Communications Biology最新文献

Bacteria deploy virulence factors to subvert host immunity; yet the molecular details of these interactions often remain limited. Here, we reveal the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterize the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to SpnA. This allowed us to identify an additional oligonucleotide-binding domain, whose flexible structure may play an important function in nucleolytic activity. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex (MAC) C5b67 components as key interactors. Cross-linking mass spectrometry combined with integrative modeling identified the binding interfaces between SpnA and C5b67. These interfaces are conserved among genetically diverse S. pyogenes strains. Interaction between SpnA and C5b67 is suggested to prevent the assembly of a functional MAC. Our findings uncover a novel function of SpnA in complement inhibition, and identifies new potential targets to prevent and treat S. pyogenes infections.

As we age, understanding speech in social situations imposes an increasingly difficult challenge to the auditory system. However, the attentional mechanisms underlying age-related speech comprehension difficulties in multitalker situations remain unclear. We collected EEG signals while 63 normal hearing participants (35 women) from 19 to 71 years performed a speech comprehension task involving a multitalker paradigm at individually adjusted target-to-distractor ratios. Combining trial-resolved multivariate temporal response function modeling with detailed behavioral comprehension responses, we provide a window into lower-level impairments and possible higher-level compensatory mechanisms across the adult life span. We show that reduced behavioral performance in late adulthood is associated with increased distractor representation. This points towards increased distractibility as a potential mechanism underlying age-related speech comprehension deficits. Additionally, at the behavioral and neural levels, we show that older adults rely more on higher-level linguistic information. Finally, we show that an increased reliance on word-level linguistic information may compensate for increased distractor tracking and adaptively support comprehension performance across the adult life span. Thus, an increased reliance on higher-level processing could attenuate age-related impairments in attentional filtering.

The plant-derived biopolymer pectin has been explored as sealant in lung surgery. Interpenetration of pectin's heteropolysaccharide chains with sugar-chains on components of the mesothelial glycocalyx is thought to mediate adhesion. To visualize a potential adhesion complex, we first establish a method to preserve pectin ultrastructure by limiting hydration during sample preparation for electron microscopy. Depending on actual hydration states and pectic domains selected we find distinct morphologies: Citrus pectic polysaccharides, combining both, smooth homogalacturonan and hairy rhamnogalacturonan domains, form a loose network of thin filaments. Rhamnogalacturonan and xylogalacturonan domains from soy show a denser mesh, while pectic galactan from potato or pectic arabinan from sugar beet display more globular aspects. As proof of concept, we finally apply the filamentous lemon pectin to the surface of murine lung in a surgical setting. Ultrastructural visualization of the sealant-tissue assembly shows tight association between the carbohydrate fibers, possibly driven by polymer-typical chain interactions.

Microfluidics has emerged as a powerful technology for precisely controlling mechanical and chemical environments across a wide range of biological systems, from single cells to complex co-cultures. In microbiology, the microscale dimensions of bacteria pose experimental challenges that microfluidic systems have effectively addressed, offering compatibility with live imaging and enabling quantitative investigations of bacterial behaviors and host-bacteria interactions. Historical microfluidic designs are now routinely used to quantify bacterial growth and lineage with unprecedented temporal-spatial resolution and precise control of external conditions. In parallel, organ-on-chip technologies are increasingly applied in microbiology to study host-bacteria interactions within physiologically relevant and well-controlled microenvironments. Recently, cancer tissues have been recognized as unexpected hosts for bacteria, with mounting impactful evidence showing that intratumoral microbes can influence cancer progression and response to therapy. Despite growing interest, the application of microfluidics to cancer-bacteria interactions remains limited. Addressing this gap requires the development of appropriate methodological tools that replicate the relevant tumor microenvironment features and allow the quantification of both cellular responses and bacterial colonization dynamics upon the bacterial-host interaction. In this review, we first outline the foundational applications of microfluidics in microbiology from single-cell to collective behavior studies. We then describe how organ-on-chip technology enables the fine-tuned formation of organ-specific conditions, which are critical for modeling the complex tumor microenvironment. We further examine recent findings on intratumoral bacteria across cancer types and discuss how microfluidics, especially tumor-on-chip approaches, can advance this emerging field, from mechanistic insights to therapeutic development.

Artificial light at night (ALAN) is an anthropogenic disturbance with negative effects on nocturnal flying insects, yet most studies treat "night-time" as a uniform exposure period. However, nocturnal insects exhibit pronounced temporal niche partitioning, suggesting that attraction to artificial light and the effectiveness of mitigation measures may vary over the night. Using a citizen science framework, we show how insect attraction along a lakeside road varies across five nightly intervals, comparing conventional high pressure sodium with tailored and shielded LED road lights. Complementary UV ground traps showed marked shifts in local insect abundance and taxonomic composition, with peak attraction occurring during late evening and midnight hours (09.30pm-11.30pm-00.30am). Road lights closely followed this temporal trend. Tailored and shielded LED luminaires reduced total insect attraction, with the strongest effects during peak activity, but limited efficacy during twilight and late-night periods. Both total abundances and taxonomic composition showed significant time-by-treatment interactions, demonstrating that incorporating temporal dynamics can greatly improve targeted mitigation strategies.

Aortic dissection is a life-threatening cardiovascular emergency characterized by rapid progression and high mortality. Although medial degeneration is a key pathological feature of aortic dissection, the mechanisms that drive aortic wall instability remain incompletely understood. Aortic calcification is a pathological mineralization process that can alter vascular structure and function, but its role in aortic dissection has received limited attention. Here we show that tissue nonspecific alkaline phosphatase associated calcium phosphate microdeposition is linked to aortic medial degeneration and dissection susceptibility. Human aortic dissection tissues and diseased mouse aortas show increased mineralization together with elevated tissue nonspecific alkaline phosphatase activity. Calcium phosphate deposits promote vascular smooth muscle cell phenotypic switching and inflammatory remodeling, while tissue nonspecific alkaline phosphatase facilitates mineral deposition under permissive conditions. Reducing tissue nonspecific alkaline phosphatase activity or expression attenuates aortic calcium phosphate deposition, medial degeneration and dissection in mice. These findings identify tissue nonspecific alkaline phosphatase associated microdeposition as a mechanism contributing to aortic wall vulnerability.

Mammalian gene switches enable programmable cell behavior. However, current switches on transcriptional and translational layers require de novo RNA and protein synthesis, and secreted outputs must additionally undergo folding, post-translational processing, and intracellular trafficking, imposing delays that limit rapid extracellular responses. Rapid secretion-control switches instead act on pre-synthesized proteins by controlling retention, trafficking, storage, or release. Most current platforms exploit the classical endoplasmic reticulum (ER)-Golgi pathway, including engineered stimulus-secretion coupling in specialized secretory cells and ER retention, retrieval-signal cleavage, or synchronized trafficking in general mammalian hosts. Although these strategies improve response kinetics, they remain limited by ER dependence, host-cell specificity, cargo compatibility, basal leakage, and post-release transport delays. Here, we review current secretion-control architectures and highlight unconventional protein secretion as an underexplored source of design principles for positioning regulatory control closer to terminal protein export and expanding the architectures available for mammalian secretion control.

Morphological studies of the diaphragm have provided a detailed view of its architecture, which consists of parallel skeletal muscle fibers and a central ring of neuronal innervation that includes neuromuscular junction (NMJ) units. NMJs are disease-vulnerable synapses; thus, analysis of the NMJ is essential to understand its function in both healthy and disease-related conditions. The diaphragm was analyzed by spatial proteomics and 115 proteins were enriched at the NMJ. Comparison of the protein signatures of the NMJ and myotendinous junction (MTJ) revealed 31 shared proteins, suggesting partially conserved structures between these junctions. Key mediators of synaptic transmission and extracellular matrix organization were observed among the NMJ-enriched components, which indicates the molecular complexity and regulatory potential of the NMJ. A focused study of the uncharacterized NMJ protein FXYD6 demonstrate enhanced FXYD6 expression in type IIa fibers of the diaphragm, which exhibit a unique balance of oxidative and glycolytic capacity. FXYD6 interacts with Na⁺/K⁺-ATPase subunits in the diaphragm, which supports the function of FXYD6 in the ionic homeostasis required for continuous, fatigue-resistant contraction. Overall, the dataset provides a comprehensive molecular atlas of the NMJ in the diaphragm and opens new opportunities to dissect the synaptic mechanisms underlying respiratory function and neuromuscular diseases.

Processing bodies (P-bodies) are cytoplasmic, non-membrane-bound structures involved in mRNA decay. EDC4 serves as a key scaffold for the decapping complex within P-bodies. Here, we demonstrate that N4BP1 interacts with EDC4, as well as with DCP1A, DCP2, and XRN1 - key components of 5'-cap hydrolysis. Endogenous N4BP1 colocalizes with EDC4 in P-bodies, requiring both of its KH domains. Structural analysis revealed that N4BP1 contains a type-I KH fold but lacks the canonical GXXG motif required for single-stranded RNA binding. Deletion or mutation of KH domains non-canonical GXXG motifs disrupts the N4BP1-EDC4 complex. N4BP1 reduces HIV-1 transcript levels independently of its P-body localization or association with decapping components, implying the involvement of other host factors in regulating viral mRNAs. Similarly, for N4PB1-dependend negative regulation of endogenous transcripts in HaCaT keratinocytes, EDC4 is not essential. For both HIV-1 and endogenous transcripts, the reduction is associated with the activity of the NYN domain.

Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we used whole-genome sequencing from 1,285 Samoan individuals combined with 1000 Genomes Project (1KGP) individuals to construct an imputation reference panel that better represents Pacific Islander, specifically Samoan, genetic variation. Here we show that this panel yielded up to two times more well-imputed (r² ≥ 0.80) variants than TOPMed-R3 and 1KGP and was enriched for moderate and high impact variants. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum; accuracy (r²) was greater for population-specific variants (high fixation index, F_ST) and those from larger haplotypes (high LD score). However, the gain in accuracy over TOPMed-R3 was largest for small haplotypes, reflecting the Samoan panel's ability to capture variation not well tagged by other panels.