Computational System Level Approaches for Discerning Reciprocal Regulation of IL10 and IL12 in Leishmaniasis.

IL12 and IL10 are two of the major cytokines which control the fate of Leishmaniasis. This paper presents two models healthy state and diseased state which shows how secretion of IL12 is responsible for parasite elimination and IL10 can jeopardize the parasite elimination and promote its survival. Epigenetic modification in the host IL12 and IL10 promoter can decide the fate of parasites.

Correction to: A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR.

In Volume 46 of the Journal of Biosciences, in the article titled 'A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR' by Ridim D Mote, V Shinde Laxmikant, Surya Bansi Singh, Mahak Tiwari, Hemant Singh, Juhi Srivastava, Vidisha Tripathi,Vasudevan Seshadri, Amitabha Majumdar and Deepa Subramanyam, published on 27 November 2021 (https://doi.org/10.1007/s12038-021- 00231-w), the second author's name was incorrectly set as V Shinde Laxmikant.

Synthesis and anti-HIV activity of a new isoxazole containing disubstituted 1,2,4-oxadiazoles analogs.

Continuing on our antiviral drug discovery research, we intended to diversify our lead anti-HIV-1 inhibitor by non-classical isosteric replacement of amide to 1,2,4-oxadiazoles. The resulting molecules isoxazole-1,2,4-oxadiazole analogs were synthesized using mild bases in ethanol under microwave irradiation. The anti-HIV potential was checked in human CD4 reporter cell lines, TZM-bl and CEM-GFP, at the highest non-cytotoxic concentration (HNC), demonstrating that 3-((3-(p-tolyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole and 3-((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole inhibit HIV-1 replication significantly and could be considered as a new lead candidate against HIV-1.

A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR.

Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing coronavirus pandemic has severely hampered the economy in a number of developing countries, resulting in a reduction in available research funding.

Osteopontin Signaling in Shaping Tumor Microenvironment Conducive to Malignant Progression.

Context-dependent reciprocal crosstalk between cancer and surrounding stromal cells in the tumor microenvironment is imperative for the regulation of various hallmarks of cancer. A myriad of growth factors, chemokines, and their receptors aids in the interaction between cancer cells and tumor microenvironmental components. Osteopontin is a chemokine-like protein, overexpressed in different types of cancers.

Anthraquinolone and quinolizine derivatives as an alley of future treatment for COVID-19: an in silico machine learning hypothesis.

Coronavirus disease 2019 (Covid-19), caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has come to the fore in Wuhan, China in December 2019 and has been spreading expeditiously all over the world due to its high transmissibility and pathogenicity. From the outbreak of COVID-19, many efforts are being made to find a way to fight this pandemic. More than 300 clinical trials are ongoing to investigate the potential therapeutic option for preventing/treating COVID-19.

Regulation of STAT3 signaling in IFNγ and IL10 pathways and in their cross-talk.

The pro-inflammatory IFNγ-STAT1 pathway and anti-inflammatory IL10-STAT3 pathway elicit cellular responses primarily utilizing their canonical STATs. However IL10 mediated STAT1 and IFNγ mediated STAT3 activation is also observed, suggesting crosstalk of these functionally opposing signaling pathways can potentially reshape the canonical dynamics both STATs and alter the expression of their target genes. Herein, we measured the dynamics of STATs in response to different doses of IL10 or IFNγ and in their co-stimulation and employed quantitative modeling to understand the regulatory mechanisms controlling signal responses in individual and co-simulation scenarios.

Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions.

Gamma-delta (γδ) T cells are a heterogeneous population of immune cells, which constitute <5% of total T cells in mice lymphoid tissue and human peripheral blood. However, they comprise a higher proportion of T cells in the epithelial and mucosal barrier, where they perform immune functions, help in tissue repair, and maintaining homeostasis. These tissues resident γδ T cells possess properties of innate and adaptive immune cells which enables them to perform a variety of functions during homeostasis and disease.

Transporter proteins and its implication in human diseases.

Drug transporters, classified in various ways like efflux transporters and influx transporters; secretory transporters and absorptive transporters; ATP-driven transporters and Solute Linked Carrier (SLC) transporters are of great importance while studying pharmacokinetics. They have impeccable roles in the drug discovery process of infectious diseases. Many of these find a pivotal role in synthetic antimicrobial peptides.

Epigenetic Regulation of Adipogenesis in Development of Metabolic Syndrome.

Obesity is one of the biggest public health concerns identified by an increase in adipose tissue mass as a result of adipocyte hypertrophy and hyperplasia. Pertaining to the importance of adipose tissue in various biological processes, any alteration in its function results in impaired metabolic health. In this review, we discuss how adipose tissue maintains the metabolic health through secretion of various adipokines and inflammatory mediators and how its dysfunction leads to the development of severe metabolic disorders and influences cancer progression.

Autophagy proteins and its homeostasis in cellular environment.

Autophagy is a self-destructing mechanism of cell via lysosomal degradation, which helps to degrade/destroy hazardous substances, proteins, degenerating organelles and recycling nutrients. It plays an important role is cellular homeostasis and regulates internal environment of cell, moreover, when needed causes non-apoptotic programmed death of cell. Autophagy has been observed as one of the major factors in parasite clearance in leishmaniasis.

Comparative analysis of differential gene expression of HSP40 and HSP70 family isoforms during heat stress and HIV-1 infection in T-cells.

Heat shock proteins (HSPs) are a family of cellular proteins involved in a variety of biological functions including chaperone activity. HSPs are classified based on their molecular weight and each family has several isoforms in eukaryotes. HSP40 is the most diverse family acting as a co-chaperone for the highly conserved HSP70 family.

Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness.

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of , similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency.

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics.

An epidemic caused by COVID-19 in China turned into pandemic within a short duration affecting countries worldwide. Researchers and companies around the world are working on all the possible strategies to develop a curative or preventive strategy for the same, which includes vaccine development, drug repurposing, plasma therapy, and drug discovery based on Artificial intelligence. Therapeutic approaches based on Computational biology and Machine-learning algorithms are specially considered, with a view that these could provide a fast and accurate outcome in the present scenario.

Establishment of integration free iPSC clones, NCCSi011-A and NCCSi011-B from a liver cirrhosis patient of Indian origin with hepatic encephalopathy.

Liver cirrhosis accompanied with hepatic encephalopathy commonly causes cognitive impairment in patients. To model this disease, two independent patient specific induced pluripotent stem cell-line (iPSC) clones, NCCSi011-A and NCCSi011-B were generated by reprogramming the CD4 T cells of an Indian male patient suffering from this chronic condition. Both clones expressed the stemness markers, formed embryoid bodies (EBs) with potential for spontaneous differentiation in to all the three lineages, exhibited normal karyotype (46, XY) and demonstrated alkaline phosphatase activity.

Development and characterization of two independent integration free iPSC clones NCCSi010-A and NCCSi010-B from a patient with alcoholic liver cirrhosis of Indian ethnicity.

We generated two human induced pluripotent stem cell-line (iPSC) clones, NCCSi010-A and NCCSi010-B, from a 32-year-old alcoholic cirrhosis patient with minimal hepatic encephalopathy of Indian origin by reprogramming his CD4 T cells with integration free Sendai viral vector system. The generated iPSC clones showed high alkaline phosphatase activity, expressed pluripotency markers, possessed potential for multi-lineage differentiation and exhibited a normal karyotype (46, XY). These two-patient specific iPSC clones of alcoholic liver cirrhosis can potentially serve as models for disease modeling, drug development and organoid generation (Shah and Bataller, 2016).

Systems Studies Uncover miR-146a as a Target in Infection Model.

Leishmaniasis, the second most neglected tropical disease, has been reported to affect approximately 12 million people worldwide. The causative protozoan parasite has shown drug resistance to available chemotherapies, owing to which we need to look for better approaches to deal with the clinical situations. As per recent reports, several miRNAs have been found to be differentially expressed during infection in host macrophages.

Computationally designed synthetic peptides for transporter proteins imparts allostericity in Miltefosine resistant L. major.

The emergence of drug resistance is a major concern for combating against Cutaneous Leishmaniasis, a neglected tropical disease affecting 98 countries including India. Miltefosine is the only oral drug available for the disease and Miltefosine transporter proteins play a pivotal role in the emergence of drug-resistant Leishmania major. The cause of resistance is less accumulation of drug inside the parasite either by less uptake of the drug due to a decrease in the activity of P4ATPase-CDC50 complex or by increased efflux of the drug by P-glycoprotein (P-gp, an ABC transporter).

Structural sequence evolution and computational modeling approaches of the complement system in leishmaniasis.

The complement system is one of the first barriers and consists of well-balanced cascades of reactions which generates anaphylatoxins such as C5a and C3a. A G-protein coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5AR1, also known as CD88) is the receptor for C5a which is present on cells of myeloid origin. Owing to difficulty in obtaining crystal structures of GPCRs in either inactive or active state, accurate structural modeling is still highly desirable for the majority of GPCRs.

Multiscale Process Modelling in Translational Systems Biology of Leishmania major: A Holistic view.

Present work aims to utilize systems biology and molecular modelling approach to understand the inhibition kinetics of Leishmania major GLO I and identifying potential hit followed by their validation through in vitro and animal studies. Simulation of GLO I inhibition has shown to affect reaction fluxes of almost all reactions in the model that led to increased production of various AGEs and free radicals. Further, in vitro testing of C1 and C2, selected through molecular modelling revealed remarkable morphological alterations like size reduction, membrane blebbing and loss in motility of the parasite, however, only C1 showed better antileishmanial activity.

CCR9 signaling in dendritic cells drives the differentiation of Foxp3 Tregs and suppresses the allergic IgE response in the gut.

The chemokine receptor CCR9 and its only known ligand CCL25 play an important role in gut inflammation and autoimmune colitis. The function of CCR9-CCL25 in the migration of immune cells is well characterized. However, its role in the immune cell differentiation is mostly not known.

Site specific microbiome of Leishmania parasite and its cross-talk with immune milieu.

Microbiota consists of commensal, symbiotic and pathogenic microorganisms found in all multicellular organisms. These micro-organisms are found in or on many parts of the body, including the intestinal tract, skin, mouth, and the reproductive tract. This review focuses on interplay of site specific microbiota, vector microbiota along with immune response and severity of Leishmaniasis.

Diversity of Onygenalean Fungi in Keratin-Rich Habitats of Maharashtra (India) and Description of Three Novel Taxa.

Extensive survey was carried out in the state of Maharashtra, India, as part of a 3-year project to explore keratinophilic fungal diversity for conservation and biotechnological potential. A total of 578 soil samples were collected from keratin-rich habitats across 24 districts of Maharashtra State. Hair-baiting technique and micro-dilution drop-trail method were employed for isolation and purification of keratinophilic fungi from soil.

Role of cytokines in combinatorial immunotherapeutics of non-small cell lung cancer through systems perspective.

Lung cancer is the leading cause of deaths related to cancer and accounts for more than a million deaths per year. Various new strategies have been developed and adapted for treatment; still the survival for 5 years is just 16% in patients with non-small cell lung cancer (NSCLC). Most of these strategies to combat NSCLC whether it is a drug molecule or immunotherapy/vaccine candidate require a big cost and time.