Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

We assessed somatic alleles of six receptor tyrosine kinase genes mutated in lung adenocarcinoma for oncogenic activity. Five of these genes failed to score in transformation assays; however, novel recurring extracellular domain mutations of the receptor tyrosine kinase gene ERBB2 were potently oncogenic. These ERBB2 extracellular domain mutants were activated by two distinct mechanisms, characterized by elevated C-terminal tail phosphorylation or by covalent dimerization mediated by intermolecular disulfide bond formation. These distinct mechanisms of receptor activation converged upon tyrosine phosphorylation of cellular proteins, impacting cell motility. Survival of Ba/F3 cells transformed to IL-3 independence by the ERBB2 extracellular domain mutants was abrogated by treatment with small-molecule inhibitors of ERBB2, raising the possibility that patients harboring such mutations could benefit from ERBB2-directed therapy

Possibilidades terapêuticas e risco toxicológico de Jatropha gossypiifolia L.: uma revisão narrativa Therapeutic possibilities and toxicological risk of Jatropha gossypiifolia L.: a narrative review

A espécie Jatropha gossypiifolia L. (Euphorbiaceae), popularmente conhecida como pião-roxo, entre tantos outros nomes, é um bom exemplo do tênue limiar que separa o efeito terapêutico do tóxico. Apesar de ser classicamente conhecida como planta tóxica possui usos na medicina popular. Alguns desses efeitos têm sido comprovados em estudos experimentais, como os de antimicrobiano, antineoplásico, cicatrizante e hipotensor, sendo possivelmente explicados pela presença de substâncias como alcalóides, terpenóides, flavonóides, lignanas e taninos. Esta revisão aborda aspectos importantes, com ênfase na toxicidade crônica dessa espécie, de modo a servir de fonte de informação aos interessados em avaliar a relação risco/benefício do uso terapêutico de Jatropha gossypiifolia L.<br>The species Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as bellyache bush, among several other names, is an important example of the tenuous threshold that separates the therapeutic from the toxic effect. Although traditionally known as a toxic plant, it has been used in folk medicine. Some of its effects have been proved by experimental studies as antimicrobial, antineoplastic, healing and hypotensive, likely explained by the presence of substances such as alkaloids, terpenoids, flavonoids, lignans and tannins. This review deals with important aspects, focusing on the chronic toxicity of this species, in order to serve as an information source for those interested in evaluating the risk-benefit ratio of the therapeutic use of Jatropha gossypiifolia L

A new Synbranchus (Teleostei: Synbranchiformes: Synbranchidae) from ilha de Marajó, Pará, Brazil, with notes on its reproductive biology and larval development

Synbranchus lampreia, new species, is described from rio Goiapi, Marajó Island, Pará, northern Brazil. It differs from the other two described species of the genus by its color pattern, which consists of large roundish black blotches scattered over a light brown or yellowish ground pigmentation and presence of inconspicuous brown small spots distributed among the large dark spots. The species is further distinguished from S. marmoratus by a higher number of vertebrae and from S. madeira by a shorter postanal length. Information about reproductive aspects is provided and larval stages are described and illustrated

Geochemistry of Sandstones from the Upper Cretaceous Sillakkudi Formation, Cauvery Basin, Southern India: Implication for Provenance

Major, trace and rare earth elements (REE) composition of sandstones from the Upper Cretaceous Sillakkudi Formation, Ariyalur Group, Cauvery Basin were studied to decipher their weathering and provenance history. Texturally, these sandstones are immature, poorly sorted and grain supported. Abundance of feldspars especially, plagioclase indicates rapid deposition of sediments from a nearby source rocks. Using the geochemical classification diagram the Sillakkudi sandstones are classified as fe-sand, quartz arenite, litharenite, sub-litharenite, sub-arkose, arkose, and wacke types,which is also supported by the petrography study. The transition trace elements like Co, Ni, and V are higher in theSillakkudi sandstones than upper continental crust (UCC) values. However, the Sillakkudi sandstones are lower in Cr (mean ~21) content than average UCC value (~ 35). The poor correlation between Cr and Ni (r = 0.08, number of samples n = 20) imply that these sandstones were derived from felsic source rocks. Similarly, the Eu/Eu* (0.35-1.73), La/Sc (1.93-9.36), Th/Sc (0.41-6.57), Th/Co (0.14-5.01), Th/Cr (0.23-2.94), and Cr/Th (0.34-4.28) ratios support a felsic source for the Sillakkudi sandstones.The significant enrichment of Zr, Hf, and Th in fe-sand, sub-arkose and litharenite could be related to the presence of heavy minerals, especially zircon. However, the zircon geochemistry did not affectthe REE distribution and its patterns in the Sillakkudi sandstones. The Chondrite normalized REE patterns of Sillakkudi sandstones are characterized by relatively flat HREE (Gd/YbCN = ~ 0.73-2.41; subscript CN refers to chondrite normalized value), enriched LREE (La/SmCN = ~ 3.39-5.82) and negative Eu anomaly (mean value Eu/Eu* = 0.80). The Gd/YbCN ratios (~0.73-2.50) are less than 2.5, which suggest that these Sillakkudi sandstones were derived from the less HREE depleted source rocks. The comparison of REE patterns and its Eu anomalies to the source rocks reveals that the Sillakkudi sandstones received a major contribution of sediments from Dharwar craton

Dark Energy Survey Year 3 Results: Deep Field optical + near-infrared images and catalogue

International audienceWe describe the Dark Energy Survey (DES) Deep Fields, a set of images and associated multiwavelength catalogue (ugrizJHKs) built from Dark Energy Camera (DECam) and Visible and Infrared Survey Telescope for Astronomy (VISTA) data. The DES Deep Fields comprise 11 fields (10 DES supernova fields plus COSMOS), with a total area of ∼30 sq. deg. in ugriz bands and reaching a maximum i-band depth of 26.75 (AB, 10σ, 2 arcsec). We present a catalogue for the DES 3-yr cosmology analysis of those four fields with full 8-band coverage, totalling 5.88 sq. deg. after masking. Numbering 2.8 million objects (1.6 million post-masking), our catalogue is drawn from images coadded to consistent depths of r = 25.7, i = 25, and z = 24.3 mag. We use a new model-fitting code, built upon established methods, to deblend sources and ensure consistent colours across the u-band to Ks-band wavelength range. We further detail the tight control we maintain over the point-spread function modelling required for the model fitting, astrometry and consistency of photometry between the four fields. The catalogue allows us to perform a careful star–galaxy separation and produces excellent photometric redshift performance (NMAD = 0.023 at i < 23). The Deep-Fields catalogue will be made available as part of the cosmology data products release, following the completion of the DES 3-yr weak lensing and galaxy clustering cosmology work