Communications Biology最新文献

Rapid and precise detection of multiple nucleic acid biomarkers is crucial for the development of clinically practical molecular diagnostics. The analytic specificity of biomarker detection can be greatly enhanced by utilizing the information of single-molecule probe binding kinetics. However, existing single-molecule fluorescence methods require up to 10 minutes per biomarker due to the slow binding rates of detection probes to their targets. To enable high-throughput profiling of multiple biomarkers within a short timeframe, faster detection techniques are essential. Here, we introduce Q-FISH (Quenching-based Fluorescence In-Situ Hybridization), a technology capable of detecting nucleic acid biomarkers in sub-second timeframes-achieving speeds over 600 times faster than the previously reported methods. Using Q-FISH, we demonstrated the rapid discrimination of highly homologous miRNAs and the precise quantification of endogenous miRNAs.

Campylobacter jejuni, a major cause of bacterial gastroenteritis, is capable of surviving in diverse hosts, including free-living amoebae such as Acanthamoeba. However, the molecular mechanisms that facilitate its intracellular persistence and subsequent transfer remain poorly defined. Here, we hypothesize that C. jejuni employs a biphasic actin-remodelling strategy, mediated by the effector proteins CiaI and CiaD, to reposition and remodel host mitochondria, promoting mitochondrial aggregation and iron homoeostasis. Using dual proteomics, microscopy, biochemical assays, and defined genetic mutants, we show that actin polymerization and CiaI are critical for mitochondrial interaction. We found that CiaI binds nucleotides with cooperative kinetics, acting as a molecular switch, and is crucial for C. jejuni localization near mitochondria, while CiaD promotes actin polymerization and acanthopodia formation to facilitate uptake. We propose a two-phase model: early actin polymerization repositions mitochondria, followed by localized actin depolymerization and mitochondrial remodelling. Iron chelation promotes bacterial survival, suggesting that oxidative stress functions as a host defence. These findings highlight a sophisticated mechanism of intracellular adaptation by C. jejuni that may be relevant to pathogenesis and identify new potential targets for disrupting its environmental and clinical persistence.

Since the discovery of Latimeria chalumnae, coelacanths have provided a critical comparative framework for reconstructing ancestral sarcopterygian anatomy. However, the function of several anatomical features in both extant and fossil coelacanths remains unresolved. Among these, the presence of large ossified chambers in the body cavity of fossil coelacanths has remained enigmatic, with different studies proposing respiratory or auditory functions. Here, we examine lung and inner ear anatomy based on new observations from synchrotron phase-contrast microCT scans of two 240-million-year-old latimerioid coelacanths, alongside multiple developmental stages of the extant L. chalumnae. These data, combined with archival histological sections of L. chalumnae and 3D reconstructions of a Devonian coelacanth, suggest that extinct coelacanths possessed an ossified lung capable of transmitting sound pressure to auditory sensory epithelia in the inner ear via a perilymphatic system. We propose that the lung of extinct coelacanths supported both respiratory and auditory functions.

Genetic pain loss disorders represent a heterogeneous group of rare diseases mainly characterized by defective nociception. Understanding the underlying molecular mechanism is fundamental to improve the treatment of patients affected by these rare disorders. Feline Leukemia Virus Subgroup C Receptor 1 (FLVCR1) is one of the genes previously associated with sensory neuropathy that requires further investigation. Here, we report on two additional patients with novel disease-causing variants in FLVCR1 and introduce a zebrafish model of the disease. The analyses of patient-derived fibroblasts show that distinct FLVCR1 variants compromised all the known functions associated with FLVCR1, thus affecting choline levels, heme biosynthesis and mitochondrial Ca²⁺ handling. Furthermore, we provide evidence that the alteration of these processes impairs the TCA cycle and OXPHOS, and induces lipid peroxidation. Our data points to the alterations of energetic metabolism as a potential driving pathomechanism in FLVCR1-associated sensory neuropathy.

Rosacea is a prevalent skin disorder in which neurogenic inflammation plays a significant role in its pathogenesis. Gabapentin (GBP) has garnered attention as a therapeutic option; however, its precise mechanism of action in treating rosacea remains unclear. Through a comprehensive analysis of experimental and clinical data, the research team has elucidated the molecular mechanism by which GBP inhibits neurogenic inflammation, particularly through modulating the NF-κB signaling pathway to alleviate rosacea inflammation. Using a murine rosacea model induced by LL37, the efficacy of GBP was compared to Minocycline and Hydroxychloroquine combination therapy. Various techniques assessed marker expression, transcriptomic profiles, and in vitro cell experiments with BV2 cells. Clinical data from 60 rosacea patients were analyzed through a randomized trial, comparing GBP therapy to the combination treatment. Results showed GBP effectively reduced skin inflammation and facial redness in mice and patients. Metabolomic analysis indicated significant changes in metabolites post-GBP treatment, correlating with inflammatory factors. The study concludes that GBP mitigates rosacea progression by targeting neurogenic inflammation via NF-κB pathway regulation, shedding light on novel treatment mechanisms through transcriptomics and metabolomics for future clinical application in rosacea research.

Current single-cell RNA sequencing (scRNA-seq) methods suffer from biases that restrict the detection of cellular transcripts to 10-40% of total RNAs. This hinders the identification of transcripts of interest. Additionally, information retrieved from most high-throughput scRNA-seq methods is confined to untranslated regions toward transcript ends, resulting in loss of detail in internal regions. In this review, we outline biases in scRNA-seq protocol steps that limit transcript and region detection. We then discuss the advantages and disadvantages of targeted sequencing solutions, grouped into five categories according to the protocol step they target. Finally, we present a decision tree that guides researchers in selecting the most suitable targeted method for their experiment.

The continental subsurface hosts energy-constrained groundwaters with a high diversity of ecologically elusive microorganisms adapted to the prevailing low-energy conditions. This study explored potential interactions among microbes using anaerobic enrichment incubations with three types of groundwater of contrasting hydrochemistry from the Äspö Hard Rock Laboratory, Sweden. Removing cells larger than 0.45 µm from the inoculum resulted in incubations enriched in populations characterized by very small genomes, including Patescibacteria, Nanobdellota, and Omnitrophota. These incubations had a higher diversity than non-fractionated incubations. However, cell numbers and community structure of the fractionated incubations did not change over an incubation period up to four months, despite high microbial diversity and experimental amendments with either simple (acetate) or more complex (cell lysate) carbon sources. In addition, network analysis on the groundwaters revealed multiple co-occurrences between populations affiliated with the Patescibacteria and the Desulfobacterota. Overall, these findings support that a considerable part of microbial diversity has a small cell size in these low energy groundwaters and strong co-occurrences among populations as an important survival strategy.

Oral probiotics have shown great potential in treating ulcerative colitis (UC). However, gastrointestinal obstacles substantially inactivate probiotics, impeding delivery and colonization in the colon. Here, we developed robust oral living therapeutics with high colon-accumulating effect via surface decoration of probiotic (Escherichia coli Nissle 1917, EcN) using a layer-by-layer approach. Calcium ions and carboxymethyl-modified lignin (CML) were sequentially coated on EcN to generate an acid-resistant and colitis microenvironment-responsive system (CML@EcN). After oral administration in a male C57BL/6 N mouse model, EcN were specifically delivered to the site of colitis and successfully colonized. The CML@EcN notably alleviated colitis by modulating immune dysfunction, reshaping gut microbiota (GM), and repairing the intestinal barrier. The delivery mechanism was explored based on experiments and mathematical models. Interestingly, this engineering approach can be further used to decorate other bacteria. Consequently, the robust CML@EcN shows high colon-targeting delivery efficacy and great potential in UC therapy.

Many patients suffer from incident dementia after lung infections. Previous studies demonstrated that cytotoxic tau is released from the lungs in response to bacterial pneumonia, causing cognitive deficits and tau seeding. We aimed to determine the impact pneumonia has on blood-brain barrier (BBB) permeability, glial activation, and tau phosphorylation in the brain following infection and the involvement of tau. We found that lung infection with Pseudomonas aeruginosa (P. aeruginosa) increased BBB permeability, astrocyte activation, and phosphorylated tau (ptau) levels in the brain 24-hours (h) post-infection in C57BL/6J mice. Conversely, tau knockout (KO) mice had no BBB injury or glial activation 24 h after infection. Additionally, we found increased levels of several kinases and proinflammatory cytokines with infection in C57BL/6J and tau KO mice. Thus, tau is necessary for pneumonia-induced BBB dysfunction and astrocyte reactivity in the brain and may be an innate immune response link between infection and dementia.

The G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene mutation is one of only three deafness genes identified to be implicated in X-linked recessive syndromic hearing loss (SHL) to date. However, the function of GPRASP2 in the auditory system has not yet been fully understood. In this study, we generated Gprasp2-deficient mice and found that they exhibited a hearing loss phenotype and depression-like behaviors. In addition, we observed a disordered arrangement of cochlear hair cells in Gprasp2-deficient mice. GPRASP2 binds to NCAM1. Gprasp2 deficiency decreased NCAM1 level and further enhanced ferritinophagy in cochlear hair cells. This study could improve our understanding of the role of GPRASP2 deficiency in auditory cells, which contributes to the pathophysiology of X-linked SHL.