Miracle-dz/UniFAR-FTUs huggingface dataset:
Large-Scale Modelling of the Divergent Spectrin Repeats in Nesprins: Giant Modular Proteins

Nesprin-1 and nesprin-2 are nuclear envelope (NE) proteins characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KASH [Klarsicht–ANC–Syne-homology] domain and display N-terminal actin-binding CH (calponin homology) domains. Mutations in these proteins have been described in Emery-Dreifuss muscular dystrophy and attributed to disruptions of interactions at the NE with nesprins binding partners, lamin A/C and emerin. Evolutionary analysis of the rod domains of the nesprins has shown that they are almost entirely composed of unbroken SR-like structures. We present a bioinformatical approach to accurate definition of the boundaries of each SR by comparison with canonical SR structures, allowing for a large-scale homology modelling of the 74 nesprin-1 and 56 nesprin-2 SRs. The exposed and evolutionary conserved residues identify important pbs for protein-protein interactions that can guide tailored binding experiments. Most importantly, the bioinformatics analyses and the 3D models have been central to the design of selected constructs for protein expression. 1D NMR and CD spectra have been performed of the expressed SRs, showing a folded, stable, high content α-helical structure, typical of SRs. Molecular Dynamics simulations have been performed to study the structural and elastic properties of consecutive SRs, revealing insights in the mechanical properties adopted by these modules in the cell.
Filicide: Mental Illness in Those Who Kill Their Children

Background Most child victims of homicide are killed by a parent or step-parent. This large population study provides a contemporary and detailed description of filicide perpetrators. We examined the relationship between filicide and mental illness at the time of the offence, and care received from mental health services in the past. Method All filicide and filicide-suicide cases in England and Wales (1997–2006) were drawn from a national index of homicide perpetrators. Data on people in contact with mental health services were obtained via a questionnaire from mental health teams. Additional clinical information was collected from psychiatric reports. Results 6144 people were convicted of homicide, 297 were filicides, and 45 cases were filicide-suicides. 195 (66%) perpetrators were fathers. Mothers were more likely than fathers to have a history of mental disorder (66% v 27%) and symptoms at the time of the offence (53% v 23%), most often affective disorder. 17% of mothers had schizophrenia or other delusional disorders. Overall 8% had schizophrenia. 37% were mentally ill at the time of the offence. 20% had previously been in contact with mental health services, 12% within a year of the offence. Conclusion In the majority of cases, mental illness was not a feature of filicide. However, young mothers and parents with severe mental illness, especially affective and personality disorder who are providing care for children, require careful monitoring by mental health and other support services. Identifying risk factors for filicide requires further research.
Computerized Neuropsychological Assessment Devices: Joint Position Paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology

This joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology sets forth our position on appropriate standards and conventions for computerized neuropsychological assessment devices (CNADs). In this paper, we first define CNADs and distinguish them from examiner-administered neuropsychological instruments. We then set forth position statements on eight key issues relevant to the development and use of CNADs in the healthcare setting. These statements address (a) device marketing and performance claims made by developers of CNADs; (b) issues involved in appropriate end-users for administration and interpretation of CNADs; (c) technical (hardware/software/firmware) issues; (d) privacy, data security, identity verification, and testing environment; (e) psychometric development issues, especially reliability and validity; (f) cultural, experiential, and disability factors affecting examinee interaction with CNADs; (g) use of computerized testing and reporting services; and (h) the need for checks on response validity and effort in the CNAD environment. This paper is intended to provide guidance for test developers and users of CNADs that will promote accurate and appropriate use of computerized tests in a way that maximizes clinical utility and minimizes risks of misuse. The positions taken in this paper are put forth with an eye toward balancing the need to make validated CNADs accessible to otherwise underserved patients with the need to ensure that such tests are developed and utilized competently, appropriately, and with due concern for patient welfare and quality of care.
The Burden of Genetic and Epigenetic Traits in Prematurity

Despite decades of investigations and accumulated scientific knowledge, preterm birth (PTB) remains a significant burden worldwide. Several mechanisms have been proposed to explain this condition, and a number of risk factors from infectious to behavioral and genetic/epigenetic factors influence this outcome. The heritability of PTB is estimated to be 17% to 36%, which demonstrates that genetic predisposition plays a key role in PTB. Structural DNA modifications without changes in the DNA sequence and post-transcriptional regulation also have an impact on gene expression and thus influence pregnancy outcomes. There is a complex interplay between environmental factors and the individual’s genetics and epigenetics that may culminate in PTB, but the complete regulatory pathways and networks involved in this context are still unclear. Here, we outline what is known so far about the genetic and epigenetic factors involved in preterm delivery, including polymorphisms, DNA methylation, and microRNAs, and suggest fields for research.
Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC)

Purpose: Persistent androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC) and confers resistance to AR-targeting therapies. Novel therapeutic strategies to overcome this are urgently required. We evaluated how bromodomain and extra-terminal (BET) protein inhibitors (BETi) abrogate aberrant AR signaling in CRPC. Experimental Design: We determined associations between BET expression, AR-driven transcription, and patient outcome; and the effect and mechanism by which chemical BETi (JQ1 and GSK1210151A; I-BET151) and BET family protein knockdown regulates AR-V7 expression and AR signaling in prostate cancer models. Results: Nuclear BRD4 protein expression increases significantly (P ≤ 0.01) with castration resistance in same patient treatment-naïve (median H-score; interquartile range: 100; 100–170) and CRPC (150; 110–200) biopsies, with higher expression at diagnosis associating with worse outcome (HR, 3.25; 95% CI, 1.50–7.01; P ≤ 0.001). BRD2, BRD3, and BRD4 RNA expression in CRPC biopsies correlates with AR-driven transcription (all P ≤ 0.001). Chemical BETi, and combined BET family protein knockdown, reduce AR-V7 expression and AR signaling. This was not recapitulated by C-MYC knockdown. In addition, we show that BETi regulates RNA processing thereby reducing alternative splicing and AR-V7 expression. Furthermore, BETi reduce growth of prostate cancer cells and patient-derived organoids with known AR mutations, AR amplification and AR-V7 expression. Finally, BETi, unlike enzalutamide, decreases persistent AR signaling and growth (P ≤ 0.001) of a patient-derived xenograft model of CRPC with AR amplification and AR-V7 expression. Conclusions: BETi merit clinical evaluation as inhibitors of AR splicing and function, with trials demonstrating their blockade in proof-of-mechanism pharmacodynamic studies. Clin Cancer Res; 24(13); 3149–62. ©2018 AACR.
Of Uberfleas and Krakens: Detecting Trade-offs Using Mixed Models.

SYNOPSIS All animals experience performance trade-offs as they complete tasks such as capturing prey, defending territories, acquiring mates, and escaping predators. Why then, is it so hard to detect performance trade-offs at the whole-organismal level? Why do we sometimes even obtain positive correlations between two performance traits that are predicted to be negatively associated? Here we explore two plausible explanations. First, most analyses are based on individual maximal values (i.e., personal best), which could introduce a bias in the correlation estimates. Second, phenotypic correlations alone may be poor indicators of a trade-off when contrasting processes occur at the among- versus within-individual levels. One such scenario is the "big houses big cars" model developed in life-history theory to explain the existence of "uberfleas" that are superior in all regards (because they acquire more resources than others). We highlight that the exact opposite scenario might occur for performance trade-offs, where among-individual trade-offs may be masked by within-individual changes in physical condition. One of the best ways to test among these alternative scenarios is to collect repeated pairs of performance traits and analyze them using multivariate mixed models (MMMs). MMMs allow straightforward and simultaneous examination of trait correlations at the among- and within-individual levels. We use a simple simulation tool (SQuID package in R) to create a population of Krakens, a mythical giant squid-like sea creature whose morphology generates a performance trade-off between swimming speed and strength or ability to sink ships. The simulations showed that using individual maximum values introduces a bias that is particularly severe when individuals differ in the number of repeated samples (ntrial). Finally, we show how MMMs can help detect performance (or any other type of) trade-offs and offer additional insights (e.g., help detect plasticity integration). We hope researchers will adopt MMMs when exploring trade-offs in whole-animal performances.
Perfectionistic Strivings, Motivation and Engagement in Sport-Specific Activities Among Adolescent Team Athletes

The present study sought to extend existing literature by examining the longitudinal relationships between perfectionistic strivings, autonomous motivation, and engagement in sport-specific activities among youth athletes in three team sports. Participants were 172 team sports athletes (mean age = 15.2 years, SD = 0.5; males = 94, females = 78) who completed measures of perfectionistic strivings and autonomous motivation at the start and end of a competitive season. Players also completed a training diary during the season. Cross-lagged path analysis, found a reciprocal and positive relationship between autonomous motivation and engagement in sport-specific activities. In addition, higher perfectionistic strivings at the start of a competitive season were positively associated with engagement in sport-specific activities at the end of season and not the reverse. Autonomous motivation mediated this relationship between perfectionistic strivings and sport-specific activities engagement. Thus, this study supports the reciprocal association between motivation and engagement in sport-specific activities and unidirectional relations between perfectionistic strivings and sport-specific activities engagement among youth team sports athletes.
4EHP-independent repression of endogenous mRNAs by the RNA-binding protein GIGYF2

Abstract Initially identified as a factor involved in tyrosine kinase receptor signaling, Grb10-interacting GYF protein 2 (GIGYF2) has later been shown to interact with the 5′ cap-binding protein 4EHP as part of a translation repression complex, and to mediate post-transcriptional repression of tethered reporter mRNAs. A current model proposes that GIGYF2 is indirectly recruited to mRNAs by specific RNA-binding proteins (RBPs) leading to translation repression through its association with 4EHP. Accordingly, we recently observed that GIGYF2 also interacts with the miRNA-induced silencing complex and probably modulates its translation repression activity. Here we have further investigated how GIGYF2 represses mRNA function. In a tethering reporter assay, we identify three independent domains of GIGYF2 with repressive activity. In this assay, GIGYF2-mediated repression is independent of 4EHP but largely dependent on the CCR4/NOT complex that GIGYF2 recruits through multiple interfaces. Importantly, we show that GIGYF2 is an RBP and identify for the first time endogenous mRNA targets that recapitulate 4EHP-independent repression. Altogether, we propose that GIGYF2 has two distinct mechanisms of repression: one depends on 4EHP binding and mainly affects translation; the other is 4EHP-independent and involves the CCR4/NOT complex and its deadenylation activity.
Recombination-related properties of a-screw dislocations in GaN: A combined CL, EBIC, TEM study

Cathodoluminescence (CL), electron beam current (EBIC) and transmission electron microscopy (TEM) techniques have been applied to investigate recombination properties and structure of freshly introduced dislocations in low-ohmic GaN crystals. It was confirmed that the only a-screw dislocations exhibited an intense characteristic dislocation-related luminescence (DRL) which persisted up to room temperature and was red-shifted by about 0.3 eV with respect to the band gap energy not only in HVPE but also in MOCVD grown samples. EBIC contrast of the dislocations was found to be temperature independent indicating that the dislocation-related recombination level is situated below 200 meV with respect of conduction band minimum. With the increasing of the magnification of the dislocation TEM cross-sectional images they were found to disappear, probably, due to the recombination enhanced dislocation glide (REDG) under electron beam exposure which was immediately observed in CL investigations on a large scale. The.
Factors Influencing Time to Adoption for Dogs in a Provincial Shelter System in Canada

ABSTRACT Millions of companion animals are relinquished to shelters each year. For each dog entering, their characteristics and the characteristics of the shelter holding him/her influence their time to adoption. Using a Cox proportional hazards frailty model, these issues were explored using data from 31 shelters within the British Columbia Society for the Prevention of Cruelty to Animals shelter system. Results indicated that surrender reason, age, original source, coat color, breed, human population density of the shelter location, and year the nonhuman animal entered the shelter significantly influenced time to adoption. This study identified characteristics of dogs that make them less likely to be adopted quickly. Given limited resources, these results may help inform shelters on how to best allocate resources, particularly in interventions to improve adoption rates in shelters.
Understanding Phenotypical Character Evolution in Parmelioid Lichenized Fungi (Parmeliaceae, Ascomycota)

Parmelioid lichens form a species-rich group of predominantly foliose and fruticose lichenized fungi encompassing a broad range of morphological and chemical diversity. Using a multilocus approach, we reconstructed a phylogeny including 323 OTUs of parmelioid lichens and employed ancestral character reconstruction methods to understand the phenotypical evolution within this speciose group of lichen-forming fungi. Specifically, we were interested in the evolution of growth form, epicortex structure, and cortical chemistry. Since previous studies have shown that results may differ depending on the reconstruction method used, here we employed both maximum-parsimony and maximum-likelihood approaches to reconstruct ancestral character states. We have also implemented binary and multistate coding of characters and performed parallel analyses with both coding types to assess for potential coding-based biases. We reconstructed the ancestral states for nine well-supported major clades in the parmelioid group, two higher-level sister groups and the ancestral character state for all parmelioid lichens. We found that different methods for coding phenotypical characters and different ancestral character state reconstruction methods mostly resulted in identical reconstructions but yield conflicting inferences of ancestral states, in some cases. However, we found support for the ancestor of parmelioid lichens having been a foliose lichen with a non-pored epicortex and pseudocyphellae. Our data suggest that some traits exhibit patterns of evolution consistent with adaptive radiation.
The Conservation Value of Traditional Rural Landscapes: The Case of Woodpeckers in Transylvania, Romania

Land use change is a major threat to global biodiversity. Forest species face the dual threats of deforestation and intensification of forest management. In regions where forests are under threat, rural landscapes that retain structural components of mature forests potentially provide valuable additional habitat for some forest species. Here, we illustrate the habitat value of traditional wood pastures for a woodpecker assemblage of six species in southern Transylvania, Romania. Wood pastures are created by long-term stable silvo-pastoral management practices, and are composed of open grassland with scattered large, old trees. Because of their demanding habitat requirements, woodpeckers share habitat with many other bird species, and have been considered as possible indicator species for bird species diversity. We first compared woodpecker assemblages between forests and wood pastures. Second, we grouped features of wood pastures into three spatial contexts and addressed how these features related to the occurrence of three woodpecker species that are formally protected. Woodpecker species composition, but not the number of species, differed between forests and wood pastures, with the green woodpecker occurring more commonly in wood pastures, and the lesser spotted woodpecker more commonly in forests. Within wood pastures, the intermediate context (especially surrounding forest cover) best explained the presence of the grey-headed and middle spotted woodpecker. By contrast, variables describing local vegetation structure and characteristics of the surrounding landscape did not affect woodpecker occurrence in wood pastures. In contrast to many other parts of Europe, in which several species of woodpeckers have declined, the traditional rural landscape of Transylvania continues to provide habitat for several woodpecker species, both in forests and wood pastures. Given the apparent habitat value of wood pastures for woodpeckers we recommend wood pastures be explicitly considered in relevant policies of the European Union, namely the Habitats Directive and the EU Common Agricultural Policy.
Increasing Burden of Stroke: The Dijon Stroke Registry (1987–2012)

Background: We aimed to provide a representation of the global burden of stroke. Methods: All cases of stroke were prospectively identified through the population-based registry of Dijon, France (1987–2012). Attack rates and mortality rates (defined as stroke leading to death within 30 days) were standardized to the European standard. Sex differences and temporal trends were evaluated by calculating rate ratios (RRs). Results: In all, 5,285 stroke cases (52.7% women) were recorded. The standardized attack rate was 98.2/100,000/year and the mortality rate was 12/100,000/year, and both were lower in women than in men (RR 0.67, p < 0.001, and RR 0.70, p < 0.001, respectively). Attack rates increased over time (RR 1.016; 95% CI 1.013–1.020) irrespective of the stroke subtype. In contrast, mortality rates declined (RR 0.985; 95% CI 0.976–0.995) with decreasing rates for ischemic stroke but no change for intracerebral hemorrhage and subarachnoid hemorrhage. The sex gap in both attack and mortality rates remained stable. Between the first (1987–1991) and the last (2007–2012) study periods, the annual number of stroke patients who survived beyond 30 days rose by 55%, Conclusions: Increasing attack rates and decreasing mortality have led to a rise in the number of stroke survivors in the population, thus indicating a growing need for the implementation of dedicated services.
Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures—the majority of paleo-colour studies involve melanin granules—is not without risks. In addition, animals with contrasting dorso-ventral colouration may be under different selection pressures beyond the need for camouflage, including, for instance, visual communication or ultraviolet (UV) protection. Melanin production is costly, and animals may invest less in areas of the integument where pigments are less needed. In addition, melanocytes exposed to UV radiation produce more melanin than unexposed melanocytes. Pigment economization may thus explain the colour pattern of some counter-shaded animals, including extinct species. Even in well-studied extant species, their diversity of hues and patterns is far from being understood; inferring colours and their functions in species only known from one or few specimens from the fossil record should be exerted with special prudence.
Derandomizing Dynamic Programming and Beyond

We consider probabilistic circuits working over the real numbers, and using arbitrary semialgebraic functions of bounded description complexity as gates. We show that such circuits can be simulated by deterministic circuits with an only polynomial blowup in size. An algorithmic consequence is that randomization cannot substantially speed up dynamic programming. In arithmetic circuits, randomization cannot spare even one single gate.
On the structural evolution of Fe-Al laminates obtained by physical vapour deposition

Abstract Physical vapour deposition (PVD) with two evaporation sources was used to produce nanometre-scale laminated structures containing alternating layers of the two source materials Fe and Al. Transmission electron microscopy was used to characterize the microstructures of laminates with different Fe-to-Al thickness ratios and different layer thicknesses. The results showed that both absolute nominal thicknesses and thickness ratios were important for the structural evolution in the as-deposited microstructures of the materials. The microstructural evolution during PVD was studied by simulating interdiffusion and nucleation, in order to clarify the roles of thermodynamics, adsorption, surface diffusion, interdiffusion and nucleation during processing. The interplay of these factors governed whether the targeted ‘laminated’ structures could be produced by PVD. Empirical laws for estimating surface, grain-boundary and interface energies were also derived.