Isolation and characterization of native Bacillus thuringiensis strains from Saudi Arabia with enhanced larvicidal toxicity against the mosquito vector Anopheles gambiae (s.l.).

BACKGROUND: Worldwide, mosquito vectors are transmitting several etiological agents of important human diseases, including malaria, causing millions of deaths every year. In Saudi Arabia, as elsewhere, vector-control is based mostly on chemical insecticides which may be toxic and cause environmental deprivation. Here, to support the development of bio-pesticide alternatives, a study was conducted to identify native Bacillus thuringiensis (Bt) isolates with improved toxicity against the malaria vector, Anopheles gambiae (s.l.). METHODS: Sixty-eight Bt isolates were obtained from 300 soil and other samples collected from 16 sites across Saudi Arabia. Bt identification was based on morphological characteristics of colonies, shape of parasporal crystals and biochemical profiles. After characterization of their mosquitocidal activity, larvicidal strains were described through 16S ribosomal DNA gene sequencing, cry, cyt and chi genes PCR-amplification profiles, and SDS-PAGE protein analyses. RESULTS: Spherical Bt crystals were predominant amongst the 68 isolates (34%), while irregular, bi-pyramidal and spore-attached crystals were found in 32, 13 and 21% of strains, respectively. LC50 and LC90 bioassays showed that 23/68 isolates were larvicidal, with distinct biochemical activity profiles compared to non-larvicidal Bt strains. Eight larvicidal strains showed larvicidal activity up to 3.4-fold higher (LC50 range: 3.90-7.40 μg/ml) than the reference Bti-H14 strain (LC50 = 13.33 μg/ml). Of these, 6 strains had cry and cyt gene profiles similar to Bti-H14 (cry4Aa, cry4Ba, cry10, cry11, cyt1Aa, cyt1Ab, cyt2Aa). The seventh strain (Bt63) displaying the highest larvicidal activity (LC50 = 3.90 μg/ml) missed the cry4Aa and cyt1Ab genes and had SDS-PAGE protein profiles and spore/crystal sizes distinct from Bti-H14. The eight strain (Bt55) with LC50 of 4.11μg/ml had cry and cyt gene profiles similar to Bti-H14 but gave a chi gene PCR product size of 2027bp. No strains harbouring cry2, cry17 + 27, cry24 + 40, cry25, cry29, cry30, or cyt2Ba were detected. CONCLUSION: This study represents the first report of several Saudi indigenous Bt strains with significantly higher larvicidal efficacy against An. gambiae than the reference Bti-H14 strain. The very high toxicity of the Bt63 strain, combined with distinct cry and cyt genes and SDS-PAGE-protein profiles makes it a promising candidate for future applications in mosquito bio-control

Four Generations: SUSY and SUSY Breaking

We revisit four generations within the context of supersymmetry. We compute the perturbativity limits for the fourth generation Yukawa couplings and show that if the masses of the fourth generation lie within reasonable limits of their present experimental lower bounds, it is possible to have perturbativity only up to scales around 1000 TeV. Such low scales are ideally suited to incorporate gauge mediated supersymmetry breaking, where the mediation scale can be as low as 10-20 TeV. The minimal messenger model, however, is highly constrained. While lack of electroweak symmetry breaking rules out a large part of the parameter space, a small region exists, where the fourth generation stau is tachyonic. General gauge mediation with its broader set of boundary conditions is better suited to accommodate the fourth generation.Comment: 27 pages, 5 figure

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Trends in HIV/AIDS morbidity and mortality in Eastern Mediterranean countries, 1990–2015: findings from the Global Burden of Disease 2015 study

OBJECTIVES: We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. METHODS: Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. RESULTS: In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. CONCLUSIONS: HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance, and scale up HIV antiretroviral therapy and comprehensive prevention services

Cross-border movement, economic development and malaria elimination in the Kingdom of Saudi Arabia

Malaria at international borders presents particular challenges with regards to elimination. International borders share common malaria ecologies, yet neighboring countries are often at different stages of the control-to-elimination pathway. Herein, we present a case study on malaria, and its control, at the border between Saudi Arabia and Yemen. Malaria program activity reports, case data, and ancillary information have been assembled from national health information systems, archives, and other related sources. Information was analyzed as a semi-quantitative time series, between 2000 and 2017, to provide a plausibility framework to understand the possible contributions of factors related to control activities, conflict, economic development, migration, and climate. The malaria recession in the Yemeni border regions of Saudi Arabia is a likely consequence of multiple, coincidental factors, including scaled elimination activities, cross-border vector control, periods of low rainfall, and economic development. The temporal alignment of many of these factors suggests that economic development may have changed the receptivity to the extent that it mitigated against surges in vulnerability posed by imported malaria from its endemic neighbor Yemen. In many border areas of the world, malaria is likely to be sustained through a complex congruence of factors, including poverty, conflict, and migration

Formulation and antioxidant properties of curcumin gum Arabic nanoparticles for delivery to cancer cells

Curcumin nanoparticles)Cur/GANPs(were formulated based on gum arabic)GA(as a stabilizer coatings for nanoparticles through efficient synthesis approach . The current study investigated the antioxidant properties and antihypertensive activity of curcumin)Cur(using various established in vitro assays, such as 1,1-diphenyl-2-picrylhydrazyl)DPPH(as well as angiotensin converting enzyme (ACE(inhibitory activity. The in vitro cytotoxicity of Cur/GANPs against human liver cancer)HepG2(, and colon cancer)HT29(was investigated. The exposure of human cancer cells to Cur/GANPs)1.56-100 µg/ml(using MTT)3-)4,5-dimethylthiazol-2-yl(2,5-diphenyl tetrazolium bromide(has revealed that the Cur/GANPs inhibited the growth of cell lines examined in a dose dependent manner. Hence, Cur/GANPs nanoparticles may have great potential to be applied for cancer treatment

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations

BACKGROUND: The Mini Mental State Examination (MMSE) is a cognitive test that is commonly used as part of the evaluation for possible dementia. OBJECTIVES: To determine the diagnostic accuracy of the Mini‐Mental State Examination (MMSE) at various cut points for dementia in people aged 65 years and over in community and primary care settings who had not undergone prior testing for dementia. SEARCH METHODS: We searched the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), LILACS (BIREME), ALOIS, BIOSIS previews (Thomson Reuters Web of Science), and Web of Science Core Collection, including the Science Citation Index and the Conference Proceedings Citation Index (Thomson Reuters Web of Science). We also searched specialised sources of diagnostic test accuracy studies and reviews: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). We attempted to locate possibly relevant but unpublished data by contacting researchers in this field. We first performed the searches in November 2012 and then fully updated them in May 2014. We did not apply any language or date restrictions to the electronic searches, and we did not use any methodological filters as a method to restrict the search overall. SELECTION CRITERIA: We included studies that compared the 11‐item (maximum score 30) MMSE test (at any cut point) in people who had not undergone prior testing versus a commonly accepted clinical reference standard for all‐cause dementia and subtypes (Alzheimer disease dementia, Lewy body dementia, vascular dementia, frontotemporal dementia). Clinical diagnosis included all‐cause (unspecified) dementia, as defined by any version of the Diagnostic and Statistical Manual of Mental Disorders (DSM); International Classification of Diseases (ICD) and the Clinical Dementia Rating. DATA COLLECTION AND ANALYSIS: At least three authors screened all citations.Two authors handled data extraction and quality assessment. We performed meta‐analysis using the hierarchical summary receiver‐operator curves (HSROC) method and the bivariate method. MAIN RESULTS: We retrieved 24,310 citations after removal of duplicates. We reviewed the full text of 317 full‐text articles and finally included 70 records, referring to 48 studies, in our synthesis. We were able to perform meta‐analysis on 28 studies in the community setting (44 articles) and on 6 studies in primary care (8 articles), but we could not extract usable 2 x 2 data for the remaining 14 community studies, which we did not include in the meta‐analysis. All of the studies in the community were in asymptomatic people, whereas two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We judged two studies to be at high risk of bias in the patient selection domain, three studies to be at high risk of bias in the index test domain and nine studies to be at high risk of bias regarding flow and timing. We assessed most studies as being applicable to the review question though we had concerns about selection of participants in six studies and target condition in one study. The accuracy of the MMSE for diagnosing dementia was reported at 18 cut points in the community (MMSE score 10, 14‐30 inclusive) and 10 cut points in primary care (MMSE score 17‐26 inclusive). The total number of participants in studies included in the meta‐analyses ranged from 37 to 2727, median 314 (interquartile range (IQR) 160 to 647). In the community, the pooled accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 (95% confidence interval (CI) 0.74 to 0.92), specificity 0.90 (95% CI 0.82 to 0.95); at a cut point of 25 (10 studies), sensitivity 0.87 (95% CI 0.78 to 0.93), specificity 0.82 (95% CI 0.65 to 0.92); and in seven studies that adjusted accuracy estimates for level of education, sensitivity 0.97 (95% CI 0.83 to 1.00), specificity 0.70 (95% CI 0.50 to 0.85). There was insufficient data to evaluate the accuracy of the MMSE for diagnosing dementia subtypes.We could not estimate summary diagnostic accuracy in primary care due to insufficient data. AUTHORS' CONCLUSIONS: The MMSE contributes to a diagnosis of dementia in low prevalence settings, but should not be used in isolation to confirm or exclude disease. We recommend that future work evaluates the diagnostic accuracy of tests in the context of the diagnostic pathway experienced by the patient and that investigators report how undergoing the MMSE changes patient‐relevant outcomes