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Diabetic retinopathy (DR) is a leading cause of vision impairment among individuals with diabetes, driven by microvascular damage and retinal degeneration. Recent evidence implicates ceramides-bioactive sphingolipids-as critical mediators in DR pathogenesis. These lipids influence critical cellular processes, including apoptosis, inflammation, and oxidative stress. Emerging data suggests that ceramide accumulation exacerbates retinal neurodegeneration in DR by modulating key molecular pathways. This review synthesizes current knowledge on the role of ceramides in DR development and progression, examines the factors influencing their activity, and explores the therapeutic potential of targeting ceramide metabolism. By integrating recent findings, this article aims to provide insights for future research and clinical strategies in DR management.
Neuromuscular fatigue (NMF) is an inherent consequence of strenuous training and competition. It arises from complex interactions between the central nervous system and peripheral skeletal muscle. Despite decades of research, the interaction between central and peripheral mechanisms of neuromuscular fatigue and their influence on sports performance remains a contentious topic. In addition, translating mechanistic insights into practical strategies for monitoring, training, and recovery in athletes is an ongoing challenge. This review synthesizes contemporary literature to build a central-peripheral integrative model of NMF and proposes an applied framework for athlete monitoring and training design. The review first summarizes central and peripheral fatigue mechanisms, highlighting the bidirectional influence of descending motor drive and afferent feedback, and discusses controversies such as the central-governor theory. It then assesses monitoring tools (subjective ratings, neuromuscular tests, electromyography, heart-rate variability, biochemical and neurochemical markers) and recovery strategies. Finally, the review translates mechanistic knowledge into evidence-based training and recovery recommendations. A conceptual model illustrating the interactions between central and peripheral mechanisms and their monitoring is included. The aim is to inform sports scientists and practitioners about the physiological bases of fatigue and provide guidance for individualized athlete management.
Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and progressive copper accumulation in multiple tissues. Ocular manifestations represent some of the most characteristic and clinically valuable features of the disease, contributing to diagnosis, monitoring, and assessment of neurological involvement. This narrative review summarizes current knowledge regarding the pathophysiology, clinical presentation, and imaging characteristics of ocular involvement in WD. Copper deposition within the eye occurs primarily through the aqueous humor, leading to accumulation in the corneal Descemet membrane and lens capsule. Kayser-Fleischer rings remain the most prevalent ocular sign being strongly associated with neurological disease, while sunflower cataracts represent a less common but highly characteristic manifestation. Anterior segment optical coherence tomography and in vivo confocal microscopy have recently improved the detection and monitoring of these lesions. Beyond copper deposition, growing evidence indicates that WD is associated with retinal and optic nerve neurodegeneration. Optical coherence tomography studies consistently demonstrate thinning of the retinal nerve fiber layer, ganglion cell complex, and macular structures, particularly in patients with neurological involvement. Electrophysiological investigations, including visual evoked potentials and electroretinography, reveal delayed neural conduction and retinal dysfunction, supporting the concept of widespread neuro-ophthalmological impairment. Optical coherence tomography angiography further identifies microvascular alterations affecting retinal and peripapillary capillary networks. Importantly, several ocular abnormalities correlate with neurological severity and may serve as non-invasive biomarkers of disease progression. Current treatments, including copper chelators and zinc therapy, can induce regression of Kayser-Fleischer rings and sunflower cataracts. Ocular assessment therefore provides a valuable window into systemic and neurological disease activity, highlighting the importance of multidisciplinary management and the potential role of emerging imaging biomarkers in Wilson disease.
Chromatin remodeling plays a central role in regulating plant development and physiology by shaping the gene expression patterns that drive biological processes. Among epigenetic modifications, histone acetylation is particularly relevant as it alters chromatin structure and influences transcriptional activity. MYST-type histone acetyltransferases (HAT) are evolutionarily conserved components of the Nucleosome Acetyltransferase of histone H4 (NuA4) complex, a key regulator that acetylates histones H4, H2A, and the histone variant H2A.Z. Growing evidence supports the presence of a canonical NuA4-C in plants, similar to that described in yeast. In this review, we summarize recent studies that have begun to uncover its broad role in plant biology, highlighting its involvement in diverse processes such as the skoto- to photomorphogenesis switch, chloroplast development, shade avoidance responses, thermomorphogenesis, the vegetative-to-reproductive transition, plant growth, reproduction and hormonal signalling. In addition, we discuss recent advances in understanding the crosstalk of NuA4-C-mediated H4ac and H2A.Z deposition with other chromatin remodeling complexes in plants. Although significant progress has been made, a full understanding of the complex functions remains unavailable. Current evidence indicates that NuA4-C in yeast and TIP60 in humans are central regulators of transcription, acting not only through histone acetylation but also by influencing transcription elongation and RNA splicing, although direct evidence for similar functions in plant NuA4-C still remains limited. This regulatory role might be critical for integrating developmental programs with environmental signalling pathways. While initial insights into the recruitment of NuA4-C to target genes have emerged, further research is needed to clarify how its activity is controlled and modulated in different biological contexts.
Soybean (Glycine max (L.) Merrill), a vital food and oilseed crop native to China, has the development of high-yield and high-quality new varieties as a core objective in soybean breeding. However, studies on genetic diversity and marker-trait associations for yield-related traits across multiple environments using simple sequence repeat (SSR) markers remain limited. This study utilized 20 pairs of SSR primers to investigate genetic diversity and marker-trait associations (MTAs) between SSR markers and yield-related traits in 150 soybean accessions of diverse origins, which were grown under two environmental conditions. Genetic diversity analysis of 12 key agronomic traits, including plant height, number of branches, number of pods per plant, and hundred-seed weight, showed substantial phenotypic variation with large ranges and high coefficients of variation among the accessions. Cluster analysis based on agronomic traits classified the germplasm into five clusters under environment E1 and four clusters under environment E2. SSR primer amplification of the accessions' genomic DNA produced an average of 7.10 amplified loci and 6.80 polymorphic loci per primer pair, with an average polymorphic locus rate of 96%. The average values of effective allele number (Ne), gene diversity index (H), Shannon's information index (I), polymorphism information content (PIC), and genetic similarity coefficient (GSC) were 1.5035, 0.3581, 0.5176, 0.3539, and 0.57, respectively. SSR-based cluster analysis divided the 150 accessions into three distinct clusters. Principal coordinate analysis (PCoA) validated that the selected SSR primers could effectively discriminate among the accessions. Population structure analysis indicated complex genetic relationships and substantial genetic diversity within the germplasm panel. Association analysis between agronomic traits and SSR markers identified 44 markers significantly associated with yield-related traits, of which 13 were simultaneously linked to two or more yield-related traits. Using generalized linear model (GLM) and mixed linear model (MLM) analyses, six SSR markers significantly associated with yield-related traits were consistently detected across the two environments. These results provide a theoretical basis for germplasm utilization and molecular breeding in soybean.
Direct electrochemical CO2 reduction is currently limited to a narrow range of multicarbon products due to limited multicarbon pathways on Cu surfaces. Biochemical methods, by contrast, are often slow due to the slow rate of gas-liquid mass transfer to microbial cells. To overcome the limitations of the individual processes, integrating electrochemical systems with biosynthetic processes has become a promising approach. However, only a narrow range of microbial strains has been explored in these combined systems. Here, we introduce a modular abiotic-biotic platform that allows electrochemically produced formate (eFormate) to be supplied independently to various microbial systems. A concentrated formate solution (0.87 M) was produced within 4 h using a SnO2 catalyst and subsequently converted into a biocompatible carbon feedstock by adjusting the pH. Based on earlier reports, we identified and evaluated 13 microbial strains known to grow on formate, 10 of which exhibited robust growth in the prepared formate solution and successfully secreted multicarbon products and important metabolic markers like acetate, ethanol, lactate, pyruvate, and polyhydroxybutyrate (PHB). This work establishes a proof of concept for a broadly applicable abiotic-biotic platform that expands the microbial design space by coupling CO2 electrolysis with carbon upgrading.
Current methods for assessing low-abundance proteins in individual cells are limited. As a result, cell functions are often inferred from single-cell RNA sequencing (scRNA-seq) data, which can be misleading due to the poor cross-gene correlation (different genes in the same cells) between messenger RNA (mRNA) and protein levels. To address this issue, we used isolated brain vascular fragments to study the blood-brain barrier. We applied a combination of deep bulk proteomic analysis, a proteomic ruler approach, and scRNA-seq, assuming a high within-gene correlation (same gene in different cells) between mRNA and protein. This approach allowed us to estimate protein copy numbers per cell for 9,940 proteins across eight cell types, including endothelium, smooth muscle, pericytes, fibroblasts, and microglia. We also evaluated protein abundance in astrocyte end-feet attached to the vessel fragments. Our data are available through an Online Database, providing a searchable resource and reference protein atlas for future studies of neurovascular proteomics in health and disease.
Continuous glucose monitoring (CGM) offers real-time and longitudinal insights into glycemic patterns, time in range, and hypoglycemia. Adopting CGMs into practice can improve clinical outcomes while strengthening patient engagement and enabling data-driven care across routine visits and population health programs. Despite strong evidence of benefit, CGM remains underused in primary care, where most patients with diabetes mellitus are managed. Barriers include limited familiarity with CGM technology, interpretation, workflow, documentation and billing, and patient access and education. The purpose of this clinical review was to help equip primary care clinicians with a concise, family medicine-focused framework for adopting CGM, including technology overview, patient selection and education, practical interpretation of standardized reports, team-based workflow, documentation, and reimbursement.
Extracellular vesicles (EVs) are membrane-bound particles that mediate intercellular communication and are being explored as carriers for antigen delivery in cancer immunotherapy. However, the molecular mechanisms underlying the uptake of antigen-carrying EVs by dendritic cells (DCs) remain unclear. EV uptake is influenced by the recognition of EV surface components by receptors on recipient cells. Phospholipids, including phosphatidylserine (PS), are common structural components of EV membrane. We therefore focused on the TAM receptor tyrosine kinases Tyro3, Axl, and Mertk, which are expressed in antigen-presenting cells and engage PS-exposing membranes through the bridging ligands Growth arrest-specific 6 (Gas6) and Protein S (Pros1). Using the DC2.4 dendritic cell line as a model system, we investigated the involvement of TAM receptors in the uptake of small EVs (sEVs) and subsequent antigen presentation. We found that Tyro3 binding to sEVs was enhanced by Gas6 and Pros1, and that Tyro3 also associated with phosphatidylserine (PS) and phosphatidylglycerol (PG) through these bridging ligands. Among TAM receptors, only Tyro3 markedly enhanced sEV internalization in DC2.4 cells. Deletion analysis indicated that the immunoglobulin C2-type domain (IG2c domain) of Tyro3 is required for efficient sEV association and uptake. Moreover, Tyro3-mediated internalization enabled cross-presentation of sEV-delivered antigens and activation of CD8+ T cells. This function required a 46-amino acid intracellular region of Tyro3, which we designated the Tyro3 antigen presentation-related domain (TAPD); deletion of TAPD impaired cross-presentation of sEV-delivered antigens. Finally, we observed an increase in the frequency of Tyro3 ⁺ DCs in the spleens of tumor-bearing mice. These findings suggest that Tyro3 mediates sEV uptake and antigen cross-presentation in DCs and may represent a candidate molecular target for EV-based cancer immunotherapy.
Mutations in STRA6, the high-affinity receptor for retinol-binding protein, cause Matthew-Wood syndrome, a congenital disorder characterized by striking phenotypic variability ranging from isolated ocular anomalies to severe multisystem malformations. The mechanisms underlying this variable expressivity and incomplete penetrance remain poorly understood. Here, we used mice to determine how maternal vitamin A status and embryonic Stra6 genotype interact to shape ocular development. Using Stra6-deficient mice bred under defined dietary conditions, we demonstrate that maternal vitamin A availability is a major modifier of phenotypic outcome. Maternal vitamin A restriction resulted in microphthalmia and markedly reduced postnatal survival of the offspring. Remarkably, offspring of Stra6-/- dams maintained on a vitamin A-sufficient diet, corresponding to the recommended dietary allowance for mice, also developed pronounced ocular abnormalities, including retinal dysplasia and impaired rod and cone opsin differentiation. In contrast, supraphysiological maternal vitamin A intake, as provided by a standard chow, partially rescued ocular development and produced near-normal eye morphology in the offspring. Strikingly, heterozygous Stra6+/- offspring born to Stra6-/- dams were protected from both lethality and ocular malformations despite maternal STRA6 deficiency and dietary vitamin A restriction. Biochemical analyses revealed that ocular retinoid availability strictly depended on the Stra6 genotype of the offspring, whereas some circulating retinol remained detectable even under maternal vitamin A deficiency. Together, these findings identify a gene-nutrient interaction that explains the variable expressivity of STRA6-associated disease and establish maternal vitamin A status as a critical determinant of ocular development and postnatal survival.
This study explores a stem-cell-based approach for diabetes treatment by enhancing the viability and functionality of insulin-producing cells (IPCs) derived from stem cells of the apical papilla (SCAP). Although SCAP can differentiate into IPCs, limited cell survival remains a challenge. To address this, the proliferation enhancer WS6 was incorporated into Eudragit RS100 nanoparticles (NPs) using microfluidics. The WS6-loaded NPs were characterized for size, charge, PDI, morphology, stability, and drug loading. An MTT assay was performed as a preliminary screening method to evaluate the cytocompatibility of blank-NPs and to optimize treatment concentration. SCAP cells were treated with free WS6 or WS6-loaded NPs, and cellular uptake of NPs was evaluated using flow cytometry and fluorescence imaging. Additionally, the viability of treated cells was determined by propidium iodide (PI) and trypan blue. Prior to differentiation, definitive endoderm formation was assessed through SOX17 and FOXA2 expressions. After differentiation into IPCs, maturation markers such as insulin, C-peptide, PDX-1, NKX2.2, and NKX6.1 were examined, and apoptosis assays measured cell viability. Functional insulin secretion was tested using an in vitro glucose-stimulated insulin secretion (GSIS) assay. Results showed that WS6-loaded NPs significantly improved SCAP viability, increased healthy cell percentages, and enhanced IPC maturation. Treated IPCs demonstrated functional insulin secretion and improved glucose regulation. Overall, WS6-loaded NPs represent a promising approach to enhance IPC proliferation and generation for diabetes therapy.
Discovery of a novel HLA class II allele, HLA-DRB3*02:02:56, identified using two NGS methods.
The dorsal vagal complex (DVC) includes a multi-component brainstem satiety centre which has gained attention as a key target of anti-obesity pharmacotherapies. Our recent studies revealed its circadian timekeeping properties, with molecular and electrophysiological 24 h rhythms persisting independently of the primary hypothalamic clock. However, the factors entraining these brainstem oscillators and the downstream transcriptional targets of the DVC molecular clock remain unclear. Here, using PERIOD2::LUCIFERASE reporter mice and fluorescent in situ hybridisation, we quantitatively demonstrate rhythms in core clock gene expression in the caudal DVC ex vivo and in vivo. We show that the molecular clock is associated with rhythmic expression of numerous neurotransmitter receptor genes in the DVC in vivo, with the phase of both clock and clock-controlled gene expression tightly regulated by meal timing. These findings uncover food-entrained circadian rhythms in the DVC and have important implications for clinical studies targeting brainstem satiety mechanisms.
The domestication of plants in southwest Asia was an evolutionary process that took place over several millennia in the Early Holocene. During this time, domestic species developed distinct traits that distinguished them from their wild counterparts. Current models of plant domestication emphasize the role of genetic selection in the evolution of these traits, viewing these as heritable adaptations that arose in response to selective pressures associated with human cultivation. In cereals, domestication resulted in the evolution of nonshattering rachis and increased grain size, two traits that can be tracked directly in the archaeobotanical record. Analyses of Early Neolithic cereal remains demonstrate that grain size increase occurred prior to the evolution of nonshattering rachis, a sequence that is often interpreted as evidence of selection for larger grains under cultivation, specifically tillage. Here, we combine morphological and metrical analyses of cereal remains, stable carbon isotope analysis, and weed ecology to test this hypothesis, using three assemblages from the southern Levant: Pre-Pottery Neolithic A Sharara (c. 9250-9200 cal BCE), Pre-Pottery Neolithic A el-Hemmeh (c. 9400-8700 cal BCE), and Late Pre-Pottery Neolithic B el-Hemmeh (c. 7500-7000 cal BCE). Our findings indicate that increased grain size in the Early Holocene can be better understood as a plastic response to variation in growing conditions, specifically moisture, rather than as a result of genetic selection for increased grain size under cultivation. We propose that cereal evolution in southwest Asia was initially driven by developmental plasticity, followed by genetic selection.
A central goal in sensory science is to establish quantitative mappings between physical stimuli and perceptual experience. Although such mappings are well defined in vision and audition, they remain elusive in olfaction, particularly for complex odor mixtures. Here, we show that perceptual distances between odor mixtures can be predicted with high fidelity and are unexpectedly well captured by a compact semantic space derived from single-molecule representations. In the Dialogue for Reverse Engineering Assessment and Methods Olfactory Mixtures Prediction Challenge, we assembled a unified dataset of odor-mixture pairs, benchmarked predictions on a hidden test set of 46 pairs, and integrated the top-performing models into a postchallenge ensemble. This model outperformed existing state-of-the-art approaches on the hidden test set, reducing RMSE by about 33% to 0.08 and increasing Pearson correlation by 53% to 0.57, and maintained strong performance on an independent validation set of 50 newly designed mixture pairs. An ensemble, retaining only olfactory semantic features for each model included, further improved predictions, raising the Pearson correlation by 7% to 0.61 on the test set and by 15% to 0.54 on the validation set. Given that semantic features were extracted from pure molecules, it suggests that mixture perception may not require fundamentally different representational principles from single-molecule olfaction. Together, these results establish a reproducible quantitative framework for olfactory mixture perception and advance efforts to measure, model, and engineer smell.
Enlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-EPVS) are part of the diagnostic criteria for cerebral amyloid angiopathy. We aimed to investigate associations of EPVS with reduced estimated glomerular filtration rate (eGFR) and glomerular hyperfiltration (higher than normal eGFR), which have scarcely been studied previously. In this cross-sectional study, we used pooled individual patient data from the Microbleeds International Collaborative Network which includes patients with ischemic stroke or transient ischemic attack. We investigated associations of impaired kidney function, defined as an eGFR of 30-60 or <30 mL/minute/1.73 m2, and glomerular hyperfiltration, defined as eGFR above the age-adjusted and sex-adjusted 95th centile, with BG-EPVS and CSO-EPVS severity. EPVS were rated according to a validated 5-point ordinal scale, and combined cSVD burden was rated using a validated 5-point ordinal scale with 1 point assigned for the presence of each of the following: severe white matter hyperintensities, ≥1 cerebral microbleed, ≥1 lacune, and BG-EPVS ≥11. Normal glomerular filtration was defined as eGFR ≥60 without hyperfiltration. We used multivariable ordinal logistic regression models to estimate risk of increased EPVS and cSVD burden severity adjusted for age, sex, and comorbidities. Seven thousand two hundred fifty-four patients (mean age 71 ± 13 years, 43% female) were included in the analysis, 357 with glomerular hyperfiltration, 1,692 with eGFR 30-60, and 256 with eGFR <30. Compared with normal glomerular filtration, hyperfiltration was independently associated with BG-EPVS (adjusted odds ratio [aOR] 1.38, 95% CI 1.11-1.70, p < 0.001) and CSO-EPVS (aOR 1.34, 95% CI 1.08-1.64, p = 0.011). Associations of eGFR 30-60 and eGFR <30 with EPVS were not statistically significant. Compared with normal glomerular filtration, eGFR <30 (aOR 1.27, 95% CI 1.03-1.57) was independently associated with increased cSVD burden, but eGFR 30-60 (aOR 1.06, 95% CI 0.95-1.20) and hyperfiltration (aOR 1.15, 95% CI 0.98-1.34) were not. Glomerular hyperfiltration was independently associated with EPVS severity, in both the basal ganglia and centrum semiovale. eGFR <30 was independently associated with total cSVD burden. A key limitation was a lack of repeated eGFR measurements.
Primary (genetic) pediatric dystonia, characterized by sustained or intermittent muscle contractions that cause abnormal movements or postures, affects 16.4 in 100,000 children worldwide. It can be caused by various factors, including pathogenic variants in genes such as TOR1A, associated with DYT-TOR1A dystonia. In this report, we present the case of a toddler with DYT-TOR1A treated with deep brain stimulation (DBS) because of his early-onset, rapidly progressive, and refractory status dystonicus. Genetic testing confirmed a maternally inherited pathogenic variant in TOR1A, c.907_909del (p.Glu303del). His dystonia was refractory to multiple optimized medications and continuous infusions. Ultimately, DBS surgery to the bilateral globus pallidus interni (GPi) provided symptomatic relief of his status dystonicus. His atypical presentation and young age made it difficult to predict expected outcomes. Thus, he required unique planning considerations before placement of bilateral GPi DBS. This case highlights challenges in symptom management, anticipatory guidance, and treatment expectations in the complex and refractory condition of status dystonicus for a young patient with DYT-TOR1A.
Whole-genome duplication (WGD) is a major driver of plant speciation and often hypothesized to promote rapid adaptation to new or changing environmental conditions. However, the extent to which WGD per se fosters phenotypic and transcriptional novelties, and the relative contribution of WGD-induced changes vs post-WGD evolution to trait differentiation between cytotypes remains poorly understood. Here, we investigated the phenotypic and transcriptomic consequences of WGD and subsequent evolution in the Biscutella laevigata diploid-autotetraploid complex by comparing replicated diploid, synthetic autotetraploids, and natural autotetraploids (originated some 24,000 to 7,000 generations ago) under moderate daily temperature fluctuations (stable) vs. daily heat stress (changing) conditions. WGD led to reduced specific leaf area and slower rosette growth but had no significant effect on biomass. Post-WGD evolution acted in contrasting directions on WGD-induced changes, either reverting traits to diploid-like values or maintaining them in natural autotetraploids. Overall, WGD induced a decrease in fitness that was mitigated by post-WGD evolution, resulting in natural autotetraploids with similar or higher fitness under changing conditions than diploids. While the genetic background modulates the effects of WGD, cytotype-level transcriptomic analyses revealed limited immediate effects of WGD under stable conditions, although heat stress induced different responses across cytotypes. Altogether, our results highlight a complex interplay between immediate WGD-induced and subsequent evolution at the phenotypic and transcriptomic levels, supporting a predominant role of post-WGD evolution in the differentiation of current cytotypes and the adaptive evolution of autotetraploids of B. laevigata.
TRK inhibitors (TRKis) have transformed the therapeutic landscape for patients with neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive tumors. However, approval of TRKis is based on evidence derived mainly from small, pooled, single-arm clinical trial cohorts. The REALTRK registry aims to describe real-world molecular diagnostic practices, treatment patterns, and clinical outcomes for adult patients with NTRK fusion-positive cancers. The REALTRK registry was a multicenter cohort study that included adults with advanced solid tumors harboring NTRK1/2/3 fusions, from Germany and Switzerland. Both retrospective and prospective data were collected from diverse clinical settings. NTRK fusions had to be diagnosed via validated assays. Of 88 patients screened, 47 adults with advanced NTRK fusion-positive solid tumors were included in the full analysis set. Across all treatment lines after NTRK fusion diagnosis, 29 patients received TRKi therapy, eight received non-TRKi therapy, and 10 received no therapy. Lung cancer, colorectal cancer, and soft tissue sarcoma were the most common tumor types. Next-generation sequencing was the primary diagnostic method, with a median turnaround time of 2 weeks. After NTRK fusion diagnosis, TRKi therapy was immediately initiated in 26 patients, of whom 13 received TRKi as first-line treatment in the advanced/metastatic setting. About half of the patients responded to TRKi treatment as the first treatment line after NTRK fusion diagnosis (46.2%), with an overall response rate of 46.2% and a disease control rate of 73.1%. The median progression-free survival was 15.7 months, and the overall survival was 27.6 months in TRKi-treated patients. The REALTRK registry provides important real-world insights into the patient path of adult patients with locally advanced or metastatic solid tumors harboring NTRK1/2/3 gene fusions.
For years, the airway microbiota have been theorized to be gatekeepers of respiratory health, as pathogens entering the airway make contact with resident microbes prior to or coincident with their interaction with host cells. Thus, modification of the native airway community may serve as a means of altering the local environment in favor of health. In this work, we hypothesize that synthetic bacterial communities introduced into the airway can serve as prophylactic countermeasures against infection by Burkholderia thailandensis in mice. We demonstrate that understanding of antagonistic interactions between a pathogen and airway microbiota in vitro can guide identification of probiotics with protective capabilities in vivo. Specifically, we show that niche overlap between the probiotic and pathogen is indicative of probiotic performance in vivo. This work serves as a foundation for the rational design of probiotic communities for protection against and treatment of respiratory infections.