bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretome Analysis of Vibrio cholerae Type VI Secretion System Reveals a New Effector-Immunity Pair
Authors: Altindis Emrah , Dong Tao , Catalano Christy , Mekalanos John 
Published: March 2015

ABSTRACT

The type VI secretion system (T6SS) is a dynamic macromolecular organelle that many Gram-negative bacteria use to inhibit or kill other prokaryotic or eukaryotic cells. The toxic effectors of T6SS are delivered to the prey cells in a contact-dependent manner. In
Vibrio cholerae
, the etiologic agent of cholera, T6SS is active during intestinal infection. Here, we describe the use of comparative proteomics coupled with bioinformatics to identify a new T6SS effector-immunity pair. This analysis was able to identify all previously identified secreted substrates of T6SS except PAAR (proline, alanine, alanine, arginine) motif-containing proteins. Additionally, this approach led to the identification of a new secreted protein encoded by VCA0285 (TseH) that carries a predicted hydrolase domain. We confirmed that TseH is toxic when expressed in the periplasm of Escherichia coli and V. cholerae cells. The toxicity observed in V. cholerae was suppressed by coexpression of the protein encoded by VCA0286 (TsiH), indicating that this protein is the cognate immunity protein of TseH. Furthermore, exogenous addition of purified recombinant TseH to permeabilized E. coli cells caused cell lysis. Bioinformatics analysis of the TseH protein sequence suggest that it is a member of a new family of cell wall-degrading enzymes that include proteins belonging to the YD repeat and Rhs superfamilies and that orthologs of TseH are likely expressed by species belonging to phyla as diverse as
Bacteroidetes
and
Proteobacteria
.

IMPORTANCE
The Gram-negative bacterium
Vibrio cholerae
causes cholera, a severe and often lethal diarrheal disease. The 2010-2012 epidemic in Haiti and new explosive epidemics in Africa show that cholera remains a significant global public health problem. The type VI secretion system (T6SS) is a dynamic organelle expressed by many Gram-negative bacteria, which use it to inject toxic effector proteins into eukaryotic and bacterial prey cells. In this study, we applied a comparative proteomics approach to the V. cholerae T6SS secretome to identify new substrates of this secretion apparatus. We show that the product of the gene VCA0285 is likely a new peptidoglycan hydrolase that is secreted by T6SS and that its cognate immunity protein is encoded by the gene that is immediately downstream (VCA0286). Bioinformatics analysis shows that VCA0285 carries four conserved motifs that likely define a large family of hydrolases with antibacterial activity. The identification of new antibacterial T6SS effectors provides useful information for the development of novel antibiotics and therapeutic agents.
Soluble plasma VE-cadherin concentrations are elevated in patients with STEC infection and haemolytic uraemic syndrome: a case–control study
Authors: Doulgere Julia , Otto Benjamin , Nassour Maher , Wolters-Eisfeld Gerrit , Rohde Holger , Magnus Tim , Wagener Christoph , Streichert Thomas 
Published: March 2015

ObjectivesTo investigate whether the adherens junction protein vascular endothelial cadherin (VE-cadherin) is released during Shiga toxin 2 producingEscherichia coli(STEC) infection with haemolytic uraemic syndrome (HUS) and thus could be used to assist diagnosis.DesignUsing data from the large 2011 STEC outbreak in northern Europe, we determined VE-cadherin plasma concentrations in 356 patients distributed over three patient cohorts: patients with STEC infection accompanied by HUS (STEC-HUS), STEC patients without HUS (STEC) and control patients with diarrhoea but without STEC infection. We then looked for associations between VE-cadherin concentrations and disease severity defined by changes in lactate dehydrogenase, haemoglobin, creatinine, platelet count, haptoglobin and neurological symptoms.SettingThis study was conducted at the University Medical Center Hamburg-Eppendorf, Germany.Participants79 STEC-HUS patients, 77 STEC patients and 200 control patients were enrolled in the study.ResultsWe analysed 864 specimens (207 STEC, 449 STEC-HUS and 208 controls) in total. At admission, VE-cadherin concentration tended to be lower in STEC-HUS patients compared to other patients. However, HUS patients later showed an increase in VE-cadherin concentrations with prolonged elevation beyond remission. This pattern clearly differs from that observed in non-HUS patients.ConclusionsVE-cadherin concentrations are elevated in STEC-HUS patients and might be a biomarker reflecting endothelial damage in patients with HUS.
The accuracy of the general practitioner's sense of alarm when confronted with dyspnoea and/or thoracic pain: protocol for a prospective observational study
Authors: Barais Marie , Barraine Pierre , Scouarnec Florie , Mauduit Anne Sophie , Le Floc'h Bernard , Van Royen Paul , Liétard Claire , Stolper Erik 
Published: March 2015

IntroductionDyspnoea and chest pain are signs shared with multiple pathologies ranging from the benign to life-threatening diseases. Gut feelings such as the sense of alarm and the sense of reassurance are known to play a substantial role in the diagnostic reasoning of general practitioners (GPs). A Gut Feelings Questionnaire (GFQ) has been validated to measure the GP's sense of alarm. A French version of the GFQ is available following a linguistic validation procedure. The aim of the study is to calculate the diagnostic test accuracy of a GP's sense of alarm when confronted with dyspnoea and chest pain.Methods and analysisProspective observational study. Patients aged between 18 and 80 years, consulting their GP for dyspnoea and/or thoracic pain will be considered for enrolment in the study. These GPs will have to complete the questionnaire immediately after the consultation for dyspnoea and/or thoracic pain. The follow-up and the final diagnosis will be collected 4 weeks later by phone contact with the GP or with the patient if their GP has no information. Life-threatening and non-life-threatening diseases have previously been defined according to the pathologies or symptoms in the (ICPC2) International Collegiate Programming Contest classification. Members of the research team, blinded to the actual outcomes shown on the index questionnaire, will judge each case in turn and will, by consensus, classify the expected outcomes as either life-threatening or non-life-threatening diseases. The sensitivity, the specificity, the positive and negative likelihood ratio of the sense of alarm will be calculated from the constructed contingency table.Ethics and disseminationThis study was approved by the ethical committee of the University de Bretagne Occidentale. A written informed consent form will be signed and dated by GPs and patients at the beginning of the study. The results will be published in due course.
BATF2 Deficiency Promotes Progression in Human Colorectal Cancer via Activation of HGF/MET Signaling: A Potential Rationale for Combining MET Inhibitors with IFNs
Authors: Liu Zebing , Wei Ping , Yang Yu , Cui Wenli , Cao Bing , Tan Cong , Yu Baohua , Bi Rui , Xia Kaiqin , Chen Weixiang , Wang Yiqin , Zhang Youyuan , Du Xiang , Zhou Xiaoyan 
Published: March 2015

Abstract
Purpose: BATF2, a novel IFN-stimulated gene, inhibits tumor cell proliferation, invasion, and migration. The objectives of this study were to determine how BATF2 expression is associated with colorectal cancer progression and patient outcome, to investigate how BATF2 overexpression inhibits hepatocyte growth factor (HGF)/MET signaling, and to elucidate the rationale for combining MET inhibitors with IFN.
Experimental Design: BATF2 expression in colorectal cancer tissues was determined and correlated with colorectal cancer patient prognosis. Cultured colorectal cancer cells were used to investigate the effects of BATF2 overexpression on the malignant phenotype of colorectal cancer cells and HGF/MET signaling. Tumor xenograft models were used to validate the effects of BATF2 on colorectal cancer xenograft growth and assess the efficacy of the combination of MET inhibitors with IFNs in colorectal cancer.
Results: In colorectal cancer tissues, BATF2 was found to be significantly downregulated, and its expression negatively correlated with MET expression. Decreased BATF2 expression was associated with progression and shorter patient survival in colorectal cancer. BATF2 overexpression promoted apoptosis and inhibited proliferation, migration, and invasion in colorectal cancer cells, as well as dramatically blunted tumor xenograft growth. In addition, MET inhibitors in combination with IFNβ produced synergistic cytotoxicity both in vitro and in vivo.
Conclusions: Together, these novel findings suggest that BATF2, a tumor suppressor gene, is a potent negative regulator of HGF/MET signaling in colorectal cancer and may serve as a prognostic tumor marker. Furthermore, these results provide a rationale for combining MET inhibitors with IFNs in preclinical trials. Clin Cancer Res; 21(7); 1752–63. ©2015 AACR.
Practice Structure Improves Unconscious Transitional Memories by Increasing Synchrony in a Premotor Network
Authors: Song Sunbin , Gotts Stephen J. , Dayan Eran , Cohen Leonardo G. 
Published: March 2015

Abstract
Sequence learning relies on formation of unconscious transitional and conscious ordinal memories. The influence of practice type on formation of these memories that compose skill and systems level neural substrates is not known. Here, we studied learning of transitional and ordinal memories in participants trained on motor sequences while scanned using fMRI. Practice structure was varied or grouped (mixing or grouping sequences during training, respectively). Memory was assessed 30 min and 1 week later. Varied practice improved transitional memory and enhanced coupling of the dorsal premotor cortex with thalamus, cerebellum, and lingual and cingulate regions and greater transitional memory correlated with this coupling. Thus, varied practice improves unconscious transitional memories in proportion to coupling within a cortico-subcortical network linked to premotor cortex. This result indicates that practice structure influences unconscious transitional memory formation and identifies underlying systems level mechanisms.
The Origin and Limits of the Near Proportionality between Climate Warming and Cumulative CO2 Emissions
Authors: MacDougall Andrew H. , Friedlingstein Pierre 
Published: March 2015

AbstractThe transient climate response to cumulative CO2 emissions (TCRE) is a useful metric of climate warming that directly relates the cause of climate change (cumulative carbon emissions) to the most used index of climate change (global mean near-surface temperature change). In this paper, analytical reasoning is used to investigate why TCRE is near constant over a range of cumulative emissions up to 2000 Pg of carbon. In addition, a climate model of intermediate complexity, forced with a constant flux of CO2 emissions, is used to explore the effect of terrestrial carbon cycle feedback strength on TCRE. The analysis reveals that TCRE emerges from the diminishing radiative forcing from CO2 per unit mass being compensated for by the diminishing ability of the ocean to take up heat and carbon. The relationship is maintained as long as the ocean uptake of carbon, which is simulated to be a function of the CO2 emissions rate, dominates changes in the airborne fraction of carbon. Strong terrestrial carbon cycle feedbacks have a dependence on the rate of carbon emission and, when present, lead to TRCE becoming rate dependent. Despite these feedbacks, TCRE remains roughly constant over the range of the representative concentration pathways and therefore maintains its primary utility as a metric of climate change.
Improved Simulation of Peak Flows under Climate Change: Postprocessing or Composite Objective Calibration?
Authors: Zhang Xujie , Booij Martijn J. , Xu Yue-Ping 
Published: March 2015

Abstract
Climate change is expected to have large impacts on peak flows. However, there may be bias in the simulation of peak flows by hydrological models. This study aims to improve the simulation of peak flows under climate change in Lanjiang catchment, east China, by comparing two approaches: postprocessing of peak flows and composite objective calibration. Two hydrological models [Soil and Water Assessment Tool (SWAT) and modèle du Génie Rural à 4 paramètres Journalier (GR4J)] are employed to simulate the daily flows, and the peaks-over-threshold method is used to extract peak flows from the simulated daily flows. Three postprocessing methods, namely, the quantile mapping method and two generalized linear models, are set up to correct the biases in the simulated raw peak flows. A composite objective calibration of the GR4J model by taking the peak flows into account in the calibration process is also carried out. The regional climate model Providing Regional Climates for Impacts Studies (PRECIS) with boundary forcing from two GCMs (HadCM3 and ECHAM5) under greenhouse gas emission scenario A1B is applied to produce the climate data for the baseline period and the future period 2011–40. The results show that the postprocessing methods, particularly quantile mapping method, can correct the biases in the raw peak flows effectively. The composite objective calibration also resulted in a good simulation performance of peak flows. The final estimated peak flows in the future period show an obvious increase compared with those in the baseline period, indicating there will probably be more frequent floods in Lanjiang catchment in the future.
Labyrinthitis Ossificans
Authors: Bloch Sune Land , McKenna Michael John , Adams Joe , Friis Morten 
Published: March 2015

Introduction: It has been suggested that remodeling of the otic capsule is highly suppressed by the action of anti-resorptive signals emanating from structures of the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to bacterial meningitis and is characterized by destruction of inner ear structures by the formation of new bone. The aim of this study was to explore the impact of LO on bone remodeling of the otic capsule. Material and Methods: In 11 human temporal bones with extensive LO and 10 control specimens, the degree of bone remodeling was explored indirectly by estimating the viability of osteocytes in perilabyrinthine bone and the mastoid. Results: The viability of osteocytes was significantly lower in the perilabyrinthine bone compared to the mastoid in both groups. However, the loss of perilabyrinthine osteocytes was the same in the 2 groups, and the presence of cartilage remnants appeared to be the same. Conclusion: This study indicates that the factors affecting bone remodeling of the otic capsule and the degeneration of osteocytes are not altered by wholesale destruction of inner ear soft tissue and its replacement by bone. Therefore, alternative mechanisms may be implicated in the suppression of capsular bone remodeling.
Dualities of Latin America
Authors: Katz Claudio 
Published: March 2015

Determining whether the current situation of Latin America is better described as “post-neoliberalism” or as “commodities consensus” requires an analysis of recent changes in the region. Capitalism has expanded in agriculture and mining, accentuating the preeminence of basic exports. Traditional industry is declining, and remittances and tourism have increased in importance. Local capitalists associated with foreign corporations have replaced the national bourgeoisie, while the exodus of peasants consolidates labor precariousness, poverty, and inequality. At the same time, the United States is deploying troops to reorganize its domination. The South American rebellions have limited neoliberal aggression and achieved unusual victories in other parts of the world. The concept of post-neoliberalism emphasizes the region’s political turn toward autonomy but overlooks the persistence of the economic model generated during the previous phase. The opposing concept, commodities consensus, highlights the extractivism prevailing throughout the region but plays down the extreme divergences among right-wing, center-left, and radical governments in all other areas. Both concepts contain part of the truth, but neither fully explains the regional scenario. Para determinar si la situación actual de Latinoamérica es mejor descrita como “post-neoliberalismo” o como un “consenso de los commodities” hay que hacer un análisis de los cambios recientes en la región. El capitalismo se ha expandido en la agricultura y la minería, acrecentando la preeminencia de las exportaciones básicas. La industria tradicional ha disminuido, y la importancia del turismo y las remesas ha aumentado. Los capitalistas locales asociados con empresas extranjeras han reemplazado a la burguesía nacional, mientras que el éxodo de los campesinos ha consolidado la precariedad laboral, la pobreza y la desigualdad. Al mismo tiempo, Estados Unidos despliega tropas para reorganizar su dominio. Las rebeliones en América del Sur han puesto barreras a la agresión neoliberal y logrado victorias inusuales en otras partes del mundo. El concepto del post-neoliberalismo destaca el giro político de la región hacia la autonomía pero con una tendencia a la persistencia del modelo económico generado durante la fase anterior. El otro concepto, el consenso de las commodities, destaca el extractivismo que prevalece en toda la región pero minoriza las divergencias entre los gobiernos de derecha, centro-izquierda y radicales en todas las demás áreas. Ambos conceptos son parcialmente ciertos, pero no explican totalmente el escenario regional.
Dose limits to the lens of the eye: International Basic Safety Standards and related guidance
Authors: Boal T.J. , Pinak M. 
Published: March 2015

The International Atomic Energy Agency (IAEA) safety requirements: ‘General Safety Requirements Part 3 – Radiation protection and safety of radiation sources: International Basic Safety Standards’ (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year−1 to 20 mSv year−1, averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit.
The effect of a structured programme to increase patient activity during inpatient stroke rehabilitation: a Phase I cohort study
Authors: Tyson SF , Burton L , McGovern A 
Published: March 2015

Objective: To develop an intervention and undertake a proof-of-concept evaluation of its feasibility, acceptability, and impact on recorded patient activity levels during inpatient stroke rehabilitation. Design: A longitudinal cohort design. Setting: Three inpatient stroke rehabilitation services. Subjects: Stroke survivors receiving inpatient rehabilitation. Intervention: A programme designed to increase patient activity, including individualised patient timetables, independent practice, therapeutic group work, and structured social activities was developed and implemented without additional resource. Main measures: Patients’ recorded activity levels were compared for two weeks before and after implementation of the programme. Data regarding the estimated time spent in different types of activity were extracted from patient treatment records, patients’ and therapists’ diaries, or timetables (if used) to measure patient activity levels Results: At baseline, recorded activity levels were low; patients undertook a mean of 61 minutes (SD = 39) of activity per day. After implementation of the programme, recorded activity levels significantly increased to a mean of 123 minutes (SD = 88) per day ( p = 0.0001). The time spent in all types of recorded activity increased ( p = 0.0001–0.002), except psychology where the increase did not reach significance ( p = 0.670). Conclusions: A structured programme can significantly increase recorded patient activity levels during inpatient stroke rehabilitation without additional resource.
Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample
Authors: Winstock Adam , Lynskey Michael , Borschmann Rohan , Waldron Jon 
Published: March 2015

Background: Synthetic cannabinoids (SCs) have become increasingly popular in recent years. Diverse in chemical structure, many have been subjected to legislative regulation, but their availability and use persists. Often marketed to reflect their similar effects to cannabis, their use has been associated with a range of negative health effects. We sought to determine the relative risk of seeking emergency medical treatment (EMT) following use of SCs and natural cannabis. Methods: We utilized an anonymous online survey of drug use, obtaining data from 22,289 respondents. We calculated the relative risk of seeking EMT between the two substances using an estimate for days used in the past year. Results: Thirty-seven cannabis users (0.2%) and 21 SC users (1.0%) had sought EMT during the past year following use. The relative risk associated with the use of SCs was 30 (95% CI 17.5–51.2) times higher than that associated with cannabis. Significantly more symptoms ( p=0.03) were reported by respondents seeking treatment for SCs than for cannabis. Conclusions: Whilst these findings must be treated with caution, SCs potentially pose a greater risk to users’ health than natural forms of cannabis. Regulation is unlikely to remove SCs from the market, so well-informed user-focused health promotion messages need to be crafted to discourage their use.