Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen.

The naked mole rat (NMR), a long-lived and cancer-resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment

Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation

The human thyroid gland acquires a differentiation program as early as weeks 3–4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks 10–11. By 12–13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level. During maturation, thyroid hormones yield increases and physiological mechanisms of thyroid hormone synthesis regulation are established. In the present work we traced the process of thyroid functional differentiation and maturation in the course of human development by performing transcriptomic analysis of human thyroids covering the period of gestation weeks 7–11 and comparing it to adult human thyroid. We obtained specific transcriptomic signatures of embryonic and adult human thyroids by comparing them to non-thyroid tissues from human embryos and adults. We defined a non-TSH (thyroid stimulating hormone) dependent transition from differentiation to maturation of thyroid. The study also sought to shed light on possible factors that could replace TSH, which is absent in this window of gestational age, to trigger transition to the emergence of thyroid function. We propose a list of possible genes that may also be involved in abnormalities in thyroid differentiation and/or maturation, hence leading to congenital hypothyroidism. To our knowledge, this study represent the first transcriptomic analysis of human embryonic thyroid and its comparison to adult thyroid

Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution

The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits

Etude de deux autoantigènes thyroïdiens: la thyroperoxydase et le récepteur de la thyrotropine. Isolement de 4 nouveaux récepteurs membres de la famille des récepteurs couplés aux protéines G.

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Structure-function relationships of the complement components.

CommentComparative StudyLetterinfo:eu-repo/semantics/publishe

The genetics of HIV coreceptors and coreceptor ligands

info:eu-repo/semantics/publishe

Changes in chromatin structure and DNA methylation associated with the expression of the thyroglobulin gene

info:eu-repo/semantics/publishe

La famille des récepteurs couplés aux protéines G et ses orphelins

G protein-coupled receptors are encoded by one of the mammalian largest gene families. These receptors share a common transmembrane organization, respond to a large variety of structurally different ligands, and regulate intracellular enzymes and channels through heterotrimeric G proteins. The first genes encoding receptors of this family were isolated following the purification of the protein and sequencing of peptides generated by proteolytic cleavage. Subsequently, a number of G protein-coupled receptor genes were cloned through expression screening procedures based either on the binding of a specific ligand, or on the functional coupling of the recombinant receptor to a transduction cascade. Most members in this gene family were however obtained by homology cloning, using cross-hybridization or low-stringency polymerase chain reaction. The result is the availability of more than 140 receptor types and subtypes (olfactory receptors excluded). With a few exceptions, all pharmacologically well-defined receptors have now been cloned. Molecular cloning confirmed the existence of poorly characterized subtypes and uncovered other unsuspected subtypes. Genes encoding uncharacterized receptors have also been made available, either related to identified subfamilies, or defining new subfamilies by themselves. These so-called orphan receptors are waiting for the identification of the corresponding ligands and of their biological function. The availability of cloned human receptors is expected to speed up the search for more specific drugs. Determination of the three dimensional structure of selected recombinant receptors, and computer modelling of receptor-ligand interaction and ligand-mediated receptor activation will probably allow in the long run die rational design of specific agonists and antagonists. The increasing number of reported orphan receptors will certainly be instrumental in the discovery of new regulatory pathways linking cells, with the potential of opening new avenues in pharmacology.info:eu-repo/semantics/publishe

Methylation and expression of the human thyroglobulin gene.

The DNA methylation pattern at the 5'end of the human thyroglobulin gene has been determined in different tissues. Out of the four HpaII/MspI sites (5'-CCGG-3') present in this region, three were found to be non-methylated in thyroid DNA, while full methylation was observed in liver, salivary gland and sperm DNA. This demethylation therefore correlates with expression of the thyroglobulin gene. However, all four sites were found to be non-methylated in placental DNA, regardless of the activity of the gene.info:eu-repo/semantics/publishe