Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10−10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = −0.40), educational attainment (years of schooling rg = −0.46) and reproductive traits (age at first birth rg = −0.58, father’s age at death rg = −0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

Schwingungsgeschuetztes Nutzfahrzeug-Fahrerhaus durch aktive Federung Schlussbericht (Kurzbericht)

The vibratory exposure of the driver and codriver of a commercial vehicle can deteriorate the wellbeing or eventually the health. Conventional (passive) suspensions offer only little possibilities of further improvement. A literature review concerning the medical evaluation of vibratory loads shows the still limited knowledge. At first, a series long haulage truck is analysed with regard to its vibratory behaviour and a specification book compiled. Simulation computations support the development. The prototype with an active hydraulic cab suspension has a good vibratory isolation in the frequency range up to 2.5. Hz, a satisfactory one up to 6 Hz and a dissatisfactory one above 6 Hz. The concept has partially to be modifiedSIGLEAvailable from TIB Hannover: F93B1067+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Schwingungsgestuetztes Nutzfahrzeug-Fahrerhaus durch aktive Federung. T. 4 und Gesamtzusammenfassung Realisierung eines Prototypen einer aktiven Fahrerhausfederung in einem Lastkraftwagen. Entwurf, Erprobung und Bewertung. Schlussbericht

The concept, realisation and test of a prototype of an active cab suspension in a suitably modified truck is described. The modifications concern the mechanic suspension components, the installation of the hydraulic system and of the computer electronics for measurement and control. The dynamic response is determined and optimized by various test functions (in parallel to simulation calculations). The dynamic position control is achieved by the superposition of an open and a closed control loop. Tests on a track simulator and road tests showed a good vibratory isolation up to 2.5 Hz, up to 6 Hz a satisfactory, and above a dissatisfactory result. The concept has to be partially modified resp. completedSIGLEAvailable from TIB Hannover: F93B1066+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Schwingungsgeschuetztes Nutzfahrzeug-Fahrerhaus durch aktive Federung. T. 2 Experimentelle Schwingungsuntersuchung an einem Lastkraftwagen im Hinblick auf die Entwicklung eines aktiv gefederten Fahrerhauses. Schlussbericht

The vibrational behaviour of a long haulage truck has been investigated both on roads of strongly varying quality and on hydrodynamic test benches. The results are necessary to show the state of the art, to draw up a precise specification book for the active suspension concerning frequency range, spring travel, power, etc., and to validate the simulation model to be configurated. As a principle problem of passive truck suspensions, it turned out that the resonance frequencies of chassis, cab and seat are too close to each other. The necessary mechanical power is only about 4 kWAvailable from TIB Hannover: F93B1064 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Schwingungsgestuetztes Nutzfahrzeug-Fahrerhaus durch aktive Federung. T. 3 Erstellung, Validierung und Anwendung eines Rechenmodells fuer einen Lastkraftwagen mit passiver und aktiver Fahrerhausfederung. Schlussbericht

In the research project active cab suspension the computer simulation plays an important role. With the aid of a mechanical multibody model (ADAMS), a truck was modelled in its complete suspension relevant structure. The vibratory excitation of the load unevenness has also been modelled close to reality. The active suspension of the cab is represented in a further simulation model. At first, the passive suspension has been investigated for further possibilities of improvement, which, however, provoke difficulties in the practical realization. In contrast to that, the active cab suspension cares for a good vibratory isolation. In the higher frequency range, however, the performance is limitedSIGLEAvailable from TIB Hannover: F93B1065+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Investigations on the Effect of Fatty Acid Additives on Casein Micelles: Role of Ethylenic Unsaturation on the Interaction and Structural Diversity

Casein, one of the major constituent of milk protein, is considered to be a good candidate for oral drug delivery system. Also, milk transports various essential fatty acid to blood through dietary supplements. In this study, we have explored the alteration in the structural characteristic in terms of the modulations in the microenvironment of the protein in the presence of different types of fatty acids. Herein, we have observed that the unsaturation of fatty acids mostly affects the structure of casein micelles (CMs) by impinging upon the hydrophobic force of interaction following a decrease in the electrostatic interaction of various amino acid unit. Alteration of such forces is responsible for the increase in the aggregate size, modification in the protein secondary structure, and different morphology of CMs. Fluorescence behavior of 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4<i>H</i>-pyran indicates that the rigidity of the microenvironment is the main characteristic of the fatty acid binding, and the binding constant increases with the fatty acid chain length for saturated fatty acid or with the introduction of unsaturation onto it. Fluorescence lifetime imaging microscopy study indicates that the microstructure of CMs becomes more compact in the presence of unsaturated fatty acids, and this is also responsible for the increase in the diffusion time of the probe. Moreover, decrease in the fluorescence of extrinsic probe 8-anilinonaphthalene-1-sulfonate with the addition of unsaturated fatty acid reveals that these fatty acids alter the electrostatic interaction between casein units, more specifically in case of the surface-bound κ-casein. Therefore, this study provides a very useful information on the binding of fatty acids and helps to evaluate other fatty acid, as well as different small molecules binding in the applicative medicinal purpose