Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

<p>Abstract</p> <p>Background</p> <p>The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish <it>cyclops </it>(<it>cyc</it>) mutants lack ventral brain, including the region that gives rise to the SCN. We have used <it>cyc </it>embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression.</p> <p>Results</p> <p>We find that pineal rhythms are present in <it>cyc </it>mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin) is a peptide hormone expressed in and around the SCN. We find <it>avpl </it>mRNA is absent in <it>cyc </it>mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, <it>cryptochrome 1b (cry1b) </it>and <it>cryptochrome 3 (cry3)</it>, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, <it>exo-rhodopsin </it>(<it>exorh) </it>and <it>serotonin-N-acetyltransferase </it>(<it>aanat2</it>), involved in photoreception and melatonin synthesis, respectively, is also similar between <it>cyc </it>embryos and their wildtype (WT) siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in <it>cyc </it>embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in <it>cyc </it>mutants kept in constant conditions decreased more quickly than in their WT siblings.</p> <p>Conclusion</p> <p>Our data suggests that circadian rhythms can be initiated and maintained in the absence of SCN and other tissues in the ventral brain. However, the SCN may have a role in regulating the amplitude of rhythms when environmental cues are absent. This provides some of the first evidence that the SCN of teleosts is not essential for establishing circadian rhythms during development. Several SCN-independent circadian rhythms have also been found in mammalian species. Thus, zebrafish may serve as a model system for understanding how vertebrate embryos coordinate rhythms that are controlled by different circadian clocks.</p

PRAJA is overexpressed in glioblastoma and contributes to neural precursor development

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the developing brain through loss of function studies, using morpholinos targeting Praja1 in embryonic zebrafish, and observed that Praja1 is expressed prominently in regions enriched with neural precursor cell subtypes. Antisense Praja morpholinos resulted in multiple embryonic defects including delayed neural development likely through increased apoptosis. Further studies revealed high levels of Cdk1 with loss of Praja1 in TGF-β or insulin treated cells, supporting the link between Praja1 and cell cycle regulation. In summary, these studies underscore Praja\u27s role in mammalian brain development and Praja1 deregulation may lead to gliomas possibly through the regulation of cell cycle and/or apoptosis

Concert recording 2018-04-08c

[Track 1]. Revolutions. Groove machine [Track 2]. Black / Marc Mellits -- [Track 3]. Adagio and allegro / G.F. Handel -- [Track 4]. Sonata. Allegro / Lawson Lunde -- [Track 5]. American quartet. Allegro ma non troppo / Antonin Dvořák -- [Track 6]. Spain / Chick Corea arranged by Eddie Jennings -- [Track 7]. First suite in E♭. Chaconne Intermezzo March / Gustav Holst

Salt consumption awareness in Portugal: comparison between the ECOS surveys of 2014 and 2018

O consumo excessivo de sal aumenta o risco de doenças crónicas, pelo que a sensibilização da população é uma medida recomendada pela Organização Mundial de Saúde (OMS) e pela Direção-Geral da Saúde (DGS) para a diminuição do seu consumo. O objetivo deste estudo foi estimar a prevalência relativa à preocupação com o consumo de sal, em 2014 e 2018 em Portugal, avaliar a sua evolução e caracterizar o perfil sociodemográfico dos participantes que manifestaram preocupação com o consumo de sal nos dois anos em análise. Os dados foram recolhidos no âmbito do inquérito telefónico ECOS (Em Casa Observamos Saúde) para esses anos. Em 2014, 77% dos inquiridos referiram ter preocupação quanto ao consumo de sal face a 75% em 2018. Em ambos os anos, as mulheres revelaram uma maior preocupação quanto ao consumo de sal, comparativamente ao sexo masculino, embora essa diferença fosse mais evidente em 2014. Adicionalmente, verificou-se que a preocupação com o consumo de sal aumenta com a idade, sendo o grupo etário com mais de 65 anos o que registou uma maior preocupação relativamente ao consumo do sal, nos dois anos em análise. Não se observaram diferenças estatisticamente significativas entre os níveis de escolaridade ou as regiões.Excessive salt consumption increases the risk of chronic diseases. Thus raising awareness is a measure to reduce its consumption, recommended by the World Health Organization (WHO) and the Portuguese Directorate General of Health. The aim of this study was to estimate the prevalence of individuals who reported awareness regarding their salt consumption in 2014 and 2018, and to investigate its distribution among several sociodemographic characteristics. Data was collected by means of a national representative panel telephonic survey, ECOS. In 2014, 77% of respondents reported watching or reducing salt consumption, compared to 75% in 2018, but this difference between years was not significant. In both years, women were more aware of salt intake than men, although this difference was more significant in 2014. Additionally, awareness regarding salt consumption increased with age, with the age group over 65 years old being the most aware, in the two years under analysis. No statistically significant differences were found among the different educational level groups, or regions.info:eu-repo/semantics/publishedVersio

Concert recording 2017-04-26

[Track 1]. Fantazia / Orlando Gibbons arranged by Fred Hemke -- [Track 2-3]. Quartette (Allegro de concert) / Caryl Florio -- [Track 4]. O magnum mysterium / Morten Lauridsen arranged by Chase Shumsky -- [Track 5]. Petite symphonie. Scherzo / Charles Gounod arranged by Aaron M. Durst -- [Track 6]. Grainger set. Mock Morris / Percy Aldridge Grainger arranged by Gary Bricault -- [Track 7]. Grainger set. Two British folk settings. I. Mo nighean dubh [Track 8]. II. The hunter in his career / Percy Aldridge Grainger arranged by Chalon Ragsdale -- [Track 9]. Molly on the shore / Percy Aldridge Grainger arranged by Jacques Larocque -- [Track 10]. The great gate of Kiev / Modest Mussorgsky and Maurice Ravel arranged by B.L. Bruske

Cost Effectiveness of Internet Interventions: Review and Recommendations

10.1007/s12160-009-9131-6Annals of Behavioral Medicine38140-45ABME

Designing a patient-centered personal health record to promote preventive care

<p>Abstract</p> <p>Background</p> <p>Evidence-based preventive services offer profound health benefits, yet Americans receive only half of indicated care. A variety of government and specialty society policy initiatives are promoting the adoption of information technologies to engage patients in their care, such as personal health records, but current systems may not utilize the technology's full potential.</p> <p>Methods</p> <p>Using a previously described model to make information technology more patient-centered, we developed an interactive preventive health record (IPHR) designed to more deeply engage patients in preventive care and health promotion. We recruited 14 primary care practices to promote the IPHR to all adult patients and sought practice and patient input in designing the IPHR to ensure its usability, salience, and generalizability. The input involved patient usability tests, practice workflow observations, learning collaboratives, and patient feedback. Use of the IPHR was measured using practice appointment and IPHR databases.</p> <p>Results</p> <p>The IPHR that emerged from this process generates tailored patient recommendations based on guidelines from the U.S. Preventive Services Task Force and other organizations. It extracts clinical data from the practices' electronic medical record and obtains health risk assessment information from patients. Clinical content is translated and explained in lay language. Recommendations review the benefits and uncertainties of services and possible actions for patients and clinicians. Embedded in recommendations are self management tools, risk calculators, decision aids, and community resources - selected to match patient's clinical circumstances. Within six months, practices had encouraged 14.4% of patients to use the IPHR (ranging from 1.5% to 28.3% across the 14 practices). Practices successfully incorporated the IPHR into workflow, using it to prepare patients for visits, augment health behavior counseling, explain test results, automatically issue patient reminders for overdue services, prompt clinicians about needed services, and formulate personalized prevention plans.</p> <p>Conclusions</p> <p>The IPHR demonstrates that a patient-centered personal health record that interfaces with the electronic medical record can give patients a high level of individualized guidance and be successfully adopted by busy primary care practices. Further study and refinement are necessary to make information systems even more patient-centered and to demonstrate their impact on care.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00589173">NCT00589173</a></p

Characterization of magnesium requirement of human 5'-tyrosyl DNA phosphodiesterase mediated reaction

<p>Abstract</p> <p>Background</p> <p>Topo-poisons can produce an enzyme-DNA complex linked by a 3'- or 5'-phosphotyrosyl covalent bond. 3'-phosphotyrosyl bonds can be repaired by tyrosyl DNA phosphodiesterase-1 (TDP1), an enzyme known for years, but a complementary human enzyme 5'-tyrosyl DNA phosphodiesterase (hTDP2) that cleaves 5'-phosphotyrosyl bonds has been reported only recently. Although hTDP2 possesses both 3'- and 5'- tyrosyl DNA phosphodiesterase activity, the role of Mg²⁺in its activity was not studied in sufficient details.</p> <p>Results</p> <p>In this study we showed that purified hTDP2 does not exhibit any 5'-phosphotyrosyl phosphodiesterase activity in the absence of Mg²⁺/Mn²⁺, and that neither Zn²⁺or nor Ca²⁺can activate hTDP2. Mg²⁺also controls 3'-phosphotyrosyl activity of TDP2. In MCF-7 cell extracts and de-yolked zebrafish embryo extracts, Mg²⁺controlled 5'-phosphotyrosyl activity. This study also showed that there is an optimal Mg²⁺concentration above which it is inhibitory for hTDP2 activity.</p> <p>Conclusion</p> <p>These results altogether reveal the optimal Mg²⁺requirement in hTDP2 mediated reaction.</p