Miracle-dz/UniFAR-FTUs huggingface dataset:
Localizing P300 Generators in Visual Target and Distractor Processing: A Combined Event-Related Potential and Functional Magnetic Resonance Imaging Study

Constraints from functional magnetic resonance imaging (fMRI) were used to identify the sources of the visual P300 event-related potential (ERP). Healthy subjects performed a visual three-stimulus oddball paradigm with a difficult discrimination task while fMRI and high-density ERP data were acquired in separate sessions. This paradigm allowed us to differentiate the P3b component of the P300, which has been implicated in the detection of rare events in general (target and distractor), from the P3a component, which is mainly evoked by distractor events. The fMRI-constrained source model explained >99% of the variance of the scalp ERP for both components. The P3b was mainly produced by parietal and inferior temporal areas, whereas frontal areas and the insula contributed mainly to the P3a. This source model reveals that both higher visual and supramodal association areas contribute to the visual P3b and that the P3a has a strong frontal contribution, which is compatible with its more anterior distribution on the scalp. The results point to the involvement of distinct attentional subsystems in target and distractor processing.
[Diabetes: Socioeconomic Inequalities in the Portuguese Population in 2014].

INTRODUCTION Diabetes is a major public health problem and it is related to socioeconomic factors. The aim of this study is to describe socioeconomic inequalities in the distribution of diabetes in the population with 25 years or more, resident in Portugal in 2014. MATERIAL AND METHODS Data from the Health National Survey 2014 was analysed, n = 16 786. We estimated the prevalence of diabetes in the population and stratified by socioeconomic variables namely educational level and income. The extent of socioeconomic inequalities was assessed using concentration index and the relative index of inequality. RESULTS Diabetes was found to be concentrated among the people with lower educational levels (concentration index = -0.26) and lower income quintiles (concentration index = -0.14). Relative index of inequality also showed a lower degree of inequality among the most educated (0,20; CI 95% = [0,12; 0,32]) and with higher income (0,59; CI 95% = [0,48; 0,74]). DISCUSSION Distribution of diabetes is associated with education and income. Previous studies have shown that although income might reflect lifestyle patterns, education reflects better social factors that are important for establishing healthier behaviours. Also, the National Health Service, of universal coverage and free of charge, might have contributed to reduce inequalities in the access to health by those with the lowest income. CONCLUSION Supporting 'Health in All Policies' might reduce inequalities, namely by improving population educational level and actions that promote health literacy.
Detection of Pyruvate Dehydrogenase E1α-subunit Deficiencies in Females by Immunohistochemical Demonstration of Mosaicism in Cultured Fibroblasts

Deficiency of the E1α-subunit of the pyruvate dehydrogenase (PDH) complex is an X-linked inborn error of metabolism and one of the major causes of lactic acidosis in children. Although most heterozygous females manifest symptoms of the disease, it is often difficult to establish the diagnosis as results based on measurement of total PDH activity, and E1α-immunoreactive protein in patient fibroblasts may be ambiguous because of the variability in the pattern of X chromosome inactivation. We report the development of a set of monoclonal antibodies (MAbs) specific to four subunits of the PDH complex that can be used for detection of PDH E1α deficiency. We also show that anti-E1α and anti-E2 MAbs, when used in immunocytochemical analysis, can detect mosaicism in cell cultures from female patients in which as few as 2–5% of cells express the deficiency. This immunocytochemical approach, which is fast, reliable, and quantitative, will be particularly useful in identifying females with PDH E1α-subunit deficiency as a precursor to mutation analysis.
Dementia, Stroke, and Vascular Risk Factors; a Review

Interest in dementia has increased over the past few decades. Stroke is an important cause of cognitive problems. The term vascular cognitive impairment is now used to describe dementia attributed to stroke or deep white matter lesions detected on imaging. Although vascular cognitive impairment is increasingly diagnosed, Alzheimer's disease remains the most common dementia worldwide. The relationship between Alzheimer's disease and vascular cognitive impairment is unclear, although there exists significant overlap, which prompts physicians to consider them opposite ends of a disease spectrum, rather than separate entities. There is also substantial evidence that stroke risk factors such as hypertension, diabetes; lipid disorders, etc. are independently associated with an increased risk of Alzheimer's disease and vascular cognitive impairment. Evidence suggests that these risk factors have a cumulative effect on Alzheimer's disease development but not on vascular cognitive impairment. This is more marked in Alzheimer's disease patients in the presence of the ε4 allelic variant of apolipoprotein E. How these risk factors increase the risk of dementia is largely unknown. Physicians must be aware that stroke causes dementia; that vascular risk factors appear to be independent risk factors in developing dementia, and that poststroke care must include cognitive assessment.
Plant Nutrition: Root Transporters on the Move1

The dynamics of nutrient transporters and channels emerges as a critical and highly regulated cellular process controlling nutrient uptake and distribution in plant roots. Nutrient and water uptake from the soil is essential for plant growth and development. In the root, absorption and radial transport of nutrients and water toward the vascular tissues is achieved by a battery of specialized transporters and channels. Modulating the amount and the localization of these membrane transport proteins appears as a way to drive their activity and is essential to maintain nutrient homeostasis in plants. This control first involves the delivery of newly synthesized proteins to the plasma membrane by establishing check points along the secretory pathway, especially during the export from the endoplasmic reticulum. Plasma membrane-localized transport proteins are internalized through endocytosis followed by recycling to the cell surface or targeting to the vacuole for degradation, hence constituting another layer of control. These intricate mechanisms are often regulated by nutrient availability, stresses, and endogenous cues, allowing plants to rapidly adjust to their environment and adapt their development.
YAP Is Ready to Rac and Rho: Elucidation of a Novel YAP-Driven Network That Potentiates Brain Cancer Cell Dispersal and Confers Poor Survival in Patients

INTRODUCTION: Molecular pathways linking cell polarization and migration to extracellular cues regulate many pathological processes, including progression of aggressive and infiltrative cancers. Glioblastoma (GBM), the most common and lethal form of primary brain cancer, is characterized by its pronounced ability to disseminate into the intricate microenvironment of the human brain, confounding surgical excision and radiotherapy, leading to a median patient survival of 14 months. Progression results from defects in molecular pathways linking cell migration and invasion into surrounding tissue. However, the molecular engines are not known.
Protein Expression Profiles of Chlamydia pneumoniae in Models of Persistence versus Those of Heat Shock Stress Response

ABSTRACT Chlamydia pneumoniae is an obligate intracellular pathogen that causes both acute and chronic human disease. Several in vitro models of chlamydial persistence have been established to mimic chlamydial persistence in vivo. We determined the expression patterns of 52 C. pneumoniae proteins, representing nine functional subgroups, from the gamma interferon (IFN-γ) treatment (primarily tryptophan limitation) and iron limitation (IL) models of persistence compared to those following heat shock (HS) at 42°C. Protein expression patterns of C. pneumoniae persistence indicates a strong stress component, as evidenced by the upregulation of proteins involved in protein folding, assembly, and modification. However, it is clearly more than just a stress response. In IFN persistence, but not IL or HS, amino acid and/or nucleotide biosynthesis proteins were found to be significantly upregulated. In contrast, proteins involved in the biosynthesis of cofactors, cellular processes, energy metabolism, transcription, and translation showed an increased in expression in only the IL model of persistence. These data represent the most extensive protein expression study of C. pneumoniae comparing the chlamydial heat shock stress response to two models of persistence and identifying the common and unique protein level responses during persistence.
Pharmacists' role in reporting adverse drug reactions in an international perspective

The participation of the pharmacist in national spontaneous reporting systems for adverse drug reactions (ADRs) has not always been a matter of course. Even today, there are a number of countries, in particular the Scandinavian countries, where pharmacists are not authorised to report ADRs. In those countries in which they are allowed to report, they do not always use this opportunity.
The effects of detergents on the polymerization properties of actin

Effects of some detergents—most frequently used in membrane raft studies—on the polymerization properties of actin were examined under in vitro and in vivo conditions, for protein and cellular investigations, respectively. Under in vitro conditions the polymerization rates were measured with pyrene‐labeled actin. We found that polymerization rate depended on the detergent concentration by following either biphasic characteristics or only decreasing tendency. The strongest effects were observed at relatively low detergent concentrations. SDS–PAGE electrophoresis and dynamic light‐scattering measurements provided further evidences for the size distribution of actin filaments formed under the influence of detergents. Comparing the polymerization rates measured in the presence of different detergents to those obtained with various magnesium and KCl concentrations showed that detergents may influence the actin polymerization at three levels by modifying: (i) the monomer–monomer interaction, (ii) the local ionic strength, and (iii) the affinity of actin for various cations. In vivo studies on NIH 3T3MDR1 cells using TRITC‐phalloidin detected fast depolymerization of large extent around the critical micellar concentrations of the detergents. We concluded that microdomain insolubility observed in the presence of detergents is hardly to be the result of the stabilization of the submembrane actin cytoskeleton merely; rather inter‐lipid and lipid–protein interactions are also involved within the detergent‐resistant membranes. © 2010 International Society for Advancement of Cytometry
High-Level Operations for Creation and Maintenance of Temporal and Conventional Schema in the tauXSchema Framework

Tauxschema is a framework for constructing and validating time-varying XML documents through the use of a temporal schema. This latter ties together a conventional schema (i.e., A standard XML Schema document) and its corresponding logical and physical annotations, which are stored in an annotation document. Conventional schema and logical and physical annotations undergo changes to respond to changes in user requirements or in the real-world. Consequently, the corresponding temporal schema is also evolving over time. In this paper, we study operations which help designers for changing such schema components. Indeed, we propose three sets of high-level operations for changing temporal schema, conventional schema, and annotations. These high-level operations are based on the low-level operations proposed in our previous work [11, 12, 14, 15, 16]. They are also consistency preserving and more user-friendly than the low-level operations. Besides, we have divided the proposed operations into basic high-level operations (i.e., High-level operations that cannot be defined by using other basic high-level operations) and complex ones.
Ruthenium Water Oxidation Catalysts based on Pentapyridyl Ligands.

Ruthenium complexes containing the pentapyridyl ligand 6,6''-(methoxy(pyridin-2-yl)methylene)di-2,2'-bipyridine (L-OMe) of general formula trans-[RuII (X)(L-OMe-κ-N5 )]n+ (X=Cl, n=1, trans-1+ ; X=H2 O, n=2, trans-22+ ) have been isolated and characterized in solution (by NMR and UV/Vis spectroscopy) and in the solid state by XRD. Both complexes undergo a series of substitution reactions at oxidation state RuII and RuIII when dissolved in aqueous triflic acid-trifluoroethanol solutions as monitored by UV/Vis spectroscopy, and the corresponding rate constants were determined. In particular, aqueous solutions of the RuIII -Cl complex trans-[RuIII (Cl)(L-OMe-κ-N5 )]2+ (trans-12+ ) generates a family of Ru aquo complexes, namely trans-[RuIII (H2 O)(L-OMe-κ-N5 )]3+ (trans-23+ ), [RuIII (H2 O)2 (L-OMe-κ-N4 )]3+ (trans-33+ ), and [RuIII (Cl)(H2 O)(L-OMe-κ-N4 )]2+ (trans-42+ ). Although complex trans-42+ is a powerful water oxidation catalyst, complex trans-23+ has only a moderate activity and trans-33+ shows no activity. A parallel study with related complexes containing the methyl-substituted ligand 6,6''-(1-pyridin-2-yl)ethane-1,1-diyl)di-2,2'-bipyridine (L-Me) was carried out. The behavior of all of these catalysts has been rationalized based on substitution kinetics, oxygen evolution kinetics, electrochemical properties, and density functional theory calculations. The best catalyst, trans-42+ , reaches turnover frequencies of 0.71 s-1 using CeIV as a sacrificial oxidant, with oxidative efficiencies above 95 %.
RNA-dependent control of gene amplification

We exploit the unusual genome organization of the ciliate cell to analyze the control of specific gene amplification during a nuclear differentiation process. Ciliates contain two types of nuclei within one cell, the macronucleus and the micronucleus; and after sexual reproduction a new macronucleus is formed from a micronuclear derivative. During macronuclear differentiation, most extensive DNA reorganization, elimination, and fragmentation processes occur, resulting in a macronucleus containing short DNA molecules (nanochromosomes) representing individual genetic units and each being present in high copy number. It is believed that these processes are controlled by small nuclear RNAs but also by a template derived from the old macronucleus. We first describe the exact copy numbers of selected nanochromosomes in the macronucleus, and define the timing during nuclear differentiation at which copy number is determined. This led to the suggestion that DNA processing and copy number control may be closely related mechanisms. Degradation of an RNA template derived from the macronucleus leads to significant decrease in copy number, whereas injection of additional template molecules results in an increase in copy number and enhanced expression of the corresponding gene. These observations can be incorporated into a mechanistic model about an RNA-dependent epigenetic regulation of gene copy number during nuclear differentiation. This highlights that RNA, in addition to its well-known biological functions, can also be involved in the control of gene amplification.
Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells

The monoclonal antibody 2B12 is directed toward p120, a 120-kDa cellular protein originally identified as a protein tyrosine kinase substrate in cells expressing membrane-associated oncogenic variants of pp60src. In this report, we show that p120 was tyrosine phosphorylated in avian cells expressing membrane-associated, enzymatically activated variants of c-src, including variants having structural alterations in the src homology regions 2 and 3. In contrast, p120 was not tyrosine phosphorylated in cells expressing enzymatically activated, nonmyristylated pp60src. Furthermore, p120 was tyrosine phosphorylated in avian cells expressing middle T antigen, the transforming protein of polyomavirus, as well as in rodent cells stimulated with either epidermal growth factor (EGF) or platelet-derived growth factor. Analysis of the time course of p120 tyrosine phosphorylation in EGF-stimulated cells revealed a rapid onset of tyrosine phosphorylation. In addition, both the extent and duration of p120 phosphorylation increased when cells overexpressing the EGF receptor were stimulated with EGF. Biochemical analysis showed that p120 (in both normal and src-transformed cells) was membrane associated, was myristylated, and was phosphorylated on serine and threonine residues. Hence, p120 appears to be a substrate of both nonreceptor- and ligand-activated transmembrane receptor tyrosine kinases and of serine/threonine kinases and is perhaps a component of both mitogen-stimulated and tyrosine kinase oncogene-induced signaling pathways.
The Arabidopsis-accelerated cell death gene ACD2 encodes red chlorophyll catabolite reductase and suppresses the spread of disease symptoms.

accelerated cell death 2 (acd2) mutants of Arabidopsis have spontaneous spreading cell death lesions and constitutive activation of defenses in the absence of pathogen infection. Lesion formation in acd2 plants can be triggered by the bacterial toxin coronatine through a light-dependent process. Coronatine-triggered and spontaneous lesion spreading in acd2 plants also requires protein translation, indicating that cell death occurs by an active process. We have cloned the ACD2 gene; its predicted product shows significant and extensive similarity to red chlorophyll catabolite reductase, which catalyzes one step in the breakdown of the porphyrin component of chlorophyll [Wüthrich, K. L. , Bovet, L. , Hunziger, P. E. , Donnison, I. S. & Hörtensteiner, S. (2000) Plant J. 21, 189-198]. Consistent with this, ACD2 protein contains a predicted chloroplast transit peptide, is processed in vivo, and purifies with the chloroplast fraction in subcellular fractionation experiments. At some stages of development, ACD2 protein also purifies with the mitochondrial fraction. We hypothesize that cell death in acd2 plants is caused by the accumulation of chlorophyll breakdown products. Such catabolites might be specific triggers for cell death or they might induce cellular damage through their ability to absorb light and emit electrons that generate free radicals. In response to infection by Pseudomonas syringae, transgenic plants expressing excess ACD2 protein show reduced disease symptoms but not reduced growth of bacteria. Thus, breakdown products of chlorophyll may act to amplify the symptoms of disease, including cell death and yellowing. We suggest that economically important plants overexpressing ACD2 might also show increased tolerance to pathogens and might be useful for increasing crop yields.
Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti‐EGFR antibody) combined with docetaxel for patients with operable, Stage II–III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m2, then 250 mg/m2) combined with six cycles of docetaxel (T: 100 mg/m2) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin‐embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3–40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre‐therapy ratio between CD8+ and FOXP3+ tumor‐infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti‐EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.
Once for All: A Novel Robust System for Co-expression of Multiple Chimeric Fluorescent Fusion Proteins in Plants

Chimeric fluorescent fusion proteins have been employed as a powerful tool to reveal the subcellular localizations and dynamics of proteins in living cells. Co-expression of a fluorescent fusion protein with well-known organelle markers in the same cell is especially useful in revealing its spatial and temporal functions of the protein in question. However, the conventional methods for co-expressing multiple fluorescent tagged proteins in plants have the drawbacks of low expression efficiency, variations in the expression level and time-consuming genetic crossing. Here, we have developed a novel robust system that allows for high-efficient co-expression of multiple chimeric fluorescent fusion proteins in plants in a time-saving fashion. This system takes advantage of employing a single expression vector which consists of multiple semi-independent expressing cassettes for the protein co-expression thereby overcoming the limitations of using multiple independent expressing plasmids. In addition, it is a highly manipulable DNA assembly system, in which modification and recombination of DNA molecules are easily achieved through an optimized one-step assembly reaction. By employing this effective system, we demonstrated that co-expression of two chimeric fluorescent fusion reporter proteins of vacuolar sorting receptor and secretory carrier membrane protein gave rise to their perspective subcellular localizations in plants via both transient expression and stable transformation. Thus, we believed that this technical advance represents a promising approach for multi-color-protein co-expression in plant cells.