Selpercatinib mitigates cancer cachexia independent of anti-tumor activity in the HT1080 tumor model.

Anorexia is a major cause of cancer cachexia and is induced by growth differentiation factor-15 (GDF15), which activates the rearranged during transfection (RET) protein tyrosine kinase in the hindbrain through GDF family receptor α-like (GFRAL), raising the possibility of targeting RET for cancer cachexia treatment. RET-altered cancer patients treated with RET-selective kinase inhibitors gain weight, however, it is unclear whether this results from tumor regression that improves the overall health of patients. Thus, the potential of using a RET inhibitor to address cancer cachexia remains unknown.

The maternal genetic history of tribal populations of Chhattisgarh, India.

The central region of India boasts a rich tribal heritage and the highest number of tribal populations in the country. Analysing the genetic history of this population can offer valuable insights into various demographic processes that shaped the gene pool of present-day settlers of this region. In this study, we utilize a recently validated Next-generation sequencing (NGS) technique to sequence 24 tribal mitogenomes from the Chhattisgarh population for genetic ancestry and forensic analysis.

Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs.

The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins.

Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein.

In order to adapt in host tissues, microbial pathogens regulate their gene expression through a variety of transcription factors. Here, we have functionally characterized Rv0792c, a HutC homolog from Mycobacterium tuberculosis. In comparison to the parental strain, a strain of M.

Tumor tissue-specific bacterial biomarker panel for colorectal cancer: Bacteroides massiliensis, Alistipes species, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, Corynebacterium appendicis.

Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients.

HigB1 Toxin in Is Upregulated During Stress and Required to Establish Infection in Guinea Pigs.

The extraordinary expansion of Toxin Antitoxin (TA) modules in the genome of has received significant attention over the last few decades. The cumulative evidence suggests that TA systems are activated in response to stress conditions and are essential for pathogenesis. In , Rv1955-Rv1956-Rv1957 constitutes the only tripartite TAC (Toxin Antitoxin Chaperone) module.

"MINES" method for genomic DNA extraction from deep biosphere biofilms.

Successful and efficient extraction of high quality, high molecular weight genomic DNA from the environmental samples is an essential primary step to understand the genetic, metabolic and evolutionary characteristics of the microbial communities. Deep mine biofilm samples that contain high amounts of mucoid exopolysaccharide often pose difficulties to obtaining refined community DNA. To circumvent this hindrance, we report our "MINES" method which we developed for optimal biofilm DNA recovery suitable for all types of high-resolution downstream applications.

Identification and characterization of drought responsive miRNAs in a drought tolerant upland rice cultivar KMJ 1-12-3.

Shortfall of rain that creates drought like situation in non-irrigated agriculture system often limits rice production, necessitating introduction of drought tolerance trait into the cultivar of interest. The mechanism governing drought tolerance is, however, largely unknown, particularly the involvement of miRNAs, the master regulators of biochemical events. In this regard, response study on a drought tolerant rice variety KMJ 1-12-3 to 20% PEG (osmolality- 315 mOsm/kg) as drought stress revealed significant changes in abundance of several conserved miRNAs targeting transcription factors like homeodomain-leucine zipper, MADS box family protein, C2H2 zinc finger protein and Myb, well known for their importance in drought tolerance in plants.

Resilience and receptivity worked in tandem to sustain a geothermal mat community amidst erratic environmental conditions.

To elucidate how geothermal irregularities affect the sustainability of high-temperature microbiomes we studied the synecological dynamics of a geothermal microbial mat community (GMMC) vis-à-vis fluctuations in its environment. Spatiotemporally-discrete editions of a photosynthetic GMMC colonizing the travertine mound of a circum-neutral hot spring cluster served as the model-system. In 2010 a strong geyser atop the mound discharged mineral-rich hot water, which nourished a GMMC continuum from the proximal channels (PC) upto the slope environment (SE) along the mound's western face.

Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae.

Background: Multidrug resistant Klebsiella pneumoniae have caused major therapeutic problems worldwide due to the emergence of the extended-spectrum β-lactamase producing strains. Although there are >10 major facilitator super family (MFS) efflux pumps annotated in the genome sequence of the K. pneumoniae bacillus, apparently less is known about their physiological relevance.

Cellular interplay among Th17, Th1, and Treg cells in HIV-1 subtype "C" infection.

CD4 T cell depletion is central to HIV pathogenesis and disease progression. Different subsets of CD4 T cells cooperate to combat an infection. Therefore, the immune balance among Th17, Th1, and Treg cells may be critical in HIV immunopathogenesis which is not adequately defined yet.

Role of oxyRKP, a novel LysR-family transcriptional regulator, in antimicrobial resistance and virulence in Klebsiella pneumoniae.

Klebsiella pneumoniae is a Gram-negative bacillus that causes serious infections in immunocompromised human hosts and exhibits significant multidrug resistance. In this study, we identified a novel lysR-family regulator (designated oxyR(KP)) in the genome of K. pneumoniae NTUH-K2044 whose functions have remained enigmatic so far.

Loss of RORγt DNA binding activity inhibits IL-17 expression in HIV-1 infected Indian individuals.

Abstract IL-17 producing CD4 T cells have recently been shown to play an important role in mucosal immunity in HIV infection. But its role in peripheral immunity and the molecular mechanism underlying its regulation during HIV-1 infection are ill defined. In this study, we report a significant negative correlation between IL-17 production in peripheral blood and HIV-1 plasma viral load (pVL).

HIV-1 diseases progression associated with loss of Th17 cells in subtype 'C' infection.

Th17 cells play a crucial role in host immune response. We examined the role of Th17 cells in HIV-1 'subtype-C' infection and report that HIV-1 specific Th17 cells are induced in early infection and slow progressors but are significantly reduced at late stage of infection. There was a further decline in Th17 cells in late stage subjects with gastrointestinal infections.

Study of CD4+CD8+ double positive T-lymphocyte phenotype and function in Indian patients infected with HIV-1.

CD4+CD8+ double positive T cells represent a minor peripheral blood lymphocyte population. CD4+ expression on CD8+ T cells is induced following cellular activation, and as chronic HIV-1 infection is associated with generalized immune activation, double positive T cells studies have become necessary to understand the immunopathology of human immunodeficiency virus (HIV). The frequency of double positive T cells in persons infected with HIV was studied in comparison to uninfected controls.

Loss of CD127 & increased immunosenescence of T cell subsets in HIV infected individuals.

Background & Objectives: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naïve T cell subsets in HIV-infected and uninfected individuals.

Usefulness of hemoglobin and albumin as prognostic markers for highly active antiretroviral therapy for HIV-1 infection.

Background: Usefulness of hemoglobin and albumin as prognostic markers for highly active anti-retroviral therapy for HIV-1 infection.

Introduction: Anemia and hypoalbuminemia are common complications in human immunodeficiency virus (HIV) infection. We aimed to investigate the changes in hemoglobin and albumin levels in response to highly active antiretroviral therapy (HAART).

Altered T cell differentiation associated with loss of CD27 and CD28 in HIV infected Indian individuals.

Background: HIV-1 infection is associated with depletion of naïve T cell subsets and skewed T cell differentiation and maturation, leading to accumulation of T cells at intermediate and end stages of differentiation. CD27 and CD28 expression have been utilized in assessing these population subsets.

Methods: We characterized T cell subsets based on expression of CD45RA, CCR7, CD27, and CD28 and compared these subsets in HIV-1 infected Indian subjects and uninfected controls.

Polyfunctional analysis of Gag and Nef specific CD8+ T-cell responses in HIV-1 infected Indian individuals.

Polyfunctional CD8+ T-cells have been described as most competent in controlling viral replication. We studied the impact of antigen persistence on the polyfunctional immune responses of CD8+ T-lymphocytes to HIV Gag and Nef peptides and polyclonal stimuli in 40 ART naïve HIV infected individuals and analyzed the alterations in T-cell functionality in early and late stages of infection. Significantly elevated level of global response and polyfunctional profile of CD8+ T-cells were observed to polyclonal stimulation, than HIV specific antigens in chronically infected individuals.

Defects in blood dendritic cell subsets in HIV-1 subtype c infected Indians.

Background & Objectives: DCs trigger both innate and adaptive immune responses to control HIV infection and represent a viral reservoir acting as target and HIV carriers for infection of permissive CD4(+) T-cells. DCs thus form a very attractive study subject to further our existing knowledge of HIV induced immunopathogenesis due to its diverse and crucial role in HIV infection establishment, viral dissemination, immune evasion, viral persistence, etc. We aimed to characterize the effect of HIV infection on myeloid and plasmacytoid dendritic cell subsets in a group of HIV-1 subtype C infected treated or untreated Indian individuals.

Late presenters to HIV care and treatment, identification of associated risk factors in HIV-1 infected Indian population.

Background: Timely access to antiretroviral therapy is a key to controlling HIV infection. Late diagnosis and presentation to care diminish the benefits of antiretrovirals and increase risk of transmission. We aimed to identify late presenters in patients sent for first CD4 T cell count after HIV diagnosis, for therapy initiation evaluation.

Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals.

Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.

Evaluation of a rapid immunochromatographic test for diagnosis of kala-azar & post kala-azar dermal leishmaniasis at a tertiary care centre of north India.

Background & Objective: Definitive diagnosis of kala-azar requires demonstration of parasites by diagnostic protocols based on invasive organ aspirations. We evaluated in the present study the diagnostic utility of an immunochromatographic test (ICT) for detection of anti- rK-39 antibodies for the non-invasive diagnosis of kala-azar and post kala-azar dermal leishmaniasis (PKDL) at a tertiary care centre of north India.

Methods: The study was conducted in the Department of Microbiology, All India Institute of Medical Sciences, New Delhi, from July 2003 to October 2004.