Miracle-dz/UniFAR-FTUs huggingface dataset:
TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells

Stimulation of Toll-like receptors (TLRs) on macrophages and dendritic cells (DCs) by pathogen-derived products induces the production of cytokines, which play an important role in immune responses. Here, we investigated the role of the TPL-2 signaling pathway in TLR induction of interferon-β (IFN-β) and interleukin-10 (IL-10) in these cell types. It has previously been suggested that IFN-β and IL-10 are coordinately regulated after TLR stimulation. However, in the absence of TPL-2 signaling, lipopolysaccharide (TLR4) and CpG (TLR9) stimulation resulted in increased production of IFN-β while decreasing IL-10 production by both macrophages and myeloid DCs. In contrast, CpG induction of both IFN-α and IFN-β by plasmacytoid DCs was decreased in the absence of TPL-2, although extracellular signal-regulated kinase (ERK) activation was blocked. Extracellular signal-related kinase–dependent negative regulation of IFN-β in macrophages was IL-10–independent, required protein synthesis, and was recapitulated in TPL-2–deficient myeloid DCs by retroviral transduction of the ERK-dependent transcription factor c-fos.
Parametric Discrete Choice Models Based on the Scale Mixtures of Multivariate Normal Distributions (running Title: Parametric Discrete Choice Models)

SUMMARY. A rich class of parametric models is proposed for discrete choice data based on the scale mixtures of multivariate normal distributions. With special connections to multinomial probit, the new models can be implemented in a Bayesian framework without much diiculty. The proposed class of models can be extended to panel data where accounting for heterogeneities is needed. This is done by building a Bayesian hierarchical model within the random utility maximization framework. Model comparison using the Bayes factor is developed. The new models and the estimation techniques are illustrated using travel mode choice and panel brand choice data.
An integrated view of changing nutrient availability in model species: the role of signaling in the plant response

The present thesis is focused on rhe responses of (i) Arabidopsis tha! ia11a to phosphate starvation, and (ii) Medicago tru11catula to different N sources. In this sense, phosphate starvation compromises electron flow through the cytochrome pathway of the mitochondrial electron transport chain, and plants commonly respond to phosphate deprivation by increasing flow through the altemative oxidase (AOX). To test whether this response is linked to the increase in nitric oxide (NO) production that also increases under phosphate starvation,Arabidopsis thaliana seedlings (wild type, WT and nitrare reductase double mutant nia) were grown for 15 days on media containing either O or 1lll\i1 inorganic phosphate. Phosphate deprivation increased NO production in WT roots, and the AOX level and the capacity of the alternative pathway to consume electrons in WT seedlings; whereas the same treatment failed to stimulate NO production and AOX expression in the nia mutant, and the plants had an altered growth phenotype. The NO donor S-nitrosoglutathione rescued the growth phenotype of the nia mutants under phosphate deprivation to sorne extent, and it also increased the respiratory capacity of AOX. It is concluded that NO is required for the induction of the AOX pathway when seedlings are grown under phosphate-limiting conditions. Regarding the second part of this thesis, ir was focused on the early identification of stress response and plant performance of Medicago truncat11/a growing in axenic medium with ammonium or urea as the sole source of nitrogen, with respect to nitrate-based nutrition. Both ammonium and ureic nutrition severely affected the root system architecture, resulting in changes in the main elongation rate, lateral root development, and insert position from the root base. The auxin content decreased in both urea- and ammonium-treated roots; however, only the ammonium-treated plants were affected at the shoot level. The analysis of chlorophyll a fluorescence transients showed that ammonium affected photosystem II, but urea did not impair photosynthetic activity. Superoxi.de dismutase isoenzymes in the plastids were moderately affected by urea and ammonium in the roots. Low <lose (1mM) of ammonium or urea did not affect the metabolism and signalling of N. Under this scenario, there was an up-regulation of aquaporins and the modulation of phenylpropanoids metabolism on roots, allowing an accurate sensing mechanism through which plants uptake and assimilated the N of the medium.
Cannabidiol Improves Vasorelaxation in Zucker Diabetic Fatty Rats through Cyclooxygenase Activation

Cannabidiol (CBD) decreases insulitis, inflammation, neuropathic pain, and myocardial dysfunction in preclinical models of diabetes. We recently showed that CBD also improves vasorelaxation in the Zucker diabetic fatty (ZDF) rat, and the objective of the present study was to establish the mechanisms underlying this effect. Femoral arteries from ZDF rats and ZDF lean controls were isolated, mounted on a myograph, and incubated with CBD (10 μM) or vehicle for 2 hours. Subsequent vasorelaxant responses were measured in combination with various interventions. Prostaglandin metabolites were detected using enzyme immunoassay. Direct effects of CBD on cyclooxygenase (COX) enzyme activity were measured by oxygraph assay. CBD enhanced the maximum vasorelaxation to acetylcholine (ACh) in femoral arteries from ZDF lean rats (P < 0.01) and especially ZDF rats (P < 0.0001). In ZDF arteries, this enhancement persisted after cannabinoid receptor (CB) type 1, endothelial CB, or peroxisome proliferator–activated receptor-γ antagonism but was inhibited by CB2 receptor antagonism. CBD also uncovered a vasorelaxant response to a CB2 agonist not previously observed. The CBD-enhanced ACh response was endothelium-, nitric oxide–, and hydrogen peroxide–independent. It was, however, COX-1/2– and superoxide dismutase–dependent, and CBD enhanced the activity of both purified COX-1 and COX-2. The CBD-enhanced ACh response in the arteries was inhibited by a prostanoid EP4 receptor antagonist. Prostaglandin E2 metabolite levels were below the limits of detection, but 6-keto prostaglandin F1α was decreased after CBD incubation. These data show that CBD exposure enhances the ability of arteries to relax via enhanced production of vasodilator COX-1/2–derived products acting at EP4 receptors.
Transcriptomic and molecular genetic analysis of the cell wall salvage response of Aspergillus niger to the absence of galactofuranose synthesis

The biosynthesis of cell surface‐located galactofuranose (Galf)‐containing glycostructures such as galactomannan, N‐glycans and O‐glycans in filamentous fungi is important to secure the integrity of the cell wall. UgmA encodes an UDP‐galactopyranose mutase, which is essential for the formation of Galf. Consequently, the ΔugmA mutant lacks Galf‐containing molecules. Our previous work in Aspergillus niger work suggested that loss of function of ugmA results in activation of the cell wall integrity (CWI) pathway which is characterized by increased expression of the agsA gene, encoding an α‐glucan synthase. In this study, the transcriptional response of the ΔugmA mutant was further linked to the CWI pathway by showing the induced and constitutive phosphorylation of the CWI‐MAP kinase in the ΔugmA mutant. To identify genes involved in cell wall remodelling in response to the absence of galactofuranose biosynthesis, a genome‐wide expression analysis was performed using RNAseq. Over 400 genes were higher expressed in the ΔugmA mutant compared to the wild‐type. These include genes that encode enzymes involved in chitin (gfaB, gnsA, chsA) and α‐glucan synthesis (agsA), and in β‐glucan remodelling (bgxA, gelF and dfgC), and also include several glycosylphosphatidylinositol (GPI)‐anchored cell wall protein‐encoding genes. In silico analysis of the 1‐kb promoter regions of the up‐regulated genes in the ΔugmA mutant indicated overrepresentation of genes with RlmA, MsnA, PacC and SteA‐binding sites. The importance of these transcription factors for survival of the ΔugmA mutant was analysed by constructing the respective double mutants. The ΔugmA/ΔrlmA and ΔugmA/ΔmsnA double mutants showed strong synthetic growth defects, indicating the importance of these transcription factors to maintain cell wall integrity in the absence of Galf biosynthesis.
The stack calculus

We introduce a functional calculus with simple syntax and operational semantics in which the calculi introduced so far in the Curry-Howard correspondence for Classical Logic can be faithfully encoded. Our calculus enjoys confluence without any restriction. Its type system enforces strong normalization of expressions and it is a sound and complete system for full implicational Classical Logic. We give a very simple denotational semantics which allows easy calculations of the interpretation of expressions.
Sex-Specific Adaptation Drives Early Sex Chromosome Evolution in Drosophila

Sex Chromosome Evolution The fly genus Drosophilia has repeatedly generated evolutionarily new sex chromosomes. To understand the changes shaping the X and Y chromosomes, Zhou and Bachtrog (p. 341), sequenced the genome of D. miranda, which formed neo-X and neo-Y chromosomes approximately 1 million years ago. The data illuminate the ongoing conflict between selection for male and female function on the sex chromosomes and show that Y chromosome evolution is characterized both by a loss of gene function and selection for male-specific adaptations in genes beneficial to male functions. Evolutionarily new X and Y chromosomes evidence how selection for sexual function shapes sex chromosomes. Most species’ sex chromosomes are derived from ancient autosomes and show few signatures of their origins. We studied the sex chromosomes of Drosophila miranda, where a neo-Y chromosome originated only approximately 1 million years ago. Whole-genome and transcriptome analysis reveals massive degeneration of the neo-Y, that male-beneficial genes on the neo-Y are more likely to undergo accelerated protein evolution, and that neo-Y genes evolve biased expression toward male-specific tissues—the shrinking gene content of the neo-Y becomes masculinized. In contrast, although older X chromosomes show a paucity of genes expressed in male tissues, neo-X genes highly expressed in male-specific tissues undergo increased rates of protein evolution if haploid in males. Thus, the response to sex-specific selection can shift at different stages of X differentiation, resulting in masculinization or demasculinization of the X-chromosomal gene content.
Introduction: The Business of Researching Family Enterprises

The Handbook of Family Business Research is a substantial collection of papers manifesting recent advances in the theory and practice of family business research. This compilation is, to a large extent, in response to the extensive growth of the family business discipline as a topic of academic inquiry. The principal objective underlying this volume was to provide readers with a compilation of authoritative and scholarly papers, providing an overview of current thinking and contributing to the further advancement of the field.
Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes

Signal Scaffolds Scaffolds in cellular signaling pathways are turning out to do way more than just hold proteins together in a complex. Kim et al. (p. 867, published online 11 April) showed the importance of the scaffold protein Axin as an active participant controlling the kinetics of activation of signaling through the pathways. Axin is part of two protein complexes that have opposing actions that may regulate the timing of signaling—either activating Wnt signaling, thus protecting β-catenin from destruction, or causing proteolytic destruction of β-catenin. Rock et al. (p. 871, published online 11 April) characterized the role of the scaffold protein Nud1 in the mitotic exit network and found that the kinase that produces the output from the signaling complex only interacts with a scaffold that is primed by its activator protein kinase, already bound to the scaffold and creating a docking site. A scaffold protein provides a two-step regulatory mechanism to control the exit from mitosis in yeast. Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.
Do Rich Parents Enjoy Children Less?

We investigate the role of individual labor income as moderator of the parental subjective well-being trajectories around the first childbirth. By analyzing the German Socioeconomic Panel Survey data, we find that high-income parents enjoy their first child less than low-income ones. In a low fertility country such as Germany, income seems therefore to matter negatively for parental subjective well-being after childbirth, though with important differences by gender. Among mothers, there is a positive and significant anticipation effect (i.e. increased subjective well-being) from becoming a parent, and this is higher for lower-income women. Conversely, during the years after the childbearing event, middle and high income women present a significant negative variation with respect to pre-child subjective well-being set-point, but only starting from the second year after childbirth. Among men, the anticipation effect is not present, whereas in the years following the childbirth there is an immediate strong decline in subjective well-being for fathers in the higher income groups. We discuss these findings in terms of preferences among different groups of parents and the differential costs of children – the latter closely related to difficulties in reconciling work and family.
Investigating Pre-Service Early Childhood Education Teachers’ Technological Pedagogical Content Knowledge (TPACK) Competencies Regarding Digital Literacy Skills and Their Technology Attitudes and Usage

The integration of technology into education is a substantial issue for supporting and updating teachers’ professional development in today’s world and bringing up digitally literate generations and well-educated human capital. Studies have shown that technology integration in education is a complex and multidimensional issue. TPACK transcends the triad of core knowledge types and comprises the basis for the effective integration of technology into teaching. Therefore, the present study sought to understand the contribution of the technology attitudes and usage, digital literacy skills, and online reading comprehension strategies in pre-service early childhood teachers’ TPACK competencies. The participants in the study were 481 voluntary pre-service early childhood teachers (female=398, male=83). The data were collected as a cross-sectional survey. The study findings revealed that pre-service teachers’ TPACK competencies are associated with their technology attitude and usage, digital literacy skills, and online reading comprehension strategies, as well as that the variables explained 38% of the variance. However, pre-service teachers’ grade level and GPA are not related to their self-reported TPACK competencies. These findings can be seen as signals of the necessity for theoretical knowledge and practice to be developed in pre-service teachers’ technology integration in education.
A case for query by image and text content: searching computer help using screenshots and keywords

The multimedia information retrieval community has dedicated extensive research effort to the problem of content-based image retrieval (CBIR). However, these systems find their main limitation in the difficulty of creating pictorial queries. As a result, few systems offer the option of querying by visual examples, and rely on automatic concept detection and tagging techniques to provide support for searching visual content using textual queries. This paper proposes and studies a practical multimodal web search scenario, where CBIR fits intuitively to improve the retrieval of rich information queries. Many online articles contain useful know-how knowledge about computer applications. These articles tend to be richly illustrated by screenshots. We present a system to search for such software know-how articles that leverages the visual correspondences between screenshots. Users can naturally create pictorial queries simply by taking a screenshot of the application to retrieve a list of articles containing a matching screenshot. We build a prototype comprising 150k articles that are classified into walkthrough, book, gallery, and general categories, and provide a comprehensive evaluation of this system, focusing on technical (accuracy of CBIR techniques) and usability (perceived system usefulness) aspects. We also consider the study of added value features of such a visual-supported search, including the ability to perform cross-lingual queries. We find that the system is able to retrieve matching screenshots for a wide variety of programs, across language boundaries, and provide subjectively more useful results than keyword-based web and image search engines.
For Peer Review 1 Miniature Underwater Glider : Design and Experimental Results

The concept of gliding robotic fish combines gliding and fin-actuation mechanisms to realize energy-efficient lo comotion and high maneuverability. Such robots hold strong promise for mobile sensing in versatile aquatic environments. In this paper we present the design and implementation of a miniature glid er, a key enabling component for gliding robotic fish. The steady state glide equation is first presented and then solved numer ically for given net-buoyancy and movable mass displacement. Scal ing analysis is conducted to understand the trade-off between t he glide performance and energy cost. Comprehensive design fo r the glider is provided. Experimentation and modeling analysis are further conducted to investigate the impacts of movable mass displacement, net buoyancy, and wing size on the glidin g performance.
Which cephalometric analysis for maxillo-mandibular surgery in patients with obstructive sleep apnoea syndrome?

SUMMARY Maxillo-mandibular advancement MMA is considered an efficacious treatment for patients affected by severe obstructive sleep apnoea syndrome (OSAS). Even though OSAS improvement is the main goal of MMA, excessive maxillo-mandibular protrusion should be avoided to guarantee pleasant postoperative facial aesthetics. In order to attain such a result, the amount of MMA should be planned preoperatively by both aesthetic and cephalometric analyses. Steiner and Delaire cephalometric analyses are commonly used in the preoperative planning of orthognatic surgery for dentofacial deformities, however controversies still exist about the basis and postoperative aesthetic results of such cephalometric analyses in OSAS patients candidate for MMA. Forty-eight patients affected by severe OSAS were submitted to MMA. Pre- and post-operative Steiner and Delaire cephalometric tracings were assessed in each subject. For Steiner analysis, the variation in the SNA and SNB angles was measured, while for Delaire tracings the variation in the C3/FM-CPA and C3/FM-Me angles was assessed. Mean MMA was 6.9 + 3.8 mm for the maxilla and 13.6 + 5 mm for the mandible. After surgery, an improvement of the apnoea-hypopnoea index was recorded (40.47 + 7.64 preoperative vs. 12.56 + 5.78 postoperative). In all patients, both cephalometric analyses showed presurgical bimaxillary retrusion. After surgery, the mean value of Steiner's SNA angle increased from 78.18° to 85.58° (p < 0.001), while mean Delaire's C3/FM-CPA angle increased from 81.19° to 89.71° (p < 0.001). The mean value of Steiner's SNB angle increased from 74.33° to 80.73° (p < 0.001), while Delaire's C3/FM-Me angle increased from 80.10° to 87.29° (p < 0.001). Postoperatively, both the maxilla and mandible were in a more protrusive position (p < 0.001) according to Steiner analysis compared with Delaire tracing. Basing MMA on Delaire cephalometric analysis leads to an increased advancement of the maxillo-mandibular complex than Steiner tracing. The consequences of this aspect on facial aesthetics should be considered during surgical planning and preoperative informed consent in OSAS patients candidate for MMA.
Increased conditioned place preference for cocaine in high anxiety related behavior (HAB) mice is associated with an increased activation in the accumbens corridor

Anxiety disorders and substance use disorders are strongly associated in humans. Accordingly, a widely held but controversial concept in the addiction field, the so-called “self-medication hypothesis,” posits that anxious individuals are more vulnerable for drug dependence because they use drugs of abuse to alleviate their anxiety. We tested this hypothesis under controlled experimental conditions by quantifying the conditioned place preference (CPP) to 15 mg/kg i.p. cocaine given contingently (COCAINE) in CD1 mice selectively bred for high anxiety-related behavior (HAB) vs. normal anxiety-related behavior (NAB). Cocaine was conditioned to the initially non-preferred compartment in an alternate day design (cocaine vs. saline, four pairings each). HAB and NAB mice were also tested for the effects of non-contingent (NONCONT) cocaine administration. HAB mice showed a slightly higher bias for one of the conditioning compartments during the pretest than NAB mice that became statistically significant (p = 0.045) only after pooling COCAINE and NONCONT groups. Cocaine CPP was higher (p = 0.0035) in HAB compared to NAB mice. The increased cocaine CPP was associated with an increased expression of the immediate early genes (IEGs) c-Fos and Early Growth Related Protein 1 (EGR1) in the accumbens corridor, i.e., a region stretching from the anterior commissure to the interhemispheric border and comprising the medial nucleus accumbens core and shell, the major island of Calleja and intermediate part of the lateral septum, as well as the vertical limb of the diagonal band and medial septum. The cocaine CPP-induced EGR1 expression was only observed in D1- and D2-medium spiny neurons, whereas other types of neurons or glial cells were not involved. With respect to the activation by contingent vs. non-contingent cocaine EGR1 seemed to be a more sensitive marker than c-Fos. Our findings suggest that cocaine may be more rewarding in high anxiety individuals, plausibly due to an anxiolytic effect.