PAK1 Protein Expression in the Auditory Cortex of Schizophrenia Subjects

Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

The interaction between the proliferating macroalga Asparagopsis taxiformis and the coral Astroides calycularis induces changes in microbiome and metabolomic fingerprints

Mediterranean Sea ecosystems are considered as hotspots of biological introductions, exposed to possible negative effects of non-indigenous species. In such temperate marine ecosystems, macroalgae may be dominant, with a great percentage of their diversity represented by introduced species. Their interaction with temperate indigenous benthic organisms have been poorly investigated. To provide new insights, we performed an experimental study on the interaction between the introduced proliferative red alga Asparagopsis taxiformis and the indigenous Mediterranean coral Astroides calycularis. The biological response measurements included meta-barcoding of the associated microbial communities and metabolomic fingerprinting of both species. Significant changes were detected among both associated microbial communities, the interspecific differences decreasing with stronger host interaction. No short term effects of the macroalga on the coral health, neither on its polyp activity or its metabolism, were detected. In contrast, the contact interaction with the coral induced a change in the macroalgal metabolomic fingerprint with a significant increase of its bioactivity against the marine bacteria Aliivibrio fischeri. This induction was related to the expression of bioactive metabolites located on the macroalgal surface, a phenomenon which might represent an immediate defensive response of the macroalga or an allelopathic offense against coral.ERA-NET Biome project "SEAPROLIF"; CNRS; Provence Alpes Cote d'Azur Region; TOTAL Fundation; Fundacao para a Ciencia e a Tecnologia (FCT) [Netbiome/0002/2011]; FCT fellowships [SFRH/BPD/63703/2009, SFRH/BPD/107878/2015]info:eu-repo/semantics/publishedVersio

Gene Expression Analysis Implicates a Death Receptor Pathway in Schizophrenia Pathology

An increase in apoptotic events may underlie neuropathology in schizophrenia. By data-mining approaches, we identified significant expression changes in death receptor signaling pathways in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia, particularly implicating the Tumor Necrosis Factor Superfamily member 6 (FAS) receptor and the Tumor Necrosis Factor [ligand] Superfamily member 13 (TNFSF13) in schizophrenia. We sought to confirm and replicate in an independent tissue collection the noted mRNA changes with quantitative real-time RT-PCR. To test for regional and diagnostic specificity, tissue from orbital frontal cortex (OFC) was examined and a bipolar disorder group included. In schizophrenia, we confirmed and replicated significantly increased expression of TNFSF13 mRNA in the DLPFC. Also, a significantly larger proportion of subjects in the schizophrenia group had elevated FAS receptor expression in the DLPFC relative to unaffected controls. These changes were not observed in the bipolar disorder group. In the OFC, there were no significant differences in TNFSF13 or FAS receptor mRNA expression. Decreases in BH3 interacting domain death agonist (BID) mRNA transcript levels were found in the schizophrenia and bipolar disorder groups affecting both the DLPFC and the OFC. We tested if TNFSF13 mRNA expression correlated with neuronal mRNAs in the DLPFC, and found significant negative correlations with interneuron markers, parvalbumin and somatostatin, and a positive correlation with PPP1R9B (spinophilin), but not DLG4 (PSD-95). The expression of TNFSF13 mRNA in DLPFC correlated negatively with tissue pH, but decreasing pH in cultured cells did not cause increased TNFSF13 mRNA nor did exogenous TNFSF13 decrease pH. We concluded that increased TNFSF13 expression may be one of several cell-death cytokine abnormalities that contribute to the observed brain pathology in schizophrenia, and while increased TNFSF13 may be associated with lower brain pH, the change is not necessarily causally related to brain pH

Balancing, Proportionality, and Constitutional Rights

In the theory and practice of constitutional adjudication, proportionality review plays a crucial role. At a theoretical level, it lies at core of the debate on rights adjudication; in judicial practice, it is a widespread decision-making model characterizing the action of constitutional, supra-national and international courts. Despite its circulation and centrality in contemporary legal discourse, proportionality in rights-adjudication is still extremely controversial. It raises normative questions—concerning its justification and limits—and descriptive questions—regarding its nature and distinctive features. The chapter addresses both orders of questions. Part I centres on the justification of proportionality review, the connection between proportionality, balancing and theories of rights and the critical aspects of this connection. Part II identifies and analyses the different forms of proportionality both in review, as a template for rights-adjudication, and of review, as a way of defining the scope and limits of adjudication

DNase Sda1 Allows Invasive M1T1 Group A Streptococcus to Prevent TLR9-Dependent Recognition

Group A Streptococcus (GAS) has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase

The SAMI Galaxy Survey: The cluster redshift survey, target selection and cluster properties

We describe the selection of galaxies targeted in eight low redshift clusters (APMCC0917, A168, A4038, EDCC442, A3880, A2399, A119 and A85; $0.029 < z < 0.058$) as part of the Sydney-AAO Multi-Object integral field Spectrograph Galaxy Survey (SAMI-GS). We have conducted a redshift survey of these clusters using the AAOmega multi-object spectrograph on the 3.9m Anglo-Australian Telescope. The redshift survey is used to determine cluster membership and to characterise the dynamical properties of the clusters. In combination with existing data, the survey resulted in 21,257 reliable redshift measurements and 2899 confirmed cluster member galaxies. Our redshift catalogue has a high spectroscopic completeness ($\sim 94\%$) for $r_{\rm petro} \leq 19.4$ and clustercentric distances $R< 2\rm{R}_{200}$. We use the confirmed cluster member positions and redshifts to determine cluster velocity dispersion, $\rm{R}_{200}$, virial and caustic masses, as well as cluster structure. The clusters have virial masses $14.25 \leq {\rm log }({\rm M}_{200}/\rm{M}_{\odot}) \leq 15.19$. The cluster sample exhibits a range of dynamical states, from relatively relaxed-appearing systems, to clusters with strong indications of merger-related substructure. Aperture- and PSF-matched photometry are derived from SDSS and VST/ATLAS imaging and used to estimate stellar masses. These estimates, in combination with the redshifts, are used to define the input target catalogue for the cluster portion of the SAMI-GS. The primary SAMI-GS cluster targets have $R< \rm{R}_{200}$, velocities $|v_{\rm pec}| < 3.5\sigma_{200}$ and stellar masses $9.5 \leq {\rm log(M}^*_{approx}/\rm{M}_{\odot}) \leq 12$. Finally, we give an update on the SAMI-GS progress for the cluster regions

The SAMI Galaxy Survey: Early Data Release

We present the Early Data Release of the Sydney–AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of _3400 low-redshift (z < 0:12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated datacubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All datacubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated datacubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals in the continuum of 0.9–1.2 per cent, a relative flux calibration uncertainty of 4.1 per cent (systematic) plus 4.3 per cent (statistical), and atmospheric dispersion removed with an accuracy of 0:0009, less than a fifth of a spaxel

The SAMI Galaxy Survey: Early Data Release

We present the Early Data Release of the Sydney–AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of _3400 low-redshift (z < 0:12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated datacubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All datacubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated datacubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals in the continuum of 0.9–1.2 per cent, a relative flux calibration uncertainty of 4.1 per cent (systematic) plus 4.3 per cent (statistical), and atmospheric dispersion removed with an accuracy of 0:0009, less than a fifth of a spaxel