Type 1 conventional dendritic cells (cDC1s) acquire and cross-present tumor antigens to prime CD8⁺ T cells. Whether this selects for specific neoantigens is unclear. DNGR-1 (CLEC9A), a cDC1 receptor for F-actin exposed on dead cells, promotes cross-presentation of cell-associated antigens. Here we show that DNGR-1-deficient mice develop chemically induced tumors more rapidly and at higher incidence, and these are more frequently rejected on transplantation into wild-type recipients. Whole-exome sequencing reveals enrichment of predicted neoantigens derived from mutated F-actin-binding proteins. Consistent with this observation, tethering model antigens to F-actin enhances DNGR-1-dependent cross-presentation. These results suggest that DNGR-1-mediated recognition of F-actin exposed by dead cancer cells favors priming of CD8⁺ T cells specific for cytoskeletal neoantigens, which can then drive immune escape of cancer cells lacking or reverting those mutations. Thus, neoantigen cross-presentation by cDC1 can determine the immune visibility of the tumor mutational landscape and sculpt cancer evolution by immunoediting. Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.
Background Dilatation of the common bile duct (CBD) after cholecystectomy is frequently observed during follow-up imaging; however, its extent and clinical implications remain incompletely defined. Distinguishing physiological postoperative ductal enlargement from pathological dilatation is essential to avoid unnecessary diagnostic evaluation. This study aimed to compare CBD diameter in post-cholecystectomy patients with non-operated controls and to assess its association with time since surgery, age, and body mass index (BMI). Materials and methods This retrospective observational study included 165 adult patients who underwent abdominal ultrasound examination, comprising 91 post-cholecystectomy patients and 74 controls with an intact gallbladder. The CBD diameter was measured in the suprahilar segment. Group differences were evaluated using independent t-tests and chi-square tests. Logistic and linear regression analyses were used to assess predictors of CBD dilatation and continuous diameter change. All multivariable models were adjusted for age, sex, and BMI. Results CBD diameter was significantly greater in post-cholecystectomy patients compared with controls (6.61 mm vs. 4.56 mm; p < 0.001). Dilatation ≥7 mm occurred in 38.5% of post-cholecystectomy patients versus 5.4% of controls (p < 0.001), and prior cholecystectomy remained a strong independent predictor of dilatation after adjustment (aOR = 14.583; 95% CI: 4.449-47.807). Using a fixed ≥7 mm cutoff, increasing age was associated with lower odds of categorical CBD dilatation, whereas sex and BMI were not significant predictors. Linear regression analyses demonstrated a significant positive association between CBD diameter and both time elapsed since surgery and age, indicating gradual ductal enlargement over time. Marked dilatation (>10 mm) was uncommon and did not reach statistical significance in relation to cholecystectomy. Conclusion Cholecystectomy is associated with measurable and progressive enlargement of the CBD. While CBD diameter increases gradually with advancing age and postoperative duration, categorical dilation thresholds are more strongly influenced by surgical status than by age alone. Recognition of this expected postoperative anatomical pattern may help clinicians avoid unnecessary imaging and interventions in asymptomatic patients.
Introduction Spinal tumor surgery mandates complete removal with preserved neurological function and stability. Total Laminectomy (TL) provides access but risks complications (pain, deformity) from extensive tissue removal. The safer, tissue-sparing Unilateral Hemilaminectomy (UHL) is limited by concerns about complete resection via its narrower corridor. Research question This study was comparing the clinical and radiological characteristic between unilateral TL and total laminectomy UHL and they clinical outcomes and complications. Material and methods This was a retrospective cohort study comparing UHL and TL for intradural/extradural spinal tumors. We analyzed consecutive patients operated between January 2018 and December 2024, excluding those with confounding factors. Surgical approach was selected based on tumor location and intraoperative needs. Data on patient demographics, pre/postoperative neurological status, surgical parameters, and tumor characteristics were collected. Primary outcomes were postoperative neurological status and complications rate. Statistical analysis compared variables between groups using appropriate tests, with significance at p = 0.05. Results Baseline characteristics were similar between groups, and the overall postoperative complication rate was low (6.3 %) and comparable. The postoperative KPS score between UHL and TL showed improvement, without significant difference between them. Both approaches yielded significant improvements in functional status and neurological recovery from preoperative baselines. Discussion and conclusion Our findings indicate that the tissue-sparing UHL approach can achieve similar functional outcomes and complication rates as TL for similarly sized tumors. This supports UHL as a safe and effective option, although the final surgical approach must remain individualized based on specific tumor complexity and radiological findings.
The Balkan mountain ranges are major hotspots of genetic diversity and endemism, yet many species remain poorly studied. One such species is Alyssum bosniacum, a narrow endemic of the Central Dinaric Alps. To fill this gap, we examined 143 individuals from 15 populations across the species’ range using flow-cytometric ploidy determination, amplified fragment length polymorphisms (AFLPs), nuclear microsatellites, and chloroplast DNA sequences. Microsatellite data revealed two genetic clusters, showing moderate differentiation and relatively high diversity. AFLP profiles indicated shallow but geographically structured variation, while chloroplast haplotypes showed limited divergence and regional clustering. Our data suggest possible persistence in multiple microrefugia within the Central Dinaric Alps, although further evidence is needed to confirm this scenario. Despite range fragmentation, genetic variation within the population remains high, indicating evolutionary resilience and supporting the species’ long-term future population stability under current conditions.
Studies have rarely examined the effects of changes in legal anti-doping knowledge (LADK) on doping tendencies in athletes. This study aimed to evaluate the effectiveness of a structured educational intervention focused on LADK and to analyze how LADK changes affect elite athletes’ doping tendency. The participants were athletes (n = 310; 156 females; 24.1 ± 4.2 years of age), all actively competing at the senior national or international level in either individual (N = 119) or team sports (N = 191), tested on sociodemographic-, sport-, doping-factors (including doping tendency—DT), and LADK. Participants were randomly divided into an experimental group (E: N = 140) and a control group (C: N = 170). The E group participated in a structured educational program on LADK. A pre- and posttest design was used to evaluate changes in LADK (dependent variable). Logistic regression was calculated to evaluate the association between LADK and binarized DT (negative vs. neutral/positive DT). Factorial ANOVA for repeated measurements revealed significant improvement in LADK in the E group, with significant ANOVA effects for time (F test = 35.8, p < 0.05) and time × group interaction (F test = 12.27, p < 0.05). The logistic regression did not reveal significant correlations between LADK and DT. Further studies exploring younger athletes, as well as long-term, multidimensional interventions, are warranted.
Seed biopriming is increasingly recognized as a strategy capable of inducing molecular memory that enhances plant performance under heavy-metal stress. Here, we investigated how biopriming Silene sendtneri seeds with Paraburkholderia phytofirmans PsJN establishes a transcriptional state that predisposes seedlings for improved cadmium (Cd) tolerance. RNA-seq profiling revealed that primed seeds exhibited differential gene expression prior to Cd exposure, with strong upregulation of detoxification enzymes, antioxidant machinery, metal transporters, photosynthetic stabilizers, and osmoprotectant biosynthetic genes. Enrichment of gene ontology categories related to metal ion detoxification, redox homeostasis, phenylpropanoid metabolism, and cell wall organization indicated that biopriming imprints a preparatory transcriptional signature resembling early stress responses. Upon Cd exposure, primed plants displayed enhanced physiological performance, including preserved integrity, elevated antioxidant activity, particularly peroxidases in roots, higher osmolyte accumulation, stabilized micronutrient levels, and substantially increased Cd uptake and sequestration. These coordinated responses demonstrate that biopriming induces a sustained molecular memory that accelerates and strengthens downstream defense activation. These findings demonstrate that PGPR-based biopriming establishes a stable transcriptomic memory in seeds that enhances cadmium tolerance, metal sequestration, and stress resilience, highlighting its potential for improving hyperaccumulator performance in phytoremediation and stress adaptation strategies.
Sex-biased dispersal may affect the genetic structure of wild populations, often leading to distinct patterns of relatedness between males and females. We examined this phenomenon in the golden jackal (Canis aureus) population from the northern lowlands of Bosnia and Herzegovina (BiH) by analyzing 36 individuals (18 males and 18 females) using 16 polymorphic microsatellite loci. The population exhibited moderate genetic diversity, consistent with the diversity in the region. Analyses of population structure, including STRUCTURE, PCoA, and pairwise Fst (Fst = 0.004; p = 0.190), revealed no significant genetic differentiation between males and females, suggesting a lack of sex-biased structuring. This pattern may be further explained by recent demographic expansion. Analyses of local relatedness showed that the observed patterns reflect local kinship rather than relatedness determined by sex. Although the corrected Assignment Index (AIc) indicated a trend consistent with male-biased dispersal, this difference was not statistically significant. However, male dispersal warrants further investigation with an increased sample size and broader sample distribution.
Gastrointestinal nematodes, particularly Haemonchus contortus, represent a major threat to ruminant health and productivity worldwide, largely due to the widespread emergence of anthelmintic resistance. In Bosnia and Herzegovina, benzimidazole resistance has previously been confirmed in domestic ruminants; however, data on wildlife remain lacking. Given the frequent spatial and temporal overlap between domestic and wild ruminants on shared pastures, this study aimed to investigate the occurrence of benzimidazole-resistant H. contortus genotypes within a multi-host system. During the 2024/2025 season, a total of 111 abomasal samples were collected from sheep (n = 20), lambs (n = 12), goats (n = 17), roe deer (n = 40) and chamois (n = 22) across four localities in Bosnia and Herzegovina (Laktaši, Banja Luka, Modriča and Višegrad). Adult H. contortus specimens were morphologically identified and confirmed using real-time quantitative PCR (rt-qPCR). Benzimidazole resistance was assessed by allele-specific rt-qPCR targeting the F200Y mutation in the β-tubulin isotype 1 gene. Statistically significant interspecies differences in β-tubulin genotype distribution were observed (p < 0.05), primarily driven by variation in the homozygous resistant (RR) genotype. High RR prevalence was detected in sheep (60%), lambs (50%) and roe deer (52.5%), whereas lower proportions were observed in chamois (27.3%) and goats (23.5%). Overall, 44.1% of all analyzed H. contortus isolates carried homozygous resistant alleles, indicating an advanced stage of benzimidazole resistance within this multi-host system. These findings demonstrate that benzimidazole resistance in H. contortus is not confined to domestic livestock but is also present in wild ruminants sharing the same grazing areas, consistent with circulation of resistant parasites within shared grazing systems.
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder that typically affects young adults and is primarily characterized by demyelinating lesions in the central nervous system (CNS). According to the Revised McDonald Criteria, the clinical diagnosis of MS can be established based on a combination of clinical observations, the presence of focal lesions in at least two distinct CNS areas on magnetic resonance imaging (MRI) and the detection of specific oligoclonal bands in the cerebrospinal fluid. Conventional MRI remains a cornerstone of MS diagnosis and disease monitoring, providing high-resolution assessments of lesion burden and brain atrophy. In addition, advanced MRI methods are increasingly applied in research settings to probe myelin integrity, iron deposition, and biochemical changes, with the potential to complement established diagnostic workflows in the future. Despite remarkable advances in the management of MS over the past two decades, complex differential diagnoses and the lack of effective imaging tools for therapy monitoring remain major obstacles, thus channeling the development of innovative molecular imaging probes that can be harnessed in clinical practice. Indeed, positron emission tomography (PET) has a significant potential to advance the contemporary diagnosis and management of MS. Given the solid body of evidence implicating myelin dysfunction in the pathophysiology of MS, myelin-targeted imaging probes have been developed, and are currently under clinical evaluation for MS diagnosis and therapy monitoring. In parallel, ligands for the 18 kDa translocator protein (TSPO) and the cannabinoid receptor type 2 (CB2R) have been employed to capture neuroinflammatory processes by visualizing microglial activation, while other tracers allow the assessment of synaptic integrity across various disease stages of MS. Further, PET probes have been employed to delineate the role of activated microglia and facilitate the assessment of synaptic dysfunction across all disease stages of MS. This review discusses the challenges and opportunities of translational molecular imaging by highlighting key molecular concepts that are currently leveraged for diagnostic imaging, patient stratification, therapy monitoring and drug development in MS. Moreover, we shed light on potential future developments that hold promise to advance our understanding of MS pathophysiology, with the ultimate goal to provide the best possible patient care for every individual MS patient.
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