Growth factor induced receptor dimerization and activation of downstream pathways can modulate cell fate decisions. Here, we investigate the potential of de novo designed synthetic ligands, termed Nov Show more
Growth factor induced receptor dimerization and activation of downstream pathways can modulate cell fate decisions. Here, we investigate the potential of de novo designed synthetic ligands, termed Novokines, to reprogram cell identity by inducing proximity of novel pairs of receptor subunits. We find that a design, H2F, that brings together HER2 (which has no known natural ligand) and the FGF receptor has potent signaling activity. H2F induces robust signaling and reprograms fibroblasts into myogenic cells. Unlike native FGF ligands, H2F selectively activates the MAPK pathway without engaging PLCγ-mediated Ca²⁺ signaling. FRET assays confirm H2F-mediated HER2-FGFR proximity, and phosphoproteomic analysis reveals activation of MAPK effectors. H2F-induced ERK phosphorylation is abolished in cells expressing a kinase-dead FGFR1 (K514M) mutant, confirming the requirement for FGFR catalytic activity. H2F treatment significantly increases myofiber formation from adult patient-derived primary myoblasts, demonstrating its capacity to promote myogenic regeneration. Our findings demonstrate that synthetic receptor pairings can rewire signaling outputs to drive regeneration, providing a programmable platform for cell fate engineering. Show less
With less than two years remaining from 2027-the year which the government has targeted to achieve zero Indigenous cases, we map the malaria indicators across the 700 + districts for five years betwee Show more
With less than two years remaining from 2027-the year which the government has targeted to achieve zero Indigenous cases, we map the malaria indicators across the 700 + districts for five years between 2019 and 2023 using spatiotemporal maps and also assess the potential drivers of malaria transmission in different regions. We used the annual district-wise malaria data from the National Center for Vector Borne Disease Control Programme (NCVBDC) and the cross-sectional socio-economic data from the National Family Health Survey. We also collated the meteorological and land-use land-cover data from the MERRA-2 and Sentinel-LPA satellites, respectively. We then developed region-specific ensembles of spatiotemporal models that allowed us to identify the associated covariates while the regions were identified using the Getis-Ord Gi* statistics. With 0.33 million malaria cases in 2019, the COVID-19 pandemic led to a significant reduction in reported cases. The P. falciparum affected regions are widespread in North-eastern and Central India. However, after the pandemic, an emerging geographical expansion into the north-eastern parts is observed for the P. vivax, which is evident from the clusters and the spatiotemporal ensemble models. Population belonging to scheduled castes and scheduled tribes and those economically marginalised are among the most vulnerable, but lifestyle habits such as drinking water practices, maternal education, and healthcare accessibility are associated with malaria transmission. We also developed a digital dashboard that allows the general public and the stakeholders to track the malaria indicators for each district and the corresponding year. Show less
Household contact (HHC) investigation helps in early identification of people with tuberculosis (TB) and initiation of TB preventive treatment (TPT) among those at high risk of developing TB. This cro Show more
Household contact (HHC) investigation helps in early identification of people with tuberculosis (TB) and initiation of TB preventive treatment (TPT) among those at high risk of developing TB. This cross-sectional study uses National TB Elimination Program data of all people notified with bacteriologically confirmed pulmonary TB and their HHCs from October to December 2023, from Chhattisgarh, a central Indian state, to assess coverage of HHC investigation, proportions identified with TB and put on TPT (all age groups and age < 5 years). Sociodemographic, clinical, and health system-related factors were used to identify predictors of HHC investigation not done, as determined through modified Poisson regression. Of the 4,221 people notified with TB, an HHC investigation was conducted for 3,177 (75%) cases. Among a total of 11670 contacts screened, TB was diagnosed in 0.9%(n = 109) for all age groups and 0.7%(n = 9) for children<5 years. TPT was initiated in 66% (n = 7740) for all age groups and 73% (n = 903) for children<5 years. Women (adjusted prevalence risk aPR 1.10; 95%CI:1.01-1.19), those notified from non-tribal districts (aPR 1.14; 95%CI:1.01-1.29), current facility being tertiary care (aPR 1.50; 95%CI:1.12-2.00) and private (aPR 1.42; 95%CI:1.08-1.86) facility, diagnosed with test other than sputum microscopy (aPR NAAT 3.19; 95%CI:2.39-4.28; LPA 8.88 95%CI:6.15-12.82; culture 9.69; 95%CI:5.99-15.68) and for whom diabetes (aPR 1.40; 95%CI:1.16-1.70) and HIV screening (aPR 1.55, 95% CI:1.17-2.05) was missing predicted higher risk of HHC investigation not done. The study highlights the need to improve HHC investigation, as well as the low yield of TB and TPT initiation. Predictors of HHC investigation not done suggest a need to decentralize it to the primary level and improve data-based program monitoring. A statewide capacity-building initiative for improving the investigation of HHC is the way forward. Show less