Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Cholesteryl Ester Transfer Protein (CETP) Polymorphisms Affect mRNA Splicing, HDL Levels, and Sex-Dependent Cardiovascular Risk

Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5–7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4×10−5, allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8×10−10) and intron 8 polymorphism rs9930761-T>C (5.6×10−8) (in high linkage disequilibrium with allele frequencies 6–7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9

Prospect and potential of Burkholderia sp. against Phytophthora capsici Leonian: a causative agent for foot rot disease of black pepper

Foot rot disease is a very destructive disease in black pepper in Malaysia. It is caused by Phytophthora capsici Leonian, which is a soilborne pathogenic protist (phylum, Oomycota) that infects aerial and subterranean structures of many host plants. This pathogen is a polycyclic, such that multiple cycles of infection and inoculum production occur in a single growing season. It is more prevalent in the tropics because of the favourable environmental conditions. The utilization of plant growth-promoting rhizobacteria (PGPR) as a biological control agent has been successfully implemented in controlling many plant pathogens. Many studies on the exploration of beneficial organisms have been carried out such as Pseudomonas fluorescens, which is one of the best examples used for the control of Fusarium wilt in tomato. Similarly, P. fluorescens is found to be an effective biocontrol agent against the foot rot disease in black pepper. Nowadays there is tremendous novel increase in the species of Burkholderia with either mutualistic or antagonistic interactions in the environment. Burkholderia sp. is an indigenous PGPR capable of producing a large number of commercially important hydrolytic enzymes and bioactive substances that promote plant growth and health; are eco-friendly, biodegradable and specific in their actions; and have a broad spectrum of antimicrobial activity in keeping down the population of phytopathogens, thus playing a great role in promoting sustainable agriculture today. Hence, in this book chapter, the potential applications of Burkholderia sp. to control foot rot disease of black pepper in Malaysia, their control mechanisms, plant growth promotion, commercial potentials and the future prospects as indigenous PGPR were discussed in relation to sustainable agriculture

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Not AvailableAn in-vitro toxicity study was undertaken for the validation, laydown the standards, supplement some of the information on assessment and define the nature of toxicity of different solvent extracts of Terminalia arjuna considering Artemia salina model, as a case study. In the present study, experimental conditions such as yellow color light of 100 W at 5% salinity for 48 hours with pH 8.0-8.5 at 30 0C, picking up of nauplii with 3mL dropper cut at its tip, 24 hours incubation in same experimental conditions and visualization with 50X magnifying glass were modified unlike previous studies. Functional screening of solvent extracts with their mother solvents revealed that hex, Etac, Chlo, Acet, Etoh, and Meoh exhibited, the LC50 values as 118.50, 101.75, 93.36, 278.32, 528.78 and 477.67 ppm, respectively, designating them as; medium, medium, high, medium, low, medium toxic, while in their solvent extract forms the toxicity nature gets changed indicating the effectiveness of the extracts. Study, also defines the toxicity level for universal solvents such as DMSO and Dw as to be non-toxic as per the Meyers toxicity index and Clarkson’s toxicity criterion. Among solvent extracts of T. arjuna, all were found to be toxic as per Meyers toxicity index. However, with reference to Clarkson’s toxicity criterion, solvent extracts comprehended extended toxicity classes as low, medium and high toxic. The PCA 1 and 2 showed, 69.46% and 19.74% variations indicating strong correlation between the parameters. The results confirmed that LC50 of any solvent extract could be treated as relative LC50, which is the fraction of mother solvent and could be treated as absolute LC50, which is the actual potential of the solvent extracts that might be positive for less effective and negative for highly effective solvent extracts. For smoothening of experimental results, negative sign was ignored. Relative LC50, relative LC50%, absolute LC50, and absolute LC50% could find liner relation with their % fractions and inverse relation with their counterparts. Thus present study advocates the inclusion of relative LC50, relative LC50%, absolute LC50, absolute LC50%, considerating 95% upper and lower fiducial class intervals and TI values while fixing the nature of toxicity and designating the safety aspect to the host. Also, the study recommends for the collective effort to make BSLA as an internationally accepted and robust standard by revisiting and supplementing the existing toxicity criterion for the BSLANot Availabl

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Not AvailableAgarose gel electrophoresis is the most useful and revolutionary process for separating, analyzing, identifying, and purifying different DNA fragments (in shape or size) from any cell or organism. This process is an amalgamation of four associated techniques viz. gel casting, electrophoresis, staining, and imaging, which are consecutively accomplished to get desired results. Various types of commercialized/non-commercialized device and reagent kits are available with manufacturers to perform the associated techniques with simplicity. All these devices need secure space, separate operating procedures, and timely maintenance for the long run. In the absence of a low-cost integrated electrophoresis device that can be utilized for the complete gel electrophoresis process, untimely operational failure of any individual equipment affects the experiment. In this paper, we describe an integrated gel electrophoresis instrument, which provides all facilities for agarose gel casting, electrophoresis, staining, and imaging techniques without any exposure to harmful chemicals. Construction of this four-in-one instrument in the laboratory requires off-the-shelf and pre-existing components. Overall estimated cost is nearly US$ ∼222.00; and it can be assembled within 1 h, which makes it an inexpensive, user-friendly, and effortless system. It has proved to be advantageous for researchers working in wide varieties of laboratories on the evaluation of nucleic acids.Not Availabl

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Not AvailablePresent experiment was conducted to evaluate and establish the effects of processing/pretreatment on biochemical composition, mineral profiling and yield (%) of selected solvent extract of Terminalia arjuna (Arjuna). Analyses revealed that maximum yield (%) was ascertained in ethanolic bark extract for both fractions, individual (23.6±0.026%), and serial (22.23±0.017%). Non-significant difference (p≥0.05) was observed in yield of ethanolic and methanolic bark extracts while non-polar solvent extracts showed significant differences (p≤0.05). The mineral profiling revealed a wide variation among dry powder and their solvent extracts. After fractionation, the Zn content of fruit extracts increased and recorded highest to be in methanolic extract in the tune of 45.29 mg/l. The ash and moisture content established an inverse relationship for all solvent extracts. The maximum ash content was observed in arjuna bark powder 28.95±0.001% (serial) and 28.19±0.008 % (individual). The ash content does not follow the same pattern for mineral profiling ascribing more acid insoluble ash in bark followed by leaf and fruit which might be contributing towards bio-efficacy of the solvent extracts which can be depicted from present study that arjuna bark can be incorporated as ingredient for harnessing its bioactive properties and solvent extracts might be utilized for designing the drug. Thus, the present experiment showed a way to maximize the mineral profiling particularly Zn a potent neuro-transmitter which can be incorporated in developing the suitable feed for livestock’s and fisheries in one hand, and pave a way for mitigating the nervous disorders in human health is concernedNot Availabl