bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actin Pedestal Formation by Enterohemorrhagic Escherichia coli Enhances Bacterial Host Cell Attachment and Concomitant Type III Translocation
Authors: Battle Scott E. , Brady Michael J. , Vanaja Sivapriya Kailasan , Leong John M. , Hecht Gail A. 
Published: June 2014

ABSTRACT

Attachment of enterohemorrhagic
Escherichia coli
(EHEC) to intestinal epithelial cells is critical for colonization and is associated with localized actin assembly beneath bound bacteria. The formation of these actin “pedestals” is dependent on the translocation of effectors into mammalian cells via a type III secretion system (T3SS). Tir, an effector required for pedestal formation, localizes in the host cell plasma membrane and promotes attachment of bacteria to mammalian cells by binding to the EHEC outer surface protein Intimin. Actin pedestal formation has been shown to foster intestinal colonization by EHEC in some animal models, but the mechanisms responsible for this remain undefined. Investigation of the role of Tir-mediated actin assembly promoting host cell binding is complicated by other, potentially redundant EHEC-encoded binding pathways, so we utilized cell binding assays that specifically detect binding mediated by Tir-Intimin interaction. We also assessed the role of Tir-mediated actin assembly in two-step assays that temporally segregated initial translocation of Tir from subsequent Tir-Intimin interaction, thereby permitting the distinction of effects on translocation from effects on cell attachment. In these experimental systems, we compromised Tir-mediated actin assembly by chemically inhibiting actin assembly or by infecting mammalian cells with EHEC mutants that translocate Tir but are specifically defective in Tir-mediated pedestal formation. We found that an inability of Tir to promote actin assembly resulted in a significant and striking decrease in bacterial binding mediated by Tir and Intimin. Bacterial mutants defective for pedestal formation translocated type III effectors to mammalian cells with reduced efficiency, but the decrease in translocation could be entirely accounted for by the decrease in host cell attachment.
Characterization of Two UDP-Gal:GalNAc-Diphosphate-Lipid β1,3-Galactosyltransferases WbwC from Escherichia coli Serotypes O104 and O5
Authors: Wang Shuo , Czuchry Diana , Liu Bin , Vinnikova Anna N. , Gao Yin , Vlahakis Jason Z. , Szarek Walter A. , Wang Lei , Feng Lu , Brockhausen Inka 
Published: June 2014

ABSTRACT

Escherichia coli
displays O antigens on the outer membrane that play an important role in bacterial interactions with the environment. The O antigens of enterohemorrhagic
E. coli
O104 and O5 contain a Galβ1-3GalNAc disaccharide at the reducing end of the repeating unit. Several other O antigens contain this disaccharide, which is identical to the mammalian O-glycan core 1 or the cancer-associated Thomsen-Friedenreich (TF) antigen. We identified the
wbwC
genes responsible for the synthesis of the disaccharide in
E. coli
serotypes O104 and O5. To functionally characterize WbwC, an acceptor substrate analog, GalNAcα-diphosphate-phenylundecyl, was synthesized. WbwC reaction products were isolated by high-pressure liquid chromatography and analyzed by mass spectrometry, nuclear magnetic resonance, galactosidase and O-glycanase digestion, and anti-TF antibody. The results clearly showed that the Galβ1-3GalNAcα linkage was synthesized, confirming WbwC
ECO104
and WbwC
ECO5
as UDP-Gal:GalNAcα-diphosphate-lipid β1,3-Gal-transferases. Sequence analysis revealed a conserved DxDD motif, and mutagenesis showed the importance of these Asp residues in catalysis. The purified enzymes require divalent cations (Mn
2+
) for activity and are specific for UDP-Gal and GalNAc-diphosphate lipid substrates. WbwC was inhibited by bis-imidazolium salts having aliphatic chains of 18 to 22 carbons. This work will help to elucidate mechanisms of polysaccharide synthesis in pathogenic bacteria and provide technology for vaccine synthesis.
Alkali Metals in Addition to Acidic pH Activate the EvgS Histidine Kinase Sensor in Escherichia coli
Authors: Eguchi Yoko , Utsumi Ryutaro 
Published: June 2014

ABSTRACT

Two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to
Escherichia coli
cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes. We searched for signals activating EvgS and found that a high concentration of alkali metals (Na
+
, K
+
) in addition to low pH was essential for the activation. EvgS is a histidine kinase, with a large periplasmic sensor region consisting of two tandem PBPb (bacterial periplasmic solute-binding protein) domains at its N terminus. The periplasmic sensor region of EvgS was necessary for EvgS activation, and Leu152, located within the first PBPb domain, was involved in the activation. Furthermore, chimeras of EvgS and PhoQ histidine kinases suggested that alkali metals were perceived at the periplasmic sensor region, whereas the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain, was required for low-pH perception.
Sensitive and Selective Culture Medium for Detection of Environmental Clostridium difficile Isolates without Requirement for Anaerobic Culture Conditions
Authors: Cadnum Jennifer L. , Hurless Kelly N. , Deshpande Abhishek , Nerandzic Michelle M. , Kundrapu Sirisha , Donskey Curtis J. 
Published: June 2014

ABSTRACT

Effective and easy-to-use methods for detecting
Clostridium difficile
spore contamination would be useful for identifying environmental reservoirs and monitoring the effectiveness of room disinfection. Culture-based detection methods are sensitive for detecting
C. difficile
, but their utility is limited due to the requirement of anaerobic culture conditions and microbiological expertise. We developed a low-cost selective broth medium containing thioglycolic acid and
l
-cystine, termed
C. difficile
brucella broth with thioglycolic acid and
l
-cystine (CDBB-TC), for the detection of
C. difficile
from environmental specimens under aerobic culture conditions. The sensitivity and specificity of CDBB-TC (under aerobic culture conditions) were compared to those of CDBB (under anaerobic culture conditions) for the recovery of
C. difficile
from swabs collected from hospital room surfaces. CDBB-TC was significantly more sensitive than CDBB for recovering environmental
C. difficile
(36/41 [88%] versus 21/41 [51%], respectively;
P
= 0.006).
C. difficile
latex agglutination, an enzyme immunoassay for toxins A and B or glutamate dehydrogenase, and a PCR for toxin B genes were all effective as confirmatory tests. For 477 total environmental cultures, the specificity of CDBB-TC versus that of CDBB based upon false-positive yellow-color development of the medium without recovery of
C. difficile
was 100% (0 false-positive results) versus 96% (18 false-positive results), respectively. False-positive cultures for CDBB were attributable to the growth of anaerobic non-
C. difficile
organisms that did not grow in CDBB-TC. Our results suggest that CDBB-TC provides a sensitive and selective medium for the recovery of
C. difficile
organisms from environmental samples, without the need for anaerobic culture conditions.
Circadian clock desynchronisation and metabolic syndrome
Authors: Sheikh-Ali Mae , Maharaj Jaisri 
Published: June 2014

AbstractThere is emerging evidence in the literature to suggest that disruption of the normal circadian rhythm (sleep–wake cycle signalling) is a potential risk factor to explain the increased incidence of metabolic syndrome. Over the last century, obesity, diabetes and other components of metabolic syndrome have been on the rise. On the other hand, the amount of sleep has decreased from an average of 6–8 h per night. Furthermore, the quality of sleep has declined with more individuals voluntarily decreasing their amount of sleep to work or enjoy leisure activities. Over the last decade, researchers have examined the relationship between disruption in human circadian system and the emergence of symptoms related to metabolic syndrome. Indeed, epidemiological studies suggest a relation between sleep duration and diabetes and obesity. Moreover, experimental animal and human studies suggest such a relation. These studies propose optimum sleep duration of 7–8 h per night to avoid circadian rhythm disruption and suggest that sleep disturbance, whether iatrogenic or disease-related, should be considered as a risk factor for metabolic syndrome, and be addressed. This field is in its infancy and further understanding of specific pathophysiological pathways of circadian desynchronisation will help in developing novel preventive and therapeutic strategies.
Anaesthetic management and complications of pacemaker implantation in dogs
Authors: Sanchis‐Mora S. , Viscasillas J. , Mathis A. , Palacios C. , Brodbelt D. C. , Alibhai H. I. 
Published: June 2014

The aim of this study was to report the anaesthetic management and peri‐anaesthetic complications of 57 dogs undergoing pacemaker implantation at a referral institution over 10 years (2002–2012). The median duration of the procedure was 135 minutes (range 25–260 minutes). Patients were classified as American Society of Anaesthesiologist (ASA) III (42 cases) and ASA IV (15 cases). Forty‐three patients had third‐degree atrioventricular block, and 14 patients had sick sinus syndrome. The anaesthetic protocol most frequently chosen was pethidine (41 cases), etomidate‐midazolam (43 cases) and isoflurane in oxygen for maintenance (57 cases). Transthoracic external pacing was used (43 cases) until the internal pacing lead was implanted. Atracurium was administered (48 cases) and intermittent positive pressure ventilation was applied in 52 cases. Complications observed included hypothermia (19 cases) and hypotension (5 cases). Three patients died (5.8%, 95% CI 1.1% to 14.6%) within the first 48 hours after termination of anaesthesia. The outcome for this procedure in sick animals appeared generally good though a number of complications were documented.
Socio-hydrology modelling for an uncertain future, with examples from the USA and Canada
Authors: Gober Patricia , White Dave D. , Quay Ray , Sampson David A. , Kirkwood Craig W. 
Published: June 2014

Abstract
Socio-hydrology brings an interest in human values, markets, social organizations and public policy to the traditional emphasis of water science on climate, hydrology, toxicology and ecology. It also conveys a decision focus in the form of decision support tools, stakeholder engagement and new knowledge about the science–policy interface. This paper demonstrates how policy decisions and human behaviour can be better integrated into climate and hydrological models to improve their usefulness for decision support. Examples from SW USA and western Canada highlight uncertainties, vulnerabilities and critical tradeoffs facing water decision makers in the face of rapidly changing environmental and societal conditions. Irreducible uncertainties in downscaled climate and hydrological models limit the usefulness of climate-driven, predict-and-plan methods of water resource planning and management. Thus, it is argued that such methods should be replaced by approaches that use exploratory modelling, scenario planning and risk assessment in which the emphasis is on managing uncertainty rather than on reducing it. Model fusion supports all of these processes in integrating human and biophysical aspects of water systems, allowing policy impacts to be quantified and clarified, and fostering public engagement with water resource modelling.
A Novel KLF4/LDHA Signaling Pathway Regulates Aerobic Glycolysis in and Progression of Pancreatic Cancer
Authors: Shi Min , Cui Jiujie , Du Jiawei , Wei Daoyan , Jia Zhiliang , Zhang Jun , Zhu Zhenggang , Gao Yong , Xie Keping 
Published: June 2014

Abstract
Purpose: Krüppel-like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its effect on aerobic glycolysis in pancreatic tumors. Therefore, we investigated the clinical significance, biologic effects, and mechanisms of dysregulated KLF4 signaling in aerobic glycolysis in pancreatic cancer cells.
Experimental Design: Expression of KLF4 and lactate dehydrogenase A (LDHA) in 70 primary pancreatic tumors and 10 normal pancreatic tissue specimens was measured. Also, the underlying mechanisms of altered KLF4 expression and its impact on aerobic glycolysis in pancreatic cancer cells were investigated.
Results: We found a negative correlation between KLF4 and LDHA expression in pancreatic cancer cells and tissues and that their expression was associated with clinicopathologic features of pancreatic cancer. KLF4 underexpression and LDHA overexpression were correlated with disease stage and tumor differentiation. Experimentally, KLF4 overexpression significantly attenuated the aerobic glycolysis in and growth of pancreatic cancer cells both in vitro and in orthotopic mouse models, whereas knockdown of KLF4 expression had the opposite effect. Enforced KLF4 expression decreased LDHA expression, whereas small interfering RNA–mediated knockdown of KLF4 expression had the opposite effect. Mechanistically, KLF4 bound directly to the promoter regions of the LDHA gene and negatively regulated its transcription activity.
Conclusions: Dysregulated signaling in this novel KLF4/LDHA pathway significantly impacts aerobic glycolysis in and development and progression of pancreatic cancer. Clin Cancer Res; 20(16); 4370–80. ©2014 AACR.
Transplanted Perivascular Adipose Tissue Accelerates Injury-Induced Neointimal Hyperplasia
Authors: Manka David , Chatterjee Tapan K. , Stoll Lynn L. , Basford Joshua E. , Konaniah Eddy S. , Srinivasan Ramprasad , Bogdanov Vladimir Y. , Tang Yaoliang , Blomkalns Andra L. , Hui David Y. , Weintraub Neal L. 
Published: June 2014

Objective—
Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms.

Approach and Results—
We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet–fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells.

Conclusions—
These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1–dependent mechanisms.
Longitudinal Assessment of Growth in Hypoplastic Left Heart Syndrome: Results From the Single Ventricle Reconstruction Trial
Authors: Burch Phillip T. , Gerstenberger Eric , Ravishankar Chitra , Hehir David A. , Davies Ryan R. , Colan Steven D. , Sleeper Lynn A. , Newburger Jane W. , Clabby Martha L. , Williams Ismee A. , Li Jennifer S. , Uzark Karen , Cooper David S. , Lambert Linda M. , Pemberton Victoria L. , Pike Nancy A. , Anderson Jeffrey B. , Dunbar‐Masterson Carolyn , Khaikin Svetlana , Zyblewski Sinai C. , Minich L. LuAnn ,   the Pediatric Heart Network Investigators
Published: June 2014

Background
We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure.

Methods and Results

We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length‐for‐age
z
score (
LAZ
) and weight‐for‐age
z
score (
WAZ
) at birth and age 3 years and change in
WAZ
over 4 clinically relevant time periods. We identified correlates of change in
WAZ
and
LAZ
using multivariable linear regression with bootstrapping. Mean
WAZ
and
LAZ
were below average relative to the general population at birth (
P
<0.001,
P
=0.05, respectively) and age 3 years (
P
<0.001 each). The largest decrease in
WAZ
occurred between birth and Norwood discharge; the greatest gain occurred between stage
II
and 14 months. At age 3 years,
WAZ
and
LAZ
were <−2 in 6% and 18%, respectively. Factors associated with change in
WAZ
differed among time periods. Shunt type was associated with change in
WAZ
only in the Norwood discharge to stage II period; subjects with a Blalock‐Taussig shunt had a greater decline in
WAZ
than those with a right ventricle‐pulmonary artery shunt (
P
=0.002).

Conclusions

WAZ
changed over time and the predictors of change in
WAZ
varied among time periods. By age 3 years, subjects remained small and three times as many children were short as were underweight (>2
SD
below normal). Failure to find consistent risk factors supports the strategy of tailoring nutritional therapies to patient‐ and stage‐specific targets.

Clinical Trial Registration

URL:
http://clinicaltrials.gov/
. Unique identifier: NCT00115934.
Revision of the genus Tanycypris (Ostracoda, Cypricercinae) with the description of Tanycypris alfonsi n. sp., and an identification key to the genus
Authors: NAGLER CHRISTINA , GEIST JUERGEN , MATZKE-KARASZ RENATE 
Published: June 2014

Specimens of a new species of the non-marine ostracod genus, Tanycypris Triebel, 1959 were found in samples from water plant containers, displayed in a greenhouse of the botanical garden in Munich, Germany. Beside the ubiquitous species Cypridopsis vidua O.F. Müller, 1776, the samples contained four alien species of the subfamily Cypricercinae, namely Chlamydotheca arcuata Sars, 1901, Strandesia bicuspis Claus, 1892, Tanycypris centa Chang et al., 2012, and Tanycypris alfonsi n. sp.. The genus Tanycypris has mainly been reported (native) from Asia, and (invasive) from Italian rice fields. The Cypricercinae unite all species possessing a Triebel loop, a character of the caudal rami attachment. The subfamily is split into the tribes Cypricercini McKenzie, 1971, Bradleystrandesiini Savatenalinton & Martens, 2009 and Nealecypridini Savatenalinton & Martens, 2009, the latter of which comprises the genera Tanycypris Triebel, 1959, Astenocypris G.W. Müller, 1912, Diaphanocypris Würdig & Pinto, 1990 and Nealecypris Savatenalinton & Martens, 2009. During the process of describing the new species, a number of taxonomic uncertainties were detected within the genus Tanycypris, leading to a revision of the nine species currently ascribed to it: Tanycypris camaguinensis (Tressler, 1937), Tanycypris centa Chang et al., 2012 Tanycypris clavigera (G.W. Müller, 1898) (now: Nealecypris clavigera nov. comb.), Tanycypris madagascarensis (G.W. Müller, 1898), Tanycypris marina (Hartmann, 1965) (now: Dolerocypris marina nov. comb.), Tanycypris pedroensis (Tressler, 1950) (now: Diaphanocypris pedroensis nov. comb.), Tanycypris pellucida (Klie, 1932), Tanycypris siamensis Savatenalinton & Martens, 2009a, and Tanycypris telavivensis (Krampner, 1928) (now: Herpetocypris telavivensis). An identification key has been developed to the species of the genus Tanycypris.
Regulation and time: temporal patterns in regulatory development
Authors: Newman Joshua , Howlett Michael 
Published: June 2014

Given the complex decision-making that goes into policy choices for regulatory regimes, it would seem intuitive that such regimes might develop under distinct national styles. By revisiting several historical models of regulatory development, including Bernstein's classic life-cycle model, and then by analyzing six case studies from the US and UK, for example, we explore the possibility that regulatory regimes vary more prominently along the temporal dimension rather than along spatial ones. We conclude that regulatory regimes have similar developmental patterns, although the time spent at each stage in the process can vary significantly according to unique domestic factors. Points for practitioners Existing theories of regulation would suggest that regulatory activity should either follow identical development trajectories in different countries or it should be entirely idiosyncratic in every jurisdiction in which it is used. Clearly neither is true, as some regulatory regimes display similar qualities and development patterns, while others appear to be unique. A comparison of regulatory activities in the US and UK reveals that regulatory regimes in these countries develop through similar stages along similar pathways, but that the rate of development and the transition through the stages can occur at different speeds. This development is mainly stimulated by periodic crises that force changes in regulation.
Test Characteristics of Faecal Immunochemical Tests (FIT) Compared with Optical Colonoscopy
Authors: Levy Barcey T , Bay Camden , Xu Yinghui , Daly Jeanette M , Bergus George , Dunkelberg Jeffrey , Moss Carol 
Published: June 2014

Background Faecal occult blood tests are often the initial test in population-based screening. We aimed to: 1) compare the results of single sample faecal immunochemical tests (FITs) with colonoscopy, and 2) calculate the sensitivity for proximal vs. distal adenomatous polyps or cancer. Methods Individuals scheduled for a colonoscopy were invited to complete a FIT prior to their colonoscopy preparation. FIT results were classified as positive, negative, or invalid. Colonoscopy reports were reviewed and abstracted. Because of product issues, four different FIT manufacturers were used. The test characteristics for each FIT manufacturer were calculated for advanced adenomatous polyps or cancer according to broad reason for colonoscopy (screening or surveillance/diagnostic). Results Of those invited, 1,026 individuals (43.9%) completed their colonoscopy and had a valid FIT result. The overall sensitivity of the FITs (95% confidence intervals) was 0.18 (0.10 to 0.28) and specificity was 0.90 (0.87 to 0.91) for advanced adenomas or cancer. The sensitivity for distal lesions was 0.23 (0.11 to 0.38) and for proximal lesions was 0.09 (0.02 to 0.25). The odds ratio of an individual with a distal advanced adenoma or cancer testing positive was 2.68 (1.20 to 5.99). The two individuals with colorectal cancer tested negative, as did one individual with high-grade dysplasia. Conclusions The sensitivity of a single-sample FIT for advanced adenomas or cancer was low. Individuals with distal adenomas had a higher odds of testing positive than those with proximal lesions or no lesions.