Developmental and functional effects of steroid hormones on the neuroendocrine axis and spinal cord

This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas.Fil: Zubeldia Brenner, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Roselli, C. E.. Oregon Health and Science University Portland; Estados UnidosFil: Recabarren, S. E.. Universidad de Concepción; ChileFil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lara, H. E.. Universidad de Chile; Chil

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

Assessing visuospatial abilities in healthy aging: a novel visuometor task

Sherpa Romeo green journal: open accessThis study examined the efficacy of a novel reaching-and-grasping task in determining visuospatial abilities across adulthood. The task required male and female young (18–25 years) and older adults (60–82 years) to replicate a series of complex models by locating and retrieving the appropriate building blocks from an array. The task allows visuospatial complexity to be manipulated independently from the visuomotor demands. Mental rotation and spatial visualization abilities were assessed. The results showed that the time taken to complete the tasks increased with increased mental rotation complexity. Patterns of hand use were also influenced by the complexity of the models being constructed with right hand use being greater for the less complex models. In addition, although older adults consistently performed the visuomotor tasks slower than the younger adults, their performance was comparable when expressed as the percent change in task demands. This is suggestive that spatial abilities are preserved in older adults. Given the ecologically validity, the described task is an excellent candidate for investigating: (1) developmental; (2) sex-based; and (3) pathology-based differences in spatial abilities in the visuomotor domain.Ye

Fitting Neutrino Physics with a U(1)_R Lepton Number

We study neutrino physics in the context of a supersymmetric model where a continuous R-symmetry is identified with the total Lepton Number and one sneutrino can thus play the role of the down type Higgs. We show that R-breaking effects communicated to the visible sector by Anomaly Mediation can reproduce neutrino masses and mixing solely via radiative contributions, without requiring any additional degree of freedom. In particular, a relatively large reactor angle (as recently observed by the Daya Bay collaboration) can be accommodated in ample regions of the parameter space. On the contrary, if the R-breaking is communicated to the visible sector by gravitational effects at the Planck scale, additional particles are necessary to accommodate neutrino data.Comment: 19 pages, 3 figures; v2: references added, constraints updated, overall conclusions unchange

Perception of safe horizontal reaching distance changes with repetitive occupational loading in novice lifters

Sherpa Romeo blue journal. Open access article. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) applies.Safe work behaviours rely on accurate perceptions of injury risks, and workers who have a misperception of risk can be injured. Despite the importance of perception-action coupling, little is known about modification of those perceptions with changing physical or cognitive STATE. It is hypothesized that changing values for perceived affordances could evidence these modifications. A better understanding of how worker characteristics (e.g., level of fatigue) affect perceptions of affordance and their corresponding behaviours, may help when developing strategies for ergonomic best practices, particularly in manual material handling (MMH) activities. The aim of this study was to compare safe perceptions of affordance from workers that completed repetitive STATE loading. Seventy-five novice MMH workers (23 male; mean age = 21.43, SD = 3.24) made perceived affordances of their safest horizontal reaching distance (acceptable limit) to complete a model task. STATE loading consisted of physical or cognitive fatigue or a control. The levels of fatigue were assessed at five-minute intervals using Ratings of Perceived Exertion (RPE) values and Multi-Fatigue Inventory (MFI) values, respectively. A significant main effect of TIME indicated a decrease of perceived safest reaching distance observed from baseline through subsequent measurements (p<.001). The magnitude of these changes did not differ significantly between groups, suggesting that general learning more than specific STATE loading may be a major contributor to modification of affordance perceptions. However, it remains important to consider TIME and STATE influences on perceptions for safe occupational handling. Novice workers’ initial perceptions of safe working affordance may put them at risk for soft tissue injury. Physical and cognitive loading similarly affect perceived safe affordances.Ye

A unified multiwavelength model of galaxy formation

We present a new version of the GALFORM semi-analytical model of galaxy formation. This brings together several previous developments of GALFORM into a single unified model, including a different initial mass function (IMF) in quiescent star formation and in starbursts, feedback from active galactic nuclei supressing gas cooling in massive halos, and a new empirical star formation law in galaxy disks based on their molecular gas content. In addition, we have updated the cosmology, introduced a more accurate treatment of dynamical friction acting on satellite galaxies, and updated the stellar population model. The new model is able to simultaneously explain both the observed evolution of the K-band luminosity function and stellar mass function, and the number counts and redshift distribution of sub-mm galaxies selected at 850μm. This was not previously achieved by a single physical model within the ΛCDM framework, but requires having an IMF in starbursts that is somewhat top-heavy. The new model is tested against a wide variety of observational data covering wavelengths from the far-UV to sub-mm, and redshifts from z = 0 to z = 6, and is found to be generally successful. These observations include the optical and near-IR luminosity functions, HI mass function, fraction of early type galaxies, Tully-Fisher, metallicity-luminosity and size-luminosity relations at z = 0, as well as far-IR number counts, and far-UV luminosity functions at z ∼ 3 − 6. Discrepancies are however found in galaxy sizes and metallicities at low luminosities, and in the abundance of low mass galaxies at high-z, suggesting the need for a more sophisticated model of supernova feedback

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance

<p>Abstract</p> <p>Background</p> <p>The prevalence of infections with <it>Mycobacterium tuberculosis </it>(MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the <it>Mycobacterium tuberculosis </it>complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in <it>kat</it>G, <it>rpo</it>B and <it>inh</it>A genes, resulting in isoniazid (INH) and rifampin (RIF) resistance.</p> <p>Results</p> <p>Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as <it>M. bovis</it>, 9 as <it>M. avium </it>and 1 as <it>M. intracellulare</it>. IS<it>6110</it>-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 <it>M. bovis </it>strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG → TCG (Glu → Ser) at codon 469 of <it>rpo</it>B gene.</p> <p>Conclusions</p> <p>This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.</p

Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines.

Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE: Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines