bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rab11-FIP3 is a cell cycle-regulated phosphoprotein
Authors: Collins Louise L , Simon Glenn , Matheson Johanne , Wu Christine , Miller M Clare , Otani Tetsuhisa , Yu Xinzi , Hayashi Shigeo , Prekeris Rytis , Gould Gwyn W 
Published: March 2012

Abstract

Background
Rab11 and its effector molecule, Rab11-FIP3 (FIP3), associate with recycling endosomes and traffic into the furrow and midbody of cells during cytokinesis. FIP3 also controls recycling endosome distribution during interphase. Here, we examine whether phosphorylation of FIP3 is involved in these activities.

Results
We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase. Over-expression of FIP3-S102D increased the frequency of binucleate cells consistent with a role for this phospho-acceptor site in cytokinesis. Mutation of S-280, S-347 or S-450 or other previously identified phospho-acceptor sites (S-488, S-538, S-647 and S-648) was without effect on binucleate cell formation and did not modulate the distribution of FIP3 during the cell cycle. In an attempt to identify a functional role for FIP3 phosphorylation, we report that the change in FIP3 distribution from cytosolic to membrane-associated observed during progression from anaphase to telophase is accompanied by a concomitant dephosphorylation of FIP3. However, the phospho-acceptor sites identified here did not control this change in distribution.

Conclusions
Our data thus identify FIP3 as a cell cycle regulated phosphoprotein and suggest dephosphorylation of FIP3 accompanies its translocation from the cytosol to membranes during telophase. S102 is dephosphorylated during telophase; mutation of S102 exerts a modest effect on cytokinesis. Finally, we show that de/phosphorylation of the phospho-acceptor sites identified here (S-102, S-280, S-347 and S-450) is not required for the spatial control of recycling endosome distribution or function.
Antistaphylococcal activity of bacteriophage derived chimeric protein P128
Authors: Vipra Aradhana A , Desai Srividya Narayanamurthy , Roy Panchali , Patil Raghu , Raj Juliet Mohan , Narasimhaswamy Nagalakshmi , Paul Vivek Daniel , Chikkamadaiah Ravisha , Sriram Bharathi 
Published: March 2012

Abstract

Background
Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) are urgently needed. A causal relationship between nasal commensal S. aureus and infection has been reported. Accordingly, elimination of nasal S. aureus reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin.
Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein.

Results
Using the broth microdilution method adapted for lysostaphin, we found that P128 is effective against S. aureus clinical strains including MRSA, methicillin-sensitive S. aureus (MSSA), and a mupirocin-resistant S. aureus. Minimum bactericidal concentrations and minimum inhibitory concentrations of P128 (1-64 μg/mL) were similar across the 32 S. aureus strains tested, demonstrating its bactericidal nature.
In time-kill assays, P128 reduced colony-forming units by 99.99% within 1 h and inhibited growth up to 24 h.
In an assay simulating topical application of P128 to skin or other biological surfaces, P128 hydrogel was efficacious when layered on cells seeded on solid media. P128 hydrogel was lethal to Staphylococci recovered from nares of healthy people and treated without any processing or culturing steps, indicating its in situ efficacy. This methodology used for in vitro assessment of P128 as an agent for eradicating nasal carriage is unique.

Conclusions
The novel chimeric protein P128 is a staphylococcal cell wall-degrading enzyme under development for clearance of S. aureus nasal colonization and MRSA infection. The protein is active against globally prevalent antibiotic-resistant clinical isolates and other clinically significant staphylococcal species including S. epidermidis. The P128 hydrogel formulation was bactericidal against Staphylococci including S. aureus recovered from the nares of 31 healthy people, demonstrating its in situ efficacy.
Genomes-based phylogeny of the genus Xanthomonas
Authors: Rodriguez-R Luis M , Grajales Alejandro , Arrieta-Ortiz Mario L , Salazar Camilo , Restrepo Silvia , Bernal Adriana 
Published: March 2012

AbstractBackgroundThe genusXanthomonascomprises several plant pathogenic bacteria affecting a wide range of hosts. Despite the economic, industrial and biological importance ofXanthomonas, the classification and phylogenetic relationships within the genus are still under active debate. Some of the relationships between pathovars and species have not been thoroughly clarified, with old pathovars becoming new species. A change in the genus name has been recently suggested forXanthomonas albilineans, an early branching species currently located in this genus, but a thorough phylogenomic reconstruction would aid in solving these and other discrepancies in this genus.ResultsHere we report the results of the genome-wide analysis of DNA sequences from 989 orthologous groups from 17Xanthomonasspp. genomes available to date, representing all major lineages within the genus. The phylogenetic and computational analyses used in this study have been automated in a Perl package designated Unus, which provides a framework for phylogenomic analyses which can be applied to other datasets at the genomic level. Unus can also be easily incorporated into other phylogenomic pipelines.ConclusionsOur phylogeny agrees with previous phylogenetic topologies on the genus, but revealed that the genomes ofXanthomonas citriandXanthomonas fuscansbelong to the same species, and that ofXanthomonas albilineansis basal to the joint clade ofXanthomonasandXylella fastidiosa. Genome reduction was identified in the speciesXanthomonas vasicolain addition to the previously identified reduction inXanthomonas albilineans. Lateral gene transfer was also observed in two gene clusters.
Office and 24-hour heart rate and target organ damage in hypertensive patients
Authors: García-García Ángel , Gómez-Marcos Manuel A , Recio-Rodríguez José I , Patino-Alonso Maria C , Rodríguez-Sánchez Emiliano , Agudo-Conde Cristina , García-Ortiz Luis ,   the Vaso-risk group
Published: March 2012

Abstract

Background
We investigated the association between heart rate and its variability with the parameters that assess vascular, renal and cardiac target organ damage.

Methods
A cross-sectional study was performed including a consecutive sample of 360 hypertensive patients without heart rate lowering drugs (aged 56 ± 11 years, 64.2% male). Heart rate (HR) and its standard deviation (HRV) in clinical and 24-hour ambulatory monitoring were evaluated. Renal damage was assessed by glomerular filtration rate and albumin/creatinine ratio; vascular damage by carotid intima-media thickness and ankle/brachial index; and cardiac damage by the Cornell voltage-duration product and left ventricular mass index.

Results
There was a positive correlation between ambulatory, but not clinical, heart rate and its standard deviation with glomerular filtration rate, and a negative correlation with carotid intima-media thickness, and night/day ratio of systolic and diastolic blood pressure. There was no correlation with albumin/creatinine ratio, ankle/brachial index, Cornell voltage-duration product or left ventricular mass index. In the multiple linear regression analysis, after adjusting for age, the association of glomerular filtration rate and intima-media thickness with ambulatory heart rate and its standard deviation was lost. According to the logistic regression analysis, the predictors of any target organ damage were age (OR = 1.034 and 1.033) and night/day systolic blood pressure ratio (OR = 1.425 and 1.512). Neither 24 HR nor 24 HRV reached statistical significance.

Conclusions
High ambulatory heart rate and its variability, but not clinical HR, are associated with decreased carotid intima-media thickness and a higher glomerular filtration rate, although this is lost after adjusting for age.

Trial Registration
ClinicalTrials.gov: NCT01325064
On summary measure analysis of linear trend repeated measures data: performance comparison with two competing methods
Authors: Vossoughi Mehrdad , Ayatollahi SMT , Towhidi Mina , Ketabchi Farzaneh 
Published: March 2012

Abstract

Background
The summary measure approach (SMA) is sometimes the only applicable tool for the analysis of repeated measurements in medical research, especially when the number of measurements is relatively large. This study aimed to describe techniques based on summary measures for the analysis of linear trend repeated measures data and then to compare performances of SMA, linear mixed model (LMM), and unstructured multivariate approach (UMA).

Methods
Practical guidelines based on the least squares regression slope and mean of response over time for each subject were provided to test time, group, and interaction effects. Through Monte Carlo simulation studies, the efficacy of SMA vs. LMM and traditional UMA, under different types of covariance structures, was illustrated. All the methods were also employed to analyze two real data examples.

Results
Based on the simulation and example results, it was found that the SMA completely dominated the traditional UMA and performed convincingly close to the best-fitting LMM in testing all the effects. However, the LMM was not often robust and led to non-sensible results when the covariance structure for errors was misspecified. The results emphasized discarding the UMA which often yielded extremely conservative inferences as to such data.

Conclusions
It was shown that summary measure is a simple, safe and powerful approach in which the loss of efficiency compared to the best-fitting LMM was generally negligible. The SMA is recommended as the first choice to reliably analyze the linear trend data with a moderate to large number of measurements and/or small to moderate sample sizes.
Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance
Authors: Heise Michael , Lautem Anja , Knapstein Johanna , Schattenberg Jörn M , Hoppe-Lotichius Maria , Foltys Daniel , Weiler Nina , Zimmermann Anca , Schad Arno , Gründemann Dirk , Otto Gerd , Galle Peter R , Schuchmann Marcus , Zimmermann Tim 
Published: March 2012

Abstract

Background
Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).

Methods
OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.

Results
Real time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ≤ 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.
In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.

Conclusion
The downregulation of OCT1 is associated with tumor progression and a worse patient survival.
Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival
Authors: Slipicevic Ana , Holm Ruth , Emilsen Elisabeth , Ree Rosnes Anne Katrine , Welch Danny R , Mælandsmo Gunhild M , Flørenes Vivi Ann 
Published: March 2012

AbstractBackground/aimsBreast cancer metastasis suppressor 1 (BRMS1) blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis.MethodsParaffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines.ResultsA significantly higher percentage of nevi (87%), compared to primary melanomas (20%) and metastases (48%), expressed BRMS1 in the nucelus (p < 0.0001). Strong nuclear staining intensity was observed in 67% of nevi, and in 9% and 24% of the primary and metastatic melanomas, respectively (p < 0.0001). Comparable cytoplasmic expression was observed (nevi; 87%, primaries; 86%, metastases; 72%). However, a decline in cytoplasmic staining intensity was observed in metastases compared to nevi and primary tumors (26%, 47%, and 58%, respectively, p < 0.0001). Score index (percentage immunopositive celles multiplied with staining intensity) revealed that high cytoplasmic score index (≥ 4) was associated with thinner tumors (p = 0.04), lack of ulceration (p = 0.02) and increased disease-free survival (p = 0.036). When intensity and percentage BRMS1 positive cells were analyzed separately, intensity remained associated with tumor thickness (p = 0.024) and ulceration (p = 0.004) but was inversely associated with expression of proliferation markers (cyclin D3 (p = 0.008), cyclin A (p = 0.007), and p21Waf1/Cip1(p = 0.009)). Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013) and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033). Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016) and decreased relapse-free period (p = 0.043). Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011), a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invadein vitro.ConclusionOur data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines itsin vivoeffect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion.Please see related article:http://www.biomedcentral.com/1741-7015/10/19
Assessment of utilization of provider-initiated HIV testing and counseling as an intervention for prevention of mother to child transmission of HIV and associated factors among pregnant women in Gondar town, North West Ethiopia
Authors: Malaju Marelign Tilahun , Alene Getu Degu 
Published: March 2012

Abstract

Background
Detection of maternal HIV infection early in pregnancy is critical for prevention of mother to child transmission of HIV/AIDS. Most efforts have focused on VCT as the primary means of encouraging people to become aware of their HIV status. However, its uptake is low in many parts of sub-Saharan Africa including Ethiopia. Provider-initiated HIV testing and counseling provides a critical opportunity to diagnose HIV infection, to begin chronic care, and to prevent mother to child transmission. However, little is known about its acceptance and associated factors among pregnant women in the country and particularly in the present study area.

Methods
Health institution based cross-sectional quantitative study was conducted in Gondar town from July 22-August 18, 2010. A total of 400 pregnant women were involved in the study using stratified sampling technique and multiple logistic regression analysis was employed using SPSS version 16.

Results
A total of 400 pregnant women actively participated in this study and 330 (82.5%) of them accepted provider-initiated HIV testing and counseling to be tested for HIV and 70(17.5%) of them refused. Acceptance of provider-initiated HIV testing and counseling was positively associated with greater number of antenatal care visits [Adj. OR (95%CI)=2.64(1.17, 5.95)], residing in the urban areas[Adj. OR (95%CI)=2.85(1.10, 7.41)], having comprehensive knowledge on HIV [Adj. OR (95%CI)=4.30(1.72, 10.73)], positive partners reaction for HIV positive result [Adj. OR (95%CI)=8.19(3.57, 18.80)] and having knowledge on prevention of mother to child transmission of HIV[Adj. OR (95%CI)=3.27(1.34, 7.94)], but negatively associated with increased maternal age and education level.

Conclusion
Utilization of provider-initiated HIV testing and counseling during antenatal care was relatively high among pregnant women in Gondar town. Couple counseling and HIV testing should be strengthened to promote provider-initiated HIV testing and counseling among male partners and to reduce HIV related violence of women from their partner and access to and consistent use of antenatal care should be improved to increase the uptake of provider-initiated HIV testing and counseling service.
Cardiovascular disease and air pollution in Scotland: no association or insufficient data and study design?
Authors: Willocks Lorna J , Bhaskar Abita , Ramsay Colin N , Lee Duncan , Brewster David H , Fischbacher Colin M , Chalmers James , Morris George , Scott E Marian 
Published: March 2012

Abstract

Background
Coronary heart disease and stroke are leading causes of mortality and ill health in Scotland, and clear associations have been found in previous studies between air pollution and cardiovascular disease. This study aimed to use routinely available data to examine whether there is any evidence of an association between short-term exposure to particulate matter (measured as PM10, particles less than 10 micrograms per cubic metre) and hospital admissions due to cardiovascular disease, in the two largest cities in Scotland during the years 2000 to 2006.

Methods
The study utilised an ecological time series design, and the analysis was based on overdispersed Poisson log-linear models.

Results
No consistent associations were found between PM10 concentrations and cardiovascular hospital admissions in either of the cities studied, as all of the estimated relative risks were close to one, and all but one of the associated 95% confidence intervals contained the null risk of one.

Conclusions
This study suggests that in small cities, where air quality is relatively good, then either PM10 concentrations have no effect on cardiovascular ill health, or that the routinely available data and the corresponding study design are not sufficient to detect an association.
High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels
Authors: Ichinomiya Taiga , Cho Sungsam , Higashijima Ushio , Matsumoto Shuhei , Maekawa Takuji , Sumikawa Koji 
Published: March 2012

Abstract

Background
The current study was carried out to determine whether fasudil hydrochloride (fasudil), a Rho-kinase inhibitor, has myocardial postconditioning (PostC) activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP) channels.

Methods
Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg) or high-dose (0.5 mg/kg) fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD), an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR).

Results
Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively) compared with that in the control (42 ± 7%). Under hyperglycemia, low-dose fasudil (40 ± 11%) and diazoxide (44 ± 14%) could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%). 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%).

Conclusion
Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.
Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates
Authors: Ju Hye-Lim , Kang Jung-Mi , Moon Sung-Ung , Kim Jung-Yeon , Lee Hyeong-Woo , Lin Khin , Sohn Woon-Mok , Lee Jin-Soo , Kim Tong-Soo , Na Byoung-Kuk 
Published: March 2012

Abstract

Background

Plasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed.

Methods
Fifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs.

Results
Thirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII.

Conclusions
PvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.