Two-pore channels (TPCs) acts as a hub for excitation-contraction coupling, metabolism and cardiac hypertrophy signalling.

Ca signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation "two-pore channel" (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (Tpcn1/2) and evaluated their cardiac function.

CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca dysregulation linked to Ca influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD glycohydrolase-producing modulators of Ca signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers.

Netrins and their roles in placental angiogenesis.

Netrins, a family of laminin-related proteins, were originally identified as axonal guidance molecules. Subsequently, netrins were found to modulate various biological processes including morphogenesis, tumorogenesis, adhesion, and, recently, angiogenesis. In human placenta, the most vascularized organ, the presence of netrins has also been reported.

Hypoxia-inducible factor 1 controls the expression of the uncoordinated-5-B receptor, but not of netrin-1, in first trimester human placenta.

Uncoordinated-5 homologs 1-4 (UNC5H1-4) transmembrane netrin receptors are reported to control a number of cellular processes, including axonal guidance, angiogenesis and cell proliferation. These receptors are known as "dependence receptors" because they are able to induce apoptosis in the absence of their ligand, netrin. We have recently reported the localization of netrin-1 and its uncoordinated-5-B (UNC5B) receptor in both villous and extravillous cytotrophoblasts in the human placenta.

Characterization and expression of netrin-1 and its receptors UNC5B and DCC in human placenta.

Netrins are a family of proteins that mediate axonal guidance in the central nervous system (CNS). In addition to the CNS, netrins are involved in cell adhesion, motility, proliferation, differentiation, and survival. Because these processes occur in the placenta, we raised the question of whether netrin-1 is expressed by placental cells during development.

Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies.

Objective: To evaluate the influence of aging on the achondroplasia mutation rate in the male germline.

Design: Studies in sperm and testis biopsy DNA according to donor's age.

Setting: University teaching hospital.

Association between androgen receptor gene CAG trinucleotide repeat length and testicular histology in older men.

Objective: To determine whether the size of CAG repeat in exon 1 of the androgen receptor (AR) gene is related to impaired spermatogenesis in older men.

Design: Study of two groups of older men: one with preserved spermatogenesis and the other with arrested spermatogenesis.

Setting: University teaching hospital.