Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro.

Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate.This work was supported by grants from the UK Multiple Sclerosis Society and from Qatar Foundation. The work was further supported by core funding from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. The authors acknowledge the excellent technical support in GC-MS and HPLC analysis from Lars Evje (NTNU, Norway).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s11064-016-1985-y

Reverse Myocardial Remodeling in Hypertrophic Cardiomyopathy: Little Explored Benefit of Exercise

International Journal of Exercise Science 14(2): 1018-1026, 2021. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that causes myocardial remodeling. Physical exercise (PE) is a therapeutic resource used in Supervised Cardiac Rehabilitation (SCR) to improve Quality of Life (QL), reducing cardiovascular morbidity and mortality. Therefore, the aim of this study is to report how SCR using a personalized exercise prescription, promoted Reverse Myocardial Remodeling (RMR), improved functionality and QL of a patient with HCM. This is a case report of a 43-year-old sedentary female patient with a Body Mass Index (BMI) of 24.7 kg/m2. The patient was diagnosed with Septal Type Asymmetric HCM. Heart Failure (HF) grade III / IV, according to the New York Heart Association (NYHA), was initially treated with 40mg of Propranolol Hydrochloride twice a day, and presented with excessive fatigue, and angina. The echocardiogram showed a final diastolic volume (FDV) of 130 ml, a final systolic volume (FSV) of 44 ml, a left ventricular mass (LVM) of 236 g, interventricular septum thickness of 14 mm, left ventricular posterior wall (LVPW) thickness of 9 mm, left atrium diameter 46 mm, left ventricular end diastolic diameter of 52mm, septum/left ventricular wall ratio of 1.55 mm, and ejection fraction (EF) of 66% (Teicholz). It was obtained as a result of decreased FDV 130 vs. 102ml, decreased FSV 44 vs. 32 ml, decreased LVM 236 vs. 201 g, increased EF 66 vs. 69%, 26% improvement in QL, and 50% reduction in the dosage of Propranolol Hydrochloride. These results suggest that a personalized SCR program is an adjuvant treatment capable of promoting RMR and improving QL and functionality in a patient with HCM

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage

Point process model of 1/f noise versus a sum of Lorentzians

We present a simple point process model of $1/f^{\beta}$ noise, covering different values of the exponent $\beta$. The signal of the model consists of pulses or events. The interpulse, interevent, interarrival, recurrence or waiting times of the signal are described by the general Langevin equation with the multiplicative noise and stochastically diffuse in some interval resulting in the power-law distribution. Our model is free from the requirement of a wide distribution of relaxation times and from the power-law forms of the pulses. It contains only one relaxation rate and yields $1/f^ {\beta}$ spectra in a wide range of frequency. We obtain explicit expressions for the power spectra and present numerical illustrations of the model. Further we analyze the relation of the point process model of $1/f$ noise with the Bernamont-Surdin-McWhorter model, representing the signals as a sum of the uncorrelated components. We show that the point process model is complementary to the model based on the sum of signals with a wide-range distribution of the relaxation times. In contrast to the Gaussian distribution of the signal intensity of the sum of the uncorrelated components, the point process exhibits asymptotically a power-law distribution of the signal intensity. The developed multiplicative point process model of $1/f^{\beta}$ noise may be used for modeling and analysis of stochastic processes in different systems with the power-law distribution of the intensity of pulsing signals.Comment: 23 pages, 10 figures, to be published in Phys. Rev.

Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.Comment: 28 pages, 13 figure

Co-evolution of density and topology in a simple model of city formation

We study the influence that population density and the road network have on each others' growth and evolution. We use a simple model of formation and evolution of city roads which reproduces the most important empirical features of street networks in cities. Within this framework, we explicitely introduce the topology of the road network and analyze how it evolves and interact with the evolution of population density. We show that accessibility issues -pushing individuals to get closer to high centrality nodes- lead to high density regions and the appearance of densely populated centers. In particular, this model reproduces the empirical fact that the density profile decreases exponentially from a core district. In this simplified model, the size of the core district depends on the relative importance of transportation and rent costs.Comment: 13 pages, 13 figure

Ion-beam mixing and solid-state reaction in Zr-Fe multilayers

Vapor-deposited Zr-Fe multilayered thin films with various wavelengths and of overall composition either 50% Fe or Fe-rich up to 57% Fe were either irradiated with 300 keV Kr ions at temperatures from 25 K to 623 K to fluences up to 2 {times} 10{sup 16} cm{sup {minus}2}, or simply annealed at 773 K in-situ in the Intermediate Voltage Electron microscope At Argonne National Laboratory. Under irradiation, the final reaction product is the amorphous phase in all cases studied, but the dose to amorphization depends on the temperature and on the wavelength. In the purely thermal case (annealing at 773 K), the 50-50 composition produces the amorphous phase but for the Fe-rich multilayers the reaction products depend on the multilayer wavelength. For small wavelength, the amorphous phase is still formed, but at large wavelength the Zr-Fe crystalline intermetallic compounds appear. These results are discussed in terms of existing models of irradiation kinetics and phase selection during solid state reaction

Quantifying the Performance of Individual Players in a Team Activity

Teamwork is a fundamental aspect of many human activities, from business to art and from sports to science. Recent research suggest that team work is of crucial importance to cutting-edge scientific research, but little is known about how teamwork leads to greater creativity. Indeed, for many team activities, it is not even clear how to assign credit to individual team members. Remarkably, at least in the context of sports, there is usually a broad consensus on who are the top performers and on what qualifies as an outstanding performance.In order to determine how individual features can be quantified, and as a test bed for other team-based human activities, we analyze the performance of players in the European Cup 2008 soccer tournament. We develop a network approach that provides a powerful quantification of the contributions of individual players and of overall team performance.We hypothesize that generalizations of our approach could be useful in other contexts where quantification of the contributions of individual team members is important

Cell populations in lesions of cutaneous leishmaniasis of leishmania (L.) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 ± 13.1% of the infiltrate in active lesions (versus CD2+= 40.3 ± 5.7% in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 ± 7.1%) was significantly higher (P < 0.005) from the healing lesions (42.7 ± 12.7%). Moreover, the expression of the activation molecules CD25 (@ 16%), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis

Measurement of the charm structure function F_{2,c)^{γ} of the photon at LEP

The production of charm quarks is studied in deep-inelastic electron–photon scattering using data recorded by the OPAL detector at LEP at nominal e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. The charm quarks have been identified by full reconstruction of charged D* mesons using their decays into D⁰π with the D⁰ observed in two decay modes with charged particle final states, Kπ and Kπππ. The cross-section σ^{D*} for production of charged D* in the reaction e⁺e⁻→e⁺e⁻D*Χ is measured in a restricted kinematical region using two bins in Bjorken x, 0.00140.1 the perturbative QCD calculation at next-to-leading order agrees perfectly with the measured cross-section. For x<0.1 the measured cross-section is 43.8±14.3±6.3±2.8 pb with a next-to-leading order prediction of 17.0⁺²·⁹_₂.₃ pb