Miracle-dz/UniFAR-FTUs huggingface dataset:
PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185erbB2/neu Tumor Immunotherapy

Regulatory T cells (Tregs) are a subpopulation of T cells that are specialized in suppressing immune responses. Here we show that the arginine methyl transferase protein PRMT5 can complex with FOXP3 transcription factors in Tregs. Mice with conditional knock out (cKO) of PRMT5 expression in Tregs develop severe scurfy-like autoimmunity. In these PRMT5 cKO mice, the spleen has reduced numbers of Tregs, but normal numbers of Tregs are found in the peripheral lymph nodes. These peripheral Tregs that lack PRMT5, however, display a limited suppressive function. Mass spectrometric analysis showed that FOXP3 can be di-methylated at positions R27, R51, and R146. A point mutation of Arginine (R) 51 to Lysine (K) led to defective suppressive functions in human CD4 T cells. Pharmacological inhibition of PRMT5 by DS-437 also reduced human Treg functions and inhibited the methylation of FOXP3. In addition, DS-437 significantly enhanced the anti-tumor effects of anti-erbB2/neu monoclonal antibody targeted therapy in Balb/c mice bearing CT26Her2 tumors by inhibiting Treg function and induction of tumor immunity. Controlling PRMT5 activity is a promising strategy for cancer therapy in situations where host immunity against tumors is attenuated in a FOXP3 dependent manner.
Retrieval Practice in Classroom Settings: A Review of Applied Research

Tests have been vastly used for the assessment of learning in educational contexts. Recently, however, a growing body of research have shown that the practice of remembering previously studied information (i.e., retrieval practice) is more advantageous for long-term retention than restudying that same information; a phenomenon often termed “testing effect”. The question remains, however, whether such practice can be useful to improve learning in actual educational contexts, and whether in these contexts specific types of tests are particularly beneficial. We address these issues by reviewing studies that investigated the use of retrieval practice as a learning strategy in actual educational contexts. The reviewed studies adopted from free-recall to multiple-choice tests, and involved from elementary school children to medical school students. In general, their results are favorable to the use of retrieval practice in classroom settings, regardless of whether feedback is provided or not. Importantly, however, the majority of the reviewed studies compared retrieval practice to repeated study or to “no-activity”. The results of the studies comparing retrieval practice to alternative control conditions were less conclusive, and a subset of them found no advantage for tests. These findings raise the question whether retrieval practice is more beneficial than alternative learning strategies, especially learning strategies and activities already adopted in classroom settings (e.g., concept mapping). Thus, even though retrieval practice emerges as a promising strategy to improve learning in classroom environments, there is not enough evidence available at this moment to determine whether it is as beneficial as alternative learning activities frequently adopted in classroom settings.
The Role of B Cells and Antibodies in Multiple Sclerosis, Neuromyelitis Optica, and Related Disorders

Our pathophysiological concept of the most common central nervous system demyelinating disease, multiple sclerosis, strikingly evolved by recent discoveries suggesting that B lymphocytes substantially contribute in its initiation and chronic propagation. In this regard, activated B cells are nowadays considered to act as important antigen-presenting cells for the activation of T cells and as essential source of pro-inflammatory cytokines. Hereby, they create a milieu in which other immune cells differentiate and join an orchestrated inflammatory infiltration of the CNS. Without a doubt, this scientific leap was critically pioneered by the empirical use of anti-CD20 antibodies in recent clinical MS trials, which revealed that the therapeutic removal of immature and mature B cells basically halted development of new inflammatory flares in otherwise relapsing MS patients. This stabilization occurred largely independent of any indirect effect on plasma cell-produced antibody levels. On the contrary, peripherally produced autoantibodies are probably the most important B cell component in two other CNS demyelinating diseases which are currently in the process of being delineated as separate disease entities. The first one is neuromyelitis optica in which an antibody response against aquaporin-4 targets and destroys astrocytes, the second, likely distinct entity embraces a group of patients containing antibodies against myelin oligodendrocyte glycoprotein. In this review, we will describe and summarize pro-inflammatory B cell properties in these three CNS demyelinating disorders; we will however also provide an overview on the emerging concept that B cells or B cell subsets may exert immunologically counterbalancing properties, which may be therapeutically desirable to maintain and foster in inflammatory CNS demyelination. In an outlook, we will discuss accordingly, how this potentially important aspect can be harnessed to advance future B cell-directed therapeutic approaches in multiple sclerosis and related diseases.
Sustained Intermittent Hypoxemia Induces Adiponectin Oligomers Redistribution and a Tissue-Specific Modulation of Adiponectin Receptor in Mice

Introduction: Hypoxemia is a critical component of several respiratory diseases and is known to be involved in the processes underlying co-morbidities associated to such disorders, notably at the cardiovascular level. Circulating level of Adiponectin (Ad), known as a metabolic regulator and cardio-protective hormone was previously suggested to be reduced by hypoxia but consequences of such variation are unclear. The evaluation of the specific effect of hypoxemia on Ad forms and receptors could improve the understanding of the involvement of Ad axis in hypoxemia-related diseases. Methods: Ad-pathway components were investigated in a murine model of sustained intermittent hypoxemia (FiO2 10%, 8 h/day, 35 days). Results: Sustained intermittent hypoxemia (SIH) induced a redistribution of Ad multimers in favor of HMW forms, without change in total plasmatic level. Mice submitted to hypoxia also exhibited tissue-specific modification of adiporeceptor (AdipoR) protein level without mRNA expression change. A decreased AdipoR2 abundance was observed in skeletal muscle and heart whereas AdipoR1 level was only reduced in muscle. No change was observed in liver regarding AdipoR. Lipid profile was unchanged but glucose tolerance increased in hypoxemic mice. Conclusion: Sustained intermittent hypoxemia, per se, modify Ad oligomerization state as well as AdipoR protein abundance in a tissue-specific way. That suggests alteration in Ad-dependant pathways in pathological conditions associated to SIH. Investigation of Ad-pathway components could therefore constitute useful complementary criteria for the clustering of patients with hypoxemia-related diseases and management of co-morbidities, as well as to develop new therapeutic strategies.
The Role of Volume Fraction and Additives on the Rheology of Suspensions of Micron Sized Iron Particles

The increase of the yield stress versus the magnetic field is the most important quantity characterizing the efficiency of a magnetorheological suspension. The theory based on the formation of columnar aggregates predicts a linear variation with the volume fraction of magnetic particles. We shall review previous models for the calculation of forces and yield stress and will introduce a new one based on rupture at zero strain. The predictions of these models are compared with the experimental data obtained for carbonyl iron particles by different authors. Whereas previous analytical prediction strongly overestimates experimental yield stress, the one calculated from Finite Element Method (FEM) used with affine trajectories well reproduce the experiments and show a linear dependence with the volume fraction and a H3/2 behavior between 50 and 200kA/m. Nevertheless, at very high volume fractions (>55%) where the suspension can only flow in the presence of specific additives, the dependence of the yield stress versus the volume fraction and the magnetic field is dramatically changed. We observe a jamming transition which is triggered by the application of a low magnetic field and which depends strongly of the volume fraction. We will discuss the new perspectives arising by the use of these very high volume fractions.
Hsp60 as a Novel Target in IBD Management: A Prospect

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be considered a putatively important driver of events and could play an etiopathogenic role. This possibility is discussed in this review. We also indicate that Hsp60 can be a biomarker useful in disease diagnosing and monitoring and, if found active in pathogenesis, should become a target for developing new therapies. The latter are particularly needed to alleviate patient suffering and to prevent complications, including colon cancer.
Spermine Differentially Refines Plant Defense Responses Against Biotic and Abiotic Stresses

Roles of the major polyamines (mPA), putrescine, spermidine, and spermine (Spm), in various developmental and physiological processes in plants have been well documented. Recently, there has been increasing focus on the link between mPA metabolism and defense response during plant-stress interactions. Empirical evidence is available for a unique role of Spm, distinct from the other mPA, in eliciting an effective defense response to (a)biotic stresses. Our understanding of the precise molecular mechanism(s) by which Spm modulates these defense mechanisms is limited. Further analysis of recent studies indicates that plant Spm functions differently during biotic and abiotic interactions in the regulation of oxidative homeostasis and phytohormone signaling. Here, we summarize and integrate current knowledge about Spm-mediated modulation of plant defense responses to (a)biotic stresses, highlighting the importance of Spm as a potent plant defense activator with broad-spectrum protective effects. A model is proposed to explain how Spm refines defense mechanisms to tailor an optimal resistance response.
An Overview of Sucrose Synthases in Plants

Sucrose is the end product of photosynthesis and the primary sugar transported in the phloem of most plants. Sucrose synthase (SuSy) is a glycosyl transferase enzyme that plays a key role in sugar metabolism, primarily in sink tissues. SuSy catalyzes the reversible cleavage of sucrose into fructose and either uridine diphosphate glucose (UDP-G) or adenosine diphosphate glucose (ADP-G). The products of sucrose cleavage by SuSy are available for many metabolic pathways, such as energy production, primary-metabolite production, and the synthesis of complex carbohydrates. SuSy proteins are usually homotetramers with an average monomeric molecular weight of about 90 kD (about 800 amino acids long). Plant SuSy isozymes are mainly located in the cytosol or adjacent to plasma membrane, but some SuSy proteins are found in the cell wall, vacuoles, and mitochondria. Plant SUS gene families are usually small, containing between four to seven genes, with distinct exon-intron structures. Plant SUS genes are divided into three separate clades, which are present in both monocots and dicots. A comprehensive phylogenetic analysis indicates that a first SUS duplication event may have occurred before the divergence of the gymnosperms and angiosperms and a second duplication event probably occurred in a common angiosperm ancestor, leading to the existence of all three clades in both monocots and dicots. Plants with reduced SuSy activity have been shown to have reduced growth, reduced starch, cellulose or callose synthesis, reduced tolerance to anaerobic-stress conditions and altered shoot apical meristem function and leaf morphology. Plants overexpressing SUS have shown increased growth, increased xylem area and xylem cell-wall width, and increased cellulose and starch contents, making SUS high-potential candidate genes for the improvement of agricultural traits in crop plants. This review summarizes the current knowledge regarding plant SuSy, including newly discovered possible developmental roles for SuSy in meristem functioning that involve sugar and hormonal signaling.
The Environment and Cyanophage Diversity: Insights From Environmental Sequencing of DNA Polymerase

Globally distributed and abundant cyanophages in the family Myoviridae have dsDNA genomes with variable gene content, including host-derived auxiliary metabolic genes (AMGs) that potentially can facilitate viral replication. However, it is not well understood how this variation in gene content interacts with environmental variables to shape cyanomyovirus communities. This project correlated the genetic repertoire of cyanomyoviruses with their phyologeny, and investigated cyanomyovirus ecotype distribution as a function of environmental conditions across locations and seasons. Reference cyanomyovirus genomes were compared for their overlap in gene content to infer phyologenetic distances, and these distances were compared to distances calculated based on DNA polymerase (gp43) gene sequences. In turn, gp43 partial gene sequences amplified from natural cyanophage communities were used to describe cyanomyovirus community composition and to assess the relationship between environmental variables. The results showed the following: (1) DNA polymerase gene phylogeny generally correlated with the similarity in gene content among reference cyanomyoviruses, and thus can be used to describe environmental cyanomyovirus communities; (2) spatial and seasonal patterns in cyanomyovirus communities were related to environmental variables; (3) salinity and temperature, combined with nutrient concentration were predictors of cyanomyovirus richness, diversity and community composition. This study shows that environmental variables shape viral communities by drawing on a diverse seed bank of viral genotypes. From these results it is evident that that viral ecotypes with their corresponding genetic repertoires underlie selection pressures. However, the mechanisms involved in selecting for specific viral genotypes remain to be fully understood.
Optical and Electrochemical Properties of Self-Organized TiO2 Nanotube Arrays From Anodized Ti−6Al−4V Alloy

Due to their high specific surface area and advanced properties, TiO2 nanotubes (TiO2 NTs) have a great significance for production and storage of energy. In this paper, TiO2 NTs were synthesized from anodization of Ti-6Al-4V alloy at 60 V for 3 h in fluoride ethylene glycol electrolyte by varying the water content and further annealing treatment. The morphological, structural, optical and electrochemical performances of TiO2 NTs were investigated by scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), UV-Visible spectroscopy and electrochemical characterization techniques. By varying the water content in the solution, a honeycomb and porous structure was obtained at low water content and the presence of (α + β) phase in Ti-6Al-4V alloy caused not uniform etching. With an additional increase in water content, a nanotubular structure is formed in the (α + β) phases with different morphological parameters. The anatase TiO2 NTs synthesized with 20 wt% H2O shows an improvement in absorption band that extends into the visible region due the presence of vanadium oxide in the structure and the effective band gap energy (Eg) value of 2.25 eV. The TiO2 NTs electrode also shows a good cycling performance, delivering a reversible capacity of 82 mAh.g−1 (34 μAh.cm−2.μm−1) at 1C rate over 50 cycles.
First Impressions: A Survey on Vision-Based Apparent Personality Trait Analysis

Personality analysis has been widely studied in psychology, neuropsychology, and signal processing fields, among others. From the past few years, it also became an attractive research area in visual computing. From the computational point of view, by far speech and text have been the most considered cues of information for analyzing personality. However, recently there has been an increasing interest from the computer vision community in analyzing personality from visual data. Recent computer vision approaches are able to accurately analyze human faces, body postures and behaviors, and use these information to infer apparent personality traits. Because of the overwhelming research interest in this topic, and of the potential impact that this sort of methods could have in society, we present in this paper an up-to-date review of existing vision-based approaches for apparent personality trait recognition. We describe seminal and cutting edge works on the subject, discussing and comparing their distinctive features and limitations. Future venues of research in the field are identified and discussed. Furthermore, aspects on the subjectivity in data labeling/evaluation, as well as current datasets and challenges organized to push the research on the field are reviewed.
Matrine Mediates Inflammatory Response via Gut Microbiota in TNBS-Induced Murine Colitis

This study mainly investigated the effect of matrine on TNBS-induced intestinal inflammation in mice. TNBS treatment caused colonic injury and gut inflammation. Matrine (1, 5, and 10 mg/kg) treatment alleviated colonic injury and gut inflammation via reducing bleeding and diarrhea and downregulating cytokines expression (IL-1β and TNF-α). Meanwhile, serum immunoglobulin G (IgG) was markedly reduced in TNBS treated mice, while 5 and 10 mg/kg matrine alleviated IgG reduction. Fecal microbiota was tested using 16S sequencing and the results showed that TNBS caused gut microbiota dysbiosis, while matrine treatment markedly improved gut microbiota communities (i.e., Bacilli and Mollicutes). Functional analysis showed that cell motility, nucleotide metabolism, and replication and repair were markedly altered in the TNBS group, while matrine treatment significantly affected cell growth and death, membrane transport, nucleotide metabolism, and replication and repair. In conclusion, matrine may serve as a protective mechanism in TNBS-induced colonic inflammation and the beneficial effect may be associated with gut microbiota.
Optimizing Seed Inputs in Fuzzing with Machine Learning

The success of a fuzzing campaign is heavily de-pending on the quality of seed inputs used for test generation. It is however challenging to compose a corpus of seed inputs that enable high code and behavior coverage of the target program, especially when the target program requires complex input formats such as PDF files. We present a machine learning based framework to improve the quality of seed inputs for fuzzing programs that take PDF files as input. Given an initial set of seed PDF files, our framework utilizes a set of neural networks to 1) discover the correlation between these PDF files and the execution in the target program, and 2) leverage such correlation to generate new seed files that more likely explore new paths in the target program. Our experiments on a set of widely used PDF viewers demonstrate that the improved seed inputs produced by our framework could significantly increase the code coverage of the target program and the likelihood of detecting program crashes.
Understanding the Biostimulant Action of Vegetal-Derived Protein Hydrolysates by High-Throughput Plant Phenotyping and Metabolomics: A Case Study on Tomato

Designing and developing new biostimulants is a crucial process which requires an accurate testing of the product effects on the morpho-physiological traits of plants and a deep understanding of the mechanism of action of selected products. Product screening approaches using omics technologies have been found to be more efficient and cost effective in finding new biostimulant substances. A screening protocol based on the use of high-throughput phenotyping platform for screening new vegetal-derived protein hydrolysates (PHs) for biostimulant activity followed by a metabolomic analysis to elucidate the mechanism of the most active PHs has been applied on tomato crop. Eight PHs (A–G, I) derived from enzymatic hydrolysis of seed proteins of Leguminosae and Brassicaceae species were foliarly sprayed twice during the trial. A non-ionic surfactant Triton X-100 at 0.1% was also added to the solutions before spraying. A control treatment foliarly sprayed with distilled water containing 0.1% Triton X-100 was also included. Untreated and PH-treated tomato plants were monitored regularly using high-throughput non-invasive imaging technologies. The phenotyping approach we used is based on automated integrative analysis of photosynthetic performance, growth analysis, and color index analysis. The digital biomass of the plants sprayed with PH was generally increased. In particular, the relative growth rate and the growth performance were significantly improved by PHs A and I, respectively, compared to the untreated control plants. Kinetic chlorophyll fluorescence imaging did not allow to differentiate the photosynthetic performance of treated and untreated plants. Finally, MS-based untargeted metabolomics analysis was performed in order to characterize the functional mechanisms of selected PHs. The treatment modulated the multi-layer regulation process that involved the ethylene precursor and polyamines and affected the ROS-mediated signaling pathways. Although further investigation is needed to strengthen our findings, metabolomic data suggest that treated plants experienced a metabolic reprogramming following the application of the tested biostimulants. Nonetheless, our experimental data highlight the potential for combined use of high-throughput phenotyping and metabolomics to facilitate the screening of new substances with biostimulant properties and to provide a morpho-physiological and metabolomic gateway to the mechanisms underlying PHs action on plants.