Inherited human group IVA cytosolic phospholipase A(2) deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

This research was supported by an Imperial College Junior Research Fellowship (to N.S.K.), Wellcome Trust program grant (0852551Z108/Z to J.A.M. and T.D.W.), British Heart Foundation Ph.D. studentship (FS/10/033/28271 to F.R.), British Heart Foundation project grant (PG/11/39/28890 to D.B.-B.), and by the Intramural Research Program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES025034 to D.C.Z.)

Digitaalinen nuorisotyö : Nykytila, hyvät käytänteet ja nuorten toiveet

Opinnäytetyön tarve on noussut korona-ajan tuomista muutoksista nuorisotyöhön. Muutokset näkyvät digitaalisuuden lisääntymisenä nuorisotyössä. Työmme tavoitteena on kehittää digitaalista nuorisotyötä ja luoda työkalupakki tutkimuksemme tuloksien pohjalta. Tarkoituksenamme on tutkia digitaalisen nuorisotyön nykytilaa, hyviä käytänteitä sekä nuorten toiveita ja kokemuksia siitä. Työn tilaajana toimii kunnallisen nuorisotyön osaamiskeskus Kanuuna. Tilaajamme toiveena työllemme oli keskittyä ja tuoda esiin nuorten toiveita ja kokemuksia digitaalisesta nuorisotyöstä. Muotoilimme tilaajamme toiveesta pääkysymyksen tutkimuksellemme: “miten tehdä/ kehittää digitaalista nuorisotyötä nuorten toiveet ja kokemukset huomioon ottaen?” Työmme on laadullista tutkimusta. Toimenpiteinä ja menetelminä käytimme havainnointia, haastattelua ja kyselyä. Näiden lisäksi keräsimme teoriapohjaa olemassa olevista materiaaleista ja tutkimuksista. Aineisto on analysoitu yhtenä kokonaisuutena pelkistämällä, koodamalla ja teemoittelemalla. Työmme tulokset ovat laajoja, sillä aiheemmekin on laaja. Tuloksissa käsittelemme digitaalisen nuorisotyön nykytilaa, hyviä käytänteitä sekä nuorten toiveita. Erityisesti nostamme esille nuorten osallistamisen, digipedagogiikan, kouluttautumisen ja suunnitelmallisuuden. Työmme tuloksien pohjalta loimme ohjenuoran, eli työkalupakin, jota alan ammattilaiset voivat hyödyntää työssään. Työkalupakki on työmme tuotos, joka sisältää hyviksi koettuja käytänteitä ja toimenpide-ehdotuksia ammattilaisille. Työkalupakissa käsitellään vuosikelloa ja konkreettisia esimerkkejä tavoista, joilla digitaalista nuorisotyötä voi toteuttaa toimintana, sisältönä tai välineenä

Copper(II) complexes with different diamines as inhibitors of bacterial quorum sensing activity

Three copper(II) complexes, trans-[Cu(1,3-pd)(2)Cl-2]center dot H2O (Cu1; 1,3-pd is 1,3-propanediamine), trans-[Cu(2,2-diMe-1,3-pd)(2)Cl-2] (Cu2; 2,2-diMe-1,3-pd is 2,2-dimethyl-1,3-propanediamine) and trans-[Cu(1,3-pnd)(2)Cl-2]center dot H2O (Cu3; 1,3-pnd is (+/-)-1,3-pentanediamine), were synthesized and structurally characterized by elemental microanalyses, IR, electronic absorption and reflectance spectroscopy and molar conductivity measurements. The antimicrobial efficiency of the complexes against four clinically relevant microorganisms and their antiproliferative effect on the normal human lung fibroblast cell line MRC-5 were evaluated. Since in many bacteria, pathogenicity is regulated by an intercellular communication process called quorum sensing (QS), the effect of the copper(II) complexes Cu1-3 on bacterial QS was examined. The obtained results showed that these complexes inhibited violacein production in Chromobacterium violaceum CV026, indicating their anti-QS activity via the homoserine lactone (HSL) pathway. Two biosensor strains were used to determine which pathway, C4-HSL (N-butanoylhomoserine lactone) or 3OC12-HSL (N-(3-oxododecanoyl) homoserine lactone), was affected by the copper(II) complexes. The biological activities of the copper(II) complexes were compared with those for the nickel(II) complexes of the general formula trans-[Ni(L)(2)(H2O)(2)]Cl-2 (L = 1,3-pd, 2,2-diMe-1,3-pd and 1,3-pnd)

COX isoforms in aortic endothelial cells from young adult and mature adult mice

Non peer reviewe

Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies

In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies. (c) 2022 Elsevier B.V. All rights reserved

Effect of COX-1 or COX-2 gene deletion on prostacyclin formation in the heart

Non peer reviewe

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD

<p>Objective: Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n = 85), and war trauma-exposed individuals with current PTSD (n = 113), with life-time PTSD (n = 61) and without PTSD (trauma controls; n = 88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD.</p><p>Methods: Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting.</p><p>Results: Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (B-max) in PBMCs. Hormone-binding potential (B-max/K-D ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between B-max and K-D that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting B-max data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD.</p><p>Conclusions: Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between B-max and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs. (C) 2013 Elsevier Inc. All rights reserved.</p>