Differential tropisms of old and new world hantaviruses influence virulence and developing host-directed antiviral candidates.

Hantaviruses are zoonotically transmitted from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The recent discovery of interhuman-transmitted Andes virus (ANDV) necessitates the systematic identification of cell tropism, infective potential, and potent therapeutic agents. We utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses.

High-Throughput Targeted Drug Screening for NF1-associated High-Grade Gliomas with ATRX Deficiency.

Neurofibromatosis type 1 (NF1)-associated high-grade gliomas (HGGs) harboring ATRX mutations exhibit an aggressive clinical phenotype, driven by heightened genomic instability and metabolic reprogramming. Existing therapies, including chemotherapy and radiotherapy, are limited by resistance mechanisms and formation of secondary malignancy, underscoring the need for novel therapeutic strategies. Here, we report the results of a high-throughput screening of 10,000 small molecules aimed at identifying compounds selectively targeting vulnerabilities associated with concurrent ATRX and NF1 loss.

Master control of protein secretion by .

Tuberculosis is the leading cause of death from a single infectious disease. secretes proteins using five ESX systems with distinctive functions essential for its growth and virulence. Here we show that a non-canonical supercomplex of the EsxU-EsxT proteins, encoded in the locus, with the orphan EsxE-EsxF proteins, encoded in the operon, is required for toxin secretion by .

Utilizing Plant Phytoconstituents in Metal Oxide Nanoparticle Synthesis for Cancer Therapies.

Background: The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as Cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.

Comparative Analysis of Molecular Pathogenic Mechanisms and Antiviral Development Targeting Old and New World Hantaviruses.

Background: Hantaviruses - dichotomized into New World (i.e. Andes virus, ANDV; Sin Nombre virus, SNV) and Old-World viruses (i.

Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees.

Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses.

RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak.

Impact of aquatic microplastics and nanoplastics pollution on ecological systems and sustainable remediation strategies of biodegradation and photodegradation.

The extreme degree of microplastics contamination and its negative impact on ecosystems has become a serious and emerging global concern. Microplastics are mainly generated from products that are used primarily in our everyday lives and are also generated from the fragmentation of larger plastic wastes. It easily penetrates the food chain and, when ingested by aquatic animals or humans, can pose serious health problems.

Validation of absolute point dosimetry by the analytical anisotropic algorithm and Acuros XB algorithm employing intensity-modulated radiotherapy technique on an in-house develop cost-effective heterogeneous thorax phantom.

Introduction: Dose validation inside the human body needs a medium which can simulate the actual heterogeneities of a specific body site. The aim of the present work is to study the properties of a cost-effective heterogeneous thorax phantom (HTP) developed in-house by the author and its application for the evaluation of patient-specific absolute point dosimetry by employing analytic anisotropic algorithm (AAA) and Acuros XB (AXB) algorithm.

Materials And Methods: HTP was made from the dust of porous pinewood, rib cage, and honeybee's wax.

Topological analyses of the L-lysine exporter LysO reveal a critical role for a conserved pair of intramembrane solvent-exposed acidic residues.

LysO, a prototypical member of the LysO family, mediates export of L-lysine (Lys) and resistance to the toxic Lys antimetabolite, L-thialysine (Thl) in Escherichia coli. Here, we have addressed unknown aspects of LysO function pertaining to its membrane topology and the mechanism by which it mediates Lys/Thl export. Using substituted cysteine (Cys) accessibility, here we delineated the membrane topology of LysO.

3-D macro/microporous-nanofibrous bacterial cellulose scaffolds seeded with BMP-2 preconditioned mesenchymal stem cells exhibit remarkable potential for bone tissue engineering.

Bone repair using BMP-2 is a promising therapeutic approach in clinical practices, however, high dosages required to be effective pose issues of cost and safety. The present study explores the potential of low dose BMP-2 treatment via tissue engineering approach, which amalgamates 3-D macro/microporous-nanofibrous bacterial cellulose (mNBC) scaffolds and low dose BMP-2 primed murine mesenchymal stem cells (C3H10T1/2 cells). Initial studies on cell-scaffold interaction using unprimed C3H10T1/2 cells confirmed that scaffolds provided a propitious environment for cell adhesion, growth, and infiltration, owing to its ECM-mimicking nano-micro-macro architecture.

Production and characterization of Komagataeibacter xylinus SGP8 nanocellulose and its calcite based composite for removal of Cd ions.

In the present study, fermentative production of bacterial nanocellulose (BNC) by using Komagataeibacter xylinus strain SGP8 and characterization of nanocellulose is presented. The bacterium was able to produce 1.82 g L of cellulose in the form of pellicle in standard Hestrin-Schramn (HS) medium.

Biotransformation of sweet lime pulp waste into high-quality nanocellulose with an excellent productivity using Komagataeibacter europaeus SGP37 under static intermittent fed-batch cultivation.

Herein, sweet lime pulp waste (SLPW) was utilized as a low- or no-cost feedstock for the production of bacterial nanocellulose (BNC) alone and in amalgamation with other nutritional supplements by the isolate K. europaeus SGP37 under static batch and static intermittent fed-batch cultivation. The highest yield (26.

Plasmodium Hsp40 and human Hsp70: A potential cochaperone-chaperone complex.

Out of the total forty four members of Plasmodium falciparum Hsp40 protein family, nineteen of them possess a PEXEL motif, and are predicted to be exported into the cytosol of an infected RBC. It is speculated that the human Hsp70 (hHsp70), which resides into the cytosol of the host erythrocyte, along with the exported PfHsp40s assists in the folding of parasitic proteins, thus playing a crucial role in the establishment of virulence. However, till date no experimental evidence supports this hypothesis.

PA2 Tyrosinase Covalently Immobilized on a Novel Eco-Friendly Bio-Composite of Chitosan-Gelatin and Its Evaluation for L-DOPA Production.

Tyrosinase (EC 1.14.18.

From rotten grapes to industrial exploitation: Komagataeibacter europaeus SGP37, a micro-factory for macroscale production of bacterial nanocellulose.

Bacterial nanocellulose (BNC), being ultrapure and unique in its properties, is a booming and ageless precursor of several breakthrough technologies of materials sciences; however, its low yield and high cost has created a challenge for its usage at industrial level. Herein, we report a novel, high yielding bacterial cell factory Komagataeibacter europaeus SGP37, isolated from rotten grapes, for the production of high quality and value added BNC. The strain was kinetically analyzed to evaluate BNC production under different physiological conditions and had demonstrated the production of 9.

KAP Study on HIV/AIDS Among Antenatal Women Attending Central Referral Hospital of North East India.

Background: This study was conducted to determine whether antenatal mothers in Sikkim have adequate knowledge about awareness, attitude, and preventive practices regarding HIV infection.

Methods: Cross-sectional study using structured questionnaire. 220 Antenatal mothers attending the outpatient department of Central Referral Hospital of Sikkim were taken for the study for a period of 1 year from April 2011 to April 2012.

The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function.

Unlabelled: ArgO and LysE are members of the LysE family of exporter proteins and ordinarily mediate the export of l-arginine (Arg) in Escherichia coli and l-lysine (Lys) and Arg in Corynebacterium glutamicum, respectively. Under certain conditions, ArgO also mediates Lys export. To delineate the arrangement of ArgO in the cytoplasmic membrane of E.

Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA.

L-DOPA (3,4-dihydroxyphenyl-L-alanine), an amino acid derivative is the most widely used drug of choice for the treatment of Parkinson's disease and other neurologic injuries. The present study deals with the elevated biochemical transformation of L-tyrosine to L-DOPA by Aspergillus niger PA2, a potent tyrosinase producer, isolated from decomposed food wastes. This appears to be the first report on A.

Determination of disulfiram by micellar liquid chromatography in illicit preparations.

Presently, disulfiram is used in aversion therapy for recovering alcoholics. It acts by inhibiting aldehyde dehydrogenase, leading to high blood levels of acetaldehyde. A simple direct injection micellar liquid chromatographic procedure was developed to determine disulfiram in illicit preparations (ayurvedic, herbal, divine ash, and traditional medicine), as well as in pharmaceuticals and biological samples (urine).