bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein
Authors: Butler-Cole Christine , Wagner Mary J , Da Silva Melissa , Brown Gordon D , Burke Robert D , Upton Chris 
Published: July 2007

Abstract

Background
Profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. In this study, a poxviral profilin homolog, ectromelia virus strain Moscow gene 141 (ECTV-PH), was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins.

Results
Profilin-like proteins are encoded by all orthopoxviruses sequenced to date, and share over 90% amino acid (aa) identity. Sequence comparisons show highest similarity to mammalian type 1 profilins; however, a conserved 3 aa deletion in mammalian type 3 and poxviral profilins suggests that these homologs may be more closely related. Structural analysis shows that ECTV-PH can be successfully modelled onto both the profilin 1 crystal structure and profilin 3 homology model, though few of the surface residues thought to be required for binding actin, poly(L-proline), and PIP2 are conserved. Immunoprecipitation and mass spectrometry identified two proteins that interact with ECTV-PH within infected cells: alpha-tropomyosin, a 38 kDa cellular actin-binding protein, and the 84 kDa product of vaccinia virus strain Western Reserve (VACV-WR) 148, which is the truncated VACV counterpart of the orthopoxvirus A-type inclusion (ATI) protein. Western and far-western blots demonstrated that the interaction with alpha-tropomyosin is direct, and immunofluorescence experiments suggest that ECTV-PH and alpha-tropomyosin may colocalize to structures that resemble actin tails and cellular protrusions. Sequence comparisons of the poxviral ATI proteins show that although full-length orthologs are only present in cowpox and ectromelia viruses, an ~ 700 aa truncated ATI protein is conserved in over 90% of sequenced orthopoxviruses. Immunofluorescence studies indicate that ECTV-PH localizes to cytoplasmic inclusion bodies formed by both truncated and full-length versions of the viral ATI protein. Furthermore, colocalization of ECTV-PH and truncated ATI protein to protrusions from the cell surface was observed.

Conclusion
These results suggest a role for ECTV-PH in intracellular transport of viral proteins or intercellular spread of the virus. Broader implications include better understanding of the virus-host relationship and mechanisms by which cells organize and control the actin cytoskeleton.
Prevalence and associated factors of physical fighting among school-going adolescents in Namibia
Authors: Rudatsikira Emmanuel , Siziya Seter , Kazembe Lawrence N , Muula Adamson S 
Published: July 2007

AbstractBackgroundInterpersonal physical violence is an important global public health concern that has received limited attention in the developing world. There is in particular a paucity of data regarding physical violence and its socio-demographic correlates among in-school adolescents in Namibia.MethodsWe analysed cross-sectional data from the Namibia Global School-Based Health Survey (GSHS) conducted in 2004. We aimed to estimate the prevalence and socio-demographic correlates of physical fighting within the last 12 months. We obtained frequencies of socio-demographic attributes. We also assessed the association between self-reported history of having engaging in a physical fight and a selected list of independent variables using logistic regression analysis.ResultsOf the 6283 respondents, 50.6% (55.2% males and 46.2% females) reported having been in a physical fight in the past 12 months. Males were more likely to have been in a physical fight than females (OR = 1.71, 95% CI (1.44, 2.05)). Smoking, drinking alcohol, using drugs and bullying victimization were positively associated with fighting (OR = 1.91, 95% CI (1.49, 2.45); OR = 1.48, 95% CI (1.21, 1.81); OR = 1.55, 95% CI (1.22, 1.81); and OR = 3.12, 95% CI (2.62, 3.72), respectively). Parental supervision was negatively associated with physical fighting (OR = 0.82, 95% CI (0.69, 0.98)). Both male and female substance users (cigarette smoking, alcohol and drug use) were more likely to engage in physical fighting than non-substance users (OR = 3.53, 95% CI (2.60, 4.81) for males and OR = 11.01, 95% CI (7.25, 16.73) for females). Parental supervision was negatively associated with physical fighting (OR = 0.85, 95% CI (0.72, 0.99)).ConclusionPrevalence of physical fighting within the last 12 months was comparable to estimates obtained in European countries. We also found clustering of problem behaviours or experiences among adolescents who reported having engaged in physical violence in the past 12 months. There is a need to bring adolescent violent behaviour to the fore of the public health agenda in Namibia.
Transcriptional profiling of the model Archaeon Halobacteriumsp. NRC-1: responses to changes in salinity and temperature
Authors: Coker James A , DasSarma Priya , Kumar Jeffrey , Müller Jochen A , DasSarma Shiladitya 
Published: July 2007

Abstract

Background
The model halophile Halobacterium sp. NRC-1 was among the first Archaea to be completely sequenced and many post-genomic tools, including whole genome DNA microarrays are now being applied to its analysis. This extremophile displays tolerance to multiple stresses, including high salinity, extreme (non-mesophilic) temperatures, lack of oxygen, and ultraviolet and ionizing radiation.

Results
In order to study the response of Halobacterium sp. NRC-1 to two common stressors, salinity and temperature, we used whole genome DNA microarrays to assay for changes in gene expression under differential growth conditions. Cultures grown aerobically in rich medium at 42°C were compared to cultures grown at elevated or reduced temperature and high or low salinity. The results obtained were analyzed using a custom database and microarray analysis tools. Growth under salt stress conditions resulted in the modulation of genes coding for many ion transporters, including potassium, phosphate, and iron transporters, as well as some peptide transporters and stress proteins. Growth at cold temperature altered the expression of genes involved in lipid metabolism, buoyant gas vesicles, and cold shock proteins. Heat shock showed induction of several known chaperone genes. The results showed that Halobacterium sp. NRC-1 cells are highly responsive to environmental changes at the level of gene expression.

Conclusion
Transcriptional profiling showed that Halobacterium sp. NRC-1 is highly responsive to its environment and provided insights into some of the specific responses at the level of gene expression. Responses to changes in salt conditions appear to be designed to minimize the loss of essential ionic species and abate possible toxic effects of others, while exposure to temperature extremes elicit responses to promote protein folding and limit factors responsible for growth inhibition. This work lays the foundation for further bioinformatic and genetic studies which will lead to a more comprehensive understanding of the biology of a model halophilic Archaeon.
Short-term prolactin administration causes expressible galactorrhea but does not affect bone turnover: pilot data for a new lactation agent
Authors: Page-Wilson Gabrielle , Smith Patricia C , Welt Corrine K 
Published: July 2007

AbstractBackgroundMedications used to augment lactation increase prolactin secretion but can have intolerable side effects. We examined the biological activity of recombinant human prolactin (r-hPRL) as preliminary data for its use to augment lactation.MethodsHealthy, non-postpartum women (n = 21) with regular menstrual cycles underwent a seven day randomized, double-blind, placebo-controlled trial of r-hPRL. Expressible galactorrhea, markers of bone turnover, calcium homeostasis and gonadal function were measured and side effects recorded.ResultsProlactin levels increased during r-hPRL administration (20.0 ± 2.8 to 231.7 ± 48.9 μg/L at 6 hours; p < 0.05). Five of nine participants who received r-hPRL developed expressible galactorrhea (p < 0.001). Urinary deoxypyridinoline decreased and bone specific alkaline phosphatase increased in r-hPRL and placebo groups. Menstrual cycle lengths were not altered and side effects were similar between r-hPRL and placebo groups.ConclusionIn summary, r-hPRL can cause expressible galactorrhea. Seven days of r-hPRL administration does not adversely affect bone turnover or menstrual cyclicity. Thus, r-hPRL may be a viable option for short-term lactation augmentation.Trial registrationClinical Trials.gov NCT00438490
Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer
Authors: Uitterhoeve Apollonia LJ , Koolen Mia GJ , van Os Rob M , Koedooder Kees , van de Kar Marlou , Pieters Bradley R , Koning Caro CE 
Published: July 2007

Abstract
Background
Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.

Material
Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).

Treatment
Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m2: 56 pts (standard).
Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m2 d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.
Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.

Results
The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.
At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.
Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.

Conclusion
In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.
Identification of an altered peptide ligand based on the endogenously presented, rheumatoid arthritis-associated, human cartilage glycoprotein-39(263–275) epitope: an MHC anchor variant peptide for immune modulation
Authors: Boots Annemieke MH , Hubers Henk , Kouwijzer Milou , den Hoed-van Zandbrink Leontien , Westrek-Esselink Bernice M , van Doorn Cindy , Stenger Rachel , Bos Ebo S , van Lierop Marie-jose C , Verheijden Gijs F , Timmers Cornelis M , van Staveren Catharina J 
Published: July 2007

AbstractWe sought to identify an altered peptide ligand (APL) based on the endogenously expressed synovial auto-epitope of human cartilage glycoprotein-39 (HC gp-39) for modulation of cognate, HLA-DR4-restricted T cells. For this purpose we employed a panel of well-characterized T cell hybridomas generated from HC gp-39-immunized HLA-DR4 transgenic mice. The hybridomas all respond to the HC gp-39(263–275) epitope when bound to HLA-DR4(B1*0401) but differ in their fine specificities. First, the major histocompatibility complex (MHC) and T-cell receptor (TCR) contact residues were identified by analysis of single site substituted analogue peptides for HLA-DR4 binding and cognate T cell recognition using both T hybridomas and polyclonal T cells from peptide-immunized HLA-DR4 transgenic mice. Analysis of single site substituted APL by cognate T cells led to identification of Phe265 as the dominant MHC anchor. The amino acids Ala268, Ser269, Glu271 and Thr272 constituted the major TCR contact residues, as substitution at these positions did not affect HLA-DR4(B1*0401) binding but abrogated T cell responses. A structural model for visualisation of TCR recognition was derived. Second, a set of non-classical APLs, modified at the MHC key anchor position but with unaltered TCR contacts, was developed. When these APLs were analysed, a partial TCR agonist was identified and found to modulate the HC gp-39(263–275)-specific, pro-inflammatory response in HLA-DR4 transgenic mice. We identified a non-classical APL by modification of the p1 MHC anchor in a synovial auto-epitope. This APL may qualify for rheumatoid arthritis immunotherapy.
Application of the multicellular tumour spheroid model to screen PET tracers for analysis of early response of chemotherapy in breast cancer
Authors: Monazzam Azita , Josephsson Raymond , Blomqvist Carl , Carlsson Jörgen , Långström Bengt , Bergström Mats 
Published: July 2007

Abstract
Introduction
Positron emission tomography (PET) is suggested for early monitoring of treatment response, assuming that effective anticancer treatment induces metabolic changes that precede morphology alterations and changes in growth. The aim of this study was to introduce multicellular tumour spheroids (MTS) to study the effect of anticancer drugs and suggest an appropriate PET tracer for further studies.

Methods
MTS of the breast cancer cell line MCF7 were exposed to doxorubicin, paclitaxel, docetaxel, tamoxifen or imatinib for 7 days for growth pattern studies and for 3 or 5 days for PET tracer studies. The effect on growth was computed using the semi-automated size determination method (SASDM). The effect on the uptake of PET tracers [18F]3'-deoxy-3'-fluorothymidine (FLT), [1-11C]acetate (ACE), [11C]choline (CHO), [11C]methionine (MET), and 2-[18F]fluoro-2-deoxyglucose (FDG) was calculated in form of uptake/viable volume of the MTS at the end of the drug exposures, and finally the uptake was related to effects on growth rate.

Results
The drugs paclitaxel, docetaxel and doxorubicin gave severe growth inhibition, which correlated well with inhibition of the FLT uptake. FLT had, compared with ACE, CHO, MET and FDG, higher sensitivity in monitoring the therapy effects.

Conclusion
SASDM provides an effective, user-friendly, time-saving and accurate method to record the growth pattern of the MTS, and also to calculate the effect of the drug on PET tracer uptake. This study demonstrate the use of MTS and SASDM in combination with PET tracers as a promising approach to probe and select PET tracer for treatment monitoring of anticancer drugs and that can hopefully be applied for optimisation in breast cancer treatment.
Vasopressin improves survival in a porcine model of abdominal vascular injury
Authors: Stadlbauer Karl H , Wagner-Berger Horst G , Krismer Anette C , Voelckel Wolfgang G , Konigsrainer Alfred , Lindner Karl H , Wenzel Volker 
Published: July 2007

Abstract
Introduction
We sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs.

Methods
During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.

Results
After 68 ± 19 min (mean ± standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).

Conclusion
Vasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.
Global analysis of patterns of gene expression during Drosophilaembryogenesis
Authors: Tomancak Pavel , Berman Benjamin P , Beaton Amy , Weiszmann Richard , Kwan Elaine , Hartenstein Volker , Celniker Susan E , Rubin Gerald M 
Published: July 2007

Abstract
Background
Cell and tissue specific gene expression is a defining feature of embryonic development in multi-cellular organisms. However, the range of gene expression patterns, the extent of the correlation of expression with function, and the classes of genes whose spatial expression are tightly regulated have been unclear due to the lack of an unbiased, genome-wide survey of gene expression patterns.

Results
We determined and documented embryonic expression patterns for 6,003 (44%) of the 13,659 protein-coding genes identified in the Drosophila melanogaster genome with over 70,000 images and controlled vocabulary annotations. Individual expression patterns are extraordinarily diverse, but by supplementing qualitative in situ hybridization data with quantitative microarray time-course data using a hybrid clustering strategy, we identify groups of genes with similar expression. Of 4,496 genes with detectable expression in the embryo, 2,549 (57%) fall into 10 clusters representing broad expression patterns. The remaining 1,947 (43%) genes fall into 29 clusters representing restricted expression, 20% patterned as early as blastoderm, with the majority restricted to differentiated cell types, such as epithelia, nervous system, or muscle. We investigate the relationship between expression clusters and known molecular and cellular-physiological functions.

Conclusion
Nearly 60% of the genes with detectable expression exhibit broad patterns reflecting quantitative rather than qualitative differences between tissues. The other 40% show tissue-restricted expression; the expression patterns of over 1,500 of these genes are documented here for the first time. Within each of these categories, we identified clusters of genes associated with particular cellular and developmental functions.
Combined analysis reveals a core set of cycling genes
Authors: Lu Yong , Mahony Shaun , Benos Panayiotis V , Rosenfeld Roni , Simon Itamar , Breeden Linda L , Bar-Joseph Ziv 
Published: July 2007

Abstract
Background
Global transcript levels throughout the cell cycle have been characterized using microarrays in several species. Early analysis of these experiments focused on individual species. More recently, a number of studies have concluded that a surprisingly small number of genes conserved in two or more species are periodically transcribed in these species. Combining and comparing data from multiple species is challenging because of noise in expression data, the different synchronization and scoring methods used, and the need to determine an accurate set of homologs.

Results
To solve these problems, we developed and applied a new algorithm to analyze expression data from multiple species simultaneously. Unlike previous studies, we find that more than 20% of cycling genes in budding yeast have cycling homologs in fission yeast and 5% to 7% of cycling genes in each of four species have cycling homologs in all other species. These conserved cycling genes display much stronger cell cycle characteristics in several complementary high throughput datasets.
Essentiality analysis for yeast and human genes confirms these findings. Motif analysis indicates conservation in the corresponding regulatory mechanisms. Gene Ontology analysis and analysis of the genes in the conserved sets sheds light on the evolution of specific subfunctions within the cell cycle.

Conclusion
Our results indicate that the conservation in cyclic expression patterns is much greater than was previously thought. These genes are highly enriched for most cell cycle categories, and a large percentage of them are essential, supporting our claim that cross-species analysis can identify the core set of cycling genes.
Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial
Authors: Suter Thomas M. , Procter Marion , van Veldhuisen Dirk J. , Muscholl Michael , Bergh Jonas , Carlomagno Chiara , Perren Timothy , Passalacqua Rodolfo , Bighin Claudia , Klijn Jan G.M. , Ageev Fail T. , Hitre Erika , Groetz Juergen , Iwata Hiroji , Knap Malgorzata , Gnant Michael , Muehlbauer Susanne , Spence Alison , Gelber Richard D. , Piccart-Gebhart Martine J. 
Published: July 2007

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.