bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized trial of a hypocaloric high-protein diet, with and without exercise, on weight loss, fitness, and markers of the Metabolic Syndrome in overweight and obese women
Authors: Meckling Kelly A. , Sherfey Rachel 
Published: July 2007

The purpose of this study was to examine the effects of 3:1 and 1:1 carbohydrate to protein ratios, hypocaloric diets with and without exercise, and risk factors associated with the Metabolic Syndrome in overweight and obese Canadian women. Groups were designated as control diet (CON), control diet with exercise (CONEx), high-protein (HP), or high-protein with exercise (HPEx). Free-living women from the Guelph community were studied in a university health and fitness facility. The participants were 44 of 60 overweight and obese women who had been randomized to the 4 weight-loss programs. Habitual diets of the subjects were energy restricted and were to contain either a 1:1 or 3:1 ratio of carbohydrate to protein energy. Subjects either exercised 3 times/week or maintained their normal level of activity for 12 weeks. The main outcome measures were weight loss, blood lipids, blood pressure, insulin, body composition, nitrogen balance, fitness, and resting energy expenditure. All groups lost weight over the 12 week period: –2.1 kg for the CON group, –4.0 kg in the CONEx group, –4.6 kg in the HP group, and –7.0 kg in the HPEx. All participants exhibited improved body composition, decreased blood pressure, and decreased waist and hip circumference. Actual diets consumed by the subjects contained ratios of carbohydrate to protein of 3.0:1, 2.7:1, 1.5:1, and 0.96:1 for the CON, CONEx, HP, and HPEx groups, respectively. Cardiovascular fitness improved in both exercise groups. There were no changes in resting energy expenditure. No adverse events were reported. Significant changes in blood lipids included decreased total cholesterol in the HP and CONEx groups, decreased low-density lipoprotein cholesterol in the HP group only, and decreased blood triglycerides in the HPEx group only. High-density lipoprotein cholesterol, fasting blood glucose, and fasting insulin levels were unaltered by diet or exercise. A high-protein diet was superior to a low-fat, high-carbohydrate diet either alone or when combined with an aerobic/resistance-training program in promoting weight loss and nitrogen balance, while similarly improving body composition and risk factors for the Metabolic Syndrome in overweight and obese Canadian women.
The Ubiquitin-Interacting Motif–Containing Protein RAP80 Interacts with BRCA1 and Functions in DNA Damage Repair Response
Authors: Yan Jun , Kim Yong-Sik , Yang Xiao-Ping , Li Li-Ping , Liao Grace , Xia Fen , Jetten Anton M. 
Published: July 2007

Abstract
In this study, we examine the potential role of receptor-associated protein 80 (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), in DNA damage response and double-strand break (DSB) repair. We show that following ionizing radiation and treatment with DNA-damaging agents, RAP80 translocates to discrete nuclear foci that colocalize with those of γ-H2AX. The UIMs and the region of amino acids 204 to 304 are critical for the relocalization of RAP80 to ionizing radiation–induced foci (IRIF). These observations suggest that RAP80 becomes part of a DNA repair complex at the sites of IRIF. We also show that RAP80 forms a complex with the tumor repressor BRCA1 and that this interaction is mediated through the BRCA1 COOH-terminal repeats of BRCA1. The UIMs are not required for the interaction of RAP80 with BRCA1. Knockdown of RAP80 in HEK293 cells significantly reduced DSB-induced homology-directed recombination (HDR). Moreover, inhibition of RAP80 expression by small interfering RNA increased radiosensitivity, whereas increased radioresistance was observed in human breast cancer MCF-7 cells with overexpression of RAP80. Taken together, our data suggest that RAP80 plays an important role in DNA damage response signaling and HDR-mediated DSB repair. We further show that RAP80 can function as a substrate of the ataxia-telangiectasia mutated protein kinase in vitro, which phosphorylates RAP80 at Ser205 and Ser402. We show that this phosphorylation is not required for the migration of RAP80 to IRIF. [Cancer Res 2007;67(14):6647–56]
Automatic extraction of gene ontology annotation and its correlation with clusters in protein networks
Authors: Daraselia Nikolai , Yuryev Anton , Egorov Sergei , Mazo Ilya , Ispolatov Iaroslav 
Published: July 2007

Abstract

Background
Uncovering cellular roles of a protein is a task of tremendous importance and complexity that requires dedicated experimental work as well as often sophisticated data mining and processing tools. Protein functions, often referred to as its annotations, are believed to manifest themselves through topology of the networks of inter-proteins interactions. In particular, there is a growing body of evidence that proteins performing the same function are more likely to interact with each other than with proteins with other functions. However, since functional annotation and protein network topology are often studied separately, the direct relationship between them has not been comprehensively demonstrated. In addition to having the general biological significance, such demonstration would further validate the data extraction and processing methods used to compose protein annotation and protein-protein interactions datasets.

Results
We developed a method for automatic extraction of protein functional annotation from scientific text based on the Natural Language Processing (NLP) technology. For the protein annotation extracted from the entire PubMed, we evaluated the precision and recall rates, and compared the performance of the automatic extraction technology to that of manual curation used in public Gene Ontology (GO) annotation. In the second part of our presentation, we reported a large-scale investigation into the correspondence between communities in the literature-based protein networks and GO annotation groups of functionally related proteins. We found a comprehensive two-way match: proteins within biological annotation groups form significantly denser linked network clusters than expected by chance and, conversely, densely linked network communities exhibit a pronounced non-random overlap with GO groups. We also expanded the publicly available GO biological process annotation using the relations extracted by our NLP technology. An increase in the number and size of GO groups without any noticeable decrease of the link density within the groups indicated that this expansion significantly broadens the public GO annotation without diluting its quality. We revealed that functional GO annotation correlates mostly with clustering in a physical interaction protein network, while its overlap with indirect regulatory network communities is two to three times smaller.

Conclusion
Protein functional annotations extracted by the NLP technology expand and enrich the existing GO annotation system. The GO functional modularity correlates mostly with the clustering in the physical interaction network, suggesting that the essential role of structural organization maintained by these interactions. Reciprocally, clustering of proteins in physical interaction networks can serve as an evidence for their functional similarity.
Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways
Authors: Dybkaer Karen , Iqbal Javeed , Zhou Guimei , Geng Huimin , Xiao Li , Schmitz Alexander , d'Amore Francesco , Chan Wing C 
Published: July 2007

AbstractBackgroundHuman natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways in resting and IL2 activated NK cell isolated from peripheral blood of healthy donors.ResultsGene expression profiling of resting NK cells showed high expression of a number of cytotoxic factors, cytokines, chemokines and inhibitory and activating surface NK receptors. Resting NK cells expressed many genes associated with cellular quiescence and also appeared to have an active TGFβ (TGFB1) signaling pathway. IL2 stimulation induced rapid downregulation of quiescence associated genes and upregulation of genes associated with cell cycle progression and proliferation. Numerous genes that may enhance immune function and responsiveness including activating receptors (DNAM1, KLRC1andKLRC3), death receptor ligand (TNFSF6 (FASL) andTRAIL), chemokine receptors (CX3CR1, CCR5andCCR7), interleukin receptors (IL2RG, IL18RABandIL27RA) and members of secretory pathways (DEGS1, FKBP11, SSR3, SEC61GandSLC3A2) were upregulated. The expression profile suggested PI3K/AKT activation and NF-κB activation through multiple pathways (TLR/IL1R, TNF receptor induced and TCR-like possibly involving BCL10). Activation of NFAT signaling was supported by increased expression of many pathway members and downstream target genes. The transcription factorGATA3was expressed in resting cells whileT-BETwas upregulated on activation concurrent with the change in cytokine expression profile. The importance of NK cells in innate immune response was also reflected by late increased expression of inflammatory chemotactic factors and receptors and molecules involved in adhesion and lymphocyte trafficking or migration.ConclusionThis analysis allowed us to identify genes implicated in cellular quiescence and the cytokines and cytotoxic factors ready for immediate immune response. It also allowed us to observe the sequential immunostimulatory effects of IL2 on NK cells improving our understanding of the biology and molecular mediators behind NK cell activation.
Secretory granule neuroendocrine protein 1 (SGNE1) genetic variation and glucose intolerance in severe childhood and adult obesity
Authors: Bouatia-Naji Nabila , Vatin Vincent , Lecoeur Cécile , Heude Barbara , Proença Christine , Veslot Jacques , Jouret Béatrice , Tichet Jean , Charpentier Guillaume , Marre Michel , Balkau Beverley , Froguel Philippe , Meyre David 
Published: July 2007

Abstract

Background
7B2 is a regulator/activator of the prohormone convertase 2 which is involved in the processing of numerous neuropeptides, including insulin, glucagon and pro-opiomelanocortin. We have previously described a suggestive genetic linkage peak with childhood obesity on chr15q12-q14, where the 7B2 encoding gene, SGNE1 is located. The aim of this study is to analyze associations of SGNE1 genetic variation with obesity and metabolism related quantitative traits.

Methods
We screened SGNE1 for genetic variants in obese children and genotyped 12 frequent single nucleotide polymorphisms (SNPs). Case control analyses were performed in 1,229 obese (534 children and 695 adults), 1,535 individuals with type 2 diabetes and 1,363 controls, all French Caucasians. We also studied 4,922 participants from the D.E.S.I.R prospective population-based cohort.

Results
We did not find any association between SGNE1 SNPs and childhood or adult obesity. However, the 5' region SNP -1,701A>G associated with higher area under glucose curve after oral glucose tolerance test (p = 0.0005), higher HOMA-IR (p = 0.005) and lower insulinogenic index (p = 0.0003) in obese children. Similar trends were found in obese adults. SNP -1,701A>G did not associate with risk of T2D but tends to associate with incidence of type 2 diabetes (HR = 0.75 95%CI [0.55–1.01]; p = 0.06) in the prospective cohort.

Conclusion

SGNE1 genetic variation does not contribute to obesity and common forms of T2D but may worsen glucose intolerance and insulin resistance, especially in the background of severe and early onset obesity. Further molecular studies are required to understand the molecular bases involved in this process.
The structure of quality systems is important to the process and outcome, an empirical study of 386 hospital departments in Sweden
Authors: Kunkel Stefan , Rosenqvist Urban , Westerling Ragnar 
Published: July 2007

Abstract
Background
Clinicians, nurses, and managers in hospitals are continuously confronted by new technologies and methods that require changes to working practice. Quality systems can help to manage change while maintaining a high quality of care. A new model of quality systems inspired by the works of Donabedian has three factors: structure (resources and administration), process (culture and professional co-operation), and outcome (competence development and goal achievement). The objectives of this study were to analyse whether structure, process, and outcome can be used to describe quality systems, to analyse whether these components are related, and to discuss implications.

Methods
A questionnaire was developed and sent to a random sample of 600 hospital departments in Sweden. The adjusted response rate was 75%. The data were analysed with confirmatory factor analysis and structural equation modeling in LISREL. This is to our knowledge the first large quantitative study that applies Donabedian's model to quality systems.

Results
The model with relationships between structure, process, and outcome was found to be a reasonable representation of quality systems at hospital departments (p = 0.095, indicating no significant differences between the model and the data set). Structure correlated strongly with process (0.72) and outcome (0.60). Given structure, process also correlated with outcome (0.20).

Conclusion
The model could be used to describe and evaluate single quality systems or to compare different quality systems. It could also be an aid to implement a systematic and evidence-based system for working with quality improvements in hospital departments.
DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets
Authors: Wu Qinghua , Lothe Ragnhild A , Ahlquist Terje , Silins Ilvars , Tropé Claes G , Micci Francesca , Nesland Jahn M , Suo Zhenhe , Lind Guro E 
Published: July 2007

AbstractBackgroundThe epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and theirin vitromodels (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features.ResultsEight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation ofHOXA9,RASSF1A,APC,CDH13,HOXB5,SCGB3A1 (HIN-1),CRABP1, andMLH1was found in 51% (26/51), 49% (23/47), 24% (12/51), 20% (10/51), 12% (6/52), 10% (5/52), 4% (2/48), and 2% (1/51) of the carcinomas, respectively, whereasADAMTS1,MGMT,NR3C1,p14ARF, andp16INK4awere unmethylated in all samples. The methylation frequencies ofHOXA9andSCGB3A1were higher among relatively early-stage carcinomas (FIGO I-II) than among carcinomas of later stages (FIGO III-IV;P= 0.002,P= 0.020, respectively). The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally,HOXA9hypermethylation was more common in tumours from patients older than 60 years of age (15/21) than among those of younger age (11/30;P= 0.023). Finally, there was a significant difference inHOXA9methylation frequency among the histological types (P= 0.007).ConclusionDNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis andHOXA9,HOXB5,SCGB3A1, andCRABP1are identified as novel hypermethylated target genes in this tumour type.
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs
Authors: Takahama Kazuo , Shirasaki Tetsuya 
Published: July 2007

AbstractNarcotic antitussives such as codeine reveal the antitussive effect primarily via the μ-opioid receptor in the central nervous system (CNS). The κ-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether δ-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic antitussives are the most potent antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO2gas exposure, coughing is difficult to inhibit with centrally acting antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results.
Trunk rotational strength asymmetry in adolescents with idiopathic scoliosis: an observational study
Authors: McIntire Kevin L , Asher Marc A , Burton Douglas C , Liu Wen 
Published: July 2007

AbstractBackgroundRecent reports have suggested a rotational strength weakness in rotations to the concave side in patients with idiopathic scoliosis. There have been no studies presenting normative values of female adolescent trunk rotational strength to which a comparison of female adolescents with idiopathic scoliosis could be made. The purpose of this study was to determine trunk rotational strength asymmetry in a group of female adolescents with AIS and a comparison group of healthy female adolescents without scoliosis.MethodsTwenty-six healthy adolescent females served as the healthy group (HG) (average age 14 years) and fourteen otherwise healthy adolescent females with idiopathic scoliosis served as the idiopathic scoliosis group (ISG) (average age 13.5 years, average Cobb 28°). Participant's isometric trunk rotational strength was measured in five randomly ordered trunk positions: neutral, 18° and 36° of right and left pre-rotation. Rotational strength asymmetry was compared within each group and between the two groups using several different measures.ResultsThe HG showed strength asymmetry in the 36° pre-rotated trunk positions when rotating towards the midline (p < 0.05). The ISG showed strength asymmetry when rotating towards the concavity of their primary curve from the neutral position (p < 0.05) and when rotating towards the concavity from the 18° (p < 0.05) and 36° (p < 0.05) concave pre-rotated positions. The ISG is significantly weaker than the HG when rotating away from the midline toward the concave (ISG)-left (HG) side from the concave/left pre-rotated 18° (p < 0.05) and 36° (p < 0.05) positions.ConclusionThe AIS females were found to be significantly weaker when contracting toward their main curve concavity in the neutral and concave pre-rotated positions compared to contractions toward the convexity. These weaknesses were also demonstrated when compared to the group of healthy female adolescent controls. Possible mechanisms for the strength asymmetry in ISG are discussed.
ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity
Authors: Fuentealba Rodrigo A , Barría Maria Ines , Lee Jiyeon , Cam Judy , Araya Claudia , Escudero Claudia A , Inestrosa Nibaldo C , Bronfman Francisca C , Bu Guojun , Marzolo Maria-Paz 
Published: July 2007

Abstract

Background
The generation of the amyloid-β peptide (Aβ) through the proteolytic processing of the amyloid precursor protein (APP) is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R) family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing.

Results
Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production.

Conclusion
These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.