Detection of ALK fusion transcripts in FFPE lung cancer samples by NanoString technology

Background: ALK-rearranged lung cancers exhibit specific pathologic and clinical features and are responsive to anti-ALK therapies. Therefore, the detection of ALK-rearrangement is fundamental for personalized lung cancer therapy. Recently, new molecular techniques, such as NanoString nCounter, have been developed to detect ALK fusions with more accuracy and sensitivity. Methods: In the present study, we intended to validate a NanoString nCounter ALK-fusion panel in routine biopsies of FFPE lung cancer patients. A total of 43 samples were analyzed, 13 ALK-positive and 30 ALK-negative, as previously detected by FISH and/or immunohistochemistry. Results: The NanoString panel detected the presence of the EML4-ALK, KIF5B-ALK and TFG-ALK fusion variants. We observed that all the 13 ALK-positive cases exhibited genetic aberrations by the NanoString methodology. Namely, six cases (46.15%) presented EML-ALK variant 1, two (15.38%) presented EML-ALK variant 2, two (15.38%) presented EML-ALK variant 3a, and three (23.07%) exhibited no variant but presented unbalanced expression between 5'/3' exons, similar to other positive samples. Importantly, for all these analyses, the initial input of RNA was 100 ng, and some cases displayed poor RNA quality measurements. Conclusions: In this study, we reported the great utility of NanoString technology in the assessment of ALK fusions in routine lung biopsies of FFPE specimens.This study was partially funded by FINEP (MCTI/FINEP/MS/SCTIE/DECIT), Brazil. BIOPLAT (1302/13).info:eu-repo/semantics/publishedVersio

Electric double-layer capacitance between an ionic liquid and few-layer graphene

Ionic-liquid gates have a high carrier density due to their atomically thin electric double layer (EDL) and extremely large geometrical capacitance C-g. However, a high carrier density in graphene has not been achieved even with ionic-liquid gates because the EDL capacitance C-EDL between the ionic liquid and graphene involves the series connection of C-g and the quantum capacitance C-q, which is proportional to the density of states. We investigated the variables that determine C-EDL at the molecular level by varying the number of graphene layers n and thereby optimising C-q. The C-EDL value is governed by C-q at n, 4, and by C-g at n > 4. This transition with n indicates a composite nature for C-EDL. Our finding clarifies a universal principle that determines capacitance on a microscopic scale, and provides nanotechnological perspectives on charge accumulation and energy storage using an ultimately thin capacitor

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient’s clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.This project was partially supported by Barretos Cancer Hospital internal research funds (PAIP) and CNPq Universal Grant (476192/2013-7) to RMR. NCC is a recipient of an FAPESP Doctoral Fellowship (2013/25787-3). Further funding from the project ‘Microenvironment, metabolism and cancer’ that was partially supported by Programa Operacional Regional do Norte (ON.2—O Novo Norte) under the Quadro de Referência Estratégico Nacional (QREN) and the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education that is partially supported by the FCT

Genetic diversity and structure of Iberian Peninsula cowpeas compared to world-wide cowpea accessions using high density SNP markers

Cowpea (Vigna unguiculata L. Walp) is an important legume crop due to its high protein content, adaptation to heat and drought and capacity to fix nitrogen. Europe has a deficit of cowpea production. Knowledge of genetic diversity among cowpea landraces is important for the preservation of local varieties and is the basis to obtain improved varieties. The aims of this study were to explore diversity and the genetic structure of a set of Iberian Peninsula cowpea accessions in comparison to a worldwide collection and to infer possible dispersion routes of cultivated cowpea.This study was supported by EUROLEGUME project. This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 613781. European Investment Funds by FEDER/COMPETE/ POCI – Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. MMA was partially supported by the Feed the Future Innovation Lab for Climate Resilient Cowpea (USAID Cooperative Agreement AID-OAA-A-13-00070), which is directed by TJC. The funding entities had no role in the design of the study, collection, analysis and interpretation of data, or in writing the manuscript.info:eu-repo/semantics/publishedVersio

A low-cost HPV immunochromatographic assay to detect high-grade cervical intraepithelial neoplasia

Objective To evaluate the reproducibility and accuracy of the HPV16/18-E6 test. Methods The study population was comprised of 448 women with a previously abnormal Pap who were referred to the Barretos Cancer Hospital (Brazil) for diagnosis and treatment. Two cervical samples were collected immediately before colposcopy, one for the hr-HPV-DNA test and cytology and the other for the HPV16/18-E6 test using high-affinity monoclonal antibodies (mAb). Women with a histologic diagnosis of cervical intraepithelial neoplasia grade 2 or 3 were considered to be positive cases. Different strategies using a combination of screening methods (HPV-DNA) and triage tests (cytology and HPV16/18-E6) were also examined and compared. Results The HPV16/18-E6 test exhibited a lower positivity rate compared with the HPV-DNA test (19.0% vs. 29.3%, p<0.001) and a moderate/high agreement (kappa = 0.68, 95% CI: 0.60-0.75). It also exhibited a significantly lower sensitivity for CIN2+ and CIN3+ detection compared to the HPV-DNA test and a significantly higher specificity. The HPV16/18-E6 test was no different from cytology in terms of sensitivity, but it exhibited a significantly higher specificity in comparison to ASCH+. A triage test after HPV-DNA detection using the HPV16/18-E6 test exhibited a significantly higher specificity compared with a triage test of ASCH+ to CIN2+ (91.8% vs. 87.4%, p = 0.04) and CIN3+ (88.6% vs. 84.0%, p = 0.05). Conclusion The HPV16/18-E6 test exhibited moderate/high agreement with the HPV-DNA test but lower sensitivity and higher specificity for the detection of CIN2+ and CIN3+. In addition, its performance was quite similar to cytology, but because of the structural design addressed for the detection of HPV16/18-E6 protein, the test can miss some CIN2/3+ lesions caused by other high-risk HPV types.Cancer Prevention Department, Center for the Researcher Support and Pathology Department of the Barretos Cancer Hospital. This study was supported by CNPq 573799/2008-3 and FAPESP 2008/57889-1info:eu-repo/semantics/publishedVersio

Background matching in the brown shrimp Crangon crangon : adaptive camouflage and behavioural-plasticity

A combination of burrowing behaviour and very efficient background matching makes the brown shrimp Crangon crangon almost invisible to potential predators and preys. This raises questions on how shrimp succeed in concealing themselves in the heterogeneous and dynamic estuarine habitats they inhabit and what type of environmental variables and behavioural factors affect their colour change abilities. Using a series of behavioural experiments, we show that the brown shrimp is capable of repeated fast colour adaptations (20% change in dark pigment cover within one hour) and that its background matching ability is mainly influenced by illumination and sediment colour. Novel insights are provided on the occurrence of non-adaptive (possibly stress) responses to background changes after long-time exposure to a constant background colour or during unfavourable conditions for burying. Shrimp showed high levels of intra- and inter-individual variation, demonstrating a complex balance between behavioural-plasticity and environmental adaptation. As such, the study of crustacean colour changes represents a valuable opportunity to investigate colour adaptations in dynamic habitats and can help us to identify the mayor environmental and behavioural factors influencing the evolution of animal background matching

Guidelines of the Brazilian Association of Studies on Alcohol and Other Drugs (ABEAD) for diagnoses and treatment of psychiatric comorbidity with alcohol and other drugs dependence

Recently, several studies have focused on comorbity psychiatric disorders with alcohol and other substance dependence. The Brazilian Association of Studies on Alcohol and Other Drugs proposed the Brazilian Guidelines project. This study review diagnostic and therapeutic criteria to the most prevalent psychiatric comorbidities. Randomized clinical trials, epidemiological, animal studies and other forms of research are reviewed. The main psychiatric comorbidities are studied based on guidelines adopted by other countries and the literature data resumed. Epidemiological aspects, diagnoses, integrated treatment and service organization, as well as specific psychotherapic and pharmacological treatment are discussed. The Brazilian Association of Studies on Alcohol and Other Drugs Guidelines reassures the importance of adequate diagnoses and treatment regarding alcoholic and drug dependent patients suffering of comorbid psychiatric disorders.O diagnóstico e tratamento de comorbidade psiquiátrica e dependência de álcool e outras substâncias tem sido objeto de inúmeros estudos nos últimos anos. A Associação Brasileira de Estudos do Álcool e Outras Drogas desenvolveu o projeto Diretrizes. Este trabalho visa o desenvolvimento de critérios diagnósticos e terapêuticos atualizados para as comorbidades psiquiátricas mais prevalentes. Ensaios clínicos randomizados, estudos epidemiológicos, com animais e outros estudos são revisados. As principais comorbidades psiquiátricas são estudadas e os dados de literatura resumidos, tendo como referência diretrizes adotadas em outros países. São abordados aspectos epidemiológicos, critérios diagnósticos, tratamento integrado e organização de serviço especializado, assim como especificidades do tratamento psicoterápico e farmacológico. As Diretrizes da Associação Brasileira de Estudos do Álcool e Outras Drogas reforçam a importância da abordagem adequada do dependente químico portador de comorbidade psiquiátrica.Universidade Federal de Santa Catarina Núcleo de PsiquiatriaInstituto de Psiquiatria de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP) Unidade de Pesquisa em Álcool e DrogasSanta Casa de Misericórdia de São Paulo Unidade de Álcool e DrogasUniversidade de São Paulo Faculdade de Medicina Hospital das ClinicasCentro de Atendimento Médico e SocialHospital de Clínicas de Porto AlegreHospital Israelita Albert EinsteinSanta Casa do Rio de Janeiro Setor de Dependência QuímicaUniversidade Gama FilhoUNIFESP, Unidade de Pesquisa em Álcool e DrogasSciEL

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta