Human and mouse ZFY genes produce a conserved testis-specific transcript encoding a zinc finger protein with a short acidic domain and modified transactivation potential

Mammalian ZFY genes are located on the Y chromosome, and code putative transcription factors with 12–13 zinc fingers preceded by a large acidic (activating) domain. In mice, there are two genes, Zfy1 and Zfy2, which are expressed mainly in the testis. Their transcription increases in germ cells as they enter meiosis, both are silenced by meiotic sex chromosome inactivation (MSCI) during pachytene, and Zfy2 is strongly reactivated later in spermatids. Recently, we have shown that mouse Zfy2, but not Zfy1, is involved in triggering the apoptotic elimination of specific types of sex chromosomally aberrant spermatocytes. In humans, there is a single widely transcribed ZFY gene, and there is no evidence for a specific role in the testis. Here, we characterize ZFY transcription during spermatogenesis in mice and humans. In mice, we define a variety of Zfy transcripts, among which is a Zfy2 transcript that predominates in spermatids, and a Zfy1 transcript, lacking an exon encoding approximately half of the acidic domain, which predominates prior to MSCI. In humans, we have identified a major testis-specific ZFY transcript that encodes a protein with the same short acidic domain. This represents the first evidence that ZFY has a conserved function during human spermatogenesis. We further show that, in contrast to the full acidic domain, the short domain does not activate transcription in yeast, and we hypothesize that this explains the functional difference observed between Zfy1 and Zfy2 during mouse meiosis

VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

Objective To identify novel genetic loci that predispose to early‐onset myasthenia gravis (EOMG) applying a two‐stage association study, exploration, and replication strategy. Methods Thirty‐four loci and one confirmation loci, human leukocyte antigen (HLA)‐DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B‐cell activating factor (BAFF), and tumor necrosis factor‐alpha (TNF‐α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA‐DRA and TNF‐α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T‐ and B‐cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B‐cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor‐kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG

New Lobane and Cembrane Diterpenes from Two Comorian Soft Corals

Preliminary biological investigation of a collection of Comorian soft corals resulted in the selection of two specimens, one of Sarcophyton and the other of Lobophytum, on the basis of their toxicity on larvae of the brine shrimp (Artemia salina) and inhibition of acetylcholinesterase, respectively. Bioassay-guided fractionations provided a known antitumor promoter cembrane diterpenoid, (+)-sarcophytol-A (1), along with a new lobane diterpenoid, carbomethoxyfuscol (2), from Sarcophyton sp., and a new cembranoid, crassumolide E (3), from Lobophytum sp. The structures of compounds 1–3 were determined by spectroscopic analysis and by comparison of the spectral data with previously reported values. The cembranoid 3 was found to exhibit a moderate inhibitory effect on acetylcholinesterase

Lack of Association between Genetic Polymorphisms in Enzymes Associated with Folate Metabolism and Unexplained Reduced Sperm Counts

BACKGROUND: The metabolic pathway of folate is thought to influence DNA stability either by inducing single/double stranded breaks or by producing low levels of S-adenosyl-methionine leading to abnormal gene expression and chromosome segregation. Polymorphisms in the genes encoding enzymes in the folate metabolism pathway show distinct geographic and/or ethnic variations and in some cases have been linked to disease. Notably, the gene Methylenetetrahydrofolate reductase (MTHFR) in which the homozygous (TT) state of the polymorphism c.665C>T (p.A222V) is associated with reduced specific activity and increased thermolability of the enzyme causing mild hyperhomocysteinemia. Recently several studies have suggested that men carrying this polymorphism may be at increased risk to develop infertility. METHODOLOGY/PRINCIPAL FINDINGS: We have tested this hypothesis in a case/control study of ethnic French individuals. We examined the incidence of polymorphisms in the genes MTHFR (R68Q, A222V and E429A), Methionine synthase reductase MTRR; (I22M and S175L) and Cystathionine beta-synthase (CBS; G307S). The case population consisted of DNA samples from men with unexplained azoospermia (n = 70) or oligozoospermia (n = 182) and the control population consisted of normospermic and fertile men (n = 114). We found no evidence of an association between the incidence of any of these variants and reduced sperm counts. In addition haplotype analysis did not reveal differences between the case and control populations. CONCLUSIONS/SIGNIFICANCE: We could find no evidence for an association between reduced sperm counts and polymorphisms in enzymes involved in folate metabolism in the French population

Stratégie d'exploration moléculaire du chromosome Y dans les troubles sévères de la spermatogenèse

Les microdélétions du chromosome Y, deuxième cause génétique d'infertilité masculine, sont associées à des troubles sévères de la spermatogenèse qui relèvent de la technique d'ICSI. Après avoir évalué l'activité de recherche des microdélétions du bras long du chromosome Y en France, nous avons validé une méthode facilitant sa standardisation et comparé les performances techniques de kits commerciaux. Le génome germinal a été étudié par FISH chez dez patients avec oligozoospermie sévère d'origine non-obstructive sans anomalie chromosomiques spermatiques chez ces hommes. Enfin, nous avons montré l'inte rêt de deux techniques associées qui permettent de détecter toutes les délétions partielles de la région AZFc du chromosome Y. En conclusion, en cas de troubles sévères de la spermatogenèse, le chromosome Y doit être exploré dans le cadre du bilan avant AMPY chromosome microdeletions are the second genetic cause of male infertility. They are associated to severe spermatogenesis impairment relevant to ICSI techniques. We evaluated the research of Y chromosome long arm microdeletions in France, and then we validated a fast and easy method to facilitate standardization. We also compared technical performances of two commercial kits. The germinal genome was studied by FISH in patients with severe non obstructive oligozoospermia without karyotyping anomaly. We have identified four clinical and / or biological factors associated with higher numbers of aneuploid sperm. Finally, we showed the interest of two combined techniques to detect all the pertial deletions of the AZFc region. In conclusion, in the event of severe spermatogenesis impairment, the Y chromosome has to be screened before Assited Reproductive TechniquesLYON1-BU.Sciences (692662101) / SudocSudocFranceF

5α,8α-Epidioxysterols from the tunicate Didemnum salary

International audienceFive α,8α-epidioxysterols were isolated and identified from the tunicate Didemnum salary. The relative quantification of the compds. obtained was 5α,8α-epidioxycholest-6-en-3β-ol (50%), 5α,8α-epidioxy-24(S)-methylcholest-6-en-3β-ol + 5α,8α-epidioxy-24(R)-methylcholest-6-en-3β-ol (30%), and 5α,8α-epidioxy-24(S)-ethylcholest-6-en-3β-ol + 5α,8α-epidioxy-24(R)-ethylcholest-6-en-3β-ol (20%). [on SciFinder(R)

7-Amino-7,8-dihydro-α-bisabolene derivatives from the marine sponge Axinyssa aplysinoides

International audience(6R,7S)-7-amino-7,8-dihydro-α-bisabolene, (6R,7S)-7-amino-7,8-dihydro-α-bisabolene-HCl, and N,N'-bis[(6R,7S)-7-amino-7,8-dihydro-α-bisabolen-7-yl]urea were isolated from the sponge Axinyssa aplysinoides and structures were detd. on the basis of 1D NMR spectra. Their chemotaxonomic significance was discussed. [on SciFinder(R)

Ptilomycalin D, a Polycyclic Guanidine Alkaloid from the Marine Sponge Monanchora dianchora

International audienceA new polycyclic guanidine alkaloid, ptilomycalin D (I), and the known crambescidic acid were isolated from the marine sponge Monanchora dianchora collected in Nosy-Be, northwest of Madagascar, in the Indian Ocean. The structures were elucidated using 1- and 2-D NMR and MS data, and their biogenetic implications are discussed. [on SciFinder(R)

5α,8α-Epidioxysterol from the marine sponge Biemna triraphis Topsent

International audience5α,8α-Epidioxy-24(S)-ethylcholest-6-en-3β-ol was isolated from the marine sponge Biemna triraphis Topsent collected at Andavadoaka, near Toliary (west coast of Madagascar-Indian Ocean). The structure was elucidated from NMR spectroscopic data. This is the first report of this compd. in a marine sponge belonging to the Biemna genus. [on SciFinder(R)

Marine bifunctional sphingolipids from the sponge Oceanapia ramsayi

International audienceDuring the course of our continuing studies on marine natural lipid products, two known sphingolipids have been isolated for the first time from a specimen of the marine sponge Oceanapia ramsayi collected at Itampolo on the west coast of Madagascar in the Indian Ocean. The structures were elucidated using NMR data and by comparison with literature data. The occurrence of these sphingolipids within other Oceanapia spp. is discussed. [on SciFinder(R)