bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise‐related severe cardiac events
Authors: Vicent L. , Ariza‐Solé A. , González‐Juanatey J. R. , Uribarri A. , Ortiz J. , López de Sá E. , Sans‐Roselló J. , Querol C. T. , Codina P. , Sousa‐Casasnovas I. , Martínez‐Sellés M. ,   the Cardiac Arrest and Myocardial Infarction Notified After Marathon Or Similar effort (CAMINAMOS) registry
Published: December 2017

Physical activity has benefits on health. However, there is a small risk of effort‐related adverse events. The aim of this study is to describe exercise‐related severe cardiovascular events and to relate them with the type of sport performed. We performed a ten‐year retrospective study in eight Spanish cardiac intensive care units. Adverse cardiac events were defined as acute myocardial infarction, cardiac arrest or syncope related to physical activity. From 117 patients included, 109 were male (93.2%), and mean age was 51.6 ± 12.3 years; 56 presented acute myocardial infarction without cardiac arrest (47.9%), 55 sudden cardiac death (47.0%) and six syncope (5.1%). The sports with higher number of events were cycling (33%‐28.2%), marathon or similar running competitions (19%‐16.2%), gymnastics (18%‐15.3%) and soccer (17%‐14.5%). Myocardial infarction was observed more frequently in cyclists compared to other sports (69.7% vs 39.3%, P = .001). The most common cause of sudden cardiac death was myocardial infarction in those >35 years (23%‐63.9%) and idiopathic ventricular fibrillation in younger patients (5%‐62.5%). Significant coronary artery disease was present in 85 (79.4%). Only one patient with cardiac arrest presented with a non‐shockable rhythm (asystole). Eleven patients (9.4%) died during hospitalization; in all cases, they had presented cardiac arrest. All discharged patients were alive at the end of follow‐up. Exercise‐related severe cardiac events are mainly seen in men. Coronary heart disease is very frequent; about half present acute myocardial infarction and the other half cardiac arrest. In our cohort, prognosis was good in patients without cardiac arrest.
Grandparent support and mental and behavioural health in middle childhood
Authors: Van Heerden Ashley , Wild Lauren G. 
Published: December 2017

AbstractThis study explored the significance of grandparents in middle childhood and assessed the level of grandparental support provided to children in relation to other social network members. The association between grandparental support and grandchildren's mental and behavioural health was also examined. We conducted structured interviews with 120 grade 4 and 5 learners (mean age = 10.41 years) from four schools in Cape Town, South Africa. Results indicated that subsequent to parents, children perceived grandparents as the most important and close relationship category. Furthermore, grandparents provided the highest levels of support to grandchildren after parents. Grandmothers provided more support than grandfathers. No associations between grandparental support and children's internalizing and externalizing behaviours were found. However, results revealed that grandparental support was positively associated with children's prosocial behaviour, independent of child gender, and the amount of support provided by other relationship categories (p = .04). Findings underscore a need for research to move beyond the nuclear family when considering potential influences on children's well‐being.
Influence of soil phosphorus status, texture,pHand metal content on the efficacy of amendments to pig slurry in reducing phosphorus losses
Authors: O’ Flynn C. J. , Fenton O. , Wall D. , Brennan R. B. , McLaughlin M. J. , Healy M. G. 
Published: December 2017

AbstractCost‐effective strategies for using chemically amended organic fertilizers need to be developed to minimize nutrient losses in surface and groundwater. Coupling specific soil physical and chemical characteristics with amendment type could increase their effectiveness. This study investigated how water‐extractable phosphorus (P) was affected by chemical amendments added to pig slurry and how this effect varied with soil properties. A 3‐month incubation study was conducted on 18 different mineral soils, stored at 10 °C and 75% humidity and treated with unamended and amended slurry which was incorporated at a rate equivalent to 19 kg total P (TP)/ha. The amendments examined were commercial‐grade liquid alum, applied at a rate of 0.88:1 [Al:TP], and commercial‐grade liquid poly‐aluminium chloride (PAC), applied at a rate of 0.72:1 [Al:TP]. These amendments were previously identified by the authors as being effective in reducing incidental losses of P. The efficacy of the amendments varied with the soil test P, the degree of P saturation (DPS) and the Mehlich aluminium, iron and calcium, but not soil texture. Chemical amendments were most effective in soils withDPSover approximately 20%. Due to their high cost, the incorporation of amendments into existing management practices can only be justified as part of a holistic management plan where soils have highDPS.
Exchange rate jumps and exports: Evidence from China
Authors: Li Guangzhong , Li Jie , Zhu Jiaqing 
Published: December 2017

AbstractWe apply the autoregressive conditional jump intensity (ARJI) model to monthly exchange rate returns of China against 81 countries and investigate the impact of exchange rate volatility on exports over the period of 1995–2004. We decompose bilateral exchange rate volatility into continuous and discrete components and find that only the discrete part of exchange rate volatility, that is, the exchange rate jumps, has a significantly negative effect on exports, which to some extent reconciles the old yet unsettled debate in previous literature on the role of exchange rate volatility in international trade. There is also some evidence suggesting that the development of domestic financial market will boost international trade, but it does not help attenuate the negative effect of bilateral exchange rate jump risk on exports.
Waltzing around Sacred Cows on the Way to the Future
Authors: Brecher Stephen M. 
Published: December 2017

ABSTRACT

Our mostly manual, agar-based clinical microbiology laboratory is slowly but steadily being redefined by automation and innovation. Ironically, the oldest test, the Gram stain test, is still manually read and interpreted by trained personnel. In a proof-of-concept study, Smith et al. (J. Clin. Microbiol. 56:e01521-17, 2018,
https://doi.org/10.1128/JCM.01521-17
) used computer imaging with a deep convolutional neural network to examine and interpret Gram-stained slides from positive blood culture bottles. In light of the shortage of medical technologists/microbiologists and the need for results from positive blood culture bottles 24/7, this paper paves the way for the next innovations for the clinical microbiology laboratory of the future.
The Three-Fold Axis of the HIV-1 Capsid Lattice Is the Species-Specific Binding Interface for TRIM5α
Authors: Morger Damien , Zosel Franziska , Bühlmann Martin , Züger Sara , Mittelviefhaus Maximilian , Schuler Benjamin , Luban Jeremy , Grütter Markus G. 
Published: December 2017

ABSTRACT

Rhesus TRIM5α (rhTRIM5α) potently restricts replication of human immunodeficiency virus type 1 (HIV-1). Restriction is mediated through direct binding of the C-terminal B30.2 domain of TRIM5α to the assembled HIV-1 capsid core. This host-pathogen interaction involves multiple capsid molecules within the hexagonal HIV-1 capsid lattice. However, the molecular details of this interaction and the precise site at which the B30.2 domain binds remain largely unknown. The human orthologue of TRIM5α (hsTRIM5α) fails to block infection by HIV-1 both
in vivo
and
in vitro
. This is thought to be due to differences in binding to the capsid lattice. To map the species-specific binding surface on the HIV-1 capsid lattice, we used microscale thermophoresis and dual-focus fluorescence correlation spectroscopy to measure binding affinity of rhesus and human TRIM5α B30.2 domains to a series of HIV-1 capsid variants that mimic distinct capsid arrangements at each of the symmetry axes of the HIV-1 capsid lattice. These surrogates include previously characterized capsid oligomers, as well as a novel chemically cross-linked capsid trimer that contains cysteine substitutions near the 3-fold axis of symmetry. The results demonstrate that TRIM5α binding involves multiple capsid molecules along the 2-fold and 3-fold interfaces between hexamers and indicate that the binding interface at the 3-fold axis contributes to the well-established differences in restriction potency between TRIM5α orthologues.

IMPORTANCE
TRIM5α is a cellular protein that fends off infection by retroviruses through binding to the viruses' protein shell surrounding its genetic material. This shell is composed of several hundred capsid proteins arranged in a honeycomb-like hexagonal pattern that is conserved across retroviruses. By binding to the complex lattice formed by multiple capsid proteins, rather than to a single capsid monomer, TRIM5α restriction activity persists despite the high mutation rate in retroviruses such as HIV-1. In rhesus monkeys, but not in humans, TRIM5α confers resistance to HIV-1. By measuring the binding of human and rhesus TRIM5α to a series of engineered HIV-1 capsid mimics of distinct capsid lattice interfaces, we reveal the HIV-1 capsid surface critical for species-specific binding by TRIM5α.
HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E
Authors: Chikata Takayuki , Tran Giang Van , Murakoshi Hayato , Akahoshi Tomohiro , Qi Ying , Naranbhai Vivek , Kuse Nozomi , Tamura Yoshiko , Koyanagi Madoka , Sakai Sachiko , Nguyen Dung Hoai , Nguyen Dung Thi , Nguyen Ha Thu , Nguyen Trung Vu , Oka Shinichi , Martin Maureen P. , Carrington Mary , Sakai Keiko , Nguyen Kinh Van , Takiguchi Masafumi 
Published: December 2017

ABSTRACT
HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control.

IMPORTANCE
Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1 subtype A/E infection which are different from those identified for cohorts infected with HIV-1 subtypes B and C.
Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication
Authors: Zou Wei , Wang Zekun , Xiong Min , Chen Aaron Yun , Xu Peng , Ganaie Safder S. , Badawi Yomna , Kleiboeker Steve , Nishimune Hiroshi , Ye Shui Qing , Qiu Jianming 
Published: December 2017

ABSTRACT
Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication.

IMPORTANCE
Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly associated with the replicating single-stranded DNA viral genome and played a critical role in viral DNA replication. In contrast, the DNA damage response-induced phosphorylated forms of RPA32 were dispensable for viral DNA replication.
Human Cytomegalovirus UL111A and US27 Gene Products Enhance the CXCL12/CXCR4 Signaling Axis via Distinct Mechanisms
Authors: Tu Carolyn C. , Arnolds Kathleen L. , O'Connor Christine M. , Spencer Juliet V. 
Published: December 2017

ABSTRACTHuman cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12. Calcium flux and chemotaxis to CXCL12 were significantly greater in the presence of cmvIL-10 in monocytes, epithelial cells, and fibroblasts that express CXCR4. cmvIL-10 effects on CXCL12/CXCR4 signaling required the IL-10 receptor and Stat3 activation. Heightened signaling occurred both in HCMV-infected cells and in uninfected bystander cells, suggesting that cmvIL-10 may broadly influence chemokine networks by paracrine signaling during infection. Moreover, CXCL12/CXCR4 signaling was amplified in HCMV-infected cells compared to mock-infected cells even in the absence of cmvIL-10. Enhanced CXCL12/CXCR4 outcomes were associated with expression of the virally encoded chemokine receptor US27, and CXCL12/CXCR4 activation was reduced in cells infected with a deletion mutant lacking US27 (TB40/E-mCherry-US27Δ). US27 effects were Stat3 independent but required close proximity to CXCR4 in cell membranes of either HCMV-infected or US27-transfected cells. Thus, HCMV encodes two proteins, cmvIL-10 and US27, that exhibit distinct mechanisms for enhancing CXCR4 signaling. Either individually or in combination, cmvIL-10 and US27 may enable HCMV to exquisitely manipulate CXCR4 signaling to alter host immune responses and modify cell trafficking patterns during infection.IMPORTANCEThe human chemokine system plays a central role in host defense, as evidenced by the many strategies devised by viruses for manipulating it. Human cytomegalovirus (HCMV) is widespread in the human population, but infection rarely causes disease except in immunocompromised hosts. We found that two different HCMV proteins, cmvIL-10 and US27, act through distinct mechanisms to upregulate the signaling activity of a cellular chemokine receptor, CXCR4. cmvIL-10 is a secreted viral cytokine that affects CXCR4 signaling in both infected and uninfected cells, while US27 is a component of the virus particle and impacts CXCR4 activity only in infected cells. Both cmvIL-10 and US27 promote increased intracellular calcium signaling and cell migration in response to chemokine CXCL12 binding to CXCR4. Our results demonstrate that HCMV exerts fine control over the CXCL12/CXCR4 pathway, which could lead to enhanced virus dissemination, altered immune cell trafficking, and serious health implications for HCMV patients.
Importance of Core Genome Functions for an Extreme Antibiotic Resistance Trait
Authors: Gallagher Larry A. , Lee Samuel A. , Manoil Colin 
Published: December 2017

ABSTRACT

Extreme antibiotic resistance in bacteria is associated with the expression of powerful inactivating enzymes and other functions encoded in accessory genomic elements. The contribution of core genome processes to high-level resistance in such bacteria has been unclear. In the work reported here, we evaluated the relative importance of core and accessory functions for high-level resistance to the aminoglycoside tobramycin in the nosocomial pathogen
Acinetobacter baumannii
. Three lines of evidence establish the primacy of core functions in this resistance. First, in a genome scale mutant analysis using transposon sequencing and validation with 594 individual mutants, nearly all mutations reducing tobramycin resistance inactivated core genes, some with stronger phenotypes than those caused by the elimination of aminoglycoside-inactivating enzymes. Second, the core functions mediating resistance were nearly identical in the wild type and a deletion mutant lacking a genome resistance island that encodes the inactivating enzymes. Thus, most or all of the core resistance determinants important in the absence of the enzymes are also important in their presence. Third, reductions in tobramycin resistance caused by different core mutations were additive, and highly sensitive double and triple mutants (with 250-fold reductions in the MIC) that retained accessory resistance genes could be constructed. Core processes that contribute most strongly to intrinsic tobramycin resistance include phospholipid biosynthesis, phosphate regulation, and envelope homeostasis.

IMPORTANCE
The inexorable increase in bacterial antibiotic resistance threatens to undermine many of the procedures that transformed medicine in the last century. One strategy to meet the challenge antibiotic resistance poses is the development of drugs that undermine resistance. To identify potential targets for such adjuvants, we identified the functions underlying resistance to an important class of antibiotics for one of the most highly resistant pathogens known.
Disabling a Type I-E CRISPR-Cas Nuclease with a Bacteriophage-Encoded Anti-CRISPR Protein
Authors: Pawluk April , Shah Megha , Mejdani Marios , Calmettes Charles , Moraes Trevor F. , Davidson Alan R. , Maxwell Karen L. 
Published: December 2017

ABSTRACT
CRISPR (clustered regularly interspaced short palindromic repeat)-Cas adaptive immune systems are prevalent defense mechanisms in bacteria and archaea. They provide sequence-specific detection and neutralization of foreign nucleic acids such as bacteriophages and plasmids. One mechanism by which phages and other mobile genetic elements are able to overcome the CRISPR-Cas system is through the expression of anti-CRISPR proteins. Over 20 different families of anti-CRISPR proteins have been described, each of which inhibits a particular type of CRISPR-Cas system. In this work, we determined the structure of type I-E anti-CRISPR protein AcrE1 by X-ray crystallography. We show that AcrE1 binds to the CRISPR-associated helicase/nuclease Cas3 and that the C-terminal region of the anti-CRISPR protein is important for its inhibitory activity. We further show that AcrE1 can convert the endogenous type I-E CRISPR system into a programmable transcriptional repressor.

IMPORTANCE
The CRISPR-Cas immune system provides bacteria with resistance to invasion by potentially harmful viruses, plasmids, and other foreign mobile genetic elements. This study presents the first structural and mechanistic insight into a phage-encoded protein that inactivates the type I-E CRISPR-Cas system in
Pseudomonas aeruginosa
. The interaction of this anti-CRISPR protein with the CRISPR-associated helicase/nuclease proteins Cas3 shuts down the CRISPR-Cas system and protects phages carrying this gene from destruction. This interaction also allows the repurposing of the endogenous type I-E CRISPR system into a programmable transcriptional repressor, providing a new biotechnological tool for genetic studies of bacteria encoding this type I-E CRISPR-Cas system.