bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geometric Mismatches within the Concentric Layers of Rotavirus Particles: a Potential Regulatory Switch of Viral Particle Transcription Activity
Authors: Libersou Sonia , Siebert Xavier , Ouldali Malika , Estrozi Leandro F. , Navaza Jorge , Charpilienne Annie , Garnier Pascale , Poncet Didier , Lepault Jean 
Published: January 2008

ABSTRACT
Rotaviruses are prototypical double-stranded RNA viruses whose triple-layered icosahedral capsid constitutes transcriptional machinery activated by the release of the external layer. To understand the molecular basis of this activation, we studied the structural interplay between the three capsid layers by electron cryo-microscopy and digital image processing. Two viral particles and four virus-like particles containing various combinations of inner (VP2)-, middle (VP6)-, and outer (VP7)-layer proteins were studied. We observed that the absence of the VP2 layer increases the particle diameter and changes the type of quasi-equivalent icosahedral symmetry, as described by the shift in triangulation number (T) of the VP6 layer (from T = 13 to T = 19 or more). By fitting X-ray models of VP6 into each reconstruction, we determined the quasi-atomic structures of the middle layers. These models showed that the VP6 lattices, i.e., curvature and trimer contacts, are characteristic of the particle composition. The different functional states of VP6 thus appear as being characterized by trimers having similar conformations but establishing different intertrimeric contacts. Remarkably, the external protein VP7 reorients the VP6 trimers located around the fivefold axes of the icosahedral capsid, thereby shrinking the channel through which mRNA exits the transcribing rotavirus particle. We conclude that the constraints arising from the different geometries imposed by the external and internal layers of the rotavirus capsid constitute a potential switch regulating the transcription activity of the viral particles.
The DNA Deaminase Activity of Human APOBEC3G Is Required for Ty1, MusD, and Human Immunodeficiency Virus Type 1 Restriction
Authors: Schumacher April J. , Haché Guylaine , MacDuff Donna A. , Brown William L. , Harris Reuben S. 
Published: January 2008

ABSTRACT
Human APOBEC3G and several other APOBEC3 proteins have been shown to inhibit the replication of a variety of retrotransposons and retroviruses. All of these enzymes can deaminate cytosines within single-strand DNA, but the overall importance of this conserved activity in retroelement restriction has been questioned by reports of deaminase-independent mechanisms. Here, three distinct retroelements, a yeast retrotransposon, Ty1, a murine endogenous retrovirus, MusD, and a lentivirus, human immunodeficiency virus type 1 (HIV-1), were used to evaluate the relative contributions of deaminase-dependent and -independent mechanisms. Although human APOBEC3G can restrict the replication of all three of these retroelements, APOBEC3G lacking the catalytic glutamate (E259Q) was clearly defective. This phenotype was particularly clear in experiments with low levels of APOBEC3G expression. In contrast, purposeful overexpression of APOBEC3G-E259Q was able to cause modest to severe reductions in the replication of Ty1, MusD, and HIV-1(ΔVif). The importance of these observations was highlighted by data showing that CEM-SS T-cell lines expressing near-physiologic levels of APOBEC3G-E259Q failed to inhibit the replication of HIV-1(ΔVif), whereas similar levels of wild-type APOBEC3G fully suppressed virus infectivity. Despite the requirement for DNA deamination, uracil DNA glycosylase did not modulate APOBEC3G-dependent restriction of Ty1 or HIV-1(ΔVif), further supporting prior studies indicating that the major uracil excision repair system of cells is not involved. In conclusion, the absolute requirement for the catalytic glutamate of APOBEC3G in Ty1, MusD, and HIV-1 restriction strongly indicates that DNA cytosine deamination is an essential part of the mechanism.
New regimen for eccentric calf-muscle training in patients with chronic insertional Achilles tendinopathy: results of a pilot study
Authors: Jonsson P , Alfredson H , Sunding K , Fahlström M , Cook J 
Published: January 2008

Background:Chronic painful insertional Achilles tendinopathy is seen in both physically active and non-active individuals. Painful eccentric training, where the patients load the Achilles tendon into full dorsiflexion, has shown good results in patients with mid-portion Achilles tendinosis. However, only 32% of patients with insertional Achilles tendinopathy had good clinical results with that type of eccentric training regimen.Aim:To investigate whether a new model of painful eccentric training had an effect on chronic painful insertional Achilles tendinopathy.Patients and methods:27 patients (12 men, 15 women, mean age 53 years) with a total of 34 painful Achilles tendons with a long duration of pain (mean 26 months), diagnosed as insertional Achilles tendinopathy, were included. The patients performed a new model of painful eccentric training regimen without loading into dorsiflexion. This was done as 3×15 reps, twice a day, 7 days/week, for 12 weeks. Pain during Achilles-tendon-loading activity (VAS) and patient’s satisfaction (back to previous activity) were evaluated.Results:At follow-up (mean 4 months) 18 patients (67%, 23/34 tendons) were satisfied and back to their previous tendon-loading activity. Their mean VAS had decreased from 69.9 (SD 18.9) to 21 (SD 20.6) (p<0.001). Nine patients (11 tendons) were not satisfied with the treatment, although their VAS was significantly reduced from 77.5 (8.6) to 58.1 (14.8) (p<0.01).Conclusion:In this short-term pilot study this new model of painful eccentric calf-muscle training showed promising clinical results in 67% of the patients.
LEARNING ABOUT WOMEN. ECONOMIC DEVELOPMENT, ENTREPRENEURSHIP AND THE ENVIRONMENT IN INDIA: A CASE STUDY
Authors: BERTAUX NANCY , CRABLE ELAINE 
Published: January 2008

On a recent semester-long stay in India, students from Xavier University (Cincinnati, Ohio) learned about a variety of social and economic development issues, with an emphasis on the role and status of women. This study describes and assesses the impact and effectiveness of their learning with a particular focus on their exposure to Meerut Seva Samaj (MSS), one economic development initiative concentrating on rural women.The Indian economy has recently witnessed an increase in entrepreneurship among women. Entrepreneurship often allows women to engage in home-based work so that they still can attend to their domestic duties, while also helping to financially support the family. Banks, companies, and NGOs (non-governmental organizations) are finding that offering micro-credit, or small loans, and other types of entrepreneurial assistance can help women start businesses. Meerut Seva Samaj provides a concrete example of how Indian women, especially in rural areas, can become successful entrepreneurs with the help of technology, training and other resources. MSS also assists local communities in the use of biogas, an environmentally friendly energy source that improves the environment and fertility of land in rural areas. The study places this service learning case study from India in the context of the literature on women, economic development, entrepreneurship and environmental issues.
Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABAAα2,3subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers
Authors: de Haas S.L. , de Visser S.J. , van der Post J.P. , Schoemaker R.C. , van Dyck K. , Murphy M.G. , de Smet M. , Vessey L.K. , Ramakrishnan R. , Xue L. , Cohen A.F. , van Gerven J.M.A. 
Published: January 2008

The use of non-selective γ-aminobutyric acid (GABA) enhancers, such as benzodiazepines in the treatment of anxiety disorders is still widespread but hampered by unfavourable side effects. some of these may be associated with binding properties to certain subtypes of the GABAAreceptor that are unnecessary for therapeutic effects. MK-0343 was designed to be a less sedating anxiolytic, based on reduced efficacy at the α1 subtype and significant efficacy at α2 and α3 subtypes of the GABAAreceptor.This paper is a double-blind, four-way cross-over ( n = 12) study to investigate the effects of MK-0343 (0.25 and 0.75 mg) in comparison to placebo and an anxiolytic dose (2 mg) of the non-selective agonist lorazepam. Effects were measured by eye movements, body sway, Visual Analogue scales (VAs) and memory tests.Lorazepam impaired saccadic peak velocity (sPV), VAs alertness scores, postural stability and memory and increased saccadic latency andinaccuracy. MK-0343 0.75 mg was equipotent with lorazepam as indicated by sPV (-42.4 deg/s), saccadic latency (0.02 s) and VAs alertness scores (1.50 ln mm), while effects on memory and postural stability were smaller. MK-0343 0.25 mg only affected postural stability to a similar extent as MK-0343 0.75 mg.The effect profile of MK-0343 0.75 mg is different from the full agonist lorazepam, which could reflect the selective actions of this compound. Although less effect on VAs alertness was expected, diminished effects on memory and postural stability were present. Clinical studies in anxiety patients should show whether this dose of MK-0343 is therapeutically effective with a different side-effect profile.
Social influences in sports activity among adolescents
Authors: Keresztes Noémi , Piko Bettina F. , Pluhar Zsuzsanna F. , Page Randy M. 
Published: January 2008

Aims: Habits of leisure time sports activity, similar to other health behaviours, are established during late childhood and early adolescence. While regular leisure time sports activity is a natural part of children's lifestyle, it starts to decrease during adolescence, particularly among girls. Among the factors influencing children's sports activity, the role of parents, peers, and other members of children's social networks seem to be crucial. The purpose of this study was to determine the role of social influences in early adolescents' leisure time sports activity and to examine gender differences. Methods: Data were collected from middle school students using randomly selected classes from four schools in distinct school districts in Szeged, Hungary, using a self-administered questionnaire (n = 548) in which a response rate of 91% was achieved. Respondents were 10—15 years of age (mean = 12.2 years, SD = 1.2 years) with 54.9% of the sample male and 45.1% female. Results: Results show significant others as an important influence on sport-related behaviours and suggest that during early adolescence girls' sports participation is particularly influenced by the social influence of peers (e.g. friends, classmates, boy/girlfriend). Conclusions: Our findings suggest that health promotion programmes should build on possible social influences, i.e. the role of peers, parents and significant others in general, in fostering adolescents' physical activity.
A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through α5β1 integrin
Authors: Soro Simonetta , Orecchia Angela , Morbidelli Lucia , Lacal Pedro Miguel , Morea Veronica , Ballmer-Hofer Kurt , Ruffini Federica , Ziche Marina , D'Atri Stefania , Zambruno Giovanna , Tramontano Anna , Failla Cristina Maria 
Published: January 2008

AbstractVascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for growth factors of the VEGF family. Endothelial cells express a membrane-bound and a soluble variant of this protein, the latter being mainly considered as a negative regulator of VEGF-A signaling. We previously reported that the soluble form is deposited in the extracellular matrix produced by endothelial cells in culture and is able to promote cell adhesion and migration through binding to α5β1 integrin. In this study, we demonstrate that the Ig-like domain II of VEGFR-1, which contains the binding determinants for the growth factors, is involved in the interaction with α5β1 integrin. To identify domain regions involved in integrin binding, we designed 12 peptides putatively mimicking the domain II surface and tested their ability to inhibit α5β1-mediated endothelial cell adhesion to soluble VEGFR-1 and directly support cell adhesion. One peptide endowed with both these properties was identified and shown to inhibit endothelial cell migration toward soluble VEGFR-1 as well. This peptide directly binds α5β1 integrin, but not VEGF-A, inducing endothelial cell tubule formation in vitro and neoangiogenesis in vivo. Alanine scanning mutagenesis of the peptide defined which residues were responsible for its biologic activity and integrin binding.
Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver
Authors: Landry Josette-Renée , Kinston Sarah , Knezevic Kathy , de Bruijn Marella F.T.R. , Wilson Nicola , Nottingham Wade T. , Peitz Michael , Edenhofer Frank , Pimanda John E. , Ottersbach Katrin , Göttgens Berthold 
Published: January 2008

AbstractTranscription factors such as Scl/Tal1, Lmo2, and Runx1 are essential for the development of hematopoietic stem cells (HSCs). However, the precise mechanisms by which these factors interact to form transcriptional networks, as well as the identity of the genes downstream of these regulatory cascades, remain largely unknown. To this end, we generated an Scl−/− yolk sac cell line to identify candidate Scl target genes by global expression profiling after reintroduction of a TAT-Scl fusion protein. Bioinformatics analysis resulted in the identification of 9 candidate Scl target transcription factor genes, including Runx1 and Runx3. Chromatin immunoprecipitation confirmed that both Runx genes are direct targets of Scl in the fetal liver and that Runx1 is also occupied by Scl in the yolk sac. Furthermore, binding of an Scl-Lmo2-Gata2 complex was demonstrated to occur on the regions flanking the conserved E-boxes of the Runx1 loci and was shown to transactivate the Runx1 element. Together, our data provide a key component of the transcriptional network of early hematopoiesis by identifying downstream targets of Scl that can explain key aspects of the early Scl−/− phenotype.
Pathway analysis of primary central nervous system lymphoma
Authors: Tun Han W. , Personett David , Baskerville Karen A. , Menke David M. , Jaeckle Kurt A. , Kreinest Pamela , Edenfield Brandy , Zubair Abba C. , O'Neill Brian P. , Lai Weil R. , Park Peter J. , McKinney Michael 
Published: January 2008

Abstract
Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a “CNS signature.” Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true “CNS signature” because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.
The Leicester Cough Monitor: preliminary validation of an automated cough detection system in chronic cough
Authors: Birring S. S. , Fleming T. , Matos S. , Raj A. A. , Evans D. H. , Pavord I. D. 
Published: January 2008

Chronic cough is a common condition that presents to both primary and secondary care. Assessment and management are hampered by the absence of well-validated outcome measures. The present study comprises the validation of the Leicester Cough Monitor (LCM), an automated sound-based ambulatory cough monitor.Cough frequency was measured with the LCM and compared with coughs and other sounds counted manually over 2 h of a 6-h recording by two observers in nine patients with chronic cough in order to determine the sensitivity and specificity of the LCM. Automated cough frequency was also compared with manual counts from one observer in 15 patients with chronic cough and eight healthy subjects. All subjects underwent 6-h recordings. A subgroup consisting of six control and five patients with stable chronic cough underwent repeat automated measurements ≥3 months apart. A further 50 patients with chronic cough underwent 24-h automated cough monitoring.The LCM had a sensitivity and specificity of 91 and 99%, respectively, for detecting cough and a false-positive rate of 2.5 events·h−1. Mean±semautomated cough counts·patient·h−1was 48±9 in patients with chronic cough and 2±1 in the control group (mean difference 46 counts·patient·h−1; 95% confidence interval (CI) 20–71). The automated cough counts were repeatable (intra-subjectsd11.4 coughs·patient·h−1; intra-class correlation coefficient 0.9). The cough frequency in patients undergoing 24-h automated monitoring was 19 coughs·patient·h−1; daytime (08:00–22:00 h) cough frequency was significantly greater than overnight cough frequency (25versus10 coughs·patient·h−1; mean difference 15 coughs·patient·h−1, 95% CI 8–22).The Leicester Cough Monitor is a valid and reliable tool that can be used to assess 24-h cough frequency in patients with cough. It should be a useful tool to assess patients with cough in clinical trials and longitudinal studies.
FCI: an R-based algorithm for evaluating uncertainty of absolute real-time PCR quantification
Authors: Verderio Paolo , Pizzamiglio Sara , Gallo Fabio , Ramsden Simon C 
Published: January 2008

Abstract

Background
FCI is an R code for analyzing data from real-time PCR experiments. This algorithm estimates standard curve features as well as nucleic acid concentrations and confidence intervals according to Fieller's theorem.

Results
In order to describe the features of FCI four situations were selected from real data collected during an international external quality assessment program for quantitative assays based on real-time PCR. The code generates a diagnostic figure suitable for assessing the quality of the quantification process.

Conclusion
We have provided a freeware programme using this algorithm specifically designed to increase the information content of the real-time PCR assay.
Genetic interactions: the missing links for a better understanding of cancer susceptibility, progression and treatment
Authors: Maxwell Christopher A , Moreno Víctor , Solé Xavier , Gómez Laia , Hernández Pilar , Urruticoechea Ander , Pujana Miguel Angel 
Published: January 2008

Abstract
It is increasingly clear that complex networks of relationships between genes and/or proteins govern neoplastic processes. Our understanding of these networks is expanded by the use of functional genomic and proteomic approaches in addition to computational modeling. Concurrently, whole-genome association scans and mutational screens of cancer genomes identify novel cancer genes. Together, these analyses have vastly increased our knowledge of cancer, in terms of both "part lists" and their functional associations. However, genetic interactions have hitherto only been studied in depth in model organisms and remain largely unknown for human systems. Here, we discuss the importance and potential benefits of identifying genetic interactions at the human genome level for creating a better understanding of cancer susceptibility and progression and developing novel effective anticancer therapies. We examine gene expression profiles in the presence and absence of co-amplification of the 8q24 and 20q13 chromosomal regions in breast tumors to illustrate the molecular consequences and complexity of genetic interactions and their role in tumorigenesis. Finally, we highlight current strategies for targeting tumor dependencies and outline potential matrix screening designs for uncovering molecular vulnerabilities in cancer cells.
Employer-Based Health Insurance
Authors: Wallen Jacqueline , Williams Sherman R. 
Published: January 2008

Employer-based health insurance (insurance that is purchased by employers for their employees and financed through employer or joint employer-employee contributions) is currently subsidized in part by the federal government through tax exclusions for employer contributions to employee health insurance plans. This subsidization costs the federal government close to 10 billion dollars a year in lost revenues. Many proposed national health insurance plans assign a key role to employer-based health insurance as a vehicle for financing health care. Federal subsidization of employer-based health insurance and plans that assign employers a key role in the administration of a national health insurance plan both assume that private industry acts to realize federal health policy goals—particularly cost containment—in administering health insurance plans.
Little is known, however, about how employers go about selecting the plans they offer their employees or about the incentives and disincentives regarding cost of care that are created by employer-based health insurance. Existing evidence suggests that rather than helping to contain health care costs, employer-based health insurance may be partly responsible for their present escalation. In addition, employer-based health insurance may not be the most equitable way to implement a national health insurance plan.
A Case Study in the Politics of Free-Market Health Care
Authors: Begun James W. , Lippincott Ronald C. 
Published: January 2008

Historically, most health occupations have developed legal and ethical restrictions on price advertising and other characteristics of “commercial” practice. Many of these regulations recently have come under critical scrutiny, on the grounds that they inhibit free-market health care delivery, thus keeping prices high, and productivity and innovation low.
To help inform current health policy deliberations, we analyze the political history of anticompetitive regulations in one health occupation, optometry. Restrictions on commercial practice arose as a result of professional optometry's purge of commercial elements in the 1930s. Optometry's success in achieving commercial-practice restrictions at the state level was determined by the economic structure of the ophthalmic goods and services industry in each state in the 1930s, and by the political resources and organization of the competing interest groups.
Efforts to deregulate health occupations will precipate political conflict to the extent that economic interests are threatened. Opposition to deregulation will be based overtly on the grounds that quality of care will deteriorate, and a significant political investment by proponents of free-market health care will be required to overcome such opposition.