bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotaxis of Escherichia coli to Norepinephrine (NE) Requires Conversion of NE to 3,4-Dihydroxymandelic Acid
Authors: Pasupuleti Sasikiran , Sule Nitesh , Cohn William B. , MacKenzie Duncan S. , Jayaraman Arul , Manson Michael D. 
Published: September 2014

ABSTRACT

Norepinephrine (NE), the primary neurotransmitter of the sympathetic nervous system, has been reported to be a chemoattractant for enterohemorrhagic
Escherichia coli
(EHEC). Here we show that nonpathogenic
E. coli
K-12 grown in the presence of 2 μM NE is also attracted to NE. Growth with NE induces transcription of genes encoding the tyramine oxidase, TynA, and the aromatic aldehyde dehydrogenase, FeaB, whose respective activities can, in principle, convert NE to 3,4-dihydroxymandelic acid (DHMA). Our results indicate that the apparent attractant response to NE is in fact chemotaxis to DHMA, which was found to be a strong attractant for
E. coli
. Only strains of
E. coli
K-12 that produce TynA and FeaB exhibited an attractant response to NE. We demonstrate that DHMA is sensed by the serine chemoreceptor Tsr and that the chemotaxis response requires an intact serine-binding site. The threshold concentration for detection is ≤5 nM DHMA, and the response is inhibited at DHMA concentrations above 50 μM. Cells producing a heterodimeric Tsr receptor containing only one functional serine-binding site still respond like the wild type to low concentrations of DHMA, but their response persists at higher concentrations. We propose that chemotaxis to DHMA generated from NE by bacteria that have already colonized the intestinal epithelium may recruit
E. coli
and other enteric bacteria that possess a Tsr-like receptor to preferred sites of infection.
Enzymatic Characterization and
In Vivo
Function of Five Terminal Oxidases in Pseudomonas aeruginosa
Authors: Arai Hiroyuki , Kawakami Takuro , Osamura Tatsuya , Hirai Takehiro , Sakai Yoshiaki , Ishii Masaharu 
Published: September 2014

ABSTRACT

The ubiquitous opportunistic pathogen
Pseudomonas aeruginosa
has five aerobic terminal oxidases:
bo
3
-type quinol oxidase (Cyo), cyanide-insensitive oxidase (CIO),
aa
3
-type cytochrome
c
oxidase (
aa
3
), and two
cbb
3
-type cytochrome
c
oxidases (
cbb
3
-1 and
cbb
3
-2). These terminal oxidases are differentially regulated under various growth conditions and are thought to contribute to the survival of this microorganism in a wide variety of environmental niches. Here, we constructed multiple mutant strains of
P. aeruginosa
that express only one aerobic terminal oxidase to investigate the enzymatic characteristics and
in vivo
function of each enzyme. The

K
m

values of Cyo, CIO, and
aa
3
for oxygen were similar and were 1 order of magnitude higher than those of
cbb
3
-1 and
cbb
3
-2, indicating that Cyo, CIO, and
aa
3
are low-affinity enzymes and that
cbb
3
-1 and
cbb
3
-2 are high-affinity enzymes. Although
cbb
3
-1 and
cbb
3
-2 exhibited different expression patterns in response to oxygen concentration, they had similar

K
m

values for oxygen. Both
cbb
3
-1 and
cbb
3
-2 utilized cytochrome
c
4
as the main electron donor under normal growth conditions. The electron transport chains terminated by
cbb
3
-1 and
cbb
3
-2 generate a proton gradient across the cell membrane with similar efficiencies. The electron transport chain of
aa
3
had the highest proton translocation efficiency, whereas that of CIO had the lowest efficiency. The enzymatic properties of the terminal oxidases reported here are partially in agreement with their regulatory patterns and may explain the environmental adaptability and versatility of
P. aeruginosa
.
The Extracellular Matrix of Staphylococcus aureus Biofilms Comprises Cytoplasmic Proteins That Associate with the Cell Surface in Response to Decreasing pH
Authors: Foulston Lucy , Elsholz Alexander K. W. , DeFrancesco Alicia S. , Losick Richard 
Published: September 2014

ABSTRACTBiofilm formation byStaphylococcus aureusinvolves the formation of an extracellular matrix, but the composition of this matrix has been uncertain. Here we report that the matrix is largely composed of cytoplasmic proteins that reversibly associate with the cell surface in a manner that depends on pH. We propose a model for biofilm formation in which cytoplasmic proteins are released from cells in stationary phase. These proteins associate with the cell surface in response to decreasing pH during biofilm formation. Rather than utilizing a dedicated matrix protein,S. aureusappears to recycle cytoplasmic proteins that moonlight as components of the extracellular matrix.IMPORTANCEStaphylococcus aureusis a leading cause of multiantibiotic-resistant nosocomial infections and is often found growing as a biofilm in catheters and chronic wounds. Biofilm formation is an important pathogenicity strategy that enhances resistance to antimicrobials, thereby limiting treatment options and ultimately contributing to increased morbidity and mortality. Cells in a biofilm are held together by an extracellular matrix that consists in whole or in part of protein, but the nature of the proteins in theS. aureusmatrix is not well understood. Here we postulate thatS. aureusrecycles proteins from the cytoplasm to form the extracellular matrix. This strategy, of cytoplasmic proteins moonlighting as matrix proteins, could allow enhanced flexibility and adaptability forS. aureusin forming biofilms under infection conditions and could promote the formation of mixed-species biofilms in chronic wounds.
Genes Contributing to Staphylococcus aureus Fitness in Abscess- and Infection-Related Ecologies
Authors: Valentino Michael D. , Foulston Lucy , Sadaka Ama , Kos Veronica N. , Villet Regis A. , Santa Maria John , Lazinski David W. , Camilli Andrew , Walker Suzanne , Hooper David C. , Gilmore Michael S. 
Published: September 2014

ABSTRACT

Staphylococcus aureus
is a leading cause of both community- and hospital-acquired infections that are increasingly antibiotic resistant. The emergence of
S. aureus
resistance to even last-line antibiotics heightens the need for the development of new drugs with novel targets. We generated a highly saturated transposon insertion mutant library in the genome of
S. aureus
and used Tn-seq analysis to probe the entire genome, with unprecedented resolution and sensitivity, for genes of importance in infection. We further identified genes contributing to fitness in various infected compartments (blood and ocular fluids) and compared them to genes required for growth in rich medium. This resulted in the identification of 426 genes that were important for
S. aureus
fitness during growth in infection models, including 71 genes that could be considered essential for survival specifically during infection. These findings highlight novel as well as previously known genes encoding virulence traits and metabolic pathways important for
S. aureus
proliferation at sites of infection, which may represent new therapeutic targets.

IMPORTANCE
Staphylococcus aureus
continues to be a leading cause of antibiotic-resistant community and nosocomial infection. With the bacterium’s acquisition of resistance to methicillin and, more recently, vancomycin, the need for the development of new drugs with novel targets is urgent. Applying a highly saturated Tn-seq mutant library to analyze fitness and growth requirements in a murine abscess and in various infection-relevant fluids, we identified
S. aureus
traits that enable it to survive and proliferate during infection. This identifies potential new targeting opportunities for the development of novel therapeutics.
Iranian adolescent girls’ barriers in accessing sexual and reproductive health information and services: a qualitative study
Authors: Shariati Mohammed , Babazadeh Raheleh , Mousavi Seyed Abbas , Najmabadi Khadijeh Mirzaii 
Published: September 2014

IntroductionAdolescence is a critical period of transition from childhood to adulthood. In today's world, to pass through this period successfully it is necessary to have adequate information and knowledge about sexual and reproductive health (SRH) issues. In Iran, it is crucial that special attention be paid to reproductive health services for adolescents, especially for girls.PurposeThis study aimed to explore the views and experiences of adolescent girls and key adults around the barriers to access of Iranian adolescent girls to SRH information and services.MethodsIn this qualitative study, data were gathered through focus groups and semi-structured interviews with 247 adolescent girls and 71 key adults including mothers, teachers, health providers, governmental, nongovernmental and international managers of health programmes, health policymakers, sociologists and clergy in four Iranian cities. Data were coded and categorised using content analysis by MAXQDA10.ResultsThe main barriers identified were classified in four categories: (1) social and cultural barriers such as taboos; (2) structural and administrative barriers such as inappropriate structure of the health system; (3) political barriers such as lack of an adopted strategy by the government and (4) non-use of religious potential.ConclusionsAdolescent SRH in Iran should be firmly established as a priority for government leaders and policymakers. They should try to provide those services that are consistent with the community's cultural and religious values for adolescent girls.
RNA-seq Reveals Aurora Kinase–Driven mTOR Pathway Activation in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma
Authors: Pal Sumanta K. , He Miaoling , Tong Tommy , Wu Huiqing , Liu Xueli , Lau Clayton , Wang Jin-Hui , Warden Charles , Wu Xiwei , Signoretti Sabina , Choueiri Toni K. , Karam Jose A. , Jones Jeremy O. 
Published: September 2014

Abstract
Sarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized. RNA sequencing (RNA-seq) was performed on adjacent benign, clear cell, and sarcomatoid components from clinical specimens with sarcomatoid mRCC. M phase and cell-cycle pathways were enriched in sarcomatoid versus adjacent clear cell components, suggesting greater cell proliferation. The expression of aurora kinase A (AURKA) was increased as part of these pathways, and its increased expression was validated by quantitative PCR (qPCR). Immunohistochemical (IHC) analysis revealed that AURKA levels were increased in sarcomatoid tissue compared with their benign or clear cell parts. The increase in AURKA correlated with increased mTOR pathway activity, as evidenced by increased expression of phosphorylated mTOR (S2448) and ribosomal protein S6K (T389). When AURKA was stably expressed in a RCC cell line (Renca), it resulted in increased expression and activity of mTOR, suggesting that overexpression of AURKA can activate the mTOR pathway. These results warrant the analysis of a larger clinical cohort and suggest that targeting AURKA and/or mTOR in patients with sarcomatoid mRCC should be explored.
Implications: Comparative RNA-seq of adjacent sarcomatoid and clear cell histology of RCC indicates a proliferative phenotype and increased AURKA-dependent activation of mTOR signaling in sarcomatoid RCC, which could be targeted by available agents. Mol Cancer Res; 13(1); 130–7. ©2014 AACR.
The role of actin-binding proteins in the control of endothelial barrier integrity
Authors: García-Ponce Alexander , Citalán-Madrid Alí Francisco , Velázquez-Avila Martha , Vargas-Robles Hilda , Schnoor Michael 
Published: September 2014

SummaryThe endothelial barrier of the vasculature is of utmost importance for separating the blood stream from underlying tissues. This barrier is formed by tight and adherens junctions (TJ and AJ) that form intercellular endothelial contacts. TJ and AJ are integral membrane structures that are connected to the actin cytoskeleton via various adaptor molecules. Consequently, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts and vascular permeability. While a circumferential cortical actin ring stabilises junctions, the formation of contractile stress fibres, e. g. under inflammatory conditions, can contribute to junction destabilisation. However, the role of actin-binding proteins (ABP) in the control of vascular permeability has long been underestimated. Naturally, ABP regulate permeability via regulation of actin remodelling but some actin-binding molecules can also act independently of actin and control vascular permeability via various signalling mechanisms such as activation of small GTPases. Several studies have recently been published highlighting the importance of actin-binding molecules such as cortactin, ezrin/ radixin/moesin, Arp2/3, VASP or WASP for the control of vascular permeability by various mechanisms. These proteins have been described to regulate vascular permeability under various pathophysiological conditions and are thus of clinical relevance as targets for the development of treatment strategies for disorders that are characterised by vascular hyperpermeability such as sepsis. This review highlights recent advances in determining the role of ABP in the control of endothelial cell contacts and vascular permeability.
Prognostic Value of Rubidium-82 Positron Emission Tomography in Patients After Heart Transplant
Authors: Mc Ardle Brian A. , Davies Ross A. , Chen Li , Small Gary R. , Ruddy Terrence D. , Dwivedi Girish , Yam Yeung , Haddad Haissam , Mielniczuk Lisa M. , Stadnick Ellamae , Hessian Renee , Guo Ann , Beanlands Rob S. , deKemp Robert A. , Chow Benjamin J.W. 
Published: September 2014

Background—
Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population.

Methods and Results—
Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome.

Conclusions—
Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.
Get With The Guidelines AFIB
Authors: Lewis William R. , Piccini Jonathan P. , Turakhia Mintu P. , Curtis Anne B. , Fang Margaret , Suter Robert E. , Page Robert L. , Fonarow Gregg C. 
Published: September 2014

Background—
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is a cause of stroke, heart failure, and death. Guideline-based treatment can improve outcomes in AF. Unfortunately, adherence to these guidelines is low. Get With The Guidelines is a hospital-based performance initiative, which has been shown to improve adherence over time. Get With The Guidelines-AFIB is a novel quality improvement registry designed to improve adherence to AF guidelines.

Methods and Results—
Hospitals will be recruited by regional American Heart Association staff and key stakeholders. Inpatients or observed patients with AF or atrial flutter will be enrolled. Data collected will include demographic, medical history, and clinical characteristics including laboratory values and treatments. Decision support will guide adherence to achievement and quality measures designed to improve adherence to anticoagulation, heart rate control, safe antiarrhythmic drug use, and patient education and follow-up. Increased adherence to guidelines will be facilitated using rapid-cycle quality improvement, site-specific reporting including national and regional benchmarks and hospital recognition for achievement. Primary analyses will include adherence to American Heart Association/American College of Cardiology performance measures and guidelines. Secondary analyses will include processes of care, risk stratification, treatment of special conditions or populations and use of particular treatment techniques.

Conclusions—
AF is common clinical problem with significant morbidity and mortality. Get With The Guidelines-AFIB is a national hospital-based AF quality improvement program designed to increase adherence to evidence-based guidelines for AF.
An Anatomy of the Cooling of the North Atlantic Ocean in the 1960s and 1970s
Authors: Hodson Daniel L. R. , Robson Jon I. , Sutton Rowan T. 
Published: September 2014

Abstract
In the 1960s and early 1970s, sea surface temperatures in the North Atlantic Ocean cooled rapidly. There is still considerable uncertainty about the causes of this event, although various mechanisms have been proposed. In this observational study, it is demonstrated that the cooling proceeded in several distinct stages. Cool anomalies initially appeared in the mid-1960s in the Nordic Seas and Gulf Stream extension, before spreading to cover most of the subpolar gyre. Subsequently, cool anomalies spread into the tropical North Atlantic before retreating, in the late 1970s, back to the subpolar gyre. There is strong evidence that changes in atmospheric circulation, linked to a southward shift of the Atlantic ITCZ, played an important role in the event, particularly in the period 1972–76. Theories for the cooling event must account for its distinctive space–time evolution. The authors’ analysis suggests that the most likely drivers were 1) the “Great Salinity Anomaly” of the late 1960s; 2) an earlier warming of the subpolar North Atlantic, which may have led to a slowdown in the Atlantic meridional overturning circulation; and 3) an increase in anthropogenic sulfur dioxide emissions. Determining the relative importance of these factors is a key area for future work.
Some Dynamical Constraints on Upstream Pathways of the Denmark Strait Overflow
Authors: Yang Jiayan , Pratt Lawrence J. 
Published: September 2014

Abstract
The East Greenland Current (EGC) had long been considered the main pathway for the Denmark Strait overflow (DSO). Recent observations, however, indicate that the north Icelandic jet (NIJ), which flows westward along the north coast of Iceland, is a major separate pathway for the DSO. In this study a two-layer numerical model and complementary integral constraints are used to examine various pathways that lead to the DSO and to explore plausible mechanisms for the NIJ’s existence. In these simulations, a westward and NIJ-like current emerges as a robust feature and a main pathway for the Denmark Strait overflow. Its existence can be explained through circulation integrals around advantageous contours. One such constraint spells out the consequences of overflow water as a source of low potential vorticity. A stronger constraint can be added when the outflow occurs through two outlets: it takes the form of a circulation integral around the Iceland–Faroe Ridge. In either case, the direction of overall circulation about the contour can be deduced from the required frictional torques. Some effects of wind stress forcing are also examined. The overall positive curl of the wind forces cyclonic gyres in both layers, enhancing the East Greenland Current. The wind stress forcing weakens but does not eliminate the NIJ. It also modifies the sign of the deep circulation in various subbasins and alters the path by which overflow water is brought to the Faroe Bank Channel, all in ways that bring the idealized model more in line with observations. The sequence of numerical experiments separates the effects of wind and buoyancy forcing and shows how each is important.
Evaluation of Ensemble Configurations for the Analysis and Prediction of Heavy-Rain-Producing Mesoscale Convective Systems*
Authors: Schumacher Russ S. , Clark Adam J. 
Published: September 2014

Abstract
This study investigates probabilistic forecasts made using different convection-allowing ensemble configurations for a three-day period in June 2010 when numerous heavy-rain-producing mesoscale convective systems (MCSs) occurred in the United States. These MCSs developed both along a baroclinic zone in the Great Plains, and in association with a long-lived mesoscale convective vortex (MCV) in Texas and Arkansas. Four different ensemble configurations were developed using an ensemble-based data assimilation system. Two configurations used continuously cycled data assimilation, and two started the assimilation 24 h prior to the initialization of each forecast. Each configuration was run with both a single set of physical parameterizations and a mixture of physical parameterizations. These four ensemble forecasts were also compared with an ensemble run in real time by the Center for the Analysis and Prediction of Storms (CAPS). All five of these ensemble systems produced skillful probabilistic forecasts of the heavy-rain-producing MCSs, with the ensembles using mixed physics providing forecasts with greater skill and less overall bias compared to the single-physics ensembles. The forecasts using ensemble-based assimilation systems generally outperformed the real-time CAPS ensemble at lead times of 6–18 h, whereas the CAPS ensemble was the most skillful at forecast hours 24–30, though it also exhibited a wet bias. The differences between the ensemble precipitation forecasts were found to be related in part to differences in the analysis of the MCV and its environment, which in turn affected the evolution of errors in the forecasts of the MCSs. These results underscore the importance of representing model error in convection-allowing ensemble analysis and prediction systems.
The impact of insight on social functioning in patients with schizophrenia
Authors: Erol Almila , Delibas Hakan , Bora Ozlem , Mete Levent 
Published: September 2014

Background: It is still unclear whether insight has a direct association with social functioning in schizophrenia, independent of its association with symptoms. Aim: This study aimed to investigate the relationship of insight and its dimensions with social functioning in schizophrenia. Methods: A total of 170 outpatients with schizophrenia were included in this study. All patients were evaluated with the Scale to Assess Unawareness of Mental Disorder (SUMD), Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance Scale (PSP). Patients with impaired insight and patients with unimpaired insight were compared for PSP score through independent samples t test. Pearson’s correlation analysis was used to determine the correlations between study variables. Multiple stepwise linear regression analysis was used in order to determine the variables that predict social performance. Results: The PSP score of patients with impaired insight was significantly lower than that of patients with unimpaired insight. There were significant correlations between insight dimensions and PSP score. PANSS negative scale score, awareness of achieved effects of medication and awareness of anhedonia/asociality were significant predictors of social performance. Conclusion: Insight has a significant impact on social functioning in schizophrenia, and some, but not all, insight dimensions have direct impact on social performance, independent of their association with symptoms.