Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Conformational ensemble-based framework enables rapid development of Lassa virus vaccine candidates.

Lassa virus (LASV), an arenavirus endemic to West Africa, poses a significant public health threat due to its high pathogenicity and expanding geographic risk zone. LASV glycoprotein complex (GPC) is the only known target of neutralizing antibodies, but its inherent metastability and conformational flexibility have hindered the development of GPC-based vaccines. We employed a variant of AlphaFold2 (AF2), called subsampled AF2, to generate diverse structures of LASV GPC that capture an array of potential conformational states using MSA subsampling and dropout layers.

Optimisation of cell fate determination for cultivated muscle differentiation.

Production of cultivated meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibres in vitro. Although these formulations can drive myogenic differentiation levels comparable to serum-starvation-based protocols, the resulting cultures are often heterogeneous, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. To address this problem, we employed RNA sequencing to analyse heterogeneity in differentiating bovine satellite cells at single-nucleus resolution, identifying distinct cellular subpopulations including proliferative cells that fail to exit the cell cycle and quiescent 'reserve cells' that do not commit to myogenic differentiation.

Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.

The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses.

Advances and Challenges in Cell Biology for Cultured Meat.

Cultured meat is an emerging biotechnology that aims to produce meat from animal cell culture, rather than from the raising and slaughtering of livestock, on environmental and animal welfare grounds. The detailed understanding and accurate manipulation of cell biology are critical to the design of cultured meat bioprocesses. Recent years have seen significant interest in this field, with numerous scientific and commercial breakthroughs.