Genetic correlations estimate between meat tenderness, growth and carcass traits in a population of polled nellore cattle in Brazil.

Growth, carcass and tenderness data from 415 Polled Nellore animals were analyzed in order to estimate the genetic correlations between tenderness (WBSF) and growth (ILW, FLW and ADG) and carcass (BF, RF and LMA) traits. The covariance components and genetic parameters were estimated using the Gibbs Sampling method. The heritability estimated for WBSF was of low magnitude (0.11 ± 0.022). The genetic correlations between WBSF and the other traits were of low magnitude, with values of - 0.15; -0.18; -0.13; 0.10; -0.12 and 0.18, between WBSF and ILW, FLW, ADG, BF, RF and LMA, respectively. The results support the conclusion that selection for improved tenderness will not affect genetic progress in other economic traits and vice-versa, but more studies are required for a better knowledge of the genetic relationships between meat tenderness and other traits for Polled Nellore cattle

Análise multivariada das interrelações entre a característica de maciez da carne e características de crescimento e carcaça de bovinos da raça Nelore Mocho.

Objetivou-se com este estudo, analisar os interrelacionamentos fenotípicos entre as características de maciez (WBSF), crescimento (PI, PF e GPD) e carcaça (EG, P8 e AOL) de bovinos da raça Nelore Mocho. Foram utilizados dados do Programa OB Choice da Guaporé Agropecuária. Para análises de relacionamentos fenotípicos foram realizadas análises de fatores e correlações canônicas, utilizando o software SAS. Observou-se ausência de correlações fenotípicas entre o WBSF e as outras características produtivas avaliadas que obtiveram valores não significativos de -0,02, -0,08, -0,06, -0,03, -0,03 e -0,10 entre WBSF e PI, PF, GPD, EG, P8 e AOL, respectivamente. Esses resultados sugerem que, a seleção para a maciez não influenciará na seleção de outras características de interesse econômico e vice-versa. São necessários mais estudos para um melhor conhecimento sobre as relações genéticas de WBSF e outras características produtivas em bovinos da raça Nelore Mocho

Using Green Fluorescent Protein to Correlate Temperature and Fluorescence Intensity into Bacterial Systems

The unique and stunning spectroscopic properties of Green Fluorescent Protein (GFP) from the jellyfish Aequorea victoria, not to mention of its remarkable structural stability, have made it one of the most widely studied and used molecular tool in medicine, biochemistry, and cell biology. Its high fluorescent quantum yield is due to its chromophore, structure responsible of emitting green visible light when excited at 395 nm. Although it is noteworthy that there is enormous available information of the wonderful luminescent properties of GFP, the fact is that there are features and properties unexplored yet, particulary about its capabilities as molecular reporter in several biological processes. In this work, we used recombinant DNA technology to express the protein in bacteria; prepared the bacterial system both in liquid and solid media, and assembled an experimental set to expose those media to a laser beam; thereby we excited the protein chromophore and used emission spectroscopy in order to observe variations in fluorescence when the bacterial system is exposed to different temperatures

Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice

© 2015 Abdelraouf et al.Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC. Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently. Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features. Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC

Investigating the potential clinical benefit of Selumetinib in resensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy (SEL-I-METRY): protocol for a multicentre UK single arm phase II trial

Background Thyroid cancer is the most common endocrine malignancy. Some advanced disease is, or becomes, resistant to radioactive iodine therapy (refractory disease); this holds poor prognosis of 10% 10-year overall survival. Whilst Sorafenib and Lenvatinib are now licenced for the treatment of progressive iodine refractory thyroid cancer, these treatments require continuing treatment and can be associated with significant toxicity. Evidence from a pilot study has demonstrated feasibility of Selumetinib to allow the reintroduction of I-131 therapy; this larger, multicentre study is required to demonstrate the broader clinical impact of this approach before progression to a confirmatory trial. Methods SEL-I-METRY is a UK, single-arm, multi-centre, two-stage phase II trial. Participants with locally advanced or metastatic differentiated thyroid cancer with at least one measureable lesion and iodine refractory disease will be recruited from 8 NHS Hospitals and treated with 4-weeks of oral Selumetinib and assessed for sufficient I-123 uptake (defined as any uptake in a lesion with no previous uptake or 30% or greater increase in uptake). Those with sufficient uptake will be treated with I-131 and followed for clinical outcomes. Radiation absorbed doses will be predicted from I-123 SPECT/CT and verified from scans following the therapy. 60 patients will be recruited to assess the primary objective of whether the treatment schedule leads to increased progression-free survival compared to historical control data. Discussion The SEL-I-METRY trial will investigate the effect of Selumetinib followed by I-131 therapy on progression-free survival in radioiodine refractory patients with differentiated thyroid cancer showing increased radioiodine uptake following initial treatment with Selumetinib. In addition, information on toxicity and dosimetry will be collected. This study presents an unprecedented opportunity to investigate the role of lesional dosimetry in molecular radiotherapy, leading to greater personalisation of therapy. To date this has been a neglected area of research. The findings of this trial will be useful to healthcare professionals and patients alike to determine whether further study of this agent is warranted. It is hoped that the development of the infrastructure to deliver a multicentre trial involving molecular radiotherapy dosimetry will lead to further trials in this field. Trial registration SEL-I-METRY is registered under ISRCTN17468602, 02/12/2015

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

© 2015 Pender et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogenedriven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCRddPCRMutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma

Assessment of the psychosocial and economic impact according to sex in non-small cell lung cancer patients: an exploratory longitudinal study

Background: Little is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers. Methods: Exploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI. Results: 333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. Conclusions: This study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex. Trial registration: ClinicalTrials.gov identifier: NCT02336061. Ethics committee: Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705

New constraints on protostellar jet collimation from high-density gas UV tracers

The analysis of high-resolution profiles of the semiforbidden UV lines of C III](1908) and Si III](1892) in the spectra of T Tauri stars (TTSs) shows the following : (1) There is C III](1908) and Si III](1892) emission at velocities that are similar to those observed in the optical forbidden lines formed in the TTSs jets. The luminosity of the UV lines is comparable to that of the optical lines. (2) The comparison between the optical and UV light curves indicates that the C III](1908) and Si III](1892) emission of RY Tau is not associated with accretion shocks, but it is produced farther than 2 R-* from the star. (3) The profiles of the UV semiforbidden lines are significantly broader than those of the optical forbidden lines. These profiles cannot be produced in a narrow collimated beam, and they are most likely produced in a bow-shaped shock wave formed at the base of the optical jet, where the hot gas emits in a broad range of projected radial velocities. (4) The atmosphere of RU Lup contributes significantly to the Si III](1892) emission. (5) A puzzling narrow feature is observed close to the C III](1908) line. The feature is blueshifted by -260 km s(-1), which corresponds to the wind terminal velocity measured in the P Cygni profile of the Mg II (UV1) lines. Moreover, constraints are derived on the characteristics of the C III](1908) and Si III](1892) emitting region in RY Tau. It is shown that 4.7 less than or equal to log T-e less than or equal to 5.0 and 10(9) cm(-3) less than or equal to N-e less than or equal to 10(11) cm(-3) provided that the emission is produced in a collisional plasma and that the 1665 Angstrom feature observed in low-dispersion International Ultraviolet Explorer (IUE) spectra is confirmed to be O III](1665) emission produced in the wind. These very high densities are difficult to generate in the shocks produced by the magnetic pinching of centrifugally driven magnetized disk winds. The data also suggest that the shocked layer has a radius of some few stellar radii and it is closer than similar to 38 R-* to the star

Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer

Altres ajuts: This work was co-finaced by the European Development Regional Fund, "A way to achieve Europe" ERDF; the Cellex Foundation; and "la Caixa" Banking Foundation (LCF/PR/PR15/ 11100003).Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion

Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

Telomere erosion and fusion play an important role in the pathology of many common human malignancies including CLL.1,2 Previous studies in CLL have shown that short telomeres defined on the basis of the median value or receiver operating characteristic (ROC) analysis are associated with unmutated IGHV genes, poor risk genomic abnormalities, genomic complexity and high expression of CD38, CD49d, and ZAP70 whereas long telomeres are associated with increasing IGHV mutational load, isolated deletion of 13q and low CD49d expression. In addition, in predominantly diagnostic or mixed patient cohorts, telomere length (TL) predicts time to first treatment and/or overall survival (OS) in multivariate analyses of models incorporating established biomarkers. 3-7 However uncertainties about the most clinically relevant measure of telomere length, the optimal choice of assay, the need for assay standardisation and the lack of published data on the prognostic value of TL in patients entered into randomised trials have hindered the implementation of TL measurement into routine clinical practice. We have attempted to address these issues by measuring telomere length using monochrome multiplex Q-PCR (MMQ-PCR) in 384 patients at randomisation into the UK LRF CLL4 phase 3 chemotherapy trial (Table S1), of whom 111 samples were also screened by single telomer