bluuebunny/crossref_metadata_2025_split huggingface dataset:
α1‐Adrenergic responsiveness in human skeletal muscle feed arteries: the impact of reducing extracellular pH
Authors: Ives Stephen J. , Andtbacka Robert H. I. , Noyes R. Dirk , Morgan R. Garrett , Gifford Jayson R. , Park Song‐Young , Symons J. David , Richardson Russell S. 
Published: July 2012

New Findings
What is the central question of this study?In human arteries involved in the regulation of muscle blood flow, there is a lack of data about whether acidosis alters vascular sensitivity to vasoactive agents, as well as altering endothelium dependent vasorelaxation. Little is known about the interaction of metabolites and vascular function in human skeletal muscle feed arteries.
What is the main finding and its importance?Increasing acidosis attenuated the response and sensitivity of the arteries to phenylephrine; this effect was selective to the receptor over smooth muscle.Acidosis did not alter endothelium dependent vasorelaxation. Impaired vasoconstriction coupled with intact vasorelaxation, promotes decreased vascular tone with exposure to acidosis, and may contribute to sympatholysis during exercise.
Graded exercise results not only in the modulation of adrenergic mediated smooth muscle tone and a preferential increase in blood flow to the active skeletal muscle termed ‘functional sympatholysis’, but is also paralleled by metabolically induced reductions in pH. We therefore sought to determine whether pH attenuates α1‐adrenergic receptor sensitivity in human feed arteries. Feed arteries (560 ± 31 μm i.d.) were harvested from 24 humans (55 ± 4 years old) and studied using the isometric tension technique. Vessel function was assessed using KCl, phenylephrine (PE), ACh and sodium nitroprusside (SNP) concentration–response curves to characterize non‐receptor‐mediated and receptor‐mediated vasocontraction, as well as endothelium‐dependent and ‐independent vasorelaxation, respectively. All concentration–response curves were obtained from (originally contiguous) vessel rings in separate baths with a pH of 7.4, 7.1, 6.8 or 6.5. Reduction of the pH, via HCl, reduced maximal PE‐induced vasocontraction (pH 7.4 = 85 ± 19, pH 7.1 = 57 ± 16, pH 6.8 = 34 ± 15 and pH 6.5 = 16 ± 5% KClmax), which was partly due to reduced smooth muscle function, as assessed by KCl (pH 7.4 = 88 ± 13, pH 7.1 = 67 ± 8, pH 6.8 = 67 ± 9 and pH 6.5 = 58 ± 8% KClmax). Graded acidosis had no effect on maximal vasorelaxation. In summary, these data reveal that reductions in extracellular pH attenuate α1‐mediated vasocontraction, which is partly explained by reduced smooth muscle function, although vasorelaxation in response to ACh and SNP remained intact. These findings support the concept that local acidosis is likely to contribute to functional sympatholysis and exercise hyperaemia by opposing sympathetically mediated vasoconstriction while not impacting vasodilatation.
Effects of testosterone on cardiomyocyte calcium homeostasis and contractile function in female rats
Authors: Beesley Ronald D. , Palmer Bradley M. , Casson Peter R. , Toth Michael J. 
Published: July 2012

New Findings
What is the central question of this study?Androgen excess in women is associated with an elevated risk for heart disease. Whether some portion of this elevated risk is related to an effect of androgens on cariomyoctye function, however, has not been examined. To our knowledge, this is the first study to directly address the role of androgens in regulating cardiomyocyte contractile dynamics and calcium homeostasis.
What is the main finding and its importance?Our results suggest minimal acute or chronic effects of testosterone on cardiomyocyte shortening dynamics, calcium homeostasis or myosin heavy chain expression, suggesting that the detrimental effect of androgen excess on cardiovascular risk is not mediated through alterations in cardiomyocyte biology.
The role of testosterone (T) in the regulation of cardiovascular function in females is not well understood. Our goal was to examine the effect of T on cardiomyocyte biology by measuring sarcomere shortening/relaxation and intracellular calcium cycling in adult female Sprague–Dawley rats. The rats were divided into the following four groups: (1) sham operated; (2) ovariectomized (OVX); (3) OVX plus T; and (4) OVX + T plus an aromatase inhibitor (AI). The final group was added to rule out effects from bioconversion of T to oestradiol. Sarcomere/calcium dynamics were measured after 4 weeks at 2 and 6 Hz, then at 6 Hz following exposure to 300 nm isoprenaline. Additionally, the acute (i.e. non‐genomic) effects of T were evaluated in sham‐operated and OVX + T + AI rats. There were no group differences, nor was there evidence for an effect of T on frequency or isoprenaline response. Additionally, there were no findings to indicate an acute, non‐genomic T effect. Moreover, the relative α‐ and β‐myosin heavy chain isoform complement was unchanged by OVX or T replacement. Our results argue against acute or chronic effects of T on cardiomyocyte shortening dynamics, calcium cycling or myosin heavy chain expression, arguing against any direct effect of T on cardiomyocyte function in adult females.
Mapping the polysaccharide degradation potential of Aspergillus niger
Authors: Andersen Mikael R , Giese Malene , de Vries Ronald P , Nielsen Jens 
Published: July 2012

AbstractBackgroundThe degradation of plant materials by enzymes is an industry of increasing importance. For sustainable production of second generation biofuels and other products of industrial biotechnology, efficient degradation of non-edible plant polysaccharides such as hemicellulose is required. For each type of hemicellulose, a complex mixture of enzymes is required for complete conversion to fermentable monosaccharides. In plant-biomass degrading fungi, these enzymes are regulated and released by complex regulatory structures. In this study, we present a methodology for evaluating the potential of a given fungus for polysaccharide degradation.ResultsThrough the compilation of information from 203 articles, we have systematized knowledge on the structure and degradation of 16 major types of plant polysaccharides to form a graphical overview. As a case example, we have combined this with a list of 188 genes coding for carbohydrate-active enzymes fromAspergillus niger, thus forming an analysis framework, which can be queried. Combination of this information network with gene expression analysis on mono- and polysaccharide substrates has allowed elucidation of concerted gene expression from this organism. One such example is the identification of a full set of extracellular polysaccharide-acting genes for the degradation of oat spelt xylan.ConclusionsThe mapping of plant polysaccharide structures along with the corresponding enzymatic activities is a powerful framework for expression analysis of carbohydrate-active enzymes. Applying this network-based approach, we provide the first genome-scale characterization of all genes coding for carbohydrate-active enzymes identified inA. niger.
Making birthing safe for Pakistan women: a cluster randomized trial
Authors: Khan Muhammad Amir , Mirza Shirin , Ahmed Maqsood , Rasheed Akhtar , Khan Amanullah , Walley John , Nisar Nailah 
Published: July 2012

Abstract

Background
Two out of three neonatal deaths occur in just 10 countries and Pakistan stands third among them. Maternal mortality is also high with most deaths occurring during labor, birth, and first few hours after birth. Enhanced access and utilization of skilled delivery and emergency obstetric care is the demonstrated strategy in reducing maternal and neonatal mortality. This trial aims to compare reduction in neonate mortality and utilization of available safe birthing and Emergency Obstetric and Neonatal Care services among pregnant mothers receiving ‘structured birth planning’, and/or ‘transport facilitation’ compared to routine care.

Methods
A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Jhang, Chiniot and Khanewal districts of Punjab, Pakistan, from February 2011 to May 2013. At least 29,295 pregnancies will be registered in the three arms, seven clusters per arm; 1) structured birth planning and travel facilitation, 2) structured birth planning, and 3) control arm. Trial will be conducted through the Lady Health Worker program. Main outcomes are difference in neonatal mortality and service utilization; maternal mortality being the secondary outcome. Cluster level analysis will be done according to intention-to-treat.

Discussion
A nationwide network of about 100,000 lady health workers is already involved in antenatal and postnatal care of pregnant women. They also act as “gatekeepers” for the child birthing services. This gate keeping role mainly includes counseling and referral for skill birth attendance and travel arrangements for emergency obstetric care (if required). The review of current arrangements and practices show that the care delivery process needs enhancement to include adequate information provision as well as informed “decision” making and planned “action” by the pregnant women. The proposed three-year research is to develop, through national technical working group process, and then test a set of arrangements for achieving the enhanced utilization of safe birthing services.

Trial registration
Current Controlled Trials ISRCTN86264432
ZIC1 modulates cell-cycle distributions and cell migration through regulation of sonic hedgehog, PI3K and MAPK signaling pathways in gastric cancer
Authors: Zhong Jing , Chen Shujie , Xue Meng , Du Qin , Cai Jianting , Jin Hongchuan , Si Jianmin , Wang Liangjing 
Published: July 2012

Abstract

Background
ZIC1, a vital transcription factor with zinc finger domains, has been implicated in the process of neural development. We previously showed that ZIC1 may function as a tumour suppressor in gastrointestinal cancers. However, the molecular mechanism underlying ZIC1 participation in tumour progression remains unknown.

Methods
The role of ZIC1 on cell proliferation and migration was examined. The regulation of sonic hedgehog (Shh), phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways after ectopic expression of ZIC1 in gastric cancer cells were evaluated.

Results
Overexpression of ZIC1 contributes to the inhibition of cell proliferation migration and cell-cycle distribution in gastric cancer. The modulation of G1/S checkpoint by ZIC1 is mainly mediated through the regulation of cyclin-dependent kinases (p21 Waf1/Cip1, p27 Kip1 and cyclin D1). In addition, ZIC1 can inactivate the level of phospholated Akt and Erk1/2, and transcriptionally regulate sonic hedgehog (Shh) signaling, thus leading to regulate the expression of p21 Waf1/Cip1 and cyclin D1. Finally, we have systemically identified ZIC1 downstream targets by cDNA microarray analysis and revealed that 132 genes are down-regulated and 66 genes are up-regulated after transfection with ZIC1 in gastric cancer cells. These candidate genes play critical roles in cell proliferation, cell cycle and cell motility.

Conclusions
Overexpression of ZIC1 results in inactivation of Shh, PI3K and MAPK signaling pathways, as well as regulation of multiple downstream targets which are essential for the development and progression of gastric cancer. ZIC1 serves as a potential therapeutic target for gastric cancer.
Factors associated with suicidal behaviors in mainland China: a meta-analysis
Authors: Li Ying , Li Yafei , Cao Jia 
Published: July 2012

AbstractBackgroundSuicide is a major public health issue in China. Studies of suicide risk factors have reported both inconsistent and inconclusive results. This review aimed to determine suicide risk factors in China.MethodsMedline/PubMed, EMBASE, CNKI (China National Knowledge Infrastructure) and VIP (Chinese Journal of Science and Technology of VIP) were searched for relevant reports. Two investigators independently assessed the eligibility of identified studies and extracted data. Pooled odds ratios (and 95% confidence intervals) were calculated for each factor with Revman 5.0.ResultsForty-four studies with 192,362 subjects were included. The pooled results indicated that mood disorders and stressful life events (physical illness, suicide of relatives) increased the risk of suicide ideation among the entire population. Socio-family environment (single or remarried parent, study pressure and academic achievement) and unhealthy behaviors (smoking, alcohol drinking, and drug use) were risk factors for suicide ideation among youth. Unhealthy behaviors (smoking and alcohol drinking), mood disorders, and stressful life events (suicide of relatives) were the main risk factors for attempted suicide. Persons living in rural areas, and those with lower education, mood disorders, and/or a history of negative life events had a higher risk of completed suicide. In China, before 2000, females had a significantly higher rate of completed suicide than males, while after 2000, no significant gender difference was found.ConclusionsSocio-family environment, lifestyle, life events and psychiatric/psychological factors are associated with suicidal behaviors in China. Further case–control or cohort studies are needed to better understand suicide behaviors in China. Meanwhile, there is an urgent need for comprehensive studies of suicide interventions among high-risk populations.
Field performance of transgenic citrus trees: Assessment of the long-term expression of uidA and nptIItransgenes and its impact on relevant agronomic and phenotypic characteristics
Authors: Pons Elsa , Peris Josep E , Peña Leandro 
Published: July 2012

Abstract

Background
The future of genetic transformation as a tool for the improvement of fruit trees depends on the development of proper systems for the assessment of unintended effects in field-grown GM lines. In this study, we used eight transgenic lines of two different citrus types (sweet orange and citrange) transformed with the marker genes β-glucuronidase (uidA) and neomycin phosphotransferase II (nptII) as model systems to study for the first time in citrus the long-term stability of transgene expression and whether transgene-derived pleiotropic effects occur with regard to the morphology, development and fruit quality of orchard-grown GM citrus trees.

Results
The stability of the integration and expression of the transgenes was confirmed in 7-year-old, orchard-grown transgenic lines by Southern blot analysis and enzymatic assays (GUS and ELISA NPTII), respectively. Little seasonal variation was detected in the expression levels between plants of the same transgenic line in different organs and over the 3 years of analysis, confirming the absence of rearrangements and/or silencing of the transgenes after transferring the plants to field conditions. Comparisons between the GM citrus lines with their non-GM counterparts across the study years showed that the expression of these transgenes did not cause alterations of the main phenotypic and agronomic plant and fruit characteristics. However, when comparisons were performed between diploid and tetraploid transgenic citrange trees and/or between juvenile and mature transgenic sweet orange trees, significant and consistent differences were detected, indicating that factors other than their transgenic nature induced a much higher phenotypic variability.

Conclusions
Our results indicate that transgene expression in GM citrus remains stable during long-term agricultural cultivation, without causing unexpected effects on crop characteristics. This study also shows that the transgenic citrus trees expressing the selectable marker genes that are most commonly used in citrus transformation were substantially equivalent to the non-transformed controls with regard to their overall agronomic performance, as based on the use of robust and powerful assessment techniques. Therefore, future studies of the possible pleiotropic effects induced by the integration and expression of transgenes in field-grown GM citrus may focus on the newly inserted trait(s) of biotechnological interest.
Genetic diversity of expressed Plasmodium falciparum var genes from Tanzanian children with severe malaria
Authors: Mugasa Joseph , Qi Weihong , Rusch Sebastian , Rottmann Matthias , Beck Hans-Peter 
Published: July 2012

Abstract

Background
Severe malaria has been attributed to the expression of a restricted subset of the var multi-gene family, which encodes for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 mediates cytoadherence and sequestration of infected erythrocytes into the post-capillary venules of vital organs such as the brain, lung or placenta. var genes are highly diverse and can be classified in three major groups (ups A, B and C) and two intermediate groups (B/A and B/C) based on the genomic location, gene orientation and upstream sequences. The genetic diversity of expressed var genes in relation to severity of disease in Tanzanian children was analysed.

Methods
Children with defined severe (SM) and asymptomatic malaria (AM) were recruited. Full-length var mRNA was isolated and reversed transcribed into var cDNA. Subsequently, the DBL and N-terminal domains, and up-stream sequences were PCR amplified, cloned and sequenced. Sequences derived from SM and AM isolates were compared and analysed.

Results
The analysis confirmed that the var family is highly diverse in natural Plasmodium falciparum populations. Sequence diversity of amplified var DBL-1α and upstream regions showed minimal overlap among isolates, implying that the var gene repertoire is vast and most probably indefinite in endemic areas. var DBL-1α sequences from AM isolates were more diverse with more singletons found (p<0.05) than those from SM infections. Furthermore, few var DBL-1α sequences from SM patients were rare and restricted suggesting that certain PfEMP1 variants might induce severe disease.

Conclusions
The genetic sequence diversity of var genes of P. falciparum isolates from Tanzanian children is large and its relationship to disease severity has been studied. Observed differences suggest that different var genes might have fundamentally different roles in the host-parasite interaction. Further research is required to examine clear disease-associations of var gene subsets in different geographical settings. The importance of very strict clinical definitions and appropriate large control groups needs to be emphasized for future studies on disease associations of PfEMP1.
The role of nitric oxide on rosuvastatin-mediated S-nitrosylation and translational proteomes in human umbilical vein endothelial cells
Authors: Huang Bin , Li Fu An , Wu Chien Hsing , Wang Danny Ling 
Published: July 2012

Abstract

Background
The pleiotropic effects of 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), which are independent from their cholesterol-lowering action, have been widely recognized in various biological systems. Statins can affect endothelial homeostasis, which is partly modulated by the production of nitric oxide (NO). However, it is unclear how statin/NO-mediated posttranslational S-nitrosylation of endothelial proteins and changes in translational profiles may benefit endothelial integrity. Therefore, it is important to understand the statin/NO-mediated S-nitrosylation in endothelial cells.

Results
Rosuvastatin treatment of human umbilical vein endothelial cells (ECs) enhanced the enzymatic activity of endothelial nitric oxide synthase (eNOS) and the expression of 78 S-nitrosoproteins. Among these S-nitrosoproteins, we identified 17 proteins, including protein disulfide bond isomerase, phospholipase C, transaldolase and heat shock proteins. Furthermore, a hydrophobic Cys66 was determined as the S-nitrosylation site of the mitochondrial HSP70. In addition to the statin-modulated posttranslational S-nitrosylation, changes in the NO-mediated translational proteome were also observed. Seventeen major proteins were significantly upregulated after rosuvastatin treatment. However, 12 of these proteins were downregulated after pretreating ECs with an eNOS inhibitor (L-NAME), which indicated that their expression was modulated by NO.

Conclusions
ECs treated with rosuvastatin increase eNOS activation. The increased NO production is involved in modulating S-nitrosylation and translation of proteins. We provide further evidence of the pleiotropic effect of rosuvastatin on endothelial physiology.
Inferring domain-domain interactions from protein-protein interactions in the complex network conformation
Authors: Chen Chen , Zhao Jun-Fei , Huang Qiang , Wang Rui-Sheng , Zhang Xiang-Sun 
Published: July 2012

AbstractBackgroundAs protein domains are functional and structural units of proteins, a large proportion of protein-protein interactions (PPIs) are achieved by domain-domain interactions (DDIs), many computational efforts have been made to identify DDIs from experimental PPIs since high throughput technologies have produced a large number of PPIs for different species. These methods can be separated into two categories: deterministic and probabilistic. In deterministic methods, parsimony assumption has been utilized. Parsimony principle has been widely used in computational biology as the evolution of the nature is considered as a continuous optimization process. In the context of identifying DDIs, parsimony methods try to find a minimal set of DDIs that can explain the observed PPIs. This category of methods are promising since they can be formulated and solved easily. Besides, researches have shown that they can detect specific DDIs, which is often hard for many probabilistic methods. We notice that existing methods just view PPI networks as simply assembled by single interactions, but there is now ample evidence that PPI networks should be considered in a global (systematic) point of view for it exhibits general properties of complex networks, such as 'scale-free' and 'small-world'.ResultsIn this work, we integrate this global point of view into the parsimony-based model. Particularly, prior knowledge is extracted from these global properties by plausible reasoning and then taken as input. We investigate the role of the added information extensively through numerical experiments. Results show that the proposed method has improved performance, which confirms the biological meanings of the extracted prior knowledge.ConclusionsThis work provides us some clues for using these properties of complex networks in computational models and to some extent reveals the biological meanings underlying these general network properties.
Unilateral testicular seminoma with simultaneous contralateral torsion: a case report
Authors: Taguchil Kazumi , Yasui Takahiro , Naiki Taku , Umemoto Yukihiro , Kojima Yoshiyuki , Kawai Noriyasu , Tozawa Keiichi , Hayashi Yutaro , Kohri Kenjiro 
Published: July 2012

Abstract

Introduction
Testicular germ cell tumors are the most common malignancies in men. Testicular torsion is also a scrotal phenomenon seen in adolescence and adulthood. The co-occurrence of these two scrotal disorders is extremely rare.

Case presentation
A 28-year-old East Asian man presented at our hospital with painless bilateral scrotal swelling. Both scrotal ultrasonography and computed tomography findings showed bilateral testicular tumors, and magnetic resonance imaging demonstrated a lack of enhancement in his right testis, indicating a hemorrhagic infarction and a left testicular tumor. After a bilateral orchiectomy, the intraoperative and histopathological findings revealed a left seminoma with a complicating contralateral testicular torsion that had developed with hemorrhagic infarction.

Conclusion
Testicular germ cell tumor with contralateral torsion is extremely rare. We could differentiate this case from bilateral testicular tumors appropriately using magnetic resonance imaging, and suggest that magnetic resonance imaging examination may be necessary to diagnose bilateral testicular masses.