Biology subjects

Jayakumar, A.

Publications and source records attributed to Jayakumar, A..

3 recordsLinked to original sources

bioRxiv2023

Origin, age, and metabolisms of dominant anammox bacteria in the global oxygen deficient zones

Anammox bacteria inhabiting oxygen deficient zones (ODZs) are a major functional group mediating fixed nitrogen loss and thus exerting a critical control on the nitrogen budget in the global ocean. However, the diversity, origin, and broad metabolisms of ODZ anammox bacteria remain unknown. Here we report two novel metagenome-assembled genomes of Scalindua, which represent most, if not all, of the anammox bacteria in the global ODZs. Beyond the core anammox metabolism, both organisms contain cyanase and the more dominant one encodes a urease, indicating ODZ anammox bacteria can utilize cyanate and urea in addition to ammonium. The first ODZ Scalindua likely derived from the benthos [~]200 million years ago. Compared to benthic strains of the same clade, ODZ Scalindua uniquely encode genes for urea utilization but lost genes related to growth arrest, flagellum synthesis, and chemotaxis, presumably for adaptation to the anoxic water column.

microbiology↗

bioRxiv2023

Genome-resolved metagenomics reveals abundant nitrate reducers and partitioning of nitrite usage within global oxygen deficient zones

Oxygen deficient zones (ODZs) account for about 30% of total oceanic fixed nitrogen loss via processes including denitrification, a microbially-mediated pathway proceeding stepwise from NO3- to N2. This process may be performed entirely by complete denitrifiers capable of all four steps, but many organisms possess only partial denitrification pathways, either producing or consuming key intermediates such as the greenhouse gas N2O. Marker gene surveys have revealed a diversity of denitrification genes within ODZs, but whether these genes are primarily carried by complete or partial denitrifiers and the identities of denitrifying taxa remain open questions. From 56 metagenomes spanning all three major ODZs, we use genome-resolved metagenomics to reveal the predominance of partial denitrifiers, particularly single-step denitrifiers. We find niche differentiation among nitrogen-cycling organisms, with communities performing each nitrogen transformation distinct in taxonomic identity and motility traits. Our collection of 962 metagenome-assembled genomes presents the largest collection of pelagic ODZ microbes and reveals a clearer picture of the nitrogen cycling community within this environment.

microbiology↗

bioRxiv2019

RIPK3 inhibition prevents KRAS mutant p53 deficient lung tumor progression by impeding MDSCs

KRAS mutant p53 deficient (KP) non-small cell lung carcinoma (NSCLC) lacks targeted therapies. Existing treatments for lung cancer cause resistance and result in toxicities requiring novel effective therapies. By targeting mechanisms causing resistance such as myeloid derived suppressor cells (MDSCs), KP tumors could be inhibited. MDSCs are functionally diverse and suppress T cells in many cancers. RIPK3, a cell death inducing enzyme, also functions as a signaling component producing cytokines that mediate the suppressive function of MDSCs. Partial deletion of RIPK3 in myeloid cells reduced KP tumor growth. This also reduced accumulation of MDSCs with a consistent increase in antigen specific IFN{gamma} producing CD8 T cells. Inhibiting RIPK3 with a small molecule inhibitor such as GSK 872 effectively reduces RIPK3 activity in myeloid cells including MDSCs and reduces growth of small and large KP tumors. GSK 872 in combination with checkpoint inhibitors such as anti PD-1 and anti CTLA-4 further decreased KP tumor size. Together, our findings show that inhibiting RIPK3 in MDSCs is effective in inhibiting KP NSCLC and is a viable therapeutic option for improving existing immunotherapeutic treatments.

cancer biology↗