Delayed administration of VEGF rescues spinal motor neurons from death with a short effective time frame in excitotoxic experimental models in vivo

VEGF (vascular endothelial growth factor) prevents neuronal death in different models of ALS (amyotrophic lateral sclerosis), but few studies have addressed the efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical point when considering VEGF as a potential therapeutic target for ALS. We studied the capability of VEGF to protect motor neurons after an excitotoxic challenge in two models of spinal neurodegeneration in rats induced by AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) administered either chronically with osmotic minipumps or acutely by microdialysis. VEGF was administered through osmotic minipumps in the chronic model or injected intracerebroventricularly in the acute model, and its effects were assessed by immunohistochemical and histological analyses and motor performance tests. In the chronic model, VEGF stopped the progression of the paralysis and protected motor neurons when administered after AMPA before the onset of the motor symptoms, whereas no protection was observed when administered after the onset. VEGF was also protective in the acute model, but with a short time window, since the protection was effective when administered 1 h but not 2 h after AMPA. Our results indicate that while VEGF has an indubitable neuroprotective effect, its therapeutic potential for halting or delaying the progression of motor neuron loss in ALS would likely have a short effective time frame

Experimental models for the study of neurodegeneration in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause, characterized by the selective and progressive death of both upper and lower motoneurons, leading to a progressive paralysis. Experimental animal models of the disease may provide knowledge of the pathophysiological mechanisms and allow the design and testing of therapeutic strategies, provided that they mimic as close as possible the symptoms and temporal progression of the human disease. The principal hypotheses proposed to explain the mechanisms of motoneuron degeneration have been studied mostly in models in vitro, such as primary cultures of fetal motoneurons, organotypic cultures of spinal cord sections from postnatal rodents and the motoneuron-like hybridoma cell line NSC-34. However, these models are flawed in the sense that they do not allow a direct correlation between motoneuron death and its physical consequences like paralysis. In vivo, the most widely used model is the transgenic mouse that bears a human mutant superoxide dismutase 1, the only known cause of ALS. The major disadvantage of this model is that it represents about 2%–3% of human ALS. In addition, there is a growing concern on the accuracy of these transgenic models and the extrapolations of the findings made in these animals to the clinics. Models of spontaneous motoneuron disease, like the wobbler and pmn mice, have been used aiming to understand the basic cellular mechanisms of motoneuron diseases, but these abnormalities are probably different from those occurring in ALS. Therefore, the design and testing of in vivo models of sporadic ALS, which accounts for >90% of the disease, is necessary. The main models of this type are based on the excitotoxic death of spinal motoneurons and might be useful even when there is no definitive demonstration that excitotoxicity is a cause of human ALS. Despite their difficulties, these models offer the best possibility to establish valid correlations between cellular alterations and motor behavior, although improvements are still necessary in order to produce a reliable and integrative model that accurately reproduces the cellular mechanisms of motoneuron degeneration in ALS

Indication of Superconductivity at 35 K in Graphite-Sulfur Composites

We report magnetization measurements performed on graphite--sulfur composites which demonstrate a clear superconducting behavior below the critical temperature T$_{c0}$ = 35 K. The Meissner-Ochsenfeld effect, screening supercurrents, and magnetization hysteresis loops characteristic of type-II superconductors were measured. The results indicate that the superconductivity occurs in a small sample fraction, possibly related to the sample surface.Comment: published versio

Mass-luminosity relation for FGK main sequence stars: metallicity and age contributions

The stellar mass-luminosity relation (MLR) is one of the most famous empirical "laws", discovered in the beginning of the 20th century. MLR is still used to estimate stellar masses for nearby stars, particularly for those that are not binary systems, hence the mass cannot be derived directly from the observations. It's well known that the MLR has a statistical dispersion which cannot be explained exclusively due to the observational errors in luminosity (or mass). It is an intrinsic dispersion caused by the differences in age and chemical composition from star to star. In this work we discuss the impact of age and metallicity on the MLR. Using the recent data on mass, luminosity, metallicity, and age for 26 FGK stars (all members of binary systems, with observational mass-errors <= 3%), including the Sun, we derive the MLR taking into account, separately, mass-luminosity, mass-luminosity-metallicity, and mass-luminosity-metallicity-age. Our results show that the inclusion of age and metallicity in the MLR, for FGK stars, improves the individual mass estimation by 5% to 15%.Comment: 7 pages, 4 figures, 1 table, accepted in Astrophysics and Space Scienc

Fear of falling and postural reactivity in patients with glaucoma

Purpose To investigate the relationship between postural metrics obtained by dynamic visual stimulation in a virtual reality environment and the presence of fear of falling in glaucoma patients. Methods This cross-sectional study included 35 glaucoma patients and 26 controls that underwent evaluation of postural balance by a force platform during presentation of static and dynamic visual stimuli with head-mounted goggles (Oculus Rift). In dynamic condition, a peripheral translational stimulus was used to induce vection and assess postural reactivity. Standard deviations of torque moments (SDTM) were calculated as indicative of postural stability. Fear of falling was assessed by a standardized questionnaire. The relationship between a summary score of fear of falling and postural metrics was investigated using linear regression models, adjusting for potentially confounding factors. Results Subjects with glaucoma reported greater fear of falling compared to controls (-0.21 vs. 0.27P = 0.039). In glaucoma patients, postural metrics during dynamic visual stimulus were more associated with fear of falling (R-2 = 18.8%P = 0.001) than static (R-2 = 3.0%P = 0.005) and dark field (R-2 = 5.7%P = 0.007) conditions. In the univariable model, fear of falling was not significantly associated with binocular standard perimetry mean sensitivity (P = 0.855). In the multivariable model, each 1 Nm larger SDTM in anteroposterior direction during dynamic stimulus was associated with a worsening of 0.42 units in the fear of falling questionnaire score (P = 0.001). Conclusion In glaucoma patients, postural reactivity to a dynamic visual stimulus using a virtual reality environment was more strongly associated with fear of falling than visual field testing and traditional balance assessment.National Institutes of Health/National Eye Institute [EY021818]Brazilian National Council for Scientific and Technological Development (CNPq) [233829/2014-8]Alcon Laboratories (Fort Worth, TX)Bausch & Lomb (Garden City, NY)Carl Zeiss Meditec (Jena, Germany)Heidelberg Engineering (Heidelberg, Germany)Merck (White House Station, NJ)Allergan (Irvine, CA)Sensimed (Lausanne, Switzerland)Topcon (Livermore, CA)Reichert (Dewey, NY)National Eye Institute (Bethesda, MD)Novartis (Basel, Switzerland)nGoggle (San Diego, CA)Duke Univ, Duke Eye Ctr, Durham, NC 27708 USADuke Univ, Dept Ophthalmol, Durham, NC 27708 USAUniv Fed Sao Paulo, Dept Ophthalmol & Vis Sci, Sao Paulo, BrazilUniv Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USAUniv Fed Sao Paulo, Dept Ophthalmol & Vis Sci, Sao Paulo, BrazilCNPq [233829/2014-8]Web of Scienc

Evidence of Josephson-coupled superconducting regions at the interfaces of Highly Oriented Pyrolytic Graphite

Transport properties of a few hundreds of nanometers thick (in the graphene plane direction) lamellae of highly oriented pyrolytic graphite (HOPG) have been investigated. Current-Voltage characteristics as well as the temperature dependence of the voltage at different fixed input currents provide evidence for Josephson-coupled superconducting regions embedded in the internal two-dimensional interfaces, reaching zero resistance at low enough temperatures. The overall behavior indicates the existence of superconducting regions with critical temperatures above 100 K at the internal interfaces of oriented pyrolytic graphite.Comment: 6 Figures, 5 page

Effects of Ozone Oxidative Preconditioning on TNF-α Release and Antioxidant-Prooxidant Intracellular Balance in Mice During Endotoxic Shock

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-α levels and as a modulator of oxidative stress on hepatic tissue in endotoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-α was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-α levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-α levels in a dose-dependent manner. Statistically significant decreases in TNF-α levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-α production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems

Rare glutamic acid methyl ester peptaibols from Sepedonium ampullosporum Damon KSH 534 exhibit promising antifungal and anticancer activity

Fungal species of genus Sepedonium are rich sources of diverse secondary metabolites (e.g., alkaloids, peptaibols), which exhibit variable biological activities. Herein, two new peptaibols, named ampullosporin F (1) and ampullosporin G (2), together with five known compounds, ampullosporin A (3), peptaibolin (4), chrysosporide (5), c(Trp-Ser) (6) and c(Trp-Ala) (7), have been isolated from the culture of Sepedonium ampullosporum Damon strain KSH534. The structures of 1 and 2 were elucidated based on ESI-HRMS(n) experiments and intense 1D and 2D NMR analyses. The sequence of ampullosporin F (1) was determined to be Ac-Trp(1)-Ala(2)-Aib(3)-Aib(4)-Leu(5)-Aib(6)-Gln(7)-Aib(8)-Aib(9)-Aib(10)-GluOMe(11)-Leu(12)-Aib(13)-Gln(14)-Leuol(15), while ampullosporin G (2) differs from 1 by exchanging the position of Gln(7) with GluOMe(11). Furthermore, the total synthesis of 1 and 2 was carried out on solid-phase to confirm the absolute configuration of all chiral amino acids as L. In addition, ampullosporin F (1) and G (2) showed significant antifungal activity against B. cinerea and P. infestans, but were inactive against S. tritici. Cell viability assays using human prostate (PC-3) and colorectal (HT-29) cancer cells confirmed potent anticancer activities of 1 and 2. Furthermore, a molecular docking study was performed in silico as an attempt to explain the structure-activity correlation of the characteristic ampullosporins (1–3)

Breaking the Disk/Halo Degeneracy with Gravitational Lensing

The degeneracy between the disk and the dark matter contribution to galaxy rotation curves remains an important uncertainty in our understanding of disk galaxies. Here we discuss a new method for breaking this degeneracy using gravitational lensing by spiral galaxies, and apply this method to the spiral lens B1600+434 as an example. The combined image and lens photometry constraints allow models for B1600+434 with either a nearly singular dark matter halo, or a halo with a sizable core. A maximum disk model is ruled out with high confidence. Further information, such as the circular velocity of this galaxy, will help break the degeneracies. Future studies of spiral galaxy lenses will be able to determine the relative contribution of disk, bulge, and halo to the mass in the inner parts of galaxies.Comment: Replaced with minor revisions, a typo fixed, and reference added; 21 pages, 8 figures, ApJ accepte