Self-Organized Resonance during Search of a Diverse Chemical Space

Recent studies of active matter have stimulated interest in the driven self-assembly of complex structures. Phenomenological modeling of particular examples has yielded insight, but general thermodynamic principles unifying the rich diversity of behaviors observed have been elusive. Here, we study the stochastic search of a toy chemical space by a collection of reacting Brownian particles subject to periodic forcing. We observe the emergence of an adaptive resonance in the system matched to the drive frequency, and show that the increased work absorption by these resonant structures is key to their stabilization. Our findings are consistent with a recently proposed thermodynamic mechanism for far-from-equilibrium self-organization

Family aggregation of high myopia: estimation of the sibling recurrence risk ratio

PURPOSE. To estimate the sibling recurrence risk (KS) and the sibling recurrence risk ratio ({lambda}S) for high myopia in a cohort in the United Kingdom. METHOD. The recurrence risks for myopia and high myopia were estimated in the siblings of 296 randomly selected high myopes ascertained from an optometric practice population. A model using an age of onset of spectacle wear for myopia of 9.1 ± 0.7 years or younger was developed as a surrogate for high myopia. The influence of parental myopia on the sibling recurrence risk for high myopia was also evaluated. RESULTS. KS was estimated (95% confidence limits) to be 10.0% (5.9, 14.8) and {lambda}S to be 4.9 (2.8, 7.6). High myopes without myopic parents were surprisingly common (~40%) and were less likely to have highly myopic siblings (KS ~6%) than those with at least one myopic parent (KS ~14%). CONCLUSIONS. The sibling recurrence risk ratio reported herein ({lambda}S ~ 4.9) implies that the high penetrance autosomal dominant loci for high myopia identified to date account for only a minority of cases of high myopia in the United Kingdom. Furthermore, high-penetrance autosomal dominant inheritance or even high-penetrance recessive inheritance, per se, cannot account for most cases of high myopia. Instead, it may be necessary to consider high myopia as a "complex disease" resulting from the influence of either alleles of reduced penetrance ("susceptibility genes"), environmental factors, or both

Dancing to the Partisan Beat: A First Analysis of Political Communication on TikTok

TikTok is a video-sharing social networking service, whose popularity is increasing rapidly. It was the world's second-most downloaded app in 2019. Although the platform is known for having users posting videos of themselves dancing, lip-syncing, or showcasing other talents, user-videos expressing political views have seen a recent spurt. This study aims to perform a primary evaluation of political communication on TikTok. We collect a set of US partisan Republican and Democratic videos to investigate how users communicated with each other about political issues. With the help of computer vision, natural language processing, and statistical tools, we illustrate that political communication on TikTok is much more interactive in comparison to other social media platforms, with users combining multiple information channels to spread their messages. We show that political communication takes place in the form of communication trees since users generate branches of responses to existing content. In terms of user demographics, we find that users belonging to both the US parties are young and behave similarly on the platform. However, Republican users generated more political content and their videos received more responses; on the other hand, Democratic users engaged significantly more in cross-partisan discussions.Comment: Accepted as a full paper at the 12th International ACM Web Science Conference (WebSci 2020). Please cite the WebSci version; Second version includes corrected typo

Linkage analysis of the genetic loci for high myopia on chromosomes 18p, 12q and 17q in 51 UK families

PURPOSE. To determine the extent to which high myopia in a cohort of 51 U.K. families can be attributed to currently identified genetic loci. METHODS. The families comprised 245 subjects with phenotypic information and DNA available, of whom 170 were classified as affected. Subjects were genotyped for microsatellite markers spanning _40cM regions on 18p (MYP2), 12q (MYP3) and 17q, together with markers flanking COL2A1, COL11A1, and FBN1. Two-point linkage analyses were performed using the same disease gene segregation model as was used in the original publications, followed by nonparametric and multipoint analyses using Genehunter (http://linkage.rockefeller. edu/soft/gh/ provided in the public domain by Rockefeller University, New York, NY), with additional maximization over the parameter _, the proportion of linked families. RESULTS. Evidence of linkage was found for the MYP3 locus on 12q (two-point Zmax _ 2.54, P _ 0.0003 and multipoint hLOD _ 1.08 at _ _ 0.24, P _ 0.023 for marker D12S332; nonparametric linkage [NPL] _ 1.49, P _ 0.07 for marker D12S1607). For the 17q locus there was weak evidence of excess allele sharing and linkage under a recessive model (NPL _ 1.34, P _ 0.09 for marker D17S956; two-point hLOD _ 1.24 at _ _ 0.30 for marker D17S1795; multipoint hLOD _ 1.24 at _ _ 0.17, P _ 0.014 for marker at 77.68 cM, between markers D17S956 and D17S1853). No significant linkage was found to the MYP2 locus on 18p, or to the COL2A1, COL11A1, and FBN1 genes. CONCLUSIONS. These results suggest that the MYP3 locus on 12q could be responsible for high myopia in approximately 25% of the U.K. families showing apparent autosomal dominant transmission, but that the loci on 18p and 17q are less common causes. Thus, additional loci for high myopia are likely to be the cause of the majority of cases of high myopia in the United Kingdom

Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy

Dynamic expression of genes associated with schizophrenia and bipolar disorder across development

Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder

Impaired oxysterol-liver X receptor signaling underlies aberrant cortical neurogenesis in a human stem cell model of neurodevelopmental disorder

The mechanisms by which genomic risks contribute to the onset of neuropsychiatric conditions remains a key challenge and a prerequisite for successful development of effective therapies. 15q11.2 CNV containing the CYFIP1 gene is associated with autism and schizophrenia. Using stem cell models we show that 15q11.2 deletion and CYFIP1-LoF leads to premature neuronal differentiation while CYFIP1-GoF favors neural progenitor maintenance. CYFIP1 dosage changes led to dysregulated cholesterol metabolism and altered levels of 24S,25-epoxycholesterol, which can mimic the 15q11.2del and CYFIP1-LoF phenotype by promoting cortical neuronal differentiation and restore the impaired neuronal differentiation of CYFIP1-GoF neural progenitors. Moreover, the neurogenic activity of 24S,25-epoxycholesterol is lost following genetic deletion of LXR while compound deletion of LXR in CYFIP1-/- background rescued their premature neurogenesis. This work delineates LXR mediated oxysterol regulation of neurogenesis as a pathological mechanism in neural cells carrying 15q11.2CNV and provides a potential target for therapeutic strategies for associated disorders

Functional Transcription Factor Target Networks Illuminate Control of Epithelial Remodelling

Cell identity is governed by gene expression, regulated by transcription factor (TF) binding at cis-regulatory modules. Decoding the relationship between TF binding patterns and gene regulation is nontrivial, remaining a fundamental limitation in understanding cell decision-making. We developed the NetNC software to predict functionally active regulation of TF targets; demonstrated on nine datasets for the TFs Snail, Twist, and modENCODE Highly Occupied Target (HOT) regions. Snail and Twist are canonical drivers of epithelial to mesenchymal transition (EMT), a cell programme important in development, tumour progression and fibrosis. Predicted “neutral” (non-functional) TF binding always accounted for the majority (50% to 95%) of candidate target genes from statistically significant peaks and HOT regions had higher functional binding than most of the Snail and Twist datasets examined. Our results illuminated conserved gene networks that control epithelial plasticity in development and disease. We identified new gene functions and network modules including crosstalk with notch signalling and regulation of chromatin organisation, evidencing networks that reshape Waddington’s epigenetic landscape during epithelial remodelling. Expression of orthologous functional TF targets discriminated breast cancer molecular subtypes and predicted novel tumour biology, with implications for precision medicine. Predicted invasion roles were validated using a tractable cell model, supporting our approach

Next Generation Very Large Array Memo No. 9 Science Working Group 4: Time Domain, Fundamental Physics, and Cosmology

We report here on key science topics for the Next Generation Very Large Array in the areas of time domain, fundamental physics, and cosmology. Key science cases considered are pulsars in orbit around the Galactic Center massive black hole, Sagittarius A*, electromagnetic counterparts to gravitational waves, and astrometric cosmology. These areas all have the potential for ground-breaking and transformative discovery. Numerous other topics were discussed during the preparation of this report and some of those discussions are summarized here, as well. There is no doubt that further investigation of the science case will reveal rich and compelling opportunities

Rare copy number variations are associated with poorer cognition in schizophrenia

Background Cognitive impairment in schizophrenia is a major contributor to poor outcomes yet its causes are poorly understood. Some rare copy number variants (CNVs) are associated with schizophrenia risk and impact cognition in healthy populations but their contribution to cognitive impairment in schizophrenia has not been investigated. We examined the effect of 12 schizophrenia CNVs on cognition in those with schizophrenia. Methods General cognitive ability was measured using the MATRICS composite z-score in 875 schizophrenia cases, and in a replication sample of 519 schizophrenia cases using WAIS Full-Scale IQ. Using linear regression we tested for association between cognition and schizophrenia CNV status, covarying for age and sex. In addition, we tested whether CNVs hitting genes in schizophrenia enriched gene sets (loss of function intolerant or synaptic gene sets) were associated with cognitive impairment. Results 23 schizophrenia CNV carriers were identified. Schizophrenia CNV carriers had lower general cognitive ability than non-schizophrenia CNV carriers in discovery (β=-0.66, 95%CI = -1.31 to -0.01) and replication samples (β=-0.91, 95%CI =-1.71 to -0.11), and after meta-analysis (β=-0.76, 95%CI=-1.26 to -0.25, p=0.003). CNVs hitting loss of function intolerant genes were associated with lower cognition (β= -0.15, 95%CI=-0.29 to -0.001, p=0.048). Conclusions In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management. We also demonstrate that rare CNVs hitting genes intolerant to loss of function variation lead to more severe cognitive impairment, above and beyond the effect of known schizophrenia CNVs