bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus
Authors: Danger Jessica L. , Makthal Nishanth , Kumaraswami Muthiah , Sumby Paul 
Published: September 2015

ABSTRACT

The group A
Streptococcus
(GAS;
Streptococcus pyogenes
) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the
prtF1
and
prtF2
mRNAs within their 5′ untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the
prtF1
and
prtF2
mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection.

IMPORTANCE
More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small RNA FasX. In addition to identifying that FasX reduces the abundance of the cell surface-located fibronectin-binding proteins PrtF1/2, fibronectin is present in high abundance in human tissues, and we have determined the mechanism behind this regulation. Importantly, as FasX is the only mechanistically characterized regulatory RNA in GAS, it serves as a model RNA in this and related pathogens.
Bacillus anthracis lcp
Genes Support Vegetative Growth, Envelope Assembly, and Spore Formation
Authors: Liszewski Zilla Megan , Lunderberg J. Mark , Schneewind Olaf , Missiakas Dominique 
Published: September 2015

ABSTRACT

Bacillus anthracis
, a spore-forming pathogen, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. Surface (S)-layer proteins and
B. anthracis
S-layer-associated proteins (BSLs) function as chain length determinants and are assembled in the envelope by binding to the secondary cell wall polysaccharide (SCWP).
B. anthracis
expresses six different genes encoding LytR-CpsA-Psr (LCP) enzymes (
lcpB1
to -
4
,
lcpC
, and
lcpD
), which when expressed in
Staphylococcus aureus
promote attachment of wall teichoic acid to peptidoglycan. Mutations in
B. anthracis
lcpB3
and
lcpD
cause aberrations in cell size and chain length that can be explained as discrete defects in SCWP assembly; however, the function of the other
lcp
genes is not known. By deleting combinations of
lcp
genes from the
B. anthracis
genome, we generated variants with single
lcp
genes.
B. anthracis
expressing
lcpB3
alone displayed physiological cell size, vegetative growth, spore formation, and S-layer assembly. Strains expressing
lcpB1
or
lcpB4
displayed defects in cell size and shape, S-layer assembly, and spore formation yet sustained vegetative growth. In contrast, the
lcpB2
strain was unable to grow unless the gene was expressed from a multicopy plasmid (
lcpB2

++

), and variants expressing
lcpC
or
lcpD
displayed severe defects in growth and cell shape. The
lcpB2

++

,
lcpC
, or
lcpD
strains supported neither S-layer assembly nor spore formation. We propose a model whereby LCP enzymes fulfill partially overlapping functions in transferring SCWP molecules to discrete sites within the bacterial envelope.

IMPORTANCE
Products of genes essential for bacterial envelope assembly represent targets for antibiotic development. The LytR-CpsA-Psr (LCP) enzymes tether bactoprenol-linked intermediates of secondary cell wall polymers to the C6 hydroxyl of
N
-acetylmuramic acid in peptidoglycan; however, the role of LCPs as a target for antibiotic therapy is not defined. We show here that LCP enzymes are essential for the cell cycle, vegetative growth, and spore formation of
Bacillus anthracis
, the causative agent of anthrax disease. Furthermore, we assign functions for each of the six LCP enzymes, including cell size and shape, vegetative growth and sporulation, and S-layer and S-layer-associated protein assembly.
Involving migrants in the development of guidelines for communication in cross-cultural general practice consultations: a participatory learning and action research project
Authors: O'Reilly-de Brún Mary , MacFarlane Anne , de Brún Tomas , Okonkwo Ekaterina , Bonsenge Bokanga Jean Samuel , Manuela De Almeida Silva Maria , Ogbebor Florence , Mierzejewska Aga , Nnadi Lovina , van den Muijsenbergh Maria , van Weel-Baumgarten Evelyn , van Weel Chris 
Published: September 2015

ObjectiveThe aim of this research was to involve migrants and other key stakeholders in a participatory dialogue to develop a guideline for enhancing communication in cross-cultural general practice consultations. In this paper, we focus on findings about the use of formal versus informal interpreters because dialogues about these issues emerged as central to the identification of recommendations for best practice.DesignThis qualitative case study involved a Participatory Learning and Action (PLA) research methodology.ParticipantsThe sample comprised 80 stakeholders: 51 from migrant communities; 15 general practitioners (GPs) and general practice staff; 7 established migrants as peer researchers; 5 formal, trained interpreters; and 2 service planners from the national health authority.SettingGalway, Ireland.ResultsThere was 100% consensus across stakeholder groups that while informal interpreters haveusesfor migrants and general practice staff, they are not consideredacceptableas best practice. There was also 100% consensus that formal interpreters who are trained and working as per a professional code of practice are acceptable as best practice.ConclusionsPolicymakers and service planners need to work in partnership with service providers and migrants to progress the implementation of professional, trained interpreters as a routine way of working in general practice.
Australia's 1996 gun law reforms: faster falls in firearm deaths, firearm suicides, and a decade without mass shootings
Authors: Chapman S , Alpers P , Agho K , Jones M 
Published: September 2015

BackgroundAfter a 1996 firearm massacre in Tasmania in which 35 people died, Australian governments united to remove semi-automatic and pump-action shotguns and rifles from civilian possession, as a key component of gun law reforms.ObjectiveTo determine whether Australia's 1996 major gun law reforms were associated with changes in rates of mass firearm homicides, total firearm deaths, firearm homicides and firearm suicides, and whether there were any apparent method substitution effects for total homicides and suicides.DesignObservational study using official statistics. Negative binomial regression analysis of changes in firearm death rates and comparison of trends in pre-post gun law reform firearm-related mass killings.SettingAustralia, 1979–2003.Main outcome measuresChanges in trends of total firearm death rates, mass fatal shooting incidents, rates of firearm homicide, suicide and unintentional firearm deaths, and of total homicides and suicides per 100 000 population.ResultsIn the 18 years before the gun law reforms, there were 13 mass shootings in Australia, and none in the 10.5 years afterwards. Declines in firearm-related deaths before the law reforms accelerated after the reforms for total firearm deaths (p=0.04), firearm suicides (p=0.007) and firearm homicides (p=0.15), but not for the smallest category of unintentional firearm deaths, which increased. No evidence of substitution effect for suicides or homicides was observed. The rates per 100 000 of total firearm deaths, firearm homicides and firearm suicides all at least doubled their existing rates of decline after the revised gun laws.ConclusionsAustralia's 1996 gun law reforms were followed by more than a decade free of fatal mass shootings, and accelerated declines in firearm deaths, particularly suicides. Total homicide rates followed the same pattern. Removing large numbers of rapid-firing firearms from civilians may be an effective way of reducing mass shootings, firearm homicides and firearm suicides.
Mapping the Pathways of Resistance to Targeted Therapies
Authors: Wood Kris C. 
Published: September 2015

Abstract
Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. Recently developed methods enable the direct and scalable identification of the signaling pathways capable of driving resistance in specific contexts. Using these methods, novel pathways of resistance to clinically approved drugs have been identified and validated. By combining systematic resistance pathway mapping methods with studies revealing biomarkers of specific resistance pathways and pharmacologic approaches to block these pathways, it may be possible to rationally construct drug combinations that yield more penetrant and lasting responses in patients. Cancer Res; 75(20); 4247–51. ©2015 AACR.
Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin
Authors: Maziveyi Mazvita , Alahari Suresh K. 
Published: September 2015

Abstract
Tumor suppressor genes regulate cell growth and prevent spontaneous proliferation that could lead to aberrant tissue function. Deletions and mutations of these genes typically lead to progression through the cell-cycle checkpoints, as well as increased cell migration. Studies of these proteins are important as they may provide potential treatments for breast cancers. In this review, we discuss a comprehensive overview on Nischarin, a novel protein discovered by our laboratory. Nischarin, or imidazoline receptor antisera-selected protein, is a protein involved in a vast number of cellular processes, including neuronal protection and hypotension. The NISCH promoter experiences hypermethylation in several cancers, whereas some highly aggressive breast cancer cells exhibit genomic loss of the NISCH locus. Furthermore, we discuss data illustrating a novel role of Nischarin as a tumor suppressor in breast cancer. Analysis of this new paradigm may shed light on various clinical questions. Finally, the therapeutic potential of Nischarin is discussed. Cancer Res; 75(20); 4252–9. ©2015 AACR.
Extracellular DNA: A Bridge to Cancer
Authors: Hawes Martha C. , Wen Fushi , Elquza Emad 
Published: September 2015

Abstract
DNase I is a secreted enzyme whose function has been presumed to control “waste management” in the human system, by degrading DNA that leaks from dead and dying cells. Emerging studies have instead yielded evidence that DNase I plays a central role in newly defined dynamics of immune and autoimmune diseases, as well as cancer and vascular disorders, including thrombosis. Cancer cells have been reported to be associated with distinctive extracellular structures that facilitate aggregation and implantation. The fact that DNA is a component of such structures and that it plays a role in cancer development is illustrated by direct evidence: DNase I added to tumor cells eliminates the structures and inhibits tumorigenicity of some cancer cell lines. DNase I injected into experimental animals, moreover, results in significant inhibition of metastasis. Despite independent observations of such phenomena in diverse cancers for over 50 years, the potential for using DNase I as a clinical tool to prevent or treat cancer remains unexplored. The discovery of neutrophil extracellular traps has yielded a conceptual framework for interpreting how extracellular DNA may function in cancer development and why it may prove to be an important clinical target in stopping cancer outside the cell. Cancer Res; 75(20); 4260–4. ©2015 AACR.
Association Between High‐Sensitivity C‐Reactive Protein and Total Stroke by Hypertensive Status Among Men
Authors: Jiménez Monik C. , Rexrode Kathryn M. , Glynn Robert J. , Ridker Paul M , Gaziano J. Michael , Sesso Howard D. 
Published: September 2015

Background

High‐sensitivity C‐reactive protein (hs
CRP
), a marker of systemic inflammation, may promote atherosclerosis, particularly among adults with elevated blood pressure; however, data are sparse. We examined the association between hs
CRP
concentrations and risk of total stroke by hypertension status (normotension, prehypertension, and hypertension) among men in the Physicians’ Health Study (
PHS
).

Methods and Results

Blood samples were collected (1996–1997) and assayed for hs
CRP
among 10 456 initially healthy men from
PHS
I and
PHS II
and followed from 1997 to 2012. Self‐reported hypertension status, cardiovascular risk factors, lifestyle, and alcohol consumption were obtained from the baseline questionnaire prior to randomization in
PHS II
. Strokes were updated approximately annually and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models were used. We observed 395 incident total strokes over 115 791 person‐years. In analyses adjusted for potential confounders and stroke risk factors, clinically elevated hs
CRP
(>3 mg/L) was associated with a 40% significantly greater hazard of total stroke compared with hs
CRP
<1 mg/L (hazard ratio 1.40, 95%
CI
1.06 to 1.8
7
;
P
trend
=0.01). Additional adjustment for blood pressure and biomarkers associated with cardiovascular risk marginally attenuated the estimates. Results were similar by hypertension status, although not statistically significant among normotensive and prehypertensive participants due to limited events.

Conclusions

Elevated hs
CRP
levels were associated with a greater risk of total stroke, even after adjustment for potential confounders and cardiovascular risk factors. Risk of total stroke was significantly higher among hypertensive men with elevated hs
CRP
compared with normotensive men with low hs
CRP
.
Do Lower Target Temperatures or Prolonged Cooling Provide Improved Outcomes for Comatose Survivors of Cardiac Arrest Treated With Hypothermia?
Authors: Kagawa Eisuke , Dote Keigo , Kato Masaya , Sasaki Shota , Oda Noboru , Nakano Yoshinori , Miura Katsuya , Inoue Ichiro , Kihara Yasuki 
Published: September 2015

Background
Optimal protocols for targeted temperature management are still unclear. This study investigated whether lower target temperatures and/or prolonged cooling could provide improved outcomes in comatose survivors of cardiac arrest.

Methods and Results

This observational study was conducted using the prospectively collected targeted temperature management database in Hiroshima, Japan. Between September 2003 and September 2014, 237 patients treated with
TTM
after cardiac arrest were enrolled in this study. The target temperatures and durations were assigned by the treating physicians regardless of the patients’ conditions. Favorable outcomes were defined as a cerebral performance category scale of 1 or 2 at the 90‐day follow‐up time point. The rate of favorable outcomes were similar between the patients whose protocols of target temperature were <34°C and ≥34°C (40% versus 35%,
P
=0.41), cooling durations were <28 and ≥28 hours (33% versus 44%,
P
=0.11), and rewarming durations were <28 and ≥28 hours (35% versus 41%,
P
=0.39). However, in patients treated with extracorporeal cardiopulmonary resuscitation, target temperatures <34°C were associated with more favorable outcomes (29% versus 8%,
P
=0.01). The cooling and rewarming durations >28 hours and target temperatures <34°C were associated with more frequent lethal arrhythmia, pneumonia, and/or bleedings.

Conclusions
Prolonged durations of cooling and rewarming ≥28 hours may not improve outcomes and may increase complications. Further studies are necessary to assess the hypothesis that target temperatures <34°C provide improved outcomes in patients treated with extracorporeal cardiopulmonary resuscitation.
Increase in Aerosol Black Carbon in the 2000s over Ny-Ålesund in the Summer
Authors: Chen Liqi , Li Wei , Zhan Jianqiong , Wang Jianjun , Zhang Yuanhui , Yang Xulin 
Published: September 2015

Abstract
To investigate the concentrations, sources, and temporal variations of atmospheric black carbon (BC) in the summer Arctic, routine ground-level observations of BC by optical absorption were made in the summer from 2005 to 2008 at the Chinese Arctic “Yellow River” Station (78°55′N, 11°56′E) at Ny-Ålesund on the island of Spitsbergen in the Svalbard Archipelago. Methods of the ensemble empirical-mode decomposition analysis and back-trajectory analysis were employed to assess temporal variation embedded in the BC datasets and airmass transport patterns. The 10th-percentile and median values of BC concentrations were 7.2 and 14.6 ng m−3, respectively, and hourly average BC concentrations ranged from 2.5 to 54.6 ng m−3. A gradual increase was found by 4 ng m−3 a−1. This increase was not seen in the Zeppelin Station and it seemed to contrast with the prevalent conception of generally decreasing BC concentration since 1989 in the Arctic. Factors responsible for this increase such as changes in emissions and atmospheric transport were taken into consideration. The result indicated that BC from local emissions was mostly responsible for the observed increase from 2005 to 2008. BC temporal variation in the summer was controlled by the atmospheric circulation, which presented a significant 6–14-day variation and coherent with 1–3- and 2–5-day and longer cycle variation. Although the atmospheric circulation changes from 2005 to 2008, there was not a marked trend in long-range transportation of BC. This study suggested that local emissions might have significant implication for the regional radiative energy balance at Ny-Ålesund.
Improvement in Prediction of the Arctic Oscillation with a Realistic Ocean Initial Condition in a CGCM
Authors: Kim Hae-Jeong , Ahn Joong-Bae 
Published: September 2015

Abstract
This study verifies the impact of improved ocean initial conditions on the Arctic Oscillation (AO) forecast skill by assessing the one-month lead predictability of boreal winter AO using the Pusan National University (PNU) coupled general circulation model (CGCM). Hindcast experiments were performed on two versions of the model, one does not use assimilated ocean initial data (V1.0) and one does (V1.1), and the results were comparatively analyzed. The forecast skill of V1.1 was superior to that of V1.0 in terms of the correlation coefficient between the predicted and observed AO indices. In the regression analysis, V1.1 showed more realistic spatial similarities than V1.0 did in predicted sea surface temperature and atmospheric circulation fields. The authors suggest the relative importance of the contribution of the ocean initial condition to the AO forecast skill was because the ocean data assimilation increased the predictability of the AO, to some extent, through the improved interaction between tropical forcing induced by realistic sea surface temperature (SST) and atmospheric circulation. In V1.1, as in the observation, the cold equatorial Pacific SST anomalies generated the weakened tropical convection and Hadley circulation over the Pacific, resulting in a decelerated subtropical jet and accelerated polar front jet in the extratropics. The intensified polar front jet implies a stronger stratospheric polar vortex relevant to the positive AO phase; hence, surface manifestations of the reflected positive AO phase were then induced through the downward propagation of the stratospheric polar vortex. The results suggest that properly assimilated initial ocean conditions might contribute to improve the predictability of global oscillations, such as the AO, through large-scale tropical ocean–atmosphere interaction.
Ensemble Forecast Uncertainty of the 1 December 2011 Wasatch Windstorm
Authors: Lawson John , Horel John 
Published: September 2015

AbstractA downslope windstorm on 1 December 2011 led to considerable damage along a narrow 50-km swath at the western base of the Wasatch Mountains in northern Utah. Operational forecasts issued by the Salt Lake City National Weather Service Forecast Office provided accurate guidance for the event at 1–2-day lead times, partially based on locally generated high-resolution numerical forecasts. Forecasters highlighted the possibility of the windstorm 4 days in advance. To address the apparent reduced uncertainty for this windstorm, three 11-member three-domain ensemble forecasts were initialized at 0000 UTC 25 November, 0000 UTC 27 November, and 0000 UTC 29 November 2011 using the Weather Research and Forecasting (WRF) Model with initial and boundary conditions supplied by Global Ensemble Forecast System Reforecast, version 2 (GEFS/R2). Eight of the 11 ensemble members from the 29 November 2011 forecast (60 h before the windstorm) generated a strong, localized windstorm with outliers arising from reduced cross-barrier flow. Analysis of kinetic energy error growth suggests that the reduced uncertainty of 60-h forecasts was not primarily a result of the underdispersion of GEFS/R2 initial and boundary conditions but was related to a regional reduction in error growth in midtropospheric flow upstream of northern Utah. The ensemble initialized 2 days earlier (27 November, 108 h before the windstorm) contains fewer members that generate strong windstorms, while no members generate a windstorm in the ensemble initialized on 25 November (156 h prior). This sudden increase in uncertainty with forecast lead time results from the sensitivity of the ensemble solutions to the lateral boundary conditions imposed by the GEFS/R2 between 0000 UTC 29 November and 0000 UTC 30 November.