bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Expression and Translocation of the Ubiquitin Ligase SlrP in Salmonella enterica Serovar Typhimurium
Authors: Cordero-Alba Mar , Ramos-Morales Francisco 
Published: September 2014

ABSTRACT

SlrP is an E3 ubiquitin ligase that can be translocated into eukaryotic host cells by the two type III secretion systems that are expressed by
Salmonella enterica
serovar Typhimurium and are encoded in
Salmonella
pathogenicity islands 1 (SPI1) and 2 (SPI2). Expression of
slrP
and translocation of its product were examined using
lac
, 3×FLAG, and
cyaA
′ translational fusions. Although
slrP
was expressed in different media, optimal expression was found under conditions that imitate the intravacuolar environment and promote synthesis of the SPI2-encoded type III secretion system. Translocation into mammalian cells took place through the SPI1- or the SPI2-encoded type III secretion system, depending on specific host cell type and timing. A search for genetic factors involved in controlling the expression of
slrP
unveiled LeuO, Lon, and the two-component system PhoQ/PhoP as novel regulators of
slrP
. Our experiments suggest that LeuO and Lon act through HilD under SPI1-inducing conditions, whereas PhoP directly interacts with the
slrP
promoter to activate transcription under SPI2 inducing conditions.
Metabolic Engineering of Microorganisms for the Production of Higher Alcohols
Authors: Choi Yong Jun , Lee Joungmin , Jang Yu-Sin , Lee Sang Yup 
Published: September 2014

ABSTRACT
Due to the increasing concerns about limited fossil resources and environmental problems, there has been much interest in developing biofuels from renewable biomass. Ethanol is currently used as a major biofuel, as it can be easily produced by existing fermentation technology, but it is not the best biofuel due to its low energy density, high vapor pressure, hygroscopy, and incompatibility with current infrastructure. Higher alcohols, including 1-propanol, 1-butanol, isobutanol, 2-methyl-1-butanol, and 3-methyl-1-butanol, which possess fuel properties more similar to those of petroleum-based fuel, have attracted particular interest as alternatives to ethanol. Since microorganisms isolated from nature do not allow production of these alcohols at high enough efficiencies, metabolic engineering has been employed to enhance their production. Here, we review recent advances in metabolic engineering of microorganisms for the production of higher alcohols.
Wolbachia
Influences the Maternal Transmission of the
gypsy
Endogenous Retrovirus in Drosophila melanogaster
Authors: Touret Franck , Guiguen François , Terzian Christophe 
Published: September 2014

ABSTRACT

The endosymbiotic bacteria of the genus
Wolbachia
are present in most insects and are maternally transmitted through the germline. Moreover, these intracellular bacteria exert antiviral activity against insect RNA viruses, as in
Drosophila melanogaster
, which could explain the prevalence of
Wolbachia
bacteria in natural populations.
Wolbachia
is maternally transmitted in
D. melanogaster
through a mechanism that involves distribution at the posterior pole of mature oocytes and then incorporation into the pole cells of the embryos. In parallel, maternal transmission of several endogenous retroviruses is well documented in
D. melanogaster
. Notably,
gypsy
retrovirus is expressed in permissive follicle cells and transferred to the oocyte and then to the offspring by integrating into their genomes. Here, we show that the presence of
Wolbachia w
Mel reduces the rate of
gypsy
insertion into the
ovo
gene. However, the presence of
Wolbachia
does not modify the expression levels of
gypsy
RNA and envelope glycoprotein from either permissive or restrictive ovaries. Moreover,
Wolbachia
affects the pattern of distribution of the retroviral particles and the
gypsy
envelope protein in permissive follicle cells. Altogether, our results enlarge the knowledge of the antiviral activity of
Wolbachia
to include reducing the maternal transmission of endogenous retroviruses in
D. melanogaster
.

IMPORTANCE
Animals have established complex relationships with bacteria and viruses that spread horizontally among individuals or are vertically transmitted, i.e., from parents to offspring. It is well established that members of the genus
Wolbachia
, maternally inherited symbiotic bacteria present mainly in arthropods, reduce the replication of several RNA viruses transmitted horizontally. Here, we demonstrate for the first time that
Wolbachia
diminishes the maternal transmission of
gypsy
, an endogenous retrovirus in
Drosophila melanogaster
. We hypothesize that
gypsy
cannot efficiently integrate into the germ cells of offspring during embryonic development in the presence of
Wolbachia
because both are competitors for localization to the posterior pole of the egg. More generally, it would be of interest to analyze the influence of
Wolbachia
on vertically transmitted exogenous viruses, such as some arboviruses.
Origin Replication Complex Binding, Nucleosome Depletion Patterns, and a Primary Sequence Motif Can Predict Origins of Replication in a Genome with Epigenetic Centromeres
Authors: Tsai Hung-Ji , Baller Joshua A. , Liachko Ivan , Koren Amnon , Burrack Laura S. , Hickman Meleah A. , Thevandavakkam Mathuravani A. , Rusche Laura N. , Berman Judith 
Published: September 2014

ABSTRACT

Origins of DNA replication are key genetic elements, yet their identification remains elusive in most organisms. In previous work, we found that centromeres contain origins of replication (ORIs) that are determined epigenetically in the pathogenic yeast
Candida albicans
. In this study, we used origin recognition complex (ORC) binding and nucleosome occupancy patterns in
Saccharomyces cerevisiae
and
Kluyveromyces lactis
to train a machine learning algorithm to predict the position of active arm (noncentromeric) origins in the
C. albicans
genome. The model identified bona fide active origins as determined by the presence of replication intermediates on nondenaturing two-dimensional (2D) gels. Importantly, these origins function at their native chromosomal loci and also as autonomously replicating sequences (ARSs) on a linear plasmid. A “mini-ARS screen” identified at least one and often two ARS regions of ≥100 bp within each bona fide origin. Furthermore, a 15-bp AC-rich consensus motif was associated with the predicted origins and conferred autonomous replicating activity to the mini-ARSs. Thus, while centromeres and the origins associated with them are epigenetic, arm origins are dependent upon critical DNA features, such as a binding site for ORC and a propensity for nucleosome exclusion.

IMPORTANCE
DNA replication machinery is highly conserved, yet the definition of exactly what specifies a replication origin differs in different species. Here, we utilized computational genomics to predict origin locations in
Candida albicans
by combining locations of binding sites for the conserved origin replication complex, necessary for replication initiation, together with chromatin organization patterns. We identified predicted sequences that exhibited bona fide origin function and developed a linear plasmid assay to delimit the DNA fragments necessary for origin function. Additionally, we found that a short AC-rich motif, which is enriched in predicted origins, is required for origin function. Thus, we demonstrated a new machine learning paradigm for identification of potential origins from a genome with no prior information. Furthermore, this work suggests that
C. albicans
has two different types of origins: “hard-wired” arm origins that rely upon specific sequence motifs and “epigenetic” centromeric origins that are recruited to kinetochores in a sequence-independent manner.
All-cause and disease-specific mortality among male, former elite athletes: an average 50-year follow-up
Authors: Kettunen Jyrki A , Kujala Urho M , Kaprio Jaakko , Bäckmand Heli , Peltonen Markku , Eriksson Johan G , Sarna Seppo 
Published: September 2014

AimTo investigate life expectancy and mortality among former elite athletes and controls.MethodsHR analysis of cause-specific deaths sourced from the national death registry for former Finnish male endurance, team and power sports athletes (N=2363) and controls (N=1657). The median follow-up time was 50 years.ResultsMedian life expectancy was higher in the endurance (79.1 years, 95% CI 76.6 to 80.6) and team (78.8, 78.1 to 79.8) sports athletes than in controls (72.9, 71.8 to 74.3). Compared to controls, risk for total mortality adjusted for socioeconomic status and birth cohort was lower in the endurance ((HR 0.70, 95% CI 0.61 to 0.79)) and team (0.80, 0.72 to 0.89) sports athletes, and slightly lower in the power sports athletes (0.93, 0.85 to 1.03). HR for ischaemic heart disease mortality was lower in the endurance (0.68, 0.54 to 0.86) and team sports (0.73, 0.60 to 0.89) athletes. HR for stroke mortality was 0.52 (0.33 to 0.83) in the endurance and 0.59 (0.40 to 0.88) in the team sports athletes. Compared to controls, the risk for smoking-related cancer mortality was lower in the endurance (HR 0.20, 0.08 to 0.47) and power sports (0.40, 0.25 to 0.66) athletes. For dementia mortality, the power sports athletes, particularly boxers, had increased risk (HR 4.20, 2.30 to 7.81).ConclusionsElite athletes have 5–6 years additional life expectancy when compared to men who were healthy as young adults. Lower mortality for cardiovascular disease was in part due to lower rates of smoking, as tobacco-related cancer mortality was especially low.
Sedentary behaviour and the risk of depression: a meta-analysis
Authors: Zhai Long , Zhang Yi , Zhang Dongfeng 
Published: September 2014

BackgroundSedentary behaviour is associated with risk of depression. We review and quantitatively summarise the evidence from observational studies in a meta-analysis.MethodsWe searched the PubMed, Web of Knowledge, Chinese National Knowledge Infrastructure and Wanfang databases for observational studies related to the association of sedentary behaviour and depression risk up to 15 January 2014. Summary relative risks (RRs) were estimated by the use of a random effects model.ResultsThirteen cross-sectional studies with 110 152 participants and 11 longitudinal studies with 83 014 participants were included in this meta-analysis. The summary RR of depression for the highest versus non-occasional/occasional sedentary behaviour was 1.25 (95% CI 1.16 to 1.35, I2=50.7%) for all included studies. The pooled RRs of depression for sedentary behaviour were 1.31 (95% CI 1.16 to 1.48) in cross-sectional studies and 1.14 (95% CI 1.06 to 1.21) in longitudinal studies. In subgroup analysis by different types of sedentary behaviour, the pooled RRs of depression were 1.13 (95% CI 1.06 to 1.21) for long-time TV viewing and 1.22 (95% CI 1.10 to 1.34) for prolonged computer or internet use.ConclusionsThis meta-analysis of observational studies indicates that sedentary behaviour is associated with increased risk of depression.
Improving the quality of weekend handover at Yeovil District Hospital
Authors: Sneller Sarah , Lada Karolina , Turner Charlotte , Millwood Sinead , Jervis Bethan , Barr Julia , Farrell Louise 
Published: September 2014

Abstract“Handover of care is one of the most perilous procedures in medicine” (British Medical Association, Safe Handover, Safe Patients). The system in place for weekend handover at YDH was deemed disorganised, unstructured and frequently missing key pieces of information, leaving the on-call Foundation Year 1 (FY1) doctor with only vague jobs and management plans. Baseline surveys demonstrated that junior doctors felt the system was inadequate, potentially compromised patient safety and increased their stress levels.In order to improve this problem a structured weekend handover proforma was created, comparable with the “Out of hours handover record keeping standards: template” from the Royal College of Physicians. This was made readily accessible on the local intranet. Education sessions were organised for the FY1 and FY2 doctors. The impact of the newly introduced proforma was measured using feedback surveys each week from the FY1 on ward cover for six months. A further change implemented was the introduction of a Friday Ward Round proforma. The aim was to reduce the time required to review notes by the on-call doctor, to minimise avoidable weekend jobs and to improve compliance with the management plans.The results demonstrated 100% compliance with the new proformas. There were notable improvements in the presence of a plan (37.5% to 91.7%, max. 100%), a minimum of two patient identifiers (68.8% to 100%) and relevant background information (62.5% to 100%). Qualitative data showed a much higher level of satisfaction with the new system.Future plans include rolling out electronic handover to improve problems such as illegible handwriting and missing data (enable ‘compulsory’ fields), and also for this system to be implemented Trust-wide.
Neutrophil to lymphocyte count ratio as an early indicator of blood stream infection in the emergency department
Authors: Lowsby Richard , Gomes Clint , Jarman Ian , Lisboa Paulo , Nee Patrick A , Vardhan Madhur , Eckersley Tom , Saleh Roshan , Mills Hannah 
Published: September 2014

ObjectivesEarly identification of patients with blood stream infection (BSI), especially bacteraemia, is important as prompt treatment improves outcome. The initial stages of severe infection may be characterised by increased numbers of neutrophils in the peripheral blood and depression of the lymphocyte count (LC). The neutrophil to LC ratio (NLCR) has previously been compared with conventional tests, such as C-reactive protein (CRP) and white cell count (WCC), and has been proposed as a useful marker in the timely diagnosis of bacteraemia.MethodsData on consecutive adult patients presenting to the emergency department with pyrexial illness during the study period, November 2009 to October 2010, were analysed. The main outcome measure was positive blood cultures (bacteraemia). Sensitivity, specificity, positive and negative predictive values and likelihood ratios were determined for NLCR, CRP, WCC, neutrophil count and LC.Results1954 patients met the inclusion criteria. Blood cultures were positive in 270 patients, hence the prevalence of bacteraemia was 13.8%. With the exception of WCC, there were significant differences in the mean value for each marker between bacteraemic and non-bacteraemic patients (p<0.001). The area under the receiver operating characteristic curve was highest for NLCR (0.72; 95% CI 0.69 to 0.75) and LC (0.71; 0.68 to 0.74) and lowest for WCC (0.54; 0.40 to 0.57). The sensitivity and specificity of NLCR for predicting bacteraemia were 70% (64% to 75%) and 57% (55% to 60%), respectively. Positive and negative predictive values for NLCR were 0.20 (0.18 to 0.23) and 0.92 (0.91 to 0.94), respectively. The positive likelihood ratio was 1.63 (1.48 to 1.79) and the negative likelihood ratio was 0.53 (0.44 to 0.64).ConclusionsAlthough NLCR outperforms conventional markers of infection, it is insufficient in itself to guide clinical management of patients with suspected BSI, and it offers no advantage over LC. However, it may offer some diagnostic utility when taken into account as part of the overall assessment.
BRAF Inhibition Alleviates Immune Suppression in Murine Autochthonous Melanoma
Authors: Steinberg Shannon M. , Zhang Peisheng , Malik Brian T. , Boni Andrea , Shabaneh Tamer B. , Byrne Katelyn T. , Mullins David W. , Brinckerhoff Constance E. , Ernstoff Marc S. , Bosenberg Marcus W. , Turk Mary Jo 
Published: September 2014

Abstract
A growing body of evidence suggests that BRAF inhibitors, in addition to their acute tumor growth–inhibitory effects, can also promote immune responses to melanoma. The present study aimed to define the immunologic basis of BRAF-inhibitor therapy using the Braf/Pten model of inducible, autochthonous melanoma on a pure C57BL/6 background. In the tumor microenvironment, BRAF inhibitor PLX4720 functioned by on-target mechanisms to selectively decrease both the proportions and absolute numbers of CD4+Foxp3+ regulatory T cells (Treg) and CD11b+Gr1+ myeloid-derived suppressor cells (MDSC), while preserving numbers of CD8+ effector T cells. In PLX4720-treated mice, the intratumoral Treg populations decreased significantly, demonstrating enhanced apopotosis. CD11b+ myeloid cells from PLX4720-treated tumors also exhibited decreased immunosuppressive function on a per-cell basis. In accordance with a reversion of tumor immune suppression, tumors that had been treated with PLX4720 grew with reduced kinetics after treatment was discontinued, and this growth delay was dependent on CD8 T cells. These findings demonstrate that BRAF inhibition selectively reverses two major mechanisms of immunosuppression in melanoma and liberates host-adaptive antitumor immunity. Cancer Immunol Res; 2(11); 1044–50. ©2014 AACR.
NF-κB, an Active Player in Human Cancers
Authors: Xia Yifeng , Shen Shen , Verma Inder M. 
Published: September 2014

Abstract
NF-κB comprises a family of five transcription factors that form distinct protein complexes, which bind to consensus DNA sequences at promoter regions of responsive genes regulating cellular processes. The past three decades have witnessed remarkable progress in understanding the NF-κB signaling pathway in physiologic and pathologic conditions. The role of NF-κB in human cancer initiation, development, metastasis, and resistance to treatment has drawn particular attention. A significant number of human cancers have constitutive NF-κB activity due to the inflammatory microenvironment and various oncogenic mutations. NF-κB activity not only promotes tumor cells' proliferation, suppresses apoptosis, and attracts angiogenesis, but it also induces epithelial–mesenchymal transition, which facilitates distant metastasis. In certain circumstances, NF-κB activation may also remodel local metabolism and anergize the immune system to favor tumor growth. Suppression of NF-κB in myeloid cells or tumor cells usually leads to tumor regression, which makes the NF-κB pathway a promising therapeutic target. However, because of its vital role in various biologic activities, components of the NF-κB pathway need to be carefully selected and evaluated to design targeted therapies. Cancer Immunol Res; 2(9); 823–30. ©2014 AACR.
Prasugrel vs clopidogrel in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction
Authors: Morath Tanja , Bernlochner Isabell , Hadamitzky Martin , Braun Siegmund , Schulz Stefanie , Hoppmann Petra , Hausleiter Jörg , Tiroch Klaus , Mehilli Julinda , Schunkert Heribert , Massberg Steffen , Laugwitz Karl-Ludwig , Orban Martin , Mayer Katharina , Sibbing Dirk , Kastrati Adnan 
Published: September 2014

SummaryThere is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrelvs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29–0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.
Coated-Platelets Improve Prediction of Stroke and Transient Ischemic Attack in Asymptomatic Internal Carotid Artery Stenosis
Authors: Kirkpatrick Angelia C. , Tafur Alfonso J. , Vincent Andrea S. , Dale George L. , Prodan Calin I. 
Published: September 2014

Background and Purpose—
Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis.

Methods—
Three-hundred twenty-nine consecutive patients with technically adequate carotid Doppler evaluation without stroke or transient ischemic attack (TIA) in the previous 6 months were enrolled as part of a prospective cohort study conducted during a 40-month period. The main outcome was occurrence of stroke or TIA according to coated-platelet levels and internal carotid stenosis severity at enrollment. The optimal cutoff value of coated-platelet levels was determined by recursive partitioning analysis. Event-free survival was estimated using Kaplan–Meier and Cox proportional hazards regression analyses.

Results—

A cutoff of ≥45% for coated-platelet levels in combination with stenosis ≥50% yielded a sensitivity of 0.78 (95% confidence interval, 0.51–1.0), specificity of 0.92 (0.89–0.95), positive predictive value of 0.21 (0.07–0.34), and a negative predictive value of 0.99 (0.98–1.0) for ipsilateral stroke or TIA. The incidence rate of ipsilateral stroke or TIA for patients with ≥50% stenosis and ≥45% coated-platelets was 21.5 per 100 person-years versus 1.27 per 100 person-years for patients with ≥50% stenosis and <45% coated-platelets (
P
<0.0001).

Conclusions—
Coated-platelet levels identify asymptomatic carotid stenosis patients at high risk for stroke or TIA, which suggests a role for coated-platelets in risk stratification before revascularization.