Characterization of Bacillus thuringiensis strains from Jordan and their toxicity to the Lepidoptera, Ephestia kuehniella Zeller

Bacillus thuringiensis was investigated in four different habitats (grain dust, olive-cultivated soils, waste and industrial-byproducts contaminated soils, and animal byproducts-contaminated soils). The bacterium was highly abundant in soils contaminated with animal byproducts. Eight serotypes with Bacillus thuringiensis israelensis being the most common. Out of the twenty-six isolated strains, five strains (serotype: kenyae, kurstaki, kurstaki HD1 and thuringiensis) that produced bipyramid crystal proteins were toxic to the lepidoptera larvae of Ephestia kuehniella Zeller. The SDS-PAGE protein profile analysis showed a relationship between the crystal protein shape and the toxicity to the larvae of the tested insect. Key Words: Bacillus thuringiensis serotypes, Ephestia kuehniella, parasporal crystal proteins. African Journal of Biotechnology Vol.3(11) 2004: 622-62

Toxicity of Bacillus thuringiensis β-exotoxins and δ-endotoxins to Drosophila melanogaster, Ephestia kuhniella and human erythrocytes

A total of 73 Bacillus thuringiensis (Bt) strains were screened for the presence of non-hemolytic insecticidal β-exotoxin-free δ-endotoxins. Out of them, 45 Bt strains produced δ-endotoxins with specific insecticidal activity against Drosophila melanogaster and/or Ephestia kuhniella larvae. The thermostable β-exotoxin was observed only in 15 Bt strains and appeared to exhibit dual non-specific insecticidal activity against both D. melanogaster and E. kuhniella larvae and showed in vitro hemolysis for human erythrocytes. It was found that β-exotoxin was produced by Bt strains belonging to five serovars (israelensis, kenyae, kurstaki, pakistani, and tohokuensis) and two non-serotypable strains. This result suggests that β-exotoxin production is a strain-specific property rather than a serovar-specific property. To our knowledge, this is the first study that demonstrates β-exotoxins production association with Bt strains belonging to serovars israelensis, pakistani, and tohokuensis. The plasmid DNA profiles of some β-exotoxin producing Bt strains shared large plasmid patterns which may have the common β-exotoxin regulatory gene(s). It was found that 16 local Bt strains, 15 of which belonged to five serovars (aizawai, israelensis, kurstaki, morrisoni, and pakistani) and one was autoagglutinated strain, produced non-hemolytic insecticidal β-exotoxin-free δ-endotoxins. Based on random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), the genotypic relatedness among these 16 Bt strains was investigated. The strains were grouped into two clusters. Bt strains within serovars israelensis were grouped in two subclusters, Bt strains within serovars aizawai were genomically homogeneous and clustered together, while the other serovars were grouped together in one subcluster. The autoagglutinated strain was clustered within serovar israelensis. Thus, these δ-endotoxins can be developed for the use in Bt-based insecticidal preparations.Keywords: Endotoxin, exotoxin, hemolytic, serovar, thuringiensi

Genome-wide association studies in asthma

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to disease susceptibility. Genome-wide association studies (GWAS) have now identified novel risk alleles and loci associated with asthma diagnosis and more recently with clinical subgroups of disease. However, while providing insight into potential disease mechanisms these risk alleles have modest effect sizes and account for a small proportion of the anticipated heritability of asthma. In this article we provide an overview of GWAS in asthma to date including reproducible associations and advances in our understanding of the biology of asthma. In addition we discuss ancestry-specific findings and how genetics may contribute to the development of multiple allergic conditions known as the ‘atopic march’. Finally, we outline the strengths and weaknesses of GWAS and look to future approaches including a greater focus to functional variation and assessment of gene–gene and gene–environment interactions

Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology

Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of α1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ∼1% of Chronic Obstructive Pulmonary Disease (COPD) cases. Genome-wide association studies (GWAS) have been successful at detecting multiple loci harboring variants predicting the variation in lung function measures and risk of COPD. However, GWAS are incapable of distinguishing causal from noncausal variants. Several approaches can be used for functional translation of genetic findings. These approaches have the scope to identify underlying alleles and pathways that are important in lung function and COPD. Computational methods aim at effective functional variant prediction by combining experimentally generated regulatory information with associated region of the human genome. Classically, GWAS association follow-up concentrated on manipulation of a single gene. However association data has identified genetic variants in >50 loci predicting disease risk or lung function. Therefore there is a clear precedent for experiments that interrogate multiple candidate genes in parallel, which is now possible with genome editing technology. Gene expression profiling can be used for effective discovery of biological pathways underpinning gene function. This information may be used for informed decisions about cellular assays post genetic manipulation. Investigating respiratory phenotypes in human lung tissue and specific gene knockout mice is a valuable in vivo approach that can complement in vitro work. Herein, we review state-of-the-art in silico, in vivo, and in vitro approaches that may be used to accelerate functional translation of genetic findings

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods and measurements: We conducted genome-wide analyses across three independent studies and meta-analysed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Main results: We identified and replicated three new genome-wide significant (P<5×10−8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1 and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF susceptibility variants contribute to IPF susceptibility. Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF, supports recent studies demonstrating the importance of mTOR signalling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Antimicrobial and anticancer activities of extracts from Urginea maritime fruits

Background: Increasing antibiotic resistance among human pathogenic microorganisms and the failure of conventional cancer therapies attracting great attention among scientists in the field of herbal medicine to develop natural antimicrobial and anticancer drugs. Thus, the antimicrobial and anticancer activities from fruits of the medicinal plant Urginea maritima (L.) Baker that unexplored previously were investigated in this study.Materials and Methods: Fruits of U. maritima plant were collected, dried, ground, and extracted by hot water, ethanol, methanol, and acetone. The fruit extracts were examined for their potential as antimicrobial and anticancer agents using the agar well diffusion method and MTT assay, respectively. The gene expression of some cancer-related gene markers was determined by RT-PCR.Results: All fruit extracts of U. maritima exhibited antibacterial activity against S. aureus and E. coli. Methanol and ethanol extracts exhibited anticandidal activity. Ethanol and acetone extracts displayed non-hemolytic activity and selective cytotoxicity against breast cancer MCF7 cells with IC50 values that considered as active treatments. Concerning DNA fragmentation and gene expression after treatment of MCF7 cells with the most promising acetone extract, induction of apoptosis was proposed. The expression of cancer-related gene TNF after 6 hours, tumor suppressor genes (p53 and BRCA1), and immune response genes (IL-2 and IL-6) was induced. The expression of anti-apoptotic gene Bcl2 in treated MCF7 cells was reduced.Conclusion: Fruit extracts of U. maritima exhibited antimicrobial and anticancer activities. This result may lead to the use of these extracts for treatment of some infectious diseases and certain types of cancer.Keywords: Urginea maritime; antibacterial; antifungal; anticancer; gene expressio