High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea

This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties

T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.

HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations

Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats

<p>Abstract</p> <p>Background</p> <p>Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats.</p> <p>Methods</p> <p>Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-γ expression were examined by western blotting.</p> <p>Results</p> <p>Our data shows involvement of TNF-α in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-γ in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-γ directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications.</p> <p>Conclusion</p> <p>To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.</p

Cost-Effectiveness Analysis of Diagnostic Options for Pneumocystis Pneumonia (PCP)

Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90$189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68$109 per life-year gained) compared with several molecular diagnostic options.For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone

Decreased antibiotic susceptibility and enhanced probiotic production potential of goat milk fermented curd in comparison with cow and buffalo milk

The present study was carried out to characterize and compare the production potential and antibiotic susceptibility of probiotics isolated from goat, cow and buffalo milk. The probiotics isolated from milk fermented curd were compared with regard to their number, morphology, gram staining, motility, bile salt tolerance, pH-resistance, catalase activity, oxidase production and antibiotic resistance. We demonstrated that the probiotics isolated from milk fermented curd of all three species were gram positive, motile, catalase negative, and oxidase negative and were able to produce lactic acid. Further, we observed that buffalo milk is more potent in forming curd with the highest count of probiotics per ml (3.53 × 10!5) as compared to cow (5.8 × 10!6) and goat milk (7×10!7); moreover, goat milk bacterial isolates were more tolerant to acidic pH but were less bile-salt tolerant than cow milk. Also, probiotics isolated from goat milk curd were more resistant to antibiotics (resistant to 12 out of 15 screened antibiotics) than those from cow and buffalo milk (resistant to 8-9 antibiotics). This report shows that goat milk fermented products possess the highest antibacterial potential and are highly acid-tolerant

Emerging nano-strategies against tumour microenvironment (TME): a review

The non-cancerous cells and substances found in tumours, including the chemicals they create and release, are referred to as the tumour microenvironment. Carcinogenesis relies on the tumour microenvironment because it contains tumour cells that communicate with neighbouring cells via the circulatory and lymphatic systems. During all stages of carcinogenesis, non-malignant cells in the tumour microenvironment promote unchecked cell proliferation. Changes in the genetics and epigenetics of tumour cells and the rearrangement of TME components, which happen when these two things work together, affect the formation and growth of tumours. Tissue-specific exchanges between tumour cells and their surroundings are critical to understanding the underlying mechanism. With the tremendous advancements in nanomedicine, TME modulation has made significant strides lately. Drug distribution using nanotechnology has a number of benefits, including increased circulation time, cargo delivery to the appropriate location, enhanced bioavailability, reduced toxicity, etc. High interstitial pressure and dense stroma prevent the extravasation and uniform distribution of nanocarriers in TME, but leaky vasculature, acidic, and hypoxic circumstances of TME aid in the aggregation of customised nanoparticles. The goal of the review is to look into the idea of the tumour microenvironment by doing a critical analysis of past research. By briefly analysing stromal components, therapeutic opportunities, and limitations provided by TME for nanoparticulate drug delivery, this paper primarily analyses the potential of nanotherapeutics in targeting TME. Additionally, updated details on TME remodelling techniques for better drug delivery and precise targeting of particular stromal components are provided

Vermicomposting with microbial amendment: implications for bioremediation of industrial and agricultural waste

Improved agricultural practices and rapid industrialization have led to huge waste generation, and the management of this waste is becoming a global concern. The process of vermicomposting has emerged as a method of choice for converting waste into useful manure, with evidence of increase in crop productivity. During vermicomposting, the collective activities of decomposing microorganisms and earthworms lead to the humification of organic/inorganic waste, thereby generating the final product called vermicompost. Different types of industrial wastes such as waste from paper industries, tanneries, sugar mills, and pulp and textile industries have been effectively converted to vermicompost and successfully used to improve plant growth. The vermicompost thus formed was also demonstrated to increase the production of pharmaceutically important plant secondary metabolites such as withanolides and polyunsaturated fatty acids. Microbial amendment with different bacterial and fungal strains during vermicomposting further proves to be beneficial by increasing nitrogen content, decomposing organic waste, providing aeration, and stabilizing the vermicompost. These microorganisms after passing through the earthworm’s intestine increase in numbers in the vermicast, thus becoming enriched in vermicompost, which is particularly important for their use as biofertilizers. The precise role of different microbial pretreatments in improving the quality of vermicompost generated from industrial and agricultural waste is, however, not completely understood. To fill this gap in knowledge, the present article aims to review published literature to highlight the potential of microbial amendment during vermicomposting for bioremediation of industrial and agricultural waste. Microbial pre-composting followed by vermicomposting emerges as an ecofriendly and economical approach for managing agricultural and industrial waste

PPAR gamma agonistic activity of dillapiole: protective effects against diabetic nephropathy

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.</p