Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

Measurements of neutral vector resonance in Higgsless models at the LHC

In Higgsless models, new vector resonances appear to restore the unitarity of the W_L W_L scattering amplitude without the Higgs boson. In the ideal delocalized three site Higgsless model, one of large prodcution cross section of the neutral vector resonance (Z') at the Large Hadron Collider is the W-associated production, pp \to Z'W \to WWW. Although the dileptonic decay channnel, l\nu l'\nu 'jj, is experimentally clean to search for the Z' signals, it is difficult to reconstruct the Z' invariant mass due to the two neutrinos in the final state. We study collider signatures of Z' using the M_{T2}-Assisted On-Shell (MAOS) reconstruction of the missing neutrino momenta. We show the prospect of the Z' mass determination in the channel, l\nu l'\nu 'jj, at the Large Hadron Collider.Comment: 16 pages, 6 figures, 5 tables; v2: references added, minor corrections, version published in JHE

Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Higgs Physics: Theory

I review the theoretical aspects of the physics of Higgs bosons, focusing on the elements that are relevant for the production and detection at present hadron colliders. After briefly summarizing the basics of electroweak symmetry breaking in the Standard Model, I discuss Higgs production at the LHC and at the Tevatron, with some focus on the main production mechanism, the gluon-gluon fusion process, and summarize the main Higgs decay modes and the experimental detection channels. I then briefly survey the case of the minimal supersymmetric extension of the Standard Model. In a last section, I review the prospects for determining the fundamental properties of the Higgs particles once they have been experimentally observed.Comment: 21 pages, 15 figures. Talk given at the XXV International Symposium on Lepton Photon Interactions at High Energies (Lepton Photon 11), 22-27 August 2011, Mumbai, Indi

Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway

published_or_final_versio

First observation of psi(2S)-->K_S K_L

The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Weight management: a comparison of existing dietary approaches in a work-site setting

&lt;b&gt;OBJECTIVES:&lt;/b&gt; (1) To compare the effectiveness a 2512 kJ (600 kcal) daily energy deficit diet (ED) with a 6279 kJ (1500 kcal) generalized low-calorie diet (GLC) over a 24 week period (12 weeks weight loss plus 12 weeks weight maintenance). (2) To determine if the inclusion of lean red meat at least five times per week as part of a slimming diet is compatible with weight loss in comparison with a diet that excludes lean red meat. DESIGN: Randomized controlled trial. &lt;b&gt;SETTING:&lt;/b&gt; Large petrochemical work-site. &lt;b&gt;PARTICIPANTS:&lt;/b&gt; One-hundred and twenty-two men aged between 18 and 55 y. &lt;b&gt;MAIN OUTCOME MEASURES:&lt;/b&gt; Weight loss and maintenance of weight loss. &lt;b&gt;INTERVENTION:&lt;/b&gt; Eligible volunteers were randomized to one of the four diet=meat combinations (ED meat, ED no meat, GLC meat, GLC no meat). One-third of subjects in each diet/meat combination were randomized to an initial control period prior to receiving dietary advice. All subjects attended for review every 2 weeks during the weight loss period. For the 12 week structured weight maintenance phase, individualized energy prescriptions were re-calculated for the ED group as 1.4 (activity factor)x basal metabolic rate. Healthy eating advice was reviewed with subjects in the GLC group. All subjects were contacted by electronic mail at 2 week intervals and anthropometric and dietary information requested. &lt;b&gt;RESULTS:&lt;/b&gt; No difference was evident between diet groups in mean weight loss at 12 weeks (4.3 (s.d. 3.4) kg ED group vs 5.0 (s.d. 3.5) kg GLC group, P=0.34). Mean weight loss was closer to the intended weight loss in the 2512 kJ (600 kcal) ED group. The dropout rate was also lower than the GLC group. The inclusion of lean red meat in the diet on at least five occasions per week did not impair weight loss. Mean weight gain following 12 weeks weight maintenance was þ1.1 (s.d. 1.8) kg, P&lt;0.0001. No differences were found between groups. &lt;b&gt;CONCLUSIONS:&lt;/b&gt; This study has shown that the individualized 2512 kJ (600 kcal) ED approach was no more effective in terms of weight loss than the 6279 kJ (1500 kcal) GLC approach. However the ED approach might be considered preferable as compliance was better with this less demanding prescription. In terms of weight loss the elimination of red meat from the diet is unnecessary. The weight maintenance intervention was designed as a low-input approach, however weight regain was significant and weight maintenance strategies require further development

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Next-to-leading order QCD corrections to Higgs boson production in association with a photon via weak-boson fusion at the LHC

Higgs boson production in association with a hard central photon and two forward tagging jets is expected to provide valuable information on Higgs boson couplings in a range where it is difficult to disentangle weak-boson fusion processes from large QCD backgrounds. We present next-to-leading order QCD corrections to Higgs production in association with a photon via weak-boson fusion at a hadron collider in the form of a flexible parton-level Monte Carlo program. The QCD corrections to integrated cross sections are found to be small for experimentally relevant selection cuts, while the shape of kinematic distributions can be distorted by up to 20% in some regions of phase space. Residual scale uncertainties at next-to-leading order are at the few-percent level.Comment: 17 pages, 7 figures, 1 tabl