Communications Biology最新文献

Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here, we analyzed male mice lacking claudin-11 (Cldn11), which encodes a SCTJ component, and found autoantibodies against antigens of spermatocytes/spermatids in their sera. Defective spermatogenesis in Cldn11-deficient mice was not restored on a recombination activating gene 2 (Rag2) knockout background lacking mature T and B lymphocytes. This suggests that adaptive immune responses to spermatogenic cells are not a cause of defective spermatogenesis in Cldn11-deficient mice. Further analyses showed that Cldn11 knockout impaired Sertoli cell polarization, localization of stem cell factor (SCF) (a key molecule for maintaining differentiating spermatogonia) to the basal compartment of seminiferous tubules, and also proliferation of differentiating spermatogonia. We propose that CLDN11 creates a microenvironment for SCF-mediated spermatogonial proliferation at the basal compartment via Sertoli cell polarization.

Oxygen consumption by oceanic microbes can predict respiration (CO₂ production) but requires an assumed respiratory quotient (RQ; ΔO₂/ΔCO₂). Measured apparent RQs (ARQs) can be impacted by various processes, including nitrification and changes in dissolved organic matter (DOM) composition, leading to discrepancies between ARQ and actual RQ. In DOM remineralization experiments conducted in the eastern North Atlantic Ocean, ARQs averaged 1.39 ± 0.14, similar to predictions for complete consumption of plankton biomass. DOM removed with an elevated nominal oxidation state (i.e., more oxidized DOM), as detected by liquid chromatography-tandem mass spectrometry, coincided with increased hydrolyzable amino acid removal, increased ARQs and bacterioplankton respiration (BR), and a decreased bacterioplankton growth efficiency (BGE). Across experiments, evidence emerged that nitrification and DOM partial oxidation, driven in part by bacterioplankton members of OM43, SAR92 and Rhodobacteraceae, can elevate BR relative to bacterioplankton consumption of plankton-derived carbon. These rare synoptic measurements of interrelated variables reveal complex biochemical and cellular processes underlying variability in large-scale CO₂ production estimates.

In mammalian oocytes, large-scale chromatin organization regulates transcription, nuclear architecture, and maintenance of chromosome stability in preparation for meiosis onset. Pre-ovulatory oocytes with distinct chromatin configurations exhibit profound differences in metabolic and transcriptional profiles that ultimately determine meiotic competence and developmental potential. Here, we developed a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live mouse oocytes. Our Fluorescence prediction and Classification on Bright-field (Fluo-Cast-Bright) pipeline achieved 91.3% accuracy in the classification of chromatin state in fixed oocytes and 85.7% accuracy in live oocytes. Importantly, transcriptome analysis following non-invasive selection revealed that meiotically competent oocytes exhibit a higher expression of transcripts associated with RNA and protein nuclear export, maternal mRNA deadenylation, histone modifications, chromatin remodeling and signaling pathways regulating microtubule dynamics during the metaphase-I to metaphase-II transition. Fluo-Cast-Bright provides fast and non-invasive selection of meiotically competent oocytes for downstream research and clinical applications.

The Bartonella genus of bacteria encompasses ubiquitous species, some of which are pathogenic in humans and animals. Bartonella henselae, the causative agent of Cat Scratch disease, is responsible for a large portion of human Bartonella infections. These bacteria can grow outside of cells, replicate in erythrocytes and invade endothelial and monocytic cells. We have previously reported reduced antibiotic susceptibility of intracellular Bartonella. In this study we performed comparative transcriptomic analyses between the extracellular and intracellular B. henselae phenotypes. Overall, specific genes involved in invasion, virulence, extracellular adhesion of type 4 secretion system were downregulated following intracellular invasion of B. henselae. Downregulation included BadA, a well-characterized adhesin molecule, of critical importance for cell invasion. These studies demonstrate the ability to purify Bartonella RNA from infected cells and offer a repository of gene expression data for future research. The development of novel therapeutics will benefit from the ability to determine target expression by Bartonella in relevant microenvironments.

The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identify P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1) and show that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 results in decreased parasitemia and prevents transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibit distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggest that this deficiency impacts DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrate that recombinant PfLPLAT1 exhibits lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs.

Reduced cerebral blood flow occurs early in the development of Alzheimer's disease (AD), but the factors producing this reduction are unknown. Here, we ask whether genetic and lifestyle risk factors for AD-the ε4 allele of the Apolipoprotein (APOE) gene, and physical activity-can together produce this reduction in cerebral blood flow which leads eventually to AD. Using in vivo two-photon microscopy and haemodynamic measures, we record neurovascular function from the visual cortex of physically active or sedentary mice expressing APOE3 and APOE4 in place of murine APOE. Energy supply and demand are mismatched in APOE4 mice, with smaller increases in cerebral blood flow, blood volume and blood oxygenation occurring during neuronal activation as blood vessels frequently fail to dilate. Exercise dose-dependently overall improves neurovascular function, with an increased impact of exercise apparent after longer exposure times. Several haemodynamic measures show a larger beneficial effect of exercise in APOE4 vs. APOE3 mice. Thus, APOE4 genotype in conjunction with sedentary behaviour produces the worst neurovascular function. Promotion of physical activity may therefore be particularly important to improve cerebrovascular function and reduce dementia risk in APOE4 carriers.

Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) and associated data processing software packages. In contrast, analogous structural analysis in cells via cryo-electron tomography (cryo-ET) remains challenging due to critical technical bottlenecks, including low-throughput sample preparation and imaging, and laborious data processing methods. Here, we describe a rapid in situ cryo-ET sample preparation and data analysis workflow that results in the routine determination of sub-nm resolution ribosomal structures. We apply this workflow to E. coli, producing a 5.8 Å structure of the 70S ribosome from cells in less than 10 days and facilitating the discovery of a minor population of 100S-like disomes. We envision our approach to be widely applicable to related bacterial samples.

P4-ATPases, a subfamily of the P-type ATPase superfamily, play a crucial role in translocating membrane lipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet. This process generates and regulates transbilayer lipid asymmetry. These enzymes are conserved across all eukaryotes, and the human genome encodes 14 distinct P4-ATPases. Initially identified as aminophospholipid translocases, P4-ATPases have since been found to translocate other phospholipids, including phosphatidylcholine, phosphatidylinositol, and even glycosphingolipids. Recent advances in structural analysis have significantly improved our understanding of the lipid transport machinery associated with P4-ATPases, as documented in recent reviews. In this review, we highlight the emerging evidence related to substrate diversity, the regulation of cellular localization, enzymatic activities, and their impact on organism homeostasis and diseases.

Root-knot nematodes (RKNs) of the genus Meloidogyne pose the most significant threats to global food security due to their destructive nature as plant-parasitic nematodes. Although significant attention has been devoted to investigating the gene transcription profiling of RKNs, our understanding of the translational landscape of RKNs remains limited. In this study, we elucidated the translational landscape of Meloidogyne incognita through the integration of translatome, transcriptome and quantitative proteome analyses. Our findings revealed numerous previously unannotated translation events and refined the genome annotation. By investigating the genome-wide translational dynamics of M. incognita during parasitism, we revealed that the genes of M. incognita undergo parasitic stage-specific regulation at the translational level. Interestingly, we identified 470 micropeptides (containing fewer than 100 amino acids) with the potential to function as effectors. Additionally, we observed that the effector-coding genes in M. incognita exhibit higher translation efficiency (TE). Further analysis suggests that M. incognita has the potential to regulate the TE of effector-coding genes without simultaneous alterations in their transcript abundance, facilitating effector synthesis. Collectively, our study provides comprehensive datasets and explores the genome-wide translational landscape of M. incognita, shedding light on the contributions of translational regulation during parasitism.

Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination. We identified 25 unique inverted D genes (InvDs) in both naive and memory B cells from antibody repertoires of 13 healthy donors. These InvDs utilize all three reading frames during translation, producing distinct amino acid profiles enriched in histidine, proline, and lysine in CDR-H3s of antibodies with potential functional diversity. Notably, our analysis revealed a broader range of D-D fusions, including D-D, D-InvD, InvD-D, and InvD-InvD configurations, opening new perspectives for antibody engineering and therapeutic development.