Control of ribonucleotide reductase in Synechococcus Sp., a unicellular cyanobacterium

Cells of Synechococcus sp., a rod-shaped, unicellular cyanobacterium (blue-green alga) can be readily snychronized by depriving the cells of carbon dioxide and light for a 12 h period. On resumption of growth, a portion of the population undergoes two sharply synchronized divisions. Ribonucleotide reductase activity was found to be maximal during the time of DNA synthesis in these cells. The peak of reductase activity could be abolished by adding inhibitors such a chloramphenicol to the culture, suggesting that the enzyme is induced at the gene level in the cyanobacteria. Additional properties of ribonucleotide reductase were investigated in Synechococcus cells made permeable by treatment with ether. Cytidine triphosphate reduction is absolutely dependent on adenosylcobalamin (coenzyme B₁₂) and is subject to allosteric stimulation by deoxyadenosine triphosphate.Abbreviations ECTA ethylene glycol-cis-(-amino ethyl ether)N,N-tetra acetic acid - HEPES N-2-hydroxy ethyl piperazine-N-2-ethane sulfonic acid - EDTA ethylene diamine tetra acetate - DDT dithiothreitol     

The Emergence of Mesolithic Cemeteries in SW Europe: Insights from the El Collado (Oliva,Valencia, Spain) Radiocarbon Record

Located on the Iberian Mediterranean coast, El Collado is an open-air site where a rescue excavation was conducted over two seasons in 1987 and 1988. The archaeological work excavated a surface area of 143m2 where 14 burials were discovered, providing skeletal remains from 15 individuals. We have obtained AMS dates for 10 of the 15 individuals by means of the direct dating of human bones. The ranges of the probability distribution of the calibrated dates suggest that the cemetery was used during a long period of time (781–1020 years at a probability of 95.4%). The new dates consequently set back the chrono-cultural attribution of the cemetery from the initial proposal of Late Mesolithic to an older date in the Early Mesolithic. Therefore, El Collado becomes the oldest known cemetery in the Iberian Peninsula, earlier than the numerous Mesolithic funerary contexts documented on the Atlantic façade such as the Portuguese shell-middens in the Muge and Sado Estuaries or the funerary sites on the northern Iberian coast.     

Estrogens Induce Rapid Cytoskeleton Re-Organization in Human Dermal Fibroblasts via the Non-Classical Receptor GPR30

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.     

Online Training on Skin Cancer Diagnosis in Rheumatologists: Results from a Nationwide Randomized Web-Based Survey

Patients with inflammatory rheumatisms, such as rheumatoid arthritis, are more prone to develop skin cancers than the general population, with an additional increased incidence when receiving TNF blockers. There is therefore a need that physicians treating patients affected with inflammatory rheumatisms with TNF blockers recognize malignant skin lesions, requiring an urgent referral to the dermatologist and a potential withdrawal or modification of the immunomodulatory treatment. We aimed to demonstrate that an online training dedicated to skin tumors increase the abilities of rheumatologists to discriminate skin cancers from benign skin tumors. A nationwide randomized web-based survey involving 141 French rheumatologists was conducted. The baseline evaluation included short cases with skin lesion pictures and multiple choice questions assessing basic knowledge on skin cancers. For each case, rheumatologists had to indicate the nature of skin lesion (benign; premalignant/malignant), their level of confidence in this diagnosis (10-points Likert scale), and the precise dermatological diagnosis among 5 propositions. Different scores were established. After randomization, only one group had access to the online formation consisting in 4 e-learning modules on skin tumors, of 15 minutes each (online training group). After reevaluation, the trained and the non-trained group (control group) were compared. The primary end-point was the number of adequate diagnoses of the nature of the skin lesions. The mean number of adequate diagnosis for the benign versus premalignant/malignant nature of the lesions was higher in the online training group (13.4 vs. 11.2 points; p value <0.0001). While the other knowledge scores were also significantly higher, no statistical difference was observed on the level of self-confidence between the 2 groups. In conclusion, the online formation was effective to improve the rheumatologists’ ability to diagnose skin cancer.