The replacement of five consecutive amino acids in the cyt1a protein of bacillus thuringiensis enhances its cytotoxic activity against lung epithelial cancer cells

Cyt1A protein is a cytolytic protein encoded by the cyt gene of Bacillus thuringiensis subsp. israelensis (Bti) as part of the parasporal crystal proteins produced during the sporulation. Cyt1A protein is unique compared to the other endotoxins present in these parasporal crystals. Unlike ?-endotoxins, Cyt1A protein does not require receptors to bind to the target cell and activate the toxicity. It has the ability to affect a broad range of cell types and organisms, due to this characteristic. Cyt1A has been recognized to not only target the insect cells directly, but also recruit other endotoxins by acting as receptors. Due to these mode of actions, Cyt1A has been studied for its cytolytic activity against human cancer cell lines, although not extensively. In this study, we report a novel Cyt1A protein produced by a Bti strain QBT229 isolated from Qatar. When tested for its cytotoxicity against lung cancer cells, this local strain showed considerably higher activity compared to that of the reference Bti and other strains tested. The possible reasons for such enhanced activity were explored at the gene and protein levels. It was evidenced that five consecutive amino acid replacements in the ?8 sheet of the Cyt1A protein enhanced the cytotoxicity against the lung epithelial cancer cells. Such novel Cyt1A protein with high cytotoxicity against lung cancer cells has been characterized and reported through this study. -2018 by the authors. Licensee MDPI, Basel, Switzerland.Scopu

A systematic review and meta-analysis of salivary cortisol measurement in domestic canines

Salivary cortisol is widely used as an indicator of stress and welfare in canine research. However, much remains unclear about the basic features of this hormone marker in domestic dogs. This systematic review and meta-analysis aimed to determine a reference range for cortisol concentration in the saliva of dogs and examine how canine characteristics, environmental effects and experimental considerations relate to salivary cortisol concentrations. A systematic review of literature databases and conference proceedings from 1992 to 2012 identified 61 peer-reviewed studies using domestic dog salivary cortisol. Researchers were contacted via email, and 31 raw data sets representing a total of 5,153 samples from 1,205 dogs were shared. Meta-analysis provided a cortisol concentration range of 0 to 33.79 μg/dL (mean 0.45 μg/dL, SEM 0.13). Significant effects (P < 0.05) were found for sex and neuter status, age, regular living environment, time in environment before testing, testing environment, owner presence during testing, and collection media. Significant effects were not found for dog breed, body weight, dog type, coat color, assay type, exercise, eating, or use of salivary stimulant. Care should be taken when using cortisol studies for dogs at a group or population level as there is a large amount of intraindividual and interindividual variability and external variables could influence salivary cortisol concentration. This analysis highlights the importance of carefully controlling experimental design to compare samples within and between individual dogs, as well as establishing and using best practices for saliva collection. Caution should be exercised in comparing different studies, as the results could be the reflection of a plethora of factors

Prognostic Role of Albumin Level in Heart Failure: A Systematic Review and Meta-Analysis

BACKGROUND: Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patient. METHODS: Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias. RESULTS: A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%-37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96-7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36-1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05-2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67-0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients. CONCLUSION: Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients

Using sea-level data to constrain a finite-element primitive-equation ocean model with a local SEIK filter

Inspired by the pioneering work of Christian Le Provost on finiteelement ocean modeling a new ocean circulation model was developedover the last few years. It applies a surface triangulation and finiteelements for an accurate description of coasts and bathymetry and theirsteering effect on the ocean circulation. A novel feature is the meshdesign which allows a vertical structure in geopotential (z)coordinates without loss of flexibility and avoids pressure gradienterrors everywhere except for the lowest layer of abyssal ocean. Themodel is combined with sea level measurements and data assimilation,another major research topic of Christian Le Provost. We apply the SEIKfilter which was developed in Grenoble while Christian was teachingthere. The addition of a local analysis scheme improves the filterperformance first of all in its variance estimates but also in its meansolution

Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis.

Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy. Simultaneously inhibiting glutaminolysis and either beta oxidation with trimetazidine or autophagy with chloroquine both induced cancer cell death. Here we identified metabolic escape mechanisms contributing to cancer cell survival under treatment and we suggest potentially translational strategy for combined cancer therapy, given that chloroquine is an FDA approved drug. Our findings are first to show efficiency of combined inhibition of glutaminolysis and beta oxidation as potential anti-cancer strategy as well as add to the evidence that combined inhibition of glutaminolysis and autophagy may be effective in glutamine-addicted cancers