Miracle-dz/UniFAR-FTUs huggingface dataset:
Urokinase receptor‐dependent and ‐independent p56/59hck activation state is a molecular switch between myelomonocytic cell motility and adherence

Anchorage‐independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N‐terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)‐anchored receptor. Here, we report that urokinase‐treated differentiating U937 monocyte‐like cells exhibit a rapid and transient inhibition of p56/59hck and p55fgr whereas no changes in the activity of other Src family kinases, such as p53/56lyn and p59fyn were observed. U937 transfectants expressing a kinase‐defective (Lys267 to Met) p56/59hck variant exhibit enhanced adhesiveness and a marked F‐actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild‐type or constitutively active (Tyr499 to Phe) p56/59hck stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59hck selectively prevents urokinase receptor‐dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59hck is required for each cell response. In conclusion, modulation of the intracellular p56/59hck tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.
Nutritional advice to increase soluble fibre intake does not change plasma folate or homocysteine in men with angina: a randomised controlled trial

Abstract Objective: To study the effect of advice to increase dietary soluble fibre, including fruit and vegetables, on plasma folate and homocysteine in men with angina. Design: Data were collected on a subset of subjects from the Diet and Angina Randomised Trial (DART II). In a randomised (2 × 2) factorial design, subjects received advice on either, neither or both interventions to: (1) increase soluble fibre intake to 8.0 g day−1 (fruit, vegetables and oats); (2) increase oily fish intake to 2 portions week−1. Those who received soluble fibre advice were compared with those who did not. Subjects were genotyped for C677T variant 5,10-methylenetetrahydrofolate reductase (MTHFR). Setting/subjects: Seven hundred and fifty-three male angina patients were recruited from general practice. Results: Plasma homocysteine concentrations were at the upper end of the normal range (median 11.5, 25% 9.4, 75% 14.0 μmol l−1). Baseline intake of fruit and vegetables was positively correlated with plasma folate (rs = 0.29, P < 0.01). Smokers had lower intakes of fruit and vegetables, lower plasma folate and higher homocysteine (all P < 0.01). Homozygotes for variant MTHFR had higher homocysteine concentrations at low plasma folate (P < 0.01). Reported intakes of fruit and vegetables and estimated dietary folate increased in the intervention group (ca. +75 g day−1, P < 0.01 and ca. +20 g day−1, P < 0.05, respectively). However, neither plasma folate (baseline/follow-up 4.5 vs. 4.4 μg l−1, P = 0.40) nor homocysteine (baseline/follow-up 11.7 vs. 11.7 μmol l−1, P = 0.31) changed. Conclusions: Plasma homocysteine, a cardiovascular risk factor, is influenced by MTHFR genotype, plasma folate and smoking status. Dietary advice successfully led to changes in fruit and vegetable intake, but not to changes in plasma folate or homocysteine, possibly because the fruits and vegetables that were chosen were not those richest in folate.
GENETIC VARIATION IN PLEIOTROPY: DIFFERENTIAL EPISTASIS AS A SOURCE OF VARIATION IN THE ALLOMETRIC RELATIONSHIP BETWEEN LONG BONE LENGTHS AND BODY WEIGHT

Abstract Pleiotropy is an aspect of genetic architecture underlying the phenotypic covariance structure. The presence of genetic variation in pleiotropy is necessary for natural selection to shape patterns of covariation between traits. We examined the contribution of differential epistasis to variation in the intertrait relationship and the nature of this variation. Genetic variation in pleiotropy was revealed by mapping quantitative trait loci (QTLs) affecting the allometry of mouse limb and tail length relative to body weight in the mouse-inbred strain LG/J by SM/J intercross. These relationship QTLs (rQTLs) modify relationships between the traits affected by a common pleiotropic locus. We detected 11 rQTLs, mostly affecting allometry of multiple bones. We further identified epistatic interactions responsible for the observed allometric variation. Forty loci that interact epistatically with the detected rQTLs were identified. We demonstrate how these epistatic interactions differentially affect the body size variance and the covariance of traits with body size. We conclude that epistasis, by differentially affecting both the canalization and mean values of the traits of a pleiotropic domain, causes variation in the covariance structure. Variation in pleiotropy maintains evolvability of the genetic architecture, in particular the evolvability of its modular organization.
Assessment of the Tongue-Drive System Using a Computer, a Smartphone, and a Powered-Wheelchair by People With Tetraplegia

Tongue-Drive System (TDS) is a wireless and wearable assistive technology that enables people with severe disabilities to control their computers, wheelchairs, and smartphones using voluntary tongue motion. To evaluate the efficacy of the TDS, several experiments were conducted, in which the performance of nine able-bodied (AB) participants using a mouse, a keypad, and the TDS, as well as a cohort of 11 participants with tetraplegia (TP) using the TDS, were observed and compared. Experiments included the Fitts' law tapping, wheelchair driving, phone-dialing, and weight-shifting tasks over five to six consecutive sessions. All participants received a tongue piercing, wore a magnetic tongue stud, and completed the trials as evaluable participants. Although AB participants were already familiar with the keypad, throughputs of their tapping tasks using the keypad were only 1.4 times better than those using the TDS. The completion times of wheelchair driving task using the TDS for AB and TP participants were between 157 s and 180 s with three different control strategies. Participants with TP completed phone-dialing and weight-shifting tasks in 81.9 s and 71.5 s, respectively, using tongue motions. Results showed statistically significant improvement or trending to improvement in performance status over the sessions. Most of the learning occurred between the first and second sessions, but trends did suggest that more practice would lead to increased improvement in performance using the TDS.
Supplemental analysis on compressed sensing based interior tomography

Recently, in the compressed sensing framework we proved that an interior ROI can be exactly reconstructed via the total variation minimization if the ROI is piecewise constant. In the proofs, we implicitly utilized the property that if an artifact image assumes a constant value within the ROI, then this constant must be zero. Here we prove this property in the space of square integrable functions.
Forecasting Tourism Expenditure and Growth: A VAR/VECM Analysis for Greece at Both Aggregated and Disaggregated Levels

Tourism is one of the most important factors in the productivity of the Greek economy with significant multiplier effects on the country’s economic activity. This study tests for the existence and direction of causality between output growth and tourism expenditure using a trivariate model with real effective exchange rate, analysed as a whole and in sub-categories respectively for the period 1988-2011. Results from the aggregated model indicate that all variables return to their long-run equilibrium relationships and unidirectional causal relationship is reported from tourism expenditure to real output in the short-run. Moreover, results from the disaggregated model imply strong bidirectional causal links between growth and business travel and tourism spending (BTS) in the longrun and unidirectional causal links from leisure travel and tourism spending (LTS) to growth and to BTS. Forecasts for the period 2012-2020 indicate increasing total tourism expenditure and particularly for the case of BTS.
Establishment of in vitro spermatogenesis from spermatocytes in the medaka, Oryzias latipes

Spermatocytes of the teleost, Oryzias latipes, at meiotic prophase were cultured without contact with somatic cells. They began to divide, progressing through the meiotic divisions and differentiating into round spermatids within 48 h. The chromosome number in both the primary and secondary spermatocytes at metaphase was n= 24. In spermatids, a single flagellum was formed and the release of residual bodies was observed in vitro. The size and shape of the flagellum were the same as those seen in vivo. The expression of protamine mRNA was detected in round spermatids. This result suggests that gene expression, as well as morphological change, is regulated by the progression of spermatogenesis in cell culture. Furthermore, when the eggs of O. latipes were inseminated with germ cells cultured for 10 days, normal embryos developed and hatched out. These results suggest that the spermatocytes of O. latipes develop into fertile sperm in cell culture.
Morphometrical Characteristics of Age‐Associated Changes in the Thymus of Old Male Wistar Rats

In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3‐ and 18‐month‐old male Wistar rats and the percentages of bromodeoxyuridine‐incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7‐fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter‐lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus‐related changes in immunological aging.
Fitness effects of mutation: testing genetic redundancy in Arabidopsis thaliana

Screens of organisms with disruptive mutations in a single gene often fail to detect phenotypic consequences for the majority of mutants. One explanation for this phenomenon is that the presence of paralogous loci provides genetic redundancy. However, it is also possible that the assayed traits are affected by few loci, that effects could be subtle or that phenotypic effects are restricted to certain environments. We assayed a set of T‐DNA insertion mutant lines of Arabidopsis thaliana to determine the frequency with which mutation affected fitness‐related phenotypes. We found that between 8% and 42% of the assayed lines had altered fitness from the wild type. Furthermore, many of these lines exhibited fitness greater than the wild type. In a second experiment, we grew a subset of the lines in multiple environments and found whether a T‐DNA insert increased or decreased fitness traits depended on the assay environment. Overall, our evidence contradicts the hypothesis that genetic redundancy is a common phenomenon in A. thaliana for fitness traits. Evidence for redundancy from prior screens of knockout mutants may often be an artefact of the design of the phenotypic assays which have focused on less complex phenotypes than fitness and have used single environments. Finally, our study adds to evidence that beneficial mutations may represent a significant component of the mutational spectrum of A. thaliana.
The Diagnosis and Course of Frontotemporal Dementia

The course of frontotemporal dementia (FTD) is examined in a prospective, incipient clinical cohort. Three hundred nineteen patients were followed yearly for an average of 3.6 years. The relative frequencies at presentation were Behavioral variety (FTD-bv) 37.6%, Primary Progressive Aphasia (PPA) 31.6%, possible PPA 10.6%, Corticobasal Syndrome (CBDS) and Progressive Supranuclear Palsy (PSP) 8.1%, Semantic Dementia (SD) 6.6%, and possible FTD 5.3%. The age of onset was significantly lower in the FTD-bv and SD groups than in the rest, but survival and sex distribution was similar in all groups. The evolution is characterized by the appearance of additional FTD syndromes in two-thirds of the patients. A significant association of SD with FTD-bv and CBDS/PSP with PPA was found. The Frontal Behavioral Inventory was highly sensitive and specific for FTD-bv. Visuospatial function was preserved except in CBDS/PSP. The clinical diagnosis showed a positive predictive value of 87% against autopsy in 67 patients. Multiple syndromes increase the likelihood of FTD pathology. In conclusion, the clinical associations follow the tau-negative and tau-positive pathologic dichotomy to some extent, but there is too much overlap to consider the clinical groups or their associations separate diseases.
Prolonged pituitary down-regulation with full-dose of gonadotropin-releasing hormone agonist in different menstrual cycles: a retrospective cohort study

Background The efficiency of prolonged down-regulation caused by a full-dose of gonadotropin-releasing hormone agonist (GnRH-a) injected during different menstrual phases has not yet been researched. Our goal was to evaluate the effects of GnRH-a, which was used in different phases of the menstrual cycle in patients undergoing in vitro fertilization and embryo transfer. Methods This was a retrospective cohort study. A total of 320 patients received a prolonged pituitary down-regulated full-dose (3.75 mg) of triptorelin in the early follicular phase, and 160 patients received the same full-dose of triptorelin during the mid-luteal phase. Clinical and laboratory outcomes were compared between the two groups. Results The basic characteristics of the two groups were comparable. The mean number of retrieved oocytes, fertilized oocytes, cleavage oocytes and good quality embryos were comparable between the two groups. Although there was a higher antral follicle count, cyst formation rate, fertilization rate and cleavage rate in the follicular phase group, no statistically significant effects were seen on implantation rate (41.15% vs. 45.91%), clinical pregnancy rate (60.38% vs. 61.36%), ongoing pregnancy rate (57.74% vs. 57.58%), live birth rate (56.23% vs. 57.58%) or early abortion rate (2.64% vs. 3.79%) per fresh transfer cycle. Moreover, severe ovarian hyperstimulation syndrome rates at the early stage (1.89% vs. 2.27%) were low in both groups. Conclusions Prolonged pituitary down-regulation achieved by utilizing a full-dose of GnRH-a administrated in either phase of the menstrual cycle can have a positive effect on ongoing pregnancy rate and live-birth rate per fresh embryo transfer cycle. Ovarian cyst formation rate was higher in the follicular phase group, but this did not have any adverse impact on clinical results.
A Posterior Khodadoust Line in a Graft Rejection Episode After Descemet Stripping Automated Endothelial Keratoplasty

Purpose: To describe the presence of an endothelial rejection line in immunological graft rejection after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: Case report. Results: A 77-year-old woman underwent DSAEK procedure of the left eye because of visual limiting bullous keratopathy. One week postoperatively, the donor lamella was partially detached and an additional air bubble was injected into the anterior chamber. Thereafter, complete adherence of the lamella was seen. Four months after surgery, vision deteriorated, and a transient immunological graft rejection episode with endothelial rejection line was seen. Conclusions: In contrast to other reports, an endothelial rejection line (Khodadoust line) can be seen during the endothelial rejection episode after DSAEK.
Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner*

Background: Fatty acid-binding proteins (FABPs) chaperone intracellular transport of lipophilic ligands. Results: FABP1 and FABP2 differentially promote drug activation of peroxisome proliferator-activated receptor α (PPARα) via ligand-dependent protein-protein interactions. Conclusion: Drug activation of PPARα is regulated by the presence of different FABPs. Significance: FABPs may act in a tissue-specific manner to enhance the selectivity of PPARα agonists. Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner.
Does bimodal stimulus presentation increase ERP components usable in BCIs?

Event-related potential (ERP)-based brain–computer interfaces (BCIs) employ differences in brain responses to attended and ignored stimuli. Typically, visual stimuli are used. Tactile stimuli have recently been suggested as a gaze-independent alternative. Bimodal stimuli could evoke additional brain activity due to multisensory integration which may be of use in BCIs. We investigated the effect of visual–tactile stimulus presentation on the chain of ERP components, BCI performance (classification accuracies and bitrates) and participants’ task performance (counting of targets). Ten participants were instructed to navigate a visual display by attending (spatially) to targets in sequences of either visual, tactile or visual–tactile stimuli. We observe that attending to visual–tactile (compared to either visual or tactile) stimuli results in an enhanced early ERP component (N1). This bimodal N1 may enhance BCI performance, as suggested by a nonsignificant positive trend in offline classification accuracies. A late ERP component (P300) is reduced when attending to visual–tactile compared to visual stimuli, which is consistent with the nonsignificant negative trend of participants’ task performance. We discuss these findings in the light of affected spatial attention at high-level compared to low-level stimulus processing. Furthermore, we evaluate bimodal BCIs from a practical perspective and for future applications.
Prognostic value and determinants of a hypointense core in T2-weighted cardiac magnetic resonance in acute reperfused ST-elevation myocardial infarction

Background—A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation–myocardial infarction. Methods and Results—We analyzed 346 patients with ST-elevation–myocardial infarction undergoing primary angioplasty <12 hours after symptoms onset. T2-weighted, contrast-enhanced CMR was used for assessment of the area at risk, myocardial salvage, infarct size, hypointense core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P<0.001, respectively). The presence of a hypointense core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P=0.006) 6 months after infarction. Conclusions—A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.