Nature Communications最新文献

The promise of integrating Electronic Medical Records (EMR) and genetic data for precision medicine has largely fallen short due to its omission of environmental context over time. Post-genomic data can bridge this gap by capturing the real-time dynamic relationship between underlying genetics and the environment. This perspective highlights the pivotal role of integrating EMR and post-genomics for personalized health, reflecting on lessons from past efforts, and outlining a roadmap of challenges and opportunities that must be addressed to realize the potential of precision medicine.

The tangential expansion of the human cerebral cortex, indexed by its surface area (SA), occurs mainly during prenatal and early postnatal periods, and is influenced by genetic factors. Here we investigate the role of rare copy number variants (CNVs) in shaping SA, and the underlying mechanisms, by aggregating CNVs across the genome in community-based cohorts (N = 39,015). We reveal that genome-wide CNV deletions and duplications are associated with smaller SA. Subsequent analyses with gene expression in fetal cortex suggest that CNVs influence SA by interrupting the proliferation of neural progenitor cells during fetal development. Notably, the deletion of genes with strong (but not weak) coexpression with neural progenitor genes is associated with smaller SA. Follow up analyses reveal similar mechanisms at play in three clinical CNVs, 1q21.1, 16p11.2 and 22q11.2. Together, this study of rare CNVs expands our knowledge about genetic architecture of human cerebral cortex.

Infections caused by Staphylococcus aureus depend on its ability to acquire nutrients. One essential nutrient is iron, which is obtained from the heme of the human host hemoglobin (Hb) through a protein machinery called Iron-regulated surface determinant (Isd) system. IsdB is the protein in charge of heme extraction from Hb, which is the first step of the chain of events leading to iron transfer to the bacterium cell interior. In order to elucidate the molecular events leading from the formation of the initial IsdB:Hb complex to heme extraction, we use time-resolved X-ray solution scattering (TR-XSS) in combination with rapid mixing triggering. We succeed in defining the stoichiometry of IsdB:Hb binding and in describing the kinetics of the subsequent structural changes. The presented approach is potentially applicable to unveil the complex kinetic pathways generated by protein-protein interaction in different biological systems.

The observation of a superconducting phase, an intertwined insulating phase, and a continuous transition between the two at a commensurate filling of ν = 1 in bilayers of twisted WSe₂ at θ = 3.65⁰ raises a number of intriguing questions about the origin of this phenomenology. Here we report the possibility of a displacement-field induced continuous transition between a superconductor and a quantum spin-liquid Mott insulator at ν = 1, starting with a simplified three-orbital model of twisted WSe₂, including on-site, nearest-neighbor density-density interactions, and a chiral-exchange interaction, respectively. By employing parton mean-field theory, we discuss the nature of these correlated insulators, their expected evolution with the displacement-field, and their phenomenological properties.

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicate that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 reveals that most disease-associated missense variants are located within the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants show reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS (SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.

Precise organization of organic molecules into homochiral double-helix remains a challenge due to the difficulty in controlling both self-assembly process and chirality transfer across length scales. Here, we report that a type of bisnaphthalene bisurea molecule could assemble into chirality-controlled nanoscale double-helices by a supramolecular rosette-intermediated hierarchical self-assembly mechanism. A solvent-mixing self-assembly protocol is adopted to direct bisnaphthalene bisurea cyclization into chiral discrete rosettes through cooperative intramolecular and intermolecular hydrogen bonds. Controlled hexagonal packing of rosettes at higher concentrations gives one-dimensional single-stranded nanofibers, which intertwine into well-defined double-helix nanostructures with preferred chirality that depends on the absolute configurations of bisnaphthalene bisurea. The hierarchical organization of bisnaphthalene bisurea molecules enables effective excitation energy delocalization within the double-helix, which contributes to near-unity energy transfer from double-helix to adsorbed acceptor dyes even in donor/acceptor ratios over 1000, leading to bright circularly polarized luminescence from the originally achiral acceptor. The experimental and theoretical simulation results not only provide a hierarchical strategy to fabricate homochiral double-helix but also bring insights in understanding the high-efficiency light-harvesting process in photosystem II.

Monitoring the early-stage healing of severe traumatic nerve injuries is essential to gather physiological and pathological information for timely interventions and optimal clinical outcomes. Traditional diagnostic methods relying on physical examinations, imaging tools, and intraoperative electrophysiological testing present great challenges in continuous and remote monitoring. While implantable peripheral nerve interfaces provide direct access to nerve fibers for precise interrogation and modulation, conventional non-degradable designs pose limited utilization in nerve injury rehabilitation. Here, we introduce a biodegradable and restorative neural interface for wireless real-time tracking and recovery of long-gap nerve injuries. Leveraging machine learning techniques, this electronic platform deciphers nerve recovery status and identifies traumatic neuroma formation at the early phase, enabling timely intervention and significantly improved therapeutic outcomes. The biodegradable nature of the device eliminates the need for retrieval procedures, reducing infection risks and secondary tissue damage. This research sheds light on bioresorbable multifunctional peripheral nerve interfaces for probing neuropathic injuries, offering vital information for early diagnosis and therapeutic intervention.

The CHAMP1 complex, a little-known but highly conserved protein complex consisting of CHAMP1, POGZ, and HP1α, is enriched in heterochromatin though its cellular function in these regions of the genome remain unknown. Here we show that the CHAMP complex promotes heterochromatin assembly at multiple chromosomal sites, including centromeres and telomeres, and promotes homology-directed repair (HDR) of DNA double strand breaks (DSBs) in these regions. The CHAMP1 complex is also required for heterochromatin assembly and DSB repair in highly-specialized chromosomal regions, such as the highly-compacted telomeres of ALT (Alternative Lengthening of Telomeres) positive tumor cells. Moreover, the CHAMP1 complex binds and recruits the writer methyltransferase SETDB1 to heterochromatin regions of the genome and is required for efficient DSB repair at these sites. Importantly, peripheral blood lymphocytes from individuals with CHAMP1 syndrome, an inherited neurologic disorder resulting from heterozygous mutations in CHAMP1, also exhibit defective heterochromatin clustering and defective repair of DSBs, suggesting that a defect in DNA repair underlies this syndrome. Taken together, the CHAMP1 complex has a specific role in heterochromatin assembly and the enhancement of HDR in heterochromatin.

The effectiveness of the hepatitis E vaccine in high-risk groups, such as chronic hepatitis B (CHB) patients, remains understudied. A key clinical manifestation of CHB is the persistent positivity of hepatitis B surface antigen (HBsAg). We conducted a test-negative design study involving 2,926 HBsAg-positive individuals (born 1941–1991; median age 49.0; male-to-female ratio of 1.4), identified through a hepatitis surveillance system, as part of the phase 3 trial (NCT01014845) of the recombinant hepatitis E vaccine HEV 239 (Hecolin). This system monitored suspected hepatitis cases and performed diagnoses across 11 townships in Dongtai, Jiangsu, China, from 2007 to 2017. Vaccine effectiveness of HEV 239 was assessed by comparing vaccination status between confirmed 96 hepatitis E cases and 2830 test-negative controls, using logistic regression adjusted for sex and age. We found that HEV 239 vaccination was associated with a reduced risk of hepatitis E among HBsAg-positive individuals, with an estimated effectiveness of 72.1% [95% confidence interval (CI) 11.2–91.2], and 81.5% (95% CI 35.9–94.6) among phase 3 trial participants. Our findings show that HEV 239 is highly effective in HBsAg-positive adults, supporting its future recommended use in this population.