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Background: Although critical to the overall condition of animals under human care, there is still limited information about oral health in neotropical primates., Methods: We analyzed the main oral conditions and microbiota using mass spectrometry from 13 capuchin monkeys (Sapajus apella) under human care. The findings were registered on odontograms following the Triadan system., Results: The most prevalent conditions were dental fractures (n = 9), mainly enamel fractures, and periodontal disease (n = 8), mainly grade 1 calculi. When exanimating teeth, alterations were identified in 90 out of the 416 evaluated pieces, being periodontal disease the most common (n = 60), followed by enamel fracture (n = 15) and missing teeth (n = 10). In the oral microbiota analyses, Staphylococcus and Streptococcus species were the most prevalent, although no obvious association was observed between isolated organisms and oral conditions., Conclusions: These findings hold the potential to prevent oral disorders, including fractures and periodontal diseases, contribute to molecular identification of oral microbiota, and to improve the well-being of primates under human care., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intellectual disability (ID) is an early onset impairment in cognitive functioning and adaptive behavior, affecting approximately 1% of the population worldwide. Extreme skewing of X-chromosome inactivation (XCI) can be associated with ID phenotypes caused by pathogenic variants in the X chromosome. We analyzed the XCI pattern in blood samples of 194 women with idiopathic ID, using the androgen receptor gene (AR) methylation assay. Among the 136 patients who were informative, 11 (8%) presented with extreme or total XCI skewing (≥ 90%), which was significantly higher than expected by chance. Whole-exome data obtained from these 11 patients revealed the presence of dominant pathogenic variants in eight of them, all sporadic cases, resulting in a molecular diagnostic rate of 73% (8/11 patients). All variants were mapped to ID-related genes with dominant phenotypes: four variants in the X-linked genes DDX3X (an XCI escape gene; two cases), WDR45, and PDHA1, and four variants in the autosomal genes KCNB1, CTNNB1, YY1, and ANKRD11. Three of the autosomal genes had no obvious correlation with the observed XCI skewing. However, YY1 is a known transcriptional repressor that acts in the binding of the XIST long noncoding RNA on the inactive X chromosome, providing a mechanistic link between the pathogenic variant and the detected skewed XCI in the carrier. These data confirm that extreme XCI skewing in females with ID is highly indicative of causative X-linked pathogenic variants, and point to the possibility of identifying causative variants in autosomal genes with a XCI role., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ , KNL1 , ZFHX4 , and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B , involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein-protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.

DNA methylation may be involved in the development of osteosarcomas. Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. As a highly studied epigenetic mechanism, we investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver alterations. Methylation and genomic data were obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response, and signal transduction. Both methylation and expression data were validated in independent groups of cases. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, and WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, and RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. Copy-number changes in DNMT3B (gain) and TET1 (loss), as well as overexpression of DNMT3B in osteosarcomas provide a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Identifying geographic locations most affected by the HIV epidemic is essential to addressing disparities that impact people living with HIV. This study sought to identify individual and neighborhood-level factors that are associated with residing in geographic hotspots of poor sustained HIV viral suppression., Methods: Using data from the Miami-Dade County Ryan White HIV/AIDS program, spatial autocorrelation of poor sustained viral suppression (at least 1 laboratory test ≥ 200 copies/ml in 2017) was investigated using Global Moran's I followed by Local Moran's I and Getis Ord Gi* statistics by ZIP code tabulation areas (ZCTAs). Subsequently, multivariable logistic regression analysis was conducted to identify factors associated with residing in geographic hotspots of poor sustained viral suppression., Results: Several ZCTAs in the northern part of the county, accounting for 1/3 of the Ryan White program clients, had significantly higher clustering of poor sustained viral suppression. Client-level sociodemographic characteristics such as race/ethnicity, age, and poverty, and neighborhood-level characteristics (socioeconomic disadvantage index, residential instability index, and racial/language homogeneity index) were significantly associated with living in a hotspot of poor sustained viral suppression., Conclusion: These findings highlight that spatial variation in sustained viral suppression exists within the county. Targeted strategies that address structural factors and the needs of people with HIV living in specified geographic areas may improve their HIV health outcomes and contribute towards local, regional, and national goals of ending the HIV epidemic., (© 2022. W. Montague Cobb-NMA Health Institute.)

Albatrosses are among the most threatened seabird species. Often entangled in gillnets or hooked while longline fishing gear is being set, albatrosses are affected by fishing. This is assumed to be especially true in cases where illegal longline fishing vessels are involved, as they are less likely to implement the bycatch mitigation measures implemented to reduce the risk of albatrosses being caught on their hooks. This is the assumption that was tested in the current study, which uses environmental criminology as its guiding theoretical framework. Using the spatial units of one-half-degree by one-half-degree longitude/latitude cells, this research examined the patterns of concentration of potentially illegal longlining efforts and their relationships to commercially sought-out and illegally caught (i.e., CRAAVED-concealable, removable, abundant, accessible, valuable, enjoyable, disposable) fish species concentrations, as well as their effects on the average risk of albatrosses. The results indicated that (a) potentially illegal longlining activity is spatially concentrated; (b) this concentration is exhibited in areas with the highest concentrations of the presence of CRAAVED fish; and (c) the average risk score of albatrosses, as measured by their International Union for Conservation of Nature (IUCN) Red List status, is significantly higher in the areas where illegal longlining vessels are found controlling for the activities of legal longlining vessels. These findings provide strong grounding that illegal longline fishing poses a particularly serious threat to the survival of albatrosses. These activities, however, are not randomly spread across the vast oceans, but rather are highly spatially concentrated. Therefore, the bird conservation lobby should work closely with regional fisheries management organizations to devise and implement targeted interventions aimed at reducing potential illegal longline fishing, which, in turn, will likely have positive effects on albatrosses.