bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke
Authors: Tanaka Toshiki , Huang Xuan , Jorgensen Ellen , Gietl Diana , Traganos Frank , Darzynkiewicz Zbigniew , Albino Anthony P 
Published: June 2007

Abstract

Background
In response to DNA damage or structural alterations of chromatin, histone H2AX may be phosphorylated on Ser 139 by phosphoinositide 3-kinase related protein kinases (PIKKs) such as ataxia telangiectasia mutated (ATM), ATM-and Rad-3 related (ATR) kinase, or by DNA dependent protein kinase (DNA-PKcs). When DNA damage primarily involves formation of DNA double-strand breaks (DSBs), H2AX is preferentially phosphorylated by ATM rather than by the other PIKKs. We have recently reported that brief exposure of human pulmonary adenocarcinoma A549 cells or normal human bronchial epithelial cells (NHBE) to cigarette smoke (CS) induced phosphorylation of H2AX.

Results
We report here that H2AX phosphorylation in A549 cells induced by CS was accompanied by activation of ATM, as revealed by ATM phosphorylation on Ser 1981 (ATM-S1981P) detected immunocytochemically and by Western blotting. No cell cycle-phase specific differences in kinetics of ATM activation and H2AX phosphorylation were observed. When cells were exposed to CS from cigarettes with different tobacco and filter combinations, the expression levels of ATM-S1981P correlated well with the increase in expression of phosphorylated H2AX (γH2AX) (R = 0.89). In addition, we note that while CS-induced γH2AX expression was localized within discrete foci, the activated ATM was distributed throughout the nucleoplasm.

Conclusion
These data implicate ATM as the PIKK that phosphorylates H2AX in response to DNA damage caused by CS. Based on current understanding of ATM activation, expression and localization, these data would suggest that, in addition to inducing potentially carcinogenic DSB lesions, CS may also trigger other types of DNA lesions and cause chromatin alterations. As checkpoint kinase (Chk) 1, Chk2 and the p53 tumor suppressor gene are known to be phosphorylated by ATM, the present data indicate that exposure to CS may lead to their phosphorylation, with the downstream consequences related to the halt in cell cycle progression and increased propensity to undergo apoptosis. Defining the nature and temporal sequence of molecular events that are disrupted by CS through activation and eventual dysregulation of normal defense mechanisms such as ATM and its downstream effectors may allow a more precise understanding of how CS promotes cancer development.
Identification of genes differentially expressed during larval molting and metamorphosis of Helicoverpa armigera
Authors: Dong Du-Juan , He Hong-Juan , Chai Lian-Qin , Jiang Xiao-Juan , Wang Jin-Xing , Zhao Xiao-Fan 
Published: June 2007

Abstract

Background
Larval molting and metamorphosis are important physiological processes in the life cycle of the holometabolous insect. We used suppression subtractive hybridization (SSH) to identify genes differentially expressed during larval molting and metamorphosis.

Results
We performed SSH between tissues from a variety of developmental stages, including molting 5th and feeding 6th instar larvae, metamorphically committed and feeding 5th instar larvae, and feeding 5th instar and metamorphically committed larvae. One hundred expressed sequence tags (ESTs) were identified and included 73 putative genes with similarity to known genes, and 27 unknown ESTs. SSH results were further characterized by dot blot, Northern blot, and RT-PCR. The expression levels of eleven genes were found to change during larval molting or metamorphosis, suggesting a functional role during these processes.

Conclusion
These results provide a new set of genes expressed specifically during larval molt or metamorphosis that are candidates for further studies into the regulatory mechanisms of those stage-specific genes during larval molt and metamorphosis
The effect of natural selection on the performance of maximum parsimony
Authors: Hang Dehua , Torng Eric , Ofria Charles , Schmidt Thomas M 
Published: June 2007

Abstract

Background
Maximum parsimony is one of the most commonly used and extensively studied phylogeny reconstruction methods. While current evaluation methodologies such as computer simulations provide insight into how well maximum parsimony reconstructs phylogenies, they tell us little about how well maximum parsimony performs on taxa drawn from populations of organisms that evolved subject to natural selection in addition to the random factors of drift and mutation. It is clear that natural selection has a significant impact on Among Site Rate Variation (ASRV) and the rate of accepted substitutions; that is, accepted mutations do not occur with uniform probability along the genome and some substitutions are more likely to occur than other substitutions. However, little is know about how ASRV and non-uniform character substitutions impact the performance of reconstruction methods such as maximum parsimony. To gain insight into these issues, we study how well maximum parsimony performs with data generated by Avida, a digital life platform where populations of digital organisms evolve subject to natural selective pressures.

Results
We first identify conditions where natural selection does affect maximum parsimony's reconstruction accuracy. In general, as we increase the probability that a significant adaptation will occur in an intermediate ancestor, the performance of maximum parsimony improves. In fact, maximum parsimony can correctly reconstruct small 4 taxa trees on data that have received surprisingly many mutations if the intermediate ancestor has received a significant adaptation. We demonstrate that this improved performance of maximum parsimony is attributable more to ASRV than to non-uniform character substitutions.

Conclusion
Maximum parsimony, as well as most other phylogeny reconstruction methods, may perform significantly better on actual biological data than is currently suggested by computer simulation studies because of natural selection. This is largely due to specific sites becoming fixed in the genome that perform functions associated with an improved fitness.
TCF7L2 rs7903146 variant does not associate with smallness for gestational age in the French population
Authors: Cauchi Stéphane , Meyre David , Choquet Hélène , Deghmoun Samia , Durand Emmanuelle , Gaget Stefan , Lecoeur Cécile , Froguel Philippe , Levy-Marchal Claire 
Published: June 2007

Abstract

Background
In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes (T2D), has been also associated with a lower body mass index (BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance.

Methods
The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age (SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight (AGA). Two groups of French Caucasian subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 764), and AGA (25th < birth weight < 75th percentile; n = 627). Family-based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees.

Results
The rs7903146 genotypic distributions between AGA (30.7%) and SGA (29.0%) were not statistically different (allelic OR = 0.92 [0.78–1.09], p = 0.34). Family association-based studies did not show a distortion of T allele transmission in SGA subjects (p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion (p = 0.03) and a higher fasting glycaemia (p = 0.002) were detected in carriers of the T allele.

Conclusion
The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.
Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD)
Authors: Reamon-Buettner Stella Marie , Cho Si-Hyen , Borlak Juergen 
Published: June 2007

Abstract

Background
The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the control of nuclear transport, polyadenylation status, subcellular targetting as well as rates of translation and degradation of mRNA. Indeed, 3'-UTR mutations have been associated with disease, but frequently this region is not analyzed. To gain insights into congenital heart disease (CHD), we have been analyzing cardiac-specific transcription factor genes, including GATA4, which encodes a zinc finger transcription factor. Germline mutations in the coding region of GATA4 have been associated with septation defects of the human heart, but mutations are rather rare. Previously, we identified 19 somatically-derived zinc finger mutations in diseased tissues of malformed hearts. We now continued our search in the 609 bp 3'-UTR region of GATA4 to explore further molecular avenues leading to CHD.

Methods
By direct sequencing, we analyzed the 3'-UTR of GATA4 in DNA isolated from 68 formalin-fixed explanted hearts with complex cardiac malformations encompassing ventricular, atrial, and atrioventricular septal defects. We also analyzed blood samples of 12 patients with CHD and 100 unrelated healthy individuals.

Results
We identified germline and somatic mutations in the 3'-UTR of GATA4. In the malformed hearts, we found nine frequently occurring sequence alterations and six dbSNPs in the 3'-UTR region of GATA4. Seven of these mutations are predicted to affect RNA folding. We also found further five nonsynonymous mutations in exons 6 and 7 of GATA4. Except for the dbSNPs, analysis of tissue distal to the septation defect failed to detect sequence variations in the same donor, thus suggesting somatic origin and mosaicism of mutations. In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II.

Conclusion
Our results suggest that somatic GATA4 mutations in the 3'-UTR may provide an additional molecular rationale for CHD.
Urban and rural variations in morbidity and mortality in Northern Ireland
Authors: O'Reilly Gareth , O' Reilly Dermot , Rosato Michael , Connolly Sheelah 
Published: June 2007

Abstract

Background
From a public health perspective and for the appropriate allocation of resources it is important to understand the differences in health between areas. This paper examines the variations in morbidity and mortality between urban and rural areas.

Methods
This is a cohort study looking at morbidity levels of the population of Northern Ireland at the time of the 2001 census, and subsequent mortality over the following four years. Individual characteristics including demographic and socio-economic factors were as recorded on census forms. The urban-rural nature of residence was based on census areas (average population c1900) classified into eight settlement bands, ranging from cities to rural settlements with populations of less than 1000.

Results
The study shows that neither tenure nor car availability are unbiased measures of deprivation in the urban-rural context. There is no indication that social class is biased. There was an increasing gradient of poorer health from rural to urban areas, where mortality rates were about 22% (95% Confidence Intervals 19%–25%) higher than the most rural areas. Differences in death rates between rural and city areas were evident for most of the major causes of death but were greatest for respiratory disease and lung cancer. Conversely, death rates in the most rural areas were higher in children and adults aged less than 20.

Conclusion
Urban areas appear less healthy than the more rural areas and the association with respiratory disease and lung cancer suggests that pollution may be a factor. Rural areas however, have higher death rates amongst younger people, something which requires further research. There is also a need for additional indicators of deprivation that have equal meaning in urban and rural areas.
Influences on uptake of reproductive health services in Nsangi community of Uganda and their implications for cervical cancer screening
Authors: Mutyaba Twaha , Faxelid Elisabeth , Mirembe Florence , Weiderpass Elisabete 
Published: June 2007

Abstract

Background
Cervical cancer is the most common female cancer in Uganda. Over 80% of women diagnosed or referred with cervical cancer in Mulago national referral and teaching hospital have advanced disease. Plans are underway for systematic screening programmes based on visual inspection, as Pap smear screening is not feasible for this low resource country. Effectiveness of population screening programmes requires high uptake and for cervical cancer, minimal loss to follow up. Uganda has poor indicators of reproductive health (RH) services uptake; 10% postnatal care attendance, 23% contraceptive prevalence, and 38% skilled attendance at delivery. For antenatal attendance, attendance to one visit is 90%, but less than 50% for completion of care, i.e. three or more visits.

Methods
We conducted a qualitative study using eight focus group discussions with a total of 82 participants (16 men, 46 women and 20 health workers). We aimed to better understand factors that influence usage of available reproductive health care services and how they would relate to cervical cancer screening, as well as identify feasible interventions to improve cervical cancer screening uptake.

Results
Barriers identified after framework analysis included ignorance about cervical cancer, cultural constructs/beliefs about the illness, economic factors, domestic gender power relations, alternative authoritative sources of reproductive health knowledge, and unfriendly health care services. We discuss how these findings may inform future planned screening programmes in the Ugandan context.

Conclusion
Knowledge about cervical cancer among Ugandan women is very low. For an effective cervical cancer-screening programme, awareness about cervical cancer needs to be increased. Health planners need to note the power of the various authoritative sources of reproductive health knowledge such as paternal aunts (Sengas) and involve them in the awareness campaign. Cultural and economic issues dictate the perceived reluctance by men to participate in women's reproductive health issues; men in this community are, however, potential willing partners if appropriately informed. Health planners should address the loss of confidence in current health care units, as well as consider use of other cervical cancer screening delivery systems such as mobile clinics/camps.
Constitutive upregulation of the transforming growth factor-β pathway in rheumatoid arthritis synovial fibroblasts
Authors: Pohlers Dirk , Beyer Andreas , Koczan Dirk , Wilhelm Thomas , Thiesen Hans-Jürgen , Kinne Raimund W 
Published: June 2007

AbstractGenome-wide gene expression was comparatively investigated in early-passage rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts (SFBs; n = 6 each) using oligonucleotide microarrays; mRNA/protein data were validated by quantitative PCR (qPCR) and western blotting and immunohistochemistry, respectively. Gene set enrichment analysis (GSEA) of the microarray data suggested constitutive upregulation of components of the transforming growth factor (TGF)-β pathway in RA SFBs, with 2 hits in the top 30 regulated pathways. The growth factor TGF-β1, its receptor TGFBR1, the TGF-β binding proteins LTBP1/2, the TGF-β-releasing thrombospondin 1 (THBS1), the negative effector SkiL, and the smad-associated molecule SARA were upregulated in RA SFBs compared to OA SFBs, whereas TGF-β2 was downregulated. Upregulation of TGF-β1 and THBS1 mRNA (both positively correlated with clinical markers of disease activity/severity) and downregulation of TGF-β2 mRNA in RA SFBs were confirmed by qPCR. TGFBR1 mRNA (only numerically upregulated in RA SFBs) and SkiL mRNA were not differentially expressed. At the protein level, TGF-β1 showed a slightly higher expression, and the signal-transducing TGFBR1 and the TGF-β-activating THBS1 a significantly higher expression in RA SFBs than in OA SFBs. Consistent with the upregulated TGF-β pathway in RA SFBs, stimulation with TGF-β1 resulted in a significantly enhanced expression of matrix-metalloproteinase (MMP)-11 mRNA and protein in RA SFBs, but not in OA SFBs. In conclusion, RA SFBs show broad, constitutive alterations of the TGF-β pathway. The abundance of TGF-β, in conjunction with an augmented mRNA and/or protein expression of TGF-β-releasing THBS1 and TGFBR1, suggests a pathogenetic role of TGF-β-induced effects on SFBs in RA, for example, the augmentation of MMP-mediated matrix degradation/remodeling.
Evolutionary history and functional implications of protein domains and their combinations in eukaryotes
Authors: Itoh Masumi , Nacher Jose C , Kuma Kei-ichi , Goto Susumu , Kanehisa Minoru 
Published: June 2007

Abstract
Background
In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes.

Results
We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors.

Conclusion
Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.
Observing metabolic functions at the genome scale
Authors: Schwartz Jean-Marc , Gaugain Claire , Nacher Jose C , de Daruvar Antoine , Kanehisa Minoru 
Published: June 2007

Abstract
Background
High-throughput techniques have multiplied the amount and the types of available biological data, and for the first time achieving a global comprehension of the physiology of biological cells has become an achievable goal. This aim requires the integration of large amounts of heterogeneous data at different scales. It is notably necessary to extend the traditional focus on genomic data towards a truly functional focus, where the activity of cells is described in terms of actual metabolic processes performing the functions necessary for cells to live.

Results
In this work, we present a new approach for metabolic analysis that allows us to observe the transcriptional activity of metabolic functions at the genome scale. These functions are described in terms of elementary modes, which can be computed in a genome-scale model thanks to a modular approach. We exemplify this new perspective by presenting a detailed analysis of the transcriptional metabolic response of yeast cells to stress. The integration of elementary mode analysis with gene expression data allows us to identify a number of functionally induced or repressed metabolic processes in different stress conditions. The assembly of these elementary modes leads to the identification of specific metabolic backbones.

Conclusion
This study opens a new framework for the cell-scale analysis of metabolism, where transcriptional activity can be analyzed in terms of whole processes instead of individual genes. We furthermore show that the set of active elementary modes exhibits a highly uneven organization, where most of them conduct specialized tasks while a smaller proportion performs multi-task functions and dominates the general stress response.
Regional Changes in Hormone Therapy Use and Breast Cancer Incidence in California From 2001 to 2004
Authors: Robbins Anthony S. , Clarke Christina A. 
Published: June 2007

Purpose Recently, an unprecedented 1-year 7% decrease in the overall incidence of invasive female breast cancer in the United States was reported. It has been suggested that the decrease resulted from the mass cessation of estrogen-progestin hormone therapy (EPHT) in 2002. We took advantage of California's unique population-based cancer surveillance resources to assess whether regional changes in breast cancer incidence observed between 2001 and 2004 correlated with regional changes in EPHT use between 2001 and 2003. Methods We obtained statewide cancer registry and California Health Interview Survey (CHIS) EPHT data for almost 3 million non-Hispanic white women age 45 to 74 years, residing in California's 58 counties. We examined trends in the age-adjusted incidence of invasive female breast cancer and compared these with trends in the use of EPHT, after grouping all California counties into three groups based on EPHT use in 2001. We also examined CHIS data on trends in screening mammography. Results In 2001, there were large regional differences in EPHT use and breast cancer incidence. From 2001 to 2004, incidence declined by 8.8% in the counties with the smallest EPHT reductions, by 13.9% in those with intermediate reductions, and by 22.6% in counties with the largest EPHT reductions. Between 2001 and 2003, CHIS data did not show any significant change in the proportion of women who reported having a mammogram in the previous 2 years. Conclusion These data support the hypothesis that changes in EPHT use in 2002 may be responsible for significant declines in breast cancer incidence between 2002 and 2003 and sustained through 2004.
An analysis of the distribution of tension in a bar attached to a plate
Authors: Le Fevre E J , Mudge D R J , Dickie J F 
Published: June 2007

This analysis relates to a bar of finite length attached to the surface of a semi-infinite flat plate, with the axis of the bar parallel to the surface of the plate. The bar projects beyond the edge of the plate and is subjected to tensile load. The object of this study is to determine an equation that describes approximately how the tension in the bar varies along the length over which it is attached to the plate. As a guide to the method of dealing with boundary conditions and discontinuities a simple case of two bars lap-jointed together is first considered. Some improvements in the basic assumptions and methods used by previous investigators are incorporated and some results are shown that compare well with experimental results.
A statistical approach to micro-plastic strain in metals
Authors: Esin A , Jones W J D 
Published: June 2007

The paper presents an outline of a theory of micro-inhomogeneity of stresses and strains resulting from the micro-structural properties of engineering materials. The problem is approached from a statistical point of view and it is experimentally shown that the degree of micro-inhomogeneity can be defined by normal distribution functions. Using the experimental results a general concept is postulated which takes into account the physical reality as completely as is practicable. It is shown that the suggested approach can be used to take into account the micro-plastic strains which exist while the material is nominally within the elastic limit.