Regulators of complement activity mediate inhibitory mechanisms through a common C3b‐binding mode

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Evaluating the use of the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) to estimate IQ in children with low intellectual ability

In situations where completing a full intellectual assessment is not possible or desirable the clinician or researcher may require an alternative means of accurately estimating intellectual functioning. There has been limited research in the use of proxy IQ measures in children with an intellectual disability or low IQ. The present study aimed to provide a means of converting total scores from a screening tool (the Child and Adolescent Intellectual Disability Screening Questionnaire: CAIDS-Q) to an estimated IQ. A series of linear regression analyses were conducted on data from 428 children and young people referred to clinical services, where FSIQ was predicted from CAIDS-Q total scores. Analyses were conducted for three age groups between ages 6 and 18 years. The study presents a conversion table for converting CAIDS-Q total scores to estimates of FSIQ, with corresponding 95% prediction intervals to allow the clinician or researcher to estimate FSIQ scores from CAIDS-Q total scores. It is emphasised that, while this conversion may offer a quick means of estimating intellectual functioning in children with a below average IQ, it should be used with caution, especially in children aged between 6 and 8 years old

Non-Fermi-liquid d-wave metal phase of strongly interacting electrons

Developing a theoretical framework for conducting electronic fluids qualitatively distinct from those described by Landau's Fermi-liquid theory is of central importance to many outstanding problems in condensed matter physics. One such problem is that, above the transition temperature and near optimal doping, high-transition-temperature copper-oxide superconductors exhibit `strange metal' behaviour that is inconsistent with being a traditional Landau Fermi liquid. Indeed, a microscopic theory of a strange-metal quantum phase could shed new light on the interesting low-temperature behaviour in the pseudogap regime and on the d-wave superconductor itself. Here we present a theory for a specific example of a strange metal---the 'd-wave metal'. Using variational wavefunctions, gauge theoretic arguments, and ultimately large-scale density matrix renormalization group calculations, we show that this remarkable quantum phase is the ground state of a reasonable microscopic Hamiltonian---the usual t-J model with electron kinetic energy $t$ and two-spin exchange $J$ supplemented with a frustrated electron `ring-exchange' term, which we here examine extensively on the square lattice two-leg ladder. These findings constitute an explicit theoretical example of a genuine non-Fermi-liquid metal existing as the ground state of a realistic model.Comment: 22 pages, 12 figures: 6 pages, 7 figures of main text + 16 pages, 5 figures of Supplementary Information; this is approximately the version published in Nature, minus various subedits in the main tex

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

European Banking Union

Ulazak u Europsku uniju, za novije zemlje članice nužno znači ulazak i u europsku Ekonomsku i monetarnu uniju nakon ispunjavanja nominalnih kriterija konvergencije te ostalih propisanih preduvjeta. Budući da je propast Lehman Brothers-a 2008. godine i pojava financijske krize dovela do razdora i nesigurnosti cjelokupnog bankarskog sustava, kako u cijelom svijetu tako i u Europskoj uniji, odnosno europskoj Ekonomskoj i monetarnoj uniji, osnivanje bankovne unije kao dijela integriranog financijskog okvira predstavlja odgovor na za sve gospodarske i financijske probleme koji su pritom nastali. Cilj ovog diplomskog rada je analizirati proces nastanka bankovne unije te utvrditi njenu ulogu u bankarskom sektoru zemalja članica Europske unije, kao i saniranju posljedica financijske krize. Isto tako, cilj je opisati važnost tri stupa bankovne unije koja čine: jedinstveni nadzorni mehanizam, jedinstveni sanacijski mehanizam te povezani mehanizmi financiranja. Njihove odrednice predstavljaju glavne smjernice uspješnog djelovanja gospodarskog i financijskog sustava. Nadalje, analizira se i uloga, odnosno važnost Europske središnje banke i Europskog mehanizma stabilnosti u nadzoru bankovne unije koji je bitan za uspješno funkcioniranje sustava.Joining the European Union, for the newer Member States necessary means entering into the European Economic and Monetary Union after filling the nominal convergence criteria and other prescribed requirements. Since the collapse of Lehman Brothers in 2008 and the emergence of the financial crisis led to discord and uncertainty of the overall banking system, both worldwide and in European Union and European Economic and Monetary Union, the establishment of banking union as part of an integrated financial framework is a response to all the economic and financial problems that are pushing incurred. The aim of this diploma work is to analyze the process of creating banking union and to determine its role in the banking sector the EU Member States, as well as dealing with the consequences of the financial crisis. Also, the aim is to describe the importance of the three mechanisms that creates banking union: a Single Supervisory Mechanism, a Single Recovery Mechanism and related funding mechanisms. Their guidelines are the main guidelines for successful operation of the economic and financial system. Furthermore, assesses the role or importance of the European Central Bank and the European stability mechanism to control banking union that is essential for the successful function of the system

Nonlinear Fitness Landscape of a Molecular Pathway

Genes are regulated because their expression involves a fitness cost to the organism. The production of proteins by transcription and translation is a well-known cost factor, but the enzymatic activity of the proteins produced can also reduce fitness, depending on the internal state and the environment of the cell. Here, we map the fitness costs of a key metabolic network, the lactose utilization pathway in Escherichia coli. We measure the growth of several regulatory lac operon mutants in different environments inducing expression of the lac genes. We find a strikingly nonlinear fitness landscape, which depends on the production rate and on the activity rate of the lac proteins. A simple fitness model of the lac pathway, based on elementary biophysical processes, predicts the growth rate of all observed strains. The nonlinearity of fitness is explained by a feedback loop: production and activity of the lac proteins reduce growth, but growth also affects the density of these molecules. This nonlinearity has important consequences for molecular function and evolution. It generates a cliff in the fitness landscape, beyond which populations cannot maintain growth. In viable populations, there is an expression barrier of the lac genes, which cannot be exceeded in any stationary growth process. Furthermore, the nonlinearity determines how the fitness of operon mutants depends on the inducer environment. We argue that fitness nonlinearities, expression barriers, and gene–environment interactions are generic features of fitness landscapes for metabolic pathways, and we discuss their implications for the evolution of regulation

Gene Transcription Changes in Asthmatic Chronic Rhinosinusitis with Nasal Polyps and Comparison to Those in Atopic Dermatitis

Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases

The Binary Protein Interactome of Treponema pallidum – The Syphilis Spirochete

Protein interaction networks shed light on the global organization of proteomes but can also place individual proteins into a functional context. If we know the function of bacterial proteins we will be able to understand how these species have adapted to diverse environments including many extreme habitats. Here we present the protein interaction network for the syphilis spirochete Treponema pallidum which encodes 1,039 proteins, 726 (or 70%) of which interact via 3,649 interactions as revealed by systematic yeast two-hybrid screens. A high-confidence subset of 991 interactions links 576 proteins. To derive further biological insights from our data, we constructed an integrated network of proteins involved in DNA metabolism. Combining our data with additional evidences, we provide improved annotations for at least 18 proteins (including TP0004, TP0050, and TP0183 which are suggested to be involved in DNA metabolism). We estimate that this “minimal” bacterium contains on the order of 3,000 protein interactions. Profiles of functional interconnections indicate that bacterial proteins interact more promiscuously than eukaryotic proteins, reflecting the non-compartmentalized structure of the bacterial cell. Using our high-confidence interactions, we also predict 417,329 homologous interactions (“interologs”) for 372 completely sequenced genomes and provide evidence that at least one third of them can be experimentally confirmed

Occurrence, Distribution, and Ecological Risk of Fluoroquinolones in Rivers and Wastewaters

The use of fluoroquinolones for the treatment of infections in humans and animals has increased in Argentina, and they can be found in large amounts in water bodies. The present study investigated the occurrence and associated ecological risk of 5 fluoroquinolones in rivers and farm wastewaters of San Luis, Santa Fe, Córdoba, Entre Ríos, and Buenos Aires provinces of Argentina by high-performance liquid chromatography coupled to fast-scanning fluorescence detection and ultra–high-performance liquid chromatography coupled to triple quadrupole mass spectrometry detection. The maximum concentrations of ciprofloxacin, enrofloxacin, ofloxacin, enoxacin, and difloxacin found in wastewater were 1.14, 11.9, 1.78, 22.1, and 14.2 μg L–1, respectively. In the case of river samples, only enrofloxacin was found, at a concentration of 0.97 μg L–1. The individual risk of aquatic organisms associated with water pollution due to fluoroquinolones was higher in bacteria, cyanobacteria, algae, plants, and anurans than in crustaceae and fish, with, in some cases, risk quotients >1. The proportion of samples classified as high risk was 87.5% for ofloxacin, 63.5% for enrofloxacin, 57.1% for ciprofloxacin, and 25% for enoxacin. Our results suggest that the prevalence of fluoroquinolones in water could be potentially risky for the aquatic ecosystem, and harmful to biodiversity.Fil: Teglia, Carla Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Perez, Florencia Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Michlig, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Programa de Investigación y Análisis de Residuos y Contaminantes Químicos; ArgentinaFil: Repetti, María Rosa. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Programa de Investigación y Análisis de Residuos y Contaminantes Químicos; ArgentinaFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; Argentin

Misfolded SOD1 Associated with Motor Neuron Mitochondria Alters Mitochondrial Shape and Distribution Prior to Clinical Onset

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS