Persistent Sodium Currents through Brain Sodium Channels Induced by G Protein βγ Subunits

AbstractPersistent Na+currents are thought to be important for integration of neuronal responses. Here, we show that βγ subunits of G proteins can induce persistent Na+ currents. Coexpression of Gβ2γ3, Gβ1γ3, or Gβ5γ3, but not Gβ1γ1 subunits with rat brain type IIA Na+ channel α subunits in tsA-201 cells greatly enhances a component of Na+ current with a normal voltage dependence of activation but with dramatically slowed and incomplete inactivation and with steady-state inactivation shifted +37 mV. Synthetic peptides containing the proposed Gβγ-binding motif, Gln-X-X-Glu-Arg, from either adenylyl cyclase 2 or the Na+ channel α subunit C-terminal domain reversed the effect of Gβ2γ3 subunits. These results are consistent with direct binding of Gβγ subunits to the C-terminal domain of the Na+ channel, stabilizing a gating mode responsible for slowed and persistent Na+ current. Modulation of Na+ channel gating by Gβγ subunits is expected to have profound effects on neuronal excitability

Visualizing DIII-D Tokarnak Magnetic Field Lines

We demonstrate the use of a combination of perceptually effective techniques for visualizing magnetic field data from the DIII-D Tokamak. These techniques can be implemented to run very efficiently on machines with hardware support for OpenGL. Interactive speeds facilitate clear communication of magnetic field structure, enhancing fusion scientists' understanding of their data, and thereby accelerating their research

Isovector Giant Dipole Resonance of Stable Nuclei in a Consistent Relativistic Random Phase Approximation

A fully consistent relativistic random phase approximation is applied to study the systematic behavior of the isovector giant dipole resonance of nuclei along the $\beta$-stability line in order to test the effective Lagrangians recently developed. The centroid energies of response functions of the isovector giant dipole resonance for stable nuclei are compared with the corresponding experimental data and the good agreement is obtained. It is found that the effective Lagrangian with an appropriate nuclear symmetry energy, which can well describe the ground state properties of nuclei, could also reproduce the isovector giant dipole resonance of nuclei along the $\beta$-stability line.Comment: 4 pages, 1 Postscript figure, to be submitted to Chin.Phys.Let

Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat.

Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nM) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 ± 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 μg, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 ± 20, leptin, 135 ± 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 ± 39, leptin, 452 ± 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 ± 38; NMU IgG, 342 ± 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation. Copyright © 2006 by The Endocrine Society

Invisible Inequality Leads to Punishing the Poor and Rewarding the Rich

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Four experiments examine how lack of awareness of inequality affect behaviour towards the rich and poor. In experiment 1, participants who became aware that wealthy individuals donated a smaller percentage of their income switched from rewarding the wealthy to rewarding the poor. In experiments 2 and 3, participants who played a public goods game— and were assigned incomes reflective of the U.S. income distribution either at random or on merit—punished the poor (for small absolute contributions) and rewarded the rich (for large absolute contributions) when incomes were unknown; when incomes were revealed, participants punished the rich (for the low percentage of income contributed) and rewarded the poor (for their high percentage). In experiment 4, participants provided with public education contributions for five New York school districts levied additional taxes on mostly poorer school districts when incomes were unknown, but targeted wealthier districts when incomes were revealed. These results shed light on how income transparency shapes preferences for equity and redistribution. We discuss implications for policy-makers

Antifungal Activity of Natural Naphthoquinones and Anthraquinones against Madurella mycetomatis

Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal drugs. In this study, a series of natural naphthoquinones and anthraquinones was evaluated for their activity against Madurella mycetomatis, which is the most common causative agent of eumycetoma. The metabolic activity of Madurella mycetomatis as well as the viability of Galleria mellonella larvae upon treatment with quinones was investigated. Several hydroxy-substituted naphthoquinones exhibited activity against Madurella mycetomatis. In particular, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) was identified as a considerably active antifungal compound against Madurella mycetomatis (IC50=1.4 μM), while it showed reduced toxicity to Galleria mellonella larvae, which is a well-established in vivo invertebrate model for mycetoma drug studies

Genetics of diabetic microvascular disease

Publisher Copyright: © 2020 John Wiley & Sons, Inc.Diabetic microvascular complications, affecting the kidneys, retina, and the nervous system, are a heavy burden for both the diabetic individual and society. The complications seem to cluster in families suggesting a genetic component in their pathogenesis. However, the actual genetic factors have long remained unknown. During the past few years, major advances have been made with large-scale genetic studies that have identified common genetic risk factors, e.g. in the AFF3 and CNKSR3 gene loci affecting the risk of diabetic kidney disease (DKD) end-stage renal disease. There is increasing evidence that genetic factors affecting kidney disease in non-diabetic individuals also affect the risk in individuals with type 2 diabetes (T2D), while less evidence is found for individuals with type 1 diabetes (T1D). While genetic explorations for diabetic retinopathy remain limited in sample size, a recent genome-wide association study (GWAS) identified variants associated with retinopathy on the GRB2 gene. Nevertheless, the field is still lacking strong validated genetic markers. In the future, better phenotyping, larger studies, and exploration of the rare variation are essential to identify the genetic causes behind diabetic microvascular complications, and to understand the interplay between genes and environment.Peer reviewe