bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Methylation of the MOR Gene Proximal Promoter in Primary Sensory Neurons Plays a Crucial Role in the Decreased Analgesic Effect of Opioids in Neuropathic Pain
Authors: Zhou Xue-Long , Yu Li-Na , Wang Yin , Tang Li-Hui , Peng Yu-Nan , Cao Jun-Li , Yan Min 
Published: August 2014

Background: The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. Results: The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2′-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. Conclusions: Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain.
Evidence on the environmental impacts of farm land abandonment in high altitude/mountain regions: a systematic map
Authors: Haddaway Neal R , Styles David , Pullin Andrew S 
Published: August 2014

Abstract
Background
Many ecosystems have developed in the presence of agriculture and cessation of management resulting from land abandonment can have significant ecological impacts. Around 56 percent of the utilised agricultural area of the European Union is classified as ‘less-favourable areas’ and much of this is mountainous. The small-scale and extensively managed farmlands that are common in mountain areas are particularly vulnerable to marginalisation and abandonment. We conducted the first systematic global mapping of evidence to inform stakeholders and policy makers of the potential impacts of farm land abandonment in mountain areas.

Methods
Evidence was collated from a range of academic literature databases and grey literature sources. Identified articles (8,489) were screened for relevance at title, abstract and full text using predefined inclusion criteria set out in a published protocol. Relevant studies (165 across 189 articles) were then mapped using predefined coding and critically appraised for internal validity (i.e. susceptibility to bias).

Results
Mapping identified a number of interesting themes in the evidence base: the majority of research was undertaken in arable and mixed farming systems; large evidence bases were found in China, Spain and Italy; studies were mostly observational with spatial/successional comparators; biodiversity, soil and vegetation were most frequently studied. Several knowledge gaps were identified: including outcomes (socioeconomics and environmental hazards), regions (key mountain ranges including the Himalaya), and specific outcome-region groups (e.g. vegetation and soil measures in the UK). Several deficiencies in methodology were identified across studies: a lack of replication; non-random sample selection; lack of methodological detail (including details of spatial scale, replication, and sample selection).

Discussion
Systematic mapping has produced a searchable database of studies relating to high altitude farmland abandonment. The map identifies a number of potential areas for fruitful future synthesis, for example research on biodiversity, soil and vegetation in the Loess Hilly Plateau in China, and soil research in Spain. Such synthesis would be rapid given the effort expended here in identifying and screening relevant articles. It also points to several areas that were under-represented in the literature, such as natural hazards (avalanche, fire and flood risk), that would potentially benefit from increased primary research.
STRUCTURE PLOT: a program for drawing elegant STRUCTURE bar plots in user friendly interface
Authors: Ramasamy Ramesh Krishnan , Ramasamy Sumathy , Bindroo Bharat Bushan , Naik V Girish 
Published: August 2014

Abstract

Background
Understanding structure of the population is one of the major objective of many genetic studies. The program STRUCTURE is commonly used to infer population structure using multi-locus genotype data. However, a tool with graphical-user interface is currently not available to visualize STRUCTURE bar plots.

Results
We introduce STRUCTURE PLOT, a program for drawing STRUCTURE bar plots. The program generates publication ready, aesthetic STRUCTURE bar plots by using individual Q matrix from STRUCTURE or CLUMPP output. The program is very simple to use and includes variety of options like sorting bar by original order or by K, and selection of colors from R colors or RColorBrewer palette. Individual or population labels can be printed below or above the plot in any angle. Size of the graph and label can be defined, and option is provided to save plot in variety of picture formats in user defined resolution.

Conclusion
The program is implemented as a web application for online users and also as a standalone shiny application. Web application is compatible to majority of leading web browsers and standalone version can be launched using a simple R command. The program can be freely accessed at http://btismysore.in/strplot.
Image-based phenotyping for non-destructive screening of different salinity tolerance traits in rice
Authors: Hairmansis Aris , Berger Bettina , Tester Mark , Roy Stuart John 
Published: August 2014

Abstract

Background
Soil salinity is an abiotic stress wide spread in rice producing areas, limiting both plant growth and yield. The development of salt-tolerant rice requires efficient and high-throughput screening techniques to identify promising lines for salt affected areas. Advances made in image-based phenotyping techniques provide an opportunity to use non-destructive imaging to screen for salinity tolerance traits in a wide range of germplasm in a reliable, quantitative and efficient way. However, the application of image-based phenotyping in the development of salt-tolerant rice remains limited.

Results
A non-destructive image-based phenotyping protocol to assess salinity tolerance traits of two rice cultivars (IR64 and Fatmawati) has been established in this study. The response of rice to different levels of salt stress was quantified over time based on total shoot area and senescent shoot area, calculated from visible red-green-blue (RGB) and fluorescence images. The response of rice to salt stress (50, 75 and 100 mM NaCl) could be clearly distinguished from the control as indicated by the reduced increase of shoot area. The salt concentrations used had only a small effect on the growth of rice during the initial phase of stress, the shoot Na+ accumulation independent phase termed the ‘osmotic stress’ phase. However, after 20 d of treatment, the shoot area of salt stressed plants was reduced compared with non-stressed plants. This was accompanied by a significant increase in the concentration of Na+ in the shoot. Variation in the senescent area of the cultivars IR64 and Fatmawati in response to a high concentration of Na+ in the shoot indicates variation in tissue tolerance mechanisms between the cultivars.

Conclusions
Image analysis has the potential to be used for high-throughput screening procedures in the development of salt-tolerant rice. The ability of image analysis to discriminate between the different aspects of salt stress (shoot ion-independent stress and shoot ion dependent stress) makes it a useful tool for genetic and physiological studies to elucidate processes that contribute to salinity tolerance in rice. The technique has the potential for identifying the genetic basis of these mechanisms and assisting in pyramiding different tolerance mechanisms into breeding lines.
Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in a Chinese population
Authors: Wang Yanru , He Yisha , Qin Zhenzhen , Jiang Yue , Jin Guangfu , Ma Hongxia , Dai Juncheng , Chen Jiaping , Hu Zhibin , Guan Xiaoxiang , Shen Hongbing 
Published: August 2014

Abstract
Introduction
Single-nucleotide polymorphisms (SNPs) at 6q25.1 that are associated with breast cancer susceptibility have been identified in several genome-wide association studies (GWASs). However, the exact causal variants in this region have not been clarified.

Methods
In the present study, we genotyped six potentially functional single-nucleotide polymorphisms (SNPs) within the CCDC170 and ESR1 gene regions at 6q25.1 and accessed their associations with risk of breast cancer in a study of 1,064 cases and 1,073 cancer-free controls in Chinese women. The biological function of the risk variant was further evaluated by performing laboratory experiments.

Results
Breast cancer risk was significantly associated with three SNPs located at 6q25.1—rs9383935 in CCDC170 and rs2228480 and rs3798758 in ESR1—with variant allele attributed odds ratios (ORs) of 1.38 (95% confidence interval (CI): 1.20 to 1.57, P = 2.21 × 10-6), 0.84 (95% CI: 0.72 to 0.98, P = 0.025) and 1.19 (95% CI: 1.04 to 1.37, P = 0.013), respectively. The functional variant rs9383935 is in high linkage disequilibrium (LD) with GWAS-reported top-hit SNP (rs2046210), but only rs9383935 showed a strong independent effect in conditional regression analysis. The rs9383935 risk allele A showed decreased activity of reporter gene in both the MCF-7 and BT-474 breast cancer cell lines, which might be due to an altered binding capacity of miR-27a to the 3' untranslated region (3' UTR) sequence of CCDC170. Real-time quantitative reverse transcription PCR confirmed the correlation between rs9383935 genotypes and CCDC170 expression levels.

Conclusions
The results of this study suggest that the functional variant rs9383935, located at the 3' UTR of CCDC170, may be one candidate of the causal variants at 6q25.1 that modulate the risk of breast cancer.
Adipocyte Versus Pituitary Leptin in the Regulation of Pituitary Hormones: Somatotropes Develop Normally in the Absence of Circulating Leptin
Authors: Odle Angela K. , Haney Anessa , Allensworth-James Melody , Akhter Noor , Childs Gwen V. 
Published: August 2014

Abstract
Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and the pituitary gland among other tissues. Best known for its role in regulating appetite and energy expenditure, leptin is produced largely by and in proportion to white fat cells. Leptin is also important to the maintenance and function of the GH cells of the pituitary. This was shown when the deletion of leptin receptors on somatotropes caused decreased numbers of GH cells, decreased circulating GH, and adult-onset obesity. To determine the source of leptin most vital to GH cells and other pituitary cell types, we compared two different leptin knockout models with Cre-lox technology. The global Lep-null model is like the ob/ob mouse, whereby only the entire exon 3 is deleted. The selective adipocyte-Lep-null model lacks adipocyte leptin but retains pituitary leptin, allowing us to investigate the pituitary as a potential source of circulating leptin. Male and female mice lacking adipocyte leptin (Adipocyte-lep-null) did not produce any detectable circulating leptin and were infertile, suggesting that the pituitary does not contribute to serum levels. In the presence of only pituitary leptin, however, these same mutants were able to maintain somatotrope numbers and GH mRNA levels. Serum GH trended low, but values were not significant. However, hypothalamic GHRH mRNA was significantly reduced in these animals. Other serum hormone and pituitary mRNA differences were observed, some of which varied from previous results reported in ob/ob animals. Whereas pituitary leptin is capable of maintaining somatotrope numbers and GH mRNA production, the decreased hypothalamic GHRH mRNA and low (but not significant) serum GH levels indicate an important role for adipocyte leptin in the regulation of GH secretion in the mouse. Thus, normal GH secretion may require the coordinated actions of both adipocyte and pituitary leptin.
Decidualization Induces a Secretome Switch in Perivascular Niche Cells of the Human Endometrium
Authors: Murakami Keisuke , Lee Yie Hou , Lucas Emma S. , Chan Yi-Wah , Durairaj Ruban Peter , Takeda Satoru , Moore Jonathan D. , Tan Bee K. , Quenby Siobhan , Chan Jerry K. Y. , Gargett Caroline E. , Brosens Jan J. 
Published: August 2014

Abstract
The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and nonperivascular (W5C5−) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+:W5C5− cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared with their W5C5− counterparts. This divergence in secretomes was switched and became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of chemokines and cytokines, including leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings suggest that the decidual response is spatially organized at the embryo-maternal interface with differentiating perivascular cells establishing distinct cytokine and chemokine profiles that could potentially direct trophoblast toward maternal vessels and govern local immune responses in pregnancy.
Insulin Action on GABA Neurons Is a Critical Regulator of Energy Balance But Not Fertility in Mice
Authors: Evans Maggie C. , Rizwan Mohammed Z. , Anderson Greg M. 
Published: August 2014

Abstract
Insulin signaling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting brain-specific deletion of insulin receptors (InsRs) display a diet-sensitive obesogenic phenotype and hypothalamic hypogonadism. However, the specific neurons mediating insulin's central effects on fertility remain largely unidentified. The neurotransmitters γ-aminobutyric acid (GABA) and glutamate are important modulators of fertility and energy homeostasis and are widely distributed in the hypothalamus. We therefore investigated whether insulin signaling via GABAergic or glutamatergic neurons plays an important role in the metabolic regulation of fertility. We used the Cre-loxP system to generate mice with a selective inactivation of the Insr gene from GABAergic (Vgat+) or glutamatergic (Vglut2+) cells by crossing Insr-flox mice with Vgat-Cre or Vglut2-Cre mice, respectively. Multiple reproductive and metabolic parameters were then compared between male and female Insr-flox/Vgat-Cre+ (VgatIRKO), Insr-flox/Vglut2-Cre+ (VglutIRKO), and Insr-flox/Cre-negative control (CON) mice. Female VgatIRKO mice exhibited a significant increase in adult body weight, abdominal fat mass, and fasting plasma insulin and leptin concentrations, but normal fasting glucose concentration and glucose tolerance compared with CON mice. Surprisingly, VgatIRKO and VglutIRKO mice exhibited normal reproductive maturation and function compared with CONs. No differences in the age of puberty onset, estrous cyclicity, or fertility were observed between VgatIRKO, VglutIRKO, and CON mice. However, male VgatIRKO mice exhibited significantly augmented LH concentration and a trend toward reduced seminal vesicle weight compared with CON mice, which may be indicative of primary hypogonadism. Our results therefore demonstrate that insulin signaling via GABAergic and glutamatergic cells is not required for fertility in mice, but show that GABAergic neurons encompass circuitry through which insulin acts to modulate energy homeostasis.
Common and Rare Variants in the Exons and Regulatory Regions of Osteoporosis-Related Genes Improve Osteoporotic Fracture Risk Prediction
Authors: Lee Seung Hun , Kang Moo Il , Ahn Seong Hee , Lim Kyeong-Hye , Lee Gun Eui , Shin Eun-Soon , Lee Jong-Eun , Kim Beom-Jun , Cho Eun-Hee , Kim Sang-Wook , Kim Tae-Ho , Kim Hyun-Ju , Yoon Kun-Ho , Lee Won Chul , Kim Ghi Su , Koh Jung-Min , Kim Shin-Yoon 
Published: August 2014

Context:
Osteoporotic fracture risk is highly heritable, but genome-wide association studies have explained only a small proportion of the heritability to date. Genetic data may improve prediction of fracture risk in osteopenic subjects and assist early intervention and management.

Objective:
To detect common and rare variants in coding and regulatory regions related to osteoporosis-related traits, and to investigate whether genetic profiling improves the prediction of fracture risk.

Design and Setting:
This cross-sectional study was conducted in three clinical units in Korea.

Participants:
Postmenopausal women with extreme phenotypes (n = 982) were used for the discovery set, and 3895 participants were used for the replication set.

Main Outcome Measure:
We performed targeted resequencing of 198 genes. Genetic risk scores from common variants (GRS-C) and from common and rare variants (GRS-T) were calculated.

Results:
Nineteen common variants in 17 genes (of the discovered 34 functional variants in 26 genes) and 31 rare variants in five genes (of the discovered 87 functional variants in 15 genes) were associated with one or more osteoporosis-related traits. Accuracy of fracture risk classification was improved in the osteopenic patients by adding GRS-C to fracture risk assessment models (6.8%; P &lt; .001) and was further improved by adding GRS-T (9.6%; P &lt; .001). GRS-C improved classification accuracy for vertebral and nonvertebral fractures by 7.3% (P = .005) and 3.0% (P = .091), and GRS-T further improved accuracy by 10.2% (P &lt; .001) and 4.9% (P = .008), respectively.

Conclusions:
Our results suggest that both common and rare functional variants may contribute to osteoporotic fracture and that adding genetic profiling data to current models could improve the prediction of fracture risk in an osteopenic individual.
Aldosterone Suppression on Contralateral Adrenal During Adrenal Vein Sampling Does Not Predict Blood Pressure Response After Adrenalectomy
Authors: Monticone Silvia , Satoh Fumitoshi , Viola Andrea , Fischer Evelyn , Vonend Oliver , Bernini Giampaolo , Lucatello Barbara , Quinkler Marcus , Ronconi Vanessa , Morimoto Ryo , Kudo Masataka , Degenhart Christoph , Gao Xing , Carrara Davide , Willenberg Holger S. , Rossato Denis , Mengozzi Giulio , Riester Anna , Paci Enrico , Iwakura Yoshitsugu , Burrello Jacopo , Maccario Mauro , Giacchetti Gilberta , Veglio Franco , Ito Sadayoshi , Reincke Martin , Mulatero Paolo 
Published: August 2014

Context:
Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers.

Objective:
The objective of the study was to retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA.

Setting:
The study was carried out in eight different referral centers in Italy, Germany, and Japan.

Patients:
From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses.

Results:
Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared with basal procedures (90% vs 77%). The CL ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P = .02 and P = .01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters, and patients with CL suppression underwent a significantly larger reduction in the aldosterone levels after adrenalectomy.

Conclusions:
For patients with lateralizing indices of greater than 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.
One-pot Synthesis of Gold–Platinum Core–Shell Nanoparticles on Polybenzimidazole-decorated Carbon Nanotubes
Authors: Kim ChaeRin , Fujigaya Tsuyohiko , Nakashima Naotoshi 
Published: August 2014

Abstract
Gold (Au) nanoparticles having a Pt-shell layer (Au–Pt) deposited on a conductive support are a promising electrocatalyst for fuel cells, enabling the minimal use of Pt. We describe a facile one-pot method to grow Au–Pt having a 3.8-nm diameter on multiwalled carbon nanotubes (MWNTs) in the absence of a reducing agent, in which polybenzimidazole was used as the binding sites on the MWNTs to load the Au–Pt.
Palladium-catalyzed Annulation of 2-Substituted Silylethynyloxybiaryls through δ-C–H Activation
Authors: Minami Yasunori , Anami Tomohiro , Hiyama Tamejiro 
Published: August 2014

Abstract
The intramolecular hydroarylation of 2-(silylethynyloxy)biphenyls takes place with the aid of a palladium catalyst to give 6-methylene-6H-dibenzo[b,d]pyrans. The product can be transformed into 6,6-disubstituted dibenzopyrans via protodesilylation, followed by 1,2-addition. 1,4-Bis[2-(triisopropylsilylethynyloxy)phenyl]benzene is shown to undergo a dual intramolecular insertion reaction leading to the formation of pentacyclic condensed aromatics.
Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-
Authors: Perdigones Nieves , Morales Mariela , Mason Philip , Bessler Monica 
Published: August 2014

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A- (G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in thePIGAgene. PIGAencodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol (GPI) anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking Bactrim, a drug that precipitates hemolysis in G6PD deficient individuals. Since bothG6PDandPIGAare X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normalG6PD Ballele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode.