bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of genes with a function in axon outgrowth and synapse formation in motor neurones of the VEGFδ/δ mouse model of amyotrophic lateral sclerosis
Authors: Brockington Alice , Heath Paul R , Holden Hazel , Kasher Paul , Bender Florian LP , Claes Filip , Lambrechts Diether , Sendtner Michael , Carmeliet Peter , Shaw Pamela J 
Published: March 2010

Abstract

Background
Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that stimulates vasculogenesis. It has also been shown to act as a neurotrophic factor in vitro and in vivo. Deletion of the hypoxia response element of the promoter region of the gene encoding VEGF in mice causes a reduction in neural VEGF expression, and results in adult-onset motor neurone degeneration that resembles amyotrophic lateral sclerosis (ALS). Investigating the molecular pathways to neurodegeneration in the VEGFδ/δ mouse model of ALS may improve understanding of the mechanisms of motor neurone death in the human disease.

Results
Microarray analysis was used to determine the transcriptional profile of laser captured spinal motor neurones of transgenic and wild-type littermates at 3 time points of disease. 324 genes were significantly differentially expressed in motor neurones of presymptomatic VEGFδ/δ mice, 382 at disease onset, and 689 at late stage disease. Massive transcriptional downregulation occurred with disease progression, associated with downregulation of genes involved in RNA processing at late stage disease. VEGFδ/δ mice showed reduction in expression, from symptom onset, of the cholesterol synthesis pathway, and genes involved in nervous system development, including axonogenesis, synapse formation, growth factor signalling pathways, cell adhesion and microtubule-based processes. These changes may reflect a reduced capacity of VEGFδ/δ mice for maintenance and remodelling of neuronal processes in the face of demands of neural plasticity. The findings are supported by the demonstration that in primary motor neurone cultures from VEGFδ/δ mice, axon outgrowth is significantly reduced compared to wild-type littermates.

Conclusions
Downregulation of these genes involved in axon outgrowth and synapse formation in adult mice suggests a hitherto unrecognized role of VEGF in the maintenance of neuronal circuitry. Dysregulation of VEGF may lead to neurodegeneration through synaptic regression and dying-back axonopathy.
Physical mapping in highly heterozygous genomes: a physical contig map of the Pinot Noir grapevine cultivar
Authors: Scalabrin Simone , Troggio Michela , Moroldo Marco , Pindo Massimo , Felice Nicoletta , Coppola Giuseppina , Prete Giacomo , Malacarne Giulia , Marconi Raffaella , Faes Giorgia , Jurman Irena , Grando Stella , Jesse Taco , Segala Cinzia , Valle Giorgio , Policriti Alberto , Fontana Paolo , Morgante Michele , Velasco Riccardo 
Published: March 2010

Abstract

Background
Most of the grapevine (Vitis vinifera L.) cultivars grown today are those selected centuries ago, even though grapevine is one of the most important fruit crops in the world. Grapevine has therefore not benefited from the advances in modern plant breeding nor more recently from those in molecular genetics and genomics: genes controlling important agronomic traits are practically unknown. A physical map is essential to positionally clone such genes and instrumental in a genome sequencing project.

Results
We report on the first whole genome physical map of grapevine built using high information content fingerprinting of 49,104 BAC clones from the cultivar Pinot Noir. Pinot Noir, as most grape varieties, is highly heterozygous at the sequence level. This resulted in the two allelic haplotypes sometimes assembling into separate contigs that had to be accommodated in the map framework or in local expansions of contig maps. We performed computer simulations to assess the effects of increasing levels of sequence heterozygosity on BAC fingerprint assembly and showed that the experimental assembly results are in full agreement with the theoretical expectations, given the heterozygosity levels reported for grape. The map is anchored to a dense linkage map consisting of 994 markers. 436 contigs are anchored to the genetic map, covering 342 of the 475 Mb that make up the grape haploid genome.

Conclusions
We have developed a resource that makes it possible to access the grapevine genome, opening the way to a new era both in grape genetics and breeding and in wine making. The effects of heterozygosity on the assembly have been analyzed and characterized by using several complementary approaches which could be easily transferred to the study of other genomes which present the same features.
Healthcare workers and health care-associated infections: knowledge, attitudes, and behavior in emergency departments in Italy
Authors: Parmeggiani Cristiana , Abbate Rossella , Marinelli Paolo , Angelillo Italo F 
Published: March 2010

AbstractBackgroundThis survey assessed knowledge, attitudes, and compliance regarding standard precautions about health care-associated infections (HAIs) and the associated determinants among healthcare workers (HCWs) in emergency departments in Italy.MethodsAn anonymous questionnaire, self-administered by all HCWs in eight randomly selected non-academic acute general public hospitals, comprised questions on demographic and occupational characteristics; knowledge about the risks of acquiring and/or transmitting HAIs from/to a patient and standard precautions; attitudes toward guidelines and risk perceived of acquiring a HAI; practice of standard precautions; and sources of information.ResultsHCWs who know the risk of acquiring Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) from a patient were in practice from less years, worked fewer hours per week, knew that a HCW can transmit HCV and HIV to a patient, knew that HCV and HIV infections can be serious, and have received information from educational courses and scientific journals. Those who know that gloves, mask, protective eyewear, and hands hygiene after removing gloves are control measures were nurses, provided care to fewer patients, knew that HCWs' hands are vehicle for transmission of nosocomial pathogens, did not know that a HCW can transmit HCV and HIV to a patient, and have received information from educational courses and scientific journals. Being a nurse, knowing that HCWs' hands are vehicle for transmission of nosocomial pathogens, obtaining information from educational courses and scientific journals, and needing information were associated with a higher perceived risk of acquiring a HAI. HCWs who often or always used gloves and performed hands hygiene measures after removing gloves were nurses, provided care to fewer patients, and knew that hands hygiene after removing gloves was a control measure.ConclusionsHCWs have high knowledge, positive attitudes, but low compliance concerning standard precautions. Nurses had higher knowledge, perceived risk, and appropriate HAIs' control measures than physicians and HCWs answered correctly and used appropriately control measures if have received information from educational courses and scientific journals.
DNA methylation profiling in doxorubicin treated primary locally advanced breast tumours identifies novel genes associated with survival and treatment response
Authors: Dejeux Emelyne , Rønneberg Jo Anders , Solvang Hiroko , Bukholm Ida , Geisler Stephanie , Aas Turid , Gut Ivo G. , Børresen-Dale Anne-Lise , Lønning Per Eystein , Kristensen Vessela N. , Tost Jörg 
Published: March 2010

Abstract

Background
Breast cancer is the most frequent cancer in women and consists of a heterogeneous collection of diseases with distinct histopathological, genetic and epigenetic characteristics. In this study, we aimed to identify DNA methylation based biomarkers to distinguish patients with locally advanced breast cancer who may benefit from neoadjuvant doxorubicin treatment.

Results
We investigated quantitatively the methylation patterns in the promoter regions of 14 genes (ABCB1, ATM, BRCA1, CDH3, CDKN2A, CXCR4, ESR1, FBXW7, FOXC 1, GSTP1, IGF2, HMLH1, PPP2R2B, and PTEN) in 75 well-described pre-treatment samples from locally advanced breast cancer and correlated the results to the available clinical and molecular parameters. Six normal breast tissues were used as controls and 163 unselected breast cancer cases were used to validate associations with histopathological and clinical parameters.
Aberrant methylation was detected in 9 out of the 14 genes including the discovery of methylation at the FOXC1 promoter. Absence of methylation at the ABCB1 promoter correlated with progressive disease during doxorubicin treatment. Most importantly, the DNA methylation status at the promoters of GSTP1, FOXC1 and ABCB1 correlated with survival, whereby the combination of methylated genes improved the subdivision with respect to the survival of the patients. In multivariate analysis GSTP1 and FOXC1 methylation status proved to be independent prognostic markers associated with survival.

Conclusions
Quantitative DNA methylation profiling is a powerful tool to identify molecular changes associated with specific phenotypes. Methylation at the ABCB1 or GSTP1 promoter improved overall survival probably due to prolonged availability and activity of the drug in the cell while FOXC1 methylation might be a protective factor against tumour invasiveness. FOXC1 proved to be general prognostic factor, while ABCB1 and GSTP1 might be predictive factors for the response to and efficacy of doxorubicin treatment. Pharmacoepigenetic effects such as the reported associations in this study provide molecular explanations for differential responses to chemotherapy and it might prove valuable to take the methylation status of selected genes into account for patient management and treatment decisions.
Downregulated expression of HSP27 in human low-grade glioma tissues discovered by a quantitative proteomic analysis
Authors: Shen Guobo , Liang Shufang , Xu Zhizhong , Zhou Liangxue , Xiao Shiyin , Xia Xiangying , Li Ronghui , Liao Ying , You Chao , Wei Yuquan 
Published: March 2010

Abstract

Background
Heat shock proteins (HSPs), including mainly HSP110, HSP90, HSP70, HSP60 and small HSP families, are evolutionary conserved proteins involved in various cellular processes. Abnormal expression of HSPs has been detected in several tumor types, which indicates that specific HSPs have different prognostic significance for different tumors. In the current studies, the expression profiling of HSPs in human low-grade glioma tissues (HGTs) were investigated using a sensitive, accurate SILAC (stable isotope labeling with amino acids in cell culture)-based quantitative proteomic strategy.

Results
The five HSP family members were detected and quantified in both HGTs and autologous para-cancerous brain tissues (PBTs) by the SILAC-based mass spectrometry (MS) simultaneously. HSP90 AB1, HSP A5(70 KDa), and especially HSP27 were significantly downregulated in HGTs, whereas the expression level of HSPA9 (70 KDa) was little higher in HGTs than that in PBTs. It was noted that the downregulation ratio of HSP27 was 0.48-fold in HGTs versus PBTs, which was further validated by results from RT-PCR, western blotting and immunohistochemistry. Furthermore, we detected HSP27 expression changes along with cell growth under heat shock treatment in glioma H4 cells.

Conclusion
The SILAC-MS technique is an applicable and efficient novel method, with a high-throughput manner, to quantitatively compare the relative expression level of HSPs in brain tumors. Different HSP family members have specific protein expression levels in human low-grade glioma discovered by SILAC-MS analysis. HSP27 expression was obviously downregulated in HGTs versus PBTs, and it exhibited temporal and spatial variation under heat shock treatment (43°C/0-3 h) in vitro. HSP27's rapid upregulation was probably correlated with the temporary resistance to heat shock in order to maintain the survival of human glioma cells.
An Improved Behavioural Assay Demonstrates That Ultrasound Vocalizations Constitute a Reliable Indicator of Chronic Cancer Pain and Neuropathic Pain
Authors: Kurejova Martina , Nattenmüller Ulrike , Hildebrandt Ullrich , Selvaraj Deepitha , Stösser Sebastian , Kuner Rohini 
Published: March 2010

Background: On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs) have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results: We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions: We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain) and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.
Diagnostic challenge: bilateral infected lumbar facet cysts - a rare cause of acute lumbar spinal stenosis and back pain
Authors: Freedman Brett A , Bui Tuan L , Yoon S Timothy 
Published: March 2010

Abstract
Symptomatic synovial lumbar facet cysts are a relatively rare cause of radiculopathy and spinal stenosis. This case and brief review of the literature, details a patient who presented with acutely symptomatic bilateral spontaneously infected synovial facet (L4/5) cysts. This report highlights diagnostic clues for identifying infection of a facet cyst.
Genetic variation in the estrogen metabolic pathway and mammographic density as an intermediate phenotype of breast cancer
Authors: Li Jingmei , Eriksson Louise , Humphreys Keith , Czene Kamila , Liu Jianjun , Tamimi Rulla M , Lindström Sara , Hunter David J , Vachon Celine M , Couch Fergus J , Scott Christopher G , Lagiou Pagona , Hall Per 
Published: March 2010

Abstract
Introduction
Several studies have examined the effect of genetic variants in genes involved in the estrogen metabolic pathway on mammographic density, but the number of loci studied and the sample sizes evaluated have been small and pathways have not been evaluated comprehensively. In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway.

Methods
A total of 239 SNPs in 34 estrogen metabolic genes were studied in 1,731 Swedish women who participated in a breast cancer case-control study, of which 891 were cases and 840 were controls. Film mammograms of the medio-lateral oblique view were digitalized and the software Cumulus was used for computer-assisted semi-automated thresholding of mammographic density. Generalized linear models controlling for possible confounders were used to evaluate the effects of SNPs on mammographic density. Results found to be nominally significant were examined in two independent populations. The admixture maximum likelihood-based global test was performed to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three subpathways for androgen synthesis, androgen-to-estrogen conversion and estrogen removal.

Results
Genetic variants of genes involved in estrogen metabolism exhibited no appreciable effect on mammographic density. None of the nominally significant findings were validated. In addition, global analyses on the overall estrogen metabolic pathway and its subpathways did not yield statistically significant results.

Conclusions
Overall, there is no conclusive evidence that genetic variants in genes involved in the estrogen metabolic pathway are associated with mammographic density in postmenopausal women.
Ghrelin and Obestatin Circadian Levels Differentiate Bingeing-Purging from Restrictive Anorexia Nervosa
Authors: Germain Natacha , Galusca Bogdan , Grouselle Dominique , Frere Delphine , Billard Stephane , Epelbaum Jacques , Estour Bruno 
Published: March 2010

Abstract
Context: Anorexia nervosa (AN) patients present with restrictive food behavior (AN-R). Some of them develop episodes of bulimia (AN-BP) without any clear pathophysiological explanation to date. Their clinical differentiation is important but not easily performed. Orexigenic/anorexigenic peptides measurements could provide some clues for that matter.
Objective: The objective of the study was to determine whether the circadian profile of total and acylated ghrelin, obestatin, and peptide YY (PYY) levels is different in AN-R subjects when compared with AN-BP patients.
Design and Settings: This was a cross-sectional study in an endocrinological unit.
Patients and Control Subjects: Four groups of age-matched young women: 22 AN-R, 10 AN-BP, 16 normal-weight bulimia nervosa (BN), and nine controls.
Main Outcome Measures: Twelve-point circadian profiles of plasma total and acylated ghrelin, obestatin, and PYY were measured.
Results: Total and acylated ghrelin and obestatin circadian levels were increased in AN-R when compared with controls but decreased in both AN-BP and BN groups (P &lt; 0.001). PYY was decreased in all groups with eating disorders. Acylated to total ghrelin ratio was decreased in AN-BP and BN (P &lt; 0.001), whereas obestatin to acylated ghrelin and PYY to acylated ghrelin ratios were increased in both groups with bingeing-purging behavior (P &lt; 0.0001).
Conclusions: Patients with AN-associated bingeing-purging behavior present a very different profile of appetite regulatory peptides when compared with the pure restrictive type. The assessment of ghrelin (and eventually obestatin) could be of particular interest for differential diagnosis. Very low ghrelin levels and increased anorexigenic to orexigenic peptide ratios suggest either a lack of adaptation to a starvation state or a higher facility to cope with undernutrition.
The Expression of E-Cadherin in Somatotroph Pituitary Adenomas Is Related to Tumor Size, Invasiveness, and Somatostatin Analog Response
Authors: Fougner Stine Lyngvi , Lekva Tove , Borota Olivera Casar , Hald John K. , Bollerslev Jens , Berg Jens Petter 
Published: March 2010

Abstract
Context: Appropriate cell-to-cell adhesion is fundamental for the epithelial phenotype of pituitary cells. Loss of the adhesion protein E-cadherin has been associated with invasiveness, metastasis, and poor prognosis in cancers of epithelial origin. In somatotroph adenomas, a variable and reduced expression of E-cadherin has been demonstrated. In addition, nuclear translocation of E-cadherin was found to correlate with pituitary tumor invasion.
Objective: The objective was to examine the protein expression of E-cadherin in somatotroph pituitary adenomas in relation to adenoma size, invasiveness, and somatostatin analog (SMS) efficacy.
Patients and Methods: Eighty-three patients were included, and 29 were treated preoperatively with SMS. Adenoma E-cadherin protein expression was analyzed by Western blot (61 patients) and immunohistochemistry (IHC) (80 patients) with antibodies directed against both extracellular and intracellular domains (IHC). The acute (direct surgery group) and long-term (preoperatively treated group) SMS responses were evaluated. Baseline tumor volume and invasiveness were measured on magnetic resonance imaging scans.
Results: Membranous E-cadherin was lost in several adenomas. Nine of these were nuclear E-cadherin positive. The E-cadherin protein expression correlated negatively to tumor size and positively to acute SMS response. Low E-cadherin levels (preoperatively treated group only) and loss of membranous E-cadherin correlated to tumor invasiveness. The E-cadherin level correlated positively to tumor reduction after SMS treatment, and adenomas with nuclear E-cadherin staining had lower IGF-I reduction and tumor shrinkage. Preoperatively treated adenomas had reduced E-cadherin protein levels, but the IHC expression was unaltered.
Conclusion: Reduced E-cadherin expression may correlate to a dedifferentiated phenotype in the somatotroph pituitary adenomas.
The ADPKD genespkd1a/bandpkd2regulate extracellular matrix formation
Authors: Mangos Steve , Lam Pui-ying , Zhao Angela , Liu Yan , Mudumana Sudha , Vasilyev Aleksandr , Liu Aiping , Drummond Iain A. 
Published: March 2010

SUMMARYMutations in polycystin1 (PKD1) account for the majority of autosomal dominant polycystic kidney disease (ADPKD). PKD1 mutations are also associated with vascular aneurysm and abdominal wall hernia, suggesting a role for polycystin1 in extracellular matrix (ECM) integrity. In zebrafish, combined knockdown of the PKD1 paralogs pkd1a and pkd1b resulted in dorsal axis curvature, hydrocephalus, cartilage and craniofacial defects, and pronephric cyst formation at low frequency (10–15%). Dorsal axis curvature was identical to the axis defects observed in pkd2 knockdown embryos. Combined pkd1a/b, pkd2 knockdown demonstrated that these genes interact in axial morphogenesis. Dorsal axis curvature was linked to notochord collagen overexpression and could be reversed by knockdown of col2a1 mRNA or chemical inhibition of collagen crosslinking. pkd1a/b- and pkd2-deficient embryos exhibited ectopic, persistent expression of multiple collagen mRNAs, suggesting a loss of negative feedback signaling that normally limits collagen gene expression. Knockdown of pkd1a/b also dramatically sensitized embryos to low doses of collagen-crosslinking inhibitors, implicating polycystins directly in the modulation of collagen expression or assembly. Embryos treated with wortmannin or LY-29400 also exhibited dysregulation of col2a1 expression, implicating phosphoinositide 3-kinase (PI3K) in the negative feedback signaling pathway controlling matrix gene expression. Our results suggest that pkd1a/b and pkd2 interact to regulate ECM secretion or assembly, and that altered matrix integrity may be a primary defect underlying ADPKD tissue pathologies.