Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Methylxanthines such as caffeine and theophylline are known to inhibit glucose transport. We have studied such inhibition in the glucose transporter type 1 deficiency syndrome (Glut1DS) by erythrocyte glucose transport assays. Data from four patients with individual mutations in the GLUT1 gene are discussed: patient 1 (hemizygosity), 3 (S66F), 15 (368Ins23), and 17 (R333W). Zero-trans influx of 14C-labeled 3-O-methyl glucose (3-OMG) into erythrocytes of patients is reduced (patient 1, 51%; 3, 45%; 15, 31%; 17, 52%) compared with maternal controls. Inhibition studies on patients 1, 3, 17, and maternal controls show an IC50 for caffeine of approximately 1.5 mM both in controls (n = 3) and patients (n = 3) at 5 mM 3-OMG concentration. In the same two groups, kinetic studies show that 3 mM caffeine significantly decreases Vmax (p < 0.005), whereas the decrease in Km is significant (p < 0.01) only in the three controls and one patient (patient 3). Kinetic data from individual patients permit us to speculate that the interactions between caffeine and Glut1 are influenced by the mutation. Three mM caffeine also inhibits the transport of dehydroascorbic acid (DHA), another substrate for Glut1. The combined effects of caffeine (3 mM) and phenobarbital (10 mM) on glucose transport, as determined in patient 15 and the maternal control, show no additive or synergistic inhibition. These data indicate that caffeine and phenobarbital have similar Glut1 inhibitory properties in these two subjects. Our study suggests that Glut1DS patients may have a reduced safety margin for methylxanthines. Consumption of methylxanthine-containing products may aggravate the neurologic symptoms associated with the Glut1DS.
Nomogram of fetal middle cerebral artery peak systolic velocity at 23–35 weeks of gestation in a Brazilian population: Pilot study

Objective. To establish normative data for the peak systolic velocity of the middle cerebral artery (MCA-PSV) of fetuses in the second half of pregnancy using multiples of the median and percentile reference range. Methods. A cross-sectional study was performed in 90 healthy fetuses at between 23 and 35 weeks of gestation. A bi-dimensional axial scan of the brain, including the thalami and cavitas septi pellucidi was obtained. The circle of Willis was visualized using color flow mapping. Pulsed-wave Doppler velocimetry of the MCA was performed close to the artery's origin, with a beam-vessel angle below 20°. A table with the multiples of the median (MoM) of the MCA-PSV for each gestational age was generated and Pearson's correlation coefficient (r) was calculated. Regression modeling across gestational age was performed to obtain the reference values. Results. There was a strong correlation between the MCA-PVS and gestational age (r = 0.70; p < 0.001). Values for the MCA-PSV for the following MoM were calculated: 1.0, 1.29, 1.50, and 1.55. The MCA-PSV 2.5th and 97.5th centiles ranged from 24.33 cm2/s to 78.36 cm2/s, respectively, between weeks 23 and 35. Conclusions. A nomogram for the fetal MCA-PSV during the second half of pregnancy was generated.
N-Arachidonyl Maleimide Potentiates the Pharmacological and Biochemical Effects of the Endocannabinoid 2-Arachidonylglycerol through Inhibition of Monoacylglycerol Lipase

Inhibition of the metabolism of the endocannabinoids, anandamide (AEA) and 2-arachidonyl glycerol (2-AG), by their primary metabolic enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively, has the potential to increase understanding of the physiological functions of the endocannabinoid system. To date, selective inhibitors of FAAH, but not MAGL, have been developed. The purpose of this study was to determine the selectivity and efficacy of N-arachidonyl maleimide (NAM), a putative MAGL inhibitor, for modulation of the effects of 2-AG. Our results showed that NAM unmasked 2-AG activity in a tetrad of in vivo tests sensitive to the effects of cannabinoids in mice. The efficacy of 2-AG (and AEA) to produce hypothermia was reduced compared with Δ9-tetrahydrocannabinol; however, 2-AG differed from AEA by its lower efficacy for catalepsy. All tetrad effects were partially CB1 receptor-mediated because they were attenuated (but not eliminated) by SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-pyrazole-3-carboxamide HCl] and in CB1-/- mice. In vitro, NAM increased endogenous levels of 2-AG in the brain. Furthermore, NAM raised the potency of 2-AG, but not AEA, in agonist-stimulated guanosine 5′-O-(3-[35S]thio)triphosphate binding assay, a measure of G-protein activation. These results suggest that NAM is an MAGL inhibitor with in vivo and in vitro efficacy. NAM and other MAGL inhibitors are valuable tools to elucidate the biological functions of 2-AG and to examine the consequences of dysregulation of this endocannabinoid. In addition, NAM's unmasking of 2-AG effects that are only partially reversed by SR141716A offers support for the existence of non-CB1, non-CB2 cannabinoid receptors.
Maternal dental caries and pre-term birth: Results from the EPIPAP study

Abstract Objective. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. Materials and methods. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. Results. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01–1.45] and OR = 1.25 [1.01–1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91–1.32] and aOR = 1.14 [0.91–1.42], respectively). Conclusions. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.
Dynein participates in chromosome segregation in fission yeast

Background information. In eukaryotic cells, proper formation of the spindle is necessary for successful cell division. For faithful segregation of sister chromatids, each sister kinetochore must attach to microtubules that extend to opposite poles (chromosome bi‐orientation). At the metaphase—anaphase transition, cohesion between sister chromatids is removed, and each sister chromatid is pulled to opposite poles of the cell by microtubule‐dependent forces.
Predatory activity of nematophagous fungi on infective larvae of Ancylostoma sp.: evaluation in vitro and after passing through the gastrointestinal tract of dogs

Abstract The predatory capacity of nematophagous fungi Duddingtonia flagrans (AC001), Monacrosporium thaumasium (NF34a), M. appendiculatum (CGI), M. sinense (SF53), Arthrobotrys conoides (I-40), A. cladodes (CG719) and A. robusta (I-31) on infective Ancylostoma sp. larvae (L3) was evaluated. Compared with the control without fungi there was a significant reduction (P < 0.05) of 87.02%, 82.74%, 47.93%, 60.49%, 76.89%, 71.33% and 86.02% in the mean number of Ancylostoma sp. (L3) recovered from treatments with the isolates AC001, NF34a, CGI, SF53, I-40, CG719 and I-31, respectively. Isolates AC001, I-31 and NF34a were more effective in capturing L3 during the in vitro assay. Isolates were then in vivo evaluated for the capacity to remain viable after passing through the gastrointestinal tract of dogs, while still maintaining their predatory activity against L3. Fungal isolates survived the passage and showed efficient predation 48 h after fungal administration to the dogs (P < 0.05). After this time, only the isolate NF34a remained effective up to 96 h after administration (P < 0.05). Monacrosporium thaumasium, D. flagrans and A. robusta are potential biological control agents of Ancylostoma sp. in dogs.
Role of glycosylation in structure and stability of Erythrina corallodendron lectin (EcorL): A molecular dynamics study

The effect of glycosylation on structure and stability of glycoproteins has been a topic of considerable interest. In this work, we have investigated the solution conformation of the oligosaccharide and its effect on the structure and stability of the glycoprotein by carrying out a series of long Molecular dynamics (MD) simulations on glycosylated Erythrina corallodendron lectin (EcorL) and nonglycosylated recombinant Erythrina corallodendron lectin (rEcorL). Our results indicate that, despite the similarity in overall three dimensional structures, glycosylated EcorL has lesser nonpolar solvent accessible surface area compared to nonglycosylated EcorL. This might explain the experimental observation of higher thermodynamic stability for glycosylated EcorL compared to nonglycosylated EcorL. Analysis of the simulation results indicates that, dynamic view of interactions between protein residues and oligosaccharide is entirely different from the static picture seen in the crystal structure. The oligosaccharide moiety had dynamically stable interactions with Lys 55 and Tyr 53, both of which are separated in sequence from the site of glycosylation, Asn 17. It is possible that glycosylation helps in forming long‐range contacts between amino acids, which are separated in sequence and thus provides a folding nucleus. Thus our simulations not only reveal the conformations sampled by the oligosaccharide, but also provide novel insights into possible molecular mechanisms by which glycosylation can help in folding of the glycoprotein by formation of folding nucleus involving specific contacts with the oligosaccharide moiety.
The Impact of Leadership Style on Effective Human Resources Management and Productivity in Hospitality Organizations

This research work investigates the impact of leadership style on effective human resources management and productivity in hospitality organizations and used questionnaire as instrument of primary data collection. Tables and sample percentages were used in data presentation. For clear analysis, the study centers on two broad variables; the dependent variable which is effective human resources management and the independent variable which is leadership style adopted which will either increase or decrease productivity in a hospitality organization. Therefore, effective human resources performances in a hospitality organization depends on the leadership style adopted. The situational or contingency theory of leadership was cited in determining the leadership style that should attract a particular level of performance. Also, the behavioral theory approach of leadership was cited in the work to draw attention on two different types of leaders that exist in hospitality organizations. They are the task oriented and employee oriented leaders. Two different hypotheses were formulated and tested using various statistical tools such as a chi-square test and simple percentage. The study reveals that there is a significant – effect of leadership style that should improve the utilization of human resources and that the behaviors of leaders have a significant effect on the productivity index of hospitality organizations. The study arrives at a final conclusion that effective leadership style boosts corporate profit and growth while lack of effective leadership and corporation can cause loss in an hour, inefficiency and finally result to the close down of a hospitality organization. Hospitality organizations should adopt an effective leadership style for effective utilization of their human and material resources for efficient and effective productivity.
Mitochondrial genomes suggest that hexapods and crustaceans are mutually paraphyletic

For over a century the relationships between the four major groups of the phylum Arthropoda (Chelicerata, Crustacea, Hexapoda and Myriapoda) have been debated. Recent molecular evidence has confirmed a close relationship between the Crustacea and the Hexapoda, and has included the suggestion of a paraphyletic Hexapoda. To test this hypothesis we have sequenced the complete or near-complete mitochondrial genomes of three crustaceans (Parhyale hawaiensis, Squilla mantis and Triops longicaudatus), two collembolans (Onychiurus orientalis and Podura aquatica) and the insect Thermobia domestica. We observed rearrangement of transfer RNA genes only in O. orientalis, P. aquatica and P. hawaiensis. Of these, only the rearrangement in O. orientalis, an apparent autapomorphy for the collembolan family Onychiuridae, was phylogenetically informative. We aligned the nuclear and amino acid sequences from the mitochondrial protein-encoding genes of these taxa with their homologues from other arthropod taxa for phylogenetic analysis. Our dataset contains many more Crustacea than previous molecular phylogenetic analyses of the arthropods. Neighbour-joining, maximum-likelihood and Bayesian posterior probabilities all suggest that crustaceans and hexapods are mutually paraphyletic. A crustacean clade of Malacostraca and Branchiopoda emerges as sister to the Insecta sensu stricto and the Collembola group with the maxillopod crustaceans. Some, but not all, analyses strongly support this mutual paraphyly but statistical tests do not reject the null hypotheses of a monophyletic Hexapoda or a monophyletic Crustacea. The dual monophyly of the Hexapoda and Crustacea has rarely been questioned in recent years but the idea of both groups' paraphyly dates back to the nineteenth century. We suggest that the mutual paraphyly of both groups should seriously be considered.
‘Immune complex’ mediated intravascular hemolysis due to IgM cephalosporin‐dependent antibody

Immune hemolytic anemia (IHA) related to cephalosporins is rare and generally considered to be the result of a drug‐adsorption mechanism. In previously reported cases, the hemolysis was usually extravascular and the causative antibodies were IgG, incapable of activating complement, and demonstrable by the direct or indirect antiglobulin test using red cells (RBCs) pretreated in vitro with cephalosporin. The authors report a patient in whom acute intravascular hemolysis developed while she was receiving cefotaxime (a cephalosporin as yet not reported to cause IHA). The patient's RBCs were coated only with complement fragments (C3d), even at the peak of the hemolytic episode. Her serum and eluates repeatedly yielded negative results when tested against normal or cephalosporin‐coated RBCs. However, strong hemagglutination and C5b‐9‐mediated hemolysis were observed if the patient's serum was tested against RBCs in the presence of the drug, its ex vivo antigen and, to a lesser degree, cephalothin and ceftriaxon, but not in the presence of penicillin and other related cephalosporins. The positive reactions were not changed by preincubating the serum with different amounts of the drugs. All of these findings reflect the typical picture of drug‐induced IHA by the so‐called “immune complex” mechanism and not by the drug‐adsorption mechanism. The authors conclude that cephalosporin can cause immune hemolysis in two ways: the drug‐adsorption mechanism and, as described here, the “immune complex” mechanism.
Programmed and Magnet-Induced Vagus Nerve Stimulation for Refractory Epilepsy

Summary Vagus nerve stimulation (VNS) is an effective alternative treatment for patients with refractory epilepsy. The generator produces intermittent stimulation trains and does not require patient intervention. Using currently available technology, continuous stimulation is incompatible with a reasonable battery life. Because earlier studies have demonstrated the persistence of a stimulation effect after discontinuation of the stimulation train, we intended to evaluate the clinical efficacy of VNS in both the programmed intermittent stimulation mode and the magnet stimulation mode. Patients, companions, and caregivers were instructed on how to administer additional stimulation trains when an aura or a seizure onset occurred. We assumed that patients or caregivers could recognize habitual seizures and were able to evaluate sudden interruption of these seizures. During a mean follow-up of 35 months, 46% of patients became responders, with a reduction in seizure frequency of more than 50%. Twenty-nine percent of patients stopped having convulsive seizures. In two thirds of patients who were able to self-administer or receive additional magnet stimulation, seizures could be interrupted consistently or occasionally. More than half of the patients who reported a positive effect of magnet stimulation became responders. Only three patients were able to use the magnet themselves. In most cases, support from caregivers was necessary. This study is the first to document the efficacy of magnet-induced VNS in a larger patient population during long-term follow-up. The magnet is a useful tool that provides patients who are treated with VNS and mainly caregivers of such patients with an additional means of controlling seizures. To further confirm the self-reported results from our patients, additional studies comparing programmed stimulation and magnet-induced stimulation during monitoring conditions are needed.
Psychosocial Adjustment and Quality of Life of Children After Hematopoietic Stem Cell Transplantation in South Korea

The purpose of this study was to describe the psychosocial adjustment and health-related quality of life (HRQoL) in children who received hematopoietic stem cell transplantation (HSCT) and to examine the relationship of children’s characteristics with psychosocial adjustment and HRQoL in South Korea. Participants were 53 children who survived at least 100 days after HSCT, whose current age ranged from 5 to 17 years and their primary caregivers, mostly mothers. Parents completed the Korean version of Child Behavior Check List and Child Health Questionnaire 50-item parent-report version. Children with HSCT had significantly lower scores on the total scale for behavior problems and on most subscales than a normative sample, t = 2.09 to −4.75, P = . 043 to <. 001. Compared with the Taiwanese sample, scores in physical and psychosocial QoL (except bodily pain, mental health, and behavior) were significantly lower in children with HSCT, t = −2.91 to −9.84, P =. 005 to <. 001. Time since HSCT seemed to influence the physical (F = 8.61, P = .001) and psychosocial QoL (F = 3.98, P = .025) subscales. Social competence (r = .48, P = .001) and behavioral problems (r = −.37, P = .006) were associated with psychosocial QoL but not with physical QoL. After HSCT, children could benefit from psychological support to promote their adaptation to daily life and improve their QoL.
Deviations from Covered Interest Rate Parity

We find that deviations from the covered interest rate parity condition (CIP) imply large, persistent, and systematic arbitrage opportunities in one of the largest asset markets in the world. Contrary to the common view, these deviations for major currencies are not explained away by credit risk or transaction costs. They are particularly strong for forward contracts that appear on the banks' balance sheets at the end of the quarter, pointing to a causal effect of banking regulation on asset prices. The CIP deviations also appear significantly correlated with other fixed-income spreads and with nominal interest rates.
The Coalition Effect, 2010–2015: The coalition and society (II): Education

The accelerating pace of educational reform since the 1988 Act quickened still further in the 2010–15 parliament. There were three new acts, but also many of the powers acquired by previous acts were put to use. The heightened activity was partly because the programme had to embrace the ambitions of two parties. But the main impetus came from the new Secretary of State, Michael Gove, who in his three years shadowing the post had developed very clear ideas about what he wanted to achieve. In post, he pressed hard, anxious to embed as many of the desired changes as he could while he still held the reins. Education was prominent in the 2010 manifestos of both the Conservative and Liberal Democrat parties. Both envisaged more freedom for schools and extra money to raise the attainment of pupils from low-income families (the pupil premium). They also agreed on the need to improve the quality of teaching, proposing to increase school-led teacher training and expand the Teach First scheme. But there were differences in emphasis, with the Conservatives placing more on new schools, higher standards and improved discipline, while the Liberal Democrats stressed fairness. Inevitably, with two parties in government there have had to be compromises, but in the field of education, given the similarity of the manifestos, it was relatively easy to reach agreement, with one notable exception. Some of the compromises resulted in better policy. The Liberal Democrats pushed the pupil premium higher up the agenda than it might have been, and the Conservatives were so pleased with it that they let it be thought it was their policy. They were much less keen on Nick Clegg's free lunches for all infant school pupils, which had to be afforded a tightly constrained budget, with the additional expense of new kitchens.
Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: Gene–phenotype correlations

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0–68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2–50) and 18 ± 21 (0–48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT. © 2012 Wiley Periodicals, Inc.