A Comparative Study on Class Characteristics of Devanãgri Script Writers from Three Different States of India

India is a multilingual country. Hindi is the national language of India and Devanãgri script is used to write Hindi language. Various documents with legal value are made in Devanãgri script, which may be questioned for their authenticity and authorship. Sufficient research has been done and reported about different scripts. However, researches based on Devanãgri script are limited. This study focuses on finding the significant class characteristics of writers from three different states of India, namely, Bihar, Madhya Pradesh and Punjab. The data was also statistically analysed using Pearson’s Chi-Square test for its significance. Handwriting samples from 300 subjects were collected from three different states of India to analyze various class characteristics in Devanãgri script. The samples were examined qualitatively and statistically. Various general characteristics were selected for the analysis and characteristic features were tabulated after qualitative examination. Statistical analysis showed that the data was statistically significant. The general characteristics selected for the analysis and comparison of the handwriting samples in Devanãgri script were found to be significant. The impact of regional scripts on the Devanãgri script should be performed, as the influence of regional language could be seen in the samples collected from Punjab

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients

T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.Fil: Saini, Sunil Kumar. Technical University of Denmark; DinamarcaFil: Hersby, Ditte Stampe. Copenhagen University Hospital; DinamarcaFil: Tamhane, Tripti. Technical University of Denmark; DinamarcaFil: Povlsen, Helle Rus. Technical University of Denmark; DinamarcaFil: Amaya Hernandez, Susana Patricia. Technical University of Denmark; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Gang, Anne Ortved. Copenhagen University Hospital; DinamarcaFil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarc

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen

A Sugarcane G-Protein-Coupled Receptor, ShGPCR1, Confers Tolerance to Multiple Abiotic Stresses

Sugarcane (Saccharum spp.) is a prominent source of sugar and serves as bioenergy/biomass feedstock globally. Multiple biotic and abiotic stresses, including drought, salinity, and cold, adversely affect sugarcane yield. G-protein-coupled receptors (GPCRs) are components of G-protein-mediated signaling affecting plant growth, development, and stress responses. Here, we identified a GPCR-like protein (ShGPCR1) from sugarcane and energy cane (Saccharum spp. hybrids) and characterized its function in conferring tolerance to multiple abiotic stresses. ShGPCR1 protein sequence contained nine predicted transmembrane (TM) domains connected by four extracellular and four intracellular loops, which could interact with various ligands and heterotrimeric G proteins in the cells. ShGPCR1 sequence displayed other signature features of a GPCR, such as a putative guanidine triphosphate (GTP)-binding domain, as well as multiple myristoylation and protein phosphorylation sites, presumably important for its biochemical function. Expression of ShGPCR1 was upregulated by drought, salinity, and cold stresses. Subcellular imaging and calcium (Ca2+) measurements revealed that ShGPCR1 predominantly localized to the plasma membrane and enhanced intracellular Ca2+ levels in response to GTP, respectively. Furthermore, constitutive overexpression of ShGPCR1 in sugarcane conferred tolerance to the three stressors. The stress-tolerance phenotype of the transgenic lines corresponded with activation of multiple drought-, salinity-, and cold-stress marker genes, such as Saccharum spp. LATE EMBRYOGENESIS ABUNDANT, DEHYDRIN, DROUGHT RESPONSIVE 4, GALACTINOL SYNTHASE, ETHYLENE RESPONSIVE FACTOR 3, SALT OVERLY SENSITIVE 1, VACUOLAR Na+/H+ ANTIPORTER 1, NAM/ATAF1/2/CUC2, COLD RESPONSIVE FACTOR 2, and ALCOHOL DEHYDROGENASE 3. We suggest that ShGPCR1 plays a key role in conferring tolerance to multiple abiotic stresses, and the engineered lines may be useful to enhance sugarcane production in marginal environments with fewer resources

Deciphering the Role of Intracellular Acidic Organelles in the Gastrointestinal System

Chapter 2: In this chapter, we have provided an update on the emerging role of ion channels in gastric acid secretion, emphasizing the modulation of cellular processes by transmembrane proteins and intracellular factors. It specifically focuses on the potential structural and functional role of transmembrane proteins present on the specialized cytoplasmic organelle called ‘tubulovesicle’ and their involvement in the signaling cascade of gastric acid secretion. Chapter 3: In this chapter, we have explored a new form of autophagy, ‘Xenophagy,’ triggered by the invasion of intracellular pathogen. Xenophagy plays a crucial role in maintaining the gastrointestinal (GI) system and clearance of the virulent invading pathogen. We found a possible underlying mechanistic link of induction of xenophagy caused by an imbalance of gut microbes, mainly focused on commensal bacteria Escherichia coli (E. coli). Chapter 4: In this chapter, we have investigated the impact of naturally occurring anthocyanin on gastric xenophagy. Our study found that It triggers the cell defense pathway via potntiation of lysosome biogenesis, further boosting xenophagy. Taken together, this thesis work proves an overview on how cellular signaling pathways, including organelles such as In summary, our results suggest that targeting lysosomal biogenesis and autophagic pathways could serve as a novel therapeutic strategy to treat diseases and disorders caused by invading pathogens via GI track and how naturally occurring, the anti-oxidant rich compound can effectively boost the cell defense mechanism and helps the cells to fight against the odds

Waste Tea Leaves as an Adsorbent for the Removal of Heavy Metal Ions from Aqueous Solutions: Quantitative Estimation using Spectrophotometry and Titrimetry

The rapid increase in industrialization and globalization in the last few decades has led to increased disposal of heavy metals in the environment leading to severe water and soil contamination. Among all known pollutants, heavy metals are especially notorious due to their high toxicity, persistent and bioaccumulative nature. Heavy metal toxicity is a major threat and therefore its removal and remediation require special attention to protect human, animal and plant health and to restore soil and water quality. Waste tea leaves (Camellia sinensis) are low-cost adsorbents and their use for the removal of heavy metal ions is likely to address the problems of waste management and heavy metal ion toxicity. In the present study, we have tested the efficacy of waste tea leaves for the quantitative removal of heavy metal ions like Ni(II) and Pb(II) from their aqueous test solutions using spectrophotometric and titrimetric methods respectively. With 5 g tea leaves in the Ni(II) solution, the removal percentage of the ion was found to be 85.56%. From a Pb(II) containing test solution, 286 ppm of the ion was adsorbed by the same amount of tea leaves. The amount of adsorbent dose was found to be directly related to the removal percentage of the metal ion. However, after reaching a threshold, increasing the adsorbent dose has only a negligible effect on adsorption. The adsorption was found to be primarily physisorption and follows Freundlich's adsorption isotherm. The zero-cost and easy availability of waste tea leaves make it a substrate of interest that can be used for the cost-effective removal of heavy metal ions from water and soil.</jats:p

Comparison of the effect of I.V nalbuphine and fentanyl as premedicant in general anaesthesia for laparoscopic surgeries

Introduction: Laparoscopic surgeries are minimally invasive surgeries with reduced mortality and morbidity, minimal postoperative analgesic requirement and early mobilisation. To prevent hemodynamic response to laryngoscopy, intubation and pneumoperitoneum various drugs are used. Opioids are commonly used in premedication, being a good analgesic, to support analgesia during surgery and to provide pain relief in immediate postoperative period. Among opioids, Fentanyl and Nalbuphine effectively control the hemodynamic stress response associated with laparoscopic surgeries, especially after laryngoscopy, intubation and pneumoperitoneum. In our study, we observed and compared the potency of opioids- Fentanyl &amp; Nalbuphine used as premedicant for attenuation of hemodynamic response in laparoscopic surgeries and postoperative complications if any. Objectives: The present study was designed to compare the effect of intravenous Nalbuphine and Fentanyl as premedicant in general anaesthesia for laparoscopic surgeries. Material and Methods: After institutional ethics committee approval, the study in 60 patients belonging to ASA 1 &amp; 2 undergoing laparoscopic surgeries like appendectomy, cholecystectomyetc. whose duration was assumed to be &lt;90 min under general anaesthesia was conducted. Pre-anaesthetic assessment of the patient was done with a complete history, physical examination and routine investigations and informed written consent was obtained. Eligible patients who gave consent were kept nil orally for at least 6 hours before surgery. Pulse Rate(PR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure(DBP), Mean Arterial Pressure (MAP), Oxygen Saturation (SpO2) was recorded at baseline, after giving study drug, immediately after laryngoscopy and tracheal intubation, thereafter at 10 minutes interval intraoperatively, post extubation at 1,3 and 5 minutes. Preoperative and postoperative sedation scoring was done using RASS. Results: The mean heart rate increased post extubation in both the groups. At 1min, 3 min and 5mins post extubation heart rate is better controlled in group N than group F and is statistically significant (P value &lt; 0.05). Both groups showed a rise in SBP immediately after intubation. Group N showed a significantly lower SBP in comparison to group F (p&lt;0.005). The DBP showed a similar trend. At one, three, and five minutes after intubation, HR, SBP, DBP, and MAP were similar between the groups. Post-extubation sedation score was significantly higher in group N (p &lt; 0.005). Conclusions: From the findings of our study it is concluded that I.V. Nalbuphine when given in the dose of 0.2 mg/kg as a premedicant is significantly effective in attenuating the haemodynamic responses during intubation, laryngoscopy and pneumoperitoneum in laparoscopic surgery when compared to Fentanyl 2.0 μg/kg. It also provides better hemodynamic stability without major side effects during laparoscopic surgery

Protocol for generating postganglionic sympathetic neurons using human pluripotent stem cells for electrophysiological and functional assessments

Summary: Assessing the development and function of the sympathetic nervous system in diseases on a large scale is challenging. Here, we present a protocol to generate human pluripotent stem cell (hPSC)-derived postganglionic sympathetic neurons (symNs) differentiated via neural crest cells (NCCs), which can be cryopreserved. We describe steps for hPSC replating, NCC replating and cryobanking, and symN differentiation. We then demonstrate the functionality of the hPSC-derived symNs, focusing on electrophysiological activity, calcium flux, and norepinephrine dynamics.For complete details on the use and execution of this protocol, please refer to Wu et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Evaluation of Observed and Future Climate Change Projection for Uttarakhand, India, Using CORDEX-SA

The climate change scenarios, especially global warming, have raised significant concerns, and the Himalayan regions such as Uttarakhand are highly vulnerable to such climatic shifts. Considering 10 Coordinated Regional Climate Downscaling Experiments in South Asia (CORDEX-SA), experiments with 3 regional climate models (RCMs), driven by 13 global climate models, historical estimates and future projections are analyzed from the mid-century (MC) i.e., from 2021–2050 to the end of the century (EC) i.e., from 2070–2099 to characterize annual and seasonal variations in precipitation and temperature. The analysis shows a decrease in the annual average precipitation by 5.92% at MC and an increase of 5.97% at EC for the Representative Climate Pathway (RCP) 4.5, while precipitation may likely increase from 2.83% to 15.89% towards MC and EC in the RCP 8.5. The maximum temperature may likely increase from 0.42 °C to 3.07 °C from MC to EC in the RCP 4.5 and from 0.83 °C to 5.49 °C in the RCP 8.5. In addition, the minimum temperature may increase from 0.80 °C to 3.25 °C from MC to EC in the RCP 4.5 and from 0.30 °C to 5.86 °C from MC to EC in the RCP 8.5. Notably, a decrease in the pre-monsoon precipitation at EC and a higher increase in the maximum temperature during the monsoon season are observed. An increase in the maximum temperature along with precipitation may lead to an increase in the frequency of the monsoon season’s extreme rainfall events