Determination of developmental stages of embryo in the sea urchin, Echinometra mathaei

Sea Urchin is one of the most useful tools in developmental biology studies because this organism has the simplest kind of developmental stages. We aimed to determine developmental stages and timetable of Echinometra mathaei embryo (the species of Persian Gulf). The spawning of E. mathaei was induced by 0.5M KCl injection (1ml) into the coelomic cavity. After fertilization, embryos were placed in beakers and were incubated at 29°C and a salinity of 39 ppt until embryos reached the pluteus stage. The developmental stages of embryos and the timing of each stage including cleavage, morulae, blastula, gastrula, prism and pluteus larvae were studied under the microscope. Our results showed that after 30 hours from fertilization time, the embryos developed to pluteus larvae. E. mathaei had the shorter development time in comparison to the other Sea Urchin species. Therefore, it may be appropriate as a model organism in biological researches

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

BACKGROUND: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC). METHODS: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. RESULTS: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity. CONCLUSIONS: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients

The T cell differentiation landscape is shaped by tumour mutations in lung cancer

Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours and whether this affects patient outcomes is unknown. Here, we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets with strong phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states was associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of Chronic Obstructive Pulmonary Disease (COPD)

Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD

<span style="font-size:15.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-ansi-language:EN-GB;mso-fareast-language:EN-US; mso-bidi-language:AR-SA" lang="EN-GB">The effect of lead toxicity <span style="font-size:11.0pt;mso-bidi-font-size:15.0pt;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:EN-GB;mso-fareast-language: EN-US;mso-bidi-language:AR-SA" lang="EN-GB">on embryonic development and early larval growth of the <i>Echinometra mathaei </i>sea urchin (Persian Gulf)<span style="font-size:11.0pt;mso-bidi-font-size:15.0pt;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:EN-GB;mso-fareast-language: EN-US;mso-bidi-language:FA" lang="EN-GB">, morphologic and <span style="font-size:11.0pt;mso-bidi-font-size:15.0pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-GB">morphometric<span style="font-size:11.0pt;mso-bidi-font-size:15.0pt;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:EN-GB;mso-fareast-language: EN-US;mso-bidi-language:FA" lang="EN-GB"> studies</span></span></span></span></span>

29-34Toxic effects of increased lead in sea water on the embryonic stages and early larval growth of the Echinometra mathaei sea urchin is examined in the present study. After the spawn induction and fertilization, the toxicity test was performed in 6 lead concentrations (250, 500, 1000, 2000, 4000 and 8000 µg/L). Toxic effects of this metal were studied on development of embryos until reached the 4-arms pluteus larvae. It is observed that increasing the concentrations of lead, arrested development in the early embryonic stages and led to morphologic abnormalities in the larval growth. Morphometric studies also showed a gradual decrease in larvae size with increasing the concentration of lead. Median effective concentration (EC50) value calculated for lead was 2178.94 µg/L. </span

Erratum to: Pan-cancer deconvolution of tumour composition using DNA methylation (Nature Communications, (2018), 9, 1, (3220), 10.1038/s41467-018-05570-1)

The original version of this Article contained an error in Figure 4. In panel a, the colour code for hot and cold clusters was inadvertently inverted. In the correct version of panel a, the hot clusters are blue and the cold clusters are yellow. This error has now been corrected in both the PDF and HTML versions of the Article.</p