bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel function for p21Cip1 and acetyltransferase p/CAF as critical transcriptional regulators of TGFβ-mediated breast cancer cell migration and invasion
Authors: Dai Meiou , Al-Odaini Amal A , Arakelian Ani , Rabbani Shafaat A , Ali Suhad , Lebrun Jean-Jacques 
Published: September 2012

Abstract
Introduction
Tumor cell migration and invasion are critical initiation steps in the process of breast cancer metastasis, the primary cause of breast cancer morbidity and death. Here we investigated the role of p21Cip1 (p21), a member of the core cell cycle machinery, in transforming growth factor-beta (TGFβ)-mediated breast cancer cell migration and invasion.

Methods
A mammary fat pad xenograft mouse model was used to assess the mammary tumor growth and local invasion. The triple negative human breast cancer cell lines MDA-MB231 and its sub-progenies SCP2 and SCP25, SUM159PT, SUM149PT, SUM229PE and SUM1315MO2 were treated with 5 ng/ml TGFβ and the protein expression levels were measured by Western blot. Cell migration and invasion were examined using the scratch/wound healing and Transwell assay. TGFβ transcriptional activity was measured by a TGFβ/Smad reporter construct (CAGA12-luc) using luciferase assay. q-PCR was used for assessing TGFβ downstream target genes. The interactions among p21, p/CAF and Smad3 were performed by co-immunoprecipitation. In addition, Smad3 on DNA binding ability was measured by DNA immunoprecipitation using biotinylated Smad binding element DNA probes. Finally, the association among active TGFβ/Smad signaling, p21 and p/CAF with lymph node metastasis was examined by immunohistochemistry in tissue microarray containing 50 invasive ductal breast tumors, 25 of which are lymph node positive.

Results
We found p21 expression to correlate with poor overall and distant metastasis free survival in breast cancer patients. Furthermore, using xenograft animal models and in vitro studies, we found p21 to be essential for tumor cell invasion. The invasive effects of p21 were found to correlate with Smad3, and p/CAF interaction downstream of TGFβ. p21 and p/CAF regulates TGFβ-mediated transcription of pro-metastatic genes by controlling Smad3 acetylation, DNA binding and transcriptional activity. In addition, we found that active TGFβ/Smad signaling correlates with high p21 and p/CAF expression levels and lymph node involvement using tissue microarrays from breast cancer patients.

Conclusions
Together these results highlight an important role for p21 and p/CAF in promoting breast cancer cell migration and invasion at the transcriptional level and may open new avenues for breast cancer therapy.
Intrinsic directionality of migrating vascular smooth muscle cells is regulated by NAD+ biosynthesis
Authors: Yin Hao , van der Veer Eric , Frontini Matthew J. , Thibert Victoria , O'Neil Caroline , Watson Alanna , Szasz Peter , Chu Michael W. A. , Pickering J. Geoffrey 
Published: September 2012

Summary
Cell migration is central to tissue repair and regeneration but must proceed with precise directionality to be productive. Directional migration requires external cues but also depends on the extent to which cells can inherently maintain their direction of crawling. We report that the NAD+ biosynthetic enzyme, nicotinamide phosphoribosyltransferase (Nampt/PBEF/visfatin), mediates directionally persistent migration of vascular smooth muscle cells (SMCs). Time-lapse microscopy of human SMCs subjected to Nampt inhibition revealed chaotic motility whereas SMCs transduced with the Nampt gene displayed highly linear migration paths. Ordered motility conferred by Nampt was associated with downsizing of the lamellipodium, reduced lamellipodium wandering around the cell perimeter, and increased lamellipodial protrusion rates. These protrusive and polarity-stabilizing effects also enabled spreading SMCs to undergo bipolar elongation to an extent not typically observed in vitro. Nampt was found to localize to lamellipodia and fluorescence recovery of Nampt–eGFP after photobleaching revealed microtubule-dependent transport of Nampt to the leading edge. In addition, Nampt was found to associate with, and activate, Cdc42, and Nampt-driven directional persistence and lamellipodium anchoring required Cdc42. We conclude that high-fidelity SMC motility is coordinated by a Nampt–Cdc42 axis that yields protrusive but small and anchored lamellipodia. This novel, NAD+-synthesis-dependent control over motility may be crucial for efficient repair and regeneration of the vasculature, and possibly other tissues.
Microtubule guidance tested through controlled cell geometry
Authors: Huda Sabil , Soh Siowling , Pilans Didzis , Byrska-Bishop Marta , Kim Jiwon , Wilk Gary , Borisy Gary G. , Kandere-Grzybowska Kristiana , Grzybowski Bartosz A. 
Published: September 2012

Summary
In moving cells dynamic microtubules (MTs) target and disassemble substrate adhesion sites (focal adhesions; FAs) in a process that enables the cell to detach from the substrate and propel itself forward. The short-range interactions between FAs and MT plus ends have been observed in several experimental systems, but the spatial overlap of these structures within the cell has precluded analysis of the putative long-range mechanisms by which MTs growing through the cell body reach FAs in the periphery of the cell. In the work described here cell geometry was controlled to remove the spatial overlap of cellular structures thus allowing for unambiguous observation of MT guidance. Specifically, micropatterning of living cells was combined with high-resolution in-cell imaging and gene product depletion by means of RNA interference to study the long-range MT guidance in quantitative detail. Cells were confined on adhesive triangular microislands that determined cell shape and ensured that FAs localized exclusively at the vertices of the triangular cells. It is shown that initial MT nucleation at the centrosome is random in direction, while the alignment of MT trajectories with the targets (i.e. FAs at vertices) increases with an increasing distance from the centrosome, indicating that MT growth is a non-random, guided process. The guided MT growth is dependent on the presence of FAs at the vertices. The depletion of either myosin IIA or myosin IIB results in depletion of F-actin bundles and spatially unguided MT growth. Taken together our findings provide quantitative evidence of a role for long-range MT guidance in MT targeting of FAs.
IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes
Authors: Narayanan Ram P , Fu Bo , Heald Adrian H , Siddals Kirk W , Oliver Robert L , Hudson Julie E , Payton Antony , Anderson Simon G , White Anne , Ollier William E R , Gibson J Martin 
Published: September 2012

ObjectiveInsulin-like growth factors are implicated in the development of diabetic nephropathy. IGF-binding protein 2 (IGFBP2) and IGF2 are expressed in the kidney, but their associations with diabetic nephropathy are unclear. We therefore tested the hypothesis that circulating levels of IGF2 and IGFBP2 predict longitudinal renal function in individuals with type 2 diabetes.Design and methodsIGFBP2 and IGF2 measurements were performed in 436 individuals (263 males) with type 2 diabetes. Linear mixed-effect regression analysis was used to model the relationship between plasma IGFBP2 concentration and longitudinal changes in estimated glomerular filtration rate (eGFR) over an 8-year period. Analyses were also performed for IGF1, IGF2, IGFBP1 and IGFBP3 concentrations as predictors of longitudinal renal outcomes.ResultsHigh IGFBP2 concentration at baseline was associated with a decreased eGFR over an 8-year period (β=−0.02, (95% confidence interval −0.03 to −0.01), P<0.001). High IGFBP1, IGFBP2 and IGFBP3 were also associated with low baseline eGFR concentration.ConclusionThis study demonstrates that IGFBP2 is a predictor of longitudinal deterioration of renal function in type 2 diabetes.
Self-Help Booklets for Preventing Postpartum Smoking Relapse: A Randomized Trial
Authors: Brandon Thomas H. , Simmons Vani Nath , Meade Cathy D. , Quinn Gwendolyn P. , Lopez Khoury Elena N. , Sutton Steven K. , Lee Ji-Hyun 
Published: September 2012

Objectives. We tested a series of self-help booklets designed to prevent postpartum smoking relapse. Methods. We recruited 700 women in months 4 through 8 of pregnancy, who quit smoking for their pregnancy. We randomized the women to receive either (1) 10 Forever Free for Baby and Me (FFB) relapse prevention booklets, mailed until 8 months postpartum, or (2) 2 existing smoking cessation materials, as a usual care control (UCC). Assessments were completed at baseline and at 1, 8, and 12 months postpartum. Results. We received baseline questionnaires from 504 women meeting inclusion criteria. We found a main effect for treatment at 8 months, with FFB yielding higher abstinence rates (69.6%) than UCC (58.5%). Treatment effect was moderated by annual household income and age. Among lower income women (< $30 000), treatment effects were found at 8 and 12 months postpartum, with respective abstinence rates of 72.2% and 72.1% for FFB and 53.6% and 50.5% for UCC. No effects were found for higher income women. Conclusions. Self-help booklets appeared to be efficacious and offered a low-cost modality for providing relapse-prevention assistance to low-income pregnant and postpartum women.
Expected Ethical Competencies of Public Health Professionals and Graduate Curricula in Accredited Schools of Public Health in North America
Authors: Lee Lisa M. , Wright Brandy , Semaan Salaam 
Published: September 2012

Objectives. We assessed expected ethics competencies of public health professionals in codes and competencies, reviewed ethics instruction at schools of public health, and recommended ways to bridge the gap between them. Methods. We reviewed the code of ethics and 3 sets of competencies, separating ethics-related competencies into 3 domains: professional, research, and public health. We reviewed ethics course requirements in 2010–2011 on the Internet sites of 46 graduate schools of public health and categorized courses as required, not required, or undetermined. Results. Half of schools (n = 23) required an ethics course for graduation (master’s or doctoral level), 21 did not, and 2 had no information. Sixteen of 23 required courses were 3-credit courses. Course content varied from 1 ethics topic to many topics addressing multiple ethics domains. Conclusions. Consistent ethics education and competency evaluation can be accomplished through a combination of a required course addressing the 3 domains, integration of ethics topics in other courses, and “booster” trainings. Enhancing ethics competence of public health professionals is important to address the ethical questions that arise in public health research, surveillance, practice, and policy.
High Parenting Aggravation Among US Immigrant Families
Authors: Yu Stella M. , Singh Gopal K. 
Published: September 2012

Objectives. We examined the association between the joint effects of children’s immigrant family type and race/ethnicity on parenting aggravation. Methods. We analyzed data on a nationally representative sample of 101 032 children aged birth through 17 years from the 2003 National Survey of Children’s Health. Results. Analysis of the Aggravation in Parenting Scale showed that 26% of foreign-born parents with foreign-born children were highly aggravated, followed by 22% of foreign-born parents with US-born children and 11% of US-born parents. Multivariable analyses indicated that all minority parents experienced high parenting aggravation compared with non-Hispanic White US-born parents; the odds of reporting parenting aggravation were 5 times higher for Hispanic foreign-born parents. All foreign-born parents, regardless of race/ethnicity, reported significantly elevated parenting aggravation. Parents of adolescents, children with special health care needs, and nontraditional and lower-income households were also more likely to report high parenting aggravation. Conclusions. Our findings clearly document significantly elevated levels of parenting aggravation among immigrant and minority families. Public health programs and clinicians should target referrals and interventions for these families to avoid potential health problems for both children and their families.
The United Nations High Level Meeting on the Prevention and Control of Noncommunicable Diseases: A Missed Opportunity?
Authors: Sivaramakrishnan Kavita , Parker Richard G. 
Published: September 2012

The United Nations High Level Meeting on the Prevention and Control of Noncommunicable Diseases (September 19–20, 2011) provided an opportunity to recast the current global health agenda and offered a formidable platform to mobilize political will for concerted action. We argue that the opportunity was missed because the World Health Organization (WHO) neglected the politics of process that are key to mobilizing political support for global noncommunicable disease policies. Instead, it focused on the implementation process. The lessons to be drawn from the summit are critical because the WHO is the key agency that will be expected in the near future to steer further discussions and debate on the noncommunicable disease agenda.
Deaths From Secondhand Smoke Exposure in the United States: Economic Implications
Authors: Max Wendy , Sung Hai-Yen , Shi Yanling 
Published: September 2012

Objectives. We estimated the number of deaths attributable to secondhand smoke (SHS), years of potential life lost (YPLL), and value of lost productivity for different US racial/ethnic groups in 2006. Methods. We determined the number of SHS–related deaths among nonsmokers from 2 adult and 4 infant conditions using an epidemiological approach. We estimated adult SHS exposure using detectable serum cotinine. For each death, we determined the YPLL and the value of lost productivity. Results. SHS exposure resulted in more than 42 000 deaths: more than 41 000 adults and nearly 900 infants. Blacks accounted for 13% of all deaths but 24% to 36% of infant deaths. SHS–attributable deaths resulted in a loss of nearly 600 000 YPLL and $6.6 billion of lost productivity, or $158 000 per death. The value of lost productivity per death was highest among Blacks ($238 000) and Hispanics ($193 000). Conclusions. The economic toll of SHS exposure is substantial, with communities of color having the greatest losses. Interventions need to be designed to reduce the health and economic burden of smoking on smokers and nonsmokers alike and on particularly vulnerable groups.
Income Inequality in Health at All Ages: A Comparison of the United States and England
Authors: Martinson Melissa L. 
Published: September 2012

Objectives. I systematically examined income gradients in health in the United States and England across the life span (ages birth to 80 years), separately for females and males, for a number of health conditions. Methods. Using data from the National Health and Nutrition Examination Survey for the United States (n = 36 360) and the Health Survey for England (n = 55 783), I calculated weighted prevalence rates and risk ratios by income level for the following health risk factors or conditions: obesity, hypertension, diabetes, low high-density lipoprotein cholesterol, high cholesterol ratio, heart attack or angina, stroke, and asthma. Results. In the United States and England, the income gradients in health are very similar across age, gender, and numerous health conditions, and are robust to adjustments for race/ethnicity, health behaviors, body mass index, and health insurance. Conclusions. Health disparities by income are pervasive in England as well as in the United States, despite better overall health, universal health insurance, and more generous social protection spending in England.
Visiting the Emergency Department for Dental Problems: Trends in Utilization, 2001 to 2008
Authors: Lee Helen H. , Lewis Charlotte W. , Saltzman Babette , Starks Helene 
Published: September 2012

Objectives. We tested the hypothesis that between 2001 and 2008, Americans increasingly relied upon emergency departments (EDs) for dental care. Methods. Data from 2001 through 2008 were collected from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Population-based visit rates for dental problems, and, for comparison, asthma, were calculated using annual US Census Bureau estimates. As part of the analysis, we described patient characteristics associated with large increases in ED dental utilization. Results. Dental visit rates increased most dramatically for the following subpopulations: those aged 18 to 44 years (7.2–12.2 per 1000, P < .01); Blacks (6.0–10.4 per 1000, P < .01); and the uninsured (9.5–13.2 per 1000, P < .01). Asthma visit rates did not change although dental visit rates increased 59% from 2001 to 2008. Conclusions. There is an increasing trend in ED visits for dental issues, which was most pronounced among those aged 18 to 44 years, the uninsured, and Blacks. Dental visit rates increased significantly although there was no overall change in asthma visit rates. This suggests that community access to dental care compared with medical care is worsening over time.
Meta-Analysis of Single-Session Behavioral Interventions to Prevent Sexually Transmitted Infections: Implications for Bundling Prevention Packages
Authors: Eaton Lisa A. , Huedo-Medina Tania B. , Kalichman Seth C. , Pellowski Jennifer A. , Sagherian Michael J. , Warren Michelle , Popat Ami R. , Johnson Blair T. 
Published: September 2012

Evidence-based, single-session behavioral interventions are urgently needed for preventing the spread of HIV and other sexually transmitted infections (STIs). To estimate the efficacy of single-session, behavioral interventions for STI prevention, we collected data from 29 single-session interventions (20 studies; n = 52 465) with an STI outcome. Infection with an STI was 35% less likely (odds ratio = 0.65; 95% confidence interval = 0.55–0.77) among intervention group participants than among control group participants. Single-session interventions offer considerable benefits in terms of disease prevention and create minimal burden for both the patient and the provider. Brief and effective STI prevention interventions are a valuable tool and can be readily adapted to bolster the benefits of biomedical technologies focusing on the prevention of HIV and other STIs.
La fin de l'aide publique au développement : les enjeux de l'action hypercollective
Authors: Severino Jean-Michel , Ray Olivier 
Published: September 2012

Résumé Au cours de la dernière décennie, une transformation radicale du nombre et du type d’intervenants s’est produite dans les industries de l’aide au développement, de l’humanitaire et des biens publics globaux, tant dans les pays dits « donateurs » que dans les pays dits « bénéficiaires ». Cette double tendance à la prolifération (l’augmentation du nombre d’intervenants) et à la fragmentation (l’éparpillement de l’activité des bailleurs) est caractéristique du glissement de l’action collective vers ce que nous appelons « l’action hypercollective ». Si l’on peut se réjouir de l’énergie et des ressources supplémentaires permises par cette évolution, une importante perte d’efficacité en résulte. Nous soutenons dans cet article que le défi majeur pour la gouvernance des politiques publiques globales au cours des prochaines décennies consistera non pas à réduire la complexité, mais l’orienter vers plus d’efficacité. La Déclaration de Paris représente la première tentative d’envergure de traiter les défis de l’action « hypercollective », mais ne constitue pas une base suffisamment solide pour l’action hypercollective qu’exigent les politiques publiques globales en plein essor. Il convient d’élaborer un nouveau cadre conceptuel et développer des processus incitant la convergence d’actions initiées de façon décentralisée par de nombreux intervenants. Classification JEL : O10
« Test de réalité » et limites du relativisme
Authors: Da Costa Marques Ivan 
Published: September 2012

Cet article propose un cadre d’analyse des relations entre science et pouvoir dans le programme alimentaire MULTIMIXTURE, présent au Brésil depuis les années 1970. L’analyse porte sur la période 1970-2008. Je vous présente trois ontologies, histoires ou versions de réalité. Dans chacune, les relations entre les connaissances scientifiques sur la nutrition (institutionnalisées dans les laboratoires académiques et dans le Conseil Fédéral des Nutritionnistes) et le programme MULTIMIXTURE sont transformées. J’établis une hiérarchie entre ces trois versions de réalité en ce qui concerne leurs capacités dialogiques. La première est déterminée par l’analyse biochimique des composants de la MULTIMIXTURE. La seconde se présente comme un mélange stabilisé de science et culture, nature et société, technique et politique ; c’est une sorte de version de réalité mise en jeu par de nombreuses études dans le champ STS (Science and Technology Studies). La troisième est une histoire éclairée par l’anthropologie, qui échappe aux contraintes du « test de réalité » dominant dans la culture occidentale.
Thymic Function Is Maintained during Salmonella-Induced Atrophy and Recovery
Authors: Ross Ewan A. , Coughlan Ruth E. , Flores-Langarica Adriana , Lax Sian , Nicholson Julia , Desanti Guillaume E. , Marshall Jennifer L. , Bobat Saeeda , Hitchcock Jessica , White Andrea , Jenkinson William E. , Khan Mahmood , Henderson Ian R. , Lavery Gareth G. , Buckley Christopher D. , Anderson Graham , Cunningham Adam F. 
Published: September 2012

Abstract
Thymic atrophy is a frequent consequence of infection with bacteria, viruses, and parasites and is considered a common virulence trait between pathogens. Multiple reasons have been proposed to explain this atrophy, including premature egress of immature thymocytes, increased apoptosis, or thymic shutdown to prevent tolerance to the pathogen from developing. The severe loss in thymic cell number can reflect an equally dramatic reduction in thymic output, potentially reducing peripheral T cell numbers. In this study, we examine the relationship between systemic Salmonella infection and thymic function. During infection, naive T cell numbers in peripheral lymphoid organs increase. Nevertheless, this occurs despite a pronounced thymic atrophy caused by viable bacteria, with a peak 50-fold reduction in thymocyte numbers. Thymic atrophy is not dependent upon homeostatic feedback from peripheral T cells or on regulation of endogenous glucocorticoids, as demonstrated by infection of genetically altered mice. Once bacterial numbers fall, thymocyte numbers recover, and this is associated with increases in the proportion and proliferation of early thymic progenitors. During atrophy, thymic T cell maturation is maintained, and single-joint TCR rearrangement excision circle analysis reveals there is only a modest fall in recent CD4+ thymic emigrants in secondary lymphoid tissues. Thus, thymic atrophy does not necessarily result in a matching dysfunctional T cell output, and thymic homeostasis can constantly adjust to systemic infection to ensure that naive T cell output is maintained.