bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence and Structural Characterization of Great Salt Lake Bacteriophage CW02, a Member of the T7-Like Supergroup
Authors: Shen Peter S. , Domek Matthew J. , Sanz-García Eduardo , Makaju Aman , Taylor Ryan M. , Hoggan Ryan , Culumber Michele D. , Oberg Craig J. , Breakwell Donald P. , Prince John T. , Belnap David M. 
Published: May 2012

ABSTRACT

Halophage CW02 infects a
Salinivibrio costicola
-like bacterium, SA50, isolated from the Great Salt Lake. Following isolation, cultivation, and purification, CW02 was characterized by DNA sequencing, mass spectrometry, and electron microscopy. A conserved module of structural genes places CW02 in the T7 supergroup, members of which are found in diverse aquatic environments, including marine and freshwater ecosystems. CW02 has morphological similarities to viruses of the
Podoviridae
family. The structure of CW02, solved by cryogenic electron microscopy and three-dimensional reconstruction, enabled the fitting of a portion of the bacteriophage HK97 capsid protein into CW02 capsid density, thereby providing additional evidence that capsid proteins of tailed double-stranded DNA phages have a conserved fold. The CW02 capsid consists of bacteriophage lambda gpD-like densities that likely contribute to particle stability. Turret-like densities were found on icosahedral vertices and may represent a unique adaptation similar to what has been seen in other extremophilic viruses that infect archaea, such as
Sulfolobus
turreted icosahedral virus and halophage SH1.
Structural Analysis of Hepatitis C Virus Core-E1 Signal Peptide and Requirements for Cleavage of the Genotype 3a Signal Sequence by Signal Peptide Peptidase
Authors: Oehler Verena , Filipe Ana , Montserret Roland , da Costa Daniel , Brown Gaie , Penin François , McLauchlan John 
Published: May 2012

ABSTRACT
The maturation of the hepatitis C virus (HCV) core protein requires proteolytic processing by two host proteases: signal peptidase (SP) and the intramembrane-cleaving protease signal peptide peptidase (SPP). Previous work on HCV genotype 1a (GT1a) and GT2a has identified crucial residues required for efficient signal peptide processing by SPP, which in turn has an effect on the production of infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 signal peptide can be adapted to the GT3a sequence without affecting the production of infectious HCV. Through mutagenesis studies, we identified crucial residues required for core-E1 signal peptide processing, including a GT3a sequence-specific histidine (His) at position 187. In addition, the stable knockdown of intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers, further demonstrating the requirement for SPP for the maturation of core and the production of infectious HCV particles. Finally, our nuclear magnetic resonance (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 signal peptide provides an essential structural template for a further understanding of core processing as well as the first model for an SPP substrate within its membrane environment. Our findings give deeper insights into the mechanisms of intramembrane-cleaving proteases and the impact on viral infections.
The Interactome of the Human Respiratory Syncytial Virus NS1 Protein Highlights Multiple Effects on Host Cell Biology
Authors: Wu Weining , Tran Kim C. , Teng Michael N. , Heesom Kate J. , Matthews David A. , Barr John N. , Hiscox Julian A. 
Published: May 2012

ABSTRACT

Viral proteins can have multiple effects on host cell biology. Human respiratory syncytial virus (HRSV) nonstructural protein 1 (NS1) is a good example of this. During the virus life cycle, NS1 can act as an antagonist of host type I and III interferon production and signaling, inhibit apoptosis, suppress dendritic cell maturation, control protein stability, and regulate transcription of host cell mRNAs, among other functions. It is likely that NS1 performs these different roles through interactions with multiple host cell proteins. To investigate this and identify cellular proteins that could interact with NS1, we used quantitative proteomics in combination with green fluorescent protein (GFP)-trap immunoprecipitation and bioinformatic analysis. This analysis identified 221 proteins that were potentially part of complexes that could interact with NS1, with many of these associated with transcriptional regulation as part of the mediator complex, cell cycle regulation, and other functions previously assigned to NS1. Specific immunoprecipitation using the GFP trap was used to confirm the ability of selected cellular proteins to interact individually with NS1. Infection of A549 cells with recombinant viruses deficient in the expression of NS1 and overexpression analysis both demonstrated that NS1 was necessary and sufficient for the enrichment of cells in the G
1
phase of the cell cycle.
Expression of Human Endogenous Retrovirus Type K (HML-2) Is Activated by the Tat Protein of HIV-1
Authors: Gonzalez-Hernandez Marta J. , Swanson Michael D. , Contreras-Galindo Rafael , Cookinham Sarah , King Steven R. , Noel Richard J. , Kaplan Mark H. , Markovitz David M. 
Published: May 2012

ABSTRACT

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The expression of HERV-K (HML-2), the family of HERVs that most recently entered the genome, is tightly regulated but becomes markedly increased after infection with HIV-1. To better understand the mechanisms involved in this activation, we explored the role of the HIV-1 Tat protein in inducing the expression of these endogenous retroviral genes. Administration of recombinant HIV-1 Tat protein caused a 13-fold increase in HERV-K (HML-2)
gag
RNA transcripts in Jurkat T cells and a 10-fold increase in primary lymphocytes, and the expression of the HERV-K (HML-2)
rec
and
np9
oncogenes was also markedly increased. This activation was seen especially in lymphocytes and monocytic cells, the natural hosts for HIV-1 infection. Luciferase reporter gene assays demonstrated that the effect of Tat on HERV-K (HML-2) expression occurred at the level of the transcriptional promoter. The transcription factors NF-κB and NF-AT contribute to the Tat-induced activation of the promoter, as shown by chromatin immunoprecipitation assays, mutational analysis of the HERV-K (HML-2) long terminal repeat, and treatments with agents that inhibit NF-κB or NF-AT activation. These studies demonstrate that HIV-1 Tat plays an important role in activating expression of HERV-K (HML-2) in the setting of HIV-1 infection.
A CONSTRUCTION OF TRANSVERSELY NON-SIMPLE KNOT TYPES
Authors: MATSUDA HIROSHI 
Published: May 2012

For n = 1, 2 and 3, we construct a pair of transverse knots T1 and [Formula: see text], in the standard contact 3-sphere, satisfying the following properties: (1) the topological knot type of T1 is the same as that of [Formula: see text], (2) the self-linking number of T1 is equal to that of [Formula: see text], (3) [Formula: see text] is obtained from a transverse knot T2 by n stabilizations, and (4) T1 is not transversely isotopic to [Formula: see text].
rCUR: an R package for CUR matrix decomposition
Authors: Bodor András , Csabai István , Mahoney Michael W , Solymosi Norbert 
Published: May 2012

Abstract

Background
Many methods for dimensionality reduction of large data sets such as those generated in microarray studies boil down to the Singular Value Decomposition (SVD). Although singular vectors associated with the largest singular values have strong optimality properties and can often be quite useful as a tool to summarize the data, they are linear combinations of up to all of the data points, and thus it is typically quite hard to interpret those vectors in terms of the application domain from which the data are drawn. Recently, an alternative dimensionality reduction paradigm, CUR matrix decompositions, has been proposed to address this problem and has been applied to genetic and internet data. CUR decompositions are low-rank matrix decompositions that are explicitly expressed in terms of a small number of actual columns and/or actual rows of the data matrix. Since they are constructed from actual data elements, CUR decompositions are interpretable by practitioners of the field from which the data are drawn.

Results
We present an implementation to perform CUR matrix decompositions, in the form of a freely available, open source R-package called rCUR. This package will help users to perform CUR-based analysis on large-scale data, such as those obtained from different high-throughput technologies, in an interactive and exploratory manner. We show two examples that illustrate how CUR-based techniques make it possible to reduce significantly the number of probes, while at the same time maintaining major trends in data and keeping the same classification accuracy.

Conclusions
The package rCUR provides functions for the users to perform CUR-based matrix decompositions in the R environment. In gene expression studies, it gives an additional way of analysis of differential expression and discriminant gene selection based on the use of statistical leverage scores. These scores, which have been used historically in diagnostic regression analysis to identify outliers, can be used by rCUR to identify the most informative data points with respect to which to express the remaining data points.
Reliable structural interpretation of small-angle scattering data from bio-molecules in solution - the importance of quality control and a standard reporting framework
Authors: Jacques David A , Guss Jules Mitchell , Trewhella Jill 
Published: May 2012

Abstract
Small-angle scattering is becoming an increasingly popular tool for the study of bio-molecular structures in solution. The large number of publications with 3D-structural models generated from small-angle solution scattering data has led to a growing consensus for the need to establish a standard reporting framework for their publication. The International Union of Crystallography recently established a set of guidelines for the necessary information required for the publication of such structural models. Here we describe the rationale for these guidelines and the importance of standardising the way in which small-angle scattering data from bio-molecules and associated structural interpretations are reported.
Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study
Authors: Omar Ahmeddin H , Yasunami Michio , Yamazaki Akiko , Shibata Hiroki , Ofori Michael F , Akanmori Bartholomew D , Shuaibu Mohammed Nasir , Kikuchi Mihoko , Hirayama Kenji 
Published: May 2012

AbstractBackgroundIn areas mesoendemic for malaria transmission, symptomatic individuals play a significant role as reservoirs for malaria infection. Understanding the pathogenesis of symptomatic malaria is important in devising tools for augmenting malaria control. In this study, the effect of TLR9 polymorphisms on susceptibility to symptomatic malaria was investigated among Ghanaian children.MethodsFour hundred and twenty nine (429) healthy Ghanaian children, aged three to eleven years (3–11 years), were enrolled into a cohort study and actively followed up for symptomatic malaria for one year. Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct sequencing, and their attributable and relative risks for symptomatic malaria determined. TLR9 haplotypes were inferred using the PHASE software and analysed for the risk of symptomatic malaria. A luciferase assay was performed to investigate whether the TLR9 haplotypes influence TLR9 promoter activity.ResultsThe rs352139 GG genotype showed a significantly increased relative risk of 4.8 for symptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P = 0.04). Conversely, the rs352140 GG genotype showed a significantly reduced relative risk of 0.34 (P = 0.048). TLR9 haplotypes analyses showed that TTAG haplotype was significantly associated with reduced relative risk of 0.2 for symptomatic malaria (P = 4×10-6) and a lower mean parasitaemia (0.007), while CTGA haplotype had an increased relative risk of 3.3 (P = 0.005). Functional luciferase reporter gene expression assay revealed that the TTA haplotype had a significantly higher promoter activity than the CCG, CTG and TCG haplotypes.ConclusionsTaken together, these findings indicate a significant association of TLR9 gene polymorphisms with symptomatic malaria among Ghanaian children in Dangme-West district.
Effect of age and vaccination on extent and spread of Chlamydia pneumoniae infection in C57BL/6 mice
Authors: Eddens Taylor , Beaudoin Sarah , Steinberger Amanda , Little C Scott , Shell Dawn , Wizel Benjamin , Balin Brian , Fresa-Dillon Kerin L 
Published: May 2012

AbstractBackgroundChlamydia pneumoniaeis an obligate intracellular respiratory pathogen for humans. Infection byC. pneumoniaemay be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotesC. pneumoniaerespiratory infection and extra-respiratory spread in BALB/c mice.FindingsAged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection byChlamydia pneumoniaewhen compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting againstC. pneumoniaespread to the cardiovascular system of young mice, but failed to provide cardiovascular protection in aged animals.ConclusionsOur findings suggest that vaccine strategies that target the generation of aC. pneumoniae-specific CTL response can protect the respiratory system of both young and aged animals, but may not be adequate to prevent dissemination ofC. pneumoniaeto the cardiovascular system or control replication in those tissues in aged animals.
Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism
Authors: Churchward-Venne Tyler A , Burd Nicholas A , Phillips Stuart M 
Published: May 2012

Abstract
Provision of dietary amino acids increases skeletal muscle protein synthesis (MPS), an effect that is enhanced by prior resistance exercise. As a fundamentally necessary process in the enhancement of muscle mass, strategies to enhance rates of MPS would be beneficial in the development of interventions aimed at increasing skeletal muscle mass particularly when combined with chronic resistance exercise. The purpose of this review article is to provide an update on current findings regarding the nutritional regulation of MPS and highlight nutrition based strategies that may serve to maximize skeletal muscle protein anabolism with resistance exercise. Such factors include timing of protein intake, dietary protein type, the role of leucine as a key anabolic amino acid, and the impact of other macronutrients (i.e. carbohydrate) on the regulation of MPS after resistance exercise. We contend that nutritional strategies that serve to maximally stimulate MPS may be useful in the development of nutrition and exercise based interventions aimed at enhancing skeletal muscle mass which may be of interest to elderly populations and to athletes.
Multiple injuries after earthquakes: a retrospective analysis on 1,871 injured patients from the 2008 Wenchuan earthquake
Authors: Lu-Ping Zhao , Rodriguez-Llanes Jose Manuel , Qi Wu , van den Oever Barbara , Westman Lina , Albela Manuel , Liang Pan , Gao Chen , De-Sheng Zhang , Hughes Melany , von Schreeb Johan , Guha-Sapir Debarati 
Published: May 2012

Abstract
Introduction
Multiple injuries have been highlighted as an important clinical dimension of the injury profile following earthquakes, but studies are scarce. We investigated the pattern and combination of injuries among patients with two injuries following the 2008 Wenchuan earthquake. We also described the general injury profile, causes of injury and socio-demographic characteristics of the injured patients.

Methods
A retrospective hospital-based analysis of 1,871 earthquake injured patients, totaling 3,177 injuries, admitted between 12 and 31 May 2008 to the People's Hospital of Deyang city (PHDC). An electronic, webserver-based database with International Classification of Diseases (ICD)-10-based classification of earthquake-related injury diagnoses (IDs), anatomical sites and additional background variables of the inpatients was used. We analyzed this dataset for injury profile and number of injuries per patient. We then included all patients (856) with two injuries for more in-depth analysis. Possible spatial anatomical associations were determined a priori. Cross-tabulation and more complex frequency matrices for combination analyses were used to investigate the injury profile.

Results
Out of the 1,871 injured patients, 810 (43.3%) presented with a single injury. The rest had multiple injuries; 856 (45.8%) had two, 169 (9.0%) patients had three, 32 (1.7%) presented with four injuries, while only 4 (0.2%) were diagnosed with five injuries. The injury diagnoses of patients presenting with two-injuries showed important anatomical intra-site or neighboring clustering, which explained 49.1% of the combinations. For fractures, the result was even more marked as spatial clustering explained 57.9% of the association pattern. The most frequent combination of IDs was a double-fracture, affecting 20.7% of the two-injury patients (n = 177). Another 108 patients (12.6%) presented with fractures associated with crush injury and organ-soft tissue injury. Of the 3,177 injuries, 1,476 (46.5%) were fractures. Most injuries were located in the head (22.9%) and lower extremities (30.8%).

Conclusions
Multiple injuries are put forward as an important component of the injury profile after this earthquake. A pattern of injury combinations and spatial aggregation of injuries was also found. Clinical diagnosis and treatment should be adapted to care of these patients. More studies are needed to generalize these findings.
A disparity between physician attitudes and practice regarding hyperglycemia in pediatric intensive care units in the United States: a survey on actual practice habits
Authors: Preissig Catherine M , Rigby Mark R 
Published: May 2012

Abstract
Introduction
Hyperglycemia is common in critically ill patients and is associated with increased morbidity and mortality. Strict glycemic control improves outcomes in some adult populations and may have similar effects in children. While glycemic control has become standard care in adults, little is known regarding hyperglycemia management strategies used by pediatric critical care practitioners. We sought to assess both the beliefs and practice habits regarding glycemic control in pediatric intensive care units (ICUs) in the United States (US).

Methods
We surveyed 30 US pediatric ICUs from January to May 2009. Surveys were conducted by phone between the investigators and participating centers and consisted of a 22-point questionnaire devised to assess physician perceptions and center-specific management strategies regarding glycemic control.

Results
ICUs included a cross section of centers throughout the US. Fourteen out of 30 centers believe all critically ill hyperglycemic adults should be treated, while 3/30 believe all critically ill children should be treated. Twenty-nine of 30 believe some subsets of adults with hyperglycemia should be treated, while 20/30 believe some subsets of children should receive glycemic control. A total of 70%, 73%, 80%, 27%, and 40% of centers believe hyperglycemia adversely affects outcomes in cardiac, trauma, traumatic brain injury, general medical, and general surgical pediatric patients, respectively. However, only six centers use a standard, uniform approach to treat hyperglycemia at their institution. Sixty percent of centers believe hypoglycemia is more dangerous than hyperglycemia. Seventy percent listed fear of management-induced hypoglycemia as a barrier to glycemic control at their center.

Conclusions
Considerable disparity exists between physician beliefs and actual practice habits regarding glycemic control among pediatric practitioners, with few centers reporting the use of any consistent standard approach to screening and management. Physicians wishing to practice glycemic control in their critically ill pediatric patients may want to consider adopting center-wide uniform approaches to improve safety and efficacy of treatment.
Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry
Authors: Beale Richard , Janes Jonathan M , Brunkhorst Frank M , Dobb Geoffrey , Levy Mitchell M , Martin Greg S , Ramsay Graham , Silva Eliezer , Sprung Charles L , Vallet Benoit , Vincent Jean-Louis , Costigan Timothy M , Leishman Amy G , Williams Mark D , Reinhart Konrad 
Published: May 2012

Abstract
Introduction
The benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.

Methods
Patients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 μg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups.

Results
A total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47).

Conclusions
Widespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.