The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses

Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes

On the 3D distribution and size fractionation of microparticles in a serpentine microchannel

Suitable methods to realize a multi-dimensional fractionation of microparticles smaller than 10 μm diameter are still rare. In the present study, size and density fractionation is investigated for 3.55 μm and 9.87 μm particles in a sharp-corner serpentine microchannel of cross-sectional aspect ratio h∕w = 0.25 . Experimental results are obtained through Astigmatism Particle Tracking Velocimetry (APTV) measurements, from which three-dimensional particle distributions are reconstructed for Reynolds numbers between 100 and 150. The 3D reconstruction shows for the first time that equilibrium trajectories do not only develop over the channel width, i.e. in-plane equilibrium positions but also over the channel height at different out-of-plane positions. With increasing Reynolds number, 9.87 μm polystyrene (PS = 1.05 g cm−3) and melamine (MF = 1.51 g cm−3) particles focus on two trajectories near the channel bisector. In contrast to this, it is shown that 3.55 μm polystyrene particles develop four equilibrium trajectories at different in-plane and out-of-plane positions up to a critical Reynolds number. Beyond this critical Reynolds number, also these particles merge to two trajectories at different channel heights. While the rearrangement of 3.55 μm polystyrene particles just starts beyond Re > 140 , 9.87 μm polystyrene particles undergo this rearrangement already at Re = 100 . As the equilibrium trajectories of these two particle groups are located at similar out-of-plane positions, outlet geometries that aim to separate particles along the channel width turn out to be a good choice for size fractionation. Indeed, polystyrene particles of different size assume laterally well-separated equilibrium trajectories such that a size fractionation of nearly 100% at Re = 110 can be achieved

Autopiquer - a robust and reliable peak detection algorithm for mass spectrometry

We present a simple algorithm for robust and unsupervised peak detection by determining a noise threshold in isotopically resolved mass spectrometry data. Solving this problem will greatly reduce the subjective and time consuming manual picking of mass spectral peaks and so will prove beneficial in many research applications. The Autopiquer approach uses autocorrelation to test for the presence of (isotopic) structure in overlapping windows across the spectrum. Within each window, a noise threshold is optimized to remove the most unstructured data whilst keeping as much of the (isotopic) structure as possible. This algorithm has been successfully demonstrated for both peak detection and spectral compression on data from many different classes of mass spectrometer and for different sample types and this approach should also be extendible to other types of data that contain regularly spaced discrete peaks

Grateful parents raising grateful children: Niche selection and the socialization of child gratitude

Given that children’s exposure to gratitude-related activities may be one way that parents can socialize gratitude in their children, we examined whether parents’ niche selection (i.e., tendency to choose perceived gratitude-inducing activities for their children) mediates the association between parents’ reports of their own and their children's gratitude. Parent-child dyads (N =101; children aged 6-9; 52% girls; 80% Caucasian; 85% mothers) participated in a laboratory visit and parents also completed a seven-day online diary regarding children’s gratitude. Decomposing specific indirect effects within a structural equation model, we found that parents high in gratitude were more likely to set goals to use niche selection as a gratitude socialization strategy, and thereby more likely to place their children in gratitude-related activities. Placement in these activities, in turn, was associated with more frequent expression of gratitude in children. We describe future directions for research on parents’ role in socializing gratitude in their children

Future Directions in the Developmental Science of Addictions

This essay addresses important future directions for the study of addictions, emphasizing the incorporation of developmental perspectives into how we think about substance use and disorder as unfolding processes over time and context for a heterogeneous group of individuals. These perspectives articulate complexities in the developmental processes that underlie change and continuity in human behavior over time. We consider two key developmental concepts, namely ‘time’ and ‘heterogeneity’. We argue that a lack of attention to time sampling creates ambiguity in the meaning of time-linked assessments, challenges in discerning which of multiple clocks may govern behavior, and the inability in some instances to distinguish which of multiple etiological processes may be driving behavior within our samples. Moreover, artificial divisions among disorders that commonly co-occur with substance use are a barrier to the further integration of the study and treatment of addictions with that of psychopathology. Similar to recent changes in the study of psychiatric disorders more broadly, we argue that identifying common deficits among commonly comorbid disorders, rather than patterns of comorbidity per se, is key to identifying early emerging risk factors for substance use and disorder, with important implications for identifying risk populations and developmental periods as well as potentially malleable intervention targets. Attention to time sampling in theory-driven research designs and attempts to identify more homogenous groups of individuals who use and eventually abuse substances over time are two examples of ways to better understand some of the complexity underlying the development of addictions

Generic flow profiles induced by a beating cilium

We describe a multipole expansion for the low Reynolds number fluid flows generated by a localized source embedded in a plane with a no-slip boundary condition. It contains 3 independent terms that fall quadratically with the distance and 6 terms that fall with the third power. Within this framework we discuss the flows induced by a beating cilium described in different ways: a small particle circling on an elliptical trajectory, a thin rod and a general ciliary beating pattern. We identify the flow modes present based on the symmetry properties of the ciliary beat.Comment: 12 pages, 6 figures, to appear in EPJ

Externalizing symptoms among children of alcoholic parents: Entry points for an antisocial pathway to alcoholism.

We examined heterogeneity in risk for externalizing symptoms in children of alcoholic parents as it may inform the search for entry points into an antisocial pathway to alcoholism. Specifically, we tested whether the number of alcoholic parents in a family, the comorbid subtype of parent alcoholism, and the gender of the child predicted trajectories of externalizing symptoms over the early life course as assessed in high-risk samples of children of alcoholic parents and matched controls. Through integrative analyses of two independent, longitudinal studies, we showed that children with either antisocial alcoholic parents or two alcoholic parents were at greatest risk for externalizing symptoms. Moreover, children with a depressed alcoholic parent did not differ from those with an antisocial alcoholic parent in reported symptoms. These findings were generally consistent across mother-, father- and adolescent-reports of symptoms, child gender and child age (ages 2 through 17), and the two independent studies examined. Multi-alcoholic and comorbid-alcoholic families may thus convey a genetic susceptibility to dysregulation along with environments that both exacerbate this susceptibility and provide few supports to offset it

The early childhood generalized trust belief scale

The study was designed to develop and evaluate the Early Childhood Generalized Trust Belief Scale (ECGTBS) as a method of assessing 5-to-8-year-olds’ generalized trust. Two hundred and eleven (103 male and 108 female) children (mean age 6 years and 2 months at Time 1) completed the ECGTBS twice over a year. A subsample of participants completed the ECGTBS after two weeks to assess the scale’s test-retest reliability. Exploratory and confirmatory factor analyses confirmed that the ECGTBS assessed the expected three factors: reliability, emotional trust, and honesty with item-pairs loading most strongly on their corresponding factor. However, the ECGTBS demonstrated low to modest internal consistency and test-retest reliability which indicates a need for further development of this instrument. As evidence for the convergent validity of the ECGTBS, the reliability and emotional trust items were associated with the children’s trust in classmates at Time 2. Concurrent asymmetric quadratic relationships indicated the importance of midrange generalized trust. Specifically, children with very high generalized trust experienced greater loneliness and children with very low generalized trust had fewer friendships than children with midrange trust