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

Ultrafast optical generation of coherent phonons in CdTe1-xSex quantum dots

We report on the impulsive generation of coherent optical phonons in CdTe0.68Se0.32 nanocrystallites embedded in a glass matrix. Pump probe experiments using femtosecond laser pulses were performed by tuning the laser central energy to resonate with the absorption edge of the nanocrystals. We identify two longitudinal optical phonons, one longitudinal acoustic phonon and a fourth mode of a mixed longitudinal-transverse nature. The amplitude of the optical phonons as a function of the laser central energy exhibits a resonance that is well described by a model based on impulsive stimulated Raman scattering. The phases of the coherent phonons reveal coupling between different modes. At low power density excitations, the frequency of the optical coherent phonons deviates from values obtained from spontaneous Raman scattering. This behavior is ascribed to the presence of electronic impurity states which modify the nanocrystal dielectric function and, thereby, the frequency of the infrared-active phonons

Estimativa do balanço de energia utilizando o modelo de interação biosfera-atmosfera - CABLE.

O objetivo desse trabalho foi avaliar o desempenho do modelo CABLE (Csiro Atmosphere Biophisic Land Exchange) na estimativa do saldo de radiação, para três dias consecutivos acima da cultura da soja. Foram realizadas medições contínuas dos fluxos de massa e energia para um ciclo completo da cultura da soja durante o período de novembro de 2008 a abril de 2009, no município de Cruz Alta, RS, Brasil. Para simulação do saldo de radiação foi utilizado o modelo Biofísico de interação solo-planta-atmosfera ?CABLE?. Foram realizados quatro testes estatísticos para testar o modelo CABLE, o qual conseguiu reproduzir os valores dos dados observados dos componentes do balanço de energia durante os três dias analisados, obtendo índice de correlação ?r? e índice de concordância ?d? de 0,98 e 0,97, respectivamente

Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas.

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH-derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-κB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR-related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlation with presenting clinical features nor significant impact on survival was observed, the presence of TCR-related mutations correlated with early disease progression. Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas

Thioflavine-T and Congo Red reveal the polymorphism of insulin amyloid fibrils when probed by polarization-resolved fluorescence microscopy.

International audienceAmyloid fibrils are protein misfolding structures that involve a β-sheet structure and are associated with the pathologies of various neurodegenerative diseases. Here we show that Thioflavine-T and Congo Red, two major dyes used to image fibrils by fluorescence assays, can provide deep structural information when probed by means of polarization-resolved fluorescence microscopy. Unlike fluorescence anisotropy or fluorescence detected linear dichroism imaging, this technique allows to retrieve simultaneously both mean orientation and orientation dispersion of the dye, used here as a reporter of the fibril structure. We have observed that insulin amyloid fibrils exhibit a homogeneous behavior over the fibrils' length, confirming their structural uniformity. In addition, these results reveal the existence of various structures among the observed fibrils' population, in spite of a similar aspect when imaged with conventional fluorescence microscopy. This optical nondestructive technique opens perspectives for in vivo structural analyses or high throughput screening

An Ecophisiological Proposal to Manage Natural Grasslands: A Long Term Trial

Natural grasslands on Southern Brazil comprise the so called “Rio de La Plata Grasslands” in South America. They are an important fodder source for ruminant pastoral systems and contribute to regional ecosystem services. Strength of these grasslands is its floristic diversity that poses a dilemma to farmers: how to choose management protocols that could be applied for hundreds of species. We propose to use a functional ecophysiological approach based on groups of grasses, the most abundant on aerial biomass of this natural grasslands. We clustered the most frequent grasses in two groups based on its leaf traits (leaf dry matter content and specific leaf area). These traits are functional clues to growth rhythms and nutritive value that could separate grasses in “resource capture” and “resource conservation” groups, both important for forage production and ecosystem services. Evaluating the most frequent grasses in each group we found they have an average of 375 degree-days, for “resource capture” and 750 degree-day for “resource conservation” groups, as its leaf elongation duration. So we evaluated a rotational grazing system based on this morphogenic trait for beef heifers rearing on natural grasslands from 2010 to 2019. We chose these experimental animals, as a model by its nutrient requirements and relevance for regional rearing and breeding systems. Our results indicate an average daily gain that is adequate to reach mating age and weight targets (0,3 kg/heifer/day to mate at 24 months) and allowed a higher stocking rate and gain per area when compared to regional standards (1,100 kg of live weight/ha and 370 kg/ha versus 600 and 70 kg/ha). All this animal performance was obtained without changing floristic diversity and also enhancing ecosystem services as CO2 sequestration. We concluded that this approach could allow farmers to conciliate the dilemma of production and conservation in pastoral ecosystems

Health-related quality of life in patients with primary open-angle glaucoma. An italian multicentre observational study

PurposeAs a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. MethodsThis was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. ResultsA total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9years. A total of 93.8% had a previous diagnosis (median duration: 8.0years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. ConclusionIn this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment

Gastrointestinal strongyles burden monitoring in a flock of Zerasca sheep treated with homeopathy

Introdution The widespread use of conventional drugs in farm animals has resulted in anthelmintic resistance as well as the contamination of deleterious molecules in animal products and in the environment. Researchers are thus focusing on production systems that rely less on chemicals. The aim of this study was to monitor the gastrointestinal strongyle burden, blood count, body condition scores (BCS), and FAffa MAlan CHArt (FAMACHA) in a local Italian breed of sheep reared in natural conditions. Methods The study was carried out in a farm where homeopathy was utilised. Over a one-year period, faeces were sampled six times from ten Zerasca ewes to evaluate the fecal eggs count using a modified McMaster technique. At the same time, blood samples were collected to evaluate white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width. BCS and FAMACHA were also recorded. Results Results showed low parasite levels in most of the samples with the highest value in the spring. Blood parameters were within the normal range, with significant fluctuations during the sampling period. BCS values corresponded to an adequate nutritional condition of the animals and FAMACHA scores did not suggest a worrying state of anemia. Conclusions In this farm, a thorough monitoring of the gastrointestinal parasite burden together with a BCS and FAMACHA evaluation allowed the amount of chemical treatments to be limited, normally administered twice a year without laboratory tests