bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans
Authors: Dhamgaye Sanjiveeni , Bernard Maria , Lelandais Gaelle , Sismeiro Odile , Lemoine Sophie , Coppée Jean-Yves , Le Crom Stéphane , Prasad Rajendra , Devaux Frédéric
Published: August 2012

Background

Drug susceptible clinical isolates of Candida albicans frequently become highly tolerant to drugs during chemotherapy, with dreadful consequences to patient health. We used RNA sequencing (RNA-seq) to analyze the transcriptomes of a CDR (Candida Drug Resistance) strain and its isogenic drug sensitive counterpart.

Results

RNA-seq unveiled differential expression of 228 genes including a) genes previously identified as involved in CDR, b) genes not previously associated to the CDR phenotype, and c) novel transcripts whose function as a gene is uncharacterized. In particular, we show for the first time that CDR acquisition is correlated with an overexpression of the transcription factor encoding gene CZF1. CZF1 null mutants were susceptible to many drugs, independently of known multidrug resistance mechanisms. We show that CZF1 acts as a repressor of β-glucan synthesis, thus negatively regulating cell wall integrity. Finally, our RNA-seq data allowed us to identify a new transcribed region, upstream of the TAC1 gene, which encodes the major CDR transcriptional regulator.

Conclusion

Our results open new perspectives of the role of Czf1 and of our understanding of the transcriptional and post-transcriptional mechanisms that lead to the acquisition of drug resistance in C. albicans, with potential for future improvements of therapeutic strategies.
Comparative transcript profiling of gene expression between seedless Ponkan mandarin and its seedy wild type during floral organ development by suppression subtractive hybridization and cDNA microarray
Authors: Qiu Wen-Ming , Zhu An-Dan , Wang Yao , Chai Li-Jun , Ge Xiao-Xia , Deng Xiu-Xin , Guo Wen-Wu
Published: August 2012

Background

Seedlessness is an important agronomic trait for citrus, and male sterility (MS) is one main cause of seedless citrus fruit. However, the molecular mechanism of citrus seedlessness remained not well explored.

Results

An integrative strategy combining suppression subtractive hybridization (SSH) library with cDNA microarray was employed to study the underlying mechanism of seedlessness of a Ponkan mandarin seedless mutant (Citrus reticulataBlanco). Screening with custom microarray, a total of 279 differentially expressed clones were identified, and 133 unigenes (43 contigs and 90 singletons) were obtained after sequencing. Gene Ontology (GO) distribution based on biological process suggested that the majority of differential genes are involved in metabolic process and respond to stimulus and regulation of biology process; based on molecular function they function as DNA/RNA binding or have catalytic activity and oxidoreductase activity. A gene encoding male sterility-like protein was highly up-regulated in the seedless mutant compared with the wild type, while several transcription factors (TFs) such as AP2/EREBP, MYB, WRKY, NAC and C2C2-GATA zinc-finger domain TFs were down-regulated.

Conclusion

Our research highlighted some candidate pathways that participated in the citrus male gametophyte development and could be beneficial for seedless citrus breeding in the future.
A physical map of a BAC clone contig covering the entire autosome insertion between ovine MHC Class IIa and IIb
Authors: Li Gang , Liu Ka , Jiao Shasha , Liu Haibo , Blair Hugh T , Zhang Peng , Cui Xiaoran , Tan Pingping , Gao Jianfeng , Ma Runlin Z
Published: August 2012

Background

The ovine Major Histocompatibility Complex (MHC) harbors genes involved in overall resistance/susceptibility of the host to infectious diseases. Compared to human and mouse, the ovine MHC is interrupted by a large piece of autosome insertion via a hypothetical chromosome inversion that constitutes ~25% of ovine chromosome 20. The evolutionary consequence of such an inversion and an insertion (inversion/insertion) in relation to MHC function remains unknown. We previously constructed a BAC clone physical map for the ovine MHC exclusive of the insertion region. Here we report the construction of a high-density physical map covering the autosome insertion in order to address the question of what the inversion/insertion had to do with ruminants during the MHC evolution.

Results

A total of 119 pairs of comparative bovine oligo primers were utilized to screen an ovine BAC library for positive clones and the orders and overlapping relationships of the identified clones were determined by DNA fingerprinting, BAC-end sequencing, and sequence-specific PCR. A total of 368 positive BAC clones were identified and 108 of the effective clones were ordered into an overlapping BAC contig to cover the consensus region between ovine MHC class IIa and IIb. Therefore, a continuous physical map covering the entire ovine autosome inversion/insertion region was successfully constructed. The map confirmed the bovine sequence assembly for the same homologous region. The DNA sequences of 185 BAC-ends have been deposited into NCBI database with the access numbers HR309252 through HR309068, corresponding to dbGSS ID 30164010 through 30163826.

Conclusions

We have constructed a high-density BAC clone physical map for the ovine autosome inversion/insertion between the MHC class IIa and IIb. The entire ovine MHC region is now fully covered by a continuous BAC clone contig. The physical map we generated will facilitate MHC functional studies in the ovine, as well as the comparative MHC evolution in ruminants.
Regulation of in vitro human T cell development through interleukin-7 deprivation and anti-CD3 stimulation
Authors: Patel Ekta S , Okada Starlyn , Hachey Kevin , Yang Li-jun , Durum Scott K , Moreb Jan S , Chang Lung-Ji
Published: August 2012

Background

The role of IL-7 and pre-TCR signaling during T cell development has been well characterized in murine but not in human system. We and others have reported that human BM hematopoietic progenitor cells (HPCs) display poor proliferation, inefficient double negative (DN) to double positive (DP) transition and no functional maturation in the in vitro OP9-Delta-like 1 (DL1) culture system.

Results

In this study, we investigated the importance of optimal IL-7 and pre-TCR signaling during adult human T cell development. Using a modified OP9-DL1 culture ectopically expressing IL-7 and Fms-like tyrosine kinase 3 ligand (Flt3L), we demonstrated enhanced T cell precursor expansion. IL-7 removal at various time points during T cell development promoted a slight increase of DP cells; however, these cells did not differentiate further and underwent cell death. As pre-TCR signaling rescues DN cells from programmed cell death, we treated the culture with anti-CD3 antibody. Upon pre-TCR stimulation, the IL-7 deprived T precursors differentiated into CD3+TCRαβ+DP cells and further matured into functional CD4 T cells, albeit displayed a skewed TCR Vβ repertoire.

Conclusions

Our study establishes for the first time a critical control for differentiation and maturation of adult human T cells from HPCs by concomitant regulation of IL-7 and pre-TCR signaling.
Genetic characterization in symptomatic female DMD carriers: lack of relationship between X-inactivation, transcriptional DMD allele balancing and phenotype
Authors: Brioschi Simona , Gualandi Francesca , Scotton Chiara , Armaroli Annarita , Bovolenta Matteo , Falzarano Maria S , Sabatelli Patrizia , Selvatici Rita , D’Amico Adele , Pane Marika , Ricci Giulia , Siciliano Gabriele , Tedeschi Silvana , Pini Antonella , Vercelli Liliana , De Grandis Domenico , Mercuri Eugenio , Bertini Enrico , Merlini Luciano , Mongini Tiziana , Ferlini Alessandra
Published: August 2012

Background

Although Duchenne and Becker muscular dystrophies, X-linked recessive myopathies, predominantly affect males, a clinically significant proportion of females manifesting symptoms have also been reported. They represent an heterogeneous group characterized by variable degrees of muscle weakness and/or cardiac involvement. Though preferential inactivation of the normal X chromosome has long been considered the principal mechanism behind disease manifestation in these females, supporting evidence is controversial.

Methods

Eighteen females showing a mosaic pattern of dystrophin expression on muscle biopsy were recruited and classified as symptomatic (7) or asymptomatic (11), based on the presence or absence of muscle weakness. The causative DMD gene mutations were identified in all cases, and the X-inactivation pattern was assessed in muscle DNA. Transcriptional analysis in muscles was performed in all females, and relative quantification of wild-type and mutated transcripts was also performed in 9 carriers. Dystrophin protein was quantified by immunoblotting in 2 females.

Results

The study highlighted a lack of relationship between dystrophic phenotype and X-inactivation pattern in females; skewed X-inactivation was found in 2 out of 6 symptomatic carriers and in 5 out of 11 asymptomatic carriers. All females were characterized by biallelic transcription, but no association was found between X-inactivation pattern and allele transcriptional balancing. Either a prevalence of wild-type transcript or equal proportions of wild-type and mutated RNAs was observed in both symptomatic and asymptomatic females. Moreover, very similar levels of total and wild-type transcripts were identified in the two groups of carriers.

Conclusions

This is the first study deeply exploring the DMD transcriptional behaviour in a cohort of female carriers. Notably, no relationship between X-inactivation pattern and transcriptional behaviour of DMD gene was observed, suggesting that the two mechanisms are regulated independently. Moreover, neither the total DMD transcript level, nor the relative proportion of the wild-type transcript do correlate with the symptomatic phenotype.
Methylenetetrahydrofolate reductase C677T polymorphism is associated with estimated glomerular filtration rate in hypertensive Chinese males
Authors: Dong Qing , Tang Genfu , He Mingli , Cai Yunqing , Cai Yefeng , Xing Houxun , Sun Liming , Li Jianping , Zhang Yan , Fan Fangfang , Wang Binyan , Sun Ningling , Liu Lisheng , Xu Xiping , Hou Fanfan , Shen Hongbing , Xu Xin , Huo Yong
Published: August 2012

Background

Plasma level of total homocysteine (tHcy) is negatively correlated with kidney function in general population. However, the causal mechanism of this correlation is poorly understood. The purpose of this study is to investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which is a major genetic determinant of the plasma tHcy level, with estimated glomerular filtration rate (eGFR) in Chinese.

Methods

A total of 18 814 hypertensive patients (6 914 males, 11 900 females) were included in the study.

Results

Association between the eGFR and MTHFR C677T genotype was examined by sex-specific regression analyses. In males, TT genotype was associated with 1.37 ml/min/1.73 m2 decrease in eGFR (p = 0.004) and with an increased risk (OR = 1.32, p = 0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and blood pressures. However, such association was not observed in females (p > 0.05). This association suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.

Conclusions

MTHFR 677 T is a risk allele for decreased kidney function in Chinese males, implicating this gene in the pathogenesis of chronic kidney disease (CKD).
Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression
Authors: Byler Timothy K , Leocadio Dean , Shapiro Oleg , Bratslavsky Gennady , Stodgell Christopher J , Wood Ronald W , Messing Edward M , Reeder Jay E
Published: August 2012

Background

Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate) has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein.

Methods

Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR.

Results

Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate.

Conclusions

Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.
High glycemic load diet, milk and ice cream consumption are related to acne vulgaris in Malaysian young adults: a case control study
Authors: Ismail Noor Hasnani , Manaf Zahara Abdul , Azizan Noor Zalmy
Published: August 2012

Background

The role of dietary factors in the pathophysiology of acne vulgaris is highly controversial. Hence, the aim of this study was to determine the association between dietary factors and acne vulgaris among Malaysian young adults.

Methods

A case–control study was conducted among 44 acne vulgaris patients and 44 controls aged 18 to 30 years from October 2010 to January 2011. Comprehensive acne severity scale (CASS) was used to determine acne severity. A questionnaire comprising items enquiring into the respondent’s family history and dietary patterns was distributed. Subjects were asked to record their food intake on two weekdays and one day on a weekend in a three day food diary. Anthropometric measurements including body weight, height and body fat percentage were taken. Acne severity was assessed by a dermatologist.

Results

Cases had a significantly higher dietary glycemic load (175 ± 35) compared to controls (122 ± 28) (p < 0.001). The frequency of milk (p < 0.01) and ice-cream (p < 0.01) consumptions was significantly higher in cases compared to controls. Females in the case group had a higher daily energy intake compared to their counterparts in the control group, 1812 ± 331 and 1590 ± 148 kcal respectively (p < 0.05). No significant difference was found in other nutrient intakes, Body Mass Index, and body fat percentage between case and control groups (p > 0.05).

Conclusions

Glycemic load diet and frequencies of milk and ice cream intake were positively associated with acne vulgaris.
Utilization of rehabilitation services for inpatient with cancer in Taiwan: a descriptive analysis from national health insurance database
Authors: Lin Heui-Fen , Wu Ying-Tai , Tsauo Jau-Yih
Published: August 2012

Background

Cancer is a major cause of global morbidity and mortality. Since a high prevalence of functional impairments has been observed among cancer patients, rehabilitation has been proposed as a strategy to restore patients’ functional independence. The increasing number of cancer patients combined with a growing need for rehabilitation may result in increased utilization of rehabilitation services. This study aimed to investigate the utilization of rehabilitation services among hospitalized cancer patients in Taiwan between 2004 and 2008.

Methods

Annual admissions and total inpatient expenditures for admissions with a cancer diagnosis were calculated from the National Health Insurance Research Database (NHIRD). Rehabilitation services used by cancer and non-cancer patients, as well as the distributions of rehabilitation service type among the different hospital departments were also analyzed.

Results

The percentages of inpatient admissions with a cancer diagnosis increased from 14.01% to 17.1% between 2004 and 2008. During 2004, 5.25% of all inpatient admissions received rehabilitation services; this percentage increased to 5.62% by 2008. Among cancer admissions, 2.26% to 2.62% received rehabilitation services from 2004 to 2008. By comparison, 5.68% to 6.24% of non-cancer admissions received rehabilitation services during this period. Of the admissions who received rehabilitation services, only 6.44% and 7.96% had a cancer diagnosis in 2004 and 2008, respectively. Sixty-one percent of rehabilitation services were delivered in the departments of orthopedics (25.6%), neurology (14.4%), rehabilitation (11.9%), and neurosurgery (9.2%).

Conclusions

In Taiwan, the utilization of rehabilitation services during hospitalization increased from 2004 to 2008. Although this trend was noted for cancer and non-cancer admissions, the utilization of rehabilitation services was generally greater by non-cancer admissions. Despite the benefits of rehabilitation, the actual rehabilitation needs of cancer patients remain unmet.
GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome
Authors: Leguisamo Natalia M , Lehnen Alexandre M , Machado Ubiratan F , Okamoto Maristela M , Markoski Melissa M , Pinto Graziela H , Schaan Beatriz D
Published: August 2012

Background

Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model.

Methods

Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-α and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age.

Results

MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-α were higher (p<0.001, all comparisons) in MetS rats vs H, but adiponectin was lower in MetS at 9 months (MetS: 32 ± 2, H: 42 ± 2, C: 45 ± 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%).

Conclusions

MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.
Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border
Authors: Huang Fang , Tang Linhua , Yang Henglin , Zhou Shuisen , Sun Xiaodong , Liu Hui
Published: August 2012

Background

The aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps) and ATPase (pfatp6) genes.

Methods

Patients ≥ one year of age with fever (axillary temperature ≥37.5°C) or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days) by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction.

Results

Sixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%), and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246) was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164), and mutations in pfdhps (codons 436, 437, 540 and 581) were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K) were found in 4.6% and 9.2% of parasite isolates, respectively.

Conclusion

Plasmodium falciparum infection was associated with slow parasite clearance and suspected artemisinin resistance at the China-Myanmar border area. The prevalence of pfcrt 76 T and markers for SP resistance are still high. It should be strengthened further on parasite clearance time or clearance half life to confirm the resistance status, and molecular epidemiology should provide complementary information to assess the appropriateness of current policies based on artemisinin derivatives.
Meta-analysis of surgical resection and radiofrequency ablation for early hepatocellular carcinoma
Authors: Xu Gang , Qi Fu-zhen , Zhang Jian-huai , Cheng Guo-feng , Cai Yong , Miao Yi
Published: August 2012

Background

There is no definite agreement on the better therapy (radiofrequency ablation (RFA) versus surgical resection (SR)) for early hepatocellular carcinoma (HCC) eligible for surgical treatments. The purpose of this study is to evaluate the evidence using meta-analytical techniques.

Methods

A literature search was undertaken until December 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model.

Results

Thirteen articles, comprising two randomized controlled trials(RCTs), were included in the review, with a total of 2,535 patients (1,233 treated with SR and 1,302 with RFA). The overall survival rates were significantly higher in patients treated with SR than RFA after1, 3, and 5 years (respectively: OR, 0.60 (95% CI, 0.42 to 0.86); OR, 0.49 (95% CI, 0.36 to 0.65); OR, 0.60 (95% CI, 0.43 to 0.84)). In the SR group, the 1, 3, and 5 years recurrence rates were significantly lower than the RFA group (respectively: OR, 1.48 (95% CI, 1.05 to 2.08); OR, 1.76 (95% CI, 1.49 to 2.08); OR, 1.68 (95% CI, 1.21 to 2.34)). However, local recurrence between two groups did not exhibit significant difference. For HCC ≤ 3 cm in diameter, SR was better than RFA at the 1, 3, and 5 years overall survival rates (respectively: OR, 0.34 (95% CI, 0.13 to 0.89); OR, 0.56 (95% CI, 0.37 to 0.84); OR, 0.44 (95% CI, 0.31 to 0.62)). This meta-analysis indicated that the complication of SR was higher than RFA (OR, 6.25 (95%CI, 3.12 to 12.52); P = 0.000).

Conclusion

Although local recurrence between two groups did not exhibit significant difference, SR demonstrated significantly improved survival benefits and lower complications for patients with early HCC, especially for HCC ≤ 3 cm in diameter. These findings should be interpreted carefully, owing to the lower level of evidence.
Differential expression of extracellular matrix components in the Fallopian tubes throughout the menstrual cycle
Authors: Diaz Patricia S , Solar Paula A , Juica Natalia E , Orihuela Pedro A , Cardenas Hugo , Christodoulides Myron , Vargas Renato , Velasquez Luis A
Published: August 2012

Background

One of the unique characteristics of the female genital tract is the extensive tissue remodeling observed throughout the menstrual cycle. Multiple components of the extracellular matrix take part in this tissue rebuilding; however, the individual components involved have not been identified.

Methods

In the present study, the expression of extracellular matrix proteins and selected matrix metalloproteinase (MMP) activities in Fallopian tubes (FT) throughout the menstrual cycle were examined by PCR array, immunocytochemistry, zymography and bioinformatics.

Results

Of the eighty-four genes analyzed, eighty-three were expressed in the FT during at least one stage of the menstrual cycle. We observed a significant increase (>/=2-fold) in ADAMTS1, ADAMTS13, COL7A1, MMP3, MMP9, PECAM1, and THBS3 in the periovulatory phase compared to the follicular phase. Meanwhile, we observed a significant decrease (>/= 2-fold) in COL7A1, ICAM1, ITGA8, MMP16, MMP9, CLEC3B, SELE and TIMP2 in the lutheal phase compared to the periovulatory phase. Immunocytochemistry showed that MMP-3 and MMP-9 were localized in the endosalpinx during all phases of the menstrual cycle. Gelatin zymograms detected non-cycle-dependent protease activity.

Conclusions

Several extracellular matrix components were regulated throughout the menstrual cycle in a cyclic pattern, suggesting a possible steroid regulation and a role in tissue remodeling and FT functions.
The experience of physical activity and the transition to retirement: a systematic review and integrative synthesis of qualitative and quantitative evidence
Authors: Barnett Inka , Guell Cornelia , Ogilvie David
Published: August 2012

Background

The transition to retirement has been recognised as a critical turning point for physical activity (PA). In an earlier systematic review of quantitative studies, retirement was found to be associated with an increase in recreational PA but with a decrease in PA among retirees from lower occupational groups. To gain a deeper understanding of the quantitative review findings, qualitative evidence on experiences of and views on PA around the transition to retirement was systematically reviewed and integrated with the quantitative review findings.

Method

19 electronic databases were searched and reference lists were checked, citations tracked and journals hand-searched to identify qualitative studies on PA around the transition to retirement, published between January 1980 and August 2010 in any country or language. Independent quality appraisal, data extraction and evidence synthesis were carried out by two reviewers using a stepwise thematic approach. The qualitative findings were integrated with those of the existing quantitative systematic review using a parallel synthesis approach.

Results

Five qualitative studies met the inclusion criteria. Three overarching themes emerged from the synthesis of these studies: these related to retirees’ broad concepts of PA, the motives for and the challenges to PA in retirement. Integrative synthesis of the qualitative findings with the quantitative evidence offered several potential explanations for why adults might engage in more recreational PA after the transition to retirement. These included expected health benefits, lifelong PA patterns, opportunities for socialising and personal challenges, and the desire for a new routine. A decrease in PA among retirees from lower occupational groups might be explained by a lack of time and a perceived low personal value of recreational PA.

Conclusions

To encourage adoption and maintenance of PA after retirement, interventions should promote health-related and broader benefits of PA. Interventions for retirees from lower occupational groups should take account of busy post-retirement lifestyles and the low personal value that might be attributed to recreational PA. Future research should address predictors of maintenance of recreational PA after the transition to retirement, the broader benefits of PA, and barriers to PA among retirees from lower occupational groups.
Combination of cilostazol and clopidogrel attenuates Rat critical limb ischemia
Authors: Sheu Jiunn-Jye , Lin Kun-Chen , Tsai Ching-Yen , Tsai Tzu-Hsien , Leu Steve , Yen Chia-Hung , Chen Yung-Lung , Chang Hsueh-Wen , Sun Cheuk-Kwan , Chua Sarah , Yang Jenq-Lin , Yip Hon-Kan
Published: August 2012

Background and aim

Procedural failure and untoward clinical outcomes after surgery remain problematic in critical limb ischemia (CLI) patients. This study tested a clopidogrel-cilostazol combination treatment compared with either treatment alone in attenuating CLI and improving CLI-region blood flow in rats.

Methods

Male Sprague–Dawley rats (n = 40) were equally divided into five groups: control, CLI induction only, CL I + cilostazol (12.0 mg/day/kg), CLI + clopidogrel (8.0 mg/kg/day) and CLI + combined cilostazol-clopidogrel. After treatment for 21 days, Laser Doppler imaging was performed.

Results

On day 21, the untreated CLI group had the lowest ratio of ischemic/normal blood flow (p < 0.001). Inflammation measured by VCAM-1 protein expression; oxidative stress; PAI-1, MMP-9 and TNF-α mRNA expressions; and immunofluorescence staining (IF) of CD68+ cells was lower with combined treatment than with the other treatments, and lower in the two single-treatment groups than the untreated CLI group (all p < 0.01). Anti-inflammatory mRNA expression of interleukin-10, and eNOS showed a reverse pattern among these groups. Apoptosis measured by Bax, caspase-3 and PARP; and muscle damage measured by cytosolic cytochrome-C, and serum and muscle micro-RNA-206 were all lowest with combination treatment, and the two single-treatment groups showed lower values than the untreated group (all p < 0.001). Angiogenesis measured by eNOS, IF staining of CD31+ and vWF + cells; and number of vessels in CLI region were highest with combination treatment and higher in the single-treatment groups than the untreated group (all p < 0.001).

Conclusion

Combined cilostazol-clopidogrel therapy is superior to either agent alone in improving ischemia in rodent CLI.
Improved light extraction of InGaN/GaN blue LEDs by GaOOH NRAs using a thin ATO seed layer
Authors: Lee Hee Kwan , Joo Dong Hyuk , Kim Myung Sub , Yu Jae Su
Published: August 2012

We investigated the effect of gallium oxide hydroxide (GaOOH) nanorod arrays (NRAs) on the light extraction of InGaN/GaN multiple quantum well blue light-emitting diodes (LEDs). GaOOH NRAs were prepared on an indium tin oxide electrode (ITO) layer of LEDs by electrochemical deposition method. The GaOOH NRAs with preferred orientations were grown on the ITO surface by sputtering a thin antimony-doped tin oxide seed layer, which enhances heterogeneous reactions. Surface density and coverage were also efficiently controlled by the different growth voltages. For LEDs with GaOOH NRAs grown at −2 V, the light output power was increased by 22% without suffering from any serious electrical degradation and wavelength shift as compared with conventional LEDs.
Spontaneous formation of graphene-like stripes on high-index diamond C(331) surface
Authors: Xu Maojie , Zhang Yaozhong , Zhang Jing , Lu Jiyun , Qian Bingjian , Lu Dejiong , Zhang Yafei , Wang Liang , Chen Xiaoshuang , Shigekawa Hidemi
Published: August 2012

We employ first-principles density functional theory calculations to study the surface reconstruction, energetic stability, and electronic structure of diamond C(331) surface. Spontaneous formation of graphene-like stripes on the reconstructed surface is found to occur as the surface terrace C atoms transform from sp
3 to sp
2 hybridization upon structural relaxation. The comparison of the calculated absolute surface energies of C(331), C(111), and C(110) surfaces demonstrates the energetic stability of the graphitic-like C(331) surface. Local density of electronic states analysis reveals the occurrence of localized electronic states near the Fermi level, which may have a significant impact on the surface conductivity.
Compressive SAR raw data with principal component analysis
Authors: Wang Wei , Zhang Baoju , Mu Jiasong
Published: August 2012

The theory of synthetic aperture radar (SAR) signal model is briefly introduced which is constructed with a series of echo signals in range direction. The procedure of principal component analysis (PCA) is presented which is used as transformation basis to sparsify the signals. The joint compressive sensing (CS) and PCA algorithm is devised to realize SAR raw data compressive measurement. A SAR raw data for a point target is simulated and used to verify the performance of the joint CS and PCA algorithm. The numerical experimental results demonstrate that the PCA method has good sparse performance and the joint CS and PCA algorithm is possible to online compressively measure the SAR raw data.
Joint source and relay optimization for parallel MIMO relay networks
Authors: Toding Apriana , Khandaker Muhammad RA , Rong Yue
Published: August 2012

In this article, we study the optimal structure of the source precoding matrix and the relay amplifying matrices for multiple-input multiple-output (MIMO) relay communication systems with parallel relay nodes. Two types of receivers are considered at the destination node: (1) The linear minimal mean-squared error (MMSE) receiver; (2) The nonlinear decision feedback equalizer based on the minimal MSE criterion. We show that for both receiver schemes, the optimal source precoding matrix and the optimal relay amplifying matrices have a beamforming structure. Using such optimal structure, joint source and relay power loading algorithms are developed to minimize the MSE of the signal waveform estimation at the destination. Compared with existing algorithms for parallel MIMO relay networks, the proposed joint source and relay beamforming algorithms have significant improvement in the system bit-error-rate performance.
Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis
Authors: McNeilly Jane D , Mason Avril , Khanna Sheila , Galloway Peter J , Ahmed S Faisal
Published: August 2012

Background

Non-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty.

Methods

Urine samples were collected from 161 healthy school children (76 boys, 85 girls) aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal).

Results

Of the 161 children, 50 were pre-pubertal (28 boys; 22 girls) and 111 were pubertal (48 boys; 63 girls). Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (p<0.001). In girls, FSH:Creatinine ratios were significantly higher in the pubertal group (p = 0.006). However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal).

Conclusion

Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.
Event related desynchronization-modulated functional electrical stimulation system for stroke rehabilitation: A feasibility study
Authors: Takahashi Mitsuru , Takeda Kotaro , Otaka Yohei , Osu Rieko , Hanakawa Takashi , Gouko Manabu , Ito Koji
Published: August 2012

Background

We developed an electroencephalogram-based brain computer interface system to modulate functional electrical stimulation (FES) to the affected tibialis anterior muscle in a stroke patient. The intensity of FES current increased in a stepwise manner when the event-related desynchronization (ERD) reflecting motor intent was continuously detected from the primary cortical motor area.

Methods

We tested the feasibility of the ERD-modulated FES system in comparison with FES without ERD modulation. The stroke patient who presented with severe hemiparesis attempted to perform dorsiflexion of the paralyzed ankle during which FES was applied either with or without ERD modulation.

Results

After 20 minutes of training, the range of movement at the ankle joint and the electromyography amplitude of the affected tibialis anterior muscle were significantly increased following the ERD-modulated FES compared with the FES alone.

Conclusions

The proposed rehabilitation technique using ERD-modulated FES for stroke patients was feasible. The system holds potentials to improve the limb function and to benefit stroke patients.
Role of hepatitis B virus X protein in regulating LIM and SH3 protein 1 (LASP-1) expression to mediate proliferation and migration of hepatoma cells
Authors: Tang Renxian , Kong Fanyun , Hu Lina , You Hongjuan , Zhang Peng , Du Weidong , Zheng Kuiyang
Published: August 2012

Background

Hepatitis B virus X protein (HBx) has been shown to be responsible for the development of hepatocellular carcinoma (HCC) caused by Hepatitis B virus infection. However, its potential effect on the progression of hepatocellular carcinoma remains yet unclear. LIM and SH3 protein 1 (LASP-1), a focal adhesion protein, is expressed in an up-regulation manner in the HCC tissues. LASP-1 plays an important role in the regulation of proliferation and migration of HCC. In this study, we investigated the effect of LASP-1 involved in HBx-related tumor progression.

Methods

LASP-1 levels in the HBx stable transfected HepG2 and Huh-7 cells were detected by RT-PCR and western blot analysis. The cellular localization of LASP-1 was assessed by immunofluorescence analysis. The activity of phosphatidylinositol 3-kinase (PI3-K) pathway was demonstrated by western blot assay. The HBx-expressing cells were transfected with specific small interference RNA (siRNA) against LASP-1. The proliferation and migration ability of cells were evaluated by cell viability assay and plate clone formation assay. The migration ability of cells was detected by transwell assay and wound healing assay.

Results

RT-PCR and western blot analysis indicated the expression of LASP-1 was increased in the stable HBx-expressing cells compared with the control cells. Immunofluorescence study revealed that the distributions of LASP-1 in HepG2-HBX cells were mainly in pseudopods and the cytoplasm while they were mainly localized in the cytoplasm of HepG2-Mock cells. The cellular localizations of LASP-1 in Huh-7-HBX cells were in the perinuclear fractions while they were mainly localized in the cytoplasm of Huh-7-Mock cells. The upregulation of LASP-1 was inhibited after treatment with LY294002, PI3-K pathway inhibitor. Overexpression of LASP-1 in the stable HBx-expressing cells enhanced the proliferation and migration ability of hepatocellular cells. siRNA-mediated LASP-1 knowdown in the stable HBx-expressing cells significantly suppressed hepatocellular cells proliferation and migration.

Conclusions

These results demonstrated that HBx could upregulate LASP-1 through PI3-K pathway to promote the proliferation and migration of hepatoma cells.
Diagnostic randomized controlled trials: the final frontier
Authors: Rodger Marc , Ramsay Tim , Fergusson Dean
Published: August 2012

Clinicians, patients, governments, third-party payers, and the public take for granted that diagnostic tests are accurate, safe and effective. However, we may be seriously misled if we are relying on robust study design to ensure accurate, safe, and effective diagnostic tests. Properly conducted, randomized controlled trials are the gold standard for assessing the effectiveness and safety of interventions, yet are rarely conducted in the assessment of diagnostic tests. Instead, diagnostic cohort studies are commonly performed to assess the characteristics of a diagnostic test including sensitivity and specificity. While diagnostic cohort studies can inform us about the relative accuracy of an experimental diagnostic intervention compared to a reference standard, they do not inform us about whether the differences in accuracy are clinically important, or the degree of clinical importance (in other words, the impact on patient outcomes). In this commentary we provide the advantages of the diagnostic randomized controlled trial and suggest a greater awareness and uptake in their conduct. Doing so will better ensure that patients are offered diagnostic procedures that will make a clinical difference.
Getting DNA copy numbers without control samples
Authors: Ortiz-Estevez Maria , Aramburu Ander , Rubio Angel
Published: August 2012

Background

The selection of the reference to scale the data in a copy number analysis has paramount importance to achieve accurate estimates. Usually this reference is generated using control samples included in the study. However, these control samples are not always available and in these cases, an artificial reference must be created. A proper generation of this signal is crucial in terms of both noise and bias.

We propose NSA (Normality Search Algorithm), a scaling method that works with and without control samples. It is based on the assumption that genomic regions enriched in SNPs with identical copy numbers in both alleles are likely to be normal. These normal regions are predicted for each sample individually and used to calculate the final reference signal. NSA can be applied to any CN data regardless the microarray technology and preprocessing method. It also finds an optimal weighting of the samples minimizing possible batch effects.

Results

Five human datasets (a subset of HapMap samples, Glioblastoma Multiforme (GBM), Ovarian, Prostate and Lung Cancer experiments) have been analyzed. It is shown that using only tumoral samples, NSA is able to remove the bias in the copy number estimation, to reduce the noise and therefore, to increase the ability to detect copy number aberrations (CNAs). These improvements allow NSA to also detect recurrent aberrations more accurately than other state of the art methods.

Conclusions

NSA provides a robust and accurate reference for scaling probe signals data to CN values without the need of control samples. It minimizes the problems of bias, noise and batch effects in the estimation of CNs. Therefore, NSA scaling approach helps to better detect recurrent CNAs than current methods. The automatic selection of references makes it useful to perform bulk analysis of many GEO or ArrayExpress experiments without the need of developing a parser to find the normal samples or possible batches within the data. The method is available in the open-source R package NSA, which is an add-on to the aroma.cn framework.http://www.aroma-project.org/addons.
Integrating external biological knowledge in the construction of regulatory networks from time-series expression data
Authors: Lo Kenneth , Raftery Adrian E , Dombek Kenneth M , Zhu Jun , Schadt Eric E , Bumgarner Roger E , Yeung Ka Yee
Published: August 2012

Background

Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge.

Results

We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA) variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models.

Conclusions

We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.
Entomological profile of yellow fever epidemics in the Central African Republic, 2006–2010
Authors: Ngoagouni Carine , Kamgang Basile , Manirakiza Alexandre , Nangouma Auguste , Paupy Christophe , Nakoune Emmanuel , Kazanji Mirdad
Published: August 2012

Background

The causative agent of yellow fever is an arbovirus of the Flaviviridae family transmitted by infected Aedes mosquitoes, particularly in Africa. In the Central African Republic since 2006, cases have been notified in the provinces of Ombella-Mpoko, Ouham-Pende, Basse-Kotto, Haute-Kotto and in Bangui the capital. As the presence of a vector of yellow fever virus (YFV) represents a risk for spread of the disease, we undertook entomological investigations at these sites to identify potential vectors of YFV and their abundance.

Findings

Between 2006 and 2010, 5066 mosquitoes belonging to six genera and 43 species were identified. The 20 species of the Aedes genus identified included Ae. aegypti, the main vector of YFV in urban settings, and species found in tropical forests, such as Ae. africanus, Ae. simpsoni, Ae. luteocephalus, Ae. vittatus and Ae. opok. These species were not distributed uniformly in the various sites studied. Thus, the predominant Aedes species was Ae. aegypti in Bangui (90.7 %) and Basse-Kotto (42.2 %), Ae. africanus in Ombella-Mpoko (67.4 %) and Haute-Kotto (77.8 %) and Ae. vittatus in Ouham-Pende (62.2 %). Ae. albopictus was also found in Bangui. The distribution of these dominant species differed significantly according to study site (P < 0.0001). None of the pooled homogenates of Aedes mosquitoes analysed by polymerase chain reaction contained the YFV genome.

Conclusion

The results indicate a wide diversity of vector species for YFV in the Central African Republic. The establishment of surveillance and vector control programs should take into account the ecological specificity of each species.
Characterization and evaluation of a Sarcoptes scabiei allergen as a candidate vaccine
Authors: Zhang Runhui , Jise Quwu , Zheng Wanpeng , Ren Yongjun , Nong Xiang , Wu Xuhang , Gu Xiaobin , Wang Shuxian , Peng Xuerong , Lai Songjia , Yang Guangyou
Published: August 2012

Background

Sarcoptic mange caused by the miteSarcoptes scabieiis a worldwide disease affecting both humans and animals. Here we report the molecular characterization and evaluation of a recombinantS. scabieitropomyosin (SsTm) protein in a vaccination trial in rabbits.

Methods

The full-length cDNA was cloned in a bacterial pET vector, and the recombinant protein was expressed in BL21 (DE3) cells and purified. Using specific rabbit antiserum, tropomyosin was localized immunohistochemically in mite tissue sections. Vaccination trials with the recombiant SsTm was carried out in New Zealand rabbits.

Results

The full-length open reading frame (ORF) of the 852 bp cloned gene fromS. scabieiencodes a 32.9 kDa protein. The amino acid sequence showed 98.94%, 97.89% and 98.59% homology toDermatophagoides farinaandDermatophagoides pteronyssinusgroup 10 allergens andPsoroptes ovistropomyosin, respectively. Tropomyosin was localized immunohistochemically in mite tissue sections mainly in the mouthparts, legs and integument of the epidermis. The predicted cross-reactivity of SsTm indicated that it is an allergenic protein. While vaccination with the recombiant SsTm resulted in high levels of specific IgG (P< 0.01), a low IgE antibody response and no significant protection againstS. scabieichallenge were observed. After challenge, specific IgG levels remained significantly higher than the control (P< 0.01), while changes of total IgE levels were not significant (P> 0.05). However, the lesion areas in the vaccination group decreased at the end of the experiment compared with controls.

Conclusions

Although vaccination with recombinant SsTm did not efficiently control sarcoptic mange in rabbits, the immunogenic properties of tropomyosin suggest it may be developed as a vaccine with alternative adjuvants or delivery methods.