bluuebunny/crossref_metadata_2025_split huggingface dataset:
A receptor-like kinase gene (GbRLK) from Gossypium barbadense enhances salinity and drought-stress tolerance in Arabidopsis
Authors: Zhao Jun , Gao Yulong , Zhang Zhiyuan , Chen Tianzi , Guo Wangzhen , Zhang Tianzhen 
Published: August 2013

AbstractBackgroundCotton (Gossypiumspp.) is widely cultivated due to the important economic value of its fiber. However, extreme environmental degradation impedes cotton growth and production. Receptor-like kinase (RLK) proteins play important roles in signal transduction and participate in a diverse range of processes in response to plant hormones and environmental cues. Here, we introduced an RLK gene (GbRLK) from cotton intoArabidopsisand investigated its role in imparting abiotic stress tolerance.ResultsGbRLKtranscription was induced by exogenously supplied abscisic acid (ABA), salicylic acid, methyl jasmonate, mock drought conditions and high salinity. We cloned the promoter sequence of this geneviaself-formed adaptor PCR. Sequence analysis revealed that the promoter region contains manycis-acting stress-responsive elements such as ABRE, W-Box, MYB-core, W-Box core, TCA-element and others. We constructed a vector containing a 1,890-bp sequence in the 5′ region upstream of the initiation codon of this promoter and transformed it intoArabidopsis thaliana. GUS histochemical staining analysis showed thatGbRLKwas expressed mainly in leaf veins, petioles and roots of transgenicArabidopsis, but not in the cotyledons or root hairs.GbRLKpromoter activity was induced by ABA, PEG, NaCl andVerticillium dahliae.TransgenicArabidopsiswith constitutive overexpression ofGbRLKexhibited a reduced rate of water loss in leavesin vitro, along with improved salinity and drought tolerance and increased sensitivity to ABA compared with non-transgenic Col-0Arabidopsis. Expression analysis of stress-responsive genes inGbRLK Arabidopsisrevealed that there was increased expression of genes involved in the ABA-dependent signaling pathway (AtRD20, AtRD22andAtRD26) and antioxidant genes (AtCAT1, AtCCS, AtCSD2andAtCSD1) but not ion transporter genes (AtNHX1, AtSOS1).ConclusionsGbRLKis involved in the drought and high salinity stresses pathway by activating or participating in the ABA signaling pathway. Overexpression ofGbRLKmay improve stress tolerance by regulating stress-responsive genes to reduce water loss.GbRLKmay be employed in the genetic engineering of novel cotton cultivars in the future. Further studying ofGbRLKwill help elucidate abiotic stress signaling pathways.
Sequencing-based variant detection in the polyploid crop oilseed rape
Authors: Wells Rachel , Trick Martin , Fraser Fiona , Soumpourou Eleni , Clissold Leah , Morgan Colin , Pauquet Jérôme , Bancroft Ian 
Published: August 2013

Abstract

Background
The detection and exploitation of genetic variation underpins crop improvement. However, the polyploid nature of the genomes of many of our most important crops represents a barrier, particularly for the analysis of variation within genes. To overcome this, we aimed to develop methodologies based on amplicon sequencing that involve the incorporation of barcoded amplification tags (BATs) into PCR products.

Results
A protocol was developed to tag PCR products with 5’ 6-base oligonucleotide barcode extensions before pooling for sequencing library production using standard Illumina adapters. A computational method was developed for the de-convolution of products and the robust detection and scoring of sequence variants. Using this methodology, amplicons targeted to gene sequences were screened across a B. napus mapping population and the resulting allele scoring strings for 24 markers linkage mapped to the expected regions of the genome. Furthermore, using one-dimensional 8-fold pooling, 4608 lines of a B. napus mutation population were screened for induced mutations in a locus-specific amplicon (an orthologue of GL2.b) and mixed product of three co-amplified loci (orthologues of FAD2), identifying 10 and 41 mutants respectively.

Conclusions
The utilisation of barcode tags to de-convolute pooled PCR products in multiplexed, variation screening via Illumina sequencing provides a cost effective method for SNP genotyping and mutation detection and, potentially, markers for causative changes, even in polyploid species. Combining this approach with existing Illumina multiplexing workflows allows the analysis of thousands of lines cheaply and efficiently in a single sequencing run with minimal library production costs.
Comparison of the risk factors effects between two populations: two alternative approaches illustrated by the analysis of first and second kidney transplant recipients
Authors: Trébern-Launay Katy , Giral Magali , Dantal Jacques , Foucher Yohann 
Published: August 2013

AbstractBackgroundWhereas the prognosis of second kidney transplant recipients (STR) compared to the first ones has been frequently analyzed, no study has addressed the issue of comparing the risk factor effects on graft failure between both groups.MethodsHere, we propose two alternative strategies to study the heterogeneity of risk factors between two groups of patients:(i) a multiplicative-regression model for relative survival (MRS) and(ii) a stratified Cox model (SCM) specifying the graft rank as strata and assuming subvectors of the explicatives variables. These developments were motivated by the analysis of factors associated with time to graft failure (return-to-dialysis or patient death) in second kidney transplant recipients (STR) compared to the first ones. Estimation of the parameters was based on partial likelihood maximization. Monte-Carlo simulations associated with bootstrap re-sampling was performed to calculate the standard deviations for the MRS.ResultsWe demonstrate, for the first time in renal transplantation, that:(i) male donor gender is a specific risk factor for STR,(ii) the adverse effect of recipient age is enhanced for STR and(iii) the graft failure risk related to donor age is attenuated for STR.ConclusionWhile the traditional Cox model did not provide original results based on the renal transplantation literature, the proposed relative and stratified models revealed new findings that are useful for clinicians. These methodologies may be of interest in other medical fields when the principal objective is the comparison of risk factors between two populations.
The association between cecal insertion time and colorectal neoplasm detection
Authors: Yang Moon Hee , Cho Juhee , Rampal Sanjay , Choi Eun Kyung , Choi Yoon-Ho , Lee Jun Haeng , Kim Young-Ho , Chang Dong Kyung , Rhee Poong-Lyul , Kim Jae J , Guallar Eliseo , Rhee Jong Chul , Son Hee Jung 
Published: August 2013

Abstract

Background
Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening.

Methods
We performed a cross-sectional study of 12,679 consecutive subjects aged 40–79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009. Fixed effects logistic regression conditioning on colonoscopist was used to eliminate confounding due to differences in technical ability and other characteristics across colonoscopists.

Results
The mean cecal insertion time was 5.9 (SD, 4.4 minutes). We identified 4,249 (33.5%) participants with colorectal neoplasms, of whom 1,956 had small single adenomas (<5 mm), 595 had medium single adenomas (5–9 mm), and 1,699 had multiple adenomas or advanced colorectal neoplasms. The overall rates of colorectal neoplasm detection by quartiles of cecal insertion time were 36.8%, 33.4%, 32.7%, and 31.0%, respectively (p trend <0.001).The odds for small single colorectal adenoma detection was 16% lower (adjusted OR 0.84; 95% CI 0.71 to 0.99) in the fourth compared to the first quartile of insertion time (p trend 0.005). Insertion time was not associated with the detection rate of single adenomas ≥5 mm, multiple adenomas or advanced colorectal neoplasms.

Conclusion
Shorter insertion times were associated with increased rates of detection of small colorectal adenomas <5 mm. Cecal insertion time may be clinically relevant as missed small colorectal adenomas may progress to more advanced lesions.
Dietary quality in a sample of adults with type 2 diabetes mellitus in Ireland; a cross-sectional case control study
Authors: Murray Alison E , McMorrow Aoibheann M , O’Connor Eamonn , Kiely Catherine , Mac Ananey Oscar , O'Shea Donal , Egaña Mikel , Lithander Fiona E 
Published: August 2013

Abstract

Background
A number of dietary quality indices (DQIs) have been developed to assess the quality of dietary intake. Analysis of the intake of individual nutrients does not reflect the complexity of dietary behaviours and their association with health and disease. The aim of this study was to determine the dietary quality of individuals with type 2 diabetes mellitus (T2DM) using a variety of validated DQIs.

Methods
In this cross-sectional analysis of 111 Caucasian adults, 65 cases with T2DM were recruited from the Diabetes Day Care Services of St. Columcille’s and St. Vincent’s Hospitals, Dublin, Ireland. Forty-six controls did not have T2DM and were recruited from the general population. Data from 3-day estimated diet diaries were used to calculate 4 DQIs.

Results
Participants with T2DM had a significantly lower score for consumption of a Mediterranean dietary pattern compared to the control group, measured using the Mediterranean Diet Score (Range 0–9) and the Alternate Mediterranean Diet Score (Range 0–9) (mean ± SD) (3.4 ± 1.3 vs 4.8 ± 1.8, P < 0.001 and 3.3 ± 1.5 vs 4.2 ± 1.8, P = 0.02 respectively). Participants with T2DM also had lower dietary quality than the control population as assessed by the Healthy Diet Indicator (Range 0–9) (T2DM; 2.6 ± 2.3, control; 3.3 ± 1.1, P = 0.001). No differences between the two groups were found when dietary quality was assessed using the Alternate Healthy Eating Index. Micronutrient intake was assessed using the Micronutrient Adequacy Score (Range 0–8) and participants with T2DM had a significantly lower score than the control group (T2DM; 1.6 ± 1.4, control; 2.3 ± 1.4, P = 0.009). When individual nutrient intakes were assessed, no significant differences were observed in macronutrient intake.

Conclusion
Overall, these findings demonstrate that T2DM was associated with a lower score when dietary quality was assessed using a number of validated indices.
Combined p21-activated kinase and farnesyltransferase inhibitor treatment exhibits enhanced anti-proliferative activity on melanoma, colon and lung cancer cell lines
Authors: Porcu Giampiero , Parsons Ainslie B , Di Giandomenico Daniele , Lucisano Giuseppe , Mosca Maria Giovanna , Boone Charles , Ragnini-Wilson Antonella 
Published: August 2013

Abstract

Background
Farnesyltransferase inhibitors (FTIs) are anticancer agents with a spectrum of activity in Ras-dependent and independent tumor cellular and xenograph models. How inhibition of protein farnesylation by FTIs results in reduced cancer cell proliferation is poorly understood due to the multiplicity of potential FTase targets. The low toxicity and oral availability of FTIs led to their introduction into clinical trials for the treatment of breast cancer, hematopoietic malignancy, advanced solid tumor and pancreatic cancer treatment, and Hutchinson-Gilford Progeria Syndrome. Although their efficacy in combinatorial therapies with conventional anticancer treatment for myeloid malignancy and solid tumors is promising, the overall results of clinical tests are far below expectations. Further exploitation of FTIs in the clinic will strongly rely on understanding how these drugs affect global cellular activity.

Methods
Using FTase inhibitor I and genome-wide chemical profiling of the yeast barcoded deletion strain collection, we identified genes whose inactivation increases the antiproliferative action of this FTI peptidomimetic. The main findings were validated in a panel of cancer cell lines using FTI-277 in proliferation and biochemical assays paralleled by multiparametric image-based analyses.

Results
ABC transporter Pdr10 or p-21 activated kinase (PAK) gene deletion increases the antiproliferative action of FTase inhibitor I in yeast cells. Consistent with this, enhanced inhibition of cell proliferation by combining group I PAK inhibition, using IPA3, with FTI-277 was observed in melanoma (A375MM), lung (A549) and colon (HT29), but not in epithelial (HeLa) or breast (MCF7), cancer cell lines. Both HeLa and A375MM cells show changes in the nuclear localization of group 1 PAKs in response to FTI-277, but up-regulation of PAK protein levels is observed only in HeLa cells.

Conclusions
Our data support the view that group I PAKs are part of a pro-survival pathway activated by FTI treatment, and group I PAK inactivation potentiates the anti-proliferative action of FTIs in yeast as well as in cancer cells. These findings open new perspectives for the use of FTIs in combinatorial strategies with PAK inhibitors in melanoma, lung and colon malignancy.
Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells
Authors: Di Cello Francescopaolo , Flowers V Lynn , Li Huili , Vecchio-Pagán Briana , Gordon Brent , Harbom Kirsten , Shin James , Beaty Robert , Wang Wei , Brayton Cory , Baylin Stephen B , Zahnow Cynthia A 
Published: August 2013

Abstract

Background
Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic mammary epithelial cells and breast cancer cells using in vitro and in vivo models of chronic cigarette smoke exposure.

Results
We show that both non-tumorigenic (MCF 10A, MCF-12A) and tumorigenic (MCF7) breast epithelial cells exposed to cigarette smoke acquire mesenchymal properties such as fibroblastoid morphology, increased anchorage-independent growth, and increased motility and invasiveness. Moreover, transplantation experiments in mice demonstrate that treatment with cigarette smoke extract renders MCF 10A cells more capable to survive and colonize the mammary ducts and MCF7 cells more prone to metastasize from a subcutaneous injection site, independent of cigarette smoke effects on the host and stromal environment. The extent of transformation and the resulting phenotype thus appear to be associated with the differentiation state of the cells at the time of exposure. Analysis by flow cytometry showed that treatment with CSE leads to the emergence of a CD44hi/CD24low population in MCF 10A cells and of CD44+ and CD49f + MCF7 cells, indicating that cigarette smoke causes the emergence of cell populations bearing markers of self-renewing stem-like cells. The phenotypical alterations induced by cigarette smoke are accompanied by numerous changes in gene expression that are associated with epithelial to mesenchymal transition and tumorigenesis.

Conclusions
Our results indicate that exposure to cigarette smoke leads to a more aggressive and transformed phenotype in human mammary epithelial cells and that the differentiation state of the cell at the time of exposure may be an important determinant in the phenotype of the final transformed state.
A rare case of bilateral sequential spermatocytic seminoma
Authors: Xu Ning , Li Fubiao , Tian Runhui , Shao Mingming , Liu Lingyun , Guo Kaimin 
Published: August 2013

Abstract
Spermatocytic seminoma (SS) is a rare testicular neoplasm characterized by a palpable, painless, slowly enlarging mass in the testis. Even more rare is a synchronous bilateral presentation. Only eight cases of bilateral SS have been reported in the literature, of which three cases were present with synchronous testis enlargement, and five were sequential. Here, we report an additional case of synchronous bilateral SS and present a comprehensive relevant literature review concerning clinical features, histopathology, and treatment.
Inverse spectral problems for non-selfadjoint second-order differential operators with Dirichlet boundary conditions
Authors: Buterin Sergey A , Shieh Chung-Tsun , Yurko Vjacheslav A 
Published: August 2013

Abstract
We study the inverse problem for non-selfadjoint Sturm-Liouville operators on a finite interval with possibly multiple spectra. We prove the uniqueness theorem and obtain constructive procedures for solving the inverse problem along with the necessary and sufficient conditions of its solvability and also prove the stability of the solution.

MSC:34A55, 34B24, 47E05.
Identification of novel key amino acids at the interface of the transmembrane domains of human BST-2 and HIV-1 Vpu
Authors: Pang Xiaojing , Hu Siqi , Li Jian , Xu Fengwen , Mei Shan , Zhou Jinming , Cen Shan , Jin Qi , Guo Fei 
Published: August 2013

Abstract

Background
BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits virus release by tethering viral particles to the cell surface. This antiviral activity of BST-2 is antagonized by HIV-1 accessory protein Vpu. Vpu physically interacts with BST-2 through their mutual transmembrane (TM) domains. In this study, we utilized the BRET assay and molecular dynamics (MD) simulation method to further characterize the interaction of BST-2 and Vpu.

Results
Amino acids I34, L37, P40 and L41 in the TM domain of BST-2, and L11, A18 and W22 in the TM domain of Vpu were identified to be critical for the interaction between BST-2 and Vpu. The residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu were shown, for the first time, to be important for their interaction. Furthermore, triple-amino-acid substitutions, 14–16 (AII to VAA) and 26–28 (IIE to AAA) in Vpu TM, not the single-residue mutation, profoundly disrupted BST-2/Vpu interaction. The results of MD simulation revealed significant conformational changes of the BST-2/Vpu complex as a result of mutating P40 of BST-2 and L11, 14–16 (AII to VAA) and 26–28 (IIE to AAA) of Vpu. In addition, disrupting the interaction between BST-2 and Vpu rendered BST-2 resistant to Vpu antagonization.

Conclusions
Through use of the BRET assay, we identified novel key residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu that are important for their interaction. These results add new insights into the molecular mechanism behind BST-2 antagonization by HIV-1 Vpu.
What supports do health system organizations have in place to facilitate evidence-informed decision-making? a qualitative study
Authors: Ellen Moriah E , Léon Gregory , Bouchard Gisèle , Lavis John N , Ouimet Mathieu , Grimshaw Jeremy M 
Published: August 2013

Abstract

Background
Decisions regarding health systems are sometimes made without the input of timely and reliable evidence, leading to less than optimal health outcomes. Healthcare organizations can implement tools and infrastructures to support the use of research evidence to inform decision-making.

Objectives
The purpose of this study was to profile the supports and instruments (i.e., programs, interventions, instruments or tools) that healthcare organizations currently have in place and which ones were perceived to facilitate evidence-informed decision-making.

Methods
In-depth semi-structured telephone interviews were conducted with individuals in three different types of positions (i.e., a senior management team member, a library manager, and a ‘knowledge broker’) in three types of healthcare organizations (i.e., regional health authorities, hospitals and primary care practices) in two Canadian provinces (i.e., Ontario and Quebec). The interviews were taped, transcribed, and then analyzed thematically using NVivo 9 qualitative data analysis software.

Results
A total of 57 interviews were conducted in 25 organizations in Ontario and Quebec. The main findings suggest that, for the healthcare organizations that participated in this study, the following supports facilitate evidence-informed decision-making: facilitating roles that actively promote research use within the organization; establishing ties to researchers and opinion leaders outside the organization; a technical infrastructure that provides access to research evidence, such as databases; and provision and participation in training programs to enhance staff’s capacity building.

Conclusions
This study identified the need for having a receptive climate, which laid the foundation for the implementation of other tangible initiatives and supported the use of research in decision-making. This study adds to the literature on organizational efforts that can increase the use of research evidence in decision-making. Some of the identified supports may increase the use of research evidence by decision-makers, which may then lead to more informed decisions, and hopefully to a strengthened health system and improved health.
Genotype-phenotype correlations in recessive RYR1-related myopathies
Authors: Amburgey Kimberly , Bailey Angela , Hwang Jean H , Tarnopolsky Mark A , Bonnemann Carsten G , Medne Livija , Mathews Katherine D , Collins James , Daube Jasper R , Wellman Gregory P , Callaghan Brian , Clarke Nigel F , Dowling James J 
Published: August 2013

Abstract

Background

RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed.

Methods
In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases.

Results
Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore.

Conclusions
These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of genotype-phenotype associations in recessive RYR1-myopathies.