Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.

Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death. Reductions in mitochondrial pyruvate uptake do not compromise cellular energy metabolism, suggesting neuronal metabolic flexibility. Rather, MPC inhibition rewires mitochondrial substrate metabolism to preferentially increase reliance on glutamate to fuel energetics and anaplerosis. Mobilizing the neuronal glutamate pool for oxidation decreases the quantity of glutamate released upon depolarization and, in turn, limits the positive-feedback cascade of excitotoxic neuronal injury. The finding links mitochondrial pyruvate metabolism to glutamatergic neurotransmission and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitotoxicity

Modelling and simulation tool for off-grid PV-hydrogen energy system

This paper introduces a user-oriented software tool for simulation of a solar energy-based hydrogen production system. The developed tool goes beyond the realm of electric load and includes a hydrogen cooking load facility, as an efficient means of utilising the hydrogen produced. A model rural household in Nigeria has been used to evaluate the tool. It was found that a 2.42 kW solar photovoltaic module, 0.6 kW electrolyser and 3.7 kWh battery would be enough to provide steady 24-h power for a modest daily energy demand of 2.2 kWh. In the results, the excess energy realised was used in a H2-cooker to partly meet the estimated 1.9 kWh/day cooking demand of the household over a simulated year period

Ispitivanje fenolnog profila i antioksidacijskog učinka meda od metvice (Mentha spp.)

Research background. The composition of honey is influenced by the botanical source and geographical area of the nectar from which it is derived. Unifloral honeys reach higher market value than multifloral honeys due to their specific aromas, which result from volatile and phenolic compounds. Experimental approach. The aim of our study is to characterize the phenolic composition of a rare unifloral variety of honey – mint (Mentha spp.) honey. For this purpose, we performed standard physicochemical analyses, pollen analysis, determined total phenolic and flavonoid content, analysed antioxidant activity and performed qualitative and quantitative analyses of phenolic compounds for five mint honeys. Results and conclusions. Our results indicate that mint honey samples have high phenolic content, expressed in gallic acid equivalents, from (76.7±0.6) to (90.1±1.1) mg/100 g, and flavonoid content, expressed as quercetin equivalents, from (6.7±0.6) to (12.5±0.8) mg/100 g. These honey samples also exhibit strong antioxidant activity, expressed as Trolox equivalents, from (33.6±2.8) to (51.3±1.2) mg/100 g and from (14.4±0.8) to (55.1±2.4) mg/100 g when analysed with DPPH and ABTS assays, respectively. Quantitative LC-MS/MS analysis revealed that the most abundant phenols in all samples were chrysin, apigenin and p-coumaric acid. Qualitative LC-MS/MS analysis identified the presence of kaempferide, diosmetin, acacetin and several caffeic acid derivatives. Novelty and scientific contribution. Our study indicates that mint honey contains unique phenolic profiles, which likely contribute to its distinctive aroma and strong antioxidant activity. A detailed description of the rare honey varieties gives beekeepers greater visibility and easier access to the demanding natural product market.Pozadina istraživanja. Na sastav meda utječu botanički izvor i geografsko podrijetlo nektara iz kojeg je dobiven. Uniflorni medovi postižu veću tržišnu vrijednost od multiflornih zbog svoje specifične arome, koja je rezultat prisustva hlapljivih i fenolnih spojeva. Eksperimentalni pristup. Svrha je našeg rada bila okarakterizirati fenolni sastav rijetke uniflorne sorte meda – meda od metvice (Mentha spp.). U tu svrhu smo proveli standardne fizikalno-kemijske analize i analizu peludi, odredili ukupne udjele fenola i flavonoida, ispitali antioksidacijsku aktivnost te kvalitativno i kvantitativno ispitali fenolne spojeve u pet uzoraka meda od metvice. Rezultati i zaključci. Rezultati pokazuju da uzorci meda od metvice imaju velik udjel fenola, izražen u ekvivalentima galne kiseline, od (76,7±0,6) do (90,1±1,1) mg/100 g, te udjel flavonoida, izražen u ekvivalentima kvercetina, od (6,7±0,6) do (12,5±0,8) mg/100 g. Uzorci su također imali snažnu antioksidacijsku aktivnost, izraženu u Trolox ekvivalentima, i to prema metodi DPPH od (33,6±2,8) do (51,3±1,2) mg/100 g, a prema metodi ABTS od (14,4±0,8) do (55,1±2,4) mg/100 g. Kvantitativnim ispitivanjem pomoću spregnutog sustava tekućinske kromatografije i tandemske spektrometrije masa utvrđeno je da su najzastupljeniji fenoli u svim uzorcima bili krizin, apigenin i p-kumarinska kiselina, dok je kvalitativnom analizom pomoću istog sustava utvrđena prisutnost kemferida, diosmetina, akacetina i nekoliko derivata kafeinske kiseline. Novost i znanstveni doprinos. U istraživanju smo pokazali da med od metvice ima jedinstven fenolni profil, koji pridonosi njegovoj prepoznatljivoj aromi i snažnom antioksidativnom djelovanju. Detaljan opis rijetkih sorti meda omogućava pčelarima veću vidljivost i lakši pristup zahtjevnom tržištu prirodnih proizvoda

Low dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

Objective: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution. Methods: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells. Results: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1–4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups. Conclusions: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose

The Lifetime of FRIIs in Groups and Clusters: Implications for Radio-Mode Feedback

We determine the maximum lifetime t_max of 52 FRII radio sources found in 26 central group galaxies from cross correlation of the Berlind SDSS group catalog with the VLA FIRST survey. Mock catalogs of FRII sources were produced to match the selection criteria of FIRST and the redshift distribution of our parent sample, while an analytical model was used to calculate source sizes and luminosities. The maximum lifetime of FRII sources was then determined via a comparison of the observed and model projected length distributions. We estimate the average FRII lifetime is 1.5x10^7 years and the duty cycle is ~8x10^8 years. Degeneracies between t_max and the model parameters: jet power distribution, axial ratio, energy injection index, and ambient density introduce at most a factor of two uncertainty in our lifetime estimate. In addition, we calculate the radio active galactic nuclei (AGN) fraction in central group galaxies as a function of several group and host galaxy properties. The lifetime of radio sources recorded here is consistent with the quasar lifetime, even though these FRIIs have substantially sub-Eddington accretion. These results suggest a fiducial time frame for energy injection from AGN in feedback models. If the morphology of a given extended radio source is set by large-scale environment, while the lifetime is determined by the details of the accretion physics, this FRII lifetime is relevant for all extended radio sources.Comment: 18 pages, 7 figures. Accepted for publication in ApJ. High resolution paper available at http://www.astronomy.ohio-state.edu/~bird/BMK07.pd

A comparison of buoy meteorological systems

During May and June 2000, an intercomparison was made of buoy meteorological systems from the Woods Hole Oceanographic Institution (WHOI), the National Oceanographic and Atmospheric Administration (NOAA), Pacific Marine Environmental Laboratory (PMEL), and the Japanese Marine Science and Technology Center (JAMSTEC). Two WHOI systems mounted on a 3 m discus buoy, two PMEL systems mounted on separate buoy tower tops and one JAMSTEC system mounted on a wooden platform were lined parallel to, and 25 m from Nantucket Sound in Massachusetts. All systems used R. M. Young propeller anemometers, Rotronic relative humidity and air temperature sensors and Eppley short-wave radiation sensors. The PMEL and WHOI systems used R. M.Young self-siphoning rain gauges, while the JAMSTEC system used a Scientific Technology ORG-115 optical rain gauge. The PMEL and WHOI systems included an Eppley PIR long-wave sensor, while the JAMSTEC had no longwave sensor. The WHOI system used an AIR DB-1A barometric pressure sensor. PMEL and JAMSTEC systems used Paroscientific Digiquartz sensors. The Geophysical Instruments and Measurements Group (GIM) from Brookhaven National Laboratory (BNL) installed two Portable Radiation Package (PRP) systems that include Eppley short-wave and long-wave sensors on a platform near the site. It was apparent from the data that for most of the sensors, the correlation between data sets was better than the absolute agreement between them. The conclusions made were that the sensors and associated electronics from the three different laboratories performed comparably.Funding was provided by the National Oceanic and Atmospheric Administration under Grant Number NA96GPO429

Vertical structure of a supernova-driven turbulent magnetized ISM

Stellar feedback drives the circulation of matter from the disk to the halo of galaxies. We perform three-dimensional magnetohydrodynamic simulations of a vertical column of the interstellar medium with initial conditions typical of the solar circle in which supernovae drive turbulence and determine the vertical stratification of the medium. The simulations were run using a stable, positivity-preserving scheme for ideal MHD implemented in the FLASH code. We find that the majority (\approx 90 %) of the mass is contained in thermally-stable temperature regimes of cold molecular and atomic gas at T < 200 K or warm atomic and ionized gas at 5000 K < T < 10^{4.2} K, with strong peaks in probability distribution functions of temperature in both the cold and warm regimes. The 200 - 10^{4.2} K gas fills 50-60 % of the volume near the plane, with hotter gas associated with supernova remnants (30-40 %) and cold clouds (< 10 %) embedded within. At |z| ~ 1-2 kpc, transition-temperature (10^5 K) gas accounts for most of the mass and volume, while hot gas dominates at |z| > 3 kpc. The magnetic field in our models has no significant impact on the scale heights of gas in each temperature regime; the magnetic tension force is approximately equal to and opposite the magnetic pressure, so the addition of the field does not significantly affect the vertical support of the gas. The addition of a magnetic field does reduce the fraction of gas in the cold (< 200 K) regime with a corresponding increase in the fraction of warm (~ 10^4 K) gas. However, our models lack rotational shear and thus have no large-scale dynamo, which reduces the role of the field in the models compared to reality. The supernovae drive oscillations in the vertical distribution of halo gas, with the period of the oscillations ranging from ~ 30 Myr in the T < 200 K gas to ~ 100 Myr in the 10^6 K gas, in line with predictions by Walters & Cox.Comment: Accepted for publication in ApJ. Replacement corrects an error in the observed CNM pressure distribution in Figure 15 and associated discussio

Decreased mass specific respiration under experimental warming is robust to the microbial biomass method employed

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Ecology Letters 12 (2009): E15-E18, doi:10.1111/j.1461-0248.2009.01332.x.Hartley et al. question whether reduction in Rmass, under experimental warming, arises because of the biomass method. We show the method they treat as independent yields the same result. We describe why the substrate-depletion hypothesis cannot alone explain observed responses, and urge caution in the interpretation of the seasonal data.This research was supported by the Office of Science (BER), U.S. Department of Energy, the Andrew W. Mellon Foundation and U.S. National Science Foundation grants to the Coweeta LTER program

The radio luminosity of persistent X-ray binaries

We summarise all the reported detections of, and upper limits to, the radio emission from persistent (i.e. non-transient) X-ray binaries. A striking result is a common mean observed radio luminosity from the black hole candidates (BHCs) in the Low/Hard X-ray state and the neutron-star Z sources on the horizontal X-ray branch. This implies a common mean intrinsic radio luminosity to within a factor of twenty five (or less, if there is significant Doppler boosting of the radio emission). Unless coincidental, these results imply a physical mechanism for jet formation which requires neither a black hole event horizon or a neutron star surface. As a whole the populations of Atoll and X-ray pulsar systems are less luminous by factors of >5 and >10 at radio wavelengths than the BHCs and Z sources (while some Atoll sources have been detected, no high-field X-ray pulsar has ever been reliably detected as a radio source). We suggest that all of the persistent BHCs and the Z sources generate, at least sporadically, an outflow with physical dimensions > 1e12cm, i.e. significantly larger than the binary separations of most of the systems. We compare the physical conditions of accretion in each of the types of persistent X-ray binary and conclude that a relatively low (<1e10 G) magnetic field associated with the accreting object, and a high (>0.1 Eddington) accretion rate and/or dramatic physical change in the accretion flow, are required for formation of a radio-emitting outflow or jet.Comment: Accepted for publication in MNRA