A New Isoform of the Histone Demethylase JMJD2A/KDM4A Is Required for Skeletal Muscle Differentiation

In proliferating myoblasts, muscle specific genes are silenced by epigenetic modifications at their promoters, including histone H3K9 methylation. Derepression of the promoter of the gene encoding the myogenic factor myogenin (Myog) is key for initiation of muscle differentiation. The mechanism of H3K9 demethylation at the Myog promoter is unclear, however. Here, we identify an isoform of the histone demethylase JMJD2A/KDM4A that lacks the N-terminal demethylase domain (ΔN-JMJD2A). The amount of ΔN-JMJD2A increases during differentiation of C2C12 myoblasts into myotubes. Genome-wide expression profiling and exon-specific siRNA knockdown indicate that, in contrast to the full-length protein, ΔN-JMJD2A is necessary for myotube formation and muscle-specific gene expression. Moreover, ΔN-JMJD2A promotes MyoD-induced conversion of NIH3T3 cells into muscle cells. ChIP-on-chip analysis indicates that ΔN-JMJD2A binds to genes mainly involved in transcriptional control and that this binding is linked to gene activation. ΔN-JMJD2A is recruited to the Myog promoter at the onset of differentiation. This binding is essential to promote the demethylation of H3K9me2 and H3K9me3. We conclude that induction of the ΔN-JMJD2A isoform is crucial for muscle differentiation: by directing the removal of repressive chromatin marks at the Myog promoter, it promotes transcriptional activation of the Myog gene and thus contributes to initiation of muscle-specific gene expression

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Niche construction by non-diazotrophs for N2 fixers in the eastern tropical North Atlantic Ocean

Diazotrophic dinitrogen (N2) fixation contributes ~76% to "new" nitrogen inputs to the sunlit open ocean, but environmental factors determining N2 fixation rates are not well constrained. Excess phosphate (phosphate-nitrate/16 > 0) and iron availability control N2 fixation rates in the eastern tropical North Atlantic (ETNA), but it remains an open question how excess phosphate is generated within or supplied to the phosphate-depleted sunlit layer. Our observations in the ETNA region (8°N-15°N, 19°W-23°W) suggest that Prochlorococcus and Synechococcus, the two ubiquitous non-diazotrophic cyanobacteria with cellular N:P ratios higher than the Redfield ratio, create an environment of excess phosphate, which cannot be explained by diapycnal mixing, atmospheric, and riverine inputs. Thus, our results unveil a new biogeochemical niche construction mechanism by non-diazotrophic cyanobacteria for their diazotrophic phylum group members (N2 fixers). Our observations may help to understand the prevalence of diazotrophy in low-phosphate, oligotrophic regions

Decision factors influencing hormone replacement therapy

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Beneficial Effect of Mukaiyama Reagent on Macrobislactamization Reactions

International audienc

Principal cancers among women: Breast, lung and colorectal

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

The menopause in Europe

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Osteoporosis prevention and treatment with sex hormone replacement therapy

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Compliance to hormone replacement therapy.

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Effect of bone density evaluation on hormone replacement therapy prescription

Objectives: This study evaluates whether Bone Mineral Density (BMD) results influence HRT prescription. Methods: Successive charts of 29 postmenopausal women were summarised. For each chart, 3 'simulated cases' were created by modifying the BMD result (based on the Z-score) in order to have 4 groups with the same clinical story but a wide range of BMD values (Group I = Z-score > 0, Group II = Z-score between 0 and 1, Group III = Z- score between -1 and -2 and Group IV = Z-score < -2). The obtained cases were presented to 10 gynaecologists who were asked whether HRT should be prescribed. The gynaecologists were not aware of the above-mentioned manipulation. Results: The overall treatment rate was 74.2%, ranging from 65% for women with the highest BMD (Group I), 73% for Group II, 79% for Group III and 80% for Group IV, i.e. women with the lowest BMD (Friedman analysis of variance; chi-square 17.2; P < 0.001). In approximately a third of the patients (11/29), there was agreement for initiation of therapy, regardless of the BMD. Most of these women presented other indications and no contra- indications for therapy. The prescription frequency of the 10 gynaecologists varied between 63% and 87%; Cochran Q Statistic 39.2; P < 0.0001). For some physicians, a trend to increase prescription was observed in relation to the BMD result, but a statistical difference could only be reached for one physician (P < 0.05). Furthermore, for some physicians no modification whatsoever could be observed. Conclusions: BMD appears to be a determinant factor for HRT prescription in only a limited proportion of the patients and a small number of the physicians. From an epidemiological point of view, BMD measurements may be useful in order to help deciding women to start HRT, especially those who are reluctant or to those who present relative contra- indications, provided that their physicians are aware of the usefulness of these investigations.SCOPUS: ar.jinfo:eu-repo/semantics/publishe