Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential Role of mGBP7 for Survival of Toxoplasma gondii Infection

Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen Toxoplasma gondii. In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of T. gondii, which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with T. gondii, showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction. ABSTRACT Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Toxoplasma gondii. Previously, we identified that mGBP2 mediates disruption of the parasitophorous vacuole membrane (PVM) and directly assaults the plasma membrane of the parasite. Here, we show that mGBP7-deficient mice are highly susceptible to T. gondii infection. This is demonstrated by the loss of parasite replication control, pronounced development of ascites, and death of the animals in the acute infection phase. Interestingly, live-cell microscopy revealed that mGBP7 recruitment to the PVM occurs after mGBP2 recruitment, followed by disruption of the PVM and T. gondii integrity and accumulation of mGBP7 inside the parasite. This study defines mGBP7 as a crucial effector protein in resistance to intracellular T. gondii. IMPORTANCE Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen Toxoplasma gondii. In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of T. gondii, which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with T. gondii, showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction.
IDENTIFYING RECENT DEVELOPMENTS IN KNEE PROSTHESES THROUGH A PATENT ANALYSIS

Artificial knees represent an important issue for a global technology trends analysis. On average, the growth rate of knee replacement surgeries increased by nearly 50% over the past decade in Organization for Economic Cooperation and Development (OECD) countries. This study focuses on a patent analysis as a part of a Competitive Technical Intelligence methodology. The aim is to provide organizations in this industry with insights on knee prostheses research, particularly to determine the most active patenting entities as well as their focus of research. The topmost in each category: inventors, organisations, technology classifications, advanced materials and top keywords were determined.
Unveiling the Activity Origin of Copper-based Electrocatalyst for Selective Nitrate Reduction to Ammonia.

Unveiling the active phase of catalytic materials under reaction conditions is important for the designed construction of efficient electrocatalysts for selective nitrate reduction to ammonia. Here, we probed the origin of the prominent activity enhancement for CuO (Faradaic efficiency: 95.8%, Selectivity: 81.2%) toward selective nitrate electroreduction to ammonia. 15 N isotope labeling experiments proved that ammonia originated from nitrate reduction. Both the 1 H nuclear magnetic resonance (NMR) spectra and colorimetric methods were performed to quantify ammonia. In situ Raman and ex situ experiments revealed that CuO was electrochemically converted into Cu/Cu 2 O, which serves as an active phase. The combined results of online differential electrochemical mass spectrometry (DEMS) and density functional theory (DFT) calculations demonstrated that the electron transfer from Cu 2 O to Cu at the interface could facilitate the formation of * NOH intermediate and suppress the hydrogen evolution reaction, leading to high selectivity and Faradaic efficiency.
Electrospun metformin-loaded polycaprolactone/chitosan nanofibrous membranes as promoting guided bone regeneration membranes: Preparation and characterization of fibers, drug release, and osteogenic activity in vitro

A guided bone regeneration membrane is a pivotal therapeutic modality used to maintain sufficient space for bone regeneration, which is of great significance in curing alveolar bone defects. Metformin has been found to possess the ability of promoting osteogenic differentiation of bone mesenchymal stem cells. To develop guided bone regeneration membranes with better osteoinductive ability, metformin was incorporated into polycaprolactone/chitosan nanofibrous membranes by electrospinning technique, followed by glutaraldehyde crosslinking to reinforce chitosan stability in aqueous solutions. The fabricated nanofibrous membranes were then characterized by scanning electron microscope, Fourier transform infrared spectroscopy, water contact angle testing, mechanical properties test, and drug release test. Furthermore, rats bone mesenchymal stem cells were seeded on membranes for the evaluation of the effect of metformin-loaded polycaprolactone/chitosan nanofibrous membranes on cell morphology, alkaline phosphate activity, and osteogenic mineralization in vitro. Our results showed that nanofibers were fabricated successfully with smooth surface free from beads formation. The crosslinked-polycaprolactone/chitosan/metformin membranes had a more appropriate water contact angle of 44.25 ± 1.37° and the drug release curve of metformin featured early sudden release and slow release in the later stage over a 23-day period. Besides, in vitro studies suggested that the crosslinked-polycaprolactone/chitosan/metformin membrane was more suitable for cell adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells. Consequently, the metformin-loaded polycaprolactone/chitosan nanofibrous membranes would be promoted for bone regeneration as guided bone regeneration membranes.
Avatar Designs are in the Eye of the Beholder: About Identifying Preferred Avatar Designs in Digital Learning - Research in Progress

Gamification focuses on using game-like elements in non-entertainment-based contexts. An example for a game element is an avatar. Although lots of research has focused on analyzing avatars in gamification, little is known about which kind of avatar design users prefer. Especially avatars in gamification that are used as tutors or mentors for learning purposes do not spark the interest of users. Thus, the goal of our paper is to analyze the kinds of avatar designs users of digital learning environments such as learning management systems would prefer. For that purpose, we use a best-worst scaling approach to analyze if the familiarity and shape of avatars determine user preferences in gamification. Our research will contribute to research and practice as it delivers implications about how to design avatars in gamified learning systems. We will enrich theory by getting a better understanding about the general meaning of user-centered avatar designs in gamification.
Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt

Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes an early switch and inhibits DNA replication. ABSTRACT Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes an early switch and inhibits DNA replication. TopBP1 is often overexpressed in cancer and can bypass control by Cdk2 to interact with treslin, leading to enhanced DNA replication. Consistent with this notion, reducing the levels of TopBP1 in cancer cells restores sensitivity to a Cdk2 inhibitor. Together, our study links Cdk2 and Akt pathways to the control of DNA replication through the regulation of TopBP1-treslin interaction. These data also suggest an important role for TopBP1 in driving abnormal DNA replication in cancer.
A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer

Purpose: The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC. Experimental Design: Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from The Cancer Genome Atlas and 92 PDACs from the Australian International Cancer Genome Consortium. We explored associations between immune cell counts by immunohistochemistry, chemokine expression, and transcriptional hallmarks of antitumor immunity by RNA sequencing (RNA-seq), and mutational burden by whole-genome sequencing. Results: Among all known human chemokines, a coregulated set of four (CCL4, CCL5, CXCL9, and CXCL10) was strongly associated with CD8+ T-cell infiltration (P < 0.001). Expression of this “4-chemokine signature” positively correlated with transcriptional metrics of T-cell activation (ZAP70, ITK, and IL2RB), cytolytic activity (GZMA and PRF1), and immunosuppression (PDL1, PD1, CTLA4, TIM3, TIGIT, LAG3, FASLG, and IDO1). Furthermore, the 4-chemokine signature marked tumors with increased T-cell activation scores (MHC I presentation, T-cell/APC costimulation) and elevated expression of innate immune sensing pathways involved in T-cell priming (STING and NLRP3 inflammasome pathways, BATF3-driven dendritic cells). Importantly, expression of this 4-chemokine signature was consistently indicative of a T-cell–inflamed phenotype across primary PDAC and PDAC liver metastases. Conclusions: A conserved 4-chemokine signature marks resectable and metastatic PDAC tumors with an active antitumor phenotype. This could have implications for the appropriate selection of PDAC patients in immunotherapy trials.
Blue‐blocking glasses as additive treatment for mania: Effects on actigraphy‐derived sleep parameters

Improvement of sleep is a central treatment goal for patients in a manic state. Blue‐blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue‐light‐sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy‐derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18–70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%–95.8% in the BB group and 75.9%–90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less‐intensive sleep‐promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep‐promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting.
Characterization of fungicide sensitivity profiles of Botrytis cinerea populations sampled in Lombardy (Northern Italy) and implications for resistance management.

BACKGROUND Resistance to fungicides is one of the aspects that have to be considered when planning the treatments to achieve an optimal control of grey mould, caused by Botrytis cinerea, in vineyards. In this study, extensive fungicide resistance monitoring was carried out in Northern Italy (Lombardy region) to evaluate several aspects of fungicide resistance (frequency of resistance, effect of field treatments, mechanism of resistance and fitness) on 720 B. cinerea strains isolated from 36 vineyards. RESULTS Of the characterized strains, 12 % were resistant to a single fungicide class (3 % to the succinate dehydrogenase inhibitor boscalid, 4 % to the anilinopirimidine cyprodinil; 5 % to the phenylpirrole fludioxonil; 0.1 % to the ketoreductase inhibitor fenhexamid) and 0.8 % to two fungicide classes contemporaneously. Resistance was associated with mutations reported in the literature for boscalid (H272Y/R) and fenhexamid (P238S or I232M). Two new mutations in sdhC (A187F) and in sdhD (I189L) could be related to boscalid resistance. Strains resistant to fludioxonil did not show any known mutations. No significant differences were found in the fitness of sensitive and resistant strains. CONCLUSION Overall, field populations of B. cinerea showed a relatively low frequency of resistance, but the geographical distribution of resistance, genetic mechanisms of resistance and fitness of resistant strains suggest that management of resistance should be implemented, at local and regional levels. Particular attention should be given to the fungicide sprays planned before veraison, since they seem to be associated with a higher frequency of resistant strains in vineyards. This article is protected by copyright. All rights reserved.
The 2013/14 Thames Basin Floods: Do Improved Meteorological Forecasts Lead to More Skillful Hydrological Forecasts at Seasonal Time Scales?

The Thames basin experienced 12 major Atlantic depressions in winter 2013/14, leading to extensive and prolonged fluvial and groundwater flooding. This exceptional weather coincided with highly anomalous meteorological conditions across the globe. Atmospheric relaxation experiments, whereby conditions within specified regions are relaxed toward a reanalysis, have been used to investigate teleconnection patterns. However, no studies have examined whether improvements to seasonal meteorological forecasts translate into more skillful seasonal hydrological forecasts. This study applied relaxation experiments to reforecast the 2013/14 floods for three Thames basin catchments with different hydrogeological characteristics. The tropics played an important role in the development of extreme conditions over the Thames basin. The greatest hydrological forecasting skill was associated with the tropical Atlantic and less with the tropical Pacific, although both captured seasonal meteorological flow anomalies. Relaxation applied over the northeastern Atlantic produced confident ensemble forecasts, but hydrological extremes were underpredicted; this was unexpected with relaxation applied so close to the United Kingdom. Streamflow was most skillfully forecast for the catchment representing a large drainage area with high peak flow. Permeable lithology and antecedent conditions were important for skillfully forecasting groundwater levels. Atmospheric relaxation experiments can improve our understanding of extratropical anomalies and the potential predictability of extreme events such as the Thames 2013/14 floods. Seasonal hydrological forecasts differed from what was expected from the meteorology alone, and thus knowledge is gained by considering both components. In the densely populated Thames basin, considering the local hydrogeological context can provide an effective early alert of potential high-impact events, allowing for better preparedness.
Cross-sectional comparison of body composition and resting metabolic rate in Premier League academy soccer players: Implications for growth and maturation

ABSTRACT For the first time we aimed to: (1) assess fat-free mass (FFM) and RMR in youth soccer players, (2) compare measured RMR to estimated RMR using previously published prediction equations, and (3) develop a novel population-specific prediction equation. In a cross-sectional design, 99 males from a Premier League academy underwent assessments of body composition (DXA) and RMR (indirect-calorimetry). Measured RMR was compared to estimated values from five prediction equations. A novel RMR prediction equation was developed using stepwise multiple regression. FFM increased (P<0.05) between U12 (31.6±4.2 kg) and U16 (56.3±5.3 kg) after which no further increases occurred (P>0.05). RMR in the U12s (1655±195 kcal.day−1), U13s (1720±205 kcal.day−1) and U14s (1846±218kcal.day−1) was significantly lower than the U15s (1957±128 kcal.day−1), U16s (2042±155 kcal.day−1), U18s (1875±180 kcal.day−1) and U23s (1941±197 kcal.day−1) squads (P>0.05). FFM was the single best predictor of RMR (r2=0.43; P<0.01) and was subsequently included in the novel prediction equation: RMR (kcal.day−1) = 1315 + (11.1 x FFM in kg). Both FFM and RMR increase from 12-16 years old, thus highlighting the requirement to adjust daily energy intake to support growth and maturation. The novel prediction RMR equation developed may help to inform daily energy requirements.
EFFICIENCY OF INTERO MODEL TO PREDICT SOIL EROSION INTENSITY AND SEDIMENT YIELD IN KHAMSAN REPRESENTATIVE WATERSHED (WEST OF IRAN)

Application of empirical models is inevitable because of the complexity of process,features, spatial and temporal variation of soil erosion and non-existence or lack ofassociated data. In the present study, maximum outflow and soil erosion intensitywere predicted for Khamsan representative watershed in West of Iran, using IntEromodel. The results of production of erosion material in the river basin (W year),coefficient of the deposit retention (Ru) and real soil losses (G year) were thencompared with the measured soil erosion, SDR and sediment yield data inKhamsan watershed. The intensity of the erosion process were medium in studiedwatershed. The predicted data were compared with the measured sediment yield ofstudied watershed and verified the acceptable results of the IntEro model inKhamsan representative watershed. The results showed that the peak flow is 27.50m3s-1 for a return period of 100 years. The value of Z coefficient of 0.876 indicatesthat the river basin belongs to the second destruction category out of five. Thecalculated net soil loss from the river basin was 12263.44 m3 per year, specific282.81 m3km-2 per year. The strength of the erosion process is strong, andaccording to the erosion type, it is surface erosion.
Centromeric Non-Coding RNAs: Conservation and Diversity in Function

Chromosome segregation is strictly regulated for the proper distribution of genetic material to daughter cells. During this process, mitotic chromosomes are pulled to both poles by bundles of microtubules attached to kinetochores that are assembled on the chromosomes. Centromeres are specific regions where kinetochores assemble. Although these regions were previously considered to be silent, some experimental studies have demonstrated that transcription occurs in these regions to generate non-coding RNAs (ncRNAs). These centromeric ncRNAs (cenRNAs) are involved in centromere functions. Here, we describe the currently available information on the functions of cenRNAs in several species.
Saliva Secretion and Swallowing—The Impact of Different Types of Food and Drink on Subsequent Intake

The oral processing of food is important for eating and digestion in order to gain energy and nutrients. Due to disease, injury, or aging, individuals may experience difficulties in this process. These difficulties often lead to dysphagia, which is associated with malnutrition. Thus, it is of importance to find solutions and strategies to enable food intake. It is well known that sour and/or carbonated foods and drinks increase saliva secretion and trigger the swallowing reflex. However, knowledge regarding how subsequent food intake is impacted is lacking. The aim of this study was to clarify whether sour and/or carbonated foods and drinks had subsequent impacts on swallowing function. Twelve healthy participants evaluated eleven foods and drinks in terms of their ability to increase saliva production and ease the swallowing of subsequent food. Results showed that sourness and carbonation had positive impacts on saliva secretion and swallowing. No correlation was found between the pH/sourness of the foods and the ease of swallowing them. It was concluded that the ingestion of cherry tomatoes, natural yoghurt, and, in particular, citrus juice made swallowing of a neutral cracker easier. These results may be used to increase food intake among dysphagia patients.
INTELLECTUAL CAPITAL AS THE SOURCE OF COMPETITIVE ADVANTAGE: THE RESOURCE-BASED VIEW

The concepts of intellectual capital and competitiveness are widely studied issues among researchers during the last few decades. Intangible assets have been proved to be the fundamental source of value and competitiveness in modern enterprises. Intellectual capital is a valuable invisible resource which drives firm’s growth and provides superior value for stakeholders. Therefore, the aim of the paper is to examine the role the intellectual capital has in creating and sustaining competitive advantage of enterprises from the resource-based perspective.
Identification of a Novel Linear B-Cell Epitope on the Nucleocapsid Protein of Porcine Deltacoronavirus

Porcine deltacoronavirus (PDCoV), first identified in 2012, is a swine enteropathogen now found in many countries. The nucleocapsid (N) protein, a core component of PDCoV, is essential for virus replication and is a significant candidate in the development of diagnostics for PDCoV. In this study, monoclonal antibodies (mAbs) were generated and tested for reactivity with three truncations of the full protein (N1, N2, N3) that contained partial overlaps; of the five monoclonals chosen tested, each reacted with only the N3 truncation. The antibody designated 4E88 had highest binding affinity with the N protein and was chosen for in-depth examination. The 4E88 epitope was located to amino acids 308-AKPKQQKKPKK-318 by testing the 4E88 monoclonal for reactivity with a series of N3 truncations, then the minimal epitope, 309-KPKQQKKPK-317 (designated EP-4E88), was pinpointed by testing the 4E88 monoclonal for reactivity with a series of synthetic peptides of this region. Homology analysis showed that the EP-4E88 sequence is highly conserved among PDCoV strains, and also shares high similarity with sparrow coronavirus (HKU17), Asian leopard cat coronavirus (ALCCoV), quail coronavirus (UAE-HKU30), and sparrow deltacoronavirus (SpDCoV). Of note, the PDCoV EP-4E88 sequence shared very low similarity (<22.2%) with other porcine coronaviruses (PEDV, TGEV, PRCV, SADS-CoV, PHEV), demonstrating that it is an epitope that can be used for distinguishing PDCoV and other porcine coronavirus. 3D structural analysis revealed that amino acids of EP-4E88 were in close proximity and may be exposed on the surface of the N protein.