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The creation of private protected areas (PPA) is commonly considered an instrument of neoliberal conservation, characterized by private management and commodification of nature for (eco)tourism and other market-based instruments (MBIs). PPAs are accused of reproducing social inequalities when entailing enclosure, exclusivity, land grabbing or dispossession. Yet PPAs exist in many different forms that enact these various processes in different ways. Our research explores this variegation in PPAs by offering a more nuanced understanding of the often complex and contradictory interconnections between processes of commodification and privatization different PPAs enact, as well as how PPAs are often operationalized differently in global south and north contexts. To develop this analysis, we draw on the conceptual framework of commodification proposed by Castree (2003) to investigate a number of PPAs located in the Serra de Tramuntana mountain range on the island of Mallorca in Spain. Our results show that commodification and privatization combine in different ways and to different degrees in the various PPAs in this area. Overall, we conclude, privatization appears more pervasive than commodification in this global north context, as compared to research concerning PPAs in the global south suggesting the presence of far more commodification in such lower-income contexts. [ABSTRACT FROM AUTHOR]

Private engagement has always been central to biodiversity conservation. Recently, the role of private enterprises in (eco)tourism have increased, and private lands play a pivotal role in expanding protected areas within societies throughout the world. This paper contributes to discussions of private engagement in conservation and its relation to tourism (recreation generally), with novel insight on how the conservation-tourism nexus on private land is approached in different geographical contexts. We present a systematic literature review that results in five thematic clusters characterized by different conservation approaches to tourism in Global North and South. Research concerning Global South tends to emphasize (eco)tourism as a main inducement for conservation, while research concerning Global North emphasizes expansion of private protected areas where access for tourist-recreational use has to be compensated. We propose a future research agenda to exploring environmentally and socially just approaches to conservation and recreation in both Global North and South. [ABSTRACT FROM AUTHOR]

Kinesins are motor proteins found in all eukaryotic lineages that move along microtubules to mediate cellular processes such as mitosis and intracellular transport. In trypanosomatids, the kinesin superfamily has undergone a prominent expansion, resulting in one of the most diverse kinesin repertoires that includes the two kinetoplastid‐restricted families X1 and X2. Here, we characterize in Trypanosoma brucei TbKifX2A, an orphaned X2 kinesin. TbKifX2A tightly interacts with TbPH1, a kinesin‐like protein with a likely inactive motor domain, a rarely reported occurrence. Both TbKifX2A and TbPH1 localize to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that wraps around the flagellar pocket as it extends to the cell body anterior. The proximal proteome of TbPH1 revealed two other interacting proteins, the flagellar pocket protein FP45 and intriguingly another X2 kinesin, TbKifX2C. Simultaneous ablation of TbKifX2A/TbPH1 results in the depletion of FP45 and TbKifX2C and also an expansion of the flagellar pocket, among other morphological defects. TbKifX2A is the first motor protein to be localized to the MtQ. The observation that TbKifX2C also associates with the MtQ suggests that the X2 kinesin family may have co‐evolved with the MtQ, both kinetoplastid‐specific traits. [ABSTRACT FROM AUTHOR]

While debt is not problematic per se, it can become an additional burden when people experience negative life events–like unemployment, a severe disease, divorce, or their partner's death–which can be detrimental for individuals' subjective wellbeing. We investigate first, a potential moderating effect of economic resources or, better yet, lack thereof in the relations between negative life events and general life satisfaction, and second, whether this moderating effect is a function of state-level policies. We expect that, on average, debt has a reinforcing effect on the negative relationship between negative life events and general life satisfaction. Moreover, we expect that country-level policies protecting individuals from the negative consequences of experiencing a negative life event or indebtedness can explain the country differences in the moderating effect of debt. We test our assumptions among the population aged 50+ applying data from the Survey of Health, Ageing and Retirement (SHARE). We apply a two-stage fixed-effects regression approach to estimate the moderation effect of debt on the relationship between negative life events and general life satisfaction within and across countries. Although we find an almost zero average moderating effect of debt across countries, we find large variance in the moderating effects between countries. This variance can be explained by debt regime, but not by the generosity of the public unemployment and the public health systems, or the level of gender equality. [ABSTRACT FROM AUTHOR]

Since the beginning of the 2008 economic crisis, Majorca has experienced an increase in tourism, which has been made possible partly by the expansion of short-term renting. Research on short-term rentals is a growing field in critical urban and tourism geographies. This paper contributes to these fields by examining the structure of actors involved in the development of short-term rentals and their power relations. Our case study focuses on the municipality of Pollença (Majorca, Spain). Pollença was chosen due to its status as one of the most noteworthy airbnbificated places in Europe and because of the number of holiday rentals in the municipality's rural areas. While a great deal of research has focused on rent gaps and gentrification caused by short-term rentals in cities, the rentier coalition associated with short-term rentals has been comparatively overlooked. We address who the rentiers of short-term rentals are, the power relations that lie behind short-term rentals, and how these rentiers form part of a locally based coalition that has the ability to adapt planning regulations to suit their own interests. We used mixed methods, including quantitative spatial analysis and qualitative analysis in the form of interviews with those who benefit locally from short-term rentals. Our qualitative approach further included in-depth fieldwork and activist research. We conclude that a powerful rentier growth coalition has corrupted democracy because the regulatory framework has been adjusted to satisfy their interests and the conversion of properties into holiday rentals has been done either illegally or on the verge of legality without strong legal consequences. [ABSTRACT FROM AUTHOR]

In this paper we apply the method of stochastic characteristics to a Lighthill–Whitham–Richards model. The stochastic perturbation can be seen as errors in measurement of the traffic density. For concrete examples we solve the equation perturbed by a standard Brownian motion and the geometric Brownian motion without drift. [ABSTRACT FROM AUTHOR]

Neoliberal, territorial and environmental regulations prioritize the interests of private ownership of natural spaces, facilitating their commodification and banishing their public use. While the State is slowly withdrawing from the management of of natural sites to guarantee its public use, the private initiatives of land stewardship comes to the front and establishes the alliance between property owners and conservation associations. The residential and financial uses of farmsteads in the Balearic Islands demonstrate the appropriation of nature conservation to limit public access to natural spaces. The proposals of convivial conservation, on the other hand, pose the unavoidable integration of humanity in all nature management. [ABSTRACT FROM AUTHOR]

Introduction. Medical preparedness at mass gatherings is challenging, as little is known about the optimal planning. Most studies and case reports are based on mass casualty incidents, so the results cannot be extrapolated to mass gatherings. Aim of this study was to evaluate the preclinical medical structure and the frequency of specific injuries and medical emergencies during the event. Methods. Retrospective analysis of a prospectively collected database. Three on-site medical assistance points were set up, completed by mobile teams, and coordinated by an on-site operational management team. Medical staff requirements were calculated using Maurer’s formula. Results. A total of 1,533 patients were treated during the three-day event. Overall, the medical usage rate (MUR; patients per 10,000 visitors) was 51.1. A total of 58 patients (3.8%) required a hospital transfer. In 1,063 cases (69.3%) a diagnosis was documented. Of these, 503 patients (47.3%) suffered from hymenoptera stings; the two most common non-trauma-related diagnoses were alcohol/drug intoxication (4.1%) and gastrointestinal diseases (4.0%). Conclusion. Overall, the on-site medical care worked well. However, a high frequency of hymenoptera stings occurred, resulting in a shortage of antihistamine medication. Moreover, more than half of the patients were managed at the second largest medical assistance point. Prospective and critical evaluation of medical care at mass gatherings is crucial in order to optimize on-site medical preparedness at future events. [ABSTRACT FROM AUTHOR]

Administration of the CD28 superagonistic antibody JJ316 is an efficient means to treat autoimmune diseases in rats, but the humanized antibody TGN1412 caused devastating side effects in healthy volunteers during a clinical trial. Here we show that JJ316 treatment of rats induced a dramatic redistribution of T lymphocytes from the periphery to the secondary lymphoid organs, resulting in severe T lymphopenia. Live imaging of secondary lymphoid organs revealed that JJ316 administration almost instantaneously (<2 minutes) arrested T cells in situ. This reduction in T cell motility was accompanied by profound cytoskeletal rearrangements and increased cell size. In addition, surface expression of lymphocyte function-associated antigen-1 was enhanced, endothelial differentiation sphingolipid G protein-coupled receptor 1 and L selectin levels were downregulated, and the cells lost their responsiveness to sphingosine 1-phosphate-directed migration. These proadhesive alterations were accompanied by signs of strong activation, including upregulation of CD25, CD69, CD134, and proinflammatory mediators. However, this did not lead to a cytokine storm similar to the clinical trial. While most of the early changes disappeared within 48 hours, we observed that CD4+CD25+FoxP3+ regulatory T cells experienced a second phase of activation, which resulted in massive cell enlargement, extensive polarization, and increased motility. These data suggest that CD28 superagonists elicit 2 qualitatively distinct waves of activation. [ABSTRACT FROM AUTHOR]

Host T cell activation, a key step in obtaining adaptive immunity against pathogens, is initiated by the binding of the T cell receptor to a foreign antigenic peptide presented by the major histocompatibility complex on the surface of an antigen-presenting cell and, consequently, formation of an immunological synapse. Within the immunological synapse, the engagement of the T cell receptor in cooperation with simultaneous ligation of co-stimulatory molecules induces a precisely organized cascade of signaling events and pathways that regulate clonal expansion and differentiation of naïve T cells into effector T cells contributing to pathogen clearance. The biochemical changes that underlie T cell activation and differentiation, however, not only involve proteins but also lipids. In particular, catabolic cleavage of sphingomyelin generating ceramide can substantially influence functional responses in cells of the immune system. Changes in sphingomyelin and ceramide content have been reported to directly impact on membrane physiology, thus modifying signal transmission and interfering with diverse aspects of T cell activity. In this review we will focus on sphingomyelin breakdown/ceramide generation in T cells with regard to their function and development of T cell-mediated immunity. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) repress lymphocyte function by controlling gene expression. In this study, we investigated Ag-specific effector T cells and provide evidence that GCs also modulate these cells' cytoskeletal architecture by nongenomic mechanisms. Following GC treatment, effector T cells rapidly lose their polarized morphology, which impedes both their migratory capacity and their interaction with APCs. The cytoskeleton rearrangements are preceded by an activation of ezrin-radixin-moesin proteins, which transiently increases the cellular rigidity but seems to occur independently of altered tyrosine phosphorylation. Phospholipase C activity is critically involved in mediating these nongenomic effects, because its inhibition prevents both T cell depolarization and ezrin-radixin-moesin phosphorylation after GC exposure. GC administration in vivo induced similar morphological changes in effector T cells as observed in vitro, suggesting that the above process plays a role in modulating inflammatory diseases. Taken together, our findings identify a novel mechanism through which GCs rapidly repress T cell function independently of gene transcription. [ABSTRACT FROM AUTHOR]

Recent research reports that inequalities in health are not only the result of individual behaviour but also of environmental influences. This study analyses on household-level, whether such an environmental influence on self-rated health can be found. Using data of the German Socio-Economic Panel, three latent dimensions of environment have been constructed: „quality of life‟, „social environment‟, and „infrastructure‟. Via multilevel regressions it could be shown, that, under control of individual socio-demographic characteristics, a household's level of quality of life as well as its infrastructure do have a significant effect on its members' self-rated health, whereas no significant effect could be found for a household's social environment. [ABSTRACT FROM AUTHOR]

Problem During pregnancy, the immune and the endocrine system cooperate to ensure that the fetal allograft develops without eliciting a maternal immune response. This is presumably in part achieved by dendritic cells (DCs) that play a dominant role in maintaining peripheral tolerance. In this study, we investigated whether female sex hormones, such as human chorionic gonadotropin (hCG), progesterone (Prog), and estradiol (E2), which are highly elevated during pregnancy, induce the differentiation of DCs into a tolerance-inducing phenotype. Methods/Results Immature DCs were generated from blood-derived monocytes and differentiated in the presence of hCG, Prog, E2, or Dexamethasone (Dex) as a control. Unlike Dex, female sex hormones did not prevent the upregulation of surface markers characteristic for mature DCs, such as CD40, CD83, and CD86, except for hCG, which inhibited HLA-DR expression. Similarly, hCG, Prog, and E2 had any impact on neither the rearrangement of the F-actin cytoskeleton nor the enhanced chemokine secretion following DC maturation, both of which were strongly altered by Dex. Nevertheless, the T-cell stimulatory capacity of DCs was significantly reduced after hCG and E2 exposure. Conclusion Our findings suggest that the female sex hormones hCG and E2 inhibit the T-cell stimulatory capacity of DCs, which may help in preventing an allogenic T-cell response against the embryo. [ABSTRACT FROM AUTHOR]

Members of the tetraspanin family including CD9 contribute to the structural organization and plasticity of the plasma membrane. K41, a CD9-specific monoclonal antibody, inhibits the release of HIV-1 and canine distemper virus (CDV)- but not measles virus (MV)-induced cell–cell fusion. We now report that K41, which recognizes a conformational epitope on the large extracellular loop of CD9, induces rapid relocation and clustering of CD9 in net-like structures at cell–cell contact areas. High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated proteins β1-integrin and EWI-F were co-clustered with CD9 at cell–cell interfaces, viral proteins in infected cells were differentially affected. MV envelope proteins were detected within CD9 clusters, whereas CDV proteins were excluded from CD9 clusters. Thus, the tetraspanin CD9 can regulate cell–cell fusion by controlling the access of the fusion machinery to cell contact areas. [ABSTRACT FROM AUTHOR]

Background: Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype. Methods: To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls. Results: Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected. Conclusion: These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control the host's immune responses to pathogens. However, neither the role of hormone concentration nor the differential contribution of the glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities are known. Here we show that low levels of corticosterone enhance NO production as well as mRNA expression of pro-inflammatory cytokines, chemokines and enzymes required for mediator synthesis. In contrast, at high corticosterone concentrations macrophage function was strongly repressed. Importantly, inactivation of the GR by lentiviral delivery of siRNAs abrogated both the immunostimulatory and the immunosuppressive GC actions whereas inactivation of the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in vivo induced a preactivated state in macrophages that could be modulated by corticosterone. We conclude that GCs exert distinct effects on macrophage function dependent on their concentration, and that they primarily act through the GR despite concomitant expression of the MR. [ABSTRACT FROM AUTHOR]

CD3/CD28-induced activation of the PI3/Akt kinase pathway and proliferation is impaired in T cells after contact with the measles virus (MV) glycoprotein (gp) complex. We now show that this signal also impairs actin cytoskeletal remodeling in T cells, which loose their ability to adhere and to promote microvilli formation. MV exposure results in an almost complete collapse of membrane protrusions associated with reduced phosphorylation levels of cofilin and ezrin/radixin/moesin (ERM) proteins. Consistent with their inability to activate Cdc42 and Rac1 in response to the ligation of CD3/CD28, T cells exposed to MV fail to acquire a morphology consistent with spreading and lamellopodia formation. In spite of these impairments of cytoskeleton-driven morphological alterations, these cells are recruited into conjugates with dendritic cells as efficiently as control T cells. The signal elicited by MV, however, prevents T cells to polarize as documented by a failure to redistribute the microtubule organizing center toward the synapse. Moreover, CD3 cannot be efficiently clustered and redistributed to the central region of the immunological synapse. Thus, by inducing microvillar collapse and interfering with cytoskeletal remodeling, MV signaling disturbs the ability of T cells to adhere, spread, and cluster receptors essential for sustained T-cell activation. [ABSTRACT FROM AUTHOR]

By a contact-dependent surface interaction, the measles virus (MV) glycoprotein complex induces a pronounced inhibition of T-cell proliferation. We now show that MV directly interacts with glycosphingolipidenriched membrane microdomains on human primary T cells and alters recruitment and segregation of membrane proximal signaling components. Contact-dependent interference with T-cell receptor-stimulated tyrosine phosphorylation and Ca mobilization is a late event seen 24 h after MV treatment. In contrast, stimulated recruitment of pleckstrin homology domain-containing proteins such as Akt and Vav is inhibited early after MV contact, as is segregation of the activated Akt kinase from rafts. Tyrosine phosphorylation of the regulatory subunit of the phosphatidylinositol 3-kinase (PI3K), p85, is apparently normal then, yet this protein fails to partition to the lipid raft fraction, and this is associated with stable expression of its negative regulator Cbl-b. Thus, by interaction with lipid rafts, MV contact initially targets recruitment of PI3K by preventing stimulated Cbl-b degradation and activation of PI3K-dependent signaling components. [ABSTRACT FROM AUTHOR]

Underlying the idea of the middle classes there is a contradictory positionality, the relations of which ultimately enhance capital accumulation. By opening Marxist critique to Weberian approaches to class, we explain how the self‐ascription of short‐term rental (STR) suppliers to the middle‐class idea boosts exploitation and accumulation. Housing income, and recently that originating in STRs, has been used to maintain the symbolic and material status of the so‐called middle classes in Spain, and specifically in Palma. Based on statistical data analysis and interviews with STR suppliers, managers and workers, we analyse the contradictory class positionality of STR suppliers in Palma (Majorca, Spain). First, we argue, that STR suppliers are part of the middle classes since they bear attributes of rent, labour and also capital, as they employ workers to produce a tourism commodity. Second, we contend that STR overnight stays should not only be considered as land rent payments, but also as the sale of a tourism commodity. Third, we claim that the contradictory positionality of the middle classes fuels self‐exploitation, for STR suppliers misalign their interests with those of capital. [ABSTRACT FROM AUTHOR]

The US agrifood system is very productive, but highly centralized and resource intensive with very weak links between production and consumption. This contributes to high levels of malnutrition and greenhouse gas emissions (GHGE). A popular approach to improvement is localization-reducing direct transport (farm to retail distance, or "food miles"). We examined Santa Barbara County (SBC) California, which mirrors the high production, nutritional and environmental problems, and growing localization movement of California. SBC ranks in the top 1% of US counties in value of agricultural products, and >80% of this value is produce (fruits and vegetables). We calculated the amount of produce grown in and consumed in SBC and estimated that >99% of produce grown in SBC is exported from the county, and >95% of produce consumed in SBC is imported. If all produce consumed in SBC was grown in the county (100% localization), it would reduce GHGE from the agrifood system <1%, and not necessarily affect nutrition. While food miles capture only a portion of the environmental impact of agrifood systems, localization could be done in ways that promote synergies between improving nutrition and reducing GHGE, and many such efforts exist in SBC. [ABSTRACT FROM AUTHOR]

Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools tofurther study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions tofluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells. [ABSTRACT FROM AUTHOR]

In this article, we report the complete coding sequence and to our knowledge, the first functional analysis of two homologous nonclassical MHC class II genes: RT1-Db2 of rat and H2-Eb2 of mouse. They differ in important aspects compared with the classical class II β1 molecules: their mRNA expression by APCs is much lower, they show minimal polymorphism in the Ag-binding domain, and they lack N-glycosylation and the highly conserved histidine 81. Also, their cytoplasmic region is completely different and longer. To study and compare them with their classical counterparts, we transduced them in different cell lines. These studies show that they can pair with the classical a-chains (RT1-Da and H2-Ea) and are expressed at the cell surface where they can present superantigens. Interestingly, compared with the classical molecules, they have an extraordinary capacity to present the superantigen Yersinia pseudotuberculosis mitogen. Taken together, our findings suggest that the b2 genes, together with the respective a-chain genes, encode for H2-E2 or RT1-D2 molecules, which could function as Ag-presenting molecules for a particular class of Ags, as modulators of Ag presentation like nonclassical nonpolymorphic class II molecules DM and DO do, or even as players outside the immune system. [ABSTRACT FROM AUTHOR]

Human brain microvascular endothelial cells forming the blood-brain barrier (BBB) release soluble vascular cell adhesion molecule-1 (sVCAM-1) under inflammatory conditions. Furthermore, sVCAM-1 serum levels in untreated patients with multiple sclerosis (MS) correlate with a breakdown of the BBB as measured by gadolinium-enhanced MRI. To date, it is unknown whether sVCAM-1 itself modulates BBB permeability. Here, we provide evidence that human brain endothelium expresses integrin α-4/β-1, the molecular binding partner of sVCAM-1, and that sVCAM-1 directly impairs BBB function by inducing intracellular signalling events through integrin α-4. Primary human brain microvascular endothelial cells showed low to moderate integrin α-4 and strong β-1 but no definite β-7 expression in vitro and in situ. Increased brain endothelial integrin α-4 expression was observed in active MS lesions in situ and after angiogenic stimulation in vitro. Exposure of cultured primary brain endothelial cells to recombinant sVCAM-1 significantly increased their permeability to the soluble tracer dextran, which was paralleled by formation of actin stress fibres and reduced staining of tight junction-associated molecules. Soluble VCAM-1 was also found to activate Rho GTPase and p38 MAP kinase. Chemical inhibition of these signalling pathways partially prevented sVCAM-1-induced changes of tight junction arrangement. Importantly, natalizumab, a neutralising recombinant monoclonal antibody against integrin α-4 approved for the treatment of patients with relapsing-remitting MS, partially antagonised the barrier-disturbing effect of sVCAM-1. In summary, we newly characterised sVCAM-1 as a compromising factor of brain endothelial barrier function that may be partially blocked by the MS therapeutic natalizumab. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is characterized at the cellular level by a destruction of neuromelanin (NM)-containing dopaminergic cells and a profound reduction in striatal dopamine. It has been shown recently that anti-melanin antibodies are increased in sera of Parkinson patients, suggesting that NM may act as an autoantigen. In this study we tested whether NM is being recognized by dendritic cells (DCs), the major cell type for inducing T- and B-cell responses in vivo. This recognition of NM by DCs is a prerequisite to trigger an adaptive autoimmune response directed against NM-associated structures.Results: Murine DCs were treated with NM of substantia nigra (SN) from human subjects or with synthetic dopamine melanin (DAM). DCs effectively phagocytized NM and subsequently developed a mature phenotype (CD86(high)/MHCII(high)). NM-activated DCs secreted the proinflammatory cytokines IL-6 and TNF-α. In addition, they potently triggered T cell proliferation in a mixed lymphocyte reaction, showing that DC activation was functional to induce a primary T cell response. In contrast, DAM, which lacks the protein and lipid components of NM but mimics the dopamine-melanin backbone of NM, had only very little effect on DC phenotype and function.Conclusions: NM is recognized by DCs in vitro and triggers their maturation. If operative in vivo, this would allow the DC-mediated transport and presentation of SN antigens to the adaptive immune system, leading to autoimmmunity in susceptible individuals. Our data provide a rationale for an autoimmune-based pathomechanism of PD with NM as the initial trigger. [ABSTRACT FROM AUTHOR]