Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cells.

Farnesoid X receptor α (FXRα, NR1H4) is a bile acid-activated nuclear receptor that regulates the expression of glycolytic and lipogenic target genes by interacting with the 9-cis-retinoic acid receptor α (RXRα, NR2B1). Along with cofactors, the FXRα proteins reported thus far in humans and rodents have been observed to regulate both isoform (α1-4)- and tissue-specific gene expression profiles to integrate energy balance and metabolism. Here, we studied the biological functions of an FXRα naturally occurring spliced exon 5 isoform (FXRαse5) lacking the second zinc-binding module of the DNA-binding domain.

Understanding the role of endocrine disrupting chemicals in testicular germ cell cancer: Insights into molecular mechanisms.

This comprehensive review examines the complex interplay between endocrine disrupting chemicals (EDCs) and the development of testicular germ cell tumors (TGCTs). Despite the high cure rates of TGCTs, challenges in diagnosis and treatment remain, necessitating a deeper understanding of the etiology of the disease. Here, we emphasize current knowledge on the role of EDCs as potential risk factors for TGCTs, focusing on pesticides and perfluorinated and polyfluoroalkyl substances (PFAs/PFCs).

Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis.

Understanding the regulation of the testicular endocrine function leading to testosterone production is a major objective as the alteration of endocrine function is associated with the development of many diseases such as infertility. In the last decades, it has been demonstrated that several endogenous molecules regulate the steroidogenic pathway. Among them, bile acids have recently emerged as local regulators of testicular physiology and particularly endocrine function.

Identification of a Crosstalk among TGR5, GLIS2, and TP53 Signaling Pathways in the Control of Undifferentiated Germ Cell Homeostasis and Chemoresistance.

Spermatogonial stem cells regenerate and maintain spermatogenesis throughout life, making testis a good model for studying stem cell biology. The effects of chemotherapy on fertility have been well-documented previously. This study investigates how busulfan, an alkylating agent that is often used for chemotherapeutic purposes, affects male fertility.

Metallome deregulation and health-related impacts due to long-term exposure to recent volcanic ash deposits: New chemical and isotopic insights.

Volcanic ash exposure can lead to significant health risks. Damage to the respiratory and pulmonary systems are the most evident toxic side effects although the causes of these symptoms remain unclear. Conversely, the effects on other organs remain largely under-explored, limiting our understanding of the long-term volcanic ash-related risk at the whole-body scale.

Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes.

Spermatogenesis is a process within the testis that leads to the production of spermatozoa. It is based on a population of spermatogonial stem cells, which have the capacity to self-renew and to differentiate throughout life to ensure the functions of reproduction are maintained. Male fertility disorders are responsible for half of the cases of infertility in couples worldwide.

FXRα modulates leydig cell endocrine function in mouse.

The hypothalamic-pituitary axis exert a major control over endocrine and exocrine testicular functions. The hypothalamic-pituitary axis corresponds to a cascade with the Gonadotropin Releasing Hormone secreted by the hypothalamus, which stimulates the synthesis and the release of Luteinizing Hormone (LH) and Follicle Stimulating Hormone by the gonadotropic cells of the anterior pituitary. The LH signaling pathway controls the steroidogenic activity of the Leydig cells via the activation of the luteinizing hormone/choriogonadotropin receptor.

Differential divergence in autosomes and sex chromosomes is associated with intra-island diversification at a very small spatial scale in a songbird lineage.

Recently diverged taxa showing marked phenotypic and ecological diversity provide optimal systems to understand the genetic processes underlying speciation. We used genome-wide markers to investigate the diversification of the Reunion grey white-eye (Zosterops borbonicus) on the small volcanic island of Reunion (Mascarene archipelago), where this species complex exhibits four geographical forms that are parapatrically distributed across the island and differ strikingly in plumage colour. One form restricted to the highlands is separated by a steep ecological gradient from three distinct lowland forms which meet at narrow hybrid zones that are not associated with environmental variables.

Fxralpha gene is a target gene of hCG signaling pathway and represses hCG induced steroidogenesis.

The bile acid receptor Farnesoid-X-Receptor alpha (FXRα), a member of the nuclear receptor superfamily, is well known for its roles in the enterohepatic tract. In addition, FXRα regulates testicular physiology through the control of both endocrine and exocrine functions. The endocrine function of the Leydig cells is mainly controlled by the hypothalamo-pituitary axis viaLH/chorionic gonadotropin (CG).

Farnesoid X receptor alpha (FXRα) is a critical actor of the development and pathologies of the male reproductive system.

The farnesoid-X-receptorα (FXRα; NR1H4) is one of the main bile acid (BA) receptors. During the last decades, through the use of pharmalogical approaches and transgenic mouse models, it has been demonstrated that the nuclear receptor FXRα controls numerous physiological functions such as glucose or energy metabolisms. It is also involved in the etiology or the development of several pathologies.

Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases.

Structural and functional studies have provided numerous insights over the past years on how members of the nuclear hormone receptor superfamily tightly regulate the expression of drug-metabolizing enzymes and transporters. Besides the role of the farnesoid X receptor (FXR) in the transcriptional control of bile acid transport and metabolism, this review provides an overview on how this metabolic sensor prevents the accumulation of toxic byproducts derived from endogenous metabolites, as well as of exogenous chemicals, in coordination with the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Decrypting this network should provide cues to better understand how these metabolic nuclear receptors participate in physiologic and pathologic processes with potential validation as therapeutic targets in human disabilities and cancers.

Multigenerational impacts of bile exposure are mediated by TGR5 signaling pathways.

Besides their well-known roles in digestion and fat solubilization, bile acids (BAs) have been described as signaling molecules activating the nuclear receptor Farnesoid-X-receptor (FXRα) or the G-protein-coupled bile acid receptor-1 (GPBAR-1 or TGR5). In previous reports, we showed that BAs decrease male fertility due to abnormalities of the germ cell lineage dependent on Tgr5 signaling pathways. In the presentstudy, we tested whether BA exposure could impact germ cell DNA integrity leading to potential implications for progeny.

Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders.

Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antagonist.

The Bile Acid Nuclear Receptor FXRα Is a Critical Regulator of Mouse Germ Cell Fate.

Spermatogenesis is the process by which spermatozoa are generated from spermatogonia. This cell population is heterogeneous, with self-renewing spermatogonial stem cells (SSCs) and progenitor spermatogonia that will continue on a path of differentiation. Only SSCs have the ability to regenerate and sustain spermatogenesis.

Genome biogeography reveals the intraspecific spread of adaptive mutations for a complex trait.

Physiological novelties are often studied at macro-evolutionary scales such that their micro-evolutionary origins remain poorly understood. Here, we test the hypothesis that key components of a complex trait can evolve in isolation and later be combined by gene flow. We use C photosynthesis as a study system, a derived physiology that increases plant productivity in warm, dry conditions.

CD8 T Cells from Human Neonates Are Biased toward an Innate Immune Response.

To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8 T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8 T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species.

Vector soup: high-throughput identification of Neotropical phlebotomine sand flies using metabarcoding.

Phlebotomine sand flies are haematophagous dipterans of primary medical importance. They represent the only proven vectors of leishmaniasis worldwide and are involved in the transmission of various other pathogens. Studying the ecology of sand flies is crucial to understand the epidemiology of leishmaniasis and further control this disease.

Using metabarcoding to reveal and quantify plant-pollinator interactions.

Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded.

Shotgun sequencing of the mitochondrial genome of the Aldabra giant tortoise (Aldabrachelys gigantea).

The complete mitochondrial genome of the Aldabra giant tortoise [Aldabrachelys gigantea (Schweigger, 1812): Reptilia, Testudines, Testudinidae] was sequenced using a shotgun approach on an Illumina HiSeq 2500 platform (Illumina Inc., San Diego, CA). This genome was 16 467 bp long and presents the typical organization found in vertebrates.

Complete mitochondrial genome of the gray mouse lemur, Microcebus murinus (Primates, Cheirogaleidae).

We report the high-coverage complete mitochondrial genome sequence of the gray mouse lemur Microcebus murinus. The sequencing has been performed on an Illumina Hiseq 2500 platform, with a genome skimming strategy. The total length of this mitogenome is 16 963 bp, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 non-coding region (D-loop region).

The complete mitochondrial genome of (Amphibia: Anura: Aromobatidae).

The complete mitogenome of the rocket frog was sequenced using a shotgun approach on an Illumina HiSeq 2500 platform (Illumina Inc., San Diego, CA), providing the first mitogenome for this genus. The genome was 17,572 bp long and presents the typical organization found in other neobatrachian anurans.

A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells.

Glioblastomas are the most common primary brain tumors, highly vascularized, infiltrating, and resistant to current therapies. This cancer leads to a fatal outcome in less than 18 months. The aggressive behavior of glioblastomas, including resistance to current treatments and tumor recurrence, has been attributed to glioma stemlike/progenitor cells.