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

Rapid Phenotype-Driven Gene Sequencing with the NeoSeq Panel: A Diagnostic Tool for Critically Ill Newborns with Suspected Genetic Disease

New genomic sequencing techniques have shown considerable promise in the field of neonatology, increasing the diagnostic rate and reducing time to diagnosis. However, several obstacles have hindered the incorporation of this technology into routine clinical practice. We prospectively evaluated the diagnostic rate and diagnostic turnaround time achieved in newborns with suspected genetic diseases using a rapid phenotype-driven gene panel (NeoSeq) containing 1870 genes implicated in congenital malformations and neurological and metabolic disorders of early onset (<2 months of age). Of the 33 newborns recruited, a genomic diagnosis was established for 13 (39.4%) patients (median diagnostic turnaround time, 7.5 days), resulting in clinical management changes in 10 (76.9%) patients. An analysis of 12 previous prospective massive sequencing studies (whole genome (WGS), whole exome (WES), and clinical exome (CES) sequencing) in newborns admitted to neonatal intensive care units (NICUs) with suspected genetic disorders revealed a comparable median diagnostic rate (37.2%), but a higher median diagnostic turnaround time (22.3 days) than that obtained with NeoSeq. Our phenotype-driven gene panel, which is specific for genetic diseases in critically ill newborns is an affordable alternative to WGS and WES that offers comparable diagnostic efficacy, supporting its implementation as a first-tier genetic test in NICUs

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

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

The central engine of GRB 130831A and the energy breakdown of a relativistic explosion

Gamma-ray bursts (GRBs) are the most luminous explosions in the universe, yet the nature and physical properties of their energy sources are far from understood. Very important clues, however, can be inferred by studying the afterglows of these events. We present optical and X-ray observations of GRB 130831A obtained by Swift, Chandra, Skynet, RATIR, Maidanak, ISON, NOT, LT and GTC. This burst shows a steep drop in the X-ray light-curve at $\simeq 10^5$ s after the trigger, with a power-law decay index of $\alpha \sim 6$. Such a rare behaviour cannot be explained by the standard forward shock (FS) model and indicates that the emission, up to the fast decay at $10^5$ s, must be of "internal origin", produced by a dissipation process within an ultrarelativistic outflow. We propose that the source of such an outflow, which must produce the X-ray flux for $\simeq 1$ day in the cosmological rest frame, is a newly born magnetar or black hole. After the drop, the faint X-ray afterglow continues with a much shallower decay. The optical emission, on the other hand, shows no break across the X-ray steep decrease, and the late-time decays of both the X-ray and optical are consistent. Using both the X-ray and optical data, we show that the emission after $\simeq 10^5$ s can be explained well by the FS model. We model our data to derive the kinetic energy of the ejecta and thus measure the efficiency of the central engine of a GRB with emission of internal origin visible for a long time. Furthermore, we break down the energy budget of this GRB into the prompt emission, the late internal dissipation, the kinetic energy of the relativistic ejecta, and compare it with the energy of the associated supernova, SN 2013fu.Comment: Accepted for publication by MNRAS. 21 pages, 3 figures, 8 tables. Extra table with magnitudes in the sourc

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