dornhorst Anne 
Published: January 2017

HypothesisIn pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes.Research design and methodsUCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes.ResultsUCPCROGTTand serum C peptideOGTTof glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p<0.0001). All 7 pregnant women with type 1 diabetes had detectable first sample UCPCR (median (range) 49 (6–1038) pmol/mmol) that rose in 6 women by 477 (29–1491) pmol/mmol.ConclusionsDetectable UCPCR in pregnant women with normal glucose tolerance and type 1 diabetes is likely to reflect endogenous insulin secretion and hence β-cell activity.
Traumatic brain injuries in older adults—6 years of data for one UK trauma centre: retrospective analysis of prospectively collected data
Authors: Hawley Carol , Sakr Magdy , Scapinello Sarah , Salvo Jesse , Wrenn Paul 
Published: January 2017

ObjectivesOur aim was to determine the incidence of traumatic brain injury (TBI) in older adults and investigate the relationship between injury characteristics and outcomes.MethodsRetrospective analysis of prospectively collected data submitted to Trauma Audit and Research Network (TARN) database for a major trauma centre in the West Midlands, UK, from 2008 to 2014. The Mayo Scale was used to categorise TBI. All patients were aged ≥65 years and were admitted with head or brain injuries meeting TARN inclusion criteria: injury resulting in immediate admission to hospital for 3 days, admitted to a high dependency area or death following trauma. We determined age, gender, mechanism of injury, Injury Severity Score, presenting Glasgow Coma Scale (GCS) and Mayo Score, and the association of outcome (Glasgow Outcome Scale (GOS)) with age and clinical presentation.Results4413 patients were admitted with trauma meeting TARN criteria: 1389 were ≥65 years and 45% (624) had TBI. For patients ≥65 years with TBI, mean age was 79 (range 65–99); 56% were men. Falls accounted for 85% of all TBIs. Most TBIs were moderate/severe (80%) by the Mayo criteria. Of the 279 patients with subdural haematoma, 28% had neurosurgery. Most patients survived TBI (78%); 57% had a good outcome on GOS at discharge (not requiring care package). Mortality was associated with increased age (17% in ages 65–74 years, 19% in 75–84 years, 30% in ≥85 years, p=0.03). Outcome was significantly associated with injury severity (p=0.0001).ConclusionsPatients with TBI represented 45% of all trauma cases meeting TARN inclusion criteria. Falls at home accounted for most TBIs. Most had moderate/severe TBI, yet over half made a good recovery on GOS. Our data indicate that injury prevention initiatives should focus on home safety. Further research is needed to examine rehabilitation and follow-up after hospital discharge.
Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab
Authors: Laharie D , Bourreille A , Branche J , Allez M , Bouhnik Y , Filippi J , Zerbib F , Savoye G , Vuitton L , Moreau J , Amiot A , Cosnes J , Ricart E , Dewit O , Lopez-Sanroman A , Fumery M , Carbonnel F , Bommelaer G , Coffin B , Roblin X , van Assche G , Esteve M , Farkkila M , Gisbert JP , Marteau P , Nahon S , de Vos M , Lambert J , Mary JY , Louis E 
Published: January 2017

ObjectiveCiclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DesignBetween 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.ResultsAfter a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.ConclusionsIn this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.Trial registration numberEudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
WNT-5A regulates TGF-β-related activities in liver fibrosis
Authors: Beljaars Leonie , Daliri Sara , Dijkhuizen Christa , Poelstra Klaas , Gosens Reinoud 
Published: January 2017

WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.