TLR2 polymorphisms, Arg753Gln and Arg677Trp, are not associated with increased burden of tuberculosis in Indian patients

<p>Abstract</p> <p>Background</p> <p>In view of the role of TLR2 activation in host defense against mycobacteria, the present study was conducted to examine whether TLR2 polymorphisms could account for the increased prevalence of tuberculosis in Indian patients. Detection of such polymorphisms would help in assessing the risk of developing active tuberculosis among contacts or HIV positive patients and in identifying candidates for chemoprophylaxis.</p> <p>Findings</p> <p>One hundred patients with tuberculosis and 100 controls were investigated for the presence of two TLR2 polymorphisms, viz. Arg753Gln and Arg677Trp, using PCR-RFLP of a 340 bp region of the TLR2 gene, followed by DNA sequencing of a randomly selected group of 35 patients. While these polymorphisms were found to be non-existent in our study groups, we observed a novel polymorphism Phe749Tyr in 2 patients. However, this polymorphism was associated with negligible deviation in Delphi electrostatic potential and structural alignment from the wild-type TLR2 protein, making it an unlikely candidate for any significant structural or functional alteration at the protein level.</p> <p>Conclusion</p> <p>Hence we conclude that, contrary to reported associations in other populations, TLR2 polymorphisms are not responsible for the increased prevalence of TB in the Indian population.</p

Resonant Raman of OH/OD vibrations and photoluminescence studies in LiTaO3 thin film

Resonant Raman spectra (RRS) of O-H and O-D vibration and libration modes, their combinations and higher harmonics have been observed in LiTaO3 polycrystalline thin films. RRS peaks are superimposed on photoluminescence (PL) spectrum. Monochromatic light from a xenon lamp is used as excitation source. PL spectrum shows two broad peaks, first near the band gap in UV (4.4-4.8eV) and another in the sub band gap region (< 4.0 eV). Band gap PL along with RRS peaks are reported for the first time. Photoluminescence excitation spectrum (PLE) shows a peak at 4.8 eV. Peak positions and full width at half maximum (FWHM) of RRS peaks depend upon the excitation energy. Dispersions of the fundamental and the third harmonic of the stretching mode of O-H with excitation energy are about 800 cm-1/eV and 2000 cm-1/eV respectively. This dispersion is much higher than reported in any other material.Comment: 20 page

DETERMINATION OF TRAZODONE IN HUMAN PLASMA BY REVERSED-PHASE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY WITH ELECTROSPRAY IONISATION

Objective: The development and validation of LC-MS/MS method for quantification of Trazodone (a serotonin antagonist and reuptake inhibitor (SARI), which is a second generation antidepressant compound belonging to the class of phenyl piperazine) in human plasma is described. Methods: The method involves protein precipitation (extraction) using Trazodone d6 as an internal standard (IS). Chromatographic separation is achieved on Zorbax eclipse XDB C8 150×4.6 mm, 5 μm column with a mobile phase consisting of 2 mM ammonium formate (pH 3.0) and methanol (30:70 v/v) at a flow rate of 1.0 mL / min and the total run time was 2.5 minute. Detection was carried out by AB Sciex API 3200 tandem mass spectrometer using positive electro-spray ionization mode by multiple reactions monitoring method at m/z 372.00→176.10 and 378.20→182.10 for Trazodone and Trazodone d6 (ISTD) respectively with dwell times of 300 msecs for each of the transitions. Results: The standard curve was linear from 5.203 ng / mL to 3025.166 ng / mL with goodness of fit (r2) greater than 0.990 observed during the method validation batches. This assay allows quantification of Trazodone at a concentration as low as 5 ng / mL in human plasma. The observed mean recovery was 88% for the drug. Conclusions: The method described here is found to be simple, cost effective and suitable for the use in bioequivalence and bioavailability studies

Nanoparticles in the environment: assessment using the causal diagram approach

Nanoparticles (NPs) cause concern for health and safety as their impact on the environment and humans is not known. Relatively few studies have investigated the toxicological and environmental effects of exposure to naturally occurring NPs (NNPs) and man-made or engineered NPs (ENPs) that are known to have a wide variety of effects once taken up into an organism

Trends in Molecular Aspects and Therapeutic Applications of Drug Repurposing for Infectious Diseases

The pharmaceutical industry has undergone a severe economic crunch in antibiotic discovery research due to evolving bacterial resistance along with enormous time and money that gets consumed in de novo drug design and discovery strategies. Nevertheless, drug repurposing has evolved as an economically safer and excellent alternative strategy to identify approved drugs for new therapeutic indications. Virtual high throughput screening (vHTS) and phenotype-based high throughput screening (HTS) of approved molecules play a crucial role in identifying, developing, and repurposing old drug molecules into anti-infective agents either alone or in synergistic combination with antibiotic therapy. This chapter briefly explains the process of drug repurposing/repositioning in comparison to de novo methods utilizing vHTS and HTS technologies along with ‘omics- and poly-pharmacology-based drug repurposing strategies in the identification and development of anti-microbial agents. This chapter also gives an insightful survey of the intellectual property landscape on drug repurposing. Further, the challenges and applications of drug repurposing strategies in the discovery of anti-infective drugs are exemplified. The future perspectives of drug repurposing in the context of anti-infective agents are also discussed

Dynamics of learning motives and barriers in the context of changing human life roles

This paper promotes a theoretical discussion that focuses on the motives and barriers that make impact on adults learning as well as on their dynamics related to the change of social roles. The adult learning motives and barriers change and vary according to the prevailing social roles at different periods of one’s life. This dynamics of adult learning motives and barriers is mostly influenced by the importance and compatibility of acquired social roles, responsibility areas and spaces of a person and other factors. The qualitative data was gathered in March – April 2016 in Kaunas, Lithuania. The sample consisted of 30 narratives, written by informants, aged 35 to 65 years that were participating in professional training courses. There has been prepared 30 self-reflections that were analysed using content analysis. The analysis of empirical data shows that external learning motives and barriers prevail in the period when an individual is active in the labour market while the personal motives remain overshadowed. However, personal barriers prevail in the expression of learning barriers. This is influenced by the society’s attitude towards the performance of pupil and student roles and the value attitudes of surrounding people that partially control it

Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures

Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly aggressive bladder and breast tumors, and use network analysis methods to identify the tumor type-specific core of the network. By combining logic-based network modeling, in vitro experimentation, and gene expression profiles from patient cohorts displaying tumor aggressiveness, we identify and experimentally validate distinctive, tumor type-specific signatures of receptor proteins associated to epithelial-mesenchymal transition in bladder and breast cancer. Our integrative network-based methodology, exemplified in the case of E2F1-induced aggressive tumors, has the potential to support the design of cohort- as well as tumor type-specific treatments and ultimately, to fight metastasis and therapy resistance

Development of SSR markers and construction of a linkage map in jute

Jute is an important natural fibre crop, which is only second to cotton in its importance at the global level. It is mostly grown in Indian subcontinent and has been recently used for the development of genomics resources. We recently initiated a programme to develop simple sequence repeat markers and reported a set of 2469 SSR that were developed using four SSR-enriched libraries (Mir et al. 2009). In this communication, we report an additional set of 607 novel SSR in 393 SSR containing sequences. However, primers could be designed for only 417 potentially useful SSR. Polymorphism survey was carried out for 374 primer pairs using two parental genotypes (JRO 524 and PPO4) of a mapping population developed for fibre fineness; only 66 SSR were polymorphic. Owing to a low level of polymorphism between the parental genotypes and a high degree of segregation distortion in recombinant inbred lines, genotypic data of only 53 polymorphic SSR on the mapping population consisting of 120 RIL could be used for the construction of a linkage map; 36 SSR loci were mapped on six linkage groups that covered a total genetic distance of 784.3 cM. Hopefully, this map will be enriched with more SSR loci in future and will prove useful for identification of quantitative trait loci/genes for molecular breeding involving improvement of fibre fineness and other related traits in jute

An integrative network-driven pipeline for systematic identification of lncRNA-associated regulatory network motifs in metastatic melanoma

CITATION: Singh, N., et al. 2020. An integrative network-driven pipeline for systematic identification of lncRNA-associated regulatory network motifs in metastatic melanoma. BMC Bioinformatics, 21:329, doi:10.1186/s12859-020-03656-6.The original publication is available at https://bmcbioinformatics.biomedcentral.comBackground: Melanoma phenotype and the dynamics underlying its progression are determined by a complex interplay between different types of regulatory molecules. In particular, transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) interact in layers that coalesce into large molecular interaction networks. Our goal here is to study molecules associated with the cross-talk between various network layers, and their impact on tumor progression. Results: To elucidate their contribution to disease, we developed an integrative computational pipeline to construct and analyze a melanoma network focusing on lncRNAs, their miRNA and protein targets, miRNA target genes, and TFs regulating miRNAs. In the network, we identified three-node regulatory loops each composed of lncRNA, miRNA, and TF. To prioritize these motifs for their role in melanoma progression, we integrated patient-derived RNAseq dataset from TCGA (SKCM) melanoma cohort, using a weighted multi-objective function. We investigated the expression profile of the top-ranked motifs and used them to classify patients into metastatic and non-metastatic phenotypes. Conclusions: The results of this study showed that network motif UCA1/AKT1/hsamiR- 125b-1 has the highest prediction accuracy (ACC = 0.88) for discriminating metastatic and non-metastatic melanoma phenotypes. The observation is also confirmed by the progression-free survival analysis where the patient group characterized by the metastatic-type expression profile of the motif suffers a significant reduction in survival. The finding suggests a prognostic value of network motifs for the classification and treatment of melanoma.https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-020-03656-6Publisher's versio

Novel 4-Thiazolidinone Derivatives as Anti-Infective Agents: Synthesis, Characterization, and Antimicrobial Evaluation

A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also determined and were found to be in the range of 100–400 µg/mL. All the compounds showed moderate-to-good antimicrobial activity. Compounds 4a [2-(4-fluoro-phenyl)-3-(4-methyl-5,6,7,8-tetrahydro-quinazolin-2-yl)-thiazolidin-4-one] and 4e [3-(4,6-dimethyl-pyrimidin-2-yl)-2-(2-methoxy-phenyl)-thiazolidin-4-one] were the most potent compounds of the series, exhibiting marked antimicrobial activity against Pseudomonas fluorescens, Staphylococcus aureus, and the fungal strains. Thus, on the basis of results obtained, it may be concluded that synthesized compounds exhibit a broad spectrum of antimicrobial activity