Human coronary heart disease: importance of blood cellular miR-2909 RNomics

The characterization of atherosclerosis as a chronic inflammatory disease has triggered extensive research worldwide to dissect the pro- and anti-inflammatory, cellular as well as molecular mechanisms governing the pathogenesis of this dreadful disease. Though several microRNAs have been shown to play crucial role in regulating lipid metabolism and inflammation, we are far from resolving the role of epigenomic signals in etiology of coronary heart disease (CHD). The present study was addressed to understand the role of a novel microRNA, miR-2909, in the regulation of genes involved in the initiation and progression of human coronary occlusion. Peripheral blood mononuclear cells were isolated from human CHD subjects at various stages of coronary occlusion (n = 80) and their corresponding normal healthy counterparts (n = 20). Various experimental strategies involving gene expression and silencing, reporter plasmid assays, and flow cytometric analysis were blend together to address the current problem. The present study shows for the first time that the blood cellular miR-2909 expression increases with the severity of coronary occlusion, exhibiting a strong positive correlation (r = 0.943 at p < 0.01). Further, miR-2909 was shown to regulate genes involved in inflammation, immunity, and oxLDL uptake, thereby contributing significantly to the initiation and progression of CHD patho-physiological process. Based upon these results, we propose that miR-2909 RNomics may be a step forward in understanding human CHD at the epigenomic level and can be exploited for designing new therapeutic strategies as well as diagnostic and prognostic markers for this disease in future.     

Polymorphism of cytokine and innate immunity genes associated with bovine brucellosis in cattle

Genetic susceptibility to brucellosis is multifactorial, and it is known that impairment of the immune system could contribute to risk for getting brucellosis. The aim of the study was to find association of bovine brucellosis with 20 SNPs pertaining to bovine cytokine (IFNG, IFNGR1, IFNGR2, TNFA) and innate immunity (SLC11A1, TLR1, TLR4, and TLR9) genes using PCR-RFLP genotyping technique and it was observed that SLC11A1 (+1066 C/G), TLR1 (+1446 C/A), TLR1 (+1380 G/A), TLR4 (+10 C/T) and TLR4 (+399 C/T) loci were significantly (P ≤ 0.05) associated with bovine brucellosis. The odds ratios (OR) of CG and CC genotypes versus GG genotype were 0.31 (0.12–0.82; 95 % CI) and 0.18 (0.03–1.06; 95 % CI) at SLC11A1 (+1066 C/G) locus in cases of brucellosis affected cattle. For TLR1 (+1380 G/A) locus, the OR for AG and AA genotypes versus GG genotypes were 0.15 (0.05–0.44; 95 % CI) and 0.26 (0.04–1.47; 95 % CI) which indicated that proportion of GG homozygote was significantly higher in brucellosis affected animals as compared to control. At TLR1 (+1446 C/A) locus the OR of AC genotype versus CC genotype was 0.24 (0.08–0.68; 95 % CI) which revealed that relative proportion CC genotypes was significantly higher in case population. The TLR4 (+10 C/T) locus had three genotypes (TT, CT and CC) where OR of CT and CC genotypes versus TT genotype were near to zero. The OR of CT genotypes versus CC genotypes was 8.25 (0.94–71.92; 95 % CI) at TLR4 (+399 C/T) locus and indicated that CT genotype had higher odds of bovine brucellosis than control animals.     

Carbon nanotubes leading the way forward in new generation 3D tissue engineering

Statistics from the NHS Blood and Transplant Annual Review show that total organ transplants have increased to 4213 in 2012, while the number of people waiting to receive an organ rose to 7613 that same year. Human donors as the origin of transplanted organs no longer meet the ever-increasing demand, and so interest has shifted to synthetic organ genesis as a form of supply. This focus has given rise to new generation tissue and organ engineering, in the hope of one day designing 3D organs in vitro. While research in this field has been conducted for several decades, leading to the first synthetic trachea transplant in 2011, scaffold design for optimising complex tissue growth is still underexplored and underdeveloped. This is mostly the result of the complexity required in scaffolds, as they need to mimic the cells’ native extracellular matrix. This is an intricate nanostructured environment that provides cells with physical and chemical stimuli for optimum cell attachment, proliferation and differentiation. Carbon nanotubes are a popular addition to synthetic scaffolds and have already begun to revolutionise regenerative medicine. Discovered in 1991, these are traditionally used in various areas of engineering and technology; however, due to their excellent mechanical, chemical and electrical properties their potential is now being explored in areas of drug delivery, in vivo biosensor application and tissue engineering. The incorporation of CNTs into polymer scaffolds displays a variety of structural and chemical enhancements, some of which include: increased scaffold strength and flexibility, improved biocompatibility, reduction in cancerous cell division, induction of angiogenesis, reduced thrombosis, and manipulation of gene expression in developing cells. Moreover CNTs’ tensile properties open doors for dynamic scaffold design, while their thermal and electrical properties provide opportunities for the development of neural, bone and cardiac tissue constructs.     

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.     

A Coarray Fortran implementation to support data-intensive application development

In this paper, we describe our experiences in implementing and applying Coarray Fortran (CAF) for the development of data-intensive applications in the domain of Oil and Gas exploration. The successful porting of reverse time migration (RTM), a data-intensive algorithm and one of the largest uses of computational resources in seismic exploration, is described, and results are presented demonstrating that the CAF implementation provides comparable performance to an equivalent MPI version. We then discuss further language extensions for supporting scalable parallel I/O operating on the massive data sets that are typical of applications used in seismic exploration.     

Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme

A series of 1,2,3-trisubstituted indolizines (2a–2f, 3a–3d, and 4a–4c) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b–2d, 3a–3d, and 4a–4c were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines 4a–4c, with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16–64 µg/mL). In silico docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound 4b was also carried out. Further, a safety study (in silico and in vitro) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.     

Identification of Novel Regulatory Small RNAs in Acinetobacter baumannii

Small RNA (sRNA) molecules are non-coding RNAs that have been implicated in regulation of various cellular processes in living systems, allowing them to adapt to changing environmental conditions. Till date, sRNAs have not been reported in Acinetobacter baumannii (A. baumannii), which has emerged as a significant multiple drug resistant nosocomial pathogen. In the present study, a combination of bioinformatic and experimental approach was used for identification of novel sRNAs. A total of 31 putative sRNAs were predicted by a combination of two algorithms, sRNAPredict and QRNA. Initially 10 sRNAs were chosen on the basis of lower E- value and three sRNAs (designated as AbsR11, 25 and 28) showed positive signal on Northern blot. These sRNAs are novel in nature as they do not have homologous sequences in other bacterial species. Expression of the three sRNAs was examined in various phases of bacterial growth. Further, the effect of various stress conditions on sRNA gene expression was determined. A detailed investigation revealed differential expression profile of AbsR25 in presence of varying amounts of ethidium bromide (EtBr), suggesting that its expression is influenced by environmental or internal signals such as stress response. A decrease in expression of AbsR25 and concomitant increase in the expression of bioinformatically predicted targets in presence of high EtBr was reverberated by the decrease in target gene expression when AbsR25 was overexpressed. This hints at the negative regulation of target genes by AbsR25. Interestingly, the putative targets include transporter genes and the degree of variation in expression of one of them (A1S_1331) suggests that AbsR25 is involved in regulation of a transporter. This study provides a perspective for future studies of sRNAs and their possible involvement in regulation of antibiotic resistance in bacteria specifically in cryptic A. baumannii.