Using the United States' National Suicide and Crisis Lifeline as a case example, we discuss the tacit requirement that users of helplines disclose suicide-related thoughts and behaviors as a central barrier to suicide prevention interventions. This comment outlines the need for self-guided digital suicide prevention interventions within helpline infrastructure.

Unravelling how genomes are spatially organized and how their three-dimensional (3D) architecture drives cellular functions remains a major challenge in biology1,2. In bacteria, genomic DNA is compacted into a highly ordered, condensed state called nucleoid3-5. Despite progress in characterizing bacterial 3D genome architecture over recent decades6-8, the fine structure and functional organization of the nucleoid remain elusive due to low-resolution contact maps from methods such as Hi-C9-11. Here we developed an enhanced Micro-C chromosome conformation capture, achieving 10-base pair (bp) resolution. This ultra-high-resolution analysis reveals elemental spatial structures in the Escherichia coli nucleoid, including chromosomal hairpins (CHINs) and chromosomal hairpin domains (CHIDs). These structures, organized by histone-like proteins H-NS and StpA, have key roles in repressing horizontally transferred genes. Disruption of H-NS causes drastic reorganization of the 3D genome, decreasing CHINs and CHIDs, whereas removing both H-NS and StpA results in their complete disassembly, increased transcription of horizontally transferred genes and delayed growth. Similar effects are observed with netropsin, which competes with H-NS and StpA for AT-rich DNA binding. Interactions between CHINs further organize the genome into isolated loops, potentially insulating active operons. Our Micro-C analysis reveals that all actively transcribed genes form distinct operon-sized chromosomal interaction domains (OPCIDs) in a transcription-dependent manner. These structures appear as square patterns on Micro-C maps, reflecting continuous contacts throughout transcribed regions. This work unveils the fundamental structural elements of the E. coli nucleoid, highlighting their connection to nucleoid-associated proteins and transcription machinery.

After fertilization, early embryos undergo dissolution of conventional chromatin organization, including topologically associating domains (TADs)1,2. Zygotic genome activation then commences amid unusually slow de novo establishment of three-dimensional chromatin architecture2. How chromatin organization is established and how it interplays with transcription in early mammalian embryos remain elusive. Here we show that CTCF occupies chromatin throughout mouse early development. By contrast, cohesin poorly binds chromatin in one-cell embryos, coinciding with TAD dissolution. Cohesin binding then progressively increases from two- to eight-cell embryos, accompanying TAD establishment. Unexpectedly, strong 'genic cohesin islands' (GCIs) emerge across gene bodies of active genes in this period. GCI genes enrich for cell identity and regulatory genes, display broad H3K4me3 at promoters, and exhibit strong binding of transcription factors and the cohesin loader NIPBL at nearby enhancers. We show that transcription is hyperactive in two- to eight-cell embryos and is required for GCI formation. Conversely, induced transcription can also create GCIs. Finally, GCIs can function as insulation boundaries and form contact domains with nearby CTCF sites, enhancing both the transcription levels and stability of GCI genes. These data reveal a hypertranscription state in early embryos that both shapes and is fostered by the three-dimensional genome organization, revealing an intimate interplay between chromatin structure and transcription.

The time interval between about three and two million years ago is a critical period in human evolution-this is when the genera Homo and Paranthropus first appear in the fossil record and a possible ancestor of these genera, Australopithecus afarensis, disappears. In eastern Africa, attempts to test hypotheses about the adaptive contexts that led to these events are limited by a paucity of fossiliferous exposures that capture this interval. Here we describe the age, geologic context and dental morphology of new hominin fossils recovered from the Ledi-Geraru Research Project area, Ethiopia, which includes sediments from this critically underrepresented period. We report the presence of Homo at 2.78 and 2.59 million years ago and Australopithecus at 2.63 million years ago. Although the Australopithecus specimens cannot yet be identified to species level, their morphology differs from A. afarensis and Australopithecus garhi. These specimens suggest that Australopithecus and early Homo co-existed as two non-robust lineages in the Afar Region before 2.5 million years ago, and that the hominin fossil record is more diverse than previously known. Accordingly, there were as many as four hominin lineages living in eastern Africa between 3.0 and 2.5 million years ago: early Homo1, Paranthropus2, A. garhi3, and the newly discovered Ledi-Geraru Australopithecus.

Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging. Here we present allele-specific phylogenetic analysis of copy number alterations (ALPACA), a method to infer SNV and SCNA coevolution by leveraging phylogenetic trees reconstructed from multi-sample bulk tumour sequencing data using SNV frequencies. ALPACA estimates the SCNA evolution of simulated tumours with a higher accuracy than current state-of-the-art methods1-4. ALPACA uncovers loss-of-heterozygosity and amplification events in minor clones that may be missed using standard approaches and reveals the temporal order of somatic alterations. Analysing clone-specific copy numbers in TRACERx421 lung tumours5,6, we find evidence of increased chromosomal instability in metastasis-seeding clones and enrichment for losses affecting tumour suppressor genes and amplification affecting CCND1. Furthermore, we identify increased SCNA rates in both tumours with polyclonal metastatic dissemination and tumours with extrathoracic metastases, and an association between higher clone copy number diversity and reduced disease-free survival in patients with lung cancer.

Intrinsically elastic thermoelectric generators with superior conformal coverage and shape adaptability are highly desirable for developing self-powered wearable electronics, soft bioelectronics and personal temperature regulators1,2. Until now, all reported high-performance thermoelectric materials have realized only flexibility, rather than elasticity3,4. Here we present one of the first n-type thermoelectric elastomers by integrating uniform bulk nanophase separation, thermally activated crosslinking and targeted doping into a single material. The thermoelectric elastomers could exhibit exceptional rubber-like recovery of up to 150% strains and high figure of merit values rivalling flexible inorganic materials even under mechanical deformations. Conventional wisdom suggests that incorporating insulating polymers should dilute the active component in organic thermoelectrics, resulting in lower performance. However, we demonstrate that carefully selected elastomers and dopants can promote the formation of uniformly distributed, elastomer-wrapped and heavily n-doped semiconducting polymer nanofibrils, leading to improved electrical conductivity and decreased thermal conductivity. These thermoelectric elastomers have the potential to make elastic thermoelectric generators in wearable applications much more conformable and efficient.