ChIP-BIT: Bayesian inference of target genes using a novel joint probabilistic model of ChIP-seq profiles.

Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) has greatly improved the reliability with which transcription factor binding sites (TFBSs) can be identified from genome-wide profiling studies. Many computational tools are developed to detect binding events or peaks, however the robust detection of weak binding events remains a challenge for current peak calling tools. We have developed a novel Bayesian approach (ChIP-BIT) to reliably detect TFBSs and their target genes by jointly modeling binding signal intensities and binding locations of TFBSs. Specifically, a Gaussian mixture model is used to capture both binding and background signals in sample data. As a unique feature of ChIP-BIT, background signals are modeled by a local Gaussian distribution that is accurately estimated from the input data. Extensive simulation studies showed a significantly improved performance of ChIP-BIT in target gene prediction, particularly for detecting weak binding signals at gene promoter regions. We applied ChIP-BIT to find target genes from NOTCH3 and PBX1 ChIP-seq data acquired from MCF-7 breast cancer cells. TF knockdown experiments have initially validated about 30% of co-regulated target genes identified by ChIP-BIT as being differentially expressed in MCF-7 cells. Functional analysis on these genes further revealed the existence of crosstalk between Notch and Wnt signaling pathways

Production of 3,4-dihydroxy L-phenylalanine by a newly isolated Aspergillus niger and parameter significance analysis by Plackett-Burman design

<p>Abstract</p> <p>Background</p> <p>The amino acid derivative 3,4-dihydroxy L-phenylalanine (L-dopa) is gaining interest as a drug of choice for Parkinson's disease. <it>Aspergillus oryzae </it>is commonly used for L-dopa production; however, a slower growth rate and relatively lower tyrosinase activity of mycelia have led to an increasing interest in exploiting alternative fungal cultures. In the present investigation, we report on the microbiological transformation of L-tyrosine to L-dopa accomplished by a newly isolated filamentous fungus <it>Aspergillus niger</it>.</p> <p>Results</p> <p>The culture <it>A. niger </it>(isolate GCBT-8) was propagated in 500 ml Erlenmeyer flasks and the pre-grown mycelia (48 h old) were used in the reaction mixture as a source of enzyme tyrosinase. Grinded mycelia gave 1.26 fold higher L-dopa production compared to the intact at 6% glucose (pH 5.5). The rate of L-tyrosine consumption was improved from 0.198 to 0.281 mg/ml. Among the various nitrogen sources, 1.5% peptone, 1% yeast extract and 0.2% ammonium chloride were optimized. The maximal L-dopa was produced (0.365 mg/ml) at 0.3% potassium dihydrogen phosphate with L-tyrosine consumption of 0.403 mg/ml.</p> <p>Conclusion</p> <p>Over ~73% yield was achieved (degree of freedom 3) when the process parameters were identified using 2k-Plackett-Burman experimental design. The results are highly significant (p ≤ 0.05) and mark the commercial utility (LSD 0.016) of the mould culture which is perhaps the first ever report on L-dopa production from <it>A. niger</it>.</p

Health related quality of life of obese adolescents in Kuwait

Obesity impairs health related quality of life (HRQL) in adolescents, but most evidence in this area has mostly come from western societies. We wanted to test the hypothesis that obesity impairs HRQL in Kuwaiti adolescents, and to test for differences in HRQL assessed by self-report and parent-proxy report. In 500 Kuwaiti 10-14 year olds HRQL was assessed using the Peds QL (TM) with both adolescent self-reports (n = 500) and parent-proxy reports (n = 374). Obesity was not significantly associated with HRQL in regression analysis. In a paired comparison of 98 pairs of obese adolescents vs. 98 healthy weight peers, impairment of HRQL reached significance only for physical score (95% CI = -1.5, -9.4), not for psychosocial score or total score. In a paired comparison of parent-proxy vs. self-reports for the obese adolescents, total score (95% CI = -4.9, -10.9), physical score (95% CI = -3.2, -11.0), and psychosocial score (95% CI = -4.2, -10.8) were all significantly lower in the parent reports. Obesity is not associated with marked impairment of HRQL in adolescents in Kuwait, in contrast to studies in western societies. This may reflect cultural differences in attitudes towards obesity

An exploration of patient-reported symptoms in systemic lupus erythematosus and the relationship to health-related quality of life

Objective: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics and disease characteristics (duration, activity, organ damage). Methods: In a cross-sectional study, patients with SLE (n=324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analyzed for patient demographics, disease duration, results from the questionnaires: Medical Outcomes Study Short-Form 36, Hospital Anxiety and Depression Scale, Systemic Lupus Activity Measure, SLE disease activity index and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology damage index. Results: 23 symptom categories were identified. Fatigue (51%), Pain (50%) and Musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting Fatigue showed statistically significant impact on both mental and physical components of HRQoL.. Patients with no present symptoms (10%) had higher HRQoL (p<0.001) and lower levels of depression (p<0.001), anxiety (p<0.01) and disease activity (SLAM) (p<0.001). Conclusion: Fatigue, pain or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting Fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue

A dimensioning and tolerancing methodology for concurrent engineering applications II: comprehensive solution strategy

Dimensioning and tolerancing (D&T) is a multidisciplinary problem which requires the fulfillment of a large number of dimensional requirements. However, almost all of the currently available D&T tools are only intended for use by the designer. In addition, they typically provide solutions for the requirements one at time. This paper presents a methodology for determining the dimensional specifications of the component parts and sub-assemblies of a product by satisfying all of its requirements. The comprehensive solution strategy presented here includes: a strategy for separating D&T problems into groups, the determination of an optimum solution order for coupled functional equations, a generic tolerance allocation strategy, and strategies for solving different types of D&T problems. A number of commonly used cost minimization strategies, such as the use of standard parts, preferred sizes, preferred fits, and preferred tolerances, have also been incorporated into the proposed methodology. The methodology is interactive and intended for use in a concurrent engineering environment by members of a product development team

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission

Different Oxidative Stress Response in Keratinocytes and Fibroblasts of Reconstructed Skin Exposed to Non Extreme Daily-Ultraviolet Radiation

Experiments characterizing the biological effects of sun exposure have usually involved solar simulators. However, they addressed the worst case scenario i.e. zenithal sun, rarely found in common outdoor activities. A non-extreme ultraviolet radiation (UV) spectrum referred as “daily UV radiation” (DUVR) with a higher UVA (320–400 nm) to UVB (280–320 nm) irradiance ratio has therefore been defined. In this study, the biological impact of an acute exposure to low physiological doses of DUVR (corresponding to 10 and 20% of the dose received per day in Paris mid-April) on a 3 dimensional reconstructed skin model, was analysed. In such conditions, epidermal and dermal morphological alterations could only be detected after the highest dose of DUVR. We then focused on oxidative stress response induced by DUVR, by analyzing the modulation of mRNA level of 24 markers in parallel in fibroblasts and keratinocytes. DUVR significantly modulated mRNA levels of these markers in both cell types. A cell type differential response was noticed: it was faster in fibroblasts, with a majority of inductions and high levels of modulation in contrast to keratinocyte response. Our results thus revealed a higher sensitivity in response to oxidative stress of dermal fibroblasts although located deeper in the skin, giving new insights into the skin biological events occurring in everyday UV exposure