Facteurs de risques environnementaux et/ou professionnels du cancer du testicule

Despite a low overall incidence (1% of all malignant neoplasms), testicular cancer is the most common malignancy among young men. Over the last 40 years, this incidence rate has substantially risen in most industrialised countries. However, the aetiology of testicular cancer remains largely unknown. Only cryptorchidism, and to a lesser extent a family history of testicular cancer, may be considered to be well established risk factors. Numerous attempts have been made to assess the potential role of occupational exposures in adult life as a risk factor for TC, but no clear hypotheses have yet emerged from previous studies in this field. A major limitation of all occupational studies is that no single toxic substance has been clearly identified, and consequently the significant association observed between some job titles and risk of testicular cancer must be interpreted very carefully. In this respect, comparative occupational studies of exposed and non-exposed workers including rigorous and valid job-matrix exposure assessment are needed to study potential relationships between certain occupational exposures and testicular cancer.     

Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease

Intracranial transplantation of neural stem cells (NSCs) delayed disease onset, preserved motor function, reduced pathology and prolonged survival in a mouse model of Sandhoff disease, a lethal gangliosidosis. Although donor-derived neurons were electrophysiologically active within chimeric regions, the small degree of neuronal replacement alone could not account for the improvement. NSCs also increased brain beta-hexosaminidase levels, reduced ganglioside storage and diminished activated microgliosis. Additionally, when oral glycosphingolipid biosynthesis inhibitors (beta-hexosaminidase substrate inhibitors) were combined with NSC transplantation, substantial synergy resulted. Efficacy extended to human NSCs, both to those isolated directly from the central nervous system (CNS) and to those derived secondarily from embryonic stem cells. Appreciating that NSCs exhibit a broad repertoire of potentially therapeutic actions, of which neuronal replacement is but one, may help in formulating rational multimodal strategies for the treatment of neurodegenerative diseases.     

A glucose kinase from Mycobacterium smegmatis

Carbon metabolism and regulation is poorly understood in mycobacteria, a genus that includes some major pathogenic species like Mycobacterium tuberculosis and Mycobacterium leprae. Here, we report the identification of a glucose kinase from Mycobacterium smegmatis. This enzyme serves in glucose metabolism and global carbon catabolite repression in the related actinomycete Streptomyces coelicolor. The gene, msmeg1356 (glkA), was found by means of in silico screening. It was shown that it occurs in the same genetic context in all so far sequenced mycobacterial species, where it is located in a putative tricistronic operon together with a glycosyl hydrolase and a putative malonyl-CoA transacylase. Heterologous expression of glkA in an Escherichia coli glucose kinase mutant led to the restoration of glucose growth, which provided in vivo evidence for glucose kinase function. GlkA(Msm) was subsequently overproduced in order to study its enzymatic features. We found that it can form a dimer and that it efficiently phosphorylates glucose at the expense of ATP. The affinity constant for glucose was with 9 mM about eight times higher and the velocity was about tenfold slower when compared to the parallel measured glucose kinase of S. coelicolor. Both enzymes showed similar substrate specificity, which consists in an ATP-dependent phosphorylation of glucose and no, or very inefficient, phosphorylation of the glucose analogues 2-deoxyglucose and methyl alpha-glucoside. Hence, our data provide a basis for studying the role of mycobacterial glucose kinase in vivo to unravel possible catalytic and regulatory functions.     

Immunomodulation by maternal autoantibodies of the fetal serotoninergic 5-HT<Subscript>4</Subscript>receptor and its consequences in early BALB/c mouse embryonic development

Background  

The presence of functional 5-HT₄ receptors in human and its involvement in neonatal lupus erythematosus (NLE) have prompted us to study the receptor expression and role during embryogenesis. Earlier we managed to demonstrate that female BALB/c mice immunized against the second extracellular loop (SEL) of the 5-HT₄ receptor gave birth to pups with heart block. To explain this phenomenon we investigated the expression of 5-HT₄ receptors during mouse embryogenesis. At the same time we looked whether the consequence of 5-HT₄ receptor immunomodulation observed earlier is in relation to receptor expression.     

Expression and function of cyclooxygenase and lipoxygenase enzymes in human islets of Langerhans

Arachidonic acid (AA) is generated in pancreatic beta-cells through the activation of Ca2+-dependent cytosolic phospholipase A2 (cPLA2) and the consequent hydrolysis of membrane phospholipids in the sn-2 position of the glycerophospholipid backbone. AA acts as a second messenger in beta-cells to elevate cytosolic Ca2+ levels and stimulate insulin secretion, but it is not clear whether these are direct effects of AA or are dependent on its metabolism by cyclooxygenase (COX) and/or lipoxygenase (LOX) enzymes. In addition, much of the published data in this area have been generated using insulin-secreting cell lines or rodent islets, with very little information on AA generation and metabolism in human islets of Langerhans. This short review examines cPLA2, COX and LOX expression and function in insulin- secreting cell lines and rodent and human islets.     

Fine-scale habitat associations of Oklahoma's longspurs

Overwintering is a key demographic stage for migratory birds but remains poorly understood, especially among multiple declining grassland bird species. The non-breeding ranges all 4 species of longspur (i.e., chestnut-collared [Calcarius ornatus], Smith's [C. pictus], Lapland [C. lapponicus], thick-billed [Rhynchophanes mccownii]) overlap in Oklahoma and the Texas Panhandle, USA, making this region ideal to study their wintering ecology. We evaluated the relationship between wintering longspur occurrence and fine-scale habitat characteristics using a combination of standardized bird surveys and vegetation plot sampling. Our study encompassed large, representative tracts of 3 prairie ecosystems (i.e., shortgrass, mixed-grass, and tallgrass prairies) that intersect within the Southern Great Plains, during winters of 2018–2019 and 2019–2020. Using randomization tests and classification trees, we characterized longspur habitats and compared these associations across the 3 prairie ecosystems. Fine-scale winter habitats (horizontal structure, vertical structure, and species compositions) varied among all 4 longspur species, varied at very fine scales, and differed between grassland types. Our findings can be applied to the management of grasslands such as decreasing vegetation height in mixed-grass prairies for chestnut-collared longspurs or removing woody vegetation in shortgrass prairies for thick-billed longspurs to help develop full-life cycle conservation for longspurs, which have experienced population declines.