Frozen in time: The electrochemical processes occurring in a battery are highly dynamic. To understand the complexities of the charge and discharge cycles, you need to be able to watch the processes in situ or to freeze the battery rapidly for ex situ analysis. Li et al. applied cryo–electron microscopy techniques commonly used for studying biological samples to examine batteries. They identified the solid electrolyte interphase that forms, observed the interactions of Li with the interphase, and captured the formation of dendrites that can be detrimental to the lifetime of a battery. Science , this issue p. 506

From genetics to material to behavior: Introducing new genes into an organism can endow new biochemical functions or change the patterns of existing functions, but extending these manipulations to structure at the tissue level is challenging. Combining genetic engineering and polymer chemistry, Liu et al. directly leveraged complex cellular architectures of living organisms to synthesize, fabricate, and assemble bioelectronic materials (see the Perspective by Otto and Schmidt). An engineered enzyme expressed in genetically targeted neurons synthesized conductive polymers in tissues of freely moving animals. These polymers enabled modulation of membrane properties in specific neuron populations and manipulation of behavior in living animals. Science , this issue p. 1372 ; see also p. 1303

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical and infectious morbidity. The primary molecular chain of events leading to the initiation of adhesions has been elusive, chiefly due to the lack of an identifiable cell of origin. Using clonal analysis and lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) and mesothelin (MSLN) as a primary instigator of peritoneal adhesions after surgery in mice. We demonstrate that an anti-MSLN antibody diminished adhesion formation in a mouse model where adhesions were induced by surgical ligation to form ischemic buttons and subsequent surgical abrasion of the peritoneum. RNA sequencing and bioinformatics analyses of mouse mesothelial cells from injured mesothelium revealed aspects of the pathological mechanism of adhesion development and yielded several potential regulators of this process. Specifically, we show that PDPN⁺MSLN⁺ mesothelium responded to hypoxia by early up-regulation of hypoxia-inducible factor 1 alpha (HIF1α) that preceded adhesion development. Inhibition of HIF1α with small molecules ameliorated the injury program in damaged mesothelium and was sufficient to diminish adhesion severity in a mouse model. Analyses of human adhesion tissue suggested that similar surface markers and signaling pathways may contribute to surgical adhesions in human patients.

Huntington’s disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD.