Browsing by Author "Rajeev Kumar Pandey"

Now showing 1 - 14 of 14

Garnet-Staurolite-Mica Schist from Southern Sonbhadra District, U.P.: Constraints from Geothermobarometry and P-T Pseudosection Modelling
(Geological Society of India, 2024) Ankita Anand Singh; Divya Prakash; Birendra Pratap Singh; Chandra Kant Singh; Rajeev Kumar Pandey
The area around Renukoot town shows the exposure of garnet-staurolite-mica schist belonging to the Chhotanagpur Granite Gneiss Complex (CGGC). The characteristic mineral assemblage present in the rock are garnet–biotite–staurolite–quartz along with minor opaque minerals like rutile, ilmenite and hematite. For the constituent minerals, the calculated XMg value decreases in the order: chlorite>biotite>staurolite>garnet. The metamorphic conditions of the garnet-staurolite-mica schist were determined using the winTWQ and Perple_X programmes, and the peak pressure-temperature conditions for the rock are estimated to be 5.3 kbar and 570°C. The metamorphic episode in the CGGC during Mesoproterozoic time may be attributed to the global level Columbian Super-continental accretionary orogeny. © 2024, Geological Society of India. All rights reserved.
Geochemistry, Monazite (U–Pb–Th) Geochronology, and P-T Pseudosection Modelling of Two-Pyroxene Mafic Granulite from Sonapahar, Shillong Meghalaya Gneissic Complex, India: Implication for Tectono-Metamorphic Evolution and Global Pan-African Correlation
(2024) Bikash Mahanta; Divya Prakash; Manish Kumar; Saurabh Singh; Rajeev Kumar Pandey; Chandra Kant Singh; Suparna Tewari
Abstract: Granulites exposed in high-grade regional metamorphic belts and exhumed as xenoliths in basaltic pipes are considered as window into the deep crust thus play a key role in constraining models of crustal processes and evolution. Here we present a detailed investigation of the tectono-metamorphic history of the two-pyroxene mafic granulite located in the southern region of the Sonapahar area. This involves conducting monazite chemical dating, analyzing petrological and geochemical characteristics, applying geothermobarometry, performing phase equilibria modeling, and tracing a pressure-temperature (P-T) path. Metamorphic P-T conditions estimated for the mafic granulite using conventional thermobarometer and winTWQ shows temperature in excess of 800°C and pressure of about 8.6 kbar, stand for high temperature granulite facies metamorphism. The metamorphic evolution path obtained from P-T pseudosection suggest a clockwise P-T evolution path, thus signify isothermal decompression and indicate rapid upliftment. Geochemical study of trace and rare earth elements (REE), suggest protolith is of tholeiite basalt in nature that is derived from back arc basin setting near to subduction zone. Additionally, the analyzed rock was examined using primitive mantle-normalized trace element spider diagram. The results indicate an enrichment in large-ion lithophile elements (Th, U, K, Pb) and a depletion in high field-strength elements (Nb, Ta, Ti). The presence of negative anomalies in Nb and Ti, coupled with elevated values of Th, K, and Pb, suggests the possibility of crustal contamination. Monazite chemical data from the studied rock reveals a peak metamorphism age of 521.3 ± 4.20 Ma, which corresponds to the Kuunga Orogeny in the later phase of global Pan-African collision. © Pleiades Publishing, Ltd. 2024. ISSN 0016-7029, Geochemistry International, 2024, Vol. 62, No. 6, pp. 574–608. Pleiades Publishing, Ltd., 2024. ISSN 0016-7029, Geochemistry International, 2024. Pleiades Publishing, Ltd., 2024.
IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
(Frontiers Media S.A., 2021) Manu Kupani; Smriti Sharma; Rajeev Kumar Pandey; Rajiv Kumar; Shyam Sundar; Sanjana Mehrotra
Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production. © Copyright © 2021 Kupani, Sharma, Pandey, Kumar, Sundar and Mehrotra.
Leishmania donovani-induced increase in macrophage Bcl-2 favors parasite survival
(Frontiers Media S.A., 2016) Rajeev Kumar Pandey; Sanjana Mehrotra; Smriti Sharma; Ramachandra Subbaraya Gudde; Shyam Sundar; Chandrima Shaha
Members of the Bcl-2 family are major regulators of apoptosis in mammalian cells, and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. In this investigation, we uncover a novel role of host Bcl-2 in sustaining Leishmania donovani infection. A rapid twofold increase in Bcl-2 expression occurred in response to parasite challenge. Downregulation of post infection Bcl-2 increase using siRNA or functional inhibition using Bcl-2 small molecule inhibitors interfered with intracellular parasite survival confirming the necessity of elevated Bcl-2 during infection. An increased nitric oxide (NO) response and reduced parasitic burden was observed upon Bcl-2 inhibition, where restitution of the NO response accounted for parasite mortality. Mechanistic insights revealed a major role of elevated Th2 cytokine IL-13 in parasite-induced Bcl-2 expression via the transcription factor STAT-3, where blocking at the level of IL-13 receptor or downstream kinase JAK-2 dampened Bcl-2 induction. Increase in Bcl-2 was orchestrated through Toll like receptor (TLR)-2-MEK-ERK signaling, and changes in TLR-2 levels affected parasite uptake. In a mouse model of visceral leishmaniasis (VL), Bcl-2 inhibitors partially restored the antimicrobial NO response by at least a twofold increase that resulted in significantly reduced parasite burden. Interestingly, monocytes derived from the peripheral blood of six out of nine human VL subjects demonstrated Bcl-2 expression at significantly higher levels, and sera from these patients showed only marginally quantifiable nitrites. Collectively, our study for the first time reveals a pro-parasitic role of host Bcl-2 and the capacity of host-derived IL-13 to modulate NO levels during infection via Bcl-2. Here, we propose Bcl-2 inhibition as a possible therapeutic intervention for VL. © 2016 Pandey, Mehrotra, Sharma, Gudde, Sundar and Shaha.
Metamorphic evolution of sapphirine- and sodicgedrite-anorthite-bearing granulites, Rampur domain, Eastern Ghats Province, India
(Cambridge University Press, 2025) Rajeev Kumar Pandey; Divya Prakash; Saurabh Kumar Singh; Bikash Mahanta; Chandrakant Singh; Kamesh Sharma; Manish Kumar; Mahendra Kumar Singh
The Eastern Ghats Belt (EGB) has been extensively studied by the geoscientific community; however, this communication reports unique mineral assemblages that have not been documented previously. This study documents the occurrence of sapphirine, spinel, orthopyroxene, sodic-gedrite, calcic-amphibole, biotite and plagioclase assemblage indicating in ultrahigh temperature (UHT) metamorphic conditions. The significance of this study lies in the peculiarity of sapphirine being present within anorthite matrix which has been reported for the first time from the Indian subcontinent. The studied assemblage has been correlated with the more or less similar assemblage of rock called 'Sakenites' reported from southern Madagascar to correlate the most probable source rock 'anorthosites' that underwent metamorphic transformations and led to the unique UHT mineral assemblage. The Na-rich gedrite identified within the assemblage represents a relict mineral indicative of high-grade amphibolite-facies metamorphism. The derived pressure-temperature (P-T) trajectory reveals a decompression path with almost uniformly decreasing P-T conditions in contrast to the commonly reported isothermal decompression (ITD) path from various other domains and provinces of the EGB. The corresponding retrograde assemblage has been recalibrated by the sequential removal of sapphirine and corroborated with T-X (H2O) constraints. The analyzed EMP U-Th-Pb monazite chemical age constraints suggest mesoproterozoic to neoproterozoic episodes corresponding to a pair of ∼959 Ma and ∼846 Ma thermal events. These metamorphic events have been correlated to reconstructing the Rodinian supercontinent at ∼959 Ma and the initiation of its subsequent break-up at ∼846 Ma. © The Author(s), 2025. Published by Cambridge University Press.
Mycobacterium indicus pranii downregulates MMP-9 and iNOS through COX-2 dependent and TNF-α independent pathway in mouse peritoneal macrophages in vitro
(2012) Rajeev Kumar Pandey; Yogesh Dahiya; Ajit Sodhi
Despite the popular belief that granulomas are innate immune mechanism to restrict mycobacterial growth, evidences suggest that granulomas facilitate growth of Mycobacterium by recruiting large numbers of uninfected macrophages to the site of infection. Matrix metalloproteinase-9 (MMP-9) has been shown to be directly involved in recruitment of macrophages at the site of infection, contributing to nascent granuloma maturation and bacterial growth. In this manuscript it is reported that heat-killed Mycobacterium indicus pranii (MIP) leads to a significant downregulation of MMP-9 in murine peritoneal macrophages in vitro. The downregulation of MMP-9 is mediated through cyclooxygenase-2 (COX-2), but independent of tumor necrosis factor-α (TNF-α). By limiting nuclear to cytoplasmic export of COX-2 and iNOS transcripts, MIP inhibits excessively-high levels of nitric oxide which can be damaging to the host during acute phases of infection. MIP has been shown to provide clinical improvement in all phases of leprosy and used for treatment of leprosy and tuberculosis. © 2011 Institut Pasteur.
Mycobacterium indicus pranii mediates macrophage activation through TLR2 and NOD2 in a MyD88 dependent manner
(2012) Rajeev Kumar Pandey; Ajit Sodhi; Subhra K. Biswas; Yogesh Dahiya; Manprit K. Dhillon
Mycobacterium indicus pranii (MIP) is a non-pathogenic strain of mycobacterium and has been used as a vaccine against tuberculosis and leprosy. Here, we investigated the role of different pattern recognition receptors in the recognition of heat-killed MIP by macrophages. Treatment of macrophages with MIP caused upregulation of pro-inflammatory cytokines (like TNFα and IL-1β) which was mediated through both TLR2 and NOD2, as revealed by our knockdown and/or knockout studies. Mechanistically, MIP-induced macrophage activation was shown to result in NF-κB activation and drastically abrogated by MyD88 deficiency, suggesting its regulation via an MyD88-dependent, NF-κB pathway. Interestingly, the IFN-inducible cytokine, CXCL10, which is known target of the TRIF-dependent TLR pathway was found to be upregulated in response to MIP but, in an MyD88-dependent manner. Collectively, these results demonstrate macrophages to recognize and respond to MIP through a TLR2, NOD2 and an MyD88-dependent pathway. However, further studies should clarify whether additional TLR-dependent or -independent pathways also exist in regulating the full spectrum of MIP action on macrophage activation. © 2012 Elsevier Ltd.
Mycobacterium indicus pranii supernatant induces apoptotic cell death in mouse peritoneal macrophages in vitro
(2011) Rajeev Kumar Pandey; Kunal H. Bhatt; Yogesh Dahiya; Ajit Sodhi
Mycobacterium indicus pranii (MIP), also known as Mw, is a saprophytic, non-pathogenic strain of Mycobacterium and is commercially available as a heat-killed vaccine for leprosy and recently tuberculosis (TB) as part of MDT. In this study we provide evidence that cell-free supernatant collected from original MIP suspension induces rapid and enhanced apoptosis in mouse peritoneal macrophages in vitro. It is demonstrated that the MIP cell-free supernatant induced apoptosis is mitochondria-mediated and caspase independent and involves mitochondrial translocation of Bax and subsequent release of AIF and cytochrome c from the mitochondria. Experiments with pharmacological inhibitors suggest a possible role of PKC in mitochondria-mediated apoptosis of macrophages. © 2011 Pandey et al.
Navigating the Roadblocks: Progress and Challenges in Cell-Based Therapies for Human Immunodeficiency Virus
(John Wiley and Sons Inc, 2025) Lakshay Chhabra; Rajeev Kumar Pandey; Rajiv Kumar; Santhanam Sundar; Sanjana Mehrotra
Cell-based therapies represent a major advancement in the treatment and management of HIV/AIDS, with a goal to overcome the limitations of traditional antiretroviral therapy (ART). These innovative approaches not only promise a functional cure by reconstructing the immune landscape but also address the persistent viral reservoirs. For example, stem cell therapies have emerged from the foundational success of allogeneic hematopoietic stem cell transplantation in curing HIV infection in a limited number of cases. B cell therapies make use of genetically modified B cells constitutively expressing broadly neutralizing antibodies (bNAbs) against target viral particles and infected cells. Adoptive cell transfer (ACT), including TCR-T therapy, CAR-T cells, NK-CAR cells, and DC-based therapy, is adapted from cancer immunotherapy and repurposed for HIV eradication. In this review, we summarize the mechanisms through which these engineered cells recognize and destroy HIV-infected cells, the modification strategies, and their role in sustaining remission in the absence of ART. The review also addresses the challenges to cell-based therapies against HIV and discusses the recent advancements aimed at overcoming them. © 2024 Wiley Periodicals LLC.
Nod2 downregulates TLR2/1 mediated IL1β gene expression in mouse peritoneal macrophages
(2011) Yogesh Dahiya; Rajeev Kumar Pandey; Ajit Sodhi
Nod2 is a cytosolic pattern recognition receptor. It has been implicated in many inflammatory conditions. Its signaling has been suggested to modulate TLR responses in a variety of ways, yet little is known about the mechanistic details of the process. We show in this study that Nod2 knockdown mouse peritoneal macrophages secrete more IL1β than normal macrophages when stimulated with peptidoglycan (PGN). Muramyl dipeptide (MDP, a Nod2 ligand) + PGN co-stimulated macrophages have lower expression of IL1β than PGN (TLR2/1 ligand) stimulated macrophages. MDP co-stimulation have similar effects on Pam3CSK4 (synthetic TLR2/1 ligand) mediated IL1β expression suggesting that MDP mediated down regulating effects are receptor dependent and ligand independent. MDP mediated down regulation was specific for TLR2/1 signaling as MDP does not affect LPS (TLR4 ligand) or zymosan A (TLR2/6 ligand) mediated IL1β expression. Mechanistically, MDP exerts its down regulating effects by lowering PGN/Pam3CSK4 mediated nuclear cRel levels. Lower nuclear cRel level were observed to be because of enhanced transporting back rather than reduced nuclear translocation of cRel in MDP + PGN stimulated macrophages. These results demonstrate that Nod2 and TLR2/1 signaling pathways are independent and do not interact at the level of MAPK or NF-κB activation. © 2011 Dahiya et al.
Phase equilibria modelling, fluid inclusion study, and U-Pb zircon dating of ultra-high temperature mafic granulites from Rampur domain, Eastern Ghats province: implications for the Indo-Antarctic correlation
(Springer Science and Business Media Deutschland GmbH, 2025) Divya Prakash; Rajeev Kumar Pandey; Saurabh Kumar Singh; Chandrakant Singh; Manish Kumar; Bikash Mahanta; Aditya Kharya; Himanshu Kumar Sachan; Kamesh Sharma
The study area (Rampur domain) is situated to the east of the Eastern Ghats Boundary Shear Zone (EGBSZ) and encompasses portions of the granulite facies rocks of the exhumed Proterozoic Eastern Ghats Province (EGP), India. The EGP is characterized by a diverse array of rock types, featuring a wide variety of mineral parageneses and chemical compositions, including charnockite, mafic granulite, Mg-Al granulite, felsic granulites, amphibolite, khondalite and anorthosite. In this study, we report for the first time evidence of ultra-high temperature (UHT) metamorphism within the mafic granulites of the relatively unexplored Rampur domain of the Eastern Ghats Province, using the two-pyroxene assemblage. The stable mineral assemblage present during peak metamorphism typically includes garnet, orthopyroxene1, clinopyroxene, hornblende1, quartz, and plagioclase1. The consumption of garnet observed in different reaction textures, alongside the formation of striking orthopyroxene2–plagioclase2 and hornblende2–plagioclase2 symplectites, represent the later phases of metamorphism. By applying TWQ calculation procedures to the mineral core compositions, we have determined peak metamorphic conditions of approximately 970 °C at a pressure of 10.5 kbar. Zircon dating results from LA-HR-ICP-MS indicate upper intercept ages of 2509.9 ± 21.7 Ma and 2479.9 ± 21.0 Ma for the protolith, while lower intercept ages of 965.7 ± 40.7 Ma and 979.8 ± 18.1 Ma correspond to the metamorphic age of the analyzed samples E-185 and E-186, respectively. Based on the textural relationship, derived zircon ages, fluid-P-T constraints, and P-T pseudosection model, we propose a decompressional evolutionary P-T-t path that supports the Neo-Proterozoic assembly of the Indo-Antarctic region. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
Protein kinase Cδ and protein tyrosine kinase regulate peptidoglycan-induced nuclear factor-κB activation and inducible nitric oxide synthase expression in mouse peritoneal macrophages in vitro
(2010) Kunal H. Bhatt; Rajeev Kumar Pandey; Yogesh Dahiya; Ajit Sodhi
Bacteria and their ubiquitous cell wall component peptidoglycan (PGN) activate the innate immune system of the host and induce the release of inflammatory molecules. Nitric oxide (NO) is a potent molecule involved in the cytotoxic effects mediated by macrophages (MΦ) against microorganisms. This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide release caused by peptidoglycan from Staphylococcus aureus in mouse peritoneal macrophages. Protein tyrosine kinase inhibitor, genestein and PKCδ inhibitor, rottlerin attenuated the PGN-induced expression of iNOS and NO. H-7, a PKC inhibitor did not significantly affected the PGN-induced iNOS expression and NO release. NF-κB inhibitor, curcumin also inhibited PGN-induced NO release. Treatment of MΦ with PGN caused an increase in protein tyrosine kinase activity, expression and activation of PKCδ, IκB phosphorylation and p65 (NF-κB) nuclear translocation. The PGN-induced IκB phosphorylation and p65 nuclear translocation was inhibited in macrophages pretreated with rottlerin and genestein. No paracrine or autocrine effect of TNF-α on PGN-induced iNOS expression and NO release was observed. These observations suggest that PGN induces enhanced expression of iNOS and NO production through activation of protein tyrosine kinases and PKCδ, which in turn initiates NF-κB activation and translocation to nucleus. © 2010 Elsevier Ltd. All rights reserved.
Role of prostaglandin E2 in peptidoglycan mediated iNOS expression in mouse peritoneal macrophages in vitro
(2010) Yogesh Dahiya; Rajeev Kumar Pandey; Kunal H. Bhatt; Ajit Sodhi
Many extracellular stimuli, e.g. microbial products, cytokines etc., result in the expression of inducible nitric oxide synthase (iNOS) in macrophages. However, it is not known whether expression of the iNOS gene in response to microbial products is a primary response of macrophages, or is the result of paracrine/autocrine signalling induced by endogenous biomolecules that are synthesised as a result of host cell-microbe interaction. In this paper we demonstrate that iNOS expression in mouse peritoneal macrophages in response to bacterial peptidoglycan (PGN) is a secondary effect requiring autocrine signalling of endogenously produced prostaglandin E2, and that PGN stimulation is mandatory, but not sufficient in itself, for induction of iNOS expression. © 2010 Federation of European Biochemical Societies.
Ultrahigh-temperature granulites from the Shillong-Meghalaya Gneissic Complex, NE India: Implications for the Indo-Antarctic Correlation
(Elsevier Ltd, 2025) Bikash Mahanta; Divya Prakash; Manish Kumar; Saurabh Kumar Singh; Rajeev Kumar Pandey; Chandrakant Singh; Roopali Yadav; Jesus Solé Vinas
The Shillong-Meghalaya Gneissic Complex (SMGC) in the Riangdo region, northeastern India, is mainly composed of metamorphic rocks from upper amphibolite to ultrahigh temperature (UHT) granulite facies with several igneous intrusions. The pelitic granulite comprises biotite, garnet, K-feldspar, sillimanite, spinel, quartz, and biotite. This study is the first to report ultrahigh-temperature (UHT) metamorphism in the Riangdo (Sonapahar) block of the SMGC. Metamorphic pressure–temperature conditions estimated from the Spinel + Quartz bearing pelitic granulite using conventional thermobarometer (THERMOCALC) and pseudosection modelling in the MnO-Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–Fe2O3 system are more than 900 °C and pressure of about 8 kbars, representing UHT metamorphism. The sequence of reactions, constructed from the post-peak textural relationship, along with petrogenetic grid and pseudosection modelling, records a clockwise P–T evolution. This indicates an isothermal decompression path associated with rapid uplift before cooling of the tectonically thickened crust. Available geochronological ages suggest the presence of widespread Pan-African tectonothermal events in the SMGC. The K-Ar isotopic ages obtained from biotite suggest a cooling age of 407.20 ± 3.49 Ma. Given the general acceptance of UHT with clockwise isothermal decompression in Pan-African age metamorphism in the East-African-Antarctic Orogen (EAAO) and Eastern Ghat Mobile Belt (EGMB), the Sonapahar UHT metamorphic history is considered to be part of this record. © 2024 Elsevier Ltd