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The heparin-binding hemagglutinin protein of Mycobacterium tuberculosis is a nucleoid-associated protein
No full textNucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of ∼36% of total and ∼29% of essential genes. Deletion of hbhA resulted in the upregulation of ∼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor
Pricing and revenue management for bank home loans: a mathematical approach
No full textIn this study, we formulate both dynamic and static pricing models for home loans for a bank. These models optimize the net present value of money available at the end of 15 years, subject to pricing limits and cash flows. We collected actual data from a leading nationalized bank in India to develop a relationship between interest rate (price) and number of loans sanctioned (demand). We then assume different versions of the demand function (linear, exponential and rectangular hyperbola). We also develop the relationship of default probability as a function of interest rate. For the three demand functions, we evaluate the expected revenue at the end of the nth period for both static and dynamic pricing models for home loans and compare the results. We also discuss the sensitivity of the study result to changes in the parameters of the demand equations for dynamic pricing model
Multi-Scale Deep Supervised Attention Network for Red Lesion Segmentation
No full textDiabetic Retinopathy (DR) is one of the leading causes of blindness among the diabetic population. Early diagnosis of DR can prevent visual impairment and leads to the motivation of designing an automatic DR detection model. Non-proliferative Diabetic Retinopathy (NPDR) is detected by the formation of Red Lesions - MicroAneurysms and Hemorrhages. MicroAneurysms are minute in structure and need special care to be located. This paper targets the automatic detection of DR at the preliminary stage by implementing a modified Full-scale Deeply Supervised Attention Network (FuDSA-Net). The architecture encompasses a multi-scale feature-based attention module along with deep supervision to help achieve high-quality segmentation output. Experimental results suggest that the model with focal Tversky loss outperforms state-of-the-art architectures
Prosopis juliflora: invasive alien plant species derived biomass carbon and its application in hazardous NO<sub>2</sub> gas sensing
No full textThe conversion of hazardous bio-resources into valuable carbon materials is instrumental in sustainable material manufacturing and green electronics. The present work discourses the transformation of an invasive alien plant species (IAPS), Prosopis juliflora leaves, into a valuable biomass carbon. The characteristics and implications of Prosopis juliflora biomass carbon (PJBMC) are studied in detail. Further, biomass carbon nanocomposites are prepared by decorating SnO2 nanoparticles on the PJBMC, and it is evaluated for hazardous NO2 gas sensing applications. The PJBMC/SnO2 nanocomposite is assessed against varying concentrations of NO2 gas and shows a maximum sensitivity of 31.0 ± 0.9% for 90 ppm of the target gas. The uniform distribution of SnO2 nanoparticles on the biomass carbon support enabled the adsorption/desorption of target gas on the surface of the nanocomposite. The gas sensing mechanism of biomass nanocomposite material is discussed in detail, and a real-time NO2 gas leak detector with a warning LED system is demonstrated. In summary, this work reinforces sustainable growth by reporting the conversion and usage of IAPS Prosopis juliflora as one of the potential carbon materials in sensing applications
Docking experiments suggest that gloriosine has microtubule-targeting properties similar to colchicine
No full textGloriosine, the predominant metabolite of Gloriosa superba L., shares chemical properties with colchicine. We analyze the microtubule-binding affinity of gloriosine at the colchicine binding site (CBS) using an in silico-in vivo approach. The In silico docking of gloriosine showed a binding score of (−) 7.5 kcal/Mol towards β-tubulin at CBS and was validated by overlapping the coupling pose of the docked ligand with co-crystallized colchicine. 2D plots (Ligplot +) showed > 85% overlap between gloriosine and colchicine. The ADMET profile of gloriosine was in accordance with Lipinski’s rule of five. Gloriosine belongs to class II toxicity with anLD50 value of 6 mg/kg. In vivo and transmission electron microscopy studies revealed that gloriosine induces abnormalities in cell division such as condensed chromosomes in C-metaphase and enlarged nucleus with increased nuclear material. Gloriosine treated cells exhibited mitotic index of about 14% compared to control of 24% and high anti-proliferative activity i.e. 63.94% cell viability at a low concentration (0.0004 mg/ml). We conclude that gloriosine has a strong affinity for β-tubulin at CBS and thus can be used as a colchicine alternative in cytology and other clinical conditions
Different GCMs yet similar outcome: predicting the habitat distribution of Shorea robusta C.F. Gaertn. in the Indian Himalayas using CMIP5 and CMIP6 climate models
No full textClimate change impact on the habitat distribution of umbrella species presents a critical threat to the entire regional ecosystem. This is further perilous if the species is economically important. Sal (Shorea robusta C.F. Gaertn.), a climax forest forming Central Himalayan tree species, is one of the most valuable timber species and provides several ecological services. Sal forests are under threat due to over-exploitation, habitat destruction, and climate change. Sal’s poor natural regeneration and its unimodal density-diameter distribution in the region illustrate the peril to its habitat. We, modelled the current as well as future distribution of suitable sal habitats under different climate scenarios using 179 sal occurrence points and 8 bioclimatic environmental variables (non-collinear). The CMIP5-based RCP4.5 and CMIP6-based SSP245 climate models under 2041–2060 and 2061–2080 periods were used to predict the impact of climate change on sal’s future potential distribution area. The niche model results predict the mean annual temperature and precipitation seasonality as the most influential sal habitat governing variables in the region. The current high suitability region for sal was 4.36% of the total geographic area, which shows a drastic decline to 1.31% and 0.07% under SSP245 for 2041–60 and 2061–80, respectively. The RCP-based models predicted more severe impact than SSP; however, both RCP and SSP models showed complete loss of high suitability regions and overall shift of species northwards in the Uttarakhand state. We could identify the current and future suitable habitats for conserving sal population through assisted regeneration and management of other regional issues
Novel Pyrido[2′,1′:2,3]imidazo[4,5-<i>c</i>]quinoline Derivative Selectively Poisons <i>Leishmania donovani</i> Bisubunit Topoisomerase 1 to Inhibit the Antimony-Resistant <i>Leishmania</i> Infection <i>in Vivo</i>
No full textThe unique bisubunit structure of Leishmania donovani topoisomerase 1B (LdTop1) is a potential drug target in the parasites unlike the monomeric Top1 from its human host counterpart. Here, we report the design, synthesis, and validation of a chimeric pyrido[2',1':2,3]imidazo[4,5-c]quinoline derivative (C17) as a novel antileishmanial agent that poisons topoisomerase 1-DNA covalent complexes (LdTop1cc) inside the parasites and inhibits Top1 religation activity both in the drug sensitive and antimony-resistant L. donovani clinical isolates. Importantly, the human Top1 is not sensitive to C17. Further, C17 overcomes the chemical instability of camptothecin (CPT) by generating persistent LdTop1cc-induced DNA breaks inside the parasites even after 12 h of drug removal. Intraperitoneal administration of C17 results in marked reduction of the Leishmania amastigotes from the infected spleen and liver of BALB/c mice. C17 confers a host protective immune-response up-regulating the Th1 cytokines facilitating parasite clearance which can be exploited for treating drug-resistant leishmaniasis
Trends and Variability of PM2.5 at Different Time Scales over Delhi: Long-term Analysis 2007–2021
No full textThe present study investigated the long-term inter-annual, seasonal, and monthly trend analysis and variability of PM 2.5 on different times scales over the national capital, Delhi, India, using high-resolution surface observations from six stations during 2007–2021. The non-parametric Mann-Kendall and Theil-Sen slope estimator were used to study the temporal variations. The long-term PM 2.5 concentration showed an overall small but statistically significant decreasing trend with an average decrease of −1.35 (95% CI: −2.3, −0.47) µg m-3 year-1. Seasonal trends revealed a significant decreasing value of −3.05 µg m-3 year-1 (p < 0.1) for summer, an insignificant declining trend of −1.95 µg m-3 year-1 for monsoon. Similarly no significant trend detected for the post the post monsoon and winter season. Except for December and January, all months displayed a decreasing trend for PM2.5 concentration. These findings indicate that particle pollution over the city is declining at a very slow rate. A rising trend was found for relative humidity and surface pressure, whereas a declining trend for wind speed and PBLH was observed. No trend was observed for temperature and rainfall. The Pearson linear correlation between PM2.5 and meteorological variables was studied using monthly mean data. Rainfall, air temperature, PBLH, and wind speed showed a negative correlation with PM2.5, whereas surface pressure had a positive correlation and relative humidity displayed an inverted U-shape relationship. The average concentration of PM2.5 in the study period of 15 years remained 125 ± 86 µg m-3 (ranging between 20 to 985 µg m-3) and during winter, summer, monsoon, and post-monsoon seasons it was 174 ± 75, 101 ± 48, 66 ± 50, and 192 ± 93 µg m-3 respectively. Minimum of the monthly averaged PM2.5 concentration was observed in August, while maximum is November. Satellite data of fire events showed that the crop residue burning over the Punjab region had a significant contribution to the peak PM 2.5 levels in Delhi during the crop burning period. Government agencies need more strict action plans, especially during winter, to comply with air quality standards
Selective collection of Yb(III) over La(III) and Eu(III) from aqueous solution by bis(tetramethylammonium) salt crystals of p-tert-butylcalix[4]arene-1,3-diphosphonic acid
No full textUnprecedentedly, crystals of the bis(tetramethylammonium) salt of p-tert-butylcalix[4]arene-1,3-diphosphonic acid, having a preorganized hydrophilic guest recognition space sandwiched by hydrophobic host layers, have been prepared for the selective collection of Yb(III) from 0.01 M HCl solution under thermodynamic control
Type I strong acceptor–weak acceptor photosensitizing assemblies for the regulated aerobic oxidative coupling of anilines
No full textType I photostable photosensitizing assemblies of DPZ-TPY have been developed using phenazine as a strong acceptor and terpyridine groups as a weak acceptor. The as-prepared DPZ-TPY assemblies exhibit sufficient excited state potential to catalyse the synthesis of symmetrical azoaromatics through direct regulated oxidation of anilines in excellent yields (93%), without the formation of over-oxidized product. Consequently, DPZ-TPY assemblies also catalyse the formation of unsymmetrical azoaromatics starting from hydrazobenzenes under mild reaction conditions. The potential of DPZ-TPY assemblies to catalyse the gram-scale synthesis of azobenzene demonstrates their real-time application