Serum 25-hydroxyvitamin D level and kidney function decline in a Swiss general adult population.

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria. Baseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors. Among the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria. The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.

Abrogation of HMX1 function causes rare oculoauricular syndrome associated with congenital cataract, anterior segment dysgenesis, and retinal dystrophy.

PURPOSE: To define the phenotypic manifestation, confirm the genetic basis, and delineate the pathogenic mechanisms underlying an oculoauricular syndrome (OAS). METHODS: Two individuals from a consanguineous family underwent comprehensive clinical phenotyping and electrodiagnostic testing (EDT). Genome-wide microarray analysis and Sanger sequencing of the candidate gene were used to identify the likely causal variant. Protein modelling, Western blotting, and dual luciferase assays were used to assess the pathogenic effect of the variant in vitro. RESULTS: Complex developmental ocular abnormalities of congenital cataract, anterior segment dysgenesis, iris coloboma, early-onset retinal dystrophy, and abnormal external ear cartilage presented in the affected family members. Genetic analyses identified a homozygous c.650A>C; p.(Gln217Pro) missense mutation within the highly conserved homeodomain of the H6 family homeobox 1 (HMX1) gene. Protein modelling predicts that the variant may have a detrimental effect on protein folding and/or stability. In vitro analyses were able to demonstrate that the mutation has no effect on protein expression but adversely alters function. CONCLUSIONS: Oculoauricular syndrome is an autosomal recessive condition that has a profound effect on the development of the external ear, anterior segment, and retina, leading to significant visual loss at an early age. This study has delineated the phenotype and confirmed HMX1 as the gene causative of OAS, enabling the description of only the second family with the condition. HMX1 is a key player in ocular development, possibly in both the pathway responsible for lens and retina development, and via the gene network integral to optic fissure closure.

Radial dose function of a 90Sr 90Y seed in water and A150: Comment on Calibration and characterization of beta-particle sources for intravascular brachytherapy

Intravascular brachytherapy with beta sources has become a useful technique to prevent restenosis after cardiovascular intervention. In particular, the Beta-Cath high-dose-rate system, manufactured by Novoste Corporation, is a commercially available 90Sr 90Y source for intravascular brachytherapy that is achieving widespread use. Its dosimetric characterization has attracted considerable attention in recent years. Unfortunately, the short ranges of the emitted beta particles and the associated large dose gradients make experimental measurements particularly difficult. This circumstance has motivated the appearance of a number of papers addressing the characterization of this source by means of Monte Carlo simulation techniques.

Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.

Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs.

MHC/Peptide-Specific Interaction of the Humoral Immune System: A New Category of Antibodies.

Abs bind to unprocessed Ags, whereas cytotoxic CD8(+) T cells recognize peptides derived from endogenously processed Ags presented in the context of class I MHC complexes. We screened, by ELISA, human sera for Abs reacting specifically with the influenza matrix protein (IMP)-derived peptide58-66 displayed by HLA-A*0201 complexes. Among 653 healthy volunteers, blood donors, and women on delivery, high-titered HLA-A*0201/IMP58-66 complex-specific IgG Abs were detected in 11 females with a history of pregnancies and in 1 male, all HLA-A*0201(-). These Abs had the same specificity as HLA-A*0201/IMP58-66-specific cytotoxic T cells and bound neither to HLA-A*0201 nor the peptide alone. No such Abs were detected in HLA-A*0201(+) volunteers. These Abs were not cross-reactive to other self-MHC class I alleles displaying IMP58-66, but bound to MHC class I complexes of an HLA nonidentical offspring. HLA-A*0201/IMP58-66 Abs were also detected in the cord blood of newborns, indicating that HLA-A*0201/IMP58-66 Abs are produced in HLA-A*0201(-) mothers and enter the fetal blood system. That Abs can bind to peptides derived from endogenous Ags presented by MHC complexes opens new perspectives on interactions between the cellular and humoral immune system.

Testing Local Adaptation in a Natural Great Tit-Malaria System: An Experimental Approach.

Finding out whether Plasmodium spp. are coevolving with their vertebrate hosts is of both theoretical and applied interest and can influence our understanding of the effects and dynamics of malaria infection. In this study, we tested for local adaptation as a signature of coevolution between malaria blood parasites, Plasmodium spp. and its host, the great tit, Parus major. We conducted a reciprocal transplant experiment of birds in the field, where we exposed birds from two populations to Plasmodium parasites. This experimental set-up also provided a unique opportunity to study the natural history of malaria infection in the wild and to assess the effects of primary malaria infection on juvenile birds. We present three main findings: i) there was no support for local adaptation; ii) there was a male-biased infection rate; iii) infection occurred towards the end of the summer and differed between sites. There were also site-specific effects of malaria infection on the hosts. Taken together, we present one of the few experimental studies of parasite-host local adaptation in a natural malaria system, and our results shed light on the effects of avian malaria infection in the wild.

Asymmetrical nature of the Trollius-Chiastocheta interaction: insights into the evolution of nursery pollination systems

The mutualistic versus antagonistic nature of an interaction is defined by costs and benefits of each partner, which may vary depending on the environment. Contrasting with this dynamic view, several pollination interactions are considered as strictly obligate and mutualistic. Here, we focus on the interaction between Trollius europaeus and Chiastocheta flies, considered as a specialized and obligate nursery pollination system - the flies are thought to be exclusive pollinators of the plant and their larvae develop only in T.europaeus fruits. In this system, features such as the globelike flower shape are claimed to have evolved in a coevolutionary context. We examine the specificity of this pollination system and measure traits related to offspring fitness in isolated T.europaeus populations, in some of which Chiastocheta flies have gone extinct. We hypothesize that if this interaction is specific and obligate, the plant should experience dramatic drop in its relative fitness in the absence of Chiastocheta. Contrasting with this hypothesis, T.europaeus populations without flies demonstrate a similar relative fitness to those with the flies present, contradicting the putative obligatory nature of this pollination system. It also agrees with our observation that many other insects also visit and carry pollen among T.europaeus flowers. We propose that the interaction could have evolved through maximization of by-product benefits of the Chiastocheta visits, through the male flower function, and selection on floral traits by the most effective pollinator. We argue this mechanism is also central in the evolution of other nursery pollination systems.

Autocrine Action of IGF2 Regulates Adult β-Cell Mass and Function.

Insulin-like growth factor 2 (IGF2), produced and secreted by adult β-cells, functions as an autocrine activator of the β-cell insulin-like growth factor 1 receptor signaling pathway. Whether this autocrine activity of IGF2 plays a physiological role in β-cell and whole-body physiology is not known. Here, we studied mice with β-cell-specific inactivation of Igf2 (βIGF2KO mice) and assessed β-cell mass and function in aging, pregnancy, and acute induction of insulin resistance. We showed that glucose-stimulated insulin secretion (GSIS) was markedly reduced in old female βIGF2KO mice; glucose tolerance was, however, normal because of increased insulin sensitivity. While on a high-fat diet, both male and female βIGF2KO mice displayed lower GSIS compared with control mice, but reduced β-cell mass was observed only in female βIGF2KO mice. During pregnancy, there was no increase in β-cell proliferation and mass in βIGF2KO mice. Finally, β-cell mass expansion in response to acute induction of insulin resistance was lower in βIGF2KO mice than in control mice. Thus, the autocrine action of IGF2 regulates adult β-cell mass and function to preserve in vivo GSIS in aging and to adapt β-cell mass in response to metabolic stress, pregnancy hormones, and acute induction of insulin resistance.

Aldosterone effects on glomerular structure and function.

OBJECTIVE: Experimental evidence suggests that aldosterone directly contributes to organ damage by promoting cell growth, fibrosis, and inflammation. Based on these premises, this work aimed to assess the glomerular effects of aldosterone, alone and in combination with salt. METHODS: After undergoing uninephrectomy, 75 rats were allocated to five groups: control, salt diet, aldosterone, aldosterone + salt diet, aldosterone + salt diet and eplerenone, and they were all studied for four weeks. We focused on glomerular structural, functional, and molecular changes, including slit diaphragm components, local renin-angiotensin system activation, as well as pro-oxidative and profibrotic changes. RESULTS: Aldosterone significantly increased systolic blood pressure, led to glomerular hypertrophy, mesangial expansion, and it significantly increased the glomerular permeability to albumin and the albumin excretion rate, indicating the presence of glomerular damage. These effects were worsened by adding salt to aldosterone, while they were reduced by eplerenone. Aldosterone-induced glomerular damage was associated with glomerular angiotensin-converting enzyme (ACE) 2 downregulation, with ACE/ACE2 ratio increase, ANP decrease, as well as with glomerular pro-oxidative and profibrotic changes. CONCLUSIONS: Aldosterone damages not only the structure but also the function of the glomerulus. ACE/ACE2 upregulation, ACE2 and ANP downregulation, and pro-oxidative and profibrotic changes are possible mechanisms accounting for aldosterone-induced glomerular injury.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huët anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huët anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability. © 2015 Wiley Periodicals, Inc.

Chronic disease management programmes for adults with asthma (intervention Review)

BACKGROUND: The burden of asthma on patients and healthcare systems is substantial. Interventions have been developed to overcome difficulties in asthma management. These include chronic disease management programmes, which are more than simple patient education, encompassing a set of coherent interventions that centre on the patients' needs, encouraging the co-ordination and integration of health services provided by a variety of healthcare professionals, and emphasising patient self-management as well as patient education. OBJECTIVES: To evaluate the effectiveness of chronic disease management programmes for adults with asthma. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, MEDLINE (MEDLINE In-Process and Other Non-Indexed Citations), EMBASE, CINAHL, and PsycINFO were searched up to June 2014. We also handsearched selected journals from 2000 to 2012 and scanned reference lists of relevant reviews. SELECTION CRITERIA: We included individual or cluster-randomised controlled trials, non-randomised controlled trials, and controlled before-after studies comparing chronic disease management programmes with usual care in adults over 16 years of age with a diagnosis of asthma. The chronic disease management programmes had to satisfy at least the following five criteria: an organisational component targeting patients; an organisational component targeting healthcare professionals or the healthcare system, or both; patient education or self-management support, or both; active involvement of two or more healthcare professionals in patient care; a minimum duration of three months. DATA COLLECTION AND ANALYSIS: After an initial screen of the titles, two review authors working independently assessed the studies for eligibility and study quality; they also extracted the data. We contacted authors to obtain missing information and additional data, where necessary. We pooled results using the random-effects model and reported the pooled mean or standardised mean differences (SMDs). MAIN RESULTS: A total of 20 studies including 81,746 patients (median 129.5) were included in this review, with a follow-up ranging from 3 to more than 12 months. Patients' mean age was 42.5 years, 60% were female, and their asthma was mostly rated as moderate to severe. Overall the studies were of moderate to low methodological quality, because of limitations in their design and the wide confidence intervals for certain results.Compared with usual care, chronic disease management programmes resulted in improvements in asthma-specific quality of life (SMD 0.22, 95% confidence interval (CI) 0.08 to 0.37), asthma severity scores (SMD 0.18, 95% CI 0.05 to 0.30), and lung function tests (SMD 0.19, 95% CI 0.09 to 0.30). The data for improvement in self-efficacy scores were inconclusive (SMD 0.51, 95% CI -0.08 to 1.11). Results on hospitalisations and emergency department or unscheduled visits could not be combined in a meta-analysis because the data were too heterogeneous; results from the individual studies were inconclusive overall. Only a few studies reported results on asthma exacerbations, days off work or school, use of an action plan, and patient satisfaction. Meta-analyses could not be performed for these outcomes. AUTHORS' CONCLUSIONS: There is moderate to low quality evidence that chronic disease management programmes for adults with asthma can improve asthma-specific quality of life, asthma severity, and lung function tests. Overall, these results provide encouraging evidence of the potential effectiveness of these programmes in adults with asthma when compared with usual care. However, the optimal composition of asthma chronic disease management programmes and their added value, compared with education or self-management alone that is usually offered to patients with asthma, need further investigation.

PEC1/AtABCG32 transport function in cuticle biosynthesis

Most aerial parts of the plants are covered by a hydrophobic coating called cuticle. The cuticle is formed of cutin, a complex mixture of esterified fatty acids that are embedded and associated with waxes. The cuticle often appears as a superposition of layers of different composition: The cuticle proper formed of cutin and a mixture of waxes and underneath, the cuticle layer containing cutin, intracuticular waxes and polysaccharides of the cell wall. In addition to its involvement in plant development by preventing organ fusions, the cuticle acts as a barrier to prevent water loss and protect plants against environmental aggressions such as excessive radiation or pathogens attacks. PEC1/AtABCG32 is an ABC transporter from the PDR family involved in cutin biosynthesis. Characterization of the peci mutant in Arabidopsis thaliana showed that PEC1 plays a significant role in the diffusion barrier formation in leaves and petals. The cuticles of leaves and flowers of peci are permeable and the cuticular layer rather than the cuticular proper was altered in the petals, underlining the importance of this particular layer in the maintenance of the diffusion barrier. Chemical analysis on the flower cutin monomer composition of ped mutant revealed a decrease in hydroxylated cutin monomers, suggesting a function of PEC1 in the incorporation of these monomers in the polymer cutin. However, the exact nature of the substrates of PEC1 remained elusive. PEC1 homologues in barley and rice, respectively HvABCG31/EIBI1 and OsABCG31, are also implicated in cuticle biosynthesis. Interestingly, the rice mutant displays more severe phenotypes such as dwarfism and spreading necrosis conducting to the seedling death. In this work, we further characterized osabcg31 mutant and hairpin-RNAi downregulated OsABCG31 plant lines showing reduced growth and cuticle permeability. Our analysis showed a decrease in hydroxylated cutin monomers and severe disruptions in the cuticle, which explain the permeability. Further insights into the function of the cuticle in rice resistance/susceptibility to Pathogens were obtained after inoculation with Magnaporthe oryzae, the fungus responsible for the rice blast disease. Osabcg31 as well as the transgenic lines downregulating OsABCG31 showed increased resistance to the fungus. However, only later steps of infection are reduced . and no impact is obseived on the germination or penetration stages, suggesting that the cuticle disruption per se is not responsible for the resistance. We further investigated the cause of the resistance by analyzing the expression of defense related gene in osabcg31 prior to infection. We found that osabcg31 constitutively express defense related genes, which may explain the resistance, the dwarfism and the cell death. osabcg31 is thus a tool to study the connection between cuticle, plant development and defense signaling networks in rice. The transport function of PEC1 family members is still unknown. In order to link cutin biosynthesis and transport activity, we combined ped mutation with mutations in cutin synthesis related genes. Here, we show that PEC1 acts independently from GPAT4 and GPAT8 pathway and partially overlaps with GPAT6 biosynthesis pathway that leads to the production of hydroxylated C16 cutin precursor 2-Mono(10,16-dihydroxyhexadecanoylJglycerol (2-MHG). In addition, we noticed that despite a comparable cutin monomer composition, ped mutant leaves cuticle are permeable while that of gpat6 mutant are not. This finding raises the possibility of PEC1 being required for the incorporation of C16 hydroxylated monomers and their structural arrangement rather than their direct transport towards the cuticle. A careful investigation of the cuticle permeability, cutin composition and ultrastructure during leave development in Wt plants and ped mutants revealed a possible different regulation of several pathways of cutin biosynthesis and showed the importance of PEC1 function early during leave cuticle maturation. In order to elucidate the transport activity of PEC1, we successfully expressed PEC1 in Nicotiana benthamiana plant system for direct transport experiments. This system will be used to test the PEC 1-dependent transport of potential substrates such as sn-2-monoacylglycerol loaded with a hydroxylated C16 fatty acid. -- Toutes les parties aériennes des plantes sont recouvertes d'une couche hydrophobe appelée «cuticule». Cette cuticule est composée de cutine, un polymère d'acides gras estérifiés, et de cires. La cuticule apparaît souvent sous forme de couches superposées: une première couche extérieure appelée «cuticle proper» formée de cutine et d'un mélange de cires, et une deuxième couche, la «cuticle layer», formée de cutine associée à des cires intracuticulaires et des polysaccharides pariétaux. La cuticule joue le rôle de barrière prévenant contre la perte d'eau et les agressions environnementales. AtABCG32/PEC1 est un transporteur ABC de la famille des PDR impliqué dans la synthèse de la cutine. L'étude du mutant peci d'Arabidopsis thaliana a révélé une fonction de PEC1 dans la formation de la barrière de diffusion. La cuticule des feuilles et fleurs de peci est perméable. Des altérations de la «cuticle layer» ont été démontrées, soulignant son importance dans le maintien de la barrière. L'analyse de la composition de la cutine de peci a montré une réduction spécifique en monomères hydroxylés, suggérant un rôle de PEC1 dans leur incorporation dans la cuticule. Cependant, la nature exacte des substrats de PEC1 n'a pas été identifiée. PEC1 possède deux homologues chez l'orge et le riz, respectivement HvABCG31 et OsABCG31, et qui sont impliqués dans la biosynthèse de la cuticule. Chez le riz, des phénotypes plus sévères ont été observés tels que nanisme et nécroses conduisant à la mort des jeunes plants. Dans cette étude, nous avons continué la caractérisation de osabcg31 ainsi que des lignées de riz sous exprimant le gène OsABCG31 et présentant une cuticule perméable tout en ayant une meilleure croissance. Notre étude a démontré une réduction des monomères hydroxylés de cutine et une désorganisation de la structure de la cuticule, aggravée dans le mutant osabcg31. Ce résultat explique la perméabilité observée. Des mformations P|us approfondies sur l'implication de la cuticule dans la résistance aux pathogènes ont été obtenues après inoculation du mutant osabcg31 et les lignées sous- exprimant OsABCG31 avec une souche virulente de Magnaporthe Oryzae, le champignon responsable de la pyriculariose du riz. Les différentes lignées testées ont démontré une résistance au pathogène. Cependant, seules les étapes tardives de l'infection sont réduites et aucun impact n'est observé sur la germination des spores ou la pénétration du champignon, suggérant que les modifications de la cuticule ne sont pas directement à l'origine de la résistance. L'analyse de l'expression de gènes impliqués dans la résistance à Magnaporthe.oryzae a mis en évidence l'expression constitutive de ces gènes en l'absence de tout contact avec le pathogène. Ceci explique la résistance, le nanisme et la mort cellulaire observés. Ainsi, osabcg31 représente un outil efficace pour l'étude intégrée des systèmes de régulation de la défense, de développement des plantes et la cuticule. La nature des substrats transportés par PEC1/AtABCG32 reste inconnue. Dans le but d'établir une liaison entre biosynthèse de cutine et transport des précurseurs par PEC1, la mutation peci a été combinée avec des mutants impliqués dans différentes voies de biosynthèse. Cette étude a démontré une fonction indépendante de PEC1 de la voie de biosynthèse impliquant les enzymes GPAT4 et GPAT8, et une fonction partiellement indépendante de la voie impliquant GPAT6 qui mène à la production de précurseurs sn-2- monoacylglycerol chargés en acides gras en C16 (2-MHG). De plus, malgré un profil similaire en monomères de cutine, gpat6 conserve une cuticule imperméable alors que celle de PEC1 est perméable. Ceci suggère que PEC1 est nécessaire à l'incorporation des monomères en C16 et leur arrangement structurel plutôt que simplement à leur transport direct. L'étude approfondie de la perméabilité cuticulaire, de la structure ainsi que de la composition en cutine pendant le développement des feuilles de peci et la plante sauvage a révélé l'existence de différentes régulations des voies de biosynthèses des monomères et a démontré l'importance de PEC1 dans les premières étapes de la mise en place de la cuticule. Pour identifier les substrats transportés, l'expression de PEC1 chez le système hétérologue Nicotiana benthamiana a été conduite avec succès. Ce système sera utilisé pour tester le transport de substrats potentiels tels que le sn-2-monoacylglycerol chargé en acide gras en C16.

Chlamydiaceae and Chlamydia-like organisms in the koala (Phascolarctos cinereus)--organ distribution and histopathological findings.

Chlamydial infections in koalas can cause life-threatening diseases leading to blindness and sterility. However, little is known about the systemic spread of chlamydiae in the inner organs of the koala, and data concerning related pathological organ lesions are limited. The aim of this study was to perform a thorough investigation of organs from 23 koalas and to correlate their histopathological lesions to molecular chlamydial detection. To reach this goal, 246 formalin-fixed and paraffin embedded organ samples from 23 koalas were investigated by histopathology, Chlamydiaceae real-time PCR and immunohistochemistry, ArrayTube Microarray for Chlamydiaceae species identification as well as Chlamydiales real-time PCR and sequencing. By PCR, two koalas were positive for Chlamydia pecorum whereas immunohistochemical labelling for Chlamydiaceae was detected in 10 tissues out of nine koalas. The majority of these (n=6) had positive labelling in the urogenital tract related to histopathological lesions such as cystitis, endometritis, pyelonephritis and prostatitis. Somehow unexpected was the positive labelling in the gastrointestinal tract including the cloaca as well as in lung and spleen indicating systemic spread of infection. Uncultured Chlamydiales were detected in several organs of seven koalas by PCR, and four of these suffered from plasmacytic enteritis of unknown aetiology. Whether the finding of Chlamydia-like organisms in the gastrointestinal tract is linked to plasmacytic enteritis is unclear and remains speculative. However, as recently shown in a mouse model, the gastrointestinal tract might play a role being the site for persistent chlamydial infections and being a source for reinfection of the genital tract.

Threat Simulation- The Function of Dreaming?

Dreaming is a pure form of phenomenality, created by the brain untouched by external stimulation or behavioral activity, yet including a full range of phenomenal contents. Thus, it has been suggested that the dreaming brain could be used as a model system in a biological research program on consciousness (Revonsuo, 2006). In the present thesis, the philosophical view of biological realism is accepted, and thus, dreaming is considered as a natural biological phenomenon, explainable in naturalistic terms. The major theoretical contribution of the present thesis is that it explores dreaming from a multidisciplinary perspective, integrating information from various fields of science, such as dream research, consciousness research, evolutionary psychology, and cognitive neuroscience. Further, it places dreaming into a multilevel framework, and investigates the constitutive, etiological, and contextual explanations for dreaming. Currently, the only theory offering a full multilevel explanation for dreaming, that is, a theory including constitutive, etiological, and contextual level explanations, is the Threat Simulation Theory (TST) (Revonsuo, 2000a; 2000b). The empirical significance of the present thesis lies in the tests conducted to test this specific theory put forth to explain the form, content, and biological function of dreaming. The first step in the empirical testing of the TST was to define exact criteria for what is a ‘threatening event’ in dreams, and then to develop a detailed and reliable content analysis scale with which it is possible to empirically explore and quantify threatening events in dreams. The second step was to seek answers to the following questions derived from the TST: How frequent threatening events are in dreams? What kind of qualities these events have? How threatening events in dreams relate to the most recently encoded or the most salient memory traces of threatening events experienced in waking life? What are the effects of exposure to severe waking life threat on dreams? The results reveal that threatening events are relatively frequent in dreams, and that the simulated threats are realistic. The most common threats include aggression, are targeted mainly against the dream self, and include simulations of relevant and appropriate defensive actions. Further, real threat experiences activate the threat simulation system in a unique manner, and dream content is modulated by the activation of long term episodic memory traces with highest negative saliency. To sum up, most of the predictions of the TST tested in this thesis received considerable support. The TST presents a strong argument that explains the specific design of dreams as threat simulations. The TST also offers a plausible explanation for why dreaming would have been selected for: because dreaming interacted with the environment in such a way that enhanced fitness of ancestral humans. By referring to a single threat simulation mechanism it furthermore manages to explain a wide variety of dream content data that already exists in the literature, and to predict the overall statistical patterns of threat content in different samples of dreams. The TST and the empirical tests conducted to test the theory are a prime example of what a multidisciplinary approach to mental phenomena can accomplish. Thus far, dreaming seems to have always resided in the periphery of science, never regarded worth to be studied by the mainstream. Nevertheless, when brought to the spotlight, the study of dreaming can greatly benefit from ideas in diverse branches of science. Vice versa, knowledge learned from the study of dreaming can be applied in various disciplines. The main contribution of the present thesis lies in putting dreaming back where it belongs, that is, into the spotlight in the cross-road of various disciplines.

The scrutiny of the principle of subsidiarity by autonomous regional parliaments with particular reference to the participation of the Parliament of Catalonia in the early warning system

The purpose of this article is to offer a practical approach to the new European dimension for regional parliaments signified by the entry into force of the Treaty of Lisbon. The parliamentary scrutiny of subsidiarity by way of the early warning system has assigned a new mission to legislative assemblies with the aim of reinforcing the intervention of regions in the drafting of policies by Union institutions. In the Spanish case, the institutionalisation of this mechanism came about with Act nº 24/2009, which attributes to the Joint Committee for the European Union, in the name of the Cortes Generales [the Spanish Parliament], the function of receiving the proposals for legislative acts by the EU and transferring them to the regional parliaments in order for the latter to issue, in a brief period of four weeks, a report on compliance with the principle of subsidiarity. The majority of regional parliaments have also carried out normative reforms to regulate the procedure of participation in the early warning system.