Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.Portuguese Fundacao para Ciencia e Tecnologia (FCT) [PTDC/EXPL/MARBIO/0430/2013]; CCMAR FCT Plurianual financing [UID/Multi/04326/2013]; FCT [SFRH/BD/111226/2015, SFRH/BD/108842/2015, SFRH/BPD/89889/2012]; FCT-IF Starting Grant [IF/01274/2014]info:eu-repo/semantics/publishedVersio

Finite temperature stability and dimensional crossover of exotic superfluidity in lattices

We investigate exotic paired states of spin-imbalanced Fermi gases in anisotropic lattices, tuning the dimension between one and three. We calculate the finite temperature phase diagram of the system using real-space dynamical mean-field theory in combination with the quantum Monte Carlo method. We find that regardless of the intermediate dimensions examined, the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state survives to reach about one third of the BCS critical temperature of the spin-density balanced case. We show how the gapless nature of the state found is reflected in the local spectral function. While the FFLO state is found at a wide range of polarizations at low temperatures across the dimensional crossover, with increasing temperature we find out strongly dimensionality-dependent melting characteristics of shell structures related to harmonic confinement. Moreover, we show that intermediate dimension can help to stabilize an extremely uniform finite temperature FFLO state despite the presence of harmonic confinement.Comment: 5 pages, 3 figure

Identifying and prioritizing strategies for comprehensive liver cancer control in Asia

<p>Abstract</p> <p>Background</p> <p>Liver cancer is both common and burdensome in Asia. Effective liver cancer control, however, is hindered by a complex etiology and a lack of coordination across clinical disciplines. We sought to identify strategies for inclusion in a comprehensive liver cancer control for Asia and to compare qualitative and quantitative methods for prioritization.</p> <p>Methods</p> <p>Qualitative interviews (N = 20) with international liver cancer experts were used to identify strategies using Interpretative Phenomenological Analysis and to formulate an initial prioritization through frequency analysis. Conjoint analysis, a quantitative stated-preference method, was then applied among Asian liver cancer experts (N = 20) who completed 12 choice tasks that divided these strategies into two mutually exclusive and exhaustive subsets. Respondents' preferred plan was the primary outcome in a choice model, estimated using ordinary least squares (OLS) and logistic regression. Priorities were then compared using Spearman's Rho.</p> <p>Results</p> <p>Eleven strategies were identified: <it>Access to treatments; Centers of excellence; Clinical education; Measuring social burden; Monitoring of at-risk populations; Multidisciplinary management; National guidelines; Public awareness; Research infrastructure; Risk-assessment and referral</it>; and <it>Transplantation infrastructure</it>. Qualitative frequency analysis indicated that <it>Risk-assessment and referral </it>(85%), <it>National guidelines </it>(80%) and <it>Monitoring of at-risk populations </it>(80%) received the highest priority, while conjoint analysis pointed to <it>Monitoring of at-risk populations </it>(p < 0.001), <it>Centers of excellence </it>(p = 0.002), and <it>Access to treatments </it>(p = 0.004) as priorities, while <it>Risk-assessment and referral </it>was the lowest priority (p = 0.645). We find moderate concordance between the qualitative and quantitative methods (rho = 0.20), albeit insignificant (p = 0.554), and a strong concordance between the OLS and logistic regressions (rho = 0.979; p < 0.0001).</p> <p>Conclusions</p> <p>Identified strategies can be conceptualized as the ABCs of comprehensive liver cancer control as they focus on <it>Antecedents</it>, <it>Better care </it>and <it>Connections </it>within a national strategy. Some concordance was found between the qualitative and quantitative methods (e.g. <it>Monitoring of at-risk populations</it>), but substantial differences were also identified (e.g. qualitative methods gave highest priority to risk-assessment and referral, but it was the lowest for the quantitative methods), which may be attributed to differences between the methods and study populations, and potential framing effects in choice tasks. Continued research will provide more generalizable estimates of priorities and account for variation across stakeholders and countries.</p

Abiotic ammonium formation in the presence of Ni-Fe metals and alloys and its implications for the Hadean nitrogen cycle

Experiments with dinitrogen-, nitrite-, nitrate-containing solutions were conducted without headspace in Ti reactors (200°C), borosilicate septum bottles (70°C) and HDPE tubes (22°C) in the presence of Fe and Ni metal, awaruite (Ni80Fe20) and tetrataenite (Ni50Fe50). In general, metals used in this investigation were more reactive than alloys toward all investigated nitrogen species. Nitrite and nitrate were converted to ammonium more rapidly than dinitrogen, and the reduction process had a strong temperature dependence. We concluded from our experimental observations that Hadean submarine hydrothermal systems could have supplied significant quantities of ammonium for reactions that are generally associated with prebiotic synthesis, especially in localized environments. Several natural meteorites (octahedrites) were found to contain up to 22 ppm Ntot. While the oxidation state of N in the octahedrites was not determined, XPS analysis of metals and alloys used in the study shows that N is likely present as nitride (N3-). This observation may have implications toward the Hadean environment, since, terrestrial (e.g., oceanic) ammonium production may have been supplemented by reduced nitrogen delivered by metal-rich meteorites. This notion is based on the fact that nitrogen dissolves into metallic melts

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

Expression of phosphorylated eukaryotic initiation factor 2 alpha in neuronal apoptosis beta-amyloid toxicity

Inhibition of protein synthesis has been demonstrated in experimental ischemia. Increasing lines of evidence show that inhibiting protein translation results in apoptosis. Translation of protein is initiated by binding of initiator Met-tRNA to the 40S ribosomal subunit, which subsequently joins the 60S ribosomal subunit by hydrolyzing the GTP into GDP. The eukaryotic initiation factor 2 alpha (eIF2a)-GDP complex is released in exchange for GTP. Phosphorylation of eIF2a blocks the exchange of GTP and shutdowns protein synthesis leading to apoptosis. Since apoptosis of neurons is considered to be the one of death pathways in Alzheimer's disease (AD), this study aims to investigate whether phosphorylation of eIF2a is the key-signaling pathway leading to neuronal apoptosis in AD. Human neuroblastoma SH-SY5Y cells treated with the calcium ionophore A23187 underwent apoptosis, as reported by other laboratories. Early after treatment of A23187, phosphorylation of eIF2a was markedly increased. Flavonoids such as genistein and quercetin suppress tumor growth by inhibiting protein synthesis. Treatment of cells with both drugs induced a marked increase in eIF2a phosphorylation. Condensation and disintegration of DNA in cells shown by nuclear staining were found after 24 h. Furthermore, cells treated with b-amyloid peptide (Ab25-35) led to phosphorylation of eIF2a, and eventually resulted in apoptosis. Taken together, the results suggest that phosphorylation of eIF2a may be a key molecular pathway leading the neuronal apoptosis. Elucidation of this pathway may reshape the therapeutic interventions against AD. Supported by Research Grant Council, Hong Kong SA

Paths in the conformational space of biopolymers

This lecture will start with a survey of the present state of knowledge on the topology of potential hypersurfaces of proteins, on transitions in conformational space, and on harmonic and quasi-harmonic methods of computation of thermodynamic and kinetic quantities. The concepts of deterministics vs ergodic behaviour and of kinetic vs thermodynamic control will be discussed. More specifically, the possible connection between selectivity (or "accuracy") in enzyme catalysis and the time structure of conformational transitions will be shown, indicating the functional advantage of an unique path consisting of a sequence of transitions between substates.In a second part, two different methods used by the authors for theoretical computation of conformational paths in citrate synthase (1) will be commented, as well as the main features of the paths obtained (2). The picture which emerges from this study is that of sinuous conformational paths with essentially constant energy. A hint on the transition time will be given.Finally, in connection with the "multiple minima problem", the occurrence of lower and upper bounds in the temperatures used in molecular dynamics searches of conformational minima will be discussed with emphasis on their dependence with respect to the problem under consideration (structure refinement or path determination) and to the imposition of constraints on the conformational space investigated