bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Csr System Regulates
Escherichia coli
Fitness by Controlling Glycogen Accumulation and Energy Levels
Authors: Morin Manon , Ropers Delphine , Cinquemani Eugenio , Portais Jean-Charles , Enjalbert Brice , Cocaign-Bousquet Muriel 
Published: November 2017

ABSTRACT

In the bacterium
Escherichia coli
, the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences
E. coli
fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation.

IMPORTANCE
Glycogen is a polysaccharide and the main storage form of glucose from bacteria such as
Escherichia coli
to yeasts and mammals. Although its function as a sugar reserve in mammals is well documented, the role of glycogen in bacteria is not as clear. By studying the role of posttranscriptional regulation during metabolic adaptation, for the first time, we demonstrate the role of sugar reserve played by glycogen in
E. coli
. Indeed, glycogen not only makes it possible to maintain sufficient energy during metabolic transitions but is also the key component in the capacity of cells to resume growth. Since the essential posttranscriptional regulatory system Csr is a major regulator of glycogen accumulation, this work also sheds light on the central role of posttranscriptional regulation in metabolic adaptation.
Cryptococcus neoformans
Iron-Sulfur Protein Biogenesis Machinery Is a Novel Layer of Protection against Cu Stress
Authors: Garcia-Santamarina Sarela , Uzarska Marta A. , Festa Richard A. , Lill Roland , Thiele Dennis J. 
Published: November 2017

ABSTRACT

Copper (Cu) ions serve as catalytic cofactors to drive key biochemical processes, and yet Cu levels that exceed cellular homeostatic control capacity are toxic. The underlying mechanisms for Cu toxicity are poorly understood. During pulmonary infection by the fungal pathogen
Cryptococcus neoformans
, host alveolar macrophages compartmentalize Cu to the phagosome, and the ability to detoxify Cu is critical for its survival and virulence. Here, we report that iron-sulfur (Fe-S) clusters are critical targets of Cu toxicity in both
Saccharomyces cerevisiae
and
C. neoformans
in a manner that depends on the accessibility of Cu to the Fe-S cofactor. To respond to this Cu-dependent Fe-S stress,
C. neoformans
induces the transcription of mitochondrial ABC transporter Atm1, which functions in cytosolic-nuclear Fe-S protein biogenesis in response to Cu and in a manner dependent on the Cu metalloregulatory transcription factor Cuf1. As Atm1 functions in exporting an Fe-S precursor from the mitochondrial matrix to the cytosol,
C. neoformans
cells depleted for Atm1 are sensitive to Cu even while the Cu-detoxifying metallothionein proteins are highly expressed. We provide evidence for a previously unrecognized microbial defense mechanism to deal with Cu toxicity, and we highlight the importance for
C. neoformans
of having several distinct mechanisms for coping with Cu toxicity which together could contribute to the success of this microbe as an opportunistic human fungal pathogen.

IMPORTANCE
C. neoformans
is an opportunistic pathogen that causes lethal meningitis in over 650,000 people annually. The severity of
C. neoformans
infections is further compounded by the use of toxic or poorly effective systemic antifungal agents as well as by the difficulty of diagnosis. Cu is a natural potent antimicrobial agent that is compartmentalized within the macrophage phagosome and used by innate immune cells to neutralize microbial pathogens. While the Cu detoxification machinery of
C. neoformans
is essential for virulence, little is known about the mechanisms by which Cu kills fungi. Here we report that Fe-S cluster-containing proteins, including members of the Fe-S protein biogenesis machinery itself, are critical targets of Cu toxicity and therefore that this biosynthetic process provides an important layer of defense against high Cu levels. Given the role of Cu ionophores as antimicrobials, understanding how Cu is toxic to microorganisms could lead to the development of effective, broad-spectrum antimicrobials. Moreover, understanding Cu toxicity could provide additional insights into the pathophysiology of human diseases of Cu overload such as Wilson’s disease.
One-year outcomes following surgery for necrotising enterocolitis: a UK-wide cohort study
Authors: Allin Benjamin Saul Raywood , Long Anna-May , Gupta Amit , Lakhoo Kokila , Knight Marian 
Published: November 2017

ObjectiveThe objective was to describe outcomes and investigate factors affecting prognosis at 1 year post intervention for infants with surgical necrotising enterocolitis (NEC).DesignUsing the British Association of Paediatric Surgeons Congenital Anomalies Surveillance System, we conducted a prospective, multicentre cohort study of every infant reported to require surgical intervention for NEC in the UK and Ireland between 1 March 2013 and 28 February 2014. Association of independent variables with 1-year mortality was investigated using multivariable logistic regression analysis.SettingAll 28 paediatric surgical centres in the UK and Ireland.PatientsInfants were eligible for inclusion if they were diagnosed with NEC and deemed to require surgical intervention, regardless of whether that intervention was delivered.OutcomesPrimary outcome was mortality within 1 year of the decision to intervene surgically.Results236 infants were included in the study. 208 (88%) infants had 1-year follow-up. 59 of the 203 infants with known survival status (29%, 95% CI 23% to 36%) died within 1 year of the decision to intervene surgically. Following adjustment, key factors associated with reduced 1-year mortality included older gestational age at birth (adjusted OR (aOR) 0.87, 95% CI 0.78 to 0.96). Being small for gestational age (SGA) (aOR 3.6, 95% CI 1.4 to 9.5) and requiring parenteral nutrition at 28 days post-decision to intervene surgically (aOR 3.5, 95% CI 1.1 to 11.03) were associated with increased 1-year mortality.ConclusionsParents of infants undergoing surgery for NEC should be counselled that there is approximately a 1:3 risk of death in the first post-operative year but that the risk is lower for infants who are of greater gestational age at birth, who are not SGA and who do not require parenteral nutrition at 28 days post-intervention.
Is living in a gas-flaring host community associated with being hypertensive? Evidence from the Niger Delta region of Nigeria
Authors: Maduka Omosivie , Tobin-West Charles 
Published: November 2017

BackgroundResearchers have linked gas flaring to climate change, the hastening of the epidemiological transition and an upsurge in the prevalence of non-communicable diseases. We sought to determine if a relationship exists between residing in a gas-flaring host community and hypertension.MethodsWe conducted an analytical cross-sectional household survey among residents of 600 households in three gas-flaring and three non-gas-flaring host communities in the Niger Delta region of Nigeria. We took geo-coordinates, administered a modified WHO-STEPS questionnaire and built on Android mobile phones using Open-Data-Kit (ODK) software. We also took biological measurements and carried out descriptive and inferential statistical analysis using SPSS and STATA.ResultsWe interviewed a total of 912 adults: 437 (47.9%) from non-gas-flaring and 475 (52.1%) from gas-flaring host communities. There were differences in level of education (x2=42.99; p=0.00), occupation category (x2=25.42; p=0.00) and BMI category (x2=15.37; 0.003) among the two groups. The overall prevalence of hypertension was 23.7%: 20.7% among persons living in non-gas-flaring host communities compared with 25.3% among persons living in gas-flaring host communities (x2=2.89; p=0.89). Residence in a gas-flaring host community, (AdjOR=1.75; 95% CI=1.11 to 2.74) and mean age (AdjOR=1.05; 95% CI=1.03 to 1.07) were identified as the predictors of hypertension. There was a significant association between hypertension and age, 1.05 (1.04–1.06) while the probability of being hypertensive was higher among residents of gas-flaring host communities between 20 to 40 years and 60 to 80 years.ConclusionThere is a need for the relevant agencies to scale up environmental and biological monitoring of air pollutants. The implication of a possible relationship between gas-flaring and hypertension brings to the fore the need for interventions to regulate gas-flaring activities.
Patient preference and choice of healthcare providers in Shanghai, China: a cross-sectional study
Authors: Yu Wenya , Li Meina , Ye Feng , Xue Chen , Zhang Lulu 
Published: November 2017

ObjectivesThis study aimed to assess patients’ healthcare-seeking preferences in mild, chronic, and serious illness; identify influential factors; and examine the reasons underlying patients’ healthcare-seeking preference.DesignA retrospective study.SettingThe study was conducted in 14 tertiary hospitals in Shanghai, China.ParticipantsQuestionnaires were distributed to 1519 patients, and 1114 were completed and returned. All patients participated in the study voluntarily, provided written informed consent, and possessed the ability to complete the questionnaire.Main outcome measuresWe measured and compared preferences and choice of healthcare providers in patients if they had experienced mild, chronic, or serious illness.ResultsMore than 50% of participants, including those who were >60 years of age, had consulted a doctor more than three times during the preceding year, were single, and were most likely to decide not to seek medical treatment. Community health facilities were the most frequently selected healthcare provider in mild illness. In addition, patients who had no personal preference, did not express a preference for a good environment or first-class medical technology, were concerned about close proximity and short waiting times, and pursued low medical costs were most likely to choose a community health facility. General hospitals were the most frequently selected healthcare provider in chronic and serious illness. In addition, patients who earned higher monthly incomes, did not pursue low medical costs, were not concerned about short waiting times or close proximity, and expressed a preference for first-class medical technology, were most likely to choose general hospitals.ConclusionPatients’ healthcare-seeking preference was influenced mainly by healthcare providers’ characteristics, illness severity, and sociodemographic characteristics. These findings indicate that patients’ current healthcare-seeking preference was not ideal and requires optimisation.
Markers of pubertal timing and leisure-time physical activity from ages 36 to 68 years: findings from a British birth cohort
Authors: Elhakeem Ahmed , Cooper Rachel , Bann David , Kuh Diana , Hardy Rebecca 
Published: November 2017

ObjectivesWe aimed to examine associations between markers of pubertal timing and leisure-time physical activity (LTPA) from ages 36 to 68 years in men and women from the Medical Research Council National Survey of Health and Development.Study designPubertal timing was ascertained by physicians at age 14–15 years. Boys were grouped, based on their secondary sexual characteristics, as prepubescent, in early-stage puberty, advanced stage puberty or fully mature at age 14–15 years. Girls were grouped as reaching menarche ≤11, 12, 13 or ≥14 years. LTPA was reported at ages 36, 43, 53, 60–64 and 68 years and classified as active or inactive at each age. Associations were examined using standard and mixed-effects logistic regression models.ResultsOf 5362 singleton births recruited, 1499 men and 1409 women had at least one measure of LTPA and data on pubertal timing and selected covariates. When compared with men that were fully mature at age 14–15 years, those that were in advanced stage and early-stage puberty, but not the prepubescent stage, had lower likelihood of LTPA at younger but not older adult ages (p=0.06 for pubertal status-by-age at LTPA interaction in mixed-effects model). For example, fully adjusted ORs of LTPA (vs no LTPA) at ages 36 and 68 years, respectively, for advanced puberty versus fully mature were 0.69 (95% CIs 0.50 to 0.96) and 1.03 (0.72 to 1.47). Age at menarche was not associated with LTPA at any age (pinteractionwith age at LTPA=0.9). For example, OR (from mixed-effects model) of LTPA between 36 and 68 years was 1.23 (0.93, 1.63) for menarche at 13 vs ≤11 years.ConclusionsIn a nationally representative study, there was little evidence to suggest that pubertal timing was an important correlate of LTPA between ages 36 and 68 years. Maturity-related variations in adolescents’ LTPA may be transitory and lose importance over time.
Physiotherapy and physical activity: a cross-sectional survey exploring physical activity promotion, knowledge of physical activity guidelines and the physical activity habits of UK physiotherapists
Authors: Lowe Anna , Littlewood Chris , McLean Sionnadh , Kilner Karen 
Published: November 2017

ObjectivePhysical inactivity is a public health priority and embedding promotion of physical activity (PA) within healthcare systems is an important lever for change. Many factors influence PA promotion in routine healthcare practice; these include the PA habits of healthcare professionals and also their knowledge of the PA guidelines. Little is known about the extent to which PA is currently promoted in physiotherapy practice or the factors that influence it.MethodsFollowing ethical approval, a cross-sectional survey of UK physiotherapists was conducted. Findings were analysed and reported in accordance with STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines.ResultsThere were 522 respondents, 514 of whom were physiotherapists. Seventy-seven per cent of respondents routinely discussed PA with patients and 68% routinely delivered brief interventions. Assessment of PA status was not routine practice, neither was signposting to further sources of PA support. Only 16% of respondents correctly answered questions about the content of the PA guidelines. Only 38% of respondents met current PA recommendations. Clinicians' PA levels were not associated with PA promotion activity.ConclusionDespite the promising finding that some form of PA promotion is integrated into most respondents' practice, we report a poor understanding of brief interventions and poor knowledge of the PA guidelines. Additionally, the majority of respondents were not sufficiently active to meet current PA recommendations.
Trial registration and adherence to reporting guidelines in cardiovascular journals
Authors: Sims Matt Thomas , Bowers Aaron Marc , Fernan Jamie Morgan , Dormire Kody Duane , Herrington James Murphy , Vassar Matt 
Published: November 2017

ObjectiveThis study investigated the policies of cardiac and cardiovascular system journals concerning clinical trial registration and guideline adoption to understand how frequently journals use these mechanisms to improve transparency, trial reporting and overall study quality.MethodsWe selected the top 20 (by impact factor) journals cited in the subcategory ‘Cardiac and Cardiovascular Systems’ of the Expanded Science Citation Index of the 2014 Journal Citation Reports to extract journal policies concerning the 17 guidelines we identified. In addition, trial and systematic review registration adherence statements were extracted. 300 randomised controlled trials published in 2016 in the top 20 journals were searched for clinical trial registry numbers and CONSORT diagrams.ResultsOf the 19 cardiac and cardiovascular system journals included in our analysis, eight journals (42%) did not require or recommend trial or review registration. Seven (37%) did not recommend or require a single guideline within their instructions to authors. Consolidated Standards for Reporting Trials guidelines (10/19, 53%) were recommended or required most often. Of the trials surveyed, 122/285 (42.8%) published a CONSORT diagram in their manuscript, while 236/292 (80.8%) published a trial registry number.DiscussionCardiac and cardiovascular system journals infrequently require, recommend or enforce the use of reporting guidelines. Furthermore, too few require or enforce the use of clinical trial registration. Cardiology journal editors should consider guideline adoption due to their potential to limit bias and increase transparency.
Shadow state encoding for efficient monitoring of block-level properties
Authors: Vorobyov Kostyantyn , Signoles Julien , Kosmatov Nikolai 
Published: November 2017

Memory shadowing associates addresses from an application's memory to values stored in a disjoint memory space called shadow memory. At runtime shadow values store metadata about application memory locations they are mapped to. Shadow state encodings -- the structure of shadow values and their interpretation -- vary across different tools. Encodings used by the state-of-the-art monitoring tools have been proven useful for tracking memory at a byte-level, but cannot address properties related to memory block boundaries. Tracking block boundaries is however crucial for spatial memory safety analysis, where a spatial violation such as out-of-bounds access, may dereference an allocated location belonging to an adjacent block or a different struct member.
This paper describes two novel shadow state encodings which capture block-boundary-related properties. These encodings have been implemented in E-ACSL - a runtime verification tool for C programs. Initial experiments involving checking validity of pointer and array accesses in computationally intensive runs of programs selected from SPEC CPU benchmarks demonstrate runtime and memory overheads comparable to state-of-the-art memory debuggers.
RTHMS: a tool for data placement on hybrid memory system
Authors: Peng Ivy Bo , Gioiosa Roberto , Kestor Gokcen , Cicotti Pietro , Laure Erwin , Markidis Stefano 
Published: November 2017

Traditional scientific and emerging data analytics applications require fast, power-efficient, large, and persistent memories. Combining all these characteristics within a single memory technology is expensive and hence future supercomputers will feature different memory technologies side-by-side. However, it is a complex task to program hybrid-memory systems and to identify the best object-to-memory mapping. We envision that programmers will probably resort to use default configurations that only require minimal interventions on the application code or system settings. In this work, we argue that intelligent, fine-grained data placement can achieve higher performance than default setups.
We present an algorithm for data placement on hybrid-memory systems. Our algorithm is based on a set of single-object allocation rules and global data placement decisions. We also present RTHMS, a tool that implements our algorithm and provides recommendations about the object-to-memory mapping. Our experiments on a hybrid memory system, an Intel Knights Landing processor with DRAM and HBM, show that RTHMS is able to achieve higher performance than the default configuration. We believe that RTHMS will be a valuable tool for programmers working on complex hybrid-memory systems.
Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex
Authors: Neves Ricardo M. , van Keulen Silvia , Yang Mingyu , Logothetis Nikos K. , Eschenko Oxana 
Published: November 2017

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30–90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α2-adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.
A Containerized Software System for Generation, Management, and Exploration of Features from Whole Slide Tissue Images
Authors: Saltz Joel , Sharma Ashish , Iyer Ganesh , Bremer Erich , Wang Feiqiao , Jasniewski Alina , DiPrima Tammy , Almeida Jonas S. , Gao Yi , Zhao Tianhao , Saltz Mary , Kurc Tahsin 
Published: November 2017

Abstract
Well-curated sets of pathology image features will be critical to clinical studies that aim to evaluate and predict treatment responses. Researchers require information synthesized across multiple biological scales, from the patient to the molecular scale, to more effectively study cancer. This article describes a suite of services and web applications that allow users to select regions of interest in whole slide tissue images, run a segmentation pipeline on the selected regions to extract nuclei and compute shape, size, intensity, and texture features, store and index images and analysis results, and visualize and explore images and computed features. All the services are deployed as containers and the user-facing interfaces as web-based applications. The set of containers and web applications presented in this article is used in cancer research studies of morphologic characteristics of tumor tissues. The software is free and open source. Cancer Res; 77(21); e79–82. ©2017 AACR.