Communications Biology最新文献

Quorum sensing, first described in marine systems five decades ago, is a well-characterized chemical communication system used to coordinate bacterial gene expression and behavior; however, the impact of quorum sensing on interkingdom interactions has been vastly understudied. In this review, we examine how these molecules mediate communication between bacteria and marine eukaryotes; influencing processes such as development, disease pathogenesis, and microbiome regulation within marine ecosystems. We describe the varied mechanisms eukaryotes have evolved to interfere with bacterial quorum sensing signaling, the crucial role these signals play in host-virus interactions, and how their exchange may be governed by outer membrane vesicles, prevalent in marine systems. Here, we present a dynamic portrayal of the impact of quorum sensing signals beyond bacterial communication, laying the groundwork for future investigations on their roles in shaping marine ecosystem structure and function.

Small cell neuroendocrine cervical carcinoma (SCNECC) is an aggressive gynecological malignancy with poor prognosis. The precision therapeutic strategies for SCNECC are severely limited by the complex tumor microenvironment. Here, we mapped the single-cell landscape of a total of six samples from matched SCNECC cancerous foci and normal adjacent cervical tissues. Through analysis of 68,455 high-quality cells, malignant epithelial cells were identified with increased neuroendocrine differentiation and reduced keratinization. Within four epithelial cell clusters, the key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 defined molecular subtypes. Transitional trajectory among subtypes characterized two distinct carcinogenesis pathways in SCNECC. The P-type SCNECC showed potentially enhanced immune infiltration over other subtypes. Intercellular communication analysis identified several immune checkpoints and differentially expressed signaling pathways among subtypes. Through western blotting, the TC-YIK cell line was identified as an N-type SCNECC cell with high expression of SLFN11 and mTOR. Based on immunohistochemical staining of malignant subtyping markers, a cohort of 66 SCNECC patients from our hospital were divided into five subtypes. We further combined YAP1 expression with other clinicopathological factors (Cox p < 0.05) to establish a prognostic nomogram. Overall, these findings provide clues for tumorigenesis, precision treatments and prognostic prediction in SCNECC.

The skin, the body's largest organ, has a heterogeneous structure with various cell types and tissue layers. In vivo noninvasive 3D volumetric imaging with multi-contrast, high resolution, a large field-of-view (FOV), and no-motion artifacts is crucial for studying skin biology and diagnosing/evaluating diseases. Traditionally high-resolution in vivo skin microscopy methods capture images in the en-face (xy) plane parallel to the skin surface but are affected by involuntary motion, particularly during large-area volumetric data acquisition using xy-z mosaicking. In this work, we developed an xz-y imaging method that acquires images in the vertical (xz) plane and extends the FOV by moving the skin laterally along the y-direction. This approach is conceived based on our observation that involuntary skin movements are mostly along the vertical direction. Combined with a unique motion correction method, it enables 3D image reconstruction with subcellular resolution and an extended FOV close to a centimeter (8 mm). A multimodality microscopy system using this method provides simultaneous reflectance confocal, two-photon excited fluorescence, and second harmonic generation imaging, enabling multi-contrast capabilities. Using this system, we captured histology-like features of normal skin, vitiligo, and melanoma, demonstrating its potential for in vivo skin biology studies, clinical diagnosis, treatment planning and monitoring.

The human thalamus is a heterogeneous subcortical structure coordinating whole-brain activity. Investigations of its internal organization reveal differentiable subnuclei, however, a consensus on subnuclei boundaries remains absent. Recent work suggests that thalamic organization additionally reflects continuous axes transcending nuclear boundaries. Here, we study how low-dimensional axes of thalamocortical structural connectivity relate to intrathalamic microstructural features, functional connectivity, and structural covariance. Using diffusion MRI, we compute a thalamocortical structural connectome and derive two main axes of thalamic organization. The principal axis, extending from medial to lateral, relates to intrathalamic myelin, and functional connectivity organization. The secondary axis corresponds to the core-matrix cell distribution. Lastly, exploring multimodal associations globally, we observe the principal axis consistently differentiating limbic, frontoparietal, and default mode network nodes from dorsal and ventral attention networks across modalities. However, the link with sensory modalities varies. In sum, we show the coherence between lower dimensional patterns of thalamocortical structural connectivity and various modalities, shedding light on multiscale thalamic organization.

Bin/Amphiphysin/Rvs167 (BAR) domain containing proteins are peripheral membrane proteins that regulate intracellular membrane curvature. BAR protein endophilin B1 plays a key role in multiple cellular processes critical for oncogenesis, including autophagy and apoptosis. Amphipathic regions in endophilin B1 drive membrane association and tubulation through membrane scaffolding. Our understanding of exactly how BAR proteins like endophilin B1 promote highly diverse intracellular membrane remodeling events in the cell is severely limited due to lack of high-resolution structural information. Here we present the highest resolution cryo-EM structure of a BAR protein to date and the first structures of a BAR protein bound to a lipid bicelle. Using neural networks, we can effectively sort particle species of different stoichiometries, revealing the tremendous flexibility of post-membrane binding, pre-polymer BAR dimer organization and membrane deformation. We also show that endophilin B1 efficiently permeabilizes negatively charged liposomes that contain mitochondria-specific lipid cardiolipin and propose a new model for Bax-mediated cell death.

The listening advantage for native speech is well known, but the neural basis of the effect remains unknown. Here we test the hypothesis that attentional enhancement in auditory cortex is stronger for native speech, using magnetoencephalography. Chinese and German speech stimuli were recorded by a bilingual speaker and combined into a two-stream, cocktail-party scene, with consistent and inconsistent language combinations. A group of native speakers of Chinese and a group of native speakers of German performed a detection task in the cued target stream. Results show that attention enhances negative-going activity in the temporal response function deconvoluted from the speech envelope. This activity is stronger when the target stream is in the native compared to the non-native language, and for inconsistent compared to consistent language stimuli. We interpret the findings to show that the stronger activity for native speech could be related to better top-down prediction of the native speech streams.

The T7 phage RNA polymerase (RNAP) is a widely used expression platform, but its implementation in non-model microbial hosts poses significant challenges due to cytotoxicity. We constructed an optimized phage phi15-based expression system as alternative to the T7 platform for a wide range of applications in Pseudomonas putida. The new system employs the small phi15 RNAP, driving expression from an orthogonal phi15 promoter. By finetuning expression levels of phi15rnap and introducing a phi15 lysozyme mutant that inhibits phi15 RNAP in uninduced conditions, a stringent system was created with 200-fold inducibility. Moreover, by successfully decoupling cell growth and protein production using phi15 gp16, a host RNAP inhibitor, expression levels could be enhanced further (20%). Apart from creating four optimized platform P. putida hosts and a set of Golden Gate-compatible vectors, we demonstrate the extensive flexibility of the phi15 system. A proof-of-concept expression for industrially relevant fluorinase resulted in 2.5- and 5-fold increased yield compared to other widely-adopted expression systems. The system functions well in combination with several inducer systems, and in a variety of vector-based and genomically integrated set-ups. In conclusion, the phi15 RNAP, promoter, lysozyme and growth-decoupler provide a valuable plug-and-play set of genetic parts for the P. putida toolbox.

Throughout evolution, addition of numerous cyanobacteria-derived subunits to the photosynthetic NDH-1 complex stabilizes the complex and facilitates cyclic electron transfer around photosystem I (PSI CET), a critical antioxidant mechanism for efficient photosynthesis, but its stabilization mechanism remains elusive. Here, a cyanobacteria-derived intermolecular salt bridge is found to form between the two conserved subunits, NdhF1 and NdhD1. Its disruption destabilizes photosynthetic NDH-1 and impairs PSI CET, resulting in the production of more reactive oxygen species under high light conditions. The salt bridge and transmembrane helix 16, both situated at the C-terminus of NdhF1, collaboratively secure the linkage between NdhD1 and NdhB, akin to a cramping mechanism. The linkage is also stabilized by cyanobacteria-derived NdhP and NdhQ subunits, but their stabilization mechanisms are distinctly different. Collectively, to the best of our knowledge, this is the first study to unveil the stabilization mechanism of photosynthetic NDH-1 by incorporating photosynthetic components into its conserved subunits during evolution.

ORF3a, the most abundantly expressed accessory protein of SARS-CoV-2, plays an essential role in virus egress by inactivating lysosomes through their deacidification. However, the mechanism underlying this process remains unclear. While seminal studies suggested ORF3a being a cation-selective channel (i.e., viroporin), recent works disproved this conclusion. To unravel the potential function of ORF3a, here we employed a multidisciplinary approach including patch-clamp electrophysiology, videoimaging, molecular dynamics (MD) simulations, and electron microscopy. Preliminary structural analyses and patch-clamp recordings in HEK293 cells rule out ORF3a functioning as either viroporin or proton (H⁺) channel. Conversely, videoimaging experiments demonstrate that ORF3a mediates the transmembrane transport of water. MD simulations identify the tetrameric assembly of ORF3a as the functional water transporter, with a putative selectivity filter for water permeation that includes two essential asparagines, N82 and N119. Consistent with this, N82L and N82W mutations abolish ORF3a-mediated water permeation. Finally, ORF3a expression in HEK293 cells leads to lysosomal volume increase, mitochondrial damage, and accumulation of intracellular membranes, all alterations reverted by the N82W mutation. We propose a novel function for ORF3a as a lysosomal water-permeable channel, essential for lysosome deacidification and inactivation, key steps to promote virus egress.

Cannabinoids are unique meroterpenoids, with cannabigerolic acid (CBGA) serving as a dedicated precursor. This study introduces a fungal aromatic prenyltransferase AscC into the engineered Escherichia coli to catalyze the transfer of C₅-C₁₅ terpenoid linear precursors to olivetolic acid. Four CBGA derivatives (compounds 1-4) with diverse C₅, C₁₀, or C₁₅ prenyl chains are isolated and identified, with compound 4 being an undescribed product featuring a C₁₅ prenyl chain at the C-5 position. Compound 4 demonstrates the highest anti-neuroinflammatory and antibacterial activities, with IC₅₀ values of 3.06 µM for TNF-α and 4.31 µM for IL-6, alongside EC₅₀ values ranging from 0.87 to 3.16 µM against three Gram-positive bacteria. An efficient construct is established by incorporating an additional copy of AscC, resulting in a yield of 14.85 ± 0.91 mg/L of compound 4. Two mutants, L180Y and L180F, are engineered to selectively produce compound 4. These findings provide a foundation for enriching the chemical diversity of bioactive cannabinoid analogs with various prenyl moieties through combinatorial biosynthesis.