Probiotic actions on diseases: implications for therapeutic treatments

The ecology of gut microflora, which colonizes all body surfaces, has long coevolved with its hosts in a complicated fashion. Health benefits conferred by gut microflora include defense against invading pathogens, improvement of nutritional bioavailability, and development of the regional and systemic immune systems. The past decade has witnessed growing interest in the fact that the gut microflora affects the host's energy homeostasis by means of various mechanisms, including supplying nourishment from indigestible compounds, producing small biomolecules responsible for lipid profiles, and participating in the absorption, distribution, metabolism and excretion of nutrition. Much in vitro and in vivo research has indicated that aberrant gut microflora plays an important role in the pathogenesis of a wide spectrum of diseases. This is accomplished by a shift in focus, from laying an emphasis on pharmacotherapy to placing more effort on gut microflora normalization. The objectives of this review include illustrating trends in the clinical application of probiotics on diseases, as well as discussing current methodology limitations on probiotic selection. Furthermore, it is expected to shed light on the nature of probiotics, with the aim of giving greater insight into the implications for clinical use of probiotics in the treatment of diseases

Domain Specific Approximation for Object Detection

There is growing interest in object detection in advanced driver assistance systems and autonomous robots and vehicles. To enable such innovative systems, we need faster object detection. In this work, we investigate the trade-off between accuracy and speed with domain-specific approximations, i.e. category-aware image size scaling and proposals scaling, for two state-of-the-art deep learning-based object detection meta-architectures. We study the effectiveness of applying approximation both statically and dynamically to understand the potential and the applicability of them. By conducting experiments on the ImageNet VID dataset, we show that domain-specific approximation has great potential to improve the speed of the system without deteriorating the accuracy of object detectors, i.e. up to 7.5x speedup for dynamic domain-specific approximation. To this end, we present our insights toward harvesting domain-specific approximation as well as devise a proof-of-concept runtime, AutoFocus, that exploits dynamic domain-specific approximation.Comment: 6 pages, 6 figures. Published in IEEE Micro, vol. 38, no. 1, pp. 31-40, January/February 201

Lactobacillus plantarum MYL26 induces endotoxin tolerance phenotype in Caco-2 cells

Background: Crohn's disease and ulcerative colitis are the major types of chronic inflammatory bowel diseaseoccurring in the colon and small intestine. A growing body of research has proposed that probiotics are able toattenuate the inflammatory symptoms of these diseases in vitro and in vivo. However, the mechanism of probioticactions remains unclear.Results: Our results suggested Lactobacillus plantarum MYL26 inhibited inflammation in Caco-2 cells throughregulation of gene expressions of TOLLIP, SOCS1, SOCS3, and IκBα, rather than SHIP-1 and IRAK-3.Conclusions: We proposed that live/ heat-killed Lactobacillus plantarum MYL26 and bacterial cell wall extracttreatments impaired TLR4-NFκb signal transduction through Tollip, SOCS-1 and SOCS-3 activation, thus inducing LPStolerance. Our findings suggest that either heat-killed probiotics or probiotic cell wall extracts are able to attenuateinflammation through pathways similar to that of live bacteria

New synthetic routes to Triazolo-benzodiazepine analogues:expanding the scope of the bump-and-hole approach for selective Bromo and Extra-Terminal (BET) bromodomain inhibition

We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains

Establishment And Regulation Of Epithelial Enhancers By P63

The transcription factor p63 is a key mediator of epidermal commitment, development, and differentiation. Point mutations in p63 in human patients lead to developmental defects, including orofacial clefting, one of the most common congenital defects in humans. To date, knowledge is limited about how pivotal is p63’s role in human craniofacial development, due in part to a lack of tractable models to study de novo expression of p63 and its role at developmentally regulated genes. Using an inducible trans-differentiation model, combined with epigenomic sequencing and multi-cohort meta-analysis of GWAS data, we show that p63 establishes enhancers at craniofacial development genes to modulate their transcription. We further identify histone methyltransferase KMT2D as a key interacting partner of p63 at these enhancers and identify a novel role for this histone methyltransferase in maintaining epithelial homeostasis. Our results demonstrate that disease-specific substitution mutation in the DNA binding domain or SAM protein interaction domain of p63 respectively eliminate or reduce establishment of these enhancers. Finally, we show enhancers established by p63 are highly enriched for SNPs associated with nonsyndromic cleft lip +/- cleft palate (CL/P). These orthogonal approaches indicate a strong molecular link between p63 enhancer function and CL/P, illuminating molecular mechanisms underlying this developmental defect and revealing vital regulatory elements and new candidate causative genes

Stability Enhancement of Polymeric Sensing Films Using Fillers

Experiments have shown the stability enhancement of polymeric sensing films on mixing the polymer with colloidal filler particles (submicron-sized) of carbon black, silver, titanium dioxide, and fumed silicon dioxide. The polymer films are candidates for potential use as sensing media in micro/nano chemical sensor devices. The need for stability enhancement of polymer sensing films arises because such films have been found to exhibit unpredictable changes in sensing activity over time, which could result in a possible failure of the sensor device. The changes in the physical properties of a polymer sensing film caused by the sorption of a target molecule can be measured by any of several established transduction techniques: electrochemical, optical, calorimetric, or piezoelectric, for example. The transduction technique used in the current polymer stability experiments is based on piezoelectric principles using a quartz-crystal microbalance (QCM). The surface of the QCM is coated with the polymer, and the mass uptake by the polymer film causes a change in the oscillating frequency of the quartz crystal. The polymer used for the current study is ethyl cellulose. The polymer/ polymer composite solutions were prepared in 1,3 dioxolane solvent. The filler concentration was fixed at 10 weight percent for the composites. The polymer or polymer composite solutions were cast on the quartz crystal having a fundamental frequency of about 6 MHz. The coated crystal was subjected to a multistage drying process to remove all measurable traces of the solvent. In each experiment, the frequency of oscillation was measured while the QCM was exposed to clean, dry, flowing air for about 30 minutes, then to air containing a known concentration of isopropanol for about 30 minutes, then again to clean dry air for about 30 minutes, and so forth. This cycle of measurements for varying isopropanol concentrations was repeated at intervals for several months. The figure depicts some of the sensing film stability results for ethyl cellulose polymer, ethyl cellulose-carbon black, and ethyl cellulose-silicon dioxide composite systems. An ethyl cellulose film exhibited a marked decline in response in the first few months of study and settled to a steady average response after about four months. However, response varied widely around the average response for ethyl cellulose film. In contrast, ethyl cellulose- carbon black and ethyl cellulose-silicon dioxide composites also declined in the early months, but showed more repeatable sensing film activity after the initial decline. Similar trends were observed in experiments for ethyl cellulose-titanium dioxide and ethyl cellulose-silver composites

Meta-analyses of epigenetics risk factors for cardiovascular health: APOA5 human gene variations across different race-ethnicity groups

Session presented on Monday, July 28, 2014: Purpose: The purpose of this presentation is to disseminate current evidence on population genome health, through the meta-analyses of epigenetic risk factors, for cardiovascular (CV) health. CV Disease (CVD) continues to be the leading cause of death worldwide. Studies have associated Apolipoprotein A5 (APOA5, 1131T\u3eC, rs662799) gene polymorphism with plasma triglyceride levels for CVD. Life style risk factors such as smoking, alcohol intake, and physical inactivity were associated with increased risks for CVD. Methods: Literature searches, quality scores, and inter-rater evaluation on data coding were completed to ensure data accuracy for pooled meta-analyses. Results: Preliminary analyses included 11,340 CVD cases and 18,758 controls from 37 studies. The gene mutation variations (TC and CC subtypes) in Asian populations were higher (53.1-42.4%) than Caucasian populations (21.4-10.2%) across the world, for control and case groups. For validation, pollution indicators were checked and shown worse in Asia than other countries. For lifestyle related meta-analyses, smoking was associated with an increased risk of CVD (18 studies, 5,035 cases, 9,140 controls, RR=1.70, 95% Confidence Interval = 1.39-2.08, p \u3c 0.0001). However, alcohol intake (5 studies, 1,646 cases, 3094 controls, RR=1.42, 0.86-2.34) and physical inactivity (4 studies, 466 cases, 1,005 controls, RR=0.91, 0.74-1.13) were not significant for pooled meta-analyses. Conclusion: For association of APOA5 gene variations, genotype TT (61.1% cases, 69.9% controls) was protective against CVD for all populations combined (RR = 0.78, 0.74-0.83, p \u3c 0.0001). APOA5 is a key gene for triglyceride metabolism to reduce inflammation for epigenetics in the methylation pathways. Future studies are needed to examine epigenetic factors for population health associated with APOA5 gene variations in the prevention of CVD