StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs. It is based on careful selection, standardized processing and stringent quality control of relevant transcriptomics datasets to minimize artefacts, and includes currently over 960 transcriptomes covering a broad range of SC types. Each of the integrated datasets was individually inspected and manually curated. StemMapper's user-friendly interface enables fast querying, comparison, and interactive visualization of quality-controlled SC gene expression data in a comprehensive manner. A proof-of-principle analysis discovering novel putative astrocyte/neural SC lineage markers exemplifies the utility of the integrated data resource. We believe that StemMapper can open the way for new insights and advances in SC research by greatly simplifying the access and analysis of SC transcriptomic data. StemMapper is freely accessible at http://stemmapper.sysbiolab.eu

The unfolded protein response and its potential role in Huntington's disease elucidated by a systems biology approach.

Huntington ´s disease (HD) is a progressive, neurodegenerative disease with a fatal outcome. Although the disease-causing gene (huntingtin) has been known for over 20 years, the exact mechanisms leading to neuronal cell death are still controversial. One potential mechanism contributing to the massive loss of neurons observed in the brain of HD patients could be the unfolded protein response (UPR) activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response to counter-balance accumulation of un- or misfolded proteins, the UPR upregulates transcription of chaperones, temporarily attenuates new translation, and activates protein degradation via the proteasome. However, persistent ER stress and an activated UPR can also cause apoptotic cell death. Although different studies have indicated a role for the UPR in HD, the evidence remains inconclusive. Here, we present extensive bioinformatic analyses that revealed UPR activation in different experimental HD models based on transcriptomic data. Accordingly, we have identified 53 genes, including RAB5A, HMGB1, CTNNB1, DNM1, TUBB, TSG101, EEF2, DYNC1H1, SLC12A5, ATG5, AKT1, CASP7 and SYVN1 that provide a potential link between UPR and HD. To further elucidate the potential role of UPR as a disease-relevant process, we examined its connection to apoptosis based on molecular interaction data, and identified a set of 40 genes including ADD1, HSP90B1, IKBKB, IKBKG, RPS3A and LMNB1, which seem to be at the crossroads between these two important cellular processes. Remarkably, we also found strong correlation of UPR gene expression with the length of the polyglutamine tract of Huntingtin, which is a critical determinant of age of disease onset in human HD patients pointing to the UPR as a promising target for therapeutic intervention. The study is complemented by a newly developed web-portal called UPR-HD (http://uprhd.sysbiolab.eu) that enables visualization and interactive analysis of UPR-associated gene expression across various HD models

Cross-cultural validation of the Portuguese version of the Educational Needs Assessment Tool (PortENAT)

Objectives: To undertake a cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) into Portuguese. Methods: The first phase of this research (cross-cultural adaptation) utilised a well-established translation method comprising five sequential steps: forward- -translation, synthesis of translations, back-translation, expert committee and field-testing of the adapted version. The second phase involved collecting data from 123 patients and subjecting them to Rasch analysis for validity testing including cross-cultural invariance. Results: The translation and field-testing phase went smoothly giving rise to minor adjustments in the phrasing of some items. The preliminary analysis of the 39 items, revealed some deviations from the model with the overall item-person interaction fit statistics 2(df) = 56.025 (39), p = 0.038. Significant item-item correlations caused artificial inflation of the internal consistency, therefore violating the model assumption of local independence of items. To correct this, all locally dependent items were then grouped into their respective domains, creating a 7 testlet-scale which demonstrated a good fit to the Rasch model, 2(df) = 2.625 (7), p = 0.917 and internal consistency PSI = 0.975. Analysis of the pooled (Portuguese and the English) data revealed cross-cultural DIF, requiring adjustments in two testlets: ‘treatments’ and ‘support’ which ensured cross- -cultural equivalence. Conclusions: This study confirms the Portuguese ENAT is a robust unidimensional tool with which to assess the educational needs of Portuguese people with RA. Cross-cultural adjustments are required only if the data from Portugal and the UK are pooled or compared. The tool is now available for use in clinical practice and research

Relações entre saliva e disfagia: uma revisão sistemática

Objetivos: Revisar sistematicamente estudos sobre as relações entre saliva e disfagia e favorecer o conhecimento acerca do tema. Métodos: dezembro de 2019, em inglês ou português através dos termos Transtorno de Deglutição/ “Deglutition Disorders”, Disfagia/ “Dysphagia” e Saliva. Excluíram-se estudos com animais, artigos de opinião ou revisão da literatura. Os artigos foram categorizados de acordo com semelhanças das relações entre saliva e disfagia. Para análise, utilizou-se o instrumento STROBE adaptado. Resultados: Encontraram-se 107 artigos, sendo 20 duplicados. Após a leitura de título e resumo, excluíram-se 50 artigos, e após a leitura na íntegra, outros 23. Levantou-se as relações entre saliva e disfagia e seis artigos foram excluídos, com inclusão final de oito artigos. Os estudos selecionados discorrem sobre as influências da saliva no processo de deglutição pela alteração do fluxo salivar, pelas dificuldades no controle da mesma e/ou pela sua composição. Discussão: Observou-se associações entre disfagia e controle oral da saliva, composição da saliva e alterações do fluxo salivar, sendo estas relacionadas a tratamentos para condições oncológicas e envelhecimento. Conclusão: As pesquisas analisadas apontam que a alteração do fluxo salivar, sua composição e controle oral da saliva interferem no processo de deglutição

Experimental investigation of the air-fuel charging process in a four-valve supercharged two-stroke cycle GDI engine

Fuel consumption standards imposed in several countries for the next years have prompted the development of hybrid passenger cars with ever smaller internal combustion engines. In such powertrain, fuel consumption is as important as engine packaging and power density, so two-stroke engines may be an option due to their higher combustion frequency compared to four-stroke engines. Therefore, the present research investigates the air–fuel charging process of an overhead four-valve direct injection supercharged engine operating in the two-stroke cycle. The optimum start of fuel injection was evaluated for commercial gasoline by means of indicated and combustion efficiencies where a trade-off was found between early and late fuel injections. By advancing the injection timing, more fuel was prone to short circuit to the exhaust during the valve overlap, while late injections resulted in poor charge preparation. The gas exchange parameters, i.e. charging and trapping efficiencies, were obtained from seventy operating points running at fuel-rich conditions. The Benson–Brandham mixing-displacement scavenging model was then fit to the experimental data with a coefficient of determination better than 0.95. With such model, the air trapping and charging efficiencies could be estimated solely based on the scavenge ratio and exhaust lambda, regardless of the engine load, speed, or air/fuel ratio employed. Further twenty-five different lean-burn testing points were tested to certify the proposed methodology applied to the poppet valve two-stroke engine. The in-cylinder lambda was calculated and found different from the exhaust lambda due to mixing between burned gases and intake air during the scavenging process

Self- and peer assessment may not be an accurate measure of PBL tutorial process

<p>Abstract</p> <p>Background</p> <p>Universidade Cidade de São Paulo adopted a problem-based learning (PBL) strategy as the predominant method for teaching and learning medicine. Self-, peer- and tutor marks of the educational process are taken into account as part of the final grade, which also includes assessment of content. This study compared the different perspectives (and grades) of evaluators during tutorials with first year medical students, from 2004 to 2007 (n = 349), from seven semesters.</p> <p>Methods</p> <p>The tutorial evaluation method was comprised of the students' self assessment (SA) (10%), tutor assessment (TA) (80%) and peer assessment (PA) (10%) to calculate a final educational process grade for each tutorial. We compared these three grades from each tutorial for seven semesters using ANOVA and a post hoc test.</p> <p>Results</p> <p>A total of 349 students participated with 199 (57%) women and 150 (42%) men. The SA and PA scores were consistently greater than the TA scores. Moreover, the SA and PA groups did not show statistical difference in any semester evaluated, while both differed from tutor assessment in all semesters (Kruskal-Wallis, Dunn's test). The Spearman rank order showed significant (p < 0.0001) and positive correlation for the SA and PA groups (r = 0.806); this was not observed when we compared TA with PA (r = 0.456) or TA with SA (r = 0.376).</p> <p>Conclusion</p> <p>Peer- and self-assessment marks might be reliable but not valid for PBL tutorial process, especially if these assessments are used for summative assessment, composing the final grade. This article suggests reconsideration of the use of summative assessment for self-evaluation in PBL tutorials.</p

Recent developments of the Hierarchical Reference Theory of Fluids and its relation to the Renormalization Group

The Hierarchical Reference Theory (HRT) of fluids is a general framework for the description of phase transitions in microscopic models of classical and quantum statistical physics. The foundations of HRT are briefly reviewed in a self-consistent formulation which includes both the original sharp cut-off procedure and the smooth cut-off implementation, which has been recently investigated. The critical properties of HRT are summarized, together with the behavior of the theory at first order phase transitions. However, the emphasis of this presentation is on the close relationship between HRT and non perturbative renormalization group methods, as well as on recent generalizations of HRT to microscopic models of interest in soft matter and quantum many body physics.Comment: 17 pages, 5 figures. Review paper to appear in Molecular Physic

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality