A method for reducing animal use whilst maintaining statistical power in electrophysiological recordings from rodent nerves

The stimulus evoked compound action potential, recorded from ex vivo nerve trunks such as the rodent optic and sciatic nerve, is a popular model system used to study aspects of nervous system metabolism. This includes (1) the role of glycogen in supporting axon conduction, (2) the injury mechanisms resulting from metabolic insults, and (3) to test putative benefits of clinically relevant neuroprotective strategies. We demonstrate the benefit of simultaneously recording from pairs of nerves in the same superfusion chamber compared with conventional recordings from single nerves. Experiments carried out on mouse optic and sciatic nerves demonstrate that our new recording configuration decreased the relative standard deviation from samples when compared with recordings from an equivalent number of individually recorded nerves. The new method reduces the number of animals required to produce equivalent Power compared with the existing method, where single nerves are used. Adopting this method leads to increased experimental efficiency and productivity. We demonstrate that reduced animal use and increased Power can be achieved by recording from pairs of rodent nerve trunks simultaneously

Energy Metabolism in Mouse Sciatic Nerve A Fibres during Increased Energy Demand

The ability of sciatic nerve A fibres to conduct action potentials relies on an adequate supply of energy substrate, usually glucose, to maintain necessary ion gradients. Under our ex vivo experimental conditions, the absence of exogenously applied glucose triggers Schwann cell glycogen metabolism to lactate, which is transported to axons to fuel metabolism, with loss of the compound action potential (CAP) signalling glycogen exhaustion. The CAP failure is accelerated if tissue energy demand is increased by high-frequency stimulation (HFS) or by blocking lactate uptake into axons using cinnemate (CIN). Imposing HFS caused CAP failure in nerves perfused with 10 mM glucose, but increasing glucose to 30 mM fully supported the CAP and promoted glycogen storage. A combination of glucose and lactate supported the CAP more fully than either substrate alone, indicating the nerve is capable of simultaneously metabolising each substrate. CAP loss resulting from exposure to glucose-free artificial cerebrospinal fluid (aCSF) could be fully reversed in the absence of glycogen by addition of glucose or lactate when minimally stimulated, but imposing HFS resulted in only partial CAP recovery. The delayed onset of CAP recovery coincided with the release of lactate by Schwann cells, suggesting that functional Schwann cells are a prerequisite for CAP recovery

The Halos and Environments of Nearby Galaxies (HERON) Survey

We have used dedicated 0.7m telescopes in California and Israel to image the halos of ~200 galaxies in the Local Volume to 29 mag/sq arcsec, the sample mainly drawn from the 2MASS Large Galaxy Atlas (LGA). We supplement the LGA sample with dwarf galaxies and more distant giant ellipticals. Low surface brightness halos exceeding 50 kpc in diameter are found only in galaxies more luminous than L* and classic interaction signatures are relatively infrequent. Halo diameter is correlated with total galaxy luminosity. Extended low surface brightness halos are present even in galaxies as faint as M_V=-18. Edge-on galaxies with boxy bulges tend to lack extended spheroidal halos, while those with large classical bulges exhibit extended round halos, supporting the notions that boxy or barlike bulges originate from disks. Most face-on spiral galaxies present features that appear to be irregular extensions of spiral arms, although rare cases show smooth boundaries with no sign of star formation. Although we serendipitously discovered a dwarf galaxy undergoing tidal disruption in the halo of NGC 4449, we found no comparable examples in our general survey. A search for similar examples in the Local Volume identified hcc087, a tidally disrupting dwarf galaxy in the Hercules Cluster, but we do not confirm an anomalously large half-light radius reported for the dwarf VCC 1661

Hypothermic neuroprotection during reperfusion following exposure to aglycemia in central white matter is mediated by acidification

Hypoglycemia is a common iatrogenic consequence of type 1 diabetes therapy that can lead to central nervous system injury and even death if untreated. In the absence of clinically effective neuroprotective drugs we sought to quantify the putative neuroprotective effects of imposing hypothermia during the reperfusion phase following aglycemic exposure to central white matter. Mouse optic nerves (MONs), central white matter tracts, were superfused with oxygenated artificial cerebrospinal fluid (aCSF) containing 10 mM glucose at 37°C. The supramaximal compound action potential (CAP) was evoked and axon conduction was assessed as the CAP area. Extracellular lactate was measured using an enzyme biosensor. Exposure to aglycemia, simulated by omitting glucose from the aCSF, resulted in axon injury, quantified by electrophysiological recordings, electron microscopic analysis confirming axon damage, the extent of which was determined by the duration of aglycemia exposure. Hypothermia attenuated injury. Exposing MONs to hypothermia during reperfusion resulted in improved CAP recovery compared with control recovery measured at 37°C, an effect attenuated in alkaline aCSF. Hypothermia decreases pH implying that the hypothermic neuroprotection derives from interstitial acidification. These results have important clinical implications demonstrating that hypothermic intervention during reperfusion can improve recovery in central white matter following aglycemia

The Lantern Vol. 55, No. 1, Fall 1988

• The Third Grade Gorilla • Friend, I Am Not Yet A Poet • Twisted • The Final Journey • Ritu Miltonis • Hearthside • The Ogre • O Indestructible Everlasting • December 1, 1988 • Our Church • Louise • Gazebo For Learned Women • Hanging Mirror • Of Football and Flashlights • The Ragged Brown Peasant • Judgement of the Serpent • Sidewalk Wars • I Guess That\u27s Why I Went Awayhttps://digitalcommons.ursinus.edu/lantern/1133/thumbnail.jp

The Lantern Vol. 55, No. 1, Fall 1988

• The Third Grade Gorilla • Friend, I Am Not Yet A Poet • Twisted • The Final Journey • Ritu Miltonis • Hearthside • The Ogre • O Indestructible Everlasting • December 1, 1988 • Our Church • Louise • Gazebo For Learned Women • Hanging Mirror • Of Football and Flashlights • The Ragged Brown Peasant • Judgement of the Serpent • Sidewalk Wars • I Guess That\u27s Why I Went Awayhttps://digitalcommons.ursinus.edu/lantern/1133/thumbnail.jp

Hydrogenation of Organic Matter as a Terminal Electron Sink Sustains High CO2:CH4 Production Ratios During Anaerobic Decomposition

Once inorganic electron acceptors are depleted, organic matter in anoxic environments decomposes by hydrolysis, fermentation, and methanogenesis, requiring syntrophic interactions between microorganisms to achieve energetic favorability. In this classic anaerobic food chain, methanogenesis represents the terminal electron accepting (TEA) process, ultimately producing equimolar CO2 and CH4 for each molecule of organic matter degraded. However, CO2:CH4 production in Sphagnum-derived, mineral-poor, cellulosic peat often substantially exceeds this 1:1 ratio, even in the absence of measureable inorganic TEAs. Since the oxidation state of C in both cellulose-derived organic matter and acetate is 0, and CO2 has an oxidation state of +4, if CH4 (oxidation state -4) is not produced in equal ratio, then some other compound(s) must balance CO2 production by receiving 4 electrons. Here we present evidence for ubiquitous hydrogenation of diverse unsaturated compounds that appear to serve as organic TEAs in peat, thereby providing the necessary electron balance to sustain CO2:CH4 \u3e1. While organic electron acceptors have previously been proposed to drive microbial respiration of organic matter through the reversible reduction of quinone moieties, the hydrogenation mechanism that we propose, by contrast, reduces C-C double bonds in organic matter thereby serving as 1) a terminal electron sink, 2) a mechanism for degrading complex unsaturated organic molecules, 3) a potential mechanism to regenerate electron-accepting quinones, and, in some cases, 4) a means to alleviate the toxicity of unsaturated aromatic acids. This mechanism for CO2 generation without concomitant CH4 production has the potential to regulate the global warming potential of peatlands by elevating CO2:CH4 production ratios

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others