199 research outputs found
Valtion aluehallintovirastot ja niiden ylijohtajat: Pohjoiseurooppalainen analogia Ranskan prefeikteille
This chapter examines the closest Finnish analogy to the French function of the prefect. In Finland, since 2010, this function has been vested in the institution of the State Regional Administrative Agency (SRAA, aluehallintovirasto, ‘AVI’). There are six SRAAs, each headed by a Chief Director (ylijohtaja) nominated by the government. The study had four main findings. First, despite ambiguity in institutional terminology, classifications, boundaries and identities concerning the SRAA, one can discern few true functional or structural deficiencies. Second, the SRAA is a hybrid between an institution of its own and a territorial representative of either government ministries or government agencies, to which is related the fact that each SRAA has both responsibilities concerning its territory and nationwide responsibilities. Third, tensions between performance and institutional legitimation prevail in the institution of the SRAA, but again without serious deficiencies. Fourth, the 2010 substitution of the SRAA for the former Province comprised a radical institutional change. The 2015–2019 Finnish government intended to abolish the SRAAs, but the subsequent government abandoned that reform, and ultimately by mid-2020 it became clear that the institution of the SRAA was here to stay after all.Peer reviewe
Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor
Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis
Responses of marine benthic microalgae to elevated CO<inf>2</inf>
Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag
ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression
Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics
Chitins and Chitosans as Immunoadjuvants and Non-Allergenic Drug Carriers
Due to the fact that some individuals are allergic to crustaceans, the presumed relationship between allergy and the presence of chitin in crustaceans has been investigated. In vivo, chitin is part of complex structures with other organic and inorganic compounds: in arthropods chitin is covalently linked to proteins and tanned by quinones, in fungi it is covalently linked to glucans, while in bacteria chitin is diversely combined according to Gram(+/−) classification. On the other hand, isolated, purified chitin is a plain polysaccharide that, at the nano level, presents itself as a highly associated structure, recently refined in terms of regularity, nature of bonds, crystallinity degree and unusual colloidal behavior. Chitins and modified chitins exert a number of beneficial actions, i.e., (i) they stimulate macrophages by interacting with receptors on the macrophage surface that mediate the internalization of chitin particles to be degraded by lysozyme and N-acetyl-β-glucosaminidase (such as Nod-like, Toll-like, lectin, Dectin-1, leukotriene 134 and mannose receptors); (ii) the macrophages produce cytokines and other compounds that confer non-specific host resistance against bacterial and viral infections, and anti-tumor activity; (iii) chitin is a strong Th1 adjuvant that up-regulates Th1 immunity induced by heat-killed Mycobacterium bovis, while down- regulating Th2 immunity induced by mycobacterial protein; (iv) direct intranasal application of chitin microparticles into the lung was also able to significantly down-regulate allergic response to Dermatophagoids pteronyssinus and Aspergillus fumigatus in a murine model of allergy; (v) chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice; (vi) authors support the fact that chitin depresses the development of adaptive type 2 allergic responses. Since the expression of chitinases, chitrotriosidase and chitinase-like proteins is greatly amplified during many infections and diseases, the common feature of chitinase-like proteins and chitinase activity in all organisms appears to be the biochemical defense of the host. Unfortunately, conceptual and methodological errors are present in certain recent articles dealing with chitin and allergy, i.e., (1) omitted consideration of mammalian chitinase and/or chitotriosidase secretion, accompanied by inactive chitinase-like proteins, as an ancestral defensive means against invasion, capable to prevent the insurgence of allergy; (2) omitted consideration of the fact that the mammalian organism recognizes more promptly the secreted water soluble chitinase produced by a pathogen, rather than the insoluble and well protected chitin within the pathogen itself; (3) superficial and incomplete reports and investigations on chitin as an allergen, without mentioning the potent allergen from crustacean flesh, tropomyosine; (4) limited perception of the importance of the chemical/biochemical characteristics of the isolated chitin or chitosan for the replication of experiments and optimization of results; and (5) lack of interdisciplinarity. There is quite a large body of knowledge today on the use of chitosans as biomaterials, and more specifically as drug carriers for a variety of applications: the delivery routes being the same as those adopted for the immunological studies. Said articles, that devote attention to the safety and biocompatibility aspects, never reported intolerance or allergy in individuals and animals, even when the quantities of chitosan used in single experiments were quite large. Therefore, it is concluded that crab, shrimp, prawn and lobster chitins, as well as chitosans of all grades, once purified, should not be considered as “crustacean derivatives”, because the isolation procedures have removed proteins, fats and other contaminants to such an extent as to allow them to be classified as chemicals regardless of their origin
Socioeconomic inequalities in mortality, morbidity and diabetes management for adults with type 1 diabetes: A systematic review.
AIMS: To systematically review the evidence of socioeconomic inequalities for adults with type 1 diabetes in relation to mortality, morbidity and diabetes management. METHODS: We carried out a systematic search across six relevant databases and included all studies reporting associations between socioeconomic indicators and mortality, morbidity, or diabetes management for adults with type 1 diabetes. Data extraction and quality assessment was undertaken for all included studies. A narrative synthesis was conducted. RESULTS: A total of 33 studies were identified. Twelve cohort, 19 cross sectional and 2 case control studies met the inclusion criteria. Regardless of healthcare system, low socioeconomic status was associated with poorer outcomes. Following adjustments for other risk factors, socioeconomic status was a statistically significant independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies for adults with type 1 diabetes. There appeared to be an association between low socioeconomic status and some aspects of diabetes management. Although only 3 of 16 studies made adjustments for confounders and other risk factors, poor diabetes management was associated with lower socioeconomic status in 3/3 of these studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels of mortality and morbidity for adults with type 1 diabetes even amongst those with access to a universal healthcare system. The association between low socioeconomic status and diabetes management requires further research given the paucity of evidence and the potential for diabetes management to mitigate the adverse effects of low socioeconomic status
Relative mobility determines the efficacy of MPAs in a two species mixed fishery with conflicting management objectives
Marine Protected Areas (MPAs) have been used to protect species in need of conservation and as a fisheries management tool. It has been suggested MPAs can benefit mobile stocks by protecting spawning grounds whilst also allowing yields to be maintained as mature fish move out of the protected areas. However, the robustness of this claim in mixed species fisheries has yet to be established. We use a simulation model to explore the efficacy of spatial closures and effort regulation when other forms of fishery control (e.g., Total Allowable Catches) are absent or non-enforced as ways of addressing management objectives that are difficult to reconcile due to the contrasting life-histories of a target and a bycatch, conservation species in a two-species fishery. The mobility of each stock in such a fishery affects the benefits conferred by an MPA. The differing management objectives of the two species can be partially met by effort regulations or closures when the species exhibit similar mobility. However, a more mobile conservation species prevents both sets of aims being met by either management tool. We use simulations to explore how spatial closures and effort regulation can be used to seek compromise between stakeholders when the mobility of one stock prevents conflicting management objectives to be fully met. Our results demonstrate that stock mobility is a key factor in considering whether an MPA can meet conflicting aims in a multispecies fishery compromised of stocks with differing life histories and mobilities
The sensory dimension of tourist experiences: capturing meaningful sensory-based themes in Southwest Portugal
aspects of destinations have recently been in focus as an important dimension in the process of facilitating positive tourist experiences. The countryside embraces local resources rich in multi-sensory stimuli that could be utilized in the planning and marketing of appealing tourist experiences addressed to segments of tourists, while fitting sustainable local development. This study follows a holistic approach to the five external human senses, aiming to capture meaningful sensory-informed themes adequate for segmenting rural tourists. A self-administered survey in four languages was collected from 181 tourists in Southwest Portugal. A multiple correspondence analysis suggests four sensory-informed themes, tentatively named generic beach-related experience, nature-based experience, balanced experience, and rural experience. The proposed themes correspond to a four-solution cluster of tourists presenting different profiles. The largest segment (73 tourists) corresponds to the rural experience, regarding which tourists mainly refer to the taste of local food and the smell of fresh air
Species Richness and Trophic Diversity Increase Decomposition in a Co-Evolved Food Web
Ecological communities show great variation in species richness, composition and food web structure across similar and diverse ecosystems. Knowledge of how this biodiversity relates to ecosystem functioning is important for understanding the maintenance of diversity and the potential effects of species losses and gains on ecosystems. While research often focuses on how variation in species richness influences ecosystem processes, assessing species richness in a food web context can provide further insight into the relationship between diversity and ecosystem functioning and elucidate potential mechanisms underpinning this relationship. Here, we assessed how species richness and trophic diversity affect decomposition rates in a complete aquatic food web: the five trophic level web that occurs within water-filled leaves of the northern pitcher plant, Sarracenia purpurea. We identified a trophic cascade in which top-predators — larvae of the pitcher-plant mosquito — indirectly increased bacterial decomposition by preying on bactivorous protozoa. Our data also revealed a facultative relationship in which larvae of the pitcher-plant midge increased bacterial decomposition by shredding detritus. These important interactions occur only in food webs with high trophic diversity, which in turn only occur in food webs with high species richness. We show that species richness and trophic diversity underlie strong linkages between food web structure and dynamics that influence ecosystem functioning. The importance of trophic diversity and species interactions in determining how biodiversity relates to ecosystem functioning suggests that simply focusing on species richness does not give a complete picture as to how ecosystems may change with the loss or gain of species
Allergic sensitization: screening methods
Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute
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