Folic Acid Supplementation Stimulates Notch Signaling and Cell Proliferation in Embryonic Neural Stem Cells

The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14–16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system

A negative-U interpretation of the femto-second laser pulse induced crystallographic expansion of a cuprate HTSC material reported recently by Gedik et al

Gedik et al have very recently demonstrated using a pump/probe femto-second laser technique that the c-axis lattice parameter of LaCuO4+d temporarily becomes expanded by as much as 2.5% following pulsed laser optical excitation at 1.55 eV. Access to an out-of-equilibrium metastable excited state is observed to develop on a time scale of 30 ps. Subsequently the latter state decays displaying a still longer half-life of just over 300 ps. Observation of the temperature independence of this laser induced interstate transfer and of the linear dependence of the production of the metastable population upon the energy delivered per unit area by the initiating light pulse (beyond a key threshold fluence) have been interpreted by Gedik et al within the framework of standard p-to-d, O-to-Cu, charge transfer excitations. By contrast these same data are reinterpreted here in terms of pumped local pairs, within a negative-U scenario of cuprate HTSC behaviour long advocated by the current author. The d8-to-d10 laser-induced augmentation in the negative-U state population (10CuIII2-) brings marked c-axis expansion by virtue of (i) the local electrostatic charge imbalance, (ii) the increased antibonding nature of the electron double-loading d10(p6) configuration created at pair-receptive CuIII coordination units, and (iii) the layered nature of the cuprate crystal structure. The new observations are related through to Rohlers striking, standard crystallographic observations, to the stripe domain formation, and to previous pump/probe experiments.Comment: 14 pages, 1 figur

Folate Deficiency Induces Neural Stem Cell Apoptosis by Increasing Homocysteine In Vitro

Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays a central role in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In the present study, we investigated the effects of folate deficiency on the cell proliferation, cell apoptosis and homocysteine concentrations in NSCs. NSCs were isolated from fetal rats and identified as NSCs by their expression of immunoreactive nestin. Cell proliferation was quantitated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were detected and confirmed by flow cytometric analysis. We measured homocysteine concentrations in NSCs by high performance liquid chromatography and detected the expression of caspase-3 by western blot method. Folate deficiency not only decreased cell proliferation, but also increased the apoptotic rate of NSCs as demonstrated by the increased expression of early apoptotic markers such as caspase-3, compared to control group (p<0.05). Furthermore, There was a statistically significant increase in homocysteine concentration during folate deficiency in NSCs (p<0.05). These data suggest that folate affects the cell proliferation, apoptosis and homocysteine generation in NSC cells

Effect of ascorbate on plasminogen activator inhibitor-1 expression and release from platelets and endothelial cells in an in-vitro model of sepsis.

The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by ELISA. In platelets, PAI-1 release was measured after LPS, TNFα, or thrombin stimulation, with/without ascorbate. In endothelial cells, LPS and TNFα increased PAI-1 mRNA after 6-24 h, but no increase in PAI-1 release was observed; ascorbate did not affect these responses. In platelets, thrombin, but not LPS or TNFα, increased PAI-1 release; ascorbate inhibited this increase at low extracellular pH. In unstimulated endothelial cells and platelets, PAI-1 is released into the extracellular space. Thrombin increases this release from platelets; ascorbate inhibits it pH-dependently. The data suggest that ascorbate promotes fibrinolysis in the microvasculature under acidotic conditions in sepsis

Near-infrared spectroscopy of the Blue Compact Dwarf galaxy Markarian 59

We present near-infrared (NIR) spectroscopic observations of the blue compact dwarf (BCD) galaxy Mrk 59, obtained with the TripleSpec spectrograph mounted on the 3.5m APO telescope. The NIR spectrum of Mrk 59, which covers the 0.90 - 2.40 micron wavelength range, shows atomic hydrogen, molecular hydrogen, helium, sulfur and iron emission lines. The NIR data have been supplemented by a SDSS optical spectrum. We found extinction in the BCD to be low [A(V)=0.24 mag] and to be the same in both the optical and NIR ranges. The NIR light does not reveal hidden star formation. The H2 emission comes from dense clumps and the H2 vibrational emission line intensities can be accounted for by photon excitation. No shock excitation is needed. A CLOUDY photoinization model of Mrk 59 reproduces well the observed optical and NIR emission line fluxes. There is no need to invoke sources of ionization other than stellar radiation.The [FeII] 1.257 and 1.643 micron emission lines, often used as supernova shock indicators in low-excitation high-metallicity starburst galaxies, cannot play such a role in high-excitation low-metallicity HII regions such as Mrk 59.Comment: 23 pages, 3 figures, accepted for publication in the Astrophysical Journa

Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity

BACKGROUND: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. METHODS: Human CNS cultures were derived from 16–18 week gestation post-mortem fetal brain. Cultures were incubated with 400 μM ascorbate-2-O-phosphate (Asc-p) or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2) and astrocytic (GFAP) structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM). RESULTS: Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. CONCLUSIONS: Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures

Evolution with hole doping of the electronic excitation spectrum in the cuprate superconductors

The recent scanning tunnelling results of Alldredge et al on Bi-2212 and of Hanaguri et al on Na-CCOC are examined from the perspective of the BCS/BEC boson-fermion resonant crossover model for the mixed-valent HTSC cuprates. The model specifies the two energy scales controlling the development of HTSC behaviour and the dichotomy often now alluded to between nodal and antinodal phenomena in the HTSC cuprates. Indication is extracted from the data as to how the choice of the particular HTSC system sees these two basic energy scales (cursive-U, the local pair binding energy and, Delta-sc, the nodal BCS-like gap parameter) evolve with doping and change in degree of metallization of the structurally and electronically perturbed mixed-valent environment.Comment: 19 pages, 5 figure

An Analytic Variational Study of the Mass Spectrum in 2+1 Dimensional SU(3) Hamiltonian Lattice Gauge Theory

We calculate the masses of the lowest lying eigenstates of improved SU(2) and SU(3) lattice gauge theory in 2+1 dimensions using an analytic variational approach. The ground state is approximated by a one plaquette trial state and mass gaps are calculated in the symmetric and antisymmetric sectors by minimising over a suitable basis of rectangular states

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ

Global reconstruction reduces the uncertainty of oceanic nitrous oxide emissions and reveals a vigorous seasonal cycle

Assessment of the global budget of the greenhouse gas nitrous oxide ([Formula: see text]O) is limited by poor knowledge of the oceanic [Formula: see text]O flux to the atmosphere, of which the magnitude, spatial distribution, and temporal variability remain highly uncertain. Here, we reconstruct climatological [Formula: see text]O emissions from the ocean by training a supervised learning algorithm with over 158,000 [Formula: see text]O measurements from the surface ocean-the largest synthesis to date. The reconstruction captures observed latitudinal gradients and coastal hot spots of [Formula: see text]O flux and reveals a vigorous global seasonal cycle. We estimate an annual mean [Formula: see text]O flux of 4.2 ± 1.0 Tg N[Formula: see text], 64% of which occurs in the tropics, and 20% in coastal upwelling systems that occupy less than 3% of the ocean area. This [Formula: see text]O flux ranges from a low of 3.3 ± 1.3 Tg N[Formula: see text] in the boreal spring to a high of 5.5 ± 2.0 Tg N[Formula: see text] in the boreal summer. Much of the seasonal variations in global [Formula: see text]O emissions can be traced to seasonal upwelling in the tropical ocean and winter mixing in the Southern Ocean. The dominant contribution to seasonality by productive, low-oxygen tropical upwelling systems (>75%) suggests a sensitivity of the global [Formula: see text]O flux to El Niño-Southern Oscillation and anthropogenic stratification of the low latitude ocean. This ocean flux estimate is consistent with the range adopted by the Intergovernmental Panel on Climate Change, but reduces its uncertainty by more than fivefold, enabling more precise determination of other terms in the atmospheric [Formula: see text]O budget