A slightly slummier area? : Negotiations of place-bound identities through social spatializations and unofficial toponyms

In the article, spatializations (discourses of ideal or stereotyped spaces) are conceptualized as powerful discourses of the surrounding society, providing resources for place‐bound identity construction in interaction. We combine a sociolinguistic analysis with Bakhtinian dialogism to understand how such “third” voices in dialogue empower and pluralize self‐ and other‐positionings embedded in the evocations of unofficial place names. Empirically, the focus is on toponyms that divide the socially mixed Vuosaari suburb in Helsinki into “older” and “newer” territories. The results show that when the stereotypes of “good” and “bad” neighbourhoods or other spatializations interpenetrate the uses of “Old” and “New Vuosaari,” they open room for the (re‐)voicing of the meanings of these toponyms for highly differentiated social ends. With the Bakhtinian framework bridging between socio‐spatial theory and sociolinguistics, the article develops a spatially sensitized approach to analyse the entanglements of the micro‐level contexts of interaction with the macro‐level discourses of meaning‐giving.Peer reviewe

Lipid-Laden Macrophages and Inflammation in Atherosclerosis and Cancer : An Integrative View

Altres ajuts: Wihuri Foundation; Pulsus Foundation.Atherosclerotic arterial plaques and malignant solid tumors contain macrophages, which participate in anaerobic metabolism, acidosis, and inflammatory processes inherent in the development of either disease. The tissue-resident macrophage populations originate from precursor cells derived from the yolk sac and from circulating bone marrow-derived monocytes. In the tissues, they differentiate into varying functional phenotypes in response to local microenvironmental stimulation. Broadly categorized, the macrophages are activated to polarize into proinflammatory M1 and anti-inflammatory M2 phenotypes; yet, noticeable plasticity allows them to dynamically shift between several distinct functional subtypes. In atherosclerosis, low-density lipoprotein (LDL)-derived cholesterol accumulates within macrophages as cytoplasmic lipid droplets thereby generating macrophage foam cells, which are involved in all steps of atherosclerosis. The conversion of macrophages into foam cells may suppress the expression of given proinflammatory genes and thereby initiate their transcriptional reprogramming toward an anti-inflammatory phenotype. In this particular sense, foam cell formation can be considered anti-atherogenic. The tumor-associated macrophages (TAMs) may become polarized into anti-tumoral M1 and pro-tumoral M2 phenotypes. Mechanistically, the TAMs can regulate the survival and proliferation of the surrounding cancer cells and participate in various aspects of tumor formation, progression, and metastasis. The TAMs may accumulate lipids, but their type and their specific roles in tumorigenesis are still poorly understood. Here, we discuss how the phenotypic and functional plasticity of macrophages allows their multifunctional response to the distinct microenvironments in developing atherosclerotic lesions and in developing malignant tumors. We also discuss how the inflammatory reactions of the macrophages may influence the development of atherosclerotic plaques and malignant tumors, and highlight the potential therapeutic effects of targeting lipid-laden macrophages in either disease

Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MO and GM-MO, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MO, the M-MO expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MO foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MO strongly suppressed the high baseline expression of CCL2, whereas in GM-MO the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.Peer reviewe

Migrating 120,000 Legacy Publications from Several Systems into a Current Research Information System Using Advanced Data Wrangling Techniques

This article describes a complex CRIS (current research information system) implementation project involving the migration of around 120,000 legacy publication records from three different systems. The project, undertaken by Tampere University, encountered several challenges in data diversity, data quality, and resource allocation. To handle the extensive and heterogenous dataset, innovative approaches such as machine learning techniques and various data wrangling tools were used to process data, correct errors, and merge information from different sources. Despite significant delays and unforeseen obstacles, the project was ultimately successful in achieving its goals. The project served as a valuable learning experience, highlighting the importance of data quality and standardized practices, and the need for dedicated resources in handling complex data migration projects in research organizations. This study stands out for its comprehensive documentation of the data wrangling and migration process, which has been less explored in the context of CRIS literature.Peer reviewe

Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion

Peer reviewe

Carboxyl-Terminal Cleavage of Apolipoprotein A-I by Human Mast Cell Chymase Impairs Its Anti-Inflammatory Properties

Objective Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease-secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of apoA-I. Approach and Results Activation of human mast cells triggered the release of granule-associated proteases chymase, tryptase, cathepsin G, carboxypeptidase A, and granzyme B. Among them, chymase cleaved apoA-I with the greatest efficiency and generated C-terminally truncated apoA-I, which failed to bind with high affinity to human coronary artery endothelial cells. In tumor necrosis factor--activated human coronary artery endothelial cells, the chymase-cleaved apoA-I was unable to suppress nuclear factor-B-dependent upregulation of vascular cell adhesion molecule-1 (VCAM-1) and to block THP-1 cells from adhering to and transmigrating across the human coronary artery endothelial cells. Chymase-cleaved apoA-I also had an impaired ability to downregulate the expression of tumor necrosis factor-, interleukin-1, interleukin-6, and interleukin-8 in lipopolysaccharide-activated GM-CSF (granulocyte-macrophage colony-stimulating factor)- and M-CSF (macrophage colony-stimulating factor)-differentiated human macrophage foam cells and to inhibit reactive oxygen species formation in PMA (phorbol 12-myristate 13-acetate)-activated human neutrophils. Importantly, chymase-cleaved apoA-I showed reduced ability to inhibit lipopolysaccharide-induced inflammation in vivo in mice. Treatment with chymase blocked the ability of the apoA-I mimetic peptide L-4F, but not of the protease-resistant D-4F, to inhibit proinflammatory gene expression in activated human coronary artery endothelial cells and macrophage foam cells and to prevent reactive oxygen species formation in activated neutrophils. Conclusions The findings identify C-terminal cleavage of apoA-I by human mast cell chymase as a novel mechanism leading to loss of its anti-inflammatory functions. When targeting inflamed protease-rich atherosclerotic lesions with apoA-I, infusions of protease-resistant apoA-I might be the appropriate approach.Peer reviewe

Suomen troolilaivaston kalastusalueet Itämerellä vuosina 2010–2022

Avoin paikkatietoaineisto suomalaisten troolialusten kalastusalueista 2018-2022 Raportissa tarkastellaan suomalaisten troolialusten kalastusalueita Itämerellä saalistietojen ja VMS-aineistojen perusteella vuosina 2010–2022. Tarkastelussa on mukana myös ruotsalaisia troolialuksia koskevat vastaavat aineistot Pohjanlahdelta vuosina 2018–2022. Keskeiset tulokset esitetään karttojen avulla. Tärkein saalislaji on silakka, jonka pyynnin ohessa saaliiksi tulee myös kilohailia. Suomen troolialuksille tärkein pyyntialue vuosina 2010–2022 on ollut Selkämeri, mutta myös Suomenlahdelta, pääaltaalta ja Saaristomereltä on pyydetty merkittäviä määriä silakkaa ja kilohailia. Suomalaiset ja ruotsalaiset troolialukset kalastavat Selkämerellä osittain samoilla alueilla, mutta suomalaiset kalastajat ovat viime vuosina pyytäneet runsaat kolme neljäsosaa alueen troolisaaliista. Neljännes suomalaisten pyytämästä silakasta on viime vuosina mennyt elintarvikkeeksi. Isoin silakka fileoidaan kotimaan elintarvikkeeksi ja sitä pienempää pakastetaan elintarvikevientiin. Pääosa fileeteollisuuden raaka-aineesta pyydetään Selkämereltä Ruotsin talousvyöhykkeeltä Finngrundetin ja Saltbankenin ympäristöstä. Perämerellä on myös pienimuotoisempaa troolikalastusta, joka keskittyy muikun kutupyyntiin, vaikka sieltä saadaan jonkin verran myös silakkaa. Eniten muikun troolausta on Perämeren pohjukassa Ruotsin puolella, josta on viime vuosina (2018–2022) pyydetty vajaa kolme neljäsosaa koko Perämeren muikun troolisaaliista. Suomen puolella muikun troolaus on keskittynyt Hailuodon pohjoispuolelle. Vuosien 2010–2022 aikana on silakan troolikalastuksen toimintaympäristössä ja saalismäärissä tapahtunut merkittäviä muutoksia. Siitä huolimatta troolausalueissa ei ole samana aikana tapahtunut juurikaan muutoksia. Tietyt hyviksi todetut alueet ovat vakiintuneita ja silakan ja muikun troolikalastuksen harjoittamiselle ensisijaisen tärkeitä. Näillä alueilla on tyypillisesti troolaukseen soveltuvat hyvin tunnetut pohjat, joissa sopivan kokoista kalaa voidaan pyytää pohjan läheltä ilman riskiä troolien rikkoontumisesta. Haastateltujen kalastusyritysten edustajien mukaan isoilla trooleilla ei voitaisi pyytää silakkaa merituulivoima-alueiden sisällä. Isojen troolien vetäminen edellyttää runsaasti tilaa ja erityisesti troolien mahdollinen osuminen kaapeleihin nähtiin isona riskinä. Muikun troolauksessa Perämerellä käytettävät alukset ja troolit ovat huomattavasti pienempiä ja ainakin periaatteessa troolaaminen voisi onnistua myös tuulivoima-alueiden sisällä, mutta tässäkin tapauksessa riskinä nähtiin nimenomaan kaapelit

Food allergy alters jejunal circular muscle contractility and induces local inflammatory cytokine expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model.</p> <p>Methods</p> <p>Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR.</p> <p>Results</p> <p>Ovalbumin-specific serum IgE correlated with jejunal MMCP-1⁺cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-γ and TGF-β1 remained unchanged.</p> <p>Conclusion</p> <p>In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-γ mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1⁺cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.</p

Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation

Chronic inflammation of the arterial wall is a key element in the pathogenesis of atherosclerosis, yet the factors that trigger and sustain the inflammation remain elusive. Inflammasomes are cytoplasmic caspase-1-activating protein complexes that promote maturation and secretion of the proinflammatory cytokines interleukin(IL)-1beta and IL-18. The most intensively studied inflammasome, NLRP3 inflammasome, is activated by diverse substances, including crystalline and particulate materials. As cholesterol crystals are abundant in atherosclerotic lesions, and IL-1beta has been linked to atherogenesis, we explored the possibility that cholesterol crystals promote inflammation by activating the inflammasome pathway.Here we show that human macrophages avidly phagocytose cholesterol crystals and store the ingested cholesterol as cholesteryl esters. Importantly, cholesterol crystals induced dose-dependent secretion of mature IL-1beta from human monocytes and macrophages. The cholesterol crystal-induced secretion of IL-1beta was caspase-1-dependent, suggesting the involvement of an inflammasome-mediated pathway. Silencing of the NLRP3 receptor, the crucial component in NLRP3 inflammasome, completely abolished crystal-induced IL-1beta secretion, thus identifying NLRP3 inflammasome as the cholesterol crystal-responsive element in macrophages. The crystals were shown to induce leakage of the lysosomal protease cathepsin B into the cytoplasm and inhibition of this enzyme reduced cholesterol crystal-induced IL-1beta secretion, suggesting that NLRP3 inflammasome activation occurred via lysosomal destabilization.The cholesterol crystal-induced inflammasome activation in macrophages may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions

Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence