Natural treasures from Picrorhiza kurrooa: a computational exploration of drug-like properties and bioactivity of kutkin, cucurbitacin, apocynin and lupanine

Background: To analyse and predict the basic pharmacokinetic and toxicological properties of four compounds of interest found in Picrorhiza kurroa (Kutkin, cucurbitacin, apocynin and lupanine) using computational bioinformatics tools. Methods: The chemical structures and molecular properties of the compounds were obtained from authentic sources and processed for data profiling. 2D structures were converted to 3D structures using ChemSketch software and PHASE module. In silico screening of the 3D structures was performed using bioinformatics prediction software to assess drug-likeness, absorption, blood-brain barrier penetration, enzyme interaction potential, skin penetration, and acute oral toxicity. Results: Kutkin exhibited poor drug-likeness and low oral absorption, while the other three compounds showed promising drug-like properties and good oral absorption. Cucurbitacin and lupanine were predicted to cross the blood-brain barrier, while Kutkin and Apocynin were not. None of the compounds were substrates for P-glycoprotein, but Kutkin and cucurbitacin were substrates for CYP3A4. All four compounds had low skin penetration. Acute oral toxicity varied, with cucurbitacin classified as highly toxic and the others as slightly toxic. Conclusions: Cucurbitacin, apocynin, and lupanine have potential for further development as therapeutic agents due to their favorable drug-like properties and good absorption. Kutkin's poor drug-likeness and low absorption make it less suitable for oral drug development. This information provides valuable insights for further research on the medicinal properties of Picrorhiza kurroa and the development of new drugs based on its active compounds

ETMS: Efficient Traffic Management System for Congestion Detection and Alert using HAAR Cascade

Rapid social development has resulted in the emergence of a new major societal issue: urban traffic congestion, which many cities must address. In addition to making  it more difficult for people to get around town, traffic jams are a major source of the city's pollution crisis. In order to address the problems of automobile exhaust pollution and congestion, this paper uses the system dynamics approach to develop a model to study the urban traffic congestion system from the perspectives of trucks,private cars, bikes and public transportation. This project proposes a system for detecting vehicles and sending alerts when traffic levels rise to dangerous levels using Haar Cascade and Fuzzy Cognitive Maps (FCP). The proposed system uses Haar Cascade to detect moving vehicles, which are then classified using FCP. The system can make decisions based on partial or ambiguous information by utilising FCP, a soft computing technique, which allows it to learn from past actions. An algorithm for estimating traffic density is also used by the system to pinpoint active areas. In congested areas, the system will alert the driver if it anticipates a collision with another vehicle and also Experiments show that the proposed system is able to accurately detect vehicles and provide timely alerts to the driver, drastically lowering the probability of accidents occurring in heavily travelled areas. The importance of introducing such a system cannot be overstated in today's transportation system. It's a big deal for the future of intelligent urban planning and traffic control. Congestion relief, cleaner air, and increased security are just some of the long-term benefits that justify the high initial investment. To add, this system is adaptable to suburban and rural areas, which can also experience traffic congestion issues

Insilico analysis of Arabidopsis ferric reductase oxidases (FRO) proteins associated with iron homeostasis

The ferric reduction oxidase (FRO) gene family is involved in various biological processes of plants and plays an essential role in metal homeostasis, tolerance, and signaling networks in response to several abiotic stresses. Our study describes the structural, functional characterization, and evolutionary relationships of eight Arabidopsis FRO proteins. The studies predicted the subcellular localization of FRO proteins to the plasma membrane, mitochondria, and chloroplast organelles. The structural analysis revealed localization of proteins onto the first and fifth chromosomes having 8-9exons and 8-10 transmembrane helices. The protein features of FRO proteins revealed 699-747 amino acids having 79600.02-84126.3 (Da) molecular weight. The six highly conserved protein motifs were predicted with 45-50 amino acids long representing ferric chelate reductase family domains. The phylogeny tree constructed using Clustal W divided the FRO proteins into two clusters and the interactome network revealed the co-expression of COPT1, NRAMP1, NRAMP3, NRAMP4, FRD3, OPT3, IRT1, IRT2, ZIF1, PYE proteins along with the seven FRO proteins

Structure-function relationships among selected human coronaviruses

536-551Identifying the key proteins among different types of human disease-causing coronaviruses is essential for the molecular mechanism and thereby designing potential drug molecules. Eight selected proteins of seven types of disease-causing coronaviruses, viz.SARS-CoV-2 (severe acute respiratory syndrome coronavirus2), SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (middle east respiratory syndrome coronavirus), Human coronavirus OC43, Human coronavirus HKU1, Human coronavirus 229E and Human coronavirus NL63, were chosen for the comparison. Further, an attempt has been made to explore the most important host-pathogen interactions with a special focus on spike (RBD) protein region as this region deemed to be functionally most important. Epitope region was also identified which helps in the design of epitope-based vaccines. The structural comparison carried out among the seven types of human coronaviruses has revealed the molecular level details on the similarity among this series. This study has facilitated the identification of the important residues in the studied proteins which control the key functions such as viral replication and transmission. Thus, exploring the protein space in the family of coronaviruses, provide valuable insights into the molecular basis associated with the role of proteins and viral infections, which is expected to trigger the identification of the drug targets for coronaviruses infections, in a rational way

ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype

Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders

IMPACT OF OZONE CONCENTRATION ON OCEAN COLOUR RETRIEVALS FOR OCM-2

Ozone being an absorbing gas have a significant impact on OCM-2 bands 510 nm, 555 nm and 620 nm which are using for retrieval of major geophysical parameters like Chlorophyll and suspended sediment concentrations. A study has been carried out to analyse the impact of Ozone concentration by ingesting near real time from OMI (Ozone Monitoring Instrument) on Aura instead of Climatology V2013 (2004–13) with a resolution of 1 × 1 deg for ocean colour retrievals from OCM-2 sensor using SeaWiFS Data Analysis System (SeaDAS). The spectral behaviour of Ozone transmittance has been studied for various bands of OCM-2 by using both Climatology and near real time inputs. We could observe maximum relative error percentage about 12 % from Climatology to NRT in Ozone concentration and 0.28 %, 0.66 % and 0.72 % of maximum mean relative error in ozone transmittance at 512 nm, 557 nm and 620 nm. We calculated error budgets induced by ozone in remote sensing reflectance(/sr) where in we could observe mean relative error percentage of 0.52 % in 491 nm, 1.12 % in 512 nm and 4.28 % 557 nm a bands respectively

BAFopathies\u27 DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening

Etiology of Diarrhea in Older Children, Adolescents and Adults: A Systematic Review

Diarrhea is an important cause of illness and death around the world and among people of all ages, but unfortunately we often do not know what specific bacterium or virus causes the illness. We conducted a review of the scientific literature with the goal of finding published studies that identified bacteria and viruses among patients with diarrhea in the community and in hospital settings. We initially found nearly 26,000 papers on this topic but narrowed the list to 22 studies that met all of our specific criteria for inclusion in our review. Among patients hospitalized for diarrhea, E coli and Vibrio cholerae were found in more than 49% of people living in middle income and poor countries. Among patients who sought care from their doctor on an outpatient basis, Salmonella spp., Shigella spp., and E. histolytica were most often found. In our review we focused on the differences in the distribution of pathogens between patients in inpatient vs. outpatient settings because these estimates may best approximate what we would expect to see if the distribution were applied to global estimates of diarrhea deaths vs. uncomplicated illnesses