Reactive oxygen species in Status Epilepticus

It has long been recognized that status epilepticus can cause considerable neuronal damage, and this has become one of its defining features. The mechanisms underlying this damage are less clear. Excessive activation of NMDA receptors results in large rises in internal calcium, which eventually lead to neuronal death. Between NMDA receptor activation and neuronal death are a number of intermediary steps, key amongst which is the generation of free radicals, and reactive oxygen and nitrogen species. Although it has long been thought that mitochondria are the primary source for reactive oxygen species, more recent evidence has pointed to a prominent role for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme localized in cell membranes. There is burgeoning in vivo and in vitro evidence that therapies that target the production or removal of reactive oxygen species are not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. Moreover, combining therapies targeted at inhibiting NADPH oxidase and at increasing endogenous antioxidants seem to offer the greatest benefits

How accurately do adult patients report their absence seizures?

We depend upon self-reporting to determine seizure frequency for epilepsy management decisions, but people often misreport their seizures. Here, we determined misreporting rates in adults with absence seizures, undergoing inpatient video-EEG telemetry (VET) or outpatient ambulatory electroencephalography (aEEG). Under-reporting rates were based on VET data, where behavior could be assessed, whilst over-reporting was assessed using both VET and aEEG. Forty-two patients (31 female and 11 males, median age 28.5 years) and 759 reported absence seizures were included in this study. Overall, only 24% of the 759 reported seizures had an associated EEG correlate, indicating a high over-reporting rate, which occurred in 57% of patients. Age, sex, time of epilepsy, VET versus aEEG, epilepsy syndrome or medication were not significant predictors of over-reporting. In the VET group in which we could assess both over- and under-reporting (22 patients), only 2 patients correctly reported their seizures, and patients were predominantly over-reporters or under reporters, not both. Only 26% of 423 absence seizures were reported. Use of zonisamide or valproate was associated with under-reporting, possibly through an impact on attention. These findings indicate that self-reported AS are a poor measure to use for treatment decisions due to both over- and under-reporting

Transcriptional profiling of colicin-induced cell death of Escherichia coli MG1655 identifies potential mechanisms by which bacteriocins promote bacterial diversity

We report the transcriptional response of Escherichia coli MG1655 to damage induced by colicins E3 and E9, bacteriocins that kill cells through inactivation of the ribosome and degradation of chromosomal DNA, respectively. Colicin E9 strongly induced the LexA-regulated SOS response, while colicin E3 elicited a broad response that included the induction of cold shock genes, symptomatic of translational arrest. Colicin E3 also increased the transcription of cryptic prophage genes and other laterally acquired mobile elements. The transcriptional responses to both these toxins suggest mechanisms that may promote genetic diversity in E. coli populations, pointing to a more general role for colicins in adaptive bacterial physiology than has hitherto been realized

The Velocity Dispersion Profile of the Remote Dwarf Spheroidal Galaxy Leo I: A Tidal Hit and Run?

(abridged) We present kinematic results for a sample of 387 stars located near Leo I based on spectra obtained with the MMT's Hectochelle spectrograph near the MgI/Mgb lines. We estimate the mean velocity error of our sample to be 2.4 km/s, with a systematic error of < 1 km/s. We produce a final sample of 328 Leo I red giant members, from which we measure a mean heliocentric radial velocity of 282.9 +/- 0.5 km/s, and a mean radial velocity dispersion of 9.2 +/- 0.4 km/s for Leo I. The dispersion profile of Leo I is flat out to beyond its classical `tidal' radius. We fit the profile to a variety of equilibrium dynamical models and can strongly rule out models where mass follows light. Two-component Sersic+NFW models with tangentially anisotropic velocity distributions fit the dispersion profile well, with isotropic models ruled out at a 95% confidence level. The mass and V-band mass-to-light ratio of Leo I estimated from equilibrium models are in the ranges 5-7 x 10^7 M_sun and 9-14 (solar units), respectively, out to 1 kpc from the galaxy center. Leo I members located outside a `break radius' (about 400 arcsec = 500 pc) exhibit significant velocity anisotropy, whereas stars interior appear to have isotropic kinematics. We propose the break radius represents the location of the tidal radius of Leo I at perigalacticon of a highly elliptical orbit. Our scenario can account for the complex star formation history of Leo I, the presence of population segregation within the galaxy, and Leo I's large outward velocity from the Milky Way. The lack of extended tidal arms in Leo I suggests the galaxy has experienced only one perigalactic passage with the Milky Way, implying that Leo I may have been injected into its present orbit by a third body a few Gyr before perigalacticon.Comment: ApJ accepted, 23 figures, access paper as a pdf file at http://www.astro.lsa.umich.edu/~mmateo/research.htm

Dijet Cross Section and Longitudinal Double Spin Asymmetry Measurements in Polarized Proton-proton Collisions at \sqrt{s}=200 GeV at STAR

These proceedings show the preliminary results of the dijet cross sections and the dijet longitudinal double spin asymmetries A_LL in polarized proton-proton collisions at \sqrt{s} = 200 GeV at the mid-rapidity |eta| < 0.8. The integrated luminosity of 5.39 pb^{-1} collected during RHIC Run-6 was used in the measurements. The preliminary results are presented as functions of the dijet invariant mass M_jj. The dijet cross sections are in agreement with next-to-leading-order pQCD predictions. The A_LL is compared with theoretical predictions based on various parameterizations of polarized parton distributions of the proton. Projected precision of data analyzed to date from Run-9 are shown.Comment: 8 pages, 5 figures, Proceedings of the SPIN2010 conference (Juelich, Germany, 2010

The misuse and abuse of statistics in biomedical research

Statistics are the primary tools for assessing relationships and evaluating study questions. Unfortunately, these tools are often misused, either inadvertently because of ignorance or lack of planning, or conspicuously to achieve a specified result. Data abuses include the incorrect application of statistical tests, lack of transparency and disclosure about decisions that are made, incomplete or incorrect multivariate model building, or exclusion of outliers. Individually, each of these actions may completely invalidate a study, and often studies are victim to more than one offense. Increasingly there are tools and guidance for researchers to look to, including the development of an analysis plan and a series of study specific checklists, in order to prevent or mitigate these offenses

Monosynaptic GABAergic Signaling from Dentate to CA3 with a Pharmacological and Physiological Profile Typical of Mossy Fiber Synapses

AbstractMossy fibers are the sole excitatory projection from dentate gyrus granule cells to the hippocampus, where they release glutamate, dynorphin, and zinc. In addition, mossy fiber terminals show intense immunoreactivity for the inhibitory neurotransmitter GABA. Fast inhibitory transmission at mossy fiber synapses, however, has not previously been reported. Here, we show that electrical or chemical stimuli that recruit dentate granule cells elicit monosynaptic GABAA receptor–mediated synaptic signals in CA3 pyramidal neurons. These inhibitory signals satisfy the criteria that distinguish mossy fiber–CA3 synapses: high sensitivity to metabotropic glutamate receptor agonists, facilitation during repetitive stimulation, and NMDA receptor–independent long-term potentiation. GABAergic transmission from the dentate gyrus to CA3 has major implications not only for information flow into the hippocampus but also for developmental and pathological processes involving the hippocampus

High-CO2 Cloud Radiative Forcing Feedback Over Both Land and Ocean in a Global Climate Model

A positive feedback on high-latitude winter marine climate change involving convective clouds has recently been proposed using simple models. This feedback could help explain data from equable climates, e.g., the Eocene, and might be relevant for future climate. Here this convective cloud feedback is shown to be active in an atmospheric GCM in modern configuration (CAM) at CO2 = 2240 ppm and in a coupled GCM in Eocene configuration (CCSM) at CO2 = 560 ppm. Changes in boundary conditions that increase surface temperature have a similar effect as increases in CO2 concentration. It is also found that the high-latitude winter cloud radiative forcing over land increases with increases in surface temperature due to either increased CO2 or changes in boundary conditions, which could represent an important part of the explanation for warm continental interior winter surface temperatures during equable climates. This is due to increased low-level layered clouds caused by increased relative humidity

Generalized Linear Mixed-Effects Models for the Analysis of Odor Detection Data

Olfactory detection has become a science of interest. Seven individuals’ odor detection abilities are explored and an attempt is made to characterize all subjects with one generalized linear mixed effects model. Two methods of fitting the models were used and simulations were conducted to discover which method yielded the best results