CeLaVi: an interactive cell lineage visualization tool

Recent innovations in genetics and imaging are providing the means to reconstruct cell lineages, either by tracking cell divisions using live microscopy, or by deducing the history of cells using molecular recorders. A cell lineage on its own, however, is simply a description of cell divisions as branching events. A major goal of current research is to integrate this description of cell relationships with information about the spatial distribution and identities of the cells those divisions produce. Visualizing, interpreting and exploring these complex data in an intuitive manner requires the development of new tools. Here we present CeLaVi, a web-based visualization tool that allows users to navigate and interact with a representation of cell lineages, whilst simultaneously visualizing the spatial distribution, identities and properties of cells. CeLaVi's principal functions include the ability to explore and manipulate the cell lineage tree; to visualise the spatial distribution of cell clones at different depths of the tree; to colour cells in the 3D viewer based on lineage relationships; to visualise various cell qualities on the 3D viewer (e.g. gene expression, cell type) and to annotate selected cells/clones. All these capabilities are demonstrated with four different example data sets. CeLaVi is available at http://www.celavi.pro

Computational discovery of hidden breaks in 28S ribosomal RNAs across eukaryotes and consequences for RNA Integrity Numbers

In some eukaryotes, a ‘hidden break’ has been described in which the 28S ribosomal RNA molecule is cleaved into two subparts. The break is common in protostome animals (arthropods, molluscs, annelids etc.) but a break has also been reported in some vertebrates and non-metazoan eukaryotes. We present a new computational approach to determine the presence of the hidden break in 28S rRNAs using mapping of RNA-Seq data. We find a homologous break is present across protostomes although has been lost in a small number of taxa. We show that rare breaks in vertebrate 28S rRNAs are not homologous to the protostome break. A break is found in just 4 out of 331 species of non-animal eukaryotes studied and three of these are located in the same position as the protostome break suggesting a striking instance of convergent evolution. RNA Integrity Numbers (RIN) rely on intact 28s rRNA and will be consistently underestimated in the great majority of animal species with a break

Anti-inflammatory activity of Blutaparon portulacoides ethanolic extract against the inflammatory reaction induced by Bothrops jararacussu venom and isolated myotoxins BthTX-I and II

This article reports the anti-inflammatory effect of Blutaparon portulacoides (B. portulacoides), specifically the ethanolic extract of its aerial parts, on the edema formation and leukocyte influx caused by Bothrops jararacussu (B. jararacussu) snake venom and Bothropstoxin-I and II (BthTX-I and II) isolated from this venom as an alternative treatment for Bothrops snakebites. The anti-inflammatory effect of B. portulacoides ethanolic extract was compared with an animal group pretreated with dexamethasone. B. portulacoides ethanolic extract significantly inhibited paw edema induced by B. jararacussu venom and by BthTX-I and II. Also, results demonstrated that the extract caused a reduction of the leukocyte influx induced by BthTX-I. However, the extract was not capable of inhibiting the leukocyte influx induced by the venom and by BthTX-II. In conclusion, these results suggest that the ethanolic extract of this plant possess components able to inhibit or inactivate toxins present in B. jararacussu venom, including its myotoxins, responsible for the edema formation. However, the leukocyte migration caused by the venom and BthTX-II was not inhibited by the plant, probably due to the different mechanisms involved in the edema formation and leukocyte influx. This is the first report of B. portulacoides extract as anti-inflammatory against snake venoms and isolated toxins

Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?

Cell lineages provide the framework for understanding how cell fates are decided during development. Describing cell lineages in most organisms is challenging; even a fruit fly larva has ~50,000 cells and a small mammal has >1 billion cells. Recently, the idea of applying CRISPR to induce mutations during development, to be used as heritable markers for lineage reconstruction, has been proposed by several groups. While an attractive idea, its practical value depends on the accuracy of the cell lineages that can be generated. Here, we use computer simulations to estimate the performance of these approaches under different conditions. We incorporate empirical data on CRISPR-induced mutation frequencies in Drosophila. We show significant impacts from multiple biological and technical parameters - variable cell division rates, skewed mutational outcomes, target dropouts and different sequencing strategies. Our approach reveals the limitations of published CRISPR recorders, and indicates how future implementations can be optimised. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)

Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review

BACKGROUND: Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. METHODS: We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. RESULTS: We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate variables of left ventricular (LV) diastolic dysfunction were associated with higher sPAP on exercise. CONCLUSIONS: We found very high heterogeneity in the methods, the protocols and the estimated sPAP response to exercise. LV diastolic dysfunction was common and was associated with greater elevation of sPAP on exercise.info:eu-repo/semantics/publishedVersio

Evaluation of cardiovascular effects of edible fruits of Syzygium cumini Myrtaceae (L) skeels in rats

Purpose: To evaluate the hypotensive, vasorelaxant and antihypertensive effects elicited by the hydroalcohol extract from the fruits of Syzygium cumini (EHSCF) in non-anesthetized rats.Methods: The rats were anesthetized and polyethylene catheters were inserted into the lower abdominal aorta and into the inferior vena cava for blood pressure measurements and administration of drugs. After a recovery period of 24 h, EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg, i.v.) was administered in non-anesthetized rats. The mean arterial pressure and the heart rate were recorded. To investigate the effects of extract, doses EHSCF were administered after pretreatment with L-NAME, atropine, indomethacin, and hexamethonium. For measurement of isometric tension, a concentration-response curve was obtained after Phenylephrine and KCl (80 mM) pre-contractions. The bioactive extract was analyzed via mass spectrometry (MS) fingerprinting using direct electrospray ionization mass spectrometry (ESI-MS).Results: EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg) induced hypotension (-15 ± 1, -14 ± 1, -15 ± 1, -13 ± 1, -11 ± 1 and -13 ± 2 %) and bradycardia (-6 ± 1, -5 ± 1, -6 ± 1, -14 ± 1, -8 ± 1 and -10 ± 2 %) in normotensive rats. These responses were attenuated by pre-treatment with L-NAME, indomethacin, hexamethonium or atropine. In phenylephrine, pre-contracted mesenteric rings, EHSCF-induced relaxation (Emax = 54.6 ± 4.5 % and pD2 = 2.7 ± 0.1) that were affected by endothelium removal. EHSCF caused relaxant effect of KCl (80 mM) pre-contracted rings (Emax = 100 ± 0.2 % and pD2 = 2.2 ± 0.1). This effect was not changed in denuded rings. A single oral administration of the extract reduced significant mean arterial pressure in spontaneously hypertensive rats. ESI-MS/MS analyses of EHSCF demonstrated that the major constituents of the analyzed samples coincided with the mass of the malic, gallic, caffeic and ferulic acids.Conclusion: The results suggest that EHSCF induces hypotension probably due to a decrease in peripheral resistance, mediated by the endothelium. Bradycardia may be due to indirect cardiac muscarinic activation. The extract also causes an antihypertensive effect.Keywords: Antihypertensive, Edible fruits, Hypotension, Syzygium cumini, Vasorelaxatio

Grupos de pesquisa em enfermagem no Brasil: comparação dos perfis de 2006 e 2016

RESUMO Objetivos Comparar o perfil dos grupos de pesquisa em Enfermagem cadastrados no Diretório do CNPq em 2006 e 2016. Métodos Estudo descritivo documental. A coleta de dados aconteceu em 2006 e 2016 a partir de consulta parametrizada com o termo Enfermagem no Diretório dos Grupos de Pesquisa, na página online do CNPq, sendo realizada a análise descritiva. Os dados foram organizados em planilha do Excel. Resultados O número de Grupos de Pesquisa aumentou de 251 em 2006 para 617 em 2016, com incremento no número de participantes. Houve redução do número de grupos sem estudantes, embora 22% permaneçam sem participação de alunos de graduação. Conclusões Os grupos de pesquisa em Enfermagem refletem avanços estruturais e políticos na geração de ciência, tecnologia e inovação da área, entretanto ainda deve ser incentivada a participação de alunos de graduação e pesquisadores estrangeiros, bem como a ampliação de recursos tecnológicos e das parcerias interinstitucionais