bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective constraint, background selection, and mutation accumulation variability within and between human populations
Authors: Hodgkinson Alan , Casals Ferran , Idaghdour Youssef , Grenier Jean-Christophe , Hernandez Ryan D , Awadalla Philip 
Published: July 2013

Abstract

Background
Regions of the genome that are under evolutionary constraint across multiple species have previously been used to identify functional sequences in the human genome. Furthermore, it is known that there is an inverse relationship between evolutionary constraint and the allele frequency of a mutation segregating in human populations, implying a direct relationship between interspecies divergence and fitness in humans. Here we utilise this relationship to test differences in the accumulation of putatively deleterious mutations both between populations and on the individual level.

Results
Using whole genome and exome sequencing data from Phase 1 of the 1000 Genome Project for 1,092 individuals from 14 worldwide populations we show that minor allele frequency (MAF) varies as a function of constraint around both coding regions and non-coding sites genome-wide, implying that negative, rather than positive, selection primarily drives the distribution of alleles among individuals via background selection. We find a strong relationship between effective population size and the depth of depression in MAF around the most conserved genes, suggesting that populations with smaller effective size are carrying more deleterious mutations, which also translates into higher genetic load when considering the number of putatively deleterious alleles segregating within each population. Finally, given the extreme richness of the data, we are now able to classify individual genomes by the accumulation of mutations at functional sites using high coverage 1000 Genomes data. Using this approach we detect differences between ‘healthy’ individuals within populations for the distributions of putatively deleterious rare alleles they are carrying.

Conclusions
These findings demonstrate the extent of background selection in the human genome and highlight the role of population history in shaping patterns of diversity between human individuals. Furthermore, we provide a framework for the utility of personal genomic data for the study of genetic fitness and diseases.
Gene bionetworks that regulate ovarian primordial follicle assembly
Authors: Nilsson Eric , Zhang Bin , Skinner Michael K 
Published: July 2013

Abstract

Background
Primordial follicle assembly is the process by which ovarian primordial follicles are formed. During follicle assembly oocyte nests break down and a layer of pre-granulosa cells surrounds individual oocytes to form primordial follicles. The pool of primordial follicles formed is the source of oocytes for ovulation during a female’s reproductive life.

Results
The current study utilized a systems approach to detect all genes that are differentially expressed in response to seven different growth factor and hormone treatments known to influence (increase or decrease) primordial follicle assembly in a neonatal rat ovary culture system. One novel factor, basic fibroblast growth factor (FGF2), was experimentally determined to inhibit follicle assembly. The different growth factor and hormone treatments were all found to affect similar physiological pathways, but each treatment affected a unique set of differentially expressed genes (signature gene set). A gene bionetwork analysis identified gene modules of coordinately expressed interconnected genes and it was found that different gene modules appear to accomplish distinct tasks during primordial follicle assembly. Predictions of physiological pathways important to follicle assembly were validated using ovary culture experiments in which ERK1/2 (MAPK1) activity was increased.

Conclusions
A number of the highly interconnected genes in these gene networks have previously been linked to primary ovarian insufficiency (POI) and polycystic ovarian disease syndrome (PCOS). Observations have identified novel factors and gene networks that regulate primordial follicle assembly. This systems biology approach has helped elucidate the molecular control of primordial follicle assembly and provided potential therapeutic targets for the treatment of ovarian disease.
The FLS (Fatty liver Shionogi) mouse reveals local expressions of lipocalin-2, CXCL1 and CXCL9 in the liver with non-alcoholic steatohepatitis
Authors: Semba Toshihisa , Nishimura Motoi , Nishimura Satomi , Ohara Osamu , Ishige Takayuki , Ohno Sayaka , Nonaka Ken , Sogawa Kazuyuki , Satoh Mamoru , Sawai Setsu , Matsushita Kazuyuki , Imazeki Fumio , Yokosuka Osamu , Nomura Fumio 
Published: July 2013

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which carries a significant risk of progression to cirrhosis and hepatocellular carcinoma. Since NASH is a progressive but reversible condition, it is desirable to distinguish NASH from simple steatosis, and to treat NASH patients at an early stage. To establish appropriate diagnosis and therapy, the pathological mechanisms of the disease should be elucidated; however, these have not been fully clarified for both NASH and simple steatosis. This study aims to reveal the differences between simple steatosis and NASH.

Methods
This study used fatty liver Shionogi (FLS) mice as a NASH model, for comparison with dd Shionogi (DS) mice as a model of simple steatosis. Genome-wide gene expression analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array, which contains 45101 probe sets for known and predicted genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to investigate gene expression changes and protein localizations.

Results
DNA microarray analysis of the liver transcriptomes and qRT-PCR of both types of mice revealed that LCN2, CXCL1 and CXCL9 mRNAs were overexpressed in FLS mouse livers. Immunohistochemistry showed that CXCL1 protein was mainly localized to steatotic hepatocytes. CXCL9 protein-expressing hepatocytes and sinusoidal endothelium were localized in some areas of inflammatory cell infiltration. Most interestingly, hepatocytes expressing LCN2, a kind of adipokine, were localized around almost all inflammatory cell clusters. Furthermore, there was a positive correlation between the number of LCN2-positive hepatocytes in the specimen and the number of inflammatory foci.

Conclusions
Overexpression and distinct localization of LCN2, CXCL1 and CXCL9 in the liver of fatty liver Shionogi mice suggest significant roles of these proteins in the pathogenesis of NASH.
Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis
Authors: Wei Chen Chao , You Fan Tian , Mei Li Yu , Jian Sun , Qiang Chen Yong 
Published: July 2013

Abstract

Background
Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored.

Methods
TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues.

Results
The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group.

Conclusion
These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.
Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling
Authors: Liu Xiaobai , Wang Zhenhua , Wang Ping , Yu Bo , Liu Yunhui , Xue Yixue 
Published: July 2013

AbstractBackgroundIt has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs’ protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia.MethodsMale Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated.ResultsGTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia.ConclusionsThese results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.
Quality of life in China rural-to-urban female migrant factory workers: a before-and-after study
Authors: Zhu Chunyan , Geng Qingshan , Yang Hongling , Chen Li , Fu Xianhua , Jiang Wei 
Published: July 2013

Abstract

Background
Rural-to-urban female migrant workers have a lower quality of life compared to the general population. Improving these conditions remains highly challenging. This paper reports the health-related quality of life (HRQoL) of the female migrant workers in an educational project.

Methods
In this before-and-after study, a community-based health education intervention was developed to improve female migrant workers’ HRQoL and job satisfaction. A factory was selected as the location to implement the trial, using a before-and-after design. The education intervention included distribution and free access to study materials, monthly lectures, and counseling. The primary endpoint was HRQoL, and gynecological disease and job satisfaction were secondary endpoints. We assessed HRQoL at baseline and at 6-month follow-up using the Health Survey Short Form (SF-36).

Results
Compared to the baseline assessment, the participants at the 6-month survey reported higher General Health scores (standardized-β coefficients (Betas) of β = 0.056; P <0.001), Vitality scores (β = 0.066; P <0.001), Mental Health scores (β = 0.062; P <0.001), mental component summary scores (β = 0.040; P <0.001), and job satisfaction (Odds Ratio [OR] 2.104, 95% confidence interval [CI] 1.837-2.408; P <0.01).

Conclusions
A community-based educational intervention, targeted at female migrant workers, appears effective in improving HRQoL and job satisfaction.
Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress
Authors: Ding Ye , Zhang Zhaofeng , Dai Xiaoqian , Jiang Yanfei , Bao Lei , Li Yujie , Li Yong 
Published: July 2013

Abstract

Background
It is increasingly being realized that failure of pancreatic beta cells to secrete enough insulin to adequately compensate for obesity and insulin resistance is the primary defects of type 2 diabetes mellitus (T2DM). Pancreatic beta cells possess a highly developed and active endoplasmic reticulum (ER), reflecting their role in folding, export and processing of newly synthesized insulin. ER stress-induced pancreatic beta-cell failure is a novel event in the pathogenesis of T2DM. Some studies with antioxidants indicated a beneficial impact on ER stress. Our previous study found that strong antioxidants, grape seed proanthocyanidins (GSPs), ameliorated ER stress to protect skeletal muscle from cell death in type 2 diabetic rats. The present study continued to investigate the effect of GSPs on beta-cell failure and ER stress in diabetic pancreas.

Methods
Male Sprague–Dawley rats made type 2 diabetic with 2 injections of 25 mg/kg streptozotocin and 8 weeks of the high-carbohydrate/high-fat diet were fed a basal diet with or without GSPs administration for 16 weeks. Oral glucose tolerance, plasma glucose, serum insulin and the score of beta-cell function were measured. Morphological observation was performed by light and electron microscopic analyses. Islet cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Additionally, the level of insulin and the expression of ER stress markers in pancreatic islets were also studied using immunohistochemical staining.

Results
After 16 weeks treatment, the score of beta-cell function and the abnormal oral glucose tolerance of diabetic rats were partially reversed by GSPs treatment. The efficacious effect of GSPs was also manifested in the amelioration of pancreatic damage and ER dilatation by microscopic analyses. Moreover, GSPs treatment increased normal insulin content and decreased the number of apoptotic cells in diabetic islets. Importantly, GSPs treatment partially alleviated ER stress by decreasing some ER stress markers.

Conclusion
These findings suggest that GSPs might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction and death in T2DM.
3Omics: a web-based systems biology tool for analysis, integration and visualization of human transcriptomic, proteomic and metabolomic data
Authors: Kuo Tien-Chueh , Tian Tze-Feng , Tseng Yufeng Jane 
Published: July 2013

Abstract

Background
Integrative and comparative analyses of multiple transcriptomics, proteomics and metabolomics datasets require an intensive knowledge of tools and background concepts. Thus, it is challenging for users to perform such analyses, highlighting the need for a single tool for such purposes. The 3Omics one-click web tool was developed to visualize and rapidly integrate multiple human inter- or intra-transcriptomic, proteomic, and metabolomic data by combining five commonly used analyses: correlation networking, coexpression, phenotyping, pathway enrichment, and GO (Gene Ontology) enrichment.

Results
3Omics generates inter-omic correlation networks to visualize relationships in data with respect to time or experimental conditions for all transcripts, proteins and metabolites. If only two of three omics datasets are input, then 3Omics supplements the missing transcript, protein or metabolite information related to the input data by text-mining the PubMed database. 3Omics’ coexpression analysis assists in revealing functions shared among different omics datasets. 3Omics’ phenotype analysis integrates Online Mendelian Inheritance in Man with available transcript or protein data. Pathway enrichment analysis on metabolomics data by 3Omics reveals enriched pathways in the KEGG/HumanCyc database. 3Omics performs statistical Gene Ontology-based functional enrichment analyses to display significantly overrepresented GO terms in transcriptomic experiments. Although the principal application of 3Omics is the integration of multiple omics datasets, it is also capable of analyzing individual omics datasets. The information obtained from the analyses of 3Omics in Case Studies 1 and 2 are also in accordance with comprehensive findings in the literature.

Conclusions
3Omics incorporates the advantages and functionality of existing software into a single platform, thereby simplifying data analysis and enabling the user to perform a one-click integrated analysis. Visualization and analysis results are downloadable for further user customization and analysis. The 3Omics software can be freely accessed at http://3omics.cmdm.tw.
Psychrotrophic Pseudomonas mandelii CBS-1 produces high levels of poly-β-hydroxybutyrate
Authors: Li Rongpeng , Jiang Yuji , Wang Xinfeng , Yang Jingjing , Gao Yuan , Zi Xiaoli , Zhang Xia , Gao Haofeng , Hu Nan 
Published: July 2013

Abstract
A novel facultative psychrotroph (strain CBS-1), which accumulates poly-β-hydroxybutyrate (PHB), was isolated from soil samples taken from Changbai Mountain, China. Phylogenetic analysis based on 16S rRNA sequence data and Biolog analysis identified strain CBS-1 as Pseudomonas mandelii. Transmission electron micrographs revealed abundant electron-transparent intracellular granules. 1H-nuclear magnetic resonance analysis revealed that the granules were composed of PHB. P. mandelii CBS-1 grew optimally at 20°C. When cultured aerobically for 48 h with sucrose as the sole carbon source, strain CBS-1 yielded a maximum cell density of 29.3 g/L cell dry weight and synthesized 22.3 g/L of PHB. The ability of strain CBS-1 to grow at a low temperature and rapidly synthesize high levels of PHB may reduce the costs of industrial PHB production.
Public Availability of Results of Trials Assessing Cancer Drugs in the United States
Authors: Nguyen Thi-Anh-Hoa , Dechartres Agnes , Belgherbi Soraya , Ravaud Philippe 
Published: July 2013

Purpose To evaluate to what extent results of completed trials of cancer drugs conducted in the United States are publicly available at ClinicalTrials.gov, as required by the Food and Drug Administration Amendments Act (FDAAA), or are published in journals. Methods We searched ClinicalTrials.gov for cancer trials governed by the FDAAA: phase II to IV trials assessing drugs in the United States with a primary completion date between December 26, 2007, and May 31, 2010. For each trial, we also searched PubMed to identify the publication of results. We assessed the cumulative percentages of posted or published results over time by using the Kaplan-Meier method. Results We identified 646 trials, including 209 randomized controlled trials (RCTs). At 12 months after completion of the trials, the cumulative percentages of trials with results posted at ClinicalTrials.gov, published in journals, and available either at ClinicalTrials.gov or in journals were 9% (95% CI, 7% to 11%), 12% (95% CI, 10% to 15%), and 20% (95% CI, 17% to 23%), respectively, and for RCTs, the percentages were 12% (95% CI, 8% to 16%), 5% (95% CI, 2% to 8%), and 17% (95% CI, 12% to 22%), respectively. At 36 months, these percentages were 31% (95% CI, 28% to 35%), 35% (95% CI, 31% to 39%), and 55% (95% CI, 51% to 59%), respectively, and for RCTs, they were 38% (95% CI, 31% to 45%), 32% (95% CI, 25% to 39%), and 56% (95% CI, 48% to 62%), respectively. Public availability of phase III trials was 15% (95% CI, 7% to 23%) at 12 months, 39% (95% CI, 27% to 49%) at 24 months, and 64% (95% CI, 50% to 73%) at 36 months. Conclusion Despite the FDAAA, results for nearly half the trials of cancer drugs in the United States were not publicly available 3 years after completion of the trials.
The Limited Editions Club’s Leaves of Grass (1942) and the American imagetext
Authors: Weiss Francine 
Published: July 2013

Abstract
In 1941 photographer Edward Weston travelled around the United States photographing images for a luxury reprint edition of Walt Whitman’s Leaves of Grass to be published by the Limited Editions Club under the direction of George Macy. A case study in the fundamental challenges of combining photographs and poetry, this article discusses Weston and Macy’s disagreements over the issue of ‘illustration’ and the shortcomings of an illustrative approach to photography, and discusses one of the more successful combinations of images and texts in the final published volumes. Although these final volumes occupy an uncertain place within the American photo-book genre of the 1930s and 1940s due to the lack of consistently close or dynamic interactions of texts and images, as a project by one of America’s acclaimed modernist photographers for a canonical American text, the Limited Editions Club’s Leaves of Grass is an important book in the history of the American photo book or image-text that represents some of the essential challenges in combining photography and poetry.
Surrealist histories of language, image, media: Donald Barthelme’s ‘collage stories’
Authors: Sierra Nicole 
Published: July 2013

Abstract
Using previously neglected archival materials from the Donald Barthelme Literary Papers at the University of Houston Libraries, my article identifies the sources of Donald Barthelme’s collages and their allusive meanings. In doing so, the author’s under-appreciated relationship with artistic collage techniques is further elucidated, revealing how indebted his work is to the innovations of surrealist collage production. Principal amongst these influences is Max Ernst’s ‘historical’ collage aesthetic. Using the theories of Marshall McLuhan, I argue that Barthelme’s technique of pictorial collage is an attempt to rival contemporary systems of representation (like television and radio), while recognizing the significance of mass media on his work. Capturing the evolving landscape of contemporary mass culture, I examine the relationship between text and image in Barthelme’s short stories.