Pharmacogenetic GWAS meta-analysis of LDL cholesterol response to statins

Cardiolog

Exploring the genetic correlations of antisocial behaviour and life history traits.

UNLABELLED: Prior evolutionary theory provided reason to suspect that measures of development and reproduction would be correlated with antisocial behaviours in human and non-human species. Behavioural genetics has revealed that most quantitative traits are heritable, suggesting that these phenotypic correlations may share genetic aetiologies. We use genome-wide association study data to estimate the genetic correlations between various measures of reproductive development (N = 52 776-318 863) and antisocial behaviour (N = 31 968). Our genetic correlation analyses demonstrate that alleles associated with higher reproductive output (number of children ever born, r g = 0.50, P = 0.0065) were positively correlated with alleles associated with antisocial behaviour, whereas alleles associated with more delayed reproductive onset (age at first birth, r g = -0.64, P = 0.0008) were negatively associated with alleles linked to antisocial behaviour. Ultimately, these findings coalesce with evolutionary theories suggesting that increased antisocial behaviours may partly represent a faster life history approach, which may be significantly calibrated by genes. DECLARATION OF INTEREST: None

Investigating the structure and fragmentation of a highly filamentary IRDC

We present 3.7 arcsec (~0.05 pc) resolution 3.2 mm dust continuum observations from the IRAM PdBI, with the aim of studying the structure and fragmentation of the filamentary Infrared Dark Cloud G035.39-00.33. The continuum emission is segmented into a series of 13 quasi-regularly spaced (~0.18pc) cores, following the major axis of the IRDC. We compare the spatial distribution of the cores with that predicted by theoretical work describing the fragmentation of hydrodynamic fluid cylinders, finding a significant (factor of ~8) discrepancy between the two. Our observations are consistent with the picture emerging from kinematic studies of molecular clouds suggesting that the cores are harboured within a complex network of independent sub-filaments. This result emphasises the importance of considering the underlying physical structure, and potentially, dynamically important magnetic fields, in any fragmentation analysis. The identified cores exhibit a range in (peak) beam-averaged column density ($3.6{\rm x}10^{23}{\rm cm}^{-2}<N_{H,c}<8.0{\rm x}10^{23}{\rm cm}^{-2}$), mass ($8.1M_{\odot}<M_{c}<26.1M_{\odot}$), and number density ($6.1{\rm x}10^{5}{\rm cm}^{-3}<n_{H, c, eq}<14.7{\rm x}10^{5}{\rm cm}^{-3}$). Two of these cores, dark in the mid-infrared, centrally-concentrated, monolithic (with no traceable substructure at our PdBI resolution), and with estimated masses of the order ~20-25$M_{\odot}$, are good candidates for the progenitors of intermediate-to-high-mass stars. Virial parameters span a range $0.2<\alpha_{\rm vir}<1.3$. Without additional support, possibly from dynamically important magnetic fields with strengths of the order 230$\mu$G<B<670$\mu$G, the cores are susceptible to gravitational collapse. These results may imply a multi-layered fragmentation process, which incorporates the formation of sub-filaments, embedded cores, and the possibility of further fragmentation

The starch-deficient plastidic <em>PHOSPHOGLUCOMUTASE </em>mutant of the constitutive crassulacean acid metabolism (CAM) species <em>Kalancho\ueb fedtschenkoi</em> impacts diel regulation and timing of stomatal CO₂ responsiveness

\ua9 The Author(s) 2023.• Background and Aims Crassulacean acid metabolism (CAM) is a specialized type of photosynthesis characterized by a diel pattern of stomatal opening at night and closure during the day, which increases water-use efficiency. Starch degradation is a key regulator of CAM, providing phosphoenolpyruvate as a substrate in the mesophyll for nocturnal assimilation of CO2. Growing recognition of a key role for starch degradation in C3 photosynthesis guard cells for mediating daytime stomatal opening presents the possibility that starch degradation might also impact CAM by regulating the provision of energy and osmolytes to increase guard cell turgor and drive stomatal opening at night. In this study, we tested the hypothesis that the timing of diel starch turnover in CAM guard cells has been reprogrammed during evolution to enable nocturnal stomatal opening and daytime closure. • Methods Biochemical and genetic characterization of wild-type and starch-deficient RNAi lines of Kalancho\ueb fedtschenkoi with reduced activity of plastidic phosphoglucomutase (PGM) constituted a preliminary approach for the understanding of starch metabolism and its implications for stomatal regulation in CAM plants. • Key Results Starch deficiency reduced nocturnal net CO2 uptake but had negligible impact on nocturnal stomatal opening. In contrast, daytime stomatal closure was reduced in magnitude and duration in the starch-deficient rPGM RNAi lines, and their stomata were unable to remain closed in response to elevated concentrations of atmospheric CO2 administered during the day. Curtailed daytime stomatal closure was linked to higher soluble sugar contents in the epidermis and mesophyll. • Conclusions Nocturnal stomatal opening is not reliant upon starch degradation, but starch biosynthesis is an important sink for carbohydrates, ensuring daytime stomatal closure in this CAM species

Interstellar Plunging Waves: ALMA Resolves the Physical Structure of Nonstationary MHD Shocks

Magnetohydrodynamic (MHD) shocks are violent events that inject large amounts of energy in the interstellar medium dramatically modifying its physical properties and chemical composition. Indirect evidence for the presence of such shocks has been reported from the especial chemistry detected toward a variety of astrophysical shocked environments. However, the internal physical structure of these shocks remains unresolved since their expected spatial scales are too small to be measured with current instrumentation. Here we report the first detection of a fully spatially resolved, MHD shock toward the infrared dark cloud (IRDC) G034.77-00.55. The shock, probed by silicon monoxide (SiO) and observed with the Atacama Large Millimeter/submillimeter Array (ALMA), is associated with the collision between the dense molecular gas of the cloud and a molecular gas flow pushed toward the IRDC by the nearby supernova remnant (SNR) W44. The interaction is occurring on subparsec spatial scales thanks to the enhanced magnetic field of the SNR, making the dissipation region of the MHD shock large enough to be resolved with ALMA. Our observations suggest that molecular flow–flow collisions can be triggered by stellar feedback, inducing shocked molecular gas densities compatible with those required for massive star formation

Polynomial function intervals for floating-point software verification

The focus of our work is the verification of tight functional properties of numerical programs, such as showing that a floating-point implementation of Riemann integration computes a close approximation of the exact integral. Programmers and engineers writing such programs will benefit from verification tools that support an expressive specification language and that are highly automated. Our work provides a new method for verification of numerical software, supporting a substantially more expressive language for specifications than other publicly available automated tools. The additional expressivity in the specification language is provided by two constructs. First, the specification can feature inclusions between interval arithmetic expressions. Second, the integral operator from classical analysis can be used in the specifications, where the integration bounds can be arbitrary expressions over real variables. To support our claim of expressivity, we outline the verification of four example programs, including the integration example mentioned earlier. A key component of our method is an algorithm for proving numerical theorems. This algorithm is based on automatic polynomial approximation of non-linear real and real-interval functions defined by expressions. The PolyPaver tool is our implementation of the algorithm and its source code is publicly available. In this paper we report on experiments using PolyPaver that indicate that the additional expressivity does not come at a performance cost when comparing with other publicly available state-of-the-art provers. We also include a scalability study that explores the limits of PolyPaver in proving tight functional specifications of progressively larger randomly generated programs

Ultraluminous Infrared Galaxies

At luminosities above ~10^{11} L_sun, infrared galaxies become the dominant population of extragalactic objects in the local Universe (z < 0.5), being more numerous than optically selected starburst and Seyfert galaxies, and QSOs at comparable bolometric luminosity. At the highest luminosities, ultraluminous infrared galaxies (ULIGs: L_ir > 10^{12} L_sun), outnumber optically selected QSOs by a factor of ~1.5-2. All of the nearest ULIGs (z < 0.1) appear to be advanced mergers that are powered by both a circumnuclear starburst and AGN, both of which are fueled by an enormous concentration of molecular gas (~10^{10} M_sun) that has been funneled into the merger nucleus. ULIGs may represent a primary stage in the formation of massive black holes and elliptical galaxy cores. The intense circumnuclear starburst that accompanies the ULIG phase may also represent a primary stage in the formation of globular clusters, and the metal enrichment of the intergalactic medium by gas and dust expelled from the nucleus due to the combined forces of supernova explosions and powerful stellar winds.Comment: LaTex, 6 pages with 4 embedded .eps figures. Postscript version plus color plates available at http://www.ifa.hawaii.edu/users/sanders/astroph/s186/plates.html To appear in "Galaxy Interactions at Low and High Redshift" IAU Symposium 186, Kyoto, Japan, eds. J.E. Barnes and D.B. Sander

Inverse Modeling for MEG/EEG data

We provide an overview of the state-of-the-art for mathematical methods that are used to reconstruct brain activity from neurophysiological data. After a brief introduction on the mathematics of the forward problem, we discuss standard and recently proposed regularization methods, as well as Monte Carlo techniques for Bayesian inference. We classify the inverse methods based on the underlying source model, and discuss advantages and disadvantages. Finally we describe an application to the pre-surgical evaluation of epileptic patients.Comment: 15 pages, 1 figur

Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice

Background: CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNγ-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-$\gamma$) are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant) are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO) mice. Methods: Mice (n = 8 per group) were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL) fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT) mice. Results: Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNγ and CXCR3 ligands (particularly CXCL10). Conclusion: Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNγ and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS