Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations.

Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole-exome sequencing of 15 EATL-II tumour-normal tissue pairs. The tumour suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. In addition, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention

Atrioventricular canal defect in patients with RASopathies

Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies. © 2013 Macmillan Publishers Limited. All rights reserved

Difusão de contaminantes em condições de vento fraco empregando um modelo estocástico Lagrangeano Difusion of contaminants in low wind conditions employing a Lagrangian stochastic model

Um modelo estocástico Lagrangeano é utilizado para simular a dispersão e o transporte de contaminantes, sob condições estáveis, com velocidade do vento fraco, no experimento traçante realizado no Idaho National Engineering Laboratory (INEL). Neste trabalho é testada uma nova parametrização dos parâmetros que representam as freqüências associadas ao fenômeno de meandro do vento, presentes nas equações de Langevin para as componentes do vento horizontal. Esta nova parametrização é descrita em termos de uma quantidade adimensional que controla a freqüência de oscilação de meandro do vento e da escala de tempo, associada às estruturas coerentes em uma turbulência bem desenvolvida. As simulações demonstram que o modelo Lagrangeano considerado, incorporando esta nova parametrização, reproduz corretamente a difusão de escalares passivos em uma camada limite atmosférica estável com velocidade do vento fraco.<br>A Lagrangian stochastic particle model is utilized to simulate the dispersion and the transport of contaminants under low wind stable conditions in the tracer experiment carried in the Idaho National Engineering Laboratory (INEL). In this work a new parameterization for the parameters representing the frequencies associated to the meandering phenomenon is tested. The new parameterization is expressed in terms of a non-dimensional quantity that controls the frequencies of the meandering oscillation and of the time scale associated to a coherent structure in a fully developed turbulence. The simulations show that the considered Lagrangian model, incorporating this new parameterization, reproduces correctly the diffusion of passive scalars in a low wind speed stable atmospheric boundary layer

The need to breed crop varieties suitable for organic farming, using wheat, tomato and broccoli as examples: A review

It is estimated that more than 95% of organic production is based on crop varieties that were bred for the conventional high-input sector. Recent studies have shown that such varieties lack important traits required under organic and low-input production conditions. This is primarily due to selection in conventional breeding programmes being carried out in the background of high inorganic fertilizer and crop protection inputs. Also, some of the traits (e.g., semi-dwarf genes) that were introduced to address problems like lodging in cereals in high-input systems were shown to have negative side-effects (reduced resistance to diseases such as Septoria, lower protein content and poorer nutrient-use efficiency) on the performance of varieties under organic and low-input agronomic conditions. This review paper, using wheat, tomato and broccoli as examples, describes (1) the main traits required under low-input conditions, (2) current breeding programmes for organic, low-input agriculture, (3) currently available breeding and/or selection approaches, and (4) the benefits and potential negative side-effects of different breeding methodologies and their relative acceptability under organic farming principles. © 2010 Royal Netherlands Society for Agricultural Sciences. Published by Elsevier B.V. All rights reserved