Transit Performance Measures in California

This research is the result of a California Department of Transportation (Caltrans) request to assess the most commonly available transit performance measures in California. Caltrans wanted to understand performance measures and data used by Metropolitan Planning Organizations (MPOs) and transit agencies to help it develop statewide measures. This report serves as a summary reference guide to help Caltrans understand the numerous and diverse performance measures used by MPOs and transit agencies in California. First, investigators review the available literature to identify a complete transit performance framework for the purposes of organizing agency measures, metrics, and data sources. Next, they review the latest transit performance measures documented in planning reports for the four largest MPOs in California (San Francisco Bay Area, Los Angeles, San Diego, and Sacramento). Researchers pay special attention to the transit performance measures used by these MPOs, because these measures are available for the majority of California’s population. Finally, investigators summarize 231 performance measures used by a total 26 local transit agencies in the State of California, based on transit planning documents available on the internet

TMAO and Gut Microbial-Derived Metabolites TML and γBB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism

Background: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (gamma BB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Methods: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, gamma BB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. Results: No differences were found for TMAO, gamma BB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, gamma BB, and TML showed a positive correlation with lag time and time to peak. TMAO, gamma BB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, gamma BB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. Conclusions: No differences were found regarding TMAO, gamma BB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk

Therapeutic potential of emerging NAD+-increasing strategies for cardiovascular diseases

Altres ajuts: Fundació La Marató de TV3 (303/C/2016)(201602.30.31)Cardiovascular diseases are the leading cause of death worldwide. Aging and/or metabolic stress directly impact the cardiovascular system. Over the last few years, the contributions of altered nicotinamide adenine dinucleotide (NAD+) metabolism to aging and other pathological conditions closely related to cardiovascular diseases have been intensively investigated. NAD+ bioavailability decreases with age and cardiometabolic conditions in several mammalian tissues. Compelling data suggest that declining tissue NAD+ is commonly related to mitochondrial dysfunction and might be considered as a therapeutic target. Thus, NAD+ replenishment by either genetic or natural dietary NAD+-increasing strategies has been recently demonstrated to be effective for improving the pathophysiology of cardiac and vascular health in different experimental models, as well as human health, to a lesser extent. Here, we review and discuss recent experimental evidence illustrating that increasing NAD+ bioavailability, particularly by the use of natural NAD+ precursors, may offer hope for new therapeutic strategies to prevent and treat cardiovascular diseases

Hierarchical nanotexturing enables acoustofluidics on slippery yet sticky, flexible surfaces

The ability to actuate liquids remains a fundamental challenge in smart microsystems, such as those for soft robotics, where devices often need to conform to either natural or three-dimensional solid shapes, in various orientations. Here, we propose a hierarchical nanotexturing of piezoelectric films as active microfluidic actuators, exploiting a unique combination of both topographical and chemical properties on flexible surfaces, while also introducing design concepts of shear hydrophobicity and tensile hydrophilicity. In doing so, we create nanostructured surfaces that are, at the same time, both slippery (low in-plane pinning) and sticky (high normal-to-plane liquid adhesion). By enabling fluid transportation on such arbitrarily shaped surfaces, we demonstrate efficient fluid motions on inclined, vertical, inverted, or even flexible geometries in three dimensions. Such surfaces can also be deformed and then reformed into their original shapes, thereby paving the way for advanced microfluidic applications

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

Theoretical Characterization of the Step-by-Step Mechanism of Conversion of Leukotriene A4 to Leukotriene B4 Catalysed by the Enzyme Leukotriene A4 Hydrolase

LTA4H is a bifunctional zinc metalloenzyme that converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), one of the most potent chemotactic agents involved in acute and chronic inflammatory diseases. In this reaction, LTA4H acts as an epoxide hydrolase with a unique and fascinating mechanism, which includes the stereoselective attachment of one water molecule to the carbon backbone of LTA4 several methylene units away from the epoxide moiety. By combining Molecular Dynamics simulations and Quantum Mechanics/Molecular Mechanics calculations, we obtained a very detailed molecular picture of the different consecutive steps of that mechanism. By means of a rather unusual 1,7-nucleophilic substitution through a clear SN1 mechanism, the epoxide opens and the triene moiety of the substrate twists in such a way that the bond C6-C7 adopts its cis (Z) configuration, thus exposing the R face of C12 to the addition of a water molecule hydrogen-bonded to ASP375. Thus, the two stereochemical features that are required for the bioactivity of LTB4 appear to be closely related. The noncovalent π-π stacking interactions between the triene moiety and two tyrosines (TYR267 and, especially, TYR378) that wrap the triene system along the whole reaction explain the preference for the cis configuration inside LTA4H

Understanding the Pediatric Psychiatric Phenotype of 22q11.2 Deletion Syndrome

The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan). Besides varying levels of intellectual disability, the prevalence of autism spectrum disorders, attention deficit disorders, anxiety disorders, and psychotic disorders in young individuals with 22q11DS is significantly higher than in the general population, or in individuals with idiopathic intellectual disability. Possible explanations for this observed phenotypic variability will be discussed, including genetic pleiotropy, gene-environment interactions, the age-dependency of phenotypes, but also the impact of assessment and ascertainment bias as well as the limitations of our current diagnostic classification system. The implications inferred by these observations aforementioned bear direct relevance to both scientists and clinicians. Observations regarding the neuropsychiatric manifestations in individuals with 22q11DS exemplify the need for a dimensional approach to neuropsychiatric assessment, in addition to our current categorical diagnostic classification system. The potential usefulness of 22q11DS as a genetic model to study the early phases of schizophrenia as well as the phenomenon of neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a clinical perspective, the importance of regular neuropsychiatric evaluations with attention to symptoms not always captured in diagnostic categories and of maintaining equilibrium between individual difficulties and competencies and environmental demands will be discussed

Functional Characterization of Mouse and Human Arachidonic Acid Lipoxygenase 15B (ALOX15B) Orthologs and of Their Mutants Exhibiting Humanized and Murinized Reaction Specificities

The arachidonic acid lipoxygenase 15B (ALOX15B) orthologs of men and mice form different reaction products when arachidonic acid is used as the substrate. Tyr603Asp+His604Val double mutation in mouse arachidonic acid lipoxygenase 15b humanized the product pattern and an inverse mutagenesis strategy murinized the specificity of the human enzyme. As the mechanistic basis for these functional differences, an inverse substrate binding at the active site of the enzymes has been suggested, but experimental proof for this hypothesis is still pending. Here we expressed wildtype mouse and human arachidonic acid lipoxygenase 15B orthologs as well as their humanized and murinized double mutants as recombinant proteins and analyzed the product patterns of these enzymes with different polyenoic fatty acids. In addition, in silico substrate docking studies and molecular dynamics simulation were performed to explore the mechanistic basis for the distinct reaction specificities of the different enzyme variants. Wildtype human arachidonic acid lipoxygenase 15B converted arachidonic acid and eicosapentaenoic acid to their 15-hydroperoxy derivatives but the Asp602Tyr+Val603His exchange murinized the product pattern. The inverse mutagenesis strategy in mouse arachidonic acid lipoxygenase 15b (Tyr603Asp+His604Val exchange) humanized the product pattern with these substrates, but the situation was different with docosahexaenoic acid. Here, Tyr603Asp+His604Val substitution in mouse arachidonic acid lipoxygenase 15b also humanized the specificity but the inverse mutagenesis (Asp602Tyr+Val603His) did not murinize the human enzyme. With linoleic acid Tyr603Asp+His604Val substitution in mouse arachidonic acid lipoxygenase 15b humanized the product pattern but the inverse mutagenesis in human arachidonic acid lipoxygenase 15B induced racemic product formation. Amino acid exchanges at critical positions of human and mouse arachidonic acid lipoxygenase 15B orthologs humanized/murinized the product pattern with C20 fatty acids, but this was not the case with fatty acid substrates of different chain lengths. Asp602Tyr+Val603His exchange murinized the product pattern of human arachidonic acid lipoxygenase 15B with arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. An inverse mutagenesis strategy on mouse arachidonic acid lipoxygenase 15b (Tyr603Asp+His604Val exchange) did humanize the reaction products with arachidonic acid and eicosapentaenoic acid, but not with docosahexaenoic acid

Sostenibilitat i turisme, setembre 2015

Recurs d'aprenentatge de la Universitat Oberta de Catalunya.Recurso de aprendizaje de la "Universitat Oberta de Catalunya".Learning material of the "Universitat Oberta de Catalunya"