Comparative Tissue Identification and Characterization of Long Non-Coding RNAs in the Globally Distributed Blue Shark Prionace glauca.

Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and serve crucial regulatory functions in both animals and plants. Nevertheless, there is limited understanding of lncRNAs and their patterns of expression and roles in sharks. In the current study, we systematically identified and characterized lncRNAs in the blue shark (Prionace glauca) from four tissues (liver, spleen, muscle, and kidney) using high-throughput sequencing and bioinformatics tools. A total of 21,932 high-confidence lncRNAs were identified, with 8984 and 3067 stably and tissue-specific expressed lncRNAs, respectively. In addition, a total of 45,007 differentially expressed (DE) lncRNAs were obtained among tissues, with kidney versus muscle having the largest numbers across tissues. DE lncRNAs trans target protein-coding genes were predicted, and functional gene ontology enrichment of these genes showed GO terms such as muscle system processes, cellular/metabolic processes, and stress and immune responses, all of which correspond with the specific biological functions of each tissue analyzed. These results advance our knowledge of lncRNAs in sharks and present novel data on tissue-specific lncRNAs, providing key information to support future functional shark investigations.

Top Alzheimer's disease risk allele frequencies differ in HABS-HD Mexican- versus Non-Hispanic White Americans.

INTRODUCTION: Here we evaluate frequencies of the top 10 Alzheimer's disease (AD) risk alleles for late-onset AD in Mexican American (MA) and non-Hispanic White (NHW) American participants enrolled in the Health and Aging Brain Study-Health Disparities Study cohort. METHODS: Using DNA extracted from this community-based diverse population, we calculated the genotype frequencies in each population to determine whether a significant difference is detected between the different ethnicities. DNA genotyping was performed per manufacturers' protocols. RESULTS: Allele and genotype frequencies for 9 of the 11 single nucleotide polymorphisms (two apolipoprotein E variants, CR1, BIN1, DRB1, NYAP1, PTK2B, FERMT2, and ABCA7) differed significantly between MAs and NHWs. DISCUSSION: The significant differences in frequencies of top AD risk alleles observed here across MAs and NHWs suggest that ethnicity-specific genetic risks for AD exist. Given our results, we are advancing additional projects to further elucidate ethnicity-specific differences in AD.

Integrative blood-based characterization of oxidative mitochondrial DNA damage variants implicates Mexican American's metabolic risk for developing Alzheimer's disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65 +) expands, the impact will disproportionately affect vulnerable populations, e.g., Hispanic/Latino population, due to their AD-related health disparities. Age-related regression in mitochondrial activity and ethnic-specific differences in metabolic burden could potentially explain in part the racial/ethnic distinctions in etiology that exist for AD. Oxidation of guanine (G) to 8-oxo-guanine (8oxoG) is a prevalent lesion and an indicator of oxidative stress and mitochondrial dysfunction. Damaged mtDNA (8oxoG) can serve as an important marker of age-related systemic metabolic dysfunction and upon release into peripheral circulation may exacerbate pathophysiology contributing to AD development and/or progression. Analyzing blood samples from Mexican American (MA) and non-Hispanic White (NHW) participants enrolled in the Texas Alzheimer's Research & Care Consortium, we used blood-based measurements of 8oxoG from both buffy coat PBMCs and plasma to determine associations with population, sex, type-2 diabetes, and AD risk. Our results show that 8oxoG levels in both buffy coat and plasma were significantly associated with population, sex, years of education, and reveal a potential association with AD. Furthermore, MAs are significantly burdened by mtDNA oxidative damage in both blood fractions, which may contribute to their metabolic vulnerability to developing AD.

Limited impact of a bioeroding sponge, Cliona sp., on Ostrea chilensis from Foveaux Strait, New Zealand.

Bioeroding sponges can cause extensive damage to aquaculture and wild shellfish fisheries. It has been suggested that heavy sponge infestations that reach the inner cavity of oysters may trigger shell repair and lead to adductor detachment. Consequently, energy provision into shell repair could reduce the energy available for other physiological processes and reduce the meat quality of commercially fished oysters. Nevertheless, the impacts of boring sponges on oysters and other shellfish hosts are inconclusive. We studied the interaction between boring sponges and their hosts and examined potential detrimental effects on an economically important oyster species Ostrea chilensis from Foveaux Strait (FS), New Zealand. We investigated the effect of different infestation levels with the bioeroding sponge Cliona sp. on commercial meat quality, condition, reproduction, and disease susceptibility. Meat quality was assessed with an index based on visual assessments used in the FS O. chilensis fishery. Meat condition was assessed with a common oyster condition index, while histological methods were used to assess sex, gonad stage, reproductive capacity, and pathogen presence. Commercial meat quality and condition of O. chilensis were unaffected by sponge infestation. There was no relationship between sex ratio, gonad developmental stage, or gonad index and sponge infestation. Lastly, we found no evidence that sponge infestation affects disease susceptibility in O. chilensis. Our results suggest that O. chilensis in FS is largely unaffected by infestation with Cliona sp. and therefore reinforces the growing body of evidence that the effects of sponge infestation can be highly variable among different host species, environments, and habitats.

Integrative Blood-Based Characterization of Oxidative Mitochondrial DNA Damage Variants Implicates Mexican Americans' Metabolic Risk for Developing Alzheimer's Disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65+) expands, the impact will disproportionately affect vulnerable populations, e.g., Hispanic/Latinx population, due to their AD-related health disparities. Age-related regression in mitochondrial activity and ethnic-specific differences in metabolic burden could potentially explain in part the racial/ethnic distinctions in etiology that exist for AD. Oxidation of guanine (G) to 8-oxo-guanine (8oxoG) is a prevalent lesion and an indicator of oxidative stress and mitochondrial dysfunction. Damaged mtDNA (8oxoG) can serve as an important marker of age-related systemic metabolic dysfunction and upon release into peripheral circulation may exacerbate pathophysiology contributing to AD development and/or progression. Analyzing blood samples from Mexican American (MA) and non-Hispanic White (NHW) participants enrolled in the Texas Alzheimer's Research & Care Consortium, we used blood-based measurements of 8oxoG from both buffy coat PBMCs and plasma to determine associations with population, sex, type-2 diabetes, and AD risk. Our results show that 8oxoG levels in both buffy coat and plasma were significantly associated with population, sex, years of education, and reveal a potential association with AD. Furthermore, MAs are significantly burdened by mtDNA oxidative damage in both blood fractions, which may contribute to their metabolic vulnerability to developing AD.

Hypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort.

BACKGROUND: The aging Mexican American (MA) population is the fastest growing ethnic minority group in the US. MAs have a unique metabolic-related risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to non-Hispanic whites (NHW). This risk for cognitive impairment (CI) is multifactorial involving genetics, environmental, and lifestyle factors. Changes in environment and lifestyle can alter patterns and even possibly reverse derangement of DNA methylation (a form of epigenetic regulation). OBJECTIVE: We sought to identify ethnicity-specific DNA methylation profiles that may be associated with CI in MAs and NHWs. METHODS: DNA obtained from peripheral blood of 551 participants from the Texas Alzheimer's Research and Care Consortium was typed on the Illumina Infinium® MethylationEPIC chip array, which assesses over 850K CpG genomic sites. Within each ethnic group (N = 299 MAs, N = 252 NHWs), participants were stratified by cognitive status (control versus CI). Beta values, representing relative degree of methylation, were normalized using the Beta MIxture Quantile dilation method and assessed for differential methylation using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. RESULTS: Two differentially methylated sites were significant: cg13135255 (MAs) and cg27002303 (NHWs) based on an FDR p < 0.05. Three suggestive sites obtained were cg01887506 (MAs) and cg10607142 and cg13529380 (NHWs). Most methylation sites were hypermethylated in CI compared to controls, except cg13529380 which was hypomethylated. CONCLUSION: The strongest association with CI was at cg13135255 (FDR-adjusted p = 0.029 in MAs), within the CREBBP gene. Moving forward, identifying additional ethnicity-specific methylation sites may be useful to discern CI risk in MAs.

Characterization of Mild Cognitive Impairment and Dementia among Community-Dwelling Mexican Americans and Non-Hispanic Whites.

BACKGROUND: Despite tremendous advancements in the field, our understanding of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Mexican Americans remains limited. OBJECTIVE: The aim of this study was to characterize MCI and dementia among Mexican Americans and non-Hispanic whites. METHODS: Baseline data were analyzed from n = 1,705 (n = 890 Mexican American; n = 815 non-Hispanic white) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). RESULTS: Among Mexican Americans, age (OR = 1.07), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.01) were associated with dementia, but none of these factors were associated with MCI. Among non-Hispanic whites, male gender (OR = 0.33), neighborhood deprivation (OR = 1.34), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.03) were associated with MCI, while depression (OR = 1.09) and APOEɛ4 genotype (OR = 4.38) were associated with dementia. CONCLUSION: Findings from this study revealed that the demographic, clinical, sociocultural and biomarker characteristics of MCI and dementia are different among Mexican Americans as compared to non-Hispanic whites.

Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

Mexican Americans (MAs) are the fastest-growing Hispanic population segment in the US; as this population increases in age, so will the societal burden of age-related diseases such as Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be implicated in MA AD risk since metabolic comorbidities are more prevalent in this group. Oxidative damage to guanosine (8oxoG) is one of the most prevalent DNA lesions and a putative indicator of mitochondrial dysfunction. Testing blood samples from participants of the Texas Alzheimer's Research and Care Consortium, we found mtDNA 8oxoG mutational load to be significantly higher in MAs compared to non-Hispanic whites and that MA females are differentially affected. Furthermore, we identified specific mtDNA haplotypes that confer increased risk for oxidative damage and suggestive evidence that cognitive function may be related to 8oxoG burden. Our understanding of these phenomena will elucidate population- and sex-specific mechanisms of AD pathogenesis, informing the development of more precise interventions and therapeutic approaches for MAs with AD in the future.

Genetic evidence supports a range extension for the Brazilian cownose ray Rhinoptera brasiliensis in the western North Atlantic.

We report 24 new records of the Brazilian cownose ray Rhinoptera brasiliensis outside its accepted geographic range. Sequencing of a 442-base pair portion of the mitochondrial NADH dehydrogenase subunit 2 gene for 282 Rhinoptera samples revealed eight records off the east coast of the USA and 16 from the eastern Gulf of Mexico. Both sexes of all life stages were documented in all seasons over multiple years in the Indian River and Lake Worth lagoons, Florida, indicating that their range extends further in the western North Atlantic than previously described.

Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

The Mexican American population is among the fastest growing aging population and has a younger onset of cognitive decline. This group is also heavily burdened with metabolic conditions such as hypertension, diabetes, and obesity. Unfortunately, limited research has been conducted in this group. Understanding methylation alterations, which are influenced by both genetic and lifestyle factors, is key to identifying and addressing the root cause for mild cognitive impairment, a clinical precursor for dementia. We conducted an epigenome-wide association study on a community-based Mexican American population using the Illumina EPIC array. Following rigorous quality control measures, we identified 10 CpG sites to be differentially methylated between normal controls and individuals with mild cognitive impairment annotated to PKIB, KLHL29, SEPT9, OR2C3, CPLX3, BCL2L2-PABPN1, and CCNY. We found four regions to be differentially methylated in TMEM232, SLC17A8, ALOX12, and SEPT8. Functional gene-set analysis identified four gene-sets, RIN3, SPEG, CTSG, and UBE2L3, as significant. The gene ontology and pathway analyses point to neuronal cell death, metabolic dysfunction, and inflammatory processes. We found 1,450 processes to be enriched using empirical Bayes gene-set enrichment. In conclusion, the functional overlap of differentially methylated genes associated with cognitive impairment in Mexican Americans implies cross-talk between metabolically-instigated systemic inflammation and disruption of synaptic vesicular transport.

Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.