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Biology subjects

Meena, K.

Publications and source records attributed to Meena, K..

3 recordsLinked to original sources

A large-scale crowd-sourced annotated acoustic dataset of Indian fauna

Global rates of biodiversity loss warrant conservation action and monitoring at large geographic scales. Conservation technologies such as acoustic monitoring in conjunction with deep learning now enable us to monitor wildlife simultaneously across space and time. However, for a significant proportion of biodiversity in tropical regions, we cannot yet rely on automated recognition approaches because we lack acoustic templates to robustly train deep learning algorithms. In this paper, we relied on a novel participatory approach, enlisting researchers, conservation practitioners, and nature enthusiasts to create a unique crowd-sourced, open-access dataset of acoustic annotations across taxonomic groups for biodiversity in India. Our dataset comprises 3311 minutes of strongly labelled data (bounding boxes or annotations for a species vocalization) and 2504 minutes of weakly labelled data (indicating the presence of a species within an audio file but lacking bounding boxes) for 518 species across India, spanning 25 of 36 states and union territories. We present metadata and code for data processing and highlight the strengths of a participatory approach to biodiversity monitoring.

ecology↗

Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice

Treatments for pancreatic ductal adenocarcinoma (PDAC) are poorly effective, at least partly due to the tumors immune-suppressive stromal compartment. New evidence of positive effects on immune responses in the tumor microenvironment, compelled us to test the combination of gemcitabine (GEM), a standard chemotherapeutic for pancreatic cancer, with nicotinamide (NAM), the amide form of niacin (vitamin B3), in various mouse tumor models of pancreatic cancer, i.e. peritoneal or orthotopic of Panc-02 (KrasG12D) and orthotopic KPC (KrasG12D, p53R172H, Pdx1-Cre) grafts. A significant reduction in tumor weight and number of metastases was found, as well as a significant improved survival of the NAM+GEM group compared to all control groups. Immunohistochemistry and flow cytometry of pancreatic tumors showed a significant decrease in tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), an increase in the number of CD4 and CD8 T cells and the production of granzyme B in the NAM+GEM group. Moreover, T cell responses to tumor-associated antigen survivin were observed in spleens of the mice that received NAM+GEM but not in those that received single agents or saline. In addition, remodeling of the tumor stroma was observed with decreased collagen I and expression of hyaluronic acid binding protein, reorganization of the immune cells into lymph node like structures, and CD31 positive vessels. Expression profiling for a panel of immuno-oncology genes revealed significant changes in genes involved in migration and activation of T cells, attraction of dendritic cells, and epitope spreading. This study highlights the potential of NAM+GEM as immunotherapy for advanced pancreatic cancer.

immunology↗

A new immunotherapeutic concept for pancreatic cancer using childhood vaccine recall antigens and Listeria

Pancreatic ductal adenocarcinoma is highly metastatic, poorly immunogenic, and immune suppression prevents T cell activation in the tumor microenvironment. We developed a microbial-based immunotherapeutic concept for selective delivery of a highly immunogenic tetanus toxoid protein (TT856-1313), into tumor cells by attenuated Listeria monocytogenes, and reactivation of pre-existing TT-specific memory T cells (generated during childhood) to kill infected tumor cells. Thus, TT here functions as an alternative for neoantigens. Treatment of KPC mice with Listeria-TT resulted in TT accumulation in tumors and inside tumor cells, and attraction of predominantly TT-specific memory CD4 T cells. Moreover, gemcitabine (GEM) combined with Listeria-TT significantly improved the migration of CD4 T cells into tumors and the production of perforin and granzyme B, turning cold tumors into immunological hot tumors. In vivo depletion of T cells in Listeria-TT+GEM-treated mice demonstrated CD4 T cell-mediated eradication of tumors and metastases (Mann-Whitney p<0.05). In addition, peritumoral lymph node like structures (LNS) were observed in close contact with the pancreatic tumors displaying CD4 T cells and CD8 T cells of KPC mice treated with Listeria-TT or Listeria-TT+GEM. The production of perforin and granzyme B was observed in LNS of KPC mice that received Listeria-TT+GEM. This combination not only reduced tumor burden (80%) and metastases (87%) significantly (p<0.05, Mann-Whitney), but also improved the survival time of KPC mice with advanced pancreatic cancer substantially (Mantel-Cox p<0.0001). Our results unveil new mechanisms of Listeria and GEM improving immunotherapy for PDAC.

immunology↗