Population Substructure Research Articles

Sperm kinematic subpopulations of the American crocodile (Crocodylus acutus).

There has been very limited use of computer assisted semen analysis (CASA) to evaluate reptile sperm. The aim of this study was to examine sperm kinematic variables in American crocodile (Crocodylus acutus) semen samples and to assess whether sperm subpopulations could be characterized. Eight ejaculates (two ejaculates/male) from four sexually mature captive crocodiles were obtained. An ISAS®v1 CASA-Mot system, with an image acquisition rate of 50 Hz, and ISAS®D4C20 counting chambers were used for sperm analyses. The percentages of motile and progressively motile spermatozoa did not differ among animals (P > 0.05) but there was a significant animal effect with regards to kinematic variables (P < 0.05). Principal component (PC) analysis revealed that kinematic variables grouped into three components: PC1, related to velocity; PC2 to progressiveness and PC3 to oscillation. Subpopulation structure analysis identified four groups (P < 0.05), which represented, on average, 9.8%, 32.1%, 26.8%, and 31.3% of the total sperm population. Males differed in the proportion of sperm in each of the kinematic subpopulations. This new approach for the analysis of reptile sperm kinematic subpopulations, reflecting quantifiable parameters generated by CASA system technology, opens up possibilities for future assessments of crocodile sperm and will be useful in the future development of assisted reproduction for these species.

The Extensive Substructure and Long Star-Forming Histories of Young Stellar Populations in the Solar Neighborhood

The Extensive Substructure and Long Star-Forming Histories of Young Stellar Populations in the Solar Neighborhood

Adaptive markers distinguish North and South Pacific Albacore amid low population differentiation.

Albacore (Thunnus alalunga) support an economically valuable global fishery, but surprisingly little is known about the population structure of this highly migratory species. Physical tagging data suggest that Albacore from the North and South Pacific Ocean are separate stocks, but results from previous genetic studies did not support this two stock hypothesis. In addition, observed biological differences among juveniles suggest that there may be population substructure in the North Pacific. We used double‐digest restriction site‐associated DNA sequencing to assess population structure among 308 Albacore caught in 12 sample areas across the Pacific Ocean (10 North, 2 South). Since Albacore are highly migratory and spawning areas are unknown, sample groups were not assumed to be equivalent to populations and the genetic data were analyzed iteratively. We tested for putatively adaptive differences among groups and for genetic variation associated with sex. Results indicated that Albacore in the North and South Pacific can be distinguished using 84 putatively adaptive loci, but not using the remaining 12,788 presumed neutral sites. However, two individuals likely represent F1 hybrids between the North and South Pacific populations, and 43 Albacore potentially exhibit lower degrees of mixed ancestry. In addition, four or five cross‐hemisphere migrants were potentially identified. No genetic evidence was found for population substructure within the North Pacific, and no loci appeared to distinguish males from females. Potential functions for the putatively adaptive loci were identified, but an annotated Albacore genome is required for further exploration. Future research should try to locate spawning areas so that life history, demography, and genetic population structure can be linked and spatiotemporal patterns can be investigated.

Performance of model-based multifactor dimensionality reduction methods for epistasis detection by controlling population structure

BackgroundIn genome-wide association studies the extent and impact of confounding due to population structure have been well recognized. Inadequate handling of such confounding is likely to lead to spurious associations, hampering replication, and the identification of causal variants. Several strategies have been developed for protecting associations against confounding, the most popular one is based on Principal Component Analysis. In contrast, the extent and impact of confounding due to population structure in gene-gene interaction association epistasis studies are much less investigated and understood. In particular, the role of nonlinear genetic population substructure in epistasis detection is largely under-investigated, especially outside a regression framework.MethodsTo identify causal variants in synergy, to improve interpretability and replicability of epistasis results, we introduce three strategies based on a model-based multifactor dimensionality reduction approach for structured populations, namely MBMDR-PC, MBMDR-PG, and MBMDR-GC.ResultsSimulation results comparing the performance of various approaches show that in the presence of population structure MBMDR-PC and MBMDR-PG consistently better control type I error rate at the nominal level than MBMDR-GC. Moreover, our proposed three methods of population structure correction outperform MDR-SP in terms of statistical power.ConclusionWe demonstrate through extensive simulation studies the effect of various degrees of genetic population structure and relatedness on epistasis detection and propose appropriate remedial measures based on linear and nonlinear sample genetic similarity.

Genetic characterisation of the North-West Indian populations: analysis of mitochondrial DNA control region variations

Background Human mitochondrial DNA presents several interesting characteristics, making it a favourable tool in the field of molecular anthropology, medical genetics, population history, and forensic science. Aim The present study investigated the mitochondrial DNA (mtDNA) control region variations in diverse ethnic groups of North-West India for which population data is insufficient. Subjects and methods The complete mtDNA control regions of 197 unrelated (for up to three generations) healthy individuals belonging to different ethnic groups of North-West India were sequenced. The haplotype frequencies, haplogroup distribution, and pairwise FST values between the studied and other worldwide populations were generated to study patterns of variation in human mtDNA. Results The results ascertained high gene diversity (0.998) in the studied maternal lineages, identifying 166 distinct haplotypes, of which 158 were unique and characterised by 117 variable sites. Three haplogroups: M3, M30, and U7 were observed to be the most prevalent, and phylogeographically a total of 55.86% of sequences were characterised into South Asian, followed by West Eurasian (40.18%) and East Asian (3.96%), ancestry haplogroups. Pairwise genetic differentiation comparisons revealed maternal homogeneity in the studied groups. No population substructure was detected within the North-West Indian populations. Conclusion The results of this preliminary study will contribute to an existing database of mtDNA variations of the Indian population and facilitate prospective studies investigating population genetics and human diseases.

Relationships between fox populations and rabies virus spread in northern Canada.

Rabies spreads in both Arctic (Vulpes lagopus) and red foxes (Vulpes vulpes) throughout the Canadian Arctic but limited wildlife disease surveillance, due to the extensive landmass of the Canadian north and its small widely scattered human population, undermines our knowledge of disease transmission patterns. This study has explored genetic population structure in both the rabies virus and its fox hosts to better understand factors that impact rabies spread. Phylogenetic analysis of 278 samples of the Arctic lineage of rabies virus recovered over 40 years identified four sub-lineages, A1 to A4. The A1 lineage has been restricted to southern regions of the Canadian province of Ontario. The A2 lineage, which predominates in Siberia, has also spread to northern Alaska while the A4 lineage was recovered from southern Alaska only. The A3 sub-lineage, which was also found in northern Alaska, has been responsible for virtually all cases across northern Canada and Greenland, where it further differentiated into 18 groups which have systematically evolved from a common predecessor since 1975. In areas of Arctic and red fox sympatry, viral groups appear to circulate in both hosts, but both mitochondrial DNA control region sequences and 9-locus microsatellite genotypes revealed contrasting phylogeographic patterns for the two fox species. Among 157 Arctic foxes, 33 mitochondrial control region haplotypes were identified but little genetic structure differentiating localities was detected. Among 162 red foxes, 18 control region haplotypes delineated three groups which discriminated among the Churchill region of Manitoba, northern Quebec and Labrador populations, and the coastal Labrador locality of Cartwright. Microsatellite analyses demonstrated some genetic heterogeneity among sampling localities of Arctic foxes but no obvious pattern, while two or three clusters of red foxes suggested some admixture between the Churchill and Quebec-Labrador regions but uniqueness of the Cartwright group. The limited population structure of Arctic foxes is consistent with the rapid spread of rabies virus subtypes throughout the north, while red fox population substructure suggests that disease spread in this host moves most readily down certain independent corridors such as the northeastern coast of Canada and the central interior. Interestingly the evidence suggests that these red fox populations have limited capacity to maintain the virus over the long term, but they may contribute to viral persistence in areas of red and Arctic fox sympatry.

Genetic population structure of a top predatory fish (northern pike, Esox lucius) covaries with anthropogenic alteration of freshwater ecosystems

Abstract Esox lucius L. (northern pike) inhabits river, lake, and brackish water ecosystems of the temperate region in North America and Eurasia. In many areas of its native range, the species is confronted with human‐induced disturbances that can affect local and regional genetic diversity. Conservation of genetic diversity constitutes an important policy objective. Therefore, we investigated how the genetic population structure and patterns suggestive of hybridisation among subpopulations from different catchments vary with the type of ecosystem (river vs. lake) and the integrity of the ecosystem assessed using ecological status assessments of the European Water Framework Directive and indices of the wetland quality (in rivers) and trophic state (in lakes). In total, 1,384 pike samples from the North, Baltic, and Black Sea drainages in Germany were analysed. We differentiated between metapopulations from each hydrogeographic region using genotypes from 15 microsatellites and mitochondrial cyt b sequences. Individual populations showed signs of genetic admixture ranging from almost zero to complete replacement by foreign genotypes originating from different catchments. Hierarchical general linear modelling revealed a significantly positive association of the degree of genetic hybridisation with decreasing ecological status. An eroded population substructure indicative of hybridisation was also significantly elevated in rivers relative to lakes and in heavily modified water bodies. Results were consistent when using ecological status assessments by the Water Framework Directive and an alternative environmental quality index based on the health of wetlands in rivers and trophic state in lakes. We speculate that macrophyte loss through loss of wetlands or in response to eutrophication fostered genetic mixing among different subpopulations, which were brought into secondary contact either due to stocking or due to natural dispersal from foreign catchments. Our findings suggest that anthropogenic alteration of freshwater ecosystems may influence the genetic structures present in a freshwater top piscivore at both local and regional scales.

Differences in MTHFR and LRRK2 variant\u2019s association with sporadic Parkinson\u2019s disease in Mexican Mestizos correlated to Native American ancestry

Parkinson’s disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case–control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 in LRRK2. However, when stratification by ancestry was performed, a risk effect for MTHFR rs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect for LRRK2 rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect of LRRK2 rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors’ role in the pathophysiological mechanisms of this neurodegenerative disorder.

Genetic diversity and population structure of natural populations of the endangered grass Paspalum rawitscheri (Parodi) Chase ex G.H. Rua &amp; Valls (Paspaleae, Poaceae)

The objective of this study was to evaluate the genetic diversity and population structure of natural subpopulations of Paspalum rawitscheri (Parodi) Chase ex G.H. Rua & Valls using inter-simple sequence repeat (ISSR) molecular markers. Four natural subpopulations from State of Rio Grande do Sul, Brazil, were evaluated, using six ISSR primers. A total of 131 fragments were amplified, 34 of which were polymorphic. The genetic diversity (h) for the subpopulations was considered low, with values ranging from 0.130 to 0.217. The Vacaria subpopulation presented the lowest diversity among populations. The Shannon (I) diversity indices were also low, with values ranging from 0.187 to 0.334, with the Vacaria subpopulation also presenting the lowest values. The molecular variance (AMOVA) analysis showed, in general, the highest variation occurred within subpopulations rather than between subpopulations. The Bayesian Inference analysis separated the individuals into four genetic clusters, mixing individuals from different municipalities in the clusters. The results indicate that the species has low genetic diversity and low population structure, requiring conservation plans. Ex situ conservation becomes a necessary effort, since populations of this species are found in grasslands remnants affected by fires and implantation of crops, and is not present in any protected area of the Brazilian Conservation Units system.

Variable migration patterns of whitespotted eagle rays Aetobatus narinari along Florida’s coastlines

Basic distribution and movements of elasmobranch species, particularly mesopredatory rays, remain relatively unknown. This is especially true for the whitespotted eagle ray (Aetobatus narinari), a protected species in Florida with poorly described migratory and habitat use patterns. Passive acoustic telemetry was used to reveal multi-scale spatial patterns of A. narinari in Florida waters. Between 2016 and 2018, 54 rays were fitted with acoustic transmitters and tracked via collaborative telemetry networks. Movement patterns between the Atlantic and Gulf coast individuals were distinct; a majority of Gulf coast tagged A. narinari exhibited migratory or transient behaviors while most Atlantic coast tagged individuals remained resident in the Indian River Lagoon (IRL). On both coastlines, water temperatures during times when A. narinari were present were significantly warmer (mean = 27.8 °C) compared to temperatures when A. narinari were absent (mean = 24.9 °C), suggesting temperature may be a major abiotic factor influencing migration patterns. Ontogenetic shifts in habitat use were evident along the Atlantic coast in the IRL, but not along the Gulf coast. Immature rays spent significantly more time (mean = 91.5%) inside the IRL compared to mature counterparts (mean = 60.2%). This is the first multiyear study to examine large-scale movements of A. narinari in U.S. waters and results may be important for adaptive management strategies throughout this species’ range. Importantly, our work suggests potential sub-population structuring of A. narinari may be occurring more than previously considered within Florida, which has significant conservation implications for this species.

Integrating Linguistics, Social Structure, and Geography to Model Genetic Diversity within India.

India represents an intricate tapestry of population substructure shaped by geography, language, culture, and social stratification. Although geography closely correlates with genetic structure in other parts of the world, the strict endogamy imposed by the Indian caste system and the large number of spoken languages add further levels of complexity to understand Indian population structure. To date, no study has attempted to model and evaluate how these factors have interacted to shape the patterns of genetic diversity within India. We merged all publicly available data from the Indian subcontinent into a data set of 891 individuals from 90 well-defined groups. Bringing together geography, genetics, and demographic factors, we developed Correlation Optimization of Genetics and Geodemographics to build a model that explains the observed population genetic substructure. We show that shared language along with social structure have been the most powerful forces in creating paths of gene flow in the subcontinent. Furthermore, we discover the ethnic groups that best capture the diverse genetic substructure using a ridge leverage score statistic. Integrating data from India with a data set of additional 1,323 individuals from 50 Eurasian populations, we find that Indo-European and Dravidian speakers of India show shared genetic drift with Europeans, whereas the Tibeto-Burman speaking tribal groups have maximum shared genetic drift with East Asians.

The effects of cryopreservation and cold storage on sperm subpopulation structure of common carp (Cyprinus carpio L.)

The objectives of this study were to identify the presence of different spermatozoa subpopulations (SPs) according to their kinematic characteristics in the sperm of common carp and to test the effects of cryopreservation and prolonged (6-day) storage at room temperature (RT; 23 °C) and 4 °C on spermatozoa motility and subsequently on SP dynamics. Two-step clustering analyses identified three motile SPs based on their kinematic properties: SP1 contained spermatozoa with low velocity and low/moderate STR/LIN values (slow non-linear SP); SP2 was comprised of spermatozoa with high velocities and high STR/LIN values (fast linear SP); SP3 was characterized with high VCL, and moderate LIN/STR (fast non-linear SP); and an additional SP0 was added comprising immotile spermatozoa. Total motility, progressive motility and VCL decreased after cryopreservation to approximately 50% of their value in fresh sperm, while the frequency of SPs characterized by high values of motility parameters declined in favor of those with low motility values and SP0. Motility values of fresh and cryopreserved spermatozoa which were washed with fresh extender after thawing decreased significantly after 24 h of storage at RT and after 72 h of storage at 4 °C, while cryopreserved sperm which remained in the original cryomedium faced a steep decline in motility after only 2 h of storage. As subpopulation frequencies followed this dynamic, this indicates that cryopreserved sperm should be washed with fresh extender in order to obtain favorable sperm kinematic properties after freezing.

Transferability of Ancestry‐Specific and Cross‐Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations

The Nicotine Metabolite Ratio (NMR; 3-hydroxycotinine/cotinine), a highly heritable index of nicotine metabolic inactivation by the CYP2A6 enzyme, is associated with numerous smoking behaviors and diseases, as well as unique cessation outcomes. However, the NMR cannot be measured in nonsmokers, former smokers, or intermittent smokers, for example, in evaluating tobacco-related disease risk. Traditional pharmacogenetic groupings based on CYP2A6 * alleles capture a modest portion of NMR variation. We previously created a CYP2A6 weighted genetic risk score (wGRS) for European (EUR)-ancestry populations by incorporating independent signals from genome-wide association studies to capture a larger proportion of NMR variation. However, CYP2A6 genetic architecture is unique to ancestral populations. In this study, we developed and replicated an African-ancestry (AFR) wGRS, which captured 30-35% of the variation in NMR. We demonstrated model robustness against known environmental sources of NMR variation. Furthermore, despite the vast diversity within AFR populations, we showed that the AFR wGRS was consistent between different US geographical regions and unaltered by fine AFR population substructure. The AFR and EUR wGRSs can distinguish slow from normal metabolizers in their respective populations, and were able to reflect unique smoking cessation pharmacotherapy outcomes previously observed for the NMR. Additionally, we evaluated the utility of a cross-ancestry wGRS, and the capacity of EUR, AFR, and cross-ancestry wGRSs to predict the NMR within stratified or admixed AFR-EUR populations. Overall, our findings establish the clinical benefit of applying ancestry-specific wGRSs, demonstrating superiority of the AFR wGRS in AFRs.

Efficiency of the Artificial Reproduction of Atlantic Salmon Salmo salar, Depending on the Age of Juveniles Released to a Natural Water Body (Based on the Example of the Kola River, Kola Peninsula)

The results of a comparative analysis of the efficiency of the artificial reproduction of Atlantic salmon (Salmo salar) individuals released to the Kola River at ages of 3 years (1980–2002) and 1 year (2003–2017) are given. After the fish hatcheries began to release artificially reared anadromous salmon individuals at the age of 1 year, their qualitative parameters did not significantly change. The value of the commercial return became somewhat lower for the released yearlings than for the 3-year-old individuals; however, it remained satisfactorily high. It is recommended to reduce the release volume to avoid the overpopulation of juveniles; it is also suggested to evenly distribute them over the nursery grounds that are most suitable for their adaptation and select spawners for broodstock according to the historically established subpopulation structure.

Genetic assessment reveals no population substructure and divergent regional and sex-specific histories in the Chachapoyas from northeast Peru.

Many native populations in South America have been severely impacted by two relatively recent historical events, the Inca and the Spanish conquest. However decisive these disruptive events may have been, the populations and their gene pools have been shaped markedly also by the history prior to the conquests. This study focuses mainly on the Chachapoya peoples that inhabit the montane forests on the eastern slopes of the northern Peruvian Andes, but also includes three distinct neighboring populations (the Jívaro, the Huancas and the Cajamarca). By assessing mitochondrial, Y-chromosomal and autosomal diversity in the region, we explore questions that have emerged from archaeological and historical studies of the regional culture (s). These studies have shown, among others, that Chachapoyas was a crossroads for Coast-Andes-Amazon interactions since very early times. In this study, we examine the following questions: 1) was there pre-Hispanic genetic population substructure in the Chachapoyas sample? 2) did the Spanish conquest cause a more severe population decline on Chachapoyan males than on females? 3) can we detect different patterns of European gene flow in the Chachapoyas region? and, 4) did the demographic history in the Chachapoyas resemble the one from the Andean area? Despite cultural differences within the Chachapoyas region as shown by archaeological and ethnohistorical research, genetic markers show no significant evidence for past or current population substructure, although an Amazonian gene flow dynamic in the northern part of this territory is suggested. The data also indicates a bottleneck c. 25 generations ago that was more severe among males than females, as well as divergent population histories for populations in the Andean and Amazonian regions. In line with previous studies, we observe high genetic diversity in the Chachapoyas, despite the documented dramatic population declines. The diverse topography and great biodiversity of the northeastern Peruvian montane forests are potential contributing agents in shaping and maintaining the high genetic diversity in the Chachapoyas region.

Genomic and morphological evidence of distinct populations in the endemic common (weedy) seadragon Phyllopteryx taeniolatus (Syngnathidae) along the east coast of Australia.

The common or weedy seadragon, Phyllopteryx taeniolatus, is an iconic and endemic fish found across temperate reefs of southern Australia. Despite its charismatic nature, few studies have been published, and the extent of population sub-structuring remains poorly resolved. Here we used 7462 single nucleotide polymorphisms (SNPs) to identify the extent of population structure in the weedy seadragon along the temperate southeast coast of Australia. We identified four populations, with strong genetic structure (FST = 0.562) between them. Both Discriminant Analysis of Principle Components (DAPC) and Bayesian clustering analyses support four distinct genetic clusters (north to south: central New South Wales, southern NSW, Victoria and Tasmania). In addition to these genetic differences, geographical variation in external morphology was recorded, with individuals from New South Wales shaped differently for a few measurements to those from the Mornington Peninsula (Victoria). We posit that these genetic and morphological differences suggest that the Victorian population of P. taeniolatus was historically isolated by the Bassian Isthmus during the last glacial maximum and should now be considered at least a distinct population. We also recorded high levels of genetic structure among the other locations. Based on the genomic and to a degree morphological evidence presented in this study, we recommend that the Victorian population be managed separately from the eastern populations (New South Wales and Tasmania).

Divergence and Gene Flow Between Fusarium subglutinans and F. temperatum Isolated from Maize in Argentina.

Fusarium subglutinans and F. temperatum are two important fungal pathogens of maize whose distinctness as separate species has been difficult to assess. We isolated strains of these species from commercial and native maize varieties in Argentina and sequenced >28,000 loci to estimate genetic variation in the sample. Our objectives were to measure genetic divergence between the species, infer demographic parameters related to their split, and describe the population structure of the sample. When analyzed together, over 30% of each species' polymorphic sites (>2,500 sites) segregate as polymorphisms in the other. Demographic modeling confirmed the species split predated maize domestication, but subsequent between-species gene flow has occurred, with gene flow from F. subglutinans into F. temperatum greater than gene flow in the reverse direction. In F. subglutinans, little evidence exists for substructure or recent selective sweeps, but there is evidence for limited sexual reproduction. In F. temperatum, there is clear evidence for population substructure and signals of abundant recent selective sweeps, with sexual reproduction probably less common than in F. subglutinans. Both genetic variation and the relative number of polymorphisms shared between species increase near the telomeres of all 12 chromosomes, where genes related to plant-pathogen interactions often are located. Our results suggest that species boundaries between closely related Fusarium species can be semipermeable and merit further study. Such semipermeability could facilitate unanticipated genetic exchange between species and enable quicker permanent responses to changes in the agro-ecosystem, e.g., pathogen-resistant host varieties, new chemical and biological control agents, and agronomic practices.

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3–12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Oligoclonality and subpopulation structure of bone marrow T-cells in patients with aplastic anaemia

Introduction. The main pathogenetic mechanism of the development of aplastic anemia (AA) is a violation of the immune regulation of hematopoiesis.Aim: to study of the subpopulation composition of T-cells and the repertoire of the T-cell receptor in AA patients.Patients and Methods. The study included AA patients (n = 40) without prior immunosuppressive therapy in 2018–2020. The T-cell subpopulation structure and T-cell receptor Vβ-family (TCR-Vβ) oligoclonality were studied in samples of bone marrow using flow cytometry.Results. We report characteristic properties of T-cell subpopulations of bone marrow in all AA patients: elevated counts of cytotoxic T-cells, effector CD4+ and CD8+ cells, CD4+ memory cells, which may suggest a long-term antigenic stimulation with subsequent activation of these cell subpopulations resulting in hyperexpression of pro-inflammatory cytokines. Diminishing of naive CD4+ and CD8+ cells, regulatory and double negative T-cells may indicate a relaxing control of cytokine-producing T-cells. A relationship has been established between the AA severity and counts of effector, regulatory, double negative and PD-1 positive T-cells. A highest count of potentially cytokine-producing T-cells and lowest count of cells involved in T-cell activity regulation were observed in very severe AA patients. Studies of the TCR-Vβ repertoire revealed oligoclonal expansion in the cytotoxic T-cell subpopulation.Conclusion. Enrichment in selected Vβ families suggests autoreactive T-cell clonality and attests to the immune nature of AA. A dynamic TCR-Vβ repertoire assay may be recommended in the disease monitoring. Flow cytometry helps identify valuable biomarkers for T-cell clone monitoring in AA and a better assessment of the disease progression.

Red LED Light Acts on the Mitochondrial Electron Chain of Donkey Sperm and Its Effects Depend on the Time of Exposure to Light.

This work aimed to investigate how stimulation of donkey sperm with red LED light affects mitochondrial function. For this purpose, freshly diluted donkey semen was stimulated with red light for 1, 5, and 10 min, in the presence or absence of oligomycin A (Omy A), a specific inhibitor of mitochondrial ATP synthase, or FCCP, a specific disruptor of mitochondrial electron chain. The results obtained in the present study indicated that the effects of red LED light on fresh donkey sperm function are related to changes in mitochondria function. In effect, irradiation of donkey sperm resulted in an increase in mitochondrial membrane potential (MMP), the activity of cytochrome C oxidase and the rate of oxygen consumption. In addition, in the absence of oligomycin A and FCCP, light-stimulation augmented the average path velocity (VAP) and modified the structure of motile sperm subpopulations, increasing the fastest and most linear subpopulation. In contrast, the presence of either Omy A or FCCP abolished the aforementioned effects. Interestingly, our results also showed that the effects of red light depend on the exposure time applied, as indicated by the observed differences between irradiation protocols. In conclusion, our results suggest that exposing fresh donkey sperm to red light modulates the function of their mitochondria through affecting the activity of the electron chain. However, the extent of this effect depends on the irradiation pattern and does not exclude the existence of other mechanisms, such as those related to thermotaxis.