Search Results (2,360)

Background/Objectives: Habitat degradation and fragmentation reduce population size, genetic diversity, and connectivity, increasing extinction risk in small and isolated populations. Coastal wetlands of northwestern Peru have undergone extensive anthropogenic modification, yet the genetic and ecological status of resident carnivore populations remains poorly documented. This study aimed to assess genetic diversity, relatedness, demographic signals, and diet composition of a Pampas cat (Leopardus garleppi) population inhabiting the Mangroves San Pedro de Vice (MSPV), a Ramsar-listed coastal wetland. Methods: We combined noninvasive fecal genotyping using eight nuclear microsatellite loci with vertebrate DNA metabarcoding. Scat samples were collected across three field seasons (2019–2021). Individual identification, genetic diversity metrics, genetic mark–recapture estimation of census size (Nc), effective population size (Ne), bottleneck tests, and relatedness analyses were performed to evaluate population status and kin structure. Dietary composition was characterized using metabarcoding and assessed for sex-specific differences. Results: Sixty-eight scats yielded multilocus genotypes for nine individuals (six males, three females). Genetic analyses revealed moderate diversity (mean allelic richness = 3.47; observed heterozygosity = 0.69; expected heterozygosity = 0.58) and evidence consistent with a recent genetic bottleneck. Genetic mark–recapture analyses estimated a small census size (Nc = 9; 95% CI: 7.0–9.0), while the effective population size was markedly low (Ne = 2.4; 95% CI: 1.5–7.4), yielding an Ne/Nc ratio of ~0.27. Multiple first-order kin dyads were detected, indicating strong local kin structure and limited external recruitment. Metabarcoding identified eight vertebrate prey species, with diet dominated by the native rodent Aegialomys xanthaeolus. No significant sex-specific differences in diet composition were detected. Conclusions: The MSPV Pampas cat population represents a small, kin-structured range-edge population showing signatures consistent with recent genetic erosion and restricted connectivity. These patterns align with isolation in a degraded coastal wetland landscape, highlighting the importance of habitat protection, prey resource conservation, and restoration of functional connectivity to support long-term population persistence. Full article

The efficacy of immunotherapy in colorectal cancer (CRC) has long been considered to be closely associated with microsatellite instability (MSI) status. Patients with microsatellite stable (MSS) tumors typically exhibit poor responses to PD-1/PD-L1 inhibitors and a poor prognosis, often being categorized as immunologically ‘cold’ tumors. However, some MSS patients can still achieve favorable therapeutic responses, sometimes even surpassing those of certain MSI patients. Immune-cold and immune-hot tumor phenotypes are largely determined by the abundance, clonal expansion, and functional states of tumor-infiltrating T cells. This suggests that immunotherapy responses are driven by dynamic remodeling of T-cell clonality rather than by MSI status alone. To elucidate the underlying T cell clonal dynamics, integrated single-cell transcriptome (scRNA-seq) and T cell receptor sequencing (scTCR-seq) data analyses from 43 blood and tissue samples of MSI and MSS colorectal cancer patients before and after anti-PD-1 therapy were performed. Using our developed TCR reconstruction pipeline (TORBiT), we systematically analyzed the clonal architecture of the TCR repertoire, inter-tissue migration, and its association with T-cell functional state transitions. From a TCR clonal kinetic perspective, we revealed two distinct modes of immune Coercion that may further affect the immune response: a “high-fluctuation, deep-exhaustion” pattern in MSI tumors and a “high-baseline, strong-suppression” pattern in MSS tumors. These findings provide a novel theoretical foundation and research perspective for understanding the responsiveness and resistance mechanisms to immune checkpoint inhibitors. Full article

Glial brain tumours, including astrocytoma IDH (Isocitrate Dehydrogenase) mutant and glioblastoma IDH wild-type, are highly malignant brain tumours with poor clinical outcomes. Genomic instability, encompassing microsatellite (MIN) and chromosomal instability (CIN), drives tumour heterogeneity and evolution. In this study, genomic instability was analysed in 85 patients using AP-PCR (Arbitrarily Primed Polymerase Chain Reaction) by comparing tumour and normal tissue (blood) DNA profiles of the same patient. Both types of alterations were present in all analysed samples, contributing almost equally to the total level of genomic instability. The dominant pattern of genomic instability in our cohort was low overall instability, predominantly manifesting as low-degree microsatellite instability. A general decrease in genomic instability was observed with increasing tumour grade. Glioblastoma IDH wild-type was more prevalent in older patients, whereas astrocytoma IDH mutant predominated in younger individuals. Notably, low genomic instability (both MIN and CIN) was associated with poorer survival in patients over 50 years of age. Females, compared to males, exhibited higher MIN in grade 2 tumours and elevated CIN in grade 4 tumours. Our results confirm that genomic instability contributes to tumour progression, MIN being the pivotal factor, and could serve as a prognostic biomarker in malignant gliomas. Full article

Ash dieback is an often-fatal disease caused by the fungus Hymenoscyphus fraxineus (T. Kowalski) Baral, Queloz & Hosoya. It emerged in Europe during the 1990s and poses a substantial threat to ash populations. In Hungary, symptoms were first detected on common ash (Fraxinus excelsior L.) in 2008. The disease also severely impacts another native species, the narrow-leaved ash (Fraxinus angustifolia Vahl). An effective strategy for counteracting ash decline is to identify and utilize sources of tolerance. We are monitoring the health status of the selected trees that demonstrate low susceptibility (plus trees) and conducting molecular genetic studies to enable their genetic characterization and individual identification using 16 nuclear microsatellite (nSSR) markers. The PCoA (Principal Coordinates Analysis) separated the eight assessed groups into two distinct clusters based on the taxonomic traits. Based on the Structure analysis results, K = 2 was the most probable cluster number. Hybridization was also indicated in the case of several individuals across various groups. We intend to incorporate the results in the establishment of seed orchards using the selected plus trees, considering the taxonomical, geographical, and genetic distinctiveness of the different groups. Full article

Enterocytozoon bieneusi is a microsporidian species found ubiquitously in both invertebrate and vertebrate hosts including domestic and wild animals and humans. Enterocytozoon bieneusi typically causes severe or chronic diarrhea, malabsorption and emaciation. This study aimed to investigate the prevalence and genotypic distribution of E. bieneusi in dogs in Fujian province, China. A total of 506 fecal samples from dogs were randomly collected from eight districts in Fujian province, China. The presence of E. bieneusi was confirmed through nested PCR targeting ITS gene. Further multilocus sequence typing (MLST) focused on the three microsatellite loci (MS1, MS3, and MS7) and minisatellite locus (MS4) loci. As a result, the infection rates of E. bieneusi in dogs were found to be 5.93% (30/506). A highly significant difference in the prevalence of E. bieneusi was observed across different urban areas (p < 0.01), with Longyan city exhibiting the highest infection rate (24.62%, 16/65), Zhangzhou and Xiamen the lowest (0.00%). Prevalence also varied significantly by source (p < 0.01), age (p < 0.01), gender (p < 0.05), symptom status (p < 0.01), and season (p < 0.01). Three known genotypes of E. bieneusi were identified in 30 dogs’ positive samples, including EbpC, PigEBITS5 and PtEb IX, whereas FJLYD1, FJLYD2 and FJSMD have been identified as new genotypes. EbpC, PigEBITS5, FJLYD1, FJLYD2, and FJSMD all belong to Group 1, while PtEb IX is assigned to Group 11. Genotypes belonging to Group 1, the first major phylogenetic clade, are considered to possess potential zoonotic risks. None of the positive samples amplified at all four loci, forming a single multilocus genotype (MLG). This study contributes to a deeper understanding of E. bieneusi in dogs, which provides critical data for the development of targeted control strategies in Fujian province. Full article

Background: Deletion of the MTAP gene at chromosome 9p21.3 defines a therapeutically actionable molecular subset of cancers due to synthetic lethal vulnerability to PRMT5 and MAT2A inhibition. The real-world prevalence and genomic context of MTAP deletion in diverse solid tumors remain incompletely characterized. Methods: We retrospectively analyzed 579 solid tumor specimens subjected to next-generation sequencing-based copy-number profiling. The prevalence of MTAP deletion and its co-occurrence with CDKN2A and CDKN2B were evaluated, and genomic deletion patterns across chromosome 9 were systematically assessed. Results: MTAP deletion was detected in 14 cases (2.4%, 95% confidence interval [CI], 1.45–4.02%), with enrichment in sarcoma, pancreatic cancer, and urothelial carcinoma. Concurrent CDKN2A loss was observed in 92.9% of MTAP-deleted tumors, and 64.3% showed additional CDKN2B loss, indicating a coordinated focal deletion event at 9p21.3. Statistical analyses confirmed strong genomic associations between MTAP and neighboring tumor suppressor genes. Across the full cohort, deletion frequency peaked at the 9p21 locus, and among MTAP-deleted tumors, co-deletion frequency decreased with increasing genomic distance. All MTAP-deleted tumors were microsatellite stable and low tumor mutational burden (TMB-low). Conclusions: Our findings demonstrate that MTAP deletion is an infrequent but genomically coherent event in solid tumors, characterized by a canonical 9p21 co-deletion pattern. This real-world analysis underscores the importance of comprehensive genomic profiling to identify patients who may benefit from emerging MTAP-directed therapies. Full article

Enterocytozoon bieneusi is an important zoonotic intestinal protozoon causing diarrhea in humans and animals, threatening public health and livestock farming. This study aimed to investigate the infection and genotype distribution of E. bieneusi in black goats in Fujian, southeastern China. A total of 539 fecal samples were collected from nine regions. E. bieneusi was detected by nested PCR and sequencing targeting the ITS locus, and genotyped using four microsatellites and one minisatellite. The overall infection rate was 7.79%, with 42 positive samples. Eight genotypes were identified, including seven known genotypes and one novel genotype FJG-1. Ten multilocus genotypes (MLGs) were obtained, and all isolates belonged to Group 2. The infection rate differed significantly among regions (p < 0.01), but not among ages or genders (p > 0.05). This is the first molecular epidemiological survey of E. bieneusi in black goats in Fujian. The results enrich the genotype database and provide data for formulating regional prevention and control strategies against this pathogen. Full article

Marine species with high fecundity and larvae with long-distance dispersal potential can have complex population genetic patterns. Characterizing population structure in these species is important for understanding their ecology and life history and designing management strategies. The eastern oyster (Crassostrea virginica) is both ecologically and economically important but has experienced recent population declines. Characterizing genetic variation in regional C. virginica populations will contribute to conservation and restoration practices. We used 20 nuclear microsatellite loci to examine genetic diversity, population structure, and kinship within and among wild oyster populations in coastal Georgia. Oysters were sampled from multiple fringe reefs within a single tidal creek and from four estuarine creeks spanning approximately 115 km of coastline. Genetic diversity was high across all sites, but modest yet significant population structure was detected at both local and regional scales. Within a single creek, significant genetic differentiation was observed among reefs separated by only a few kilometers. Kinship analyses revealed significantly higher relatedness within reefs and within creeks than among locations relative to random expectations. These results indicate that regional coastal dynamics, kin aggregation, local retention, and sweepstakes reproductive success contribute to fine-scale genetic structure despite high dispersal potential. Our findings suggest that accounting for local retention is important when designing oyster restoration, broodstock selection, and management strategies in dynamic estuarine and coastal environments. Full article

Background: Tumor mutational burden (TMB) is an FDA-approved biomarker for immune checkpoint inhibitor (ICI) therapy. However, its predictive value varies among tumor types and molecular contexts. We investigated whether a very high TMB identifies a biologically distinct subset and whether a higher cutoff provides additional clinical insights beyond the conventional high TMB threshold. Methods: We analyzed 133 patients with advanced solid tumors and TMB ≥ 10 mutations/Mb (mut/Mb) who underwent tumor genomic profiling using a 523-gene DNA/RNA next-generation sequencing panel. Tumors were stratified into prespecified TMB categories: 10–20 mut/Mb (TMB-H) and >20 mut/Mb (TMB-VH). The clinical characteristics, ICI outcomes (in the treated subset), and pathway-level genomic features were compared between groups. Results: TMB-VH was observed in 42/133 (31.6%) patients and spanned more than 20 tumor types. MSI was markedly more prevalent in TMB-VH than in TMB-H tumors (38.1% vs. 2.2%; Fisher’s exact p = 8.9 × 10⁻⁸). Pathway-level comparisons did not identify statistically significant differences after false discovery rate correction (all q > 0.05), and the observed patterns were descriptive in nature. In the ICI-treated subset with complete follow-up, objective response did not differ according to the TMB group. Overall survival (OS) was also similar between groups, whether measured from metastatic diagnosis (log-rank p = 0.937) or from ICI initiation (log-rank p = 0.814), although OS was numerically longer in the TMB-VH group in both analyses without reaching statistical significance. Conclusions: In this cohort study, TMB-VH was strongly associated with MSI but not independently associated with improved ICI outcomes. Larger multicenter cohorts are needed to validate pathway-oriented patterns and clarify the clinical utility of extreme TMB thresholds across various histologies. Integrating the functional context (e.g., MSI status, gene-level context, and pathway-level features) with TMB magnitude may enable more robust, tumor-aware biomarker models for immunotherapy selection. Full article

Microsatellites or simple sequence repeats (SSRs) are valuable markers for understanding genome structure, function, and evolution. However, their distribution and characteristics remain largely unexplored in cricket species. We conducted a genome-wide identification and analysis of perfect (P-SSRs), compound (C-SSRs), and imperfect SSRs (I-SSRs) across five cricket genomes. The total number of SSRs ranged from 2,350,765 to 3,299,527, representing 5.37–7.27% of the genomes. Abundance followed the pattern I-SSRs > P-SSRs > C-SSRs across genomic regions (genome, intergenic, intronic, and coding sequences). Total SSR number, length, abundance and density showed no significant correlation with genome size. Trinucleotide repeats were consistently the most common P-SSR type. The (AAT)_n motif predominated in genomes, intergenic, and introns, while (CCG)_n was most frequent in coding sequences. Consequently, AT-rich repeats dominated non-coding regions, whereas GC-rich repeats were enriched in coding sequences. Coefficient of variation analysis of repeat copy numbers revealed distinct trends in P-SSR distribution across genomic regions and species. Functional annotation of coding sequences containing P-SSRs indicated involvement in binding, signal transduction, and transcription. This study represents, to our knowledge, the first comprehensive subtribe-level comparative analysis of SSRs in crickets, providing new insights into their genomic architecture. Full article

Colitis-associated carcinoma (CAC) represents ~1% of colorectal carcinomas and has important differences from sporadic colorectal carcinoma (sCRC). The precursors and carcinomas that arise in the setting of IBD are uniquely challenging to visualize by endoscopy and diagnose via histology, and the rising prevalence of IBD amplifies the challenges of surveillance to informed management. Although in broad strokes, CAC and sCRC share molecular features (~85% chromosomal instability pathway 15% microsatellite instability high (MSI-H)), CAC has a distinct distribution of molecular abnormalities, including lower frequencies of APC and KRAS mutations, greater prevalence of IDH1R132H, and more frequent copy number alterations (e.g., MYC amplifications), and functional data indicate that most CACs show far less dependence on Wnt signaling than sCRC, suggesting a distinct pathogenesis from the earliest stages. Although there are significant gaps in our knowledge of the pathogenesis of CAC, our understanding is growing. This review summarizes how chronic colitis reshapes epithelial homeostasis and somatic evolution, resulting in the distinctive pathogenesis of CAC, and highlights knowledge gaps that could be addressed by applying multimodal technologies to well-annotated clinical material. The review is structured in two sections, the first introducing the IBDs and the homeostatic mechanisms that preserve integrity and prevent colorectal neoplasia. The second section compares failure modes in sporadic and colitic settings and describes the differences in the resulting neoplasms. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) are among the transformative and manageable systemic therapies for several cancer types, including colorectal cancer (CRC). Nevertheless, their clinical benefit is limited to mismatch-deficient or microsatellite instability-high diseases, which represent only a small percentage of cases. Despite this initial major and stringent selection, primary and acquired resistance remain clinically relevant. Therefore, the identification of additional biomarkers is essential to refine patient selection and guide rational combinational strategies. This review aims to summarize the current evidence regarding established and emerging biomarkers of response and resistance to ICIs in CRC. Methods: This narrative review identified and synthesized relevant clinical trials, translational studies, and reviews through a literature search of emerging biomarkers of immunotherapy response in colorectal cancer. Results: Deficient mismatch repair/high microsatellite instability remains the most reliable predictive biomarker of ICI response, emphasized by high tumor mutational burden, POLE/POLD mutations, and specific tumor microenvironment features. Emerging indicators, including molecular alterations, antigen presentation machinery integrity, PD-L1-mediated signaling, microbiome connections, and circulating tumor DNA kinetics, have demonstrated significant potential as sources for therapeutic response prediction and have informed the development of innovative combination strategies in both MSI-H and MSS CRCs. Conclusions: Immunotherapy response in CRC is determined by a complex interplay between tumor-intrinsic, immune, microenvironmental, and systemic factors. Integrating multiple biomarkers may provide superior stratification and guide therapeutic strategies. Prospective validation and standardized biomarker assessment will be imperative to translate these insights into clinical practice. Full article

Background: Although the BRAF gene mutation in colorectal cancer has a prognostic value and a therapeutic interest, very few studies address the prevalence of this mutation in the Middle East, and hardly any among the Lebanese population. Moreover, we studied the correlation between this mutation and other clinical and pathological variables. Methods: In this descriptive, retrospective, single-center study, BRAF mutational status was reviewed in colorectal tumor samples collected from 2015 to 2021 of Lebanese patients with confirmed metastatic colorectal cancer. The genetic analysis was done in two different molecular laboratories. Clinical characteristics were selected from the computerized medical records of included patients. Statistical calculations were performed with SPSS (version 21.0) statistical software. Results: The study included 190 patients. BRAF mutation was detected in 10 patients (5.3%). A positive correlation was observed between the presence of a BRAF mutation and the right-sidedness of the tumor (p = 0.001) as well as with the presence of microsatellite instability (p = 0.004). However, we could not establish a relationship between BRAF mutation and other characteristics such as age (p = 0.682), gender (p = 0.392), the degree of histologic differentiation (p = 0.594), and the presence of peritoneal metastases (p = 0.707). Conclusions: The BRAF mutation was found in 5.3% of colorectal cancers in Lebanon. A positive correlation was suggested with the colon sidedness and the microsatellite instability. However, it was still insufficient to establish statistically significant associations between other variables and the BRAF mutation. Full article

Colorectal cancer (CRC) is a major public health concern in the United States. It is currently the fourth most diagnosed cancer and, despite advancements in screening and treatment, the second leading cause of cancer-related deaths. Approximately 153,000 new cases are diagnosed annually, with over 53,000 deaths reported. Understanding the molecular and genetic underpinnings of CRC biomarkers plays a crucial role in diagnosis, prognosis, and treatment planning. Specific gene mutations, including MMR deficiency leading to high microsatellite instability (MSI), as well as several other common mutations in CRC, including APC, TP53, KRAS, NRAS, SMAD4, PIK3CA and BRAF, provide valuable insights into tumor biology, therapeutic resistance, and response to targeted therapies. This review explores the mutations and co-mutations most relevant to CRC, their prevalence, prognostic significance, and implications for precision oncology. By focusing on these genetic and epigenetic alterations, we aim to contextualize how biomarker-driven strategies are reshaping the management of CRC in both early and advanced disease settings. Full article

Saussurea involucrata is a rare perennial herb endemic to the alpine zone of the Tianshan Mountains, possessing significant medicinal value yet facing severe threats from overharvesting and habitat fragmentation. The core distribution area and recognized genetic differentiation center of this species are located in the Bayinbuluke region of the Western Tianshan Mountains. In contrast, the genetic distinctiveness and conservation status of populations in the Eastern Tianshan Mountains have remained unclear. To clarify the genetic relationships, we conducted an integrated analysis using nuclear microsatellite (SSR) markers as well as chloroplast (cpDNA) and nuclear ribosomal DNA (nrDNA) sequences on 16 populations (5 from the Eastern Tianshan Mountains and 11 from the Bayinbuluke region). The results showed that the Eastern Tianshan Mountains populations exhibited higher genetic diversity (mean He = 0.5568). Bayesian clustering and principal coordinate analysis (PCoA) clearly separated all populations into two genetic groups corresponding to the two geographical regions. Notably, private haplotypes (cpDNA H1 and nrDNA H7) were identified exclusively in the Eastern Tianshan populations, and no recent genetic bottleneck was detected, indicating historical demographic stability. These findings demonstrate significant genetic differentiation and a unique evolutionary trajectory in the Eastern Tianshan Mountains populations, likely resulting from long-term geographical isolation and local adaptation to arid environments. Therefore, we propose that these populations be managed as an independent Management Unit (MU) to preserve their unique genetic legacy. This study provides critical genetic evidence for refining conservation strategies and promoting the sustainable use of this endangered species, while the established molecular marker system also offers a reliable framework for its geographical traceability. Full article