Communications Biology最新文献

The role of early auditory experience in the development of neural speech tracking remains an open question. To address this issue, we measured neural speech tracking in children with or without functional hearing during their first year of life after their hearing was restored with cochlear implants (CIs), as well as in hearing controls (HC). Neural tracking in children with CIs is unaffected by the absence of perinatal auditory experience. CI users and HC exhibit a similar neural tracking magnitude at short timescales of brain activity. However, neural tracking is delayed in CI users, and its timing depends on the age of hearing restoration. Conversely, at longer timescales, speech tracking is dampened in participants using CIs, thereby accounting for their speech comprehension deficits. These findings highlight the resilience of sensory processing in speech tracking while also demonstrating the vulnerability of higher-level processing to the lack of early auditory experience.

The rapid dissemination of colistin resistance via mcr-carrying plasmids (pMCRs) poses a significant public health challenge. This study examined the genomic diversity and conjugation mechanisms of pMCRs, with a particular focus on the role of type IV secretion systems (T4SS) in IncI2 plasmids. The 868 complete plasmid sequences revealed various replicon types of pMCRs, with IncI2 as the primary epidemic type, and the co-transfer risk of multidrug resistance genes associated with IncHI2. T4SS was identified in 89.9% of pMCRs, with the T4SS sequence exclusively carried by IncI2 being conserved and typical of the VirB/D4 type, consisting of 12 subunits. Conjugation assays confirmed the essential role of the pilus subunit VirB2 and the significant impact of VirB5_P3 on conjugation. This was further validated in the in vivo intra-species competitive conjugation of Escherichia coli. Structural predictions show that a hypervariable region at the C-terminus of the pentameric VirB5 co-evolves in sequence with VirB6, and the conserved N-terminal may act as a potential drug target to inhibit the plasmid transfer channel. This study will deepen the understanding of the pMCR epidemic patterns and provide additional insights for controlling the spread of resistant plasmids.

Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of rare variants on cerebellar traits. This study conducts a large-scale exome association analysis using data from approximately 35,000 UK Biobank participants, examining seven cerebellar traits, including total cerebellar volume and white matter microstructure. We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure. Gene enrichment analysis reveals associations with non-coding RNA processing, cognitive function, neurodegenerative diseases, and mental disorders, suggesting shared biological mechanisms between cerebellar phenotypes and neuropsychiatric diseases.

Animal pollination is common among flowering plants. Increased morphological matching between floral and pollinator traits is thought to increase pollen transfer and feeding efficiency, but we lack studies that empirically demonstrate this. Working with Australian honeyeaters, we find that there is positive correlation between bill-corolla matching and pollen deposition at flowers, but no correlation with how efficiently birds can extract floral nectar. The species with the lowest bill-corolla matching deposited the fewest pollen grains but had the highest feeding efficiency, showing that bill-corolla matching expectations were met on the plant side of this interaction but not on the pollinator side. Finally, we find different interspecific patterns of pollen deposition at the scales of a single flower visit versus the landscape, due to differences in patterns of plant visitation. This work illustrates the need for more studies that directly correlate trait matching to fitness proxies of plants and avian pollinators.

Language reconstruction from non-invasive brain recordings has been a long-standing challenge. Existing research has addressed this challenge with a classification setup, where a set of language candidates are pre-constructed and then matched with the representation decoded from brain recordings. Here, we propose a method that addresses language reconstruction through auto-regressive generation, which directly uses the representation decoded from functional magnetic resonance imaging (fMRI) as the input for a large language model (LLM), mitigating the need for pre-constructed candidates. While an LLM can already generate high-quality content, our approach produces results more closely aligned with the visual or auditory language stimuli in response to which brain recordings are sampled, especially for content deemed "surprising" for the LLM. Furthermore, we show that the proposed approach can be used in an auto-regressive manner to reconstruct a 10 min-long language stimulus. Our method outperforms or is comparable to previous classification-based methods under different task settings, with the added benefit of estimating the likelihood of generating any semantic content. Our findings demonstrate the effectiveness of employing brain language interfaces in a generative setup and delineate a powerful and efficient means for mapping functional representations of language perception in the brain.

Concussions are a current health concern and account for the vast majority of head trauma. While symptoms after a single impact are usually transient, repetitive concussions, as often occur in sports, are responsible for persistent acute and chronic deficits. Here, we used a model of bilateral midline-centered concussions in mice to show that repetitive concussions selectively induce impairments in learning ability compared to single-impact injuries. Since microglial cells and their activation are considered key factors in degenerative pathology after brain trauma, we examined their structure and function after single and repetitive concussions in the cortex underlying the concussions and in the hippocampus. We found that only repetitive concussions led to a significant long-lasting structural activation of microglia and an increase in microglia-mediated engulfment of presynaptic excitatory synapses, while the elimination of inhibitory synapses was not altered. Since the density of excitatory input did not change during the 6-week study period, we hypothesize that there is a turnover of excitatory synapses following repetitive concussion that can be compensated for, anatomically but not behaviorally.

Cell migrations are crucial for embryonic development, wound healing, the immune response, as well as for cancer progression. During mesenchymal cell migration, the Rac1-WAVE-Arp2/3 signalling pathway induces branched actin polymerisation, which protrudes the membrane and allows migration. Fine-tuning the activity of the Rac1-WAVE-Arp2/3 pathway modulates protrusion lifetime and migration persistence. Recently, NHSL1, a novel interactor of the Scar/WAVE complex has been identified as a negative regulator of cell migration in vitro. We here analysed its function in vivo, during zebrafish gastrulation, when nhsl1b is expressed in migrating mesodermal cells. Loss and gain of function experiments revealed that nhsl1b is required for the proper migration of the mesoderm, controlling cell speed and migration persistence. Nhsl1b localises to the tip of actin-rich protrusions where it controls protrusion dynamics, its loss of function reducing the length and lifetime of protrusions, whereas overexpression has the opposite effect. Within the protrusion, Nhsl1b knockdown increases F-actin assembly rate and retrograde flow. These results identify Nhsl1b as a cell type specific regulator of cell migration and highlight the importance of analysing the function of regulators of actin dynamics in physiological contexts.

Mosses, the largest lineage of seed-free plants, have smaller and less variable genome sizes than flowering plants. Nevertheless, whether this difference results from divergent genome dynamics is poorly known. Here, we use newly generated chromosome-scale genome assemblies for Funaria hygrometrica and comparative analysis with other moss and seed plant genomes to investigate moss genome dynamics. Although some aspects of moss genome dynamics are seed plant-like, such as the mechanism of genome size change and de novo gain/loss of genes, moss genomes retain higher synteny, and collinearity over evolutionary time than seed plant genomes. Furthermore, transposable elements and genes are more evenly distributed along chromosomes in mosses than in seed plants, a feature shared with other sequenced seed-free plant genomes. Overall, our findings support the hypothesis that large-scale genome structure and dynamics of mosses and seed plants differ. In particular, our data suggest a lower rate of gene order reshuffling along chromosomes in mosses compared to seed plants. We speculate that such lower rate of structural genomic variation and unique chromosome structure in mosses may contribute to their relatively smaller and less variable genome sizes.

BAG-1 interacts with multiple partners, particularly with c-Raf, and promotes cancer cell survival. Hence, modulating the BAG-1-associated interactions with novel inhibitors could provide benefit for cancer therapy. Using HDX-MS, we first demonstrate the higher-order structure of BAG-1S and identify a potential "druggable" site on its BAG domain. An LC-MS/MS-coupled cell-free binding experiment is then used to map the BAG-1S:c-Raf interface, uncovering a 20-amino acid-length region of BAG-1S that is most likely to interact with c-Raf. Site-directed mutagenesis experiments reveal that K149 and L156 are hot spots for BAG-1S:c-Raf interaction, and their substitutions with alanine attenuate the survival of MCF-7 cells. We then show that a peptide derived from the BAG-1S-interacting c-Raf region hinders BAG domain-associated partners. The peptide, engineered with a cell-penetrating peptide motif, can penetrate cells, and it induces apoptosis in cancer cells. The anticancer activity of the peptide might lead to improved treatments for BAG-1-overexpressed and/or MAPK-driven tumors.

Lipid droplets (LDs), as innate immune hubs, function in the front line of antimicrobial defense involved in the host-pathogen arms race. Particularly for intracellular bacterial pathogens, the endowed capacity to resist host LDs can effectively facilitate pathogen in vivo colonization and evasion from the host's innate immune response. Here, to investigate the genetic mechanisms of intracellular bacteria response to host LDs, we utilized transposon insertion sequencing to dissect critical fitness determinants of Edwardsiella piscicida under the treatment of LDs isolated from its native host, turbot. Targeted metabolomics indicated that LD challenge resulted in the accumulation of intracellular arginine. The core arginine metabolism regulatory factor, ArgR, was found to play a pivotal role in combating LDs, emphasizing the importance of orchestrating intracellular arginine levels for bacterial LD adaptation. Specifically, ArgR enhanced the expressions of genes involved in arginine catabolism (speA/B and arcC) and diminished gene transcripts associated with arginine import (artP) and synthesis (argD/E/H). Furthermore, ArgR contributed to the pathogenesis of E. piscicida, promoting the proliferation in host cells and virulence in turbot. Collectively, our results shed light on the underlying mechanism of intracellular pathogens resisting LDs during bacterial infections and highlighting the crucial role of arginine in the host-pathogen interactions.