The H-current secures action potential transmission at high frequencies in rat cerebellar parallel fibers

Most axons in the mammalian brain are unmyelinated and thin with pre-synaptic specializations (boutons) along their entire paths. The parallel fibers in the cerebellum are examples of such axons. Unlike most thin axons they have only one branch point. The granule cell soma, where they originate, can fire bursts of action potentials with spike intervals of about 2 ms. An important question is whether the axons are able to propagate spikes with similarly short intervals. By using extracellular single-unit and population-recording methods we showed that parallel fibers faithfully conduct spikes at high frequencies over long distances. However, when adding 20 μ m ZD7288 or 1 m m Cs⁺, or reducing the temperature from 35 to 24°C, the action potentials often failed even when successfully initiated. Ba²⁺(1 m m ), which blocks Kir channels, did not reproduce these effects. The conduction velocity was reduced by ZD7288 but not by Ba²⁺. This suggests that the parallel fibers have an H-current that is active at rest and that is important for their frequency-following properties. Interestingly, failures occurred only when the action potential had to traverse the axonal branch point, suggesting that the branch point is the weakest point in these axons.     

Insights into non-noble metal based nanophotonics: exploration of Cr-coated ZnO nanorods for optoelectronic applications

Herein, the room temperature photoluminescence and Raman spectra of hydrothermally grown ZnO nanorods coated with Cr are investigated for optoelectronic applications. A thorough examination of the photoluminescence spectra of Cr coated ZnO nanorods showed the suppression of deep level emissions by more than twenty five times with Cr coating compared to that of pristine ZnO nanorods. Moreover, the underlying mechanism was proposed and can be attributed to the formation of Schottky contacts between Cr and ZnO resulting in defect passivation, weak exciton–plasmon coupling, enhanced electric field effect and formation of hot carriers due to interband transitions. Interestingly, with the increase in sputtering time, the ratio of the intensities corresponding to the band gap emission and deep level emission was observed to increase from 6.2 to 42.7, suggesting its application for UV only emission. Further, a planar photodetector was fabricated (Ag–ZnO–Ag planar configuration) and it was observed that the dark current value got reduced by more than ten times with Cr coating, thereby opening up its potential for transistor applications. Finally, Cr coated ZnO nanorods were employed for green light sensing. Our results demonstrated that ZnO nanorods decorated with Cr shed light on developing stable and high-efficiency non-noble metal based nanoplasmonic devices such as photodetectors, phototransistors and solar cells.

Herein, the room temperature photoluminescence and Raman spectra of hydrothermally grown ZnO nanorods coated with Cr are investigated for optoelectronic applications.     

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo

We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.     

Rho Kinase Regulates Induction of T-Cell Immune Dysfunction in Abdominal Sepsis

T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present study, we hypothesized that Rho kinase signaling might regulate induction of T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were treated with the specific Rho kinase inhibitor Y-27632 (5 mg/kg of body weight) prior to cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation, and percentage of regulatory T cells (CD4⁺ CD25⁺ Foxp3⁺) were determined by flow cytometry. Formation of gamma interferon (IFN-γ) and interleukin 4 (IL-4) in the spleen and plasma levels of HMBG1, IL-17, and IL-6 were quantified by use of enzyme-linked immunosorbent assay (ELISA). It was found that CLP evoked apoptosis and decreased proliferation in splenic CD4 T cells. Inhibition of Rho kinase activity decreased apoptosis and enhanced proliferation of CD4 T cells in septic animals. In addition, CLP-evoked induction of regulatory T cells in the spleen was abolished by Rho kinase inhibition. CLP reduced the levels of IFN-γ and IL-4 in the spleen. Pretreatment with Y-27632 inhibited the sepsis-induced decrease in IFN-γ but not IL-4 formation in the spleen. CLP increased plasma levels of high-mobility group box 1 (HMGB1) by 20-fold and IL-6 by 19-fold. Inhibition of Rho kinase decreased this CLP-evoked increase of HMGB1, IL-6, and IL-17 levels in the plasma by more than 60%, suggesting that Rho kinase regulates systemic inflammation in sepsis. Moreover, we observed that pretreatment with Y-27632 abolished CLP-induced bacteremia. Together, our novel findings indicate that Rho kinase is a powerful regulator of T-cell immune dysfunction in abdominal sepsis. Thus, targeting Rho kinase signaling might be a useful strategy to improve T-cell immunity in patients with abdominal sepsis.     

Exploiting the potential of routine data to better understand the disease burden posed by allergic disorders

The Department of Health and Scottish Executive are currently undertaking independent reviews of allergy services in England (and Wales) and Scotland. Each review will assess the disease burden posed by allergic problems, involving secondary analyses of routine National Health Service (NHS) datasets. Major suggestions for re-structuring and/or re-focusing the NHS efforts to better deal with allergic disease are anticipated. The UK has some of the best datasets of routine health data in the world, but despite their strengths, they have important limitations. These include gaps in data collection, particularly in relation to monitoring of Accident & Emergency and out-patient consultations, and in-patient prescribing, thereby resulting in considerable under-estimates of hospital workload. The current gaps in service monitoring are likely to under-estimate the burden and workload associated with allergic problems, particularly in secondary care. One major limitation of existing data sources is the general inability to link individual patient level data between different datasets. By unlocking this potential there are very considerable potential gains to be made. Data linkage techniques currently being developed in the UK offer exciting new possibilities of looking across the primary-, secondary- and tertiary-care interfaces and also assessing short-and long-term social and educational outcomes in relation to allergic disorders. The current reviews of allergy services being undertaken need to be cognisant of these inherent limitations of existing data sources and would do well to recommend strategic initiatives that could enhance the availability, accessibility and quality of these datasets. Ideally, this should include investment in central data repositories staffed by teams with the necessary technical and statistical expertise, which would also take responsibility for progressing data linkage capabilities.