Miracle-dz/UniFAR-FTUs huggingface dataset:
The mediating effect of parental warmth on the association of parent pressure and athlete perfectionism in adolescent soccer

ABSTRACT Appropriately designed sport contexts have the potential to offer participants a range of positive developmental outcomes across domains. However, excessive pressure from parents and an emphasis on achievement outcomes may lead young athletes to develop maladaptive personality characteristics such as perfectionism, which may undermine the positive outcomes from participating in sport. While parenting styles have been broadly explored in relation to the development of perfectionism, individual parenting behaviours have not been examined as unique predictors. The present study was designed to test the potential mediating role of perceived parental warmth on the association of perceived parent pressure and athletes’ perfectionism in the context of competitive club soccer. Data were drawn from a sample of 149 adolescents in the United States who were participating in competitive club soccer. Results demonstrated an acceptable model fit with paternal pressure positively predicting both perfectionistic concerns and strivings, and perceived paternal warmth mediating the relationship between paternal pressure and perfectionistic strivings (β = -.18, p < .05) and concerns (β = -.19, p < .05). Perceived maternal pressure had no relationship with athlete perfectionistic strivings (β = -.03, p = .38) or concerns (β = -.02, p = .46). These findings extend knowledge of the pressure-perfectionism association while also accounting for the mediating effect of perceived parental warmth. The present study highlights the relationship between perceived paternal pressure and warmth in relation to perfectionism in competitive club soccer. Findings have the potential to inform future research examining parenting styles in the context of adolescent sport.
Parental care results in a greater mutation load, for which it is also a phenotypic antidote

Benevolent social behaviours, such as parental care, are thought to enable mildly deleterious mutations to persist. We tested this prediction experimentally using the burying beetle Nicrophorus vespilloides, an insect with biparental care. For 20 generations, we allowed replicate experimental burying beetle populations to evolve either with post-hatching care (‘Full Care’ populations) or without it (‘No Care’ populations). We then established new lineages, seeded from these experimental populations, which we inbred to assess their mutation load. Outbred lineages served as controls. We also tested whether the deleterious effects of a greater mutation load could be concealed by parental care by allowing half the lineages to receive post-hatching care, while half did not. We found that inbred lineages from the Full Care populations went extinct more quickly than inbred lineages from the No Care populations – but only when offspring received no post-hatching care. We infer that Full Care lineages carried a greater mutation load, but that the associated deleterious effects on fitness could be overcome if larvae received parental care. We suggest that the increased mutation load caused by parental care increases a population’s dependence upon care. This could explain why care is seldom lost once it has evolved.
Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels in rat

This study reports that targeting intrinsically disordered regions (IDRs) of NaV1.7 protein facilitated discovery of sodium channel inhibitory peptide aptamers (NaviPA) for adeno-associated virus (AAV)-mediated, sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, and INa1.3, but not INa1.5 and INa1.8 was found for a prototype, named NaviPA1, which was derived from the NaV1.7 intracellular loop 1 and is conserved among the TTXs NaV subtypes. NaviPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INa but not TTXr INa. DRG injection of AAV6-encoded NaviPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current-clamp of the PSNs showed that NaviPA1 expression normalized PSN excitability in TNI rats, suggesting that NaviPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. Immunohistochemistry revealed efficient NaviPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaviPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaviPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs has potential as peripheral nerve-restricted analgesic therapeutics.
Histone H3.3 lysine 9 and 27 control repressive chromatin states at cryptic cis-regulatory elements and bivalent promoters in mouse embryonic stem cells

Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutated histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here, we find that H3.3K9 is essential for controlling specific distal intergenic regions and for proper H3K27me3 deposition at promoters. The H3.3K9A mutation resulted in decreased H3K9me3 at regions encompassing endogenous retroviruses and induced a gain of H3K27ac and nascent transcription. These changes in the chromatin environment unleashed cryptic enhancers, resulting in the activation of distinctive transcriptional programs and culminating in protein expression normally restricted to specialized immune cell types. The H3.3K27A mutant disrupted deposition and spreading of the repressive H3K27me3 mark, particularly impacting bivalent genes with higher basal level of H3.3 at promoters. Therefore, H3.3K9 and K27 crucially orchestrate repressive chromatin states at cis-regulatory elements and bivalent promoters, respectively, and instruct proper transcription in mESCs.
Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation

During intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for life-long maintenance of the tissue. While the morphological changes associated with the transition are well-characterized, the molecular mechanisms underpinning the maturation process are not fully understood. Here, we leverage intestinal organoid cultures to profile transcriptional, chromatin accessibility, DNA methylation and 3D chromatin conformation landscapes defining fetal and adult epithelial cells. We observed prominent differences in gene expression and enhancer activity, accompanied by changes in 3D organization and local changes in DNA accessibility and methylation, between the two cellular states. Using integrative analyses, we identified sustained YAP transcriptional activity as a major gatekeeper of the immature fetal state. We found the YAP-associated transcriptional network to be regulated at various levels of chromatin organization, and likely to be coordinated by changes in extracellular matrix composition. Altogether, our work highlights the value of unbiased profiling of regulatory landscapes for the identification of key mechanisms underlying tissue maturation.
Item-specific memory reactivation during sleep supports memory consolidation in humans

Memory consolidation stabilizes newly acquired information. Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Via unobtrusively re-playing auditory memory cues to sleeping human participants, we identified the reactivation of individual memories during slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found functionally segregated item-specific representations: the early post-cue EEG activity (0-2 seconds) contained comparable representations for memory cues and for non-memory control cues, thus reflecting sensory processing. Critically, the later EEG activity (2.5-3 s) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, demonstrating the reactivation and consolidation of individual memories. Moreover, spindles preferentially supported item-specific memory reactivation for items that were not tested before sleep. These findings delineated how cue-triggered item-specific memory reactivation, subserved by spindles during SWS, contributed to memory consolidation. These results will benefit future research aiming to perturb specific memory episodes during sleep.
MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation

Correlative evidence has suggested that DNA methylation promotes the formation of transcriptionally silent heterochromatin. Accordingly, the methyl-CpG binding domain protein MeCP2 is often portrayed as a constituent of heterochromatin. This interpretation has been reinforced by the use of mouse cells as an experimental system for studying the mammalian epigenome, as heterochromatin, DNA methylation and MeCP2 colocalise in prominent foci. The findings presented here revise this view. We show that focal localisation of MeCP2 in mice is independent of heterochromatin, as DNA methylation-dependent MeCP2 foci persist even when the signature heterochromatin histone mark H3K9me3 is absent and heterochromatin protein HP1 is diffuse. Contrary to the proposal that MeCP2 forms condensates at mouse heterochromatic foci via liquid-liquid phase transition, the short methyl-CpG binding domain, which lacks the disordered domains thought to be required for condensation, is sufficient to target foci in mouse cells. Importantly, we find that the formation of MeCP2 foci in mice is highly atypical, as they are indetectable in 14 out of 16 other mammalian species, including humans. Notably, MeCP2 foci are absent in Mus spretus which can interbreed with Mus musculus but lacks its highly methylated pericentric satellite DNA repeats. We conclude that MeCP2 has no intrinsic tendency to form nuclear condensates and its localisation is independent of heterochromatin formation. Instead, the distribution of MeCP2 in the nucleus is primarily determined by global DNA methylation patterns and is typically euchromatic.
Isolation of a Chlamydia Strain from Lung Tissue Samples in Healthy Chickens Exhibiting Antagonistic Effects on Avian Infectious Bronchitis Virus

To assess the feasibility of isolating Chlamydia strains with antiviral activity against avian infectious bronchitis virus (IBV) from healthy chickens in farms, 58 Chlamydia strains were obtained from 160 lung tissue samples collected across ten chicken farms, yielding an overall isolation rate of 36.25%. SPF chickens co-infected with Chlamydia and IBV were employed for verification, leading to the identification of eight strains (Bi ≥ 0.800) with potent antiviral effects against IBV, accounting for 13.79% of the total isolated strains. The top-performing strain, Y17 Chlamydia strain, was selected and subjected to cell co-culture and U-tube experiments with IBV. Results demonstrated that the Y17 Chlamydia strain significantly impeded IBV replication in chicken tracheal epithelial cells (P<0.01) and did not secrete or induce host cells to secrete extracellular metabolites with antagonistic effects on IBV infection in U-tube experiments (P>0.05), suggesting that its antiviral activity was cell-autonomous. Our research highlights the feasibility of isolating Chlamydia strains with antiviral activity against IBV from healthy chickens and suggests that antiviral strains could be widespread, even though their efficacy against viruses is strain-specific. The presence of broad-spectrum antiviral Chlamydia strains may also be possible. Considering the prevalence of Chlamydia strains in vertebrate hosts, along with the fact that some strains are either non-pathogenic or display low toxicity, our findings could offer a fresh perspective on the prevention and treatment of viral infections in vertebrates.
Proteasome activity is required for reovirus entry into cells

ABSTRACT Since viruses have limited coding capacity in their genomes, they use host cell machinery to complete virtually every stage of their replication cycle. Mammalian orthoreovirus (reovirus) is comprised of two concentric protein shells, the inner core and the outer capsid. Following attachment to its receptor, reovirus enters the cell by receptor-mediated endocytosis. Within endosomes, reovirus utilizes host acid-dependent proteases to process the viral outer capsid. Specifically, the outer capsid protein σ3 is degraded, and μ1 is cleaved to form the disassembly intermediate infectious subvirion particles (ISVPs). ISVPs undergo additional conformational changes into ISVP*s that release small peptides, which mediate the penetration of endosomal membranes. Membrane penetration allows for delivery of the remaining viral core into the cytoplasm for subsequent gene expression. Here, we describe that proteasomes control an entry step of reovirus particles. We show that chemically inhibiting the proteasome blocks infection at a stage following ISVP formation but prior to transcriptional activation of cores. Specifically, inhibition of the proteasome prevents conformational changes in μ1 characteristic of ISVP-to-ISVP* conversion. In the absence of these conformational changes, cores are unable to be delivered and become transcriptionally active, thereby blocking viral replication. This work highlights a previously unknown way in which reovirus relies on host factors for successful replication. IMPORTANCE Due to their limited genetic capacity, viruses are reliant on multiple host systems to replicate successfully. Mammalian orthoreovirus (reovirus) is commonly used as a model system for understanding host-virus interactions. In this study, we identify that the proteasome system, which is critical for cellular protein turnover, affects reovirus entry. Inhibition of the proteasome using a chemical inhibitor blocks reovirus uncoating. Blocking these events reduces subsequent replication of the virus. This work identifies that additional host factors control reovirus entry. Due to their limited genetic capacity, viruses are reliant on multiple host systems to replicate successfully. Mammalian orthoreovirus (reovirus) is commonly used as a model system for understanding host-virus interactions. In this study, we identify that the proteasome system, which is critical for cellular protein turnover, affects reovirus entry. Inhibition of the proteasome using a chemical inhibitor blocks reovirus uncoating. Blocking these events reduces subsequent replication of the virus. This work identifies that additional host factors control reovirus entry.
Preferences reveal separable valuation systems in prefrontal-limbic circuits

Individual preferences for the flavor of different foods and fluids exert a strong influence on behavior. Most current theories posit that preferences are integrated with other state variables in orbitofrontal cortex (OFC), which is thought to derive the relative subjective value of available options to drive choice behavior. Here we report that instead of a single integrated valuation system in OFC, another separate one is centered in ventrolateral prefrontal cortex (vlPFC) in macaque monkeys. Specifically, we found that OFC and vlPFC preferentially represent outcome flavor and outcome probability, respectively, and that preferences are separately integrated into these two aspects of subjective valuation. In addition, vlPFC, but not OFC, represented the outcome probability for the two options separately, with the difference between these representations reflecting the degree of preference. Thus, there are at least two separable valuation systems that work in concert to guide choices and that both are biased by preferences.
De novo distillation of thermodynamic affinity from deep learning regulatory sequence models of in vivo protein-DNA binding

Transcription factors (TF) are proteins that bind DNA in a sequence-specific manner to regulate gene transcription. Despite their unique intrinsic sequence preferences, in vivo genomic occupancy profiles of TFs differ across cellular contexts. Hence, deciphering the sequence determinants of TF binding, both intrinsic and context-specific, is essential to understand gene regulation and the impact of regulatory, non-coding genetic variation. Biophysical models trained on in vitro TF binding assays can estimate intrinsic affinity landscapes and predict occupancy based on TF concentration and affinity. However, these models cannot adequately explain context-specific, in vivo binding profiles. Conversely, deep learning models, trained on in vivo TF binding assays, effectively predict and explain genomic occupancy profiles as a function of complex regulatory sequence syntax, albeit without a clear biophysical interpretation. To reconcile these complementary models of in vitro and in vivo TF binding, we developed Affinity Distillation (AD), a method that extracts thermodynamic affinities de-novo from deep learning models of TF chromatin immunoprecipitation (ChIP) experiments by marginalizing away the influence of genomic sequence context. Applied to neural networks modeling diverse classes of yeast and mammalian TFs, AD predicts energetic impacts of sequence variation within and surrounding motifs on TF binding as measured by diverse in vitro assays with superior dynamic range and accuracy compared to motif-based methods. Furthermore, AD can accurately discern affinities of TF paralogs. Our results highlight thermodynamic affinity as a key determinant of in vivo binding, suggest that deep learning models of in vivo binding implicitly learn high-resolution affinity landscapes, and show that these affinities can be successfully distilled using AD. This new biophysical interpretation of deep learning models enables high-throughput in silico experiments to explore the influence of sequence context and variation on both intrinsic affinity and in vivo occupancy.
Global practical tracking control for a class of uncertain non-linear systems [Brief Paper]

This study addresses the problem of global practical tracking via output feedback for a class of uncertain non-linear systems. First, the authors design a homogeneous state observer and controller using the generalised adding power integrator technique in a recursive way for the nominal system without the perturbing non-linearities. Then based on the homogeneous domination approach, a scaling gain is introduced into the proposed output feedback stabiliser to achieve the small tracking error arbitrarily. The simulation results worked out in an example verify the theory. The proposed approach can also widen the applicability to a broader class of systems with non-triangular structure.
Impact of polymer curing on two-dimensional and three-dimensional shape change in nanoimprint lithography

Abstract. Polymer shrinkage from curing in nanoimprint lithography (NIL) strongly affects the ultimate shapes of two- and three-dimensional structures produced following etching. We computationally study the curing step in the NIL process and predict the shape changes caused by polymer shrinkage. The shape changes are predicted for crosses, diamonds with sharp and rounded tips, and multitiered structures that are applicable for multibit memory devices and dual damascene processes. The shape changes from curing are shown to be governed by the shrinkage coefficient of the polymer resist, its Poisson’s ratio, and the geometric aspect ratios of the shapes. Finite element simulations demonstrate that shape change due to polymer densification is equal to the average volumetric contraction of the resist material, but shrinkage is not isotropic and vertical displacement dominates. The thickness of the residual layer does not impact the final profile of the imprinted shapes considered. Further analysis shows that diamonds with sharp tips stay sharp while the tips of rounded diamonds get sharper. Additionally, shape changes for multitiered structures are not uniformly distributed among the tiers. Using etch simulations, we demonstrate the significant impact of polymer shrinkage on the final feature profile.
Effect of viscoelasticity on two-dimensional laminar vortex shedding in flow past a rotating cylinder

In this work, we numerically investigate the effect of viscoelasticity on 2D laminar vortex dynamics in flows past a single rotating cylinder for rotational rates (the rotational rate ex is defined by the ratio of the circumferential rotating velocity to free stream velocity) at Re=100, in which the vortex shedding has been predicted to occur in literature for Newtonian fluids. The objective of the present research is to develop a promising technique to fully suppress the vortex shedding past a bluff body by rotating a cylinder and controlling fluid elasticity. The predicted vortex dynamics with the present method is consistent with the previous works for Newtonian flows past a rotating cylinder. We also verified our method by comparing our data with the literature in the case of viscoelastic flow past a non-rotating cylinder. For , the frequency of vortex shedding slightly decreases but the fluctuation of drag and lift coefficient significantly decreases with increasing fluid elasticity. We observe that the vortex shedding of viscoelastic flow disappears at lower than the Newtonian case. At =5, the relationship between the frequency of vortex shedding and Weissenberg number (Wi) is predicted to be non-monotonic and have a minimum around Wi=0.25. The vortex shedding finally disappears over critical Wi number. The present results suggest that the vortex shedding in the flow around a rotating cylinder can be more effectively suppressed for viscoelastic fluids than Newtonian fluids.
JOINT DOMAIN-DECOMPOSITION -LU PRECONDITIONERS FOR SADDLE POINT PROBLEMS

For saddle point problems in fluid dynamics, several popular preconditioners exploit the block struc- ture of the problem to construct block triangular preconditioners. The performance of such preconditioners depends on whether fast, approximate solvers for the linear systems on the block diagonal (representing convection-diffusion problems) as well as for the Schur complement (in the pressure variables) are available. In this paper, we will in- troduce a completely different approach in which we ignore this given block structure. We will instead compute an approximate LU-factorization of the complete system matrix using hierarchical matrix techniques. In particular, we will use domain-decomposition clustering with an additional local pivoting strategy to order the complete index set. As a result, we obtain an -matrix structure in which an -LU factorization is computed more efficiently and with higher accuracy than for the corresponding block structure based clustering. -LU preconditioners resulting from the block and joint approaches will be discussed and compared through numerical results.
Weak Approximation of Multidimensional Obliquely Reflected Brownian Motion by Solutions of SDE

Consider a multidimensional obliquely reflected Brownian motion in a domain. We approximate it by diffusion processes: We emulate the "hard barrier" of reflection by a "soft barrier" of a drift coefficient. Our results include the case of the boundary with non-non-smooth parts, as long as the reflected Brownian motion does not hit these parts. We apply these results to a semimartingale reflected Brownian motion (SRBM) in the orthant.