Jahanyne, an Apoptosis-Inducing Lipopeptide from the Marine Cyanobacterium <i>Lyngbya</i> sp.

An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium <i>Lyngbya</i> sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells

Terminal Platelet Production is Regulated by Von Willebrand Factor

<div><p>It is established that proplatelets are formed from mature megakaryocytes (MK) as intermediates before platelet production. Recently, the presence of proplatelets was described in blood incubated in static conditions. We have previously demonstrated that platelet and proplatelet formation is upregulated by MK exposure to high shear rates (1800 s⁻¹) on immobilized von Willebrand factor (VWF). The purpose of the present study was to investigate whether VWF is involved in the regulation of terminal platelet production in blood. To this end, <i>Vwf ^−/−</i> mice, a model of severe von Willebrand disease, were used to create a situation in which blood cells circulate in a vascular tree that is completely devoid of VWF. Murine platelets were isolated from <i>Vwf ^−/−</i> and <i>Vwf^+/+</i> blood, exposed to VWF at 1800 s⁻¹ in a microfluidic platform, and examined by means of videomicroscopy, as well as fluorescence and activation studies. Proplatelets became visible within 5 minutes, representing 38% of all platelets after 12 minutes and 46% after 28 min. The proportion of proplatelets was 1.8-fold higher in blood from <i>Vwf^−/−</i> mice than from <i>Vwf^+/+</i> mice, suggesting a role of VWF <i>in vivo</i>. Fragmentation of these proplatelets into smaller discoid platelets was also observed in real-time. Platelets remained fully activatable by thrombin. Compensation of plasmatic VWF following hydrodynamic gene transfer in <i>Vwf^−/−</i> mice reduced the percentage of proplatelets to wild-type levels. A thrombocytopenic mouse model was studied in the flow system, 7 days after a single 5-FU injection. Compared to untreated mouse blood, a 2-fold increase in the percentage of proplatelets was detected following exposure to 1800 s⁻¹ on VWF of samples from mice treated with 5-FU. In conclusion, VWF and shear stress together appear to upregulate proplatelet reorganization and platelet formation. This suggests a new function for VWF <i>in vivo</i> as regulator of bloodstream thrombopoiesis.</p></div

Distribution of AE clinical observations resulting from a platelet transfusion.

<p><b>A</b>. All PCs. <b>B</b>. PCs delivered before 3 days. <b>C</b>. PCs delivered from 3 to 5 days. The data are shown as percentages. FNHTR, febrile non-hemolytic transfusion reaction (fever or chill); AATRs, atypical allergic transfusion reactions (erythematous rash, urticaria, and/or pruritus or more severe reactions with angioedema); hemodynamic trouble (HT), excluding ALI (and TRALI), TACO, myocardial infarctions, and pulmonary embolism; combined ATRs, ATRs with two or more associated manifestations. We did not analyze any case with bronchospasm or anaphylaxis.</p

Discriminatory ability of soluble factors to classify PCs as belonging to either the adverse effect or control group.

<p>All AUCs with a p-value of <0.0001 (z-test) were considered different from 0.5.</p

Pearson correlation matrix of 16 soluble factors in 65 ATRs supernatants.

<p>The bold values were different from 0 at a significance level of α = 0.05.</p

Parameters of platelet donors and storage time of the platelet concentrates.

a<p>The data are shown as percentages.</p

Examples of areas under the ROC curves.

<p><b>A</b>. sCD40L; <b>B</b>. MIP-1α; <b>C</b>. IL13; <b>D</b>. BCA-1.</p

Concentrations of 17 soluble factors in the supernatants from 65 ATRs PCs and 59 control PCs.

<p>The data are adjusted to pg/10⁹ platelets and expressed as the mean ± SEM. <b>A</b>. Factors that did not display any difference between the control and AE samples. <b>B</b>. Factors that had a concentration in the AE samples that was significantly higher than in the control samples or that were detected only in the ATR samples. <b>C</b>. Factors that were not detected in the controls, regardless of the amounts in the ATR samples (concentrations in the control and ATR samples were compared using two-tailed Student's t test, *p<0.05).</p

Decision tree.

<p><b>A</b>. Assays without IL13 (among 16 assays, the success rate of the sCD40L model was the highest, 78%); <b>B</b>. Assays with IL13 (among 17 assays, the success rate of the IL13 model was the highest, 82%).</p

Release of soluble factors during platelet storage for 5 days.

<p>The data are adjusted to pg/10⁹ platelets and expressed as the mean ± SEM. <b>A</b>. Factors that increased over 5 days of storage in only the control samples. <b>B</b>. Factors that were constantly secreted with almost equivalent amounts between days 1 and 5 in the supernatants from “pathogenic” PCs but that were not detectable at any time between days 1 and 5 in the control samples. <b>C</b>. Factors with invariable trace amounts—between days 1 and 5 in the control PC supernatants and with elevated concentrations, but only on days 4 and 5, in the “pathogenic” PC supernatants. <b>D</b>. Factors that were elevated in both the control and pathogenic supernatants, although with significant variations between the control and ATR samples (concentrations of the soluble factors on days 2–5 vs. day 1 in the same group were compared using ANOVA, *p<0.05).</p