Serial Testing for Detection of Multilocus Genetic Interactions

A method to detect relationships between disease susceptibility and multilocus genetic interactions is the Multifactor-Dimensionality Reduction (MDR) technique pioneered by Ritchie et al. (2001). Since its introduction, many extensions have been pursued to deal with non-binary outcomes and/or account for multiple interactions simultaneously. Studying the effects of multilocus genetic interactions on continuous traits (blood pressure, weight, etc.) is one case that MDR does not handle. Culverhouse et al. (2004) and Gui et al. (2013) proposed two different methods to analyze such a case. In their research, Gui et al. (2013) introduced the Quantitative Multifactor-Dimensionality Reduction (QMDR) that uses the overall average of response variable to classify individuals into risk groups. The classification mechanism may not be efficient under some circumstances, especially when the overall mean is close to some multilocus means. To address such difficulties, we propose a new algorithm, the Ordered Combinatorial Quantitative Multifactor-Dimensionality Reduction (OQMDR), that uses a series of testings, based on ascending order of multilocus means, to identify best interactions of different orders with risk patterns that minimize the prediction error. Ten-fold cross-validation is used to choose from among the resulting models. Regular permutations testings are used to assess the significance of the selected model. The assessment procedure is also modified by utilizing the Generalized Extreme-Value distribution to enhance the efficiency of the evaluation process. We presented results from a simulation study to illustrate the performance of the algorithm. The proposed algorithm is also applied to a genetic data set associated with Alzheimer\u27s Disease

Molecular characterization of Anaplasma and Ehrlichia in ixodid ticks and reservoir hosts from Palestine: a pilot survey

Tick-borne anaplasmosis and ehrlichiosis are clinically important emerging zoonoses usually overlooked by veterinarians and physicians alike. This study aimed at detecting and genetically characterizing Ehrlichia and Anaplasma species in ixodid ticks and their animal hosts from the West Bank, Palestine. A total of 723 ixodid ticks belonging to three genera (Rhipicephalus, Hyalomma, Haemaphysalis) were collected from dogs, sheep, goats and camels. In addition, 189 blood samples were collected from dogs, sheep, camels, horses and a goat from the West Bank, Palestine. All tick and blood samples were investigated for the presence of Anaplasma and Ehrlichia targeting a 345 bp fragment of the 16S rRNA gene followed by sequence analysis. The infection rate of Anaplasma spp. in ticks was 6.5% (47/723). Anaplasma platys was identified in 28% (13/47) of them. Whereas, based on a partial sequence (851 bp) of msp4 gene, 38% (18/47) were identified as A. ovis. The species of the remaining 16 positive samples (16/47, 34%) could not be identified. Simultaneously, the infection rate of Ehrlichia spp. in the ticks was 0.6% (4/723). Three of which were E. canis and one was Ehrlichia spp. The infection rate of A. platys in dogs' blood samples was 10% (13/135), while it was 1.5% (2/135) for E. canis. The infection rate of Anaplasma in sheep blood samples was 40% (19/47), out of which 26% (5/19) were caused by A. ovis as revealed by msp4-PCR. Implementation of purely-spatial analysis by saTScan for all cases of Anaplasma revealed two statistically significant clusters in two districts; Tubas town and Majdal-Bani-Fadil village on the western hills of the Jordan Valley. Most cases of Anaplasma (83%) were from rural areas where life cycle components (vector, host and reservoir) abundantly interact. This study is the first in Palestine to reveal the presence of Anaplasma and Ehrlichia in ticks, dogs and sheep providing crucial platform for future epidemiological surveys and control strategies in the country and regio

Goiter and Laryngopharyngeal Reflux

The purpose of this study is to look at the prevalence of laryngopharyngeal reflux disease in patients with goiter in a group of 52 patients with goiter. All participants were asked to respond to the 9 questions on the Reflux Symptom Index (RSI). A diagnosis of LPRD based on symptoms was made for any RSI score above 10. The average score of every question was computed for all patients with goiter and compared to the corresponding average score of the controls. A P value of less than 0.05 was considered statistically significant. The total prevalence of LPRD in patients with goiter as indicated by an RSI score greater than 10 was 15.4% versus 9.1% in controls. The difference was not statistically significant (P value 0.525). Looking at the average score of the individual symptoms as listed in the RSI questionnaire, the average score of all the symptoms was higher in patients with goiter versus controls. There was no correlation between LPRD and any of the demographic variables except for nodules (P value 0.035). The presence of laryngopharyngeal symptoms in patients with goiter should alert the treating physician to the presence of laryngopharyngeal reflux disease

Neuroprotective role for RORA in Parkinson’s disease revealed by analysis of post-mortem brain and a dopaminergic cell line

Parkinson's disease (PD) is almost twice as prevalent in men, which has largely been attributed to neuroprotective effect of oestradiol in women. RORA (retinoic acid receptor-related orphan receptor alpha) regulates the transcription of central aromatase, the enzyme responsible for local oestradiol synthesis, simultaneously, RORA expression is regulated by sex hormones. Moreover, RORA protects neurones against oxidative stress, a key mechanism contributing to the loss of dopaminergic neurones in PD. Therefore, we hypothesized that there would be sex differences in RORA expression in the substantia nigra pars compacta (SNpc), which could contribute to sex differences observed in PD prevalence and pathogenesis. In a case control study, qPCR and western blot analyses were used to quantify gene and protein expression in the SNpc of post-mortem brains (n = 14 late-stage PD and 11 age and sex matched controls). The neuroprotective properties of a RORA agonist were then investigated directly using a cell culture toxin-based model of PD coupled with measures of viability, mitochondrial function and apoptosis. RORA was expressed at significantly higher levels in the SNpc from control females' brains compared to males. In PD, we found a significant increase in SNpc RORA expression in male PD compared to female PD. Treatment with a RORA agonist showed a significant neuroprotection in our cell culture model of PD and revealed significant effects on intracellular factors involved in neuronal survival and demise. This study is the first to demonstrate a sex specific pattern of RORA protein and gene expression in the SNpc of controls post-mortem human brains, and to show that this is differentially altered in male and female PD subjects, thus supporting a role for RORA in sex-specific aspects of PD. Furthermore, our in vitro PD model indicates mechanisms whereby a RORA agonist exerts its neuroprotective effect, thereby highlighting the translational potential for RORA ligands in PD

Evaluation of Streptocin SH3, a Bacteriocin produced by Streptococcus sanguinis isolated from Human Dental Plaque

Background: Bacteriocin is a peptidic toxin has many advantages to bacteria in their ecological niche and has strong antibacterial activity. Objective: The aim of this study was to evaluation of bacteriocin using Streptococcus sanguinis isolated from human dental caries. Subjects and Methods: Thirty five streptococcus isolates were diagnosed and tested for their production of bacteriocin, and then the optimal conditions for production of bacteriocin were determined.  After that, the purification of bacteriocin was made partially by ammonium sulfate at 95% saturation levels, followed by and gel filtration chromatography using Sephadex G-50 column. Finally, physical characteristics were also studied and determined the bacteriocin stability. Results: Among all streptococcal isolates, the S. sanguinis SH3 isolate with batter antimicrobial activity was selected, and used in further experiments. The optimum conditions for bacteriocin production were in Todd Hewitt broth (THB) supplemented with 1% glucose at 37°C for 24h under anaerobic conditions and inoculum size of (1.2 ˟ 109CFU/ml) and pH 7, where the inhibition zone diameter reached to 29 mm against Enterococcus faecalis. The purified bacteriocin had high inhibitory activity against S. pneumoniae, S. pyogenes, E. faecalis, E. faecium and  Leuconostoc mesenteroides. Streptocin SH3 keeps its effectiveness within the pH range 3-10, and temperature until 80ºC for 20 min. Conclusion: Bacteriocin produced from S. sanguinis has high activity against many pathogens and has high stability over wide ranges of temperature and pH, which makes it a good alternative in the medical and food preservation field

Local Thermal Non-equilibrium Analysis of Cu-Al2O3 Hybrid ‎Nanofluid Natural Convection in a Partially Layered Porous ‎Enclosure with Wavy Walls

A numerical study is performed to investigate the local thermal non-equilibrium effects on the natural convection in a two-dimensional enclosure with horizontal wavy walls, layered by a porous medium, saturated by Cu-Al2O3/water hybrid nanofluid. It is examined the influence of the nanoparticle volume fraction, varied from 0 to 0.04, the Darcy number (10-5 ≤ Da ≤ 10-2), the modified conductivity ratio (0.1 ≤ ϒ ≤ 1000), the porous layer height (0 ≤ Hp ≤ 1), and the wavy wall wavenumber (1 ≤ N ≤ 5) on natural convection in the enclosure. Predictions of the steady incompressible flow and temperature fields are obtained by the Galerkin finite element method, using the Darcy-Brinkman model in the porous layer. These are validated against previous numerical and experimental studies. By resolving separately the temperature fields of the working fluid and of the porous matrix, the local thermal non-equilibrium model exposed hot and cold spot formation and mitigation mechanisms on the heated and cooled walls. By determining the convection cell strength, the Darcy number is the first rank controlling parameter on the heat transfer performance, followed by N, Hp and γ. The heat transfer rate through the hybrid nanofluid and solid phases is highest when N = 4 at a fixed value of nanoparticle volume fraction

Hypocone Reduction and Carabelli’s Traits in Contemporary Jordanians and the Association between Carabelli’s Trait and the Dimensions of the Maxillary First Permanent Molar

The objective of this study is to determine the prevalence of expression and bilateralism of two dental morphological traits in contemporary Jordanians: The hypocone reduction trait on the maxillary second permanent molar and Carabelli’s trait on maxillary permanent first and second molars. Furthermore, inter-trait correlation and the relationship of Carabelli’s traits with upper first molar dimensions were investigated. Three hundred subjects of school children at their 10th grade and of an average age of 15.5±0.4 years were involved. Alginate impressions for the maxillary arch were taken, dental casts were reproduced. The selected accurate casts were of 132 male- and 155 female-students. The frequencies of hypocone reduction trait on the maxillary second molar and Carabelli’s trait on the maxillary molars were examined. Buccolingual and mesiodistal diameters of the maxillary first molar were measured and recorded. Paired Sample t test and Nonparametric Correlation analysis were used for data analysis. Hypocone reduction trait on the maxillary second molar was found in 29.8 % of the examined students. Positive forms of Carabelli’s trait on first and second molars were observed in 65.0 % and 3.8 %, respectively. Nonparametric correlation analysis revealed positive association between Carabelli’s trait on first molar and hypocone reduction trait on the maxillary second molar. The presence of Carabelli’s trait on first molar was strongly associated with the increase of buccolingual, but not the mesiodistal, diameter. Bilateralism was found highly significant in the tested traits and both genders (p<0.001). This finding might be a sign of relatively low environmental stresses in the living Jordanian population and/or great ability of its individuals to buffer the adverse effects of such stresses

Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction.

Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR\u27s tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent