Short communication: Genetic parameters for post-weaning visual scores and reproductive traits in Suffolk sheep

          The aim of this study was to estimate the coefficients of heritability and genetic correlations among visual scores (conformation, CPW; precocity, PPW; musculature, MPW) and reproductive traits: age at first lambing (AFL) and scrotal circumference (SC) evaluated at 180 days of age in Suffolk lambs. In the statistical model only the additive genetic effect was considered as random effect. The heritability estimates by univariate analyses for CPW, PPW, MPW, AFL and SC were 0.08, 0.12, 0.09, 0.20 and 0.22, respectively. The genetic correlations among AFL and CPW, PPW, MPW were -0.26, 0.19, and 0.08, respectively. The genetic correlation among SC and CPW, PPW, MPW were, respectively, 0.54, 0.88 and 0.86, and between AFL and SC was 0.26. The direct selection for conformation, precocity and musculature at 180 days of age and age at first lambing will provide slow genetic progress due to low heritability estimates. It is possible to obtain genetic gain in sexual precocity through selection on scrotal circumference in Suffolk rams. The favorable genetic correlation among visual scores and SC and between CPW and AFL, indicated the possibility to gain in genetic progress for reproductive traits through indirect selection of the visual scores in Suffolk sheep

The challenges of clinical trials in fragile X syndrome

RATIONALE: Advances in understanding the underlying mechanisms of conditions such as fragile X syndrome (FXS) and autism spectrum disorders have revealed heterogeneous populations. Recent trials of novel FXS therapies have highlighted several challenges including subpopulations with possibly differential therapeutic responses, the lack of specific outcome measures capturing the full range of improvements of patients with FXS, and a lack of biomarkers that can track whether a specific mechanism is responsive to a new drug and whether the response correlates with clinical improvement. OBJECTIVES: We review the phenotypic heterogeneity of FXS and the implications for clinical research in FXS and other neurodevelopmental disorders. RESULTS: Residual levels of fragile X mental retardation protein (FMRP) expression explain in part the heterogeneity in the FXS phenotype; studies indicate a correlation with both cognitive and behavioral deficits. However, this does not fully explain the extent of phenotypic variance observed or the variability of drug response. Post hoc analyses of studies involving the selective mGluR5 antagonist mavoglurant and the GABAB agonist arbaclofen have uncovered significant therapeutic responses following patient stratification according to FMR1 promoter methylation patterns or baseline severity of social withdrawal, respectively. Future studies designed to quantify disease modification will need to develop new strategies to track changes effectively over time and in multiple symptom domains. CONCLUSION: Appropriate selection of patients and outcome measures is central to optimizing future clinical investigations of these complex disorders

Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects.

Pelizaeus-Merzbacher Disease is an X-linked hypomyelinatiing leukodystrophy. We report mutations in the thyroid hormone transporter gene MCT8 in 11% of 53 families affected by hypomyelinating leukodystrophies of unknown aetiology. The 12 MCT8 mutated patients express initially a Pelizaeus-Merzbacher-Like disease phenotype with a latter unusual improvement of magnetic resonance imaging white matter signal despite absence of clinical progression. This observation underlines the interest of determining both free T3 and free T4 serum concentrations to screen for MCT8 mutations in young patients (<3 y) with a severe Pelizaeus-Merzbacher-Like disease presentation or older severe mentally retarded male patients with "hypomyelinated" regions

Classificação de touros Nelore em função de diferentes índices bioeconômicos de seleção.

O objetivo deste trabalho foi comparar a classificação de touros da raça Nelore em função de três índices bioeconômicos de seleção, além do índice de qualificação genética (IQG). Foi utilizado o banco histórico de avaliações genéticas concedido pela Embrapa Pantanal (2020), contendo 865 touros nascidos entre 1955 e 2014. Os três índices bioeconômicos de seleção utilizados consideraram características de produção, reprodução e de qualidade de carcaça. As ponderações para os critérios de seleção foram estimadas considerando o mesmo objetivo de seleção, porém para diferentes medidas de avaliação econômica utilizadas na pecuária, resultando em valores econômicos expressos com base nas avaliações: por animal (VACA), por Arroba (@) e por Unidade Animal (UA) (Portes et al., 2021). As correlações de Spearman foram altas entre os índices VACA e UA (1,0), IQG e @ (0,86), sugerindo ordenamento semelhante dos touros, e moderadas entre IQG e VACA (0,64) e UA (0,64) e entre @ e VACA (0,57) e UA (0,57), indicando reordenação dos touros. Apenas o índice arroba (@) resultará em ordem semelhante de classificação dos touros ao IQG que é o índice usualmente utilizado pelo programa de melhoramento de gado de corte - Embrapa Geneplus

Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution

Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs

Social networks and labour productivity in Europe: An empirical investigation

This paper uses firm-level data recorded in the AMADEUS database to investigate the distribution of labour productivity in different European countries. We find that the upper tail of the empirical productivity distributions follows a decaying power-law, whose exponent $\alpha$ is obtained by a semi-parametric estimation technique recently developed by Clementi et al. (2006). The emergence of "fat tails" in productivity distribution has already been detected in Di Matteo et al. (2005) and explained by means of a model of social network. Here we show that this model is tested on a broader sample of countries having different patterns of social network structure. These different social attitudes, measured using a social capital indicator, reflect in the power-law exponent estimates, verifying in this way the existence of linkages among firms' productivity performance and social network.Comment: LaTeX2e; 18 pages with 3 figures; Journal of Economic Interaction and Coordination, in pres

Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma is a severe pediatric tumor, histologically characterised by a variety of cellular phenotypes. One of the pharmacological approaches to neuroblastoma is the treatment with retinoic acid. The mechanism of action of retinoic acid is still unclear, and the development of resistance to this differentiating agent is a great therapy problem.</p> <p>Doublecortin, a microtubule-associated protein involved in neuronal migration, has recently been proposed as a molecular marker for the detection of minimal residual disease in human neuroblastoma. Nevertheless, no information is available on the expression of doublecortin in the different cell-types composing human neuroblastoma, its correlation with neuroblastoma cell motility and invasiveness, and the possible modulations exerted by retinoic acid treatment.</p> <p>Methods</p> <p>We analysed by immunofluorescence and by Western blot analysis the presence of doublecortin, lissencephaly-1 (another protein involved in neuronal migration) and of two intermediate filaments proteins, vimentin and neurofilament-68, in SK-N-SH human neuroblastoma cell line both in control conditions and under retinoic acid treatment. Migration and cell invasiveness studies were performed by wound scratch test and a modified microchemotaxis assay, respectively.</p> <p>Results</p> <p>Doublecortin is expressed in two cell subtypes considered to be the more aggressive and that show high migration capability and invasiveness.</p> <p>Vimentin expression is excluded by these cells, while lissencephaly-1 and neurofilaments-68 are immunodetected in all the cell subtypes of the SK-N-SH cell line. Treatment with retinoic acid reduces cell migration and invasiveness, down regulates doublecortin and lissencephaly-1 expression and up regulates neurofilament-68 expression. However, some cells that escape from retinoic acid action maintain migration capability and invasiveness and express doublecortin.</p> <p>Conclusion</p> <p>a) Doublecortin is expressed in human neuroblastoma cells that show high motility and invasiveness;</p> <p>b) Retinoic acid treatment reduces migration and invasiveness of the more aggressive cell components of SK-N-SH cells;</p> <p>c) The cells that after retinoic acid exposure show migration and invasive capability may be identified on the basis of doublecortin expression.</p

The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.&lt;p&gt;&lt;/p&gt; Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.&lt;p&gt;&lt;/p&gt; Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.&lt;p&gt;&lt;/p&gt; Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.&lt;p&gt;&lt;/p&gt

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors