Individual differences in naturalistic learning link negative emotionality to the development of anxiety

Organisms learn from prediction errors (PEs) to predict the future. Laboratory studies using small financial outcomes find that humans use PEs to update expectations and link individual differences in PE-based learning to internalizing disorders. Because of the low-stakes outcomes in most tasks, it is unclear whether PE learning emerges in naturalistic, high-stakes contexts and whether individual differences in PE learning predict psychopathology risk. Using experience sampling to assess 625 college students\u27 expected exam grades, we found evidence of PE-based learning and a general tendency to discount negative PEs, an optimism bias. However, individuals with elevated negative emotionality, a personality trait linked to the development of anxiety disorders, displayed a global pessimism and learning differences that impeded accurate expectations and predicted future anxiety symptoms. A sensitivity to PEs combined with an aversion to negative PEs may result in a pessimistic and inaccurate model of the world, leading to anxiety

Touchstone Stars: Highlights from the Cool Stars 18 Splinter Session

We present a summary of the splinter session on "touchstone stars" -- stars with directly measured parameters -- that was organized as part of the Cool Stars 18 conference. We discuss several methods to precisely determine cool star properties such as masses and radii from eclipsing binaries, and radii and effective temperatures from interferometry. We highlight recent results in identifying and measuring parameters for touchstone stars, and ongoing efforts to use touchstone stars to determine parameters for other stars. We conclude by comparing the results of touchstone stars with cool star models, noting some unusual patterns in the differences.Comment: Proceedings of the 18th Cambridge Workshop on Cool Stars, Stellar Systems, and the Sun, Eds G. van Belle & H. Harri

Integrated model of the vertebrate augmin complex

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but lack of structure information about augmin has hindered understanding how it promotes branching. In this work, we combine cryo-electron microscopy, protein structural prediction, and visualization of fused bulky tags via negative stain electron microscopy to identify the location and orientation of each subunit within the augmin structure. Evolutionary analysis shows that augmin\u27s structure is highly conserved across eukaryotes, and that augmin contains a previously unidentified microtubule binding site. Thus, our findings provide insight into the mechanism of branching microtubule nucleation

Precise Infrared Radial Velocities from Keck/NIRSPEC and the Search for Young Planets

We present a high-precision infrared radial velocity study of late-type stars using spectra obtained with NIRSPEC at the W. M. Keck Observatory. Radial velocity precisions of 50 m/s are achieved for old field mid-M dwarfs using telluric features for precise wavelength calibration. Using this technique, 20 young stars in the {\beta} Pic (age ~12 Myr) and TW Hya (age ~8 Myr) Associations were monitored over several years to search for low mass companions; we also included the chromospherically active field star GJ 873 (EV Lac) in this survey. Based on comparisons with previous optical observations of these young active stars, radial velocity measurements at infrared wavelengths mitigate the radial velocity noise caused by star spots by a factor of ~3. Nevertheless, star spot noise is still the dominant source of measurement error for young stars at 2.3 {\mu}m, and limits the precision to ~77 m/s for the slowest rotating stars (v sin i < 6 km/s), increasing to ~168 m/s for rapidly rotating stars (v sin i > 12 km/s). The observations reveal both GJ 3305 and TWA 23 to be single-lined spectroscopic binaries; in the case of GJ 3305, the motion is likely caused by its 0.09" companion, identified after this survey began. The large amplitude, short-timescale variations of TWA 13A are indicative of a hot Jupiter-like companion, but the available data are insufficient to confirm this. We label it as a candidate radial velocity variable. For the remainder of the sample, these observations exclude the presence of any 'hot' (P < 3 days) companions more massive than 8 MJup, and any 'warm' (P < 30 days) companions more massive than 17 MJup, on average. Assuming an edge-on orbit for the edge-on disk system AU Mic, these observations exclude the presence of any hot Jupiters more massive than 1.8 MJup or warm Jupiters more massive than 3.9 MJup.Comment: Accepted for publication in The Astrophysical Journal. 18 pages, 7 figure

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by ‘genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2′-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex diseas

Reading related white matter structures in adolescents are influenced more by dysregulation of emotion than behavior

Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension. Youth with mood disorders scored higher on the phonological test but had lower comprehension scores than children with behavioral disorders and controls; control participants scored the highest. Correlations between fractional anisotropy and phonological processing in the left Arcuate Fasciculus showed a significant difference between groups and were strongest in behavioral disorders, intermediate in mood disorders, and lowest in controls. Correlations between these measures in the left Inferior Longitudinal Fasciculus were significantly greater than in controls for mood but not for behavioral disorders. Youth with mood disorders share a deficit in the executive-limbic pathway (Arcuate Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for engaging frontal regions for phonological processing or passage comprehension tasks and increased reliance on the ventral tract (e.g., the Inferior Longitudinal Fasciculus). The low passage comprehension scores in mood disorder may result from engaging the left hemisphere. Neural pathways for reading differ mainly in executive-limbic circuitry. This new insight may aid clinicians in providing appropriate intervention for each disorder

Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab’s. Currently, therapy for pregnant women with APS is focused on preventing thrombosis, but anticoagulation is only partially successful in averting miscarriage. We hypothesized that complement activation is a central mechanism of pregnancy loss in APS and tested this in a model in which pregnant mice receive human IgG containing aPL Ab’s. Here we identify complement component C5 (and particularly its cleavage product C5a) and neutrophils as key mediators of fetal injury, and we show that Ab’s or peptides that block C5a–C5a receptor interactions prevent pregnancy complications. The fact that F(ab)′2 fragments of aPL Ab’s do not mediate fetal injury and that C4-deficient mice are protected from fetal injury suggests that activation of the complement cascade is initiated via the classical pathway. Studies in factor B–deficient mice, however, indicate that alternative pathway activation is required and amplifies complement activation. In contrast, activating FcγRs do not play an important role in mediating aPL Ab–induced fetal injury. Our findings identify the key innate immune effectors engaged by pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide novel and important targets for prevention of pregnancy loss in APS

Beat synchronization across the lifespan: intersection of development and musical experience

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample