Characterization of white matter hyperintensities in Down syndrome.

Introduction: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored.

Methods: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume.

Epigenetic and physiological alterations in zebrafish subjected to hypergravity.

Gravity is one of the most constant environmental factors across Earth's evolution and all organisms are adapted to it. Consequently, spatial exploration has captured the interest in studying the biological changes that physiological alterations are caused by gravity. In the last two decades, epigenetics has explained how environmental cues can alter gene functions in organisms.

Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.

Background: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS.

Methods: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging.

miR-210 promotes immune- and suppresses oocyte meiosis-related genes in the zebrafish ovarian cells.

microRNA-210 (miRNA), a well-documented miRNA, has been implicated in a myriad of biological processes, including responses to hypoxia, angiogenesis, cell proliferation, and male infertility in humans. However, a comprehensive understanding of its functions in fish requires further investigation. This study pursued to elucidate the downstream effect of dre-miR-210-5p on primary ovarian cell culture in zebrafish (Danio rerio), an animal model.

Exploring the Effects of Rearing Densities on Epigenetic Modifications in the Zebrafish Gonads.

Rearing density directly impacts fish welfare, which, in turn, affects productivity in aquaculture. Previous studies have indicated that high-density rearing during sexual development in fish can induce stress, resulting in a tendency towards male-biased sex ratios in the populations. In recent years, research has defined the relevance of the interactions between the environment and epigenetics playing a key role in the final phenotype.

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome.

Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS.

Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls.

Deciphering sex-specific miRNAs as heat-recorders in zebrafish.

In the last decade, a plethora of microRNAs (miRNAs) has been reported in a wide variety of physiological processes, including reproduction, in many aquatic organisms. However, miRNAome alterations occurred by environmental cues due to water temperature increment have not yet been elucidated. With the aim to identify epigenetic regulations mediated by miRNAs in the gonads in a climate change scenario, the animal model zebrafish (Danio rerio) were subjected to high temperatures during sex differentiation, a treatment that results in male-skewed sex ratios in the adulthood.

Development of epigenetic biomarkers for the identification of sex and thermal stress in fish using DNA methylation analysis and machine learning procedures.

The sex ratio is a key ecological demographic parameter crucial for population viability. However, the epigenetic mechanisms operating during gonadal development regulating gene expression and the sex ratio remain poorly understood. Moreover, there is interest in the development of epigenetic markers associated with a particular phenotype or as sentinels of environmental effects.

Improved biomarker discovery through a plot twist in transcriptomic data analysis.

Background: Transcriptomic analysis is crucial for understanding the functional elements of the genome, with the classic method consisting of screening transcriptomics datasets for differentially expressed genes (DEGs). Additionally, since 2005, weighted gene co-expression network analysis (WGCNA) has emerged as a powerful method to explore relationships between genes. However, an approach combining both methods, i.

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome.

Importance: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established.

Objective: To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments.

Environmentally-induced sex reversal in fish with chromosomal vs. polygenic sex determination.

Sex ratio depends on sex determination mechanisms and is a key demographic parameter determining population viability and resilience to natural and anthropogenic stressors. There is increasing evidence that the environment can alter sex ratio even in genetically sex-determined species (GSD), as elevated temperature can cause female-to-male sex reversal (neomales). Alarmingly, neomales are being discovered in natural populations of several fish, amphibian and reptile species worldwide.

Exposure of zebrafish to elevated temperature induces sex ratio shifts and alterations in the testicular epigenome of unexposed offspring.

Accumulating evidence shows that environmental changes can affect population sex ratios through epigenetic regulation of gene expression in species where sex depends on both genetic and environmental cues. Sometimes, altered sex ratios persist in the next generation even when the environmental cue is no longer present (a multigenerational effect). However, evidence of transgenerational effects (i.

The Model of the Conserved Epigenetic Regulation of Sex.

Epigenetics integrates genomic and environmental information to produce a given phenotype. Here, the model of Conserved Epigenetic Regulation of Sex (CERS) is discussed. This model is based on our knowledge on genes involved in sexual development and on epigenetic regulation of gene expression activation and silencing.

Ovarian transcriptomic signatures of zebrafish females resistant to different environmental perturbations.

Sex is remarkably plastic in fish and can be easily influenced by environmental cues, in which temperature has been the most studied abiotic factor. However, it has been shown that elevated population densities can increase the number of males in several species but little is known about the underlying molecular mechanisms and whether general patterns exist. Here, we studied the long-term effects of population density on the gene expression program in zebrafish gonads.

Treatment with a DNA methyltransferase inhibitor feminizes zebrafish and induces long-term expression changes in the gonads.

Background: The role of epigenetic modifications such as DNA methylation during vertebrate sexual development is far from being clear. Using the zebrafish model, we tested the effects of one of the most common DNA methyltransferase (dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment of acute myeloid leukaemia and is under active investigation for the treatment of solid tumours. Several dose-response experiments were carried out during two periods, including not only the very first days of development (0-6 days post-fertilization, dpf), as done in previous studies, but also, and as a novelty, the period of gonadal development (10-30 dpf).

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes.

Understanding environmental influences on sex ratios is important for the study of the evolution of sex-determining mechanisms and for evaluating the effects of global warming and chemical pollution. Fishes exhibit sexual plasticity, but the underlying mechanisms of environmental effects on their reproduction are unclear even in the well-established teleost research model, the zebrafish. Here we established the conditions to study the effects of elevated temperature on zebrafish sex.

Appropriate rearing density in domesticated zebrafish to avoid masculinization: links with the stress response.

The zebrafish () has become a well-established experimental model in many research fields but the loss of the primary sex-determining region during the process of domestication renders laboratory strains of zebrafish susceptible to the effects of environmental factors on sex ratios. Further, an essential husbandry aspect - the optimal rearing density to avoid stress-induced masculinization - is not known. We carried out two experiments: the first focusing on the effects of density on survival, growth and sex ratio by rearing zebrafish at different initial densities (9, 19, 37 and 74 fish per litre) for 3 months (6-90 days post-fertilization, dpf), and the second focusing on the effects of cortisol during the sex differentiation period (15-45 dpf) for zebrafish reared at low density.

Gene expression analysis at the onset of sex differentiation in turbot (Scophthalmus maximus).

Background: Controlling sex ratios is essential for the aquaculture industry, especially in those species with sex dimorphism for relevant productive traits, hence the importance of knowing how the sexual phenotype is established in fish. Turbot, a very important fish for the aquaculture industry in Europe, shows one of the largest sexual growth dimorphisms amongst marine cultured species, being all-female stocks a desirable goal for the industry. Although important knowledge has been achieved on the genetic basis of sex determination (SD) in this species, the master SD gene remains unknown and precise information on gene expression at the critical stage of sex differentiation is lacking.

Effects of changes in food supply at the time of sex differentiation on the gonadal transcriptome of juvenile fish. Implications for natural and farmed populations.

Background: Food supply is a major factor influencing growth rates in animals. This has important implications for both natural and farmed fish populations, since food restriction may difficult reproduction. However, a study on the effects of food supply on the development of juvenile gonads has never been transcriptionally described in fish.

Genetic architecture of sex determination in fish: applications to sex ratio control in aquaculture.

Controlling the sex ratio is essential in finfish farming. A balanced sex ratio is usually good for broodstock management, since it enables to develop appropriate breeding schemes. However, in some species the production of monosex populations is desirable because the existence of sexual dimorphism, primarily in growth or first time of sexual maturation, but also in color or shape, can render one sex more valuable.

Impact of daily thermocycles on hatching rhythms, larval performance and sex differentiation of zebrafish.

In the wild, water temperature cycles daily: it warms up after sunrise, and cools rapidly after sunset. Surprisingly, the impact of such daily thermocycles during the early development of fish remains neglected. We investigated the influence of constant vs daily thermocycles in zebrafish, from embryo development to sexual differentiation, by applying four temperature regimens: two constant (24°C and 28°C) and two daily thermocycles: 28:24°C, TC (thermophase coinciding with daytime, and cryophase coinciding with night-time) and 24:28°C, CT (opposite to TC) in a 12:12 h light:dark cycle (LD).

Genomic approaches to study genetic and environmental influences on fish sex determination and differentiation.

The embryonic gonad is the only organ that takes two mutually exclusive differentiating pathways and hence gives rise to two different adult organs: testes or ovaries. The recent application of genomic tools including microarrays, next-generation sequencing approaches, and epigenetics can significantly contribute to decipher the molecular mechanisms involved in the processes of sex determination and sex differentiation. However, in fish, these studies are complicated by the fact that these processes depend, perhaps to a larger extent when compared to other vertebrates, on the interplay of genetic and environmental influences.