bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the yeast two-hybrid system with permutated fusions proteins: the Varicella Zoster Virus interactome
Authors: Stellberger Thorsten , Häuser Roman , Baiker Armin , Pothineni Venkata R , Haas Jürgen , Uetz Peter 
Published: March 2010

AbstractBackgroundYeast two-hybrid (Y2H) screens have been among the most powerful methods to detect and analyze protein-protein interactions. However, they suffer from a significant degree of false negatives, i.e. true interactions that are not detected, and to a certain degree from false positives, i.e. interactions that appear to take place only in the context of the Y2H assay. While the fraction of false positives remains difficult to estimate, the fraction of false negatives in typical Y2H screens is on the order of 70-90%. Here we present novel Y2H vectors that significantly decrease the number of false negatives and help to mitigate the false positive problem.ResultsWe have constructed two new vectors (pGBKCg and pGADCg) that allow us to make both C-terminal fusion proteins of DNA-binding and activation domains. Both vectors can be combined with existing vectors for N-terminal fusions and thus allow four different bait-prey combinations: NN, CC, NC, and CN. We have tested all ~4,900 pairwise combinations of the 70 Varicella-Zoster-Virus (VZV) proteins for interactions, using all possible combinations. About ~20,000 individual Y2H tests resulted in 182 NN, 89 NC, 149 CN, and 144 CC interactions. Overlap between screens ranged from 17% (NC-CN) to 43% (CN-CC). Performing four screens (i.e. permutations) instead of one resulted in about twice as many interactions and thus much fewer false negatives. In addition, interactions that are found in multiple combinations confirm each other and thus provide a quality score. This study is the first systematic analysis of such N- and C-terminal Y2H vectors.ConclusionsPermutations of C- and N-terminal Y2H vectors dramatically increase the coverage of interactome studies and thus significantly reduce the number of false negatives. We suggest that future interaction screens should use such vector combinations on a routine basis, not the least because they provide a built-in quality score for Y2H interactions that can provide a measure of reproducibility without additional assays.
Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells
Authors: Zhang Chuanfu , Yang Yutao , Zhou Xiaowei , Liu Xuelin , Song Hongbin , He Yuxian , Huang Peitang 
Published: March 2010

Abstract

Background
It is widely considered that the multifunctional NS1 protein of influenza A viruses contributes significantly disease pathogenesis by modulating a number of virus and host-cell processes, but it is highly controversial whether this non-structural protein is a proapoptotic or antiapoptotic factor in infected cells.

Results
NS1 protein of influenza A/chicken/Jilin/2003 virus, a highly pathogenic H5N1 strain, could induce apoptosis in the carcinomic human alveolar basal epithelial cells (A549) by electron microscopic and flow cytometric analyses. NS1 protein-triggered apoptosis in A549 cells is via caspase-dependent pathway.

Conclusions
Influenza A virus NS1 protein serves as a strong inducer of apoptosis in infected human respiratory epithelial cells and plays a critical role in disease pathogenesis.
The usefulness of immunohistochemistry in tissue microarrays of Human Papillomavirus negative adenocarcinoma of the uterine cervix
Authors: Odida Michael , Lloveras Belen , Guimera Nuria , Weiderpass Elisabete 
Published: March 2010

Abstract

Background
The origin of adenocarcinomas presenting on the cervix uteri may be doubtful, i.e. whether it is of cervical or endometrial origin, due to the overlapping morphological features. In HPV negative samples, further tests may be needed to ascertain the nature of the tumours. We aimed to explore the use of immunohistochemistry profiles in tissue microarrays in archived samples of adenocarcinoma (ADC) of the cervix from Uganda that tested negative for HPV DNA.

Findings
Five commercially available antibodies were tested in tissue array sections immunostained utilizing the avidin-biotin (AB) technique. In 26 ADC samples, HPV was detected in 13, p16 in 15 (8 in HPV positive and 7 in HPV negative), CEA in 12, vimentin in 6, ER in 0, and PR in 2. Among the 13/25 HPV negative ADC samples, five were positive for CEA suggesting endocervical origin, and three were vimentin positive (one had a mucinous endocervical histological pattern and two were ADC, not otherwise specified, most likely of endometrial origin).

Conclusions
The immunoprofiles of ADC with the antibodies studied are rather nonspecific. By using immunohistochemistry in 13 HPV negative ADC, endocervical tumour origin was suspected in five CEA positive cases while two out of three vimentin positive samples were probably of endometrial origin, suggesting that CEA and vimentin may be valuable in distinguishing HPV negative cervical adenocarcinomas from endometrial adenocarcinomas.
Identification of a new mechanism for targeting myosin II heavy chain phosphorylation by Dictyostelium myosin heavy chain kinase B
Authors: Underwood Julie , Greene Jonathan , Steimle Paul A 
Published: March 2010

Abstract

Background
Heavy chain phosphorylation plays a central role in regulating myosin II bipolar filament assembly in Dictyostelium, as well as in higher eukaryotic nonmuscle cells. Our previous work has demonstrated that the WD-repeat domain of Dictyostelium myosin II heavy chain kinase B (MHCK-B), unlike its counterpart in MHCK-A, is not absolutely required for targeting of the kinase to phosphorylate MHC. Thus, we tested the hypothesis that an asparagine-rich and structurally disordered region that is unique to MHCK-B can by itself function in substrate targeting.

Findings
Biochemical assays comparing the activities of full-length MHCK-B, a truncation lacking only the WD-repeat domain (B-Δ-WD), and a truncation lacking both the N-rich region and the WD-repeat domain (B-Δ-N-WD) revealed that the N-rich region targets MHCK-B to phosphorylate MHC in a manner that leads to bipolar filament disassembly. This targeting is physiologically relevant since cellular over-expression of the B-Δ-WD truncation, but not the B-Δ-N-WD truncation, leads to dramatically reduced levels of myosin II filament assembly and associated defects in cytokinesis and multicellular development.

Conclusions
The results presented here demonstrate that an intrinsically unstructured, and asparagine-rich, region of a MHCK-B can mediate specific targeting of the kinase to phosphorylate myosin II heavy chain. This targeting involves a direct binding interaction with myosin II filaments. In terms of regulating myosin bipolar filament assembly, our results suggest that factors affecting the activity of this unique region of MHCK-B could allow for regulation of MHCK-B in a manner that is distinct from the other MHCKs in Dictyostelium.
Heel raises versus prefabricated orthoses in the treatment of posterior heel pain associated with calcaneal apophysitis (Sever's Disease): study protocol for a randomised controlled trial
Authors: James Alicia M , Williams Cylie M , Haines Terry P 
Published: March 2010

AbstractBackgroundPosterior Heel pain can present in children of 8 to 14 years, associated with or clinically diagnosed as Sever's disease, or calcaneal apophysitis. Presently, there are no comparative randomised studies evaluating treatment options for posterior heel pain in children with the clinical diagnosis of calcaneal apophysitis or Sever's disease. This study seeks to compare the clinical efficacy of some currently employed treatment options for the relief of disability and pain associated with posterior heel pain in children.MethodDesign: Factorial 2 × 2 randomised controlled trial with monthly follow‐up for 3 months.Participants: Children with clinically diagnosed posterior heel pain possibly associated with calcaneal apophysitis/Sever's disease (n = 124).Interventions: Treatment factor 1 will be two types of shoe orthoses: a heel raise or prefabricated orthoses. Both of these interventions are widely available, mutually exclusive treatment approaches that are relatively low in cost. Treatment factor 2 will be a footwear prescription/replacement intervention involving a shoe with a firm heel counter, dual density EVA midsole and rear foot control. The alternate condition in this factor is no footwear prescription/replacement, with the participant wearing their current footwear.Outcomes: Oxford Foot and Ankle Questionnaire and the Faces pain scale.DiscussionThis will be a randomised trial to compare the efficacy of various treatment options for posterior heel pain in children that may be associated with calcaneal apophysitis also known as Sever's disease.Trial RegistrationTrial Number: ACTRN12609000696291Ethics Approval Southern Health: HREC Ref: 09271B
A scaling normalization method for differential expression analysis of RNA-seq data
Authors: Robinson Mark D , Oshlack Alicia 
Published: March 2010

AbstractThe fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically important changes in expression, we show that normalization continues to be an essential step in the analysis. We outline a simple and effective method for performing normalization and show dramatically improved results for inferring differential expression in simulated and publicly available data sets.
An Innovative Method to Classify SERMs Based on the Dynamics of Estrogen Receptor Transcriptional Activity in Living Animals
Authors: Rando Gianpaolo , Horner David , Biserni Andrea , Ramachandran Balaji , Caruso Donatella , Ciana Paolo , Komm Barry , Maggi Adriana 
Published: March 2010

Abstract
Using a mouse model engineered to measure estrogen receptor (ER) transcriptional activity in living organisms, we investigated the effect of long-term (21 d) hormone replacement on ER signaling by whole-body in vivo imaging. Estrogens and selective ER modulators were administered daily at doses equivalent to those used in humans as calculated by the allometric approach. As controls, ER activity was measured also in cycling and ovariectomized mice. The study demonstrated that ER-dependent transcriptional activity oscillated in time, and the frequency and amplitude of the transcription pulses was strictly associated with the target tissue and the estrogenic compound administered. Our results indicate that the spatiotemporal activity of selective ER modulators is predictive of their structure, demonstrating that the analysis of the effect of estrogenic compounds on a single surrogate marker of ER transcriptional activity is sufficient to classify families of compounds structurally and functionally related. For more than one century, the measure of drug structure-activity relationships has been based on mathematical equations describing the interaction of the drug with its biological receptor. The understanding of the multiplicity of biological responses induced by the drug-receptor interaction demonstrated the limits of current approach and the necessity to develop novel concepts for the quantitative analysis of drug action. Here, a systematic study of spatiotemporal effects is proposed as a measure of drug efficacy for the classification of pharmacologically active compounds. The application of this methodology is expected to simplify the identification of families of molecules functionally correlated and to speed up the process of drug discovery.
Costs of Gastrointestinal Events after Outpatient Opioid Treatment for Non-Cancer Pain
Authors: Kwong Winghan Jacqueline , Diels Joris , Kavanagh Shane 
Published: March 2010

Background Gastrointestinal (GI) adverse effects are common with oral opioid treatment. Objective To estimate the costs associated with GI events after oral short-acting opioid treatment, from the payer perspective. Methods Medical and pharmacy claims from the PharMetrics’ Patient-Centric Database were used to identify opioid-naïve patients who received a new prescription for oxycodone- or hydrocodone-containing immediate-release oral products between 2002 and 2006. Health-care resource use and costs were determined for patients with claims associated with ICD-9 CM (International Classification of Diseases—9th Clinical Modification) codes for nausea/vomiting (787.0x), constipation (564.0x), bowel obstruction (560, 560.1, 560.3, 560.39, 564.81), or antiemetic and laxative prescriptions during the 3 months after opioid index prescription and compared with patients without these GI event medical or prescription claims. Resource use data were compared using negative binomial regression and cost data were compared using ordinary least squares confirmed by generalized gamma regression analysis while controlling for demographics, treatment duration, and comorbidities. Results Data from 237,447 patients were analyzed. Patients with GI event claims had significantly more hospitalizations (adjusted mean 0.20 to 0.97 vs 0.17, respectively, p < 0.001), days in the hospital (1.12 to 12.05 vs 1.00 days, p < 0.001), emergency department visits (0,36 to 1.44 vs 0.25 visits, p < 0.001), outpatient office visits (5.68 to 11.81 vs 4.11 visits, p < 0.001), and prescription claims (7.46 to 8.21 vs 6.06 claims, p < 0.001) than did patients without any GI event claims in the 3 months after index opioid prescription. Compared with patients without any GI event claims, incremental adjusted mean total health-care costs for patients with any of the GI event claims ranged from $4,880 to $36,152 and were significant (p < 0.001). Conclusions The economic burden of GI events coincident with opioid treatment is significant for patients with a GI event recorded in claims. Reducing GI adverse effects has potential cost savings for the health-care system.
Symptomatic Hypoglycemia Associated with Trimethoprim/Sulfamethoxazole and Repaglinide in a Diabetic Patient
Authors: Roustit Matthieu , Blondel Emeline , Villier Céline , Fonrose Xavier , Mallaret Michel P 
Published: March 2010

Objective To report a case of clinically significant hypoglycemia attributed to the concomitant use of trimethoprim/sulfamethoxazole (TMP/SMX) and repaglinide by a diabetic patient. Case summary A 76-year-old diabetic patient with impaired renal function and no history of hypoglycemia was receiving treatment with repaglinide 1 mg 3 times daily. Five days after TMP/SMX therapy was started for a urinary tract infection, the man developed symptomatic hypoglycemia. Repaglinide and TMP/SMX were stopped and intravenous d-glucose was administered to normalize glucose levels. Repaglinide, but not TMP/SMX, was reintroduced 5 days later and no other hypoglycemic episode occurred. Objective causality assessments revealed that the interaction was probable (World Health Organization-Uppsala Monitoring Centre) or possible (Horn Drug Interaction Probability Scale). Discussion This interaction between TMP/SMX and repaglinide was predictable according to available pharmacokinetic data in healthy subjects. Trimethoprim induced CYP2C8 inhibition, thus increasing the plasma concentration of repaglinide. This interaction is mentioned in the repaglinide product information. To our knowledge, however, no case of symptomatic hypoglycemia associated with a combination of repaglinide and trimethoprim has been described before. This discrepancy may be explained by the subtherapeutic dosage used in the pharmacokinetic study. Moreover, our patient had impaired renal function, which may have led to trimethoprim accumulation and potentiated its interaction with repaglinide. A direct lowering of blood glucose levels due to sulfamethoxazole, also potentiated by renal failure, could also be involved in triggering hypoglycemia. Conclusions This interaction between TMP/SMX and repaglinide may have involved inhibition of CYP2C8 by trimethoprim. Clinicians should be aware that this association may lead to symptomatic hypoglycemia, particularly in patients with renal dysfunction.
Das Ende der Sittenwidrigkeit sog. Geliebtentestamente?
Authors: Schnabl Daniel , Hamelmann Uwe 
Published: March 2010

Das Problem der Sittenwidrigkeit so genannter Geliebtentestamente hat Rechtsprechung und Schrifttum lange Zeit beschäftigt. Dabei stellte sich die Frage, unter welchen Voraussetzungen die Erbeinsetzung einer Geliebten gegen die guten Sitten verstößt und damit nach § 138 Abs. 1 BGB nichtig ist.
Der nachfolgende Beitrag gibt zunächst einen kurzen Überblick über den derzeitigen Stand der Rechtsprechung zu dieser Problematik und widmet sich anschließend der Frage, welche Auswirkungen das Inkrafttreten des Prostitutionsgesetzes auf diese Rechtsprechung hat. Angesichts sich mehrender Stimmen im Schrifttum und noch ausstehender Rechtsprechung zu dieser Frage, ist die Thematik der Geliebtentestamente wieder von besonderer Brisanz und Aktualität für juristische Prüfungsaufgaben, zumal sich in diesem Zusammenhang auch das Problem des maßgeblichen Zeitpunktes für die Beurteilung der Sittenwidrigkeit zwanglos abprüfen lässt.
Effect of Tire Wear on Tire Force and Moment Characteristics
Authors: Tandy D. F. , Pascarella R. J. , Neal J. W. , Baldwin J. M. , Rehkopf J. D. 
Published: March 2010

Abstract
In repeated physical testing of vehicles at or near their handling limit, shoulder wear occurs that is not typical of normal customer use. It has been observed for decades that this type of severe cornering induced tire wear can have a significant effect on the force and moment characteristics of tires. In this study, this shoulder wear effect was isolated by testing tires in a controlled environment and objectively assessed for a number of tires of various brands and sizes. This testing shows how a tire’s lateral force and overturning moment capacities increase significantly as the number of runs on a tire accumulates. Additionally, one particular tire make and model was placed on a vehicle to acquire 1000 miles of normal customer driving and then evaluated under the same simulated load conditions. The results confirmed that, irrespective of a tire break-in procedure, the increases in lateral forces of the tire in repeated limit handling maneuvers were a product of the test induced atypical shoulder wear generated during the limit handling maneuver.
Physiotherapist Classifiers Ensure Competitive Fair Play in Para-Archery
Authors: Betteridge Pauline 
Published: March 2010

Over the past 30 years, physiotherapists have played an important role in the continuous refinement of the classification system related to sports participation for athletes with disabilities. This guest editorial is intended to provide a brief history of this evolution, an evolution that in many respects has shifted the focus away from the medical diagnosis to concerns related more to the impact of a disease or condition on the person's function and overall health. J Orthop Sports Phys Ther 2010;40(3):130–132. doi:10.2519/jospt.2010.0103
Determinants of change in paternal smoking trends during pregnancy in Lebanon
Authors: MAHFOUD ZIYAD , SAAD SARA , HADDAD PASCALE , CHAAYA MONIQUE 
Published: March 2010

AbstractFor pregnant women and their fetus, secondhand smoking poses major public health effects. This study analyzes the determinants of change in smoking behavior among fathers whose partners were pregnant. The study is a secondary analysis of a nationally representative Lebanese cross‐sectional survey of 1,028 households conducted in 2007. Currently smoking fathers with a child of 5 years of age or less were included. The main outcome was the change in the father's smoking behavior during his wife's last pregnancy. The study concluded that fathers who changed their smoking patterns when their wives were pregnant were significantly more educated, more likely to smoke a lesser number of cigarettes per day (OR = 96, 95% CI (0.93, 0.99)), and more knowledgeable about cigarette constitutes and its health risks (OR = 1.37, 95% CI (1.08, 1.74). Public health practitioners and health professionals are recommended to raise awareness and provide cessation programs for parents and especially fathers.
The Heat Shock Protein Profile in Children with Chronic Kidney Disease
Authors: Musial Kinga , Szprynger Krystyna , Szczepańska Maria , Zwolińska Danuta 
Published: March 2010

Objectives Chronic kidney disease (CKD) due to inflammation, lipid disorders, and endothelial dysfunction predisposes to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSPs) and antibodies against them have been described in adults with atherosclerotic lesions and cardiovascular events. However, there are no investigations of these variables in children with CKD treated conservatively or on peritoneal dialysis. Therefore, we decided to evaluate the profile of HSPs and their potential role as markers of atherosclerosis in these groups of patients. Methods The study group consisted of 37 children with CKD treated conservatively and 19 children and young adults on automated peritoneal dialysis (APD). The control group comprised 15 age-matched subjects with normal kidney function. HSP-60, HSP-70, HSP-90alpha, anti-HSP-60, anti-HSP-70, sE-selectin, and interleukin (IL)-4 serum concentrations were assessed by ELISA; high-sensitivity C-reactive protein (hs-CRP) serum levels were assessed by nephelometry. Serum lipid profiles (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides) were also estimated. Results HSP-90α x anti-HSP-60, and sE-selectin concentrations in the CKD and APD patients were higher than in the controls and were lower in the predialysis subjects than in the children on dialysis. Median values of anti-HSP-70 were higher in the CKD patients than in the control group. Levels of IL-4 were increased in all patients versus controls. Median values of HSP-60 were decreased in the CKD and APD children versus controls. HSP-70 and hs-CRP concentrations were comparable in all groups. Conclusions The altered HSP and anti-HSP concentrations may imply that the response to stress conditions in the course of CKD is disturbed in children; APD does not aggravate that dysfunction in a significant way. Relationships between HSPs, lipid profile, and markers of inflammation suggest a possible role of the selected HSPs as markers of atherosclerosis in children with CKD.