The effect of changes in perilymphatic K+ on the vestibular evoked potential in the guinea pig

To investigate the effect on the functioning of the vestibular system of a rupture of Reissner’s membrane, artificial endolymph was injected in scala media of ten guinea pigs and vestibular evoked potentials (VsEPs), evoked by vertical acceleration pulses, were measured. Directly after injection of a sufficient volume to cause rupture, all ears showed a complete disappearance of VsEP, followed by partial recovery. To investigate the effect of perilymphatic potassium concentration on the vestibular sensory and neural structures, different concentrations of KCl were injected directly into the vestibule. The KCl injections resulted in a dose-dependent decrease of VsEP, followed by a dose-dependent slow recovery. This animal model clearly shows a disturbing effect of a higher than normal K+ concentration in perilymph on the vestibular and neural structures in the inner ear. Potassium intoxication is the most probable explanation for the observed effects. It is one of the explanations for Menière attacks

Rab6 and Rab11 Regulate Chlamydia trachomatis Development and Golgin-84-Dependent Golgi Fragmentation

Many intracellular pathogens that replicate in special membrane bound compartments exploit cellular trafficking pathways by targeting small GTPases, including Rab proteins. Members of the Chlamydiaceae recruit a subset of Rab proteins to their inclusions, but the significance of these interactions is uncertain. Using RNA interference, we identified Rab6 and Rab11 as important regulators of Chlamydia infections. Depletion of either Rab6 or Rab11, but not the other Rab proteins tested, decreased the formation of infectious particles. We further examined the interplay between these Rab proteins and the Golgi matrix components golgin-84 and p115 with regard to Chlamydia-induced Golgi fragmentation. Silencing of the Rab proteins blocked Chlamydia-induced and golgin-84 knockdown-stimulated Golgi disruption, whereas Golgi fragmentation was unaffected in p115 depleted cells. Interestingly, p115-induced Golgi fragmentation could rescue Chlamydia propagation in Rab6 and Rab11 knockdown cells. Furthermore, transport of nutrients to Chlamydia, as monitored by BODIPY-Ceramide, was inhibited by Rab6 and Rab11 knockdown. Taken together, our results demonstrate that Rab6 and Rab11 are key regulators of Golgi stability and further support the notion that Chlamydia subverts Golgi structure to enhance its intracellular development

A Structural Model of the Pore-Forming Region of the Skeletal Muscle Ryanodine Receptor (RyR1)

Ryanodine receptors (RyRs) are ion channels that regulate muscle contraction by releasing calcium ions from intracellular stores into the cytoplasm. Mutations in skeletal muscle RyR (RyR1) give rise to congenital diseases such as central core disease. The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level. Here, we report a structural model of the pore-forming region of RyR1. Molecular dynamics simulations show high ion binding to putative pore residues D4899, E4900, D4938, and D4945, which are experimentally known to be critical for channel conductance and selectivity. We also observe preferential localization of Ca2+ over K+ in the selectivity filter of RyR1. Simulations of RyR1-D4899Q mutant show a loss of preference to Ca2+ in the selectivity filter as seen experimentally. Electrophysiological experiments on a central core disease mutant, RyR1-G4898R, show constitutively open channels that conduct K+ but not Ca2+. Our simulations with G4898R likewise show a decrease in the preference of Ca2+ over K+ in the selectivity filter. Together, the computational and experimental results shed light on ion conductance and selectivity of RyR1 at an atomistic level

Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation

<p>Abstract</p> <p>Background</p> <p>Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression.</p> <p>Methods</p> <p>In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively.</p> <p>Results</p> <p>We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9), histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein and mRNA levels were increased by 1.3- and 10-fold, respectively, and acetate supplementation reduced this expression to control levels.</p> <p>Conclusion</p> <p>Based on these results, we conclude that dietary acetate supplementation attenuates neuroglial activation by effectively reducing pro-inflammatory cytokine expression by a mechanism that may involve a distinct site-specific pattern of histone acetylation and histone deacetylase expression in the brain.</p

QCD sum rule study of hidden-charm pentaquarks

We study the mass spectra of hidden-charm pentaquarks having spin $J = {1\over2}/{3\over2}/{5\over2}$ and quark contents $uud c \bar c$. We systematically construct all the relevant local hidden-charm pentaquark currents, and select some of them to perform QCD sum rule analyses. We find that the $P_c(4380)$ and $P_c(4450)$ can be identified as hidden-charm pentaquark states composed of an anti-charmed meson and a charmed baryon. Besides them, we also find a) the lowest-lying hidden-charm pentaquark state of $J^P = 1/2^-$ has the mass $4.33^{+0.17}_{-0.13}$ GeV, while the one of $J^P = 1/2^+$ is significantly higher, that is around $4.7-4.9$ GeV; b) the lowest-lying hidden-charm pentaquark state of $J^P = 3/2^-$ has the mass $4.37^{+0.18}_{-0.13}$ GeV, consistent with the $P_c(4380)$ of $J^P = 3/2^-$, while the one of $J^P = 3/2^+$ is also significantly higher, that is above $4.6$ GeV; c) the hidden-charm pentaquark state of $J^P = 5/2^-$ has a mass around $4.5-4.6$ GeV, slightly larger than the $P_c(4450)$ of $J^P = 5/2^+$.Comment: 18 pages, 5 figures and 3 tables. Accepted by Eur. Phys. J.

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Nesidioblastosis as a cause of focal pancreatic 111In-pentetreotide uptake in a patient with putative VIPoma: another differential diagnosis

Abstract In adults, nesidioblastosis is a very infrequent condition and a rare cause of symptomatic presentations. The diagnosis of nesidioblastosis may be difficult with functional and anatomical imaging modalities. “Slight focal” pancreatic abnormalities using 111In-pentetreotide imaging has been reported in patients with hyperinsulinaemic hypoglycaemia, confirmed histologically as nesidioblastosis. We describe a 60-year-old man who presented with a 1-year history of intermittent faecal urgency and refractory diarrhoea, non-specific laboratory results, negative imaging results (CT, MRI and EUS), a FNA biopsy that was inconclusive, but suggested an endocrine cell neoplasm, and a 111In-pentetreotide scan that showed a moderately intense focal uptake clearly localised to the pancreatic head on a low-dose fusion CT. The histopathology of the specimen confirmed the diagnosis of nesidioblastosis