Activated mutant NRasQ61K drives aberrant melanocyte signaling, survival, and invasiveness via a rac1-Dependent mechanism

Around a fifth of melanomas exhibit an activating mutation in the oncogene NRas that confers constitutive signaling to proliferation and promotes tumor initiation. NRas signals downstream of the major melanocyte tyrosine kinase receptor c-kit and activated NRas results in increased signaling via the extracellular signal–regulated kinase (ERK)/MAPK/ERK kinase/mitogen-activated protein kinase (MAPK) pathways to enhance proliferation. The Ras oncogene also activates signaling via the related Rho GTPase Rac1, which can mediate growth, survival, and motility signaling. We tested the effects of activated NRasQ61K on the proliferation, motility, and invasiveness of melanoblasts and melanocytes in the developing mouse and ex vivo explant culture as well as in a melanoma transplant model. We find an important role for Rac1 downstream of NRasQ61K in mediating dermal melanocyte survival in vivo in mouse, but surprisingly NRasQ61K does not appear to affect melanoblast motility or proliferation during mouse embryogenesis. We also show that genetic deletion or pharmacological inhibition of Rac1 in NRasQ61K induced melanoma suppresses tumor growth, lymph node spread, and tumor cell invasiveness, suggesting a potential value for Rac1 as a therapeutic target for activated NRas-driven tumor growth and invasiveness

Epidemiology of gastroschisis: A population-based study in California from 1995 to 2012.

BackgroundAlthough the incidence of gastroschisis is increasing, risk factors are not clearly identified.MethodsUsing the Linked Birth Database from the California Office of Statewide Health Planning and Development from 1995 to 2012, patients with gastroschisis were identified by ICD-9 diagnosis/procedure code or birth certificate designation. Logistic regressions examined demographics, birth factors, and maternal exposures on risk of gastroschisis.ResultsThe prevalence of gastroschisis was 2.7 cases per 10,000 live births. Patients with gastroschisis had no difference in fetal exposure to alcohol (p = 0.609), narcotics (p = 0.072), hallucinogenics (p = 0.239), or cocaine (p = 0.777), but had higher exposure to unspecified/other noxious substances (OR 3.27, p = 0.040; OR 2.02, p = 0.002). Gastroschisis was associated with low/very low birthweight (OR 5.08-16.21, p < 0.001) and preterm birth (OR 3.26-10.0, p < 0.001). Multivariable analysis showed lower risk in black (OR 0.44, p < 0.001), Asian/Pacific Islander (OR 0.76, p = 0.003), and Hispanic patients (OR 0.72, p < 0.001) compared to white patients. Risk was higher in rural areas (OR 1.24-1.76, p = 0.001). Compared to women age < 20, risk decreased with advancing maternal age (OR 0.49-OR 0.03, p < 0.001). Patients with gastroschisis had increased total charges ($336,270 vs.$9012, p < 0.001) and length of stay (38.1 vs. 2.9 days, p < 0.001). Mortality was 4.6%.ConclusionsThis is the largest population-based study summarizing current epidemiology of gastroschisis in California.Type of studyRetrospective comparative cohort study.Level of evidenceIII

The Iowa Perinatal Letter, July-August-September 2009, Vol. 30, no. 3

This newsletter from The Department of Public Health about perinatal health care and statistics

Interruption médicale de grossesse pour atteinte foetale grave: exploration du vécu des parents

Une interruption de grossesse est bien souvent une épreuve difficile pour les parents. La revue de littérature étoffée présentée ci-après a pour but de mieux comprendre ce que vivent les parents lors d’une interruption médicale de grossesse indiquée pour une atteinte foetale grave. La recherche de références est menée essentiellement sur la banque de données PudMed. Dix articles sont trouvés. L’analyse des études permet de mettre en relief le vécu à différents moments : lors de l’annonce de l’anomalie foetale et de la prise de décision d’interrompre la grossesse, de l’accouchement et de l’hospitalisation, de la rencontre entre les parents et leur enfant, et durant les premières semaines de deuil. La pertinence des articles est discutée. Les résultats sont également discutés, à l’aide de différents concepts : le deuil périnatal, les sentiments de douleur, de colère, de culpabilité et de honte, le coping. En guise de conclusion, quelques recommandations pour les soins infirmiers sont exposées

Evaluation of methods for one-dimensional spatial analysis of two-dimensional patterns in mouse chimaeras

The relative extent of cell mixing in tissues of mouse chimaeras or mosaics can be studied by comparing the distributions of the two cell populations in the tissues. However, the mean patch size is misleading because it is affected by both the extent of cell mixing and the relative contributions of the two cell populations. Previous work suggested that effects attributable to differences in tissue composition among chimaeras can be factored out either by correcting the mean patch size or by using the median patch size for the minority cell population and restricting the analysis to grossly unbalanced chimaeras. In the present study, computer simulations of two-dimensional mosaic arrays of black and white squares (representing cells) were used to simulate chimaeric tissues. Random arrays simulated tissues with extensive cell mixing, arrays of cell clumps (representing coherent clones) simulated less mixed tissues, and striped arrays simulated tissues with elongated but fragmented descendent clones. The computer simulations predicted that (i) the median patch length (minority cell population) and the corrected mean patch length would both distinguish between random and clumped patterns and (ii) differences in the variation of the composition of two perpendicular series of one-dimensional transects would distinguished between stripes and randomly orientated patches. Both predictions were confirmed by analysis of histological sections of the retinal pigment epithelium from fetal and adult mouse chimaeras. This study demonstrates that two types of non-random two-dimensional variegated patterns (clumps and stripes) can be identified in chimaeras without two-dimensional reconstruction of serial sections

Les menaces au droit à l’avortement et à l’autonomie des femmes enceintes

Après un bref survol de l’histoire récente de la criminalisation de l’avortement au Canada, l’auteure présente les divers projets de loi privés touchant d’une façon ou d’une autre le droit à l’avortement, principalement le projet no C-484 sur l’homicide foetal, pour en saisir les conséquences sur le droit canadien et sur l’autonomie des femmes pendant leur grossesse. Ces projets de loi se situent à l’intérieur d’une stratégie des opposants à l’avortement qui a essentiellement pour objet de faire reconnaître en droit canadien un droit à la vie et à la sécurité aux foetus et de remettre en question le libre choix des femmes en la matière. Suit une discussion sur l’instrumentalisation du droit pénal à des fins de contrôle social de questions d’ordre éthique. Le texte se termine par une réflexion concernant l’intérêt de l’État dans la protection des foetus. L’auteure soutient que toute intervention étatique doit se faire dans le respect des droits constitutionnels des femmes, soit leur droit à la vie, à la santé et à la liberté.Following a brief historical retrospective on the criminalization of abortion in Canada, the author presents various private bills dealing in one way or another with the right to an abortion, in particular Bill C‑484 on fetal homicide, in order to assess their implications in Canadian law and for women’s autonomy during pregnancy. These bills form part of a strategy set forth by abortion opponents whose purpose is essentially to introduce in Canadian law a fetal right to life and security and to call into question whether women have free choice in this matter. Thereafter follows a discussion on the instrumentalization of criminal law in an effort to gain social control over ethical issues. The text terminates with a reflection on the interest of the State in the protection of fetuses. The author maintains that any action on the part of the State must be compatible with women’s constitutional rights, namely their right to life, good health and freedom