A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks

Novel territory-specific markers from the sea urchin Strongylocentrotus purpuratus have been identified using screens for genes that are differentially expressed in lithium-treated embryos, which form an excess of endomesoderm, and in zinc-treated embryos, in which endomesoderm specification is blocked

WISH analysis of and and immunohistochemical localization of serotonergic cells in normal and zinc-treated embryos

<p><b>Copyright information:</b></p><p>Taken from "A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks"</p><p>http://genomebiology.com/2007/8/5/R85</p><p>Genome Biology 2007;8(5):R85-R85.</p><p>Published online 16 May 2007</p><p>PMCID:PMC1929154.</p><p></p> Whole-mount hybridization (WISH) analysis identified the transcription factors and as being expressed in single cells of the apical organ. Although expression is eliminated in zinc-treated embryos , the expression of is expanded and upregulated in zinc-treated embryos (also see quantitative real-time polymerase chain reaction data in Table 2). Immunohistochemical localization of serotonin in normal and zinc-treated embryos shows that whereas normal embryos produce four to six serotonergic cells (panel d), the number of serotonergic cells is elevated to at least 30 on average in zinc treated embryos (panel h). Panels d and h are fluorescent photographs of the same embryos depicted in transmitted light in panels c and g, respectively

Expression of endomesoderm markers in normal, lithium-treated and zinc-treated embryos

<p><b>Copyright information:</b></p><p>Taken from "A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks"</p><p>Genome Biology 2007;8(5):R85-R85.</p><p>Published online 16 May 2007</p><p>PMCID:PMC1929154.</p><p></p> Shown are whole-mount hybridizations (WISHs) of endomesodermal marker genes on blastula stage (columns 1, 3, and 5) and gastrula stage (columns 2, 4, and 6) sea urchin embryos. The genes under considerations are indicated on the right hand side. , , and , and is a new gene that is expressed in the endoderm. The expression is strongly expanded in lithium-treated embryos (columns 3 and 4), whereas only at the most animal pole are ectodermal tissues left in the embryo. Blastula stage zinc-treated embryos do not exhibit any expression of endodermal markers (column 5). Gastrula stage zinc-treated embryos (column 6) do occasionally begin to express early endomesodermal markers as they recover from treatment (see Materials and methods). is a transcription factor that is expressed at low levels in primary mesenchyme cells (PMCs) and predominantly in secondary mesenchyme cell (SMC) cells. Expression is upregulated in lithium-treated embryos, as determined by quantitative real-time polymerase chain reaction (Q-PCR; columns 3 and 4; compare with Table 1) but seems unchanged as determined by WISH and is eliminated in blastula stage zinc-treated embryos. P19 is a PMC-specific gene identified in the screen. Although its expression appears to be quantitatively upregulated in lithium-treated and zinc-treated embryos (see Table 2), WISH analysis indicates that the number of PMC cells forming is normal in lithium-treated or zinc-treated embryos, but that the PMCs migrate to the animal pole in lithium-treated embryos and to the vegetal pole in zinc-treated embryos. In neither case does a skeleton form

Expression of Wnt genes in lithium and zinc treated embryos

<p><b>Copyright information:</b></p><p>Taken from "A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks"</p><p>Genome Biology 2007;8(5):R85-R85.</p><p>Published online 16 May 2007</p><p>PMCID:PMC1929154.</p><p></p> Quantitative real-time polymerase chain reaction (Q-PCR) analysis of all wingless int (Wnt) genes of the sea urchin . Measurements were done at blastula stage (20 hours) for lithium-treated embryos (purple bars) and gastrula stage (38 hours) for zinc-treated embryos (pink bars). Data are presented in a logarithmic style. Bars above 1 indicate upregulation and bars below 1 indicate downregulation. The numbers given on top or bottom of bars are the number of mRNA molecules/embryo in normal or treated embryos, respectively. For instance, the number of transcripts for is 45 in normal 20 hours embryos and 17 in lithium-treated embryos (blue bar), and the number of transcripts of is 940 in normal 20 hours embryos and 5,854 in lithium-treated 20 hours embryos. Where n.e. (not expressed) is indicated the gene is not expressed at this stage at all, either in control or in treated embryos. Also see Tables 1 and 3 and the text for further detail

Expression of ectoderm markers in normal, lithium-treated, and zinc-treated embryos

<p><b>Copyright information:</b></p><p>Taken from "A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks"</p><p>Genome Biology 2007;8(5):R85-R85.</p><p>Published online 16 May 2007</p><p>PMCID:PMC1929154.</p><p></p> Shown are whole-mount hybridizations (WISHs) of ectodermal marker genes on blastula stage (columns 1, 3, and 5) and gastrula stage (columns 2, 4, and 6) sea urchin embryos. The genes under considerations are indicated on the right hand side. Expression of apical plate marker genes (, , and secreted frizzled protein 1/5 []) is lost in lithium-treated embryos (columns 3 and 4) and expanded in zinc-treated embryos (columns 5 and 6). Expression of the oral ectoderm marker is shifted to the 'new' animal pole region in lithium-treated embryos (columns 3 and 4) but lost in blastula stage zinc-treated embryos (column 5). However, ectodermal differentiation does appear to take place in zinc-treated embryos if they are left to recover for a longer period of time (column 6). The ciliated band marker gene exhibits wild-type-like expression in lithium-treated embryos, with a ring of expression around the animal pole (columns 3 and 4). The apical expression domain of co-expands like the other apical organ markers in zinc-treated embryos (panels 5 and 6). Strikingly, the expression of aboral ectoderm markers (, , and ) is lost in blastula stage lithium-treated embryos (panel 3), whereas it is enhanced in zinc-treated blastula stage embryos, in which the expression appears to be quite uniformly distributed. is expressed in mesodermal cells and in the aboral ectoderm in normal embryos (columns 1 and 2). Strikingly, the ectodermal expression only is lost in lithium-treated embryos, whereas the mesodermal domain remains (compare with Figure 4)

Art, Technique and Ideology: between Italian and Croatian New Tendencies.

The aim of this essay is to show how, from the 1950s to early 1970s, arts and technologies evolved side by side owing to the new practices borrowed from the legacy of abstract art. Both in Italy and Croatia, several left-wing scholars wrote on the relations between art and technology as an important factor of social progress. On this basis, it was implied that the leftist ideology had a decisive effect on the new artistic attitudes. These took place in Zagreb during the Nove tendencije exhibitions, held in 1961 and 1963 respectively, where several kinetic and so-called "programmed" artworks were displayed. However, just after the 1965 edition of Nove tendencije, Italian artistic research was changed by the Arte Povera movement in 1967. As a consequence, the gap between "programmed" art the Left increased. Although in Italy such changeover caused a complete break in the relationship between art and technology, in Zagreb the last Tendencije exhibitions, held in 1969 and 1973 respectively, combined the computer-based and conceptual art trends with left-wing radicalism

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

International audienceBackground and Purpose— Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset

Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.status: publishe

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None