Chan Zuckerberg Initiative (United States)

Multi-organelle signatures map cell-state diversity and metabolic adaptation in tissues

Cell-state diversity drives tissue adaptability, repair, and disease resilience, but capturing this complexity is a challenge. Current approaches rely on transcriptional profiling and overlook organelle structure, a key indicator of metabolism and stress. We developed spatial Org...

COVID-19 lockdown and coverage of maternal health and nutrition care in rural West Bengal, India: a single interrupted time-series analysis

Abstract While COVID-19 lockdowns globally disrupted healthcare, the extent of changes in India’s maternal health and nutrition services coverage in rural settings requires further empirical investigation. Utilizing data from 57,371 pregnancies recorded between January 2012 and D...

Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC

Abstract Despite a decade in, immunotherapy (IO) treatment selection in non-small cell lung cancer (NSCLC) remains largely guided by subgroup analyses and imperfect programmed death ligand 1 (PD-L1) and clinical scores. To our knowledge, I 3 LUNG ( NCT05537922 ) is currently the...

Single‐cell RNA sequencing of peripheral blood defines two immunological subtypes of Sjögren's disease distinguished by anti‐SSA antibodies and aberrant B cell populations

OBJECTIVES: Sjögren's disease (SjD) is a heterogeneous autoimmune disorder characterized by substantial clinical and molecular diversity. This heterogeneity raises key questions regarding the existence of distinct pathogenic mechanisms underlying disease subtypes. The objective o...

Multiscale physical effects of CpG methylation on DNA mechanics, nucleosome wrapping, and chromatin condensates

DNA methylation at CpG dinucleotides is a central epigenetic modification linked to transcriptional repression and heterochromatin formation, yet its physical impact on chromatin organization remains incompletely understood. Here, we integrate single-molecule force spectroscopy,...

Enhanced Osteoinduction, Rheological and Mechanical Performance of 3D-Printed Methylcellulose-Gelatin-Hydroxyapatite Scaffolds

Complex patient-specific bone defects remain difficult to reconstruct because the regenerative capacity of bone is limited and prefabricated implants cannot readily match defect geometry. In this work, methylcellulose-gelatin-hydroxyapatite (MC/GEL/HA) inks were formulated with v...

JNK signaling regulates reproductive trade-offs after Plasmodium infection in the malaria mosquito

ABSTRACT Environmental stress can limit mammalian reproduction by affecting production of sexual steroid hormones. Here we reveal a similar mechanism in the malarial mosquito Anopheles gambiae : activation of the stress-sensitive c- J un N -terminal k inase, JNK, constrains repro...

Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle

Abstract Faithful chromosome segregation is essential for producing viable gametes during meiosis, a specialized type of cell division compared to mitosis. Unlike mitosis, meiosis involves two consecutive chromosome segregation events without an intervening round of DNA replicati...

Lessons learned from a Kaggle challenge for particle picking in cryo-electron tomography

Abstract The difficulty of particle picking in cryo-electron tomography remains a barrier to routine in situ structure determination. Machine learning is well-suited to overcome this bottleneck with efficient algorithms that generalize across molecular species. To spur new algori...