Long Lasting Modulation of Cortical Oscillations after Continuous Theta Burst Transcranial Magnetic Stimulation

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4–7.5 Hz), low α (8–9.5 Hz), µ (10–12.5 Hz), low β (13–19.5 Hz), and high β (20–30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of β frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Conserved and variable correlated mutations in the plant MADS protein network

<p>Abstract</p> <p>Background</p> <p>Plant MADS domain proteins are involved in a variety of developmental processes for which their ability to form various interactions is a key requisite. However, not much is known about the structure of these proteins or their complexes, whereas such knowledge would be valuable for a better understanding of their function. Here, we analyze those proteins and the complexes they form using a correlated mutation approach in combination with available structural, bioinformatics and experimental data.</p> <p>Results</p> <p>Correlated mutations are affected by several types of noise, which is difficult to disentangle from the real signal. In our analysis of the MADS domain proteins, we apply for the first time a correlated mutation analysis to a family of interacting proteins. This provides a unique way to investigate the amount of signal that is present in correlated mutations because it allows direct comparison of mutations in various family members and assessing their conservation. We show that correlated mutations in general are conserved within the various family members, and if not, the variability at the respective positions is less in the proteins in which the correlated mutation does not occur. Also, intermolecular correlated mutation signals for interacting pairs of proteins display clear overlap with other bioinformatics data, which is not the case for non-interacting protein pairs, an observation which validates the intermolecular correlated mutations. Having validated the correlated mutation results, we apply them to infer the structural organization of the MADS domain proteins.</p> <p>Conclusion</p> <p>Our analysis enables understanding of the structural organization of the MADS domain proteins, including support for predicted helices based on correlated mutation patterns, and evidence for a specific interaction site in those proteins.</p

Reduced Stability and Increased Dynamics in the Human Proliferating Cell Nuclear Antigen (PCNA) Relative to the Yeast Homolog

Proliferating Cell Nuclear Antigen (PCNA) is an essential factor for DNA replication and repair. PCNA forms a toroidal, ring shaped structure of 90 kDa by the symmetric association of three identical monomers. The ring encircles the DNA and acts as a platform where polymerases and other proteins dock to carry out different DNA metabolic processes. The amino acid sequence of human PCNA is 35% identical to the yeast homolog, and the two proteins have the same 3D crystal structure. In this report, we give evidence that the budding yeast (sc) and human (h) PCNAs have highly similar structures in solution but differ substantially in their stability and dynamics. hPCNA is less resistant to chemical and thermal denaturation and displays lower cooperativity of unfolding as compared to scPCNA. Solvent exchange rates measurements show that the slowest exchanging backbone amides are at the β-sheet, in the structure core, and not at the helices, which line the central channel. However, all the backbone amides of hPCNA exchange fast, becoming undetectable within hours, while the signals from the core amides of scPCNA persist for longer times. The high dynamics of the α-helices, which face the DNA in the PCNA-loaded form, is likely to have functional implications for the sliding of the PCNA ring on the DNA since a large hole with a flexible wall facilitates the establishment of protein-DNA interactions that are transient and easily broken. The increased dynamics of hPCNA relative to scPCNA may allow it to acquire multiple induced conformations upon binding to its substrates enlarging its binding diversity

Salsolinol Facilitates Glutamatergic Transmission to Dopamine Neurons in the Posterior Ventral Tegmental Area of Rats

Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA) partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D1 receptors (D1Rs). In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol

Distinct Expression Profiles and Different Functions of Odorant Binding Proteins in Nilaparvata lugens Stål

Background: Odorant binding proteins (OBPs) play important roles in insect olfaction. The brown planthopper (BPH), Nilaparvata lugens Sta˚l (Delphacidae, Auchenorrhyncha, Hemiptera) is one of the most important rice pests. Its monophagy (only feeding on rice), wing form (long and short wing) variation, and annual long distance migration (seeking for rice plants of high nutrition) imply that the olfaction would play a central role in BPH behavior. However, the olfaction related proteins have not been characterized in this insect. Methodology/Principal Findings: Full length cDNA of three OBPs were obtained and distinct expression profiles were revealed regarding to tissue, developmental stage, wing form and gender for the first time for the species. The results provide important clues in functional differentiation of these genes. Binding assays with 41 compounds demonstrated that NlugOBP3 had markedly higher binding ability and wider binding spectrum than the other two OBPs. Terpenes and Ketones displayed higher binding while Alkanes showed no binding to the three OBPs. Focused on NlugOBP3, RNA interference experiments showed that NlugOBP3 not only involved in nymph olfaction on rice seedlings, but also had non-olfactory functions, as it was closely related to nymph survival. Conclusions: NlugOBP3 plays important roles in both olfaction and survival of BPH. It may serve as a potential target fo

AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below