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result(s) for
"Roy, Sumedha"
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Aam Aastha : Indian devotions
Internationally renowned photographer Charles Fréger continues to explore global traditions and cultures, by celebrating the powerful visual aspects of Indian folk culture and religious ritual. India is the home to a myriad of local traditions, legends and religions, each with their own festivals, rites and rituals. Celebrations burst with vivid colours and often wildly exuberant costumes, some representing gods and goddesses, others legendary heroes from Sanskrit epics such as the Mahabharata and the Ramayana. In Charles Fréger's photographs, those who honour local cultural traditions are represented in single or group portraits, represented against carefully chosen landscapes and backdrops, from the heart of festivals and celebrations.
Book
Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes
Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-negative (DN) 2 cells and after successful rearrangement and selection for functional TCRβ chains in DN3 thymocytes, which promotes the transition of DN4 cells to the DP stage. The signals driving the expansion of DN2 thymocytes are well studied. However, factors regulating the proliferation and survival of DN4 cells remain poorly understood. Here, we uncover an unexpected link between the transcription factor Zfp335 and control of cGAS/STING-dependent cell death in post-β-selection DN4 thymocytes. Zfp335 controls survival by sustaining expression of Ankle2, which suppresses cGAS/STING-dependent cell death. Together, this study identifies Zfp335 as a key transcription factor regulating the survival of proliferating post-β-selection thymocytes and demonstrates a key role for the cGAS/STING pathway in driving apoptosis of developing T cells.
T cell development involves extensive proliferation of developing thymocytes. Here, the authors demonstrate that the transcription factor Zfp335 regulates the survival post-β-selection thymocytes via the cGAS/STING pathway.
Journal Article
Autonomous IL-36R signaling in neutrophils activates potent antitumor effector functions
While the rapid advancement of immunotherapies has revolutionized cancer treatment, only a small fraction of patients derive clinical benefit. Eradication of large, established tumors appears to depend on engaging and activating both innate and adaptive immune system components to mount a rigorous and comprehensive immune response. Identifying such agents is a high unmet medical need, because they are sparse in the therapeutic landscape of cancer treatment. Here, we report that IL-36 cytokine can engage both innate and adaptive immunity to remodel an immune-suppressive tumor microenvironment (TME) and mediate potent antitumor immune responses via signaling in host hematopoietic cells. Mechanistically, IL-36 signaling modulates neutrophils in a cell-intrinsic manner to greatly enhance not only their ability to directly kill tumor cells but also promote T and NK cell responses. Thus, while poor prognostic outcomes are typically associated with neutrophil enrichment in the TME, our results highlight the pleiotropic effects of IL-36 and its therapeutic potential to modify tumor-infiltrating neutrophils into potent effector cells and engage both the innate and adaptive immune system to achieve durable antitumor responses in solid tumors.
Journal Article
E protein binding at the Tcra enhancer promotes Tcra repertoire diversity
V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4 + CD8 + double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Eα. To understand the contribution of E proteins to Eα function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of αβ T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jα array, along with dysregulated primary and impaired secondary Vα-Jα rearrangement. Eα E protein binding increases Tcra locus accessibility and regulates TCRα recombination, thus directly promoting Tcra repertoire diversity.
Journal Article
Comprehensive Study and Realizing an Enhanced Efficiency of the Thermoelectric Generator Along with Its Thermomechanical Properties
This paper proposes a real-time simulation model to simplify the research and outcome of a portable thermoelectric generator (TEG) system in real conditions. Consequently, the model is divided into three parts: conventional, segmented, and hybrid TEG systems. The conventional TEG system consisted of Bi
2
Te
3
as the
p
-type and the
n
-type materials, whereas the segmented and the hybrid TEG systems consisted of a different combination of materials, including PbTe and Sb
2
Te
3
. The optimization of the TEG system length was carried out to achieve the highest power output, which was found to be 2 mm. In addition, thermomechanical stress distribution analysis of the module was conducted to determine the maximum load the TEG system could withstand before undergoing fracture, depending upon the yield strength of the material. The stress was analyzed in all three TEG systems, and the results were evaluated. Results were observed from the optimized length at 2 mm. The conventional, segmented, and hybrid TEG systems showed maximum power output of 147.122 mW, 171.934 mW, and 550 mW, respectively, with a temperature difference at 50 K.
Journal Article
Oleander Stem and Root Standardized Extracts Mitigate Acute Hyperglycaemia by Limiting Systemic Oxidative Stress Response in Diabetic Mice
The extracts of different parts of Nerium oleander L. are used as antidiabetic remedy in the traditional medicinal systems of different parts of the world. Despite these uses in ethnomedicinal system, the antihyperglycemic potentials of oleander stem (NOSE) and root (NORE) extracts have not been pharmacologically evaluated. Therefore, we aimed at evaluating the antidiabetic ethnomedicinal claims of NOSE and NORE, primarily focusing on glucose homeostasis and associated metabolic implications. Alloxan-treated mice with hyperglycaemia (blood glucose >200 mg/dL) were treated with oleander 70% hydromethanolic extracts (200 mg/kg) for 20 consecutive days, and the results were compared with positive control glibenclamide. Blood glucose level was 52–65% lowered (P<0.001) in oleander treated groups, which was otherwise 4.62 times higher in diabetic mice, compared to control. Insulin resistance was lowered 51–36% irrespective of any significant (P>0.05) changes in insulin sensitivity throughout the treatments. Improved serum insulin remained associated with lowered glucose level (rP = −0.847 and −0.772; P<0.01). Markers of hyperglycaemia-related hepatic glycogen, glycated haemoglobin (HbA1c), hyperlipidaemia, hepatic injury, and diabetic nephropathy were normalized as well. Improvement of systemic intrinsic antioxidant enzymes (catalase and peroxidase) were correlated (rP = −0.952 to −0.773; P<0.01) with lower lipid peroxidation by-product malondialdehyde (MDA) in the circulation. Principal component analysis coupled with hierarchical cluster analysis represented shift in metabolic homeostasis in diabetic mice, which was further normalized by oleander and glibenclamide treatment. Additionally, molecular docking studies of the phenolic acids measured by HPLC with intracellular cytoprotective transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) revealed strong molecular interactions. The results collectively support the ethnomedicine antidiabetic claims of oleander stem and root and suggest that the oleander mediated elevation of systemic antioxidant status is likely responsible for the improved glycaemic control.
Journal Article
Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function. There is also biased rearrangement in Id-deficient DP cells that promotes selection into the iNKT lineage in these mice. The observed expansion of iNKT cells is not abrogated by blocking pre-TCR signaling, which is required for conventional αβ T cell development. Finally, E2A is found to be a key transcriptional regulator of both iNKT and γδNKT lineages, which appear to have shared lineage history. Therefore, our study reveals a previously unappreciated role of E2A in coordinating the development of the iNKT lineage at an early stage, prior to their TCR-mediated selection alongside conventional αβ T cells.
Journal Article
Monitoring the effects of a lepidopteran insecticide, Flubendiamide, on the biology of a non-target dipteran insect, Drosophila melanogaster
Various organisms are adversely affected when subjected to chronic fluoride exposure. This highly electronegative ion present in several insecticide formulations is found to be lethal to target pests. In the present study,
Drosophila melanogaster
is treated with sub-lethal concentrations of a diamide insecticide formulation, Flubendiamide. Chronic exposure to the diamide (0.5–100 μg/mL) was found to be responsible for increase in fluoride ion concentration in larval as well as adult body fluid. Interestingly, 100 μg/mL Flubendiamide exposure resulted in 107 and 298% increase in fluoride ion concentration whereas only 23 and 52% of Flubendiamide concentration increase in larval and adult body fluid, respectively. Further, in this study, selected life cycle parameters like larval duration, pupal duration and emergence time showed minimal changes, whereas percentage of emergence and fecundity revealed significant treatment-associated variation. It can be noted that nearly 79% reduction in fecundity was observed with 100 μg/mL Flubendiamide exposure. The variations in these parameters indicate probable involvement of fluoride ion in detectable alterations in the biology of the non-target model insect,
D. melanogaster
. Furthermore, the outcomes of life cycle study suggest change in resource allocation pattern in the treated flies. The altered resource allocation might have been sufficient to resist changes in selective life cycle parameters, but it could not defend the changes in fecundity. The significant alterations indicate a definite trade-off pattern, where the treated individuals happen to compromise. Thus, survival is apparently taking an upper hand in comparison to reproductive ability in response to Flubendiamide exposure.
Graphical abstract
The figure demonstrates increase in Fluoride and Flubendiamide concentrations in Drosophila melanogaster after chronic sub-lethal exposure to Flubendiamide. Treatment-induced alterations in larval and pupal duration, reduction in fecundity and alteration in male-female ratio is also observed.
Journal Article
Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells
A family of transcription factors known as Id proteins, or inhibitor of DNA binding and differentiation, is capable of regulating cell proliferation, survival and differentiation, and is often upregulated in multiple types of tumors. Due to their ability to promote self-renewal, Id proteins have been considered as oncogenes, and potential therapeutic targets in cancer models. On the contrary, certain Id proteins are reported to act as tumor suppressors in the development of Burkitt's lymphoma in humans, and hepatosplenic and innate-like T cell lymphomas in mice. The contexts and mechanisms by which Id proteins can serve in such contradictory roles to determine tumor outcomes are still not well understood. In this review, we explore the roles of Id proteins in lymphocyte development and tumorigenesis, particularly with respect to inhibition of their canonical DNA binding partners known as E proteins. Transcriptional regulation by E proteins, and their antagonism by Id proteins, act as gatekeepers to ensure appropriate lymphocyte development at key checkpoints. We re-examine the derailment of these regulatory mechanisms in lymphocytes that facilitate tumor development. These mechanistic insights can allow better appreciation of the context-dependent roles of Id proteins in cancers and improve considerations for therapy.
Journal Article
Flubendiamide induces transgenerational compound eye alterations in Drosophila melanogaster
Pesticides are one of the major sources of environmental toxicity and contamination. This study reports potential of lepidopteran insecticide formulation, named Flubendiamide, in altering compound eye architecture and bristle pattern orientation for four consecutive generations (P, F1, F2 and F3) in a non-target diptera, Drosophila melanogaster Meigen (Diptera: Drosophilidae). The concentrations of the insecticide formulation selected for treatment of Drosophila (50 and 100 μg/mL) were in accordance with practiced Indian field doses (50 μg/mL for rice and 100 μg/mL for cotton). This study showed trans-generational insecticide-induced changes in the morphology of the compound eyes of the non-target insect D. melanogaster.
Journal Article