bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin Regulates Stearoyl CoA Desaturase 1 Expression in Breast Cancer
Authors: Luyimbazi David , Akcakanat Argun , McAuliffe Priscilla F. , Zhang Li , Singh Gopal , Gonzalez-Angulo Ana Maria , Chen Huiqin , Do Kim-Anh , Zheng Yuhuan , Hung Mien-Chie , Mills Gordon B. , Meric-Bernstam Funda 
Published: September 2010

Abstract
Mammalian target of rapamycin (mTOR) signaling is a central regulator of protein translation, cell growth, and metabolism. Alterations of the mTOR signaling pathway are common in cancer, making mTOR a promising therapeutic target. In clinical trials, rapamycin analogs have shown modest response rates for most cancer types, including breast cancer. Therefore, there is an urgent need to better understand the mechanism of action of rapamycin to improve patient selection and to monitor pathway inhibition. To identify novel pharmacodynamic markers of rapamycin activity, we carried out transcriptional profiling of total and polysome-associated RNA in three breast cancer cell lines representing different subtypes. In all three cell lines, we found that rapamycin significantly decreased polysome-associated mRNA for stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis. Activators of mTOR increased SCD1 protein expression, whereas rapamycin, LY294002, and BEZ235 decreased SCD1 protein expression. Rapamycin decreased total SCD1 RNA expression without inducing a significant decline in its relative polysomal recruitment (polysome/total ratio). Rapamycin did not alter SCD1 mRNA stability. Instead, rapamycin inhibited SCD1 promoter activity and decreased expression of mature transcription factor sterol regulatory element binding protein 1 (SREBP1). Eukaryotic initiation factor 4E (eIF4E) small interfering RNA (siRNA) decreased both SCD1 and SREBP1 expression, suggesting that SCD1 may be regulated through the mTOR/eIF4E-binding protein 1 axis. Furthermore, SCD1 siRNA knockdown inhibited breast cancer cell growth, whereas overexpression increased growth. Taken together these findings show that rapamycin decreases SCD1 expression, establishing an important link between cell signaling and cancer cell fatty acid synthesis and growth. Mol Cancer Ther; 9(10); 2770–84. ©2010 AACR.
Race, Ethnicity, and Shared Decision Making for Hyperlipidemia and Hypertension Treatment: The DECISIONS Survey
Authors: Ratanawongsa Neda , Zikmund-Fisher Brian J. , Couper Mick P. , Van Hoewyk John , Powe Neil R. 
Published: September 2010

Background Racial/ethnic differences in shared decision making about cardiovascular risk-reduction therapy could affect health disparities. Objective To investigate whether patient race/ethnicity is associated with experiences discussing cardiovascular risk-reduction therapy with health care providers. Setting National sample of US adults identified by random-digit dialing. Design Cross-sectional survey conducted in November 2006 to May 2007. Participants Among participants in the National Survey of Medical Decisions (DECISIONS), a nationally representative sample of English-speaking US adults aged 40 and older, the authors analyzed respondents who reported discussing hyperlipidemia or hypertension medications with a health care provider in the previous 2 years. Measurements In multivariate linear and logistic regressions adjusting for age, gender, income, insurance status, perceived health, and current therapy, they assessed the relation between race/ethnicity (black/Hispanic v. white) and decision making: knowledge, discussion of pros and cons of therapy, discussion of patient preference, who made the final decision, preferred involvement, and confidence in the decision. Results Of respondents who discussed high cholesterol (N = 738) or hypertension (N = 745) medications, 88% were white, 9% black, and 4% Hispanic. Minorities had lower knowledge scores than whites for hyperlipidemia (42% v. 52%, difference –10% [95% confidence interval (CI): 15, –5], P < 0.001), but not for hypertension. For hyperlipidemia, minorities were more likely than whites to report that the health care provider made the final decision for treatment (31.7% v. 12.3% whites, difference 19.4% [95% CI: 6.9, 33.1%], P < 0.01); this was not true for hypertension. Limitations Possible limitations include the small percentage of minorities in the sample and potential recall bias. Conclusions Minorities considering hyperlipidemia therapy may be less informed about and less involved in the final decision-making process.
Gender, Development, and Neoliberalism: HIV/ AIDS in Cambodia
Authors: Yaşar Yavuz 
Published: September 2010

Thanks to the anti-HIV/AIDS measures of international and non-governmental organizations, Cambodia has been considered a successful case in preventing the transmission of the virus. Declaration of such a victory for the Cambodian case is premature, however, given that HIV prevalence continues to rise among women and, according to Cambodian health officials, another wave of epidemic could occur soon. This study discusses how the implementation of neoliberal economic policies without counterbalancing social policy measures undermines the sustainability and effectiveness of such short-term measures by creating a risky environment for the epidemic. Trade liberalization policies have exacerbated poverty, mobility, and gender inequality, making women more susceptible and vulnerable to HIV/AIDS. JEL classification: I18, F13, O19
Mislocalization of Lck impairs thymocyte differentiation and can promote development of thymomas
Authors: Salmond Robert J. , Filby Andrew , Pirinen Niina , Magee Anthony I. , Zamoyska Rose 
Published: September 2010

AbstractT-cell development is critically dependent on the activities of the Src-family kinases p56lck and p59fyn. While Lck plays a dominant role in the initiation of T-cell receptor (TCR) signaling and in thymocyte differentiation, Fyn plays a more subtle regulatory role. We sought to determine the role of intracellular localization in the differing functions of Lck and Fyn in T cells. By generating transgenic mice that express chimeric Lck-Fyn proteins, we showed that the N-terminal unique domain determines the intracellular localization and function of Lck in pre-TCR and mature αβTCR signaling in vivo. Furthermore, coexpression of a “domain-swap” Lck protein containing the Fyn unique domain with an inducible Lck transgene resulted in the development of thymomas. In contrast to previous reports of Lck-driven thymomas, tumor development was dependent on either pre-TCR or mature TCR signals, and was completely ablated when mice were crossed to a recombination activating gene 1 (Rag1)–deficient background. These data provide a mechanistic basis for the differing roles of Lck and Fyn in T-cell development, and show that intracellular localization as determined by the N-terminal unique domains is critical for Src-family kinase function in vivo.
Complete characterization of the microRNAome in a patient with acute myeloid leukemia
Authors: Ramsingh Giridharan , Koboldt Daniel C. , Trissal Maria , Chiappinelli Katherine B. , Wylie Todd , Koul Sunita , Chang Li-Wei , Nagarajan Rakesh , Fehniger Todd A. , Goodfellow Paul , Magrini Vincent , Wilson Richard K. , Ding Li , Ley Timothy J. , Mardis Elaine R. , Link Daniel C. 
Published: September 2010

Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and have been implicated in the pathogenesis of cancer. In this study, we applied next generation sequencing techniques to comprehensively assess miRNA expression, identify genetic variants of miRNA genes, and screen for alterations in miRNA binding sites in a patient with acute myeloid leukemia. RNA sequencing of leukemic myeloblasts or CD34+ cells pooled from healthy donors showed that 472 miRNAs were expressed, including 7 novel miRNAs, some of which displayed differential expression. Sequencing of all known miRNA genes revealed several novel germline polymorphisms but no acquired mutations in the leukemia genome. Analysis of the sequence of the 3′-untranslated regions (UTRs) of all coding genes identified a single somatic mutation in the 3′-UTR of TNFAIP2, a known target of the PML-RARα oncogene. This mutation resulted in translational repression of a reporter gene in a Dicer-dependent fashion. This study represents the first complete characterization of the “miRNAome” in a primary human cancer and suggests that generation of miRNA binding sites in the UTR regions of genes is another potential mechanism by which somatic mutations can affect gene expression.
A global optimization algorithm for protein surface alignment
Authors: Bertolazzi Paola , Guerra Concettina , Liuzzi Giampaolo 
Published: September 2010

Abstract

Background
A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved.

Results
In this paper we propose a new method for local structural alignment of protein surfaces based on continuous global optimization techniques. Given the three-dimensional structures of two proteins, the method finds the isometric transformation (rotation plus translation) that best superimposes active regions of two structures. We draw our inspiration from the well-known Iterative Closest Point (ICP) method for three-dimensional (3D) shapes registration. Our main contribution is in the adoption of a controlled random search as a more efficient global optimization approach along with a new dissimilarity measure. The reported computational experience and comparison show viability of the proposed approach.

Conclusions
Our method performs well to detect similarity in binding sites when this in fact exists. In the future we plan to do a more comprehensive evaluation of the method by considering large datasets of non-redundant proteins and applying a clustering technique to the results of all comparisons to classify binding sites.
PpiD is a player in the network of periplasmic chaperones in Escherichia coli
Authors: Matern Yvonne , Barion Birgitta , Behrens-Kneip Susanne 
Published: September 2010

Abstract

Background
The inner membrane-anchored periplasmic folding factor PpiD is described as a parvulin-like peptidyl prolyl isomerase (PPIase) that assists in the maturation of the major beta-barrel outer membrane proteins (OMPs) of Escherichia coli. More recent work however, calls these findings into question. Here, we re-examined the role of PpiD in the E. coli periplasm by analyzing its functional interplay with other folding factors that influence OMP maturation as well as general protein folding in the periplasmic compartment of the cell, such as SurA, Skp, and DegP.

Results
The analysis of the effects of both deletion and overexpression of ppiD on cell envelope phenotypes revealed that PpiD in contrast to prior observations plays only a minor role, if any, in the maturation of OMPs and cannot compensate for the lack of SurA in the periplasm. On the other hand, our results show that overproduction of PpiD rescues a surA skp double mutant from lethality. In the presence of increased PpiD levels surA skp cells show reduced activities of both the SigmaE-dependent and the Cpx envelope stress responses, and contain increased amounts of folded species of the major OMP OmpA. These effects require the anchoring of PpiD in the inner membrane but are independent of its parvulin-like PPIase domain. Moreover, a PpiD protein lacking the PPIase domain also complements the growth defects of an fkpA ppiD surA triple PPIase mutant and exhibits chaperone activity in vitro. In addition, PpiD appears to collaborate with DegP, as deletion of ppiD confers a temperature-dependent conditional synthetic phenotype in a degP mutant.

Conclusions
This study provides first direct evidence that PpiD functions as a chaperone and contributes to the network of periplasmic chaperone activities without being specifically involved in OMP maturation. Consistent with previous work, our data support a model in which the chaperone function of PpiD is used to aid in the early periplasmic folding of many newly translocated proteins.
Overexpression of a natural chloroplast-encoded antisense RNA in tobacco destabilizes 5S rRNA and retards plant growth
Authors: Hotto Amber M , Huston Zoe E , Stern David B 
Published: September 2010

Abstract

Background
The roles of non-coding RNAs in regulating gene expression have been extensively studied in both prokaryotes and eukaryotes, however few reports exist as to their roles in organellar gene regulation. Evidence for accumulation of natural antisense RNAs (asRNAs) in chloroplasts comes from the expressed sequence tag database and cDNA libraries, while functional data have been largely obtained from artificial asRNAs. In this study, we used Nicotiana tabacum to investigate the effect on sense strand transcripts of overexpressing a natural chloroplast asRNA, AS5, which is complementary to the region which encodes the 5S rRNA and tRNAArg.

Results
AS5-overexpressing (AS5ox) plants obtained by chloroplast transformation exhibited slower growth and slightly pale green leaves. Analysis of AS5 transcripts revealed four distinct species in wild-type (WT) and AS5ox plants, and additional AS5ox-specific products. Of the corresponding sense strand transcripts, tRNAArg overaccumulated several-fold in transgenic plants whereas 5S rRNA was unaffected. However, run-on transcription showed that the 5S-trnR region was transcribed four-fold more in the AS5ox plants compared to WT, indicating that overexpression of AS5 was associated with decreased stability of 5S rRNA. In addition, polysome analysis of the transformants showed less 5S rRNA and rbcL mRNA associated with ribosomes.

Conclusions
Our results suggest that AS5 can modulate 5S rRNA levels, giving it the potential to affect Chloroplast translation and plant growth. More globally, overexpression of asRNAs via chloroplast transformation may be a useful strategy for defining their functions.
Comparison of different sampling techniques and of different culture methods for detection of group B streptococcus carriage in pregnant women
Authors: El Aila Nabil A , Tency Inge , Claeys Geert , Saerens Bart , Cools Piet , Verstraelen Hans , Temmerman Marleen , Verhelst Rita , Vaneechoutte Mario 
Published: September 2010

Abstract

Background

Streptococcus agalactiae (group B streptococcus; GBS) is a significant cause of perinatal and neonatal infections worldwide. To detect GBS colonization in pregnant women, the CDC recommends isolation of the bacterium from vaginal and anorectal swab samples by growth in a selective enrichment medium, such as Lim broth (Todd-Hewitt broth supplemented with selective antibiotics), followed by subculture on sheep blood agar. However, this procedure may require 48 h to complete. We compared different sampling and culture techniques for the detection of GBS.

Methods
A total of 300 swabs was taken from 100 pregnant women at 35-37 weeks of gestation. For each subject, one rectovaginal, one vaginal and one rectal ESwab were collected. Plating onto Columbia CNA agar (CNA), group B streptococcus differential agar (GBSDA) (Granada Medium) and chromID Strepto B agar (CA), with and without Lim broth enrichment, were compared. The isolates were confirmed as S. agalactiae using the CAMP test on blood agar and by molecular identification with tDNA-PCR or by 16S rRNA gene sequence determination.

Results
The overall GBS colonization rate was 22%. GBS positivity for rectovaginal sampling (100%) was significantly higher than detection on the basis of vaginal sampling (50%), but not significantly higher than for rectal sampling (82%). Direct plating of the rectovaginal swab on CNA, GBSDA and CA resulted in detection of 59, 91 and 95% of the carriers, respectively, whereas subculturing of Lim broth yielded 77, 95 and 100% positivity, respectively. Lim broth enrichment enabled the detection of only one additional GBS positive subject. There was no significant difference between GBSDA and CA, whereas both were more sensitive than CNA. Direct culture onto GBSDA or CA (91 and 95%) detected more carriers than Lim broth enrichment and subculture onto CNA (77%). One false negative isolate was observed on GBSDA, and three false positives on CA.

Conclusions
In conclusion, rectovaginal sampling increased the number GBS positive women detected, compared to vaginal and/or rectal sampling. Direct plating on CA and/or GBSDA provided rapid detection of GBS that was at least as sensitive and specific as the CDC recommended method of Lim broth subcultured onto non chromogenic agar.
Population uptake of antiretroviral treatment through primary care in rural South Africa
Authors: Cooke Graham S , Tanser Frank C , Bärnighausen Till W , Newell Marie-Louise 
Published: September 2010

Abstract

Background
KwaZulu-Natal is the South African province worst affected by HIV and the focus of early modeling studies investigating strategies of antiretroviral treatment (ART) delivery. The reality of antiretroviral roll-out through primary care has differed from that anticipated and real world data are needed to inform the planning of further scaling up of services. We investigated the factors associated with uptake of antiretroviral treatment through a primary healthcare system in rural South Africa.

Methods
Detailed demographic, HIV surveillance and geographic information system (GIS) data were used to estimate the proportion of HIV positive adults accessing antiretroviral treatment within northern KwaZulu-Natal, South Africa in the period from initiation of antiretroviral roll-out until the end of 2008. Demographic, spatial and socioeconomic factors influencing the likelihood of individuals accessing antiretroviral treatment were explored using multivariable analysis.

Results
Mean uptake of ART among HIV positive resident adults was 21.0% (95%CI 20.1-21.9). Uptake among HIV positive men (19.2%) was slightly lower than women (21.8%, P = 0.011). An individual's likelihood of accessing ART was not associated with level of education, household assets or urban/rural locale. ART uptake was strongly negatively associated with distance from the nearest primary healthcare facility (aOR = 0.728 per square-root transformed km, 95%CI 0.658-0.963, P = 0.002).

Conclusions
Despite concerns about the equitable nature of antiretroviral treatment rollout, we find very few differences in ART uptake across a range of socio-demographic variables in a rural South African population. However, even when socio-demographic factors were taken into account, individuals living further away from primary healthcare clinics were still significantly less likely to be accessing ART
Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials
Authors: Löwenstein Oliver , Leyendecker Petra , Lux Eberhard A , Blagden Mark , Simpson Karen H , Hopp Michael , Bosse Björn , Reimer Karen 
Published: September 2010

Abstract

Background
Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted.

Methods
These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day).

Results
No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively).

Conclusions
Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy.

Trial registration numbers
ClinicalTrials.gov identifier: NCT00412100 and NCT00412152
Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease
Authors: Minami S Sakura , Sidahmed Elkhansa , Aid Saba , Shimoji Mika , Niikura Takako , Mocchetti Italo , Rebeck G William , Prendergast Jay S , Dealwis Chris , Wetzel Ronald , Bosetti Francesca , Matsuoka Yasuji , Hoe Hyang-Sook , Turner R Scott 
Published: September 2010

Abstract

Background
Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical studies, but its application is limited by neuroinflammatory side effects (autoimmune encephalitis and vasogenic edema).

Methods
We intravenously administered the monoclonal Aβ protofibril antibody PFA1 to aged (22 month) male and female 3 × tg AD mice with intermediate or advanced AD-like neuropathologies, respectively, and measured brain and serum Aβ and CNS cytokine levels. We also examined 17 month old 3 × tg AD female mice with intermediate pathology to determine the effect of amyloid burden on responses to passive immunization.

Results
The 22 month old male mice immunized with PFA1 had decreased brain Aβ, increased serum Aβ, and no change in CNS cytokine levels. In contrast, 22 month old immunized female mice revealed no change in brain Aβ, decreased serum Aβ, and increased CNS cytokine levels. Identical experiments in younger (17 month old) female 3 × tg AD mice with intermediate AD-like neuropathologies revealed a trend towards decreased brain Aβ and increased serum Aβ accompanied by a decrease in CNS MCP-1.

Conclusions
These data suggest that passive immunization with PFA1 in 3 × tg AD mice with intermediate disease burden, regardless of sex, is effective in mediating potentially therapeutic effects such as lowering brain Aβ. In contrast, passive immunization of mice with a more advanced amyloid burden may result in potentially adverse effects (encephalitis and vasogenic edema) mediated by certain proinflammatory cytokines.