Episodic synchronization in dynamically driven neurons

We examine the response of type II excitable neurons to trains of synaptic pulses, as a function of the pulse frequency and amplitude. We show that the resonant behavior characteristic of type II excitability, already described for harmonic inputs, is also present for pulsed inputs. With this in mind, we study the response of neurons to pulsed input trains whose frequency varies continuously in time, and observe that the receiving neuron synchronizes episodically to the input pulses, whenever the pulse frequency lies within the neuron's locking range. We propose this behavior as a mechanism of rate-code detection in neuronal populations. The results are obtained both in numerical simulations of the Morris-Lecar model and in an electronic implementation of the FitzHugh-Nagumo system, evidencing the robustness of the phenomenon.Comment: 7 pages, 8 figure

Actions of Histrionicotoxin on Acetylcholine Receptors

The effects of histrionicotoxin have been evaluated at the rat neuromuscular junction, the eel electroplaque and on the central nervous system of the cat, and have been shown to reduce markedly the response to acetylcholine or carbamylcholine. This toxin does not inhibit the binding of acetylcholine to Torpedo membrane fragments rich in acetylcholine receptor .protein, but rather augments its affinity for the receptor site. These findings suggest an accentuation of a desensitization phenomenon or a block of ionic channels

Actions of Histrionicotoxin on Acetylcholine Receptors

The effects of histrionicotoxin have been evaluated at the rat neuromuscular junction, the eel electroplaque and on the central nervous system of the cat, and have been shown to reduce markedly the response to acetylcholine or carbamylcholine. This toxin does not inhibit the binding of acetylcholine to Torpedo membrane fragments rich in acetylcholine receptor .protein, but rather augments its affinity for the receptor site. These findings suggest an accentuation of a desensitization phenomenon or a block of ionic channels

Spectra and waiting-time densities in firing resonant and nonresonant neurons

The response of a neural cell to an external stimulus can follow one of the two patterns: Nonresonant neurons monotonously relax to the resting state after excitation while resonant ones show subthreshold oscillations. We investigate how do these subthreshold properties of neurons affect their suprathreshold response. Vice versa we ask: Can we distinguish between both types of neuronal dynamics using suprathreshold spike trains? The dynamics of neurons is given by stochastic FitzHugh-Nagumo and Morris-Lecar models with either having a focus or a node as the stable fixpoint. We determine numerically the spectral power density as well as the interspike interval density in response to a random (noise-like) signals. We show that the information about the type of dynamics obtained from power spectra is of limited validity. In contrast, the interspike interval density gives a very sensitive instrument for the diagnostics of whether the dynamics has resonant or nonresonant properties. For the latter value we formulate a fit formula and use it to reconstruct theoretically the spectral power density, which coincides with the numerically obtained spectra. We underline that the renewal theory is applicable to analysis of suprathreshold responses even of resonant neurons.Comment: 7 pages, 8 figure

Challenges for Coring Deep Permafrost on Earth and Mars

This is the published version. Final publication is available from Mary Ann Liebert, Inc., publishers http://www.dx.doi.org/10.1089/ast.2007.0159.A scientific drilling expedition to the High Lake region of Nunavut, Canada, was recently completed with the goals of collecting samples and delineating gradients in salinity, gas composition, pH, pe, and microbial abundance in a 400 m thick permafrost zone and accessing the underlying pristine subpermafrost brine. With a triple-barrel wireline tool and the use of stringent quality assurance and quality control (QA/QC) protocols, 200 m of frozen, Archean, mafic volcanic rock was collected from the lower boundary that separates the permafrost layer and subpermafrost saline water. Hot water was used to remove cuttings and prevent the drill rods from freezing in place. No cryopegs were detected during penetration through the permafrost. Coring stopped at the 535 m depth, and the drill water was bailed from the hole while saline water replaced it. Within 24 hours, the borehole iced closed at 125 m depth due to vapor condensation from atmospheric moisture and, initially, warm water leaking through the casing, which blocked further access. Preliminary data suggest that the recovered cores contain viable anaerobic microorganisms that are not contaminants even though isotopic analyses of the saline borehole water suggests that it is a residue of the drilling brine used to remove the ice from the upper, older portion of the borehole. Any proposed coring mission to Mars that seeks to access subpermafrost brine will not only require borehole stability but also a means by which to generate substantial heating along the borehole string to prevent closure of the borehole from condensation of water vapor generated by drilling. Astrobiology 8, 623–638

Do Intervention Studies to Promote Physical Activity and Reduce Sedentary Behavior in Children and Adolescents Take Sex/Gender Into Account? A Systematic Review

Background: Physical inactivity is often reported in youth and differs among boys and girls. The aim of this study is to assess sex/gender considerations in intervention studies promoting physical activity and reducing sedentary behavior in youth using a sex/gender checklist. Methods: A systematic search was conducted in August 2018 to identify all relevant controlled trials. Studies screened must have reported a quantified measure of physical activity and/or sedentary behavior, and identified participants by sex/gender at baseline. For evaluation of the sex/gender consideration, the authors used a sex/gender checklist developed by expert consensus. Results: The authors reviewed sex/gender considerations in all aspects of intervention development, implementation, and evaluation in 217 studies. Sex/gender aspects were only rudimentarily taken into account, most frequently during statistical analyses, such as stratification or interaction analysis. Conclusions: Sex/gender effects are not sufficiently reported. To develop guidelines that are more inclusive of all girls and boys, future interventions need to document sex/gender differences and similarities, and explore whether sex/gender influences different phases of intervention programs. The newly developed sex/gender checklist can hereby be used as a tool and guidance to adequately consider sex/gender in the several steps of intervention planning, implementation, and evaluation

Spatially distributed dendritic resonance selectively filters synaptic input

© 2014 Laudanski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.An important task performed by a neuron is the selection of relevant inputs from among thousands of synapses impinging on the dendritic tree. Synaptic plasticity enables this by strenghtening a subset of synapses that are, presumably, functionally relevant to the neuron. A different selection mechanism exploits the resonance of the dendritic membranes to preferentially filter synaptic inputs based on their temporal rates. A widely held view is that a neuron has one resonant frequency and thus can pass through one rate. Here we demonstrate through mathematical analyses and numerical simulations that dendritic resonance is inevitably a spatially distributed property; and therefore the resonance frequency varies along the dendrites, and thus endows neurons with a powerful spatiotemporal selection mechanism that is sensitive both to the dendritic location and the temporal structure of the incoming synaptic inputs.Peer reviewe

Processing of Retinal Signals in Normal and HCN Deficient Mice

This study investigates the role of two different HCN channel isoforms in the light response of the outer retina. Taking advantage of HCN-deficient mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions. Specifically, HCN1 operate mainly at the level of the photoreceptor inner segment from where, together with other voltage sensitive channels, they control the time course of the response to bright light. Conversely, HCN2 channels are mainly expressed on the dendrites of bipolar cells and affect the response to dim lights. Single cell recordings in HCN1−/− mice or during a pharmacological blockade of Ih show that, contrary to previous reports, Ikx alone is able to generate the fast initial transient in the rod bright flash response. Here we demonstrate that the relative contribution of Ih and Ikx to the rods' temporal tuning depends on the membrane potential. This is the first instance in which the light response of normal and HCN1- or HCN2-deficient mice is analyzed in single cells in retinal slice preparations and in integrated full field ERG responses from intact animals. This comparison reveals a high degree of correlation between single cell current clamp data and ERG measurements. A novel picture emerges showing that the temporal profile of the visual response to dim and bright luminance changes is separately determined by the coordinated gating of distinct voltage dependent conductances in photoreceptors and bipolar cells

Janus kinase 2 regulates Bcr–Abl signaling in chronic myeloid leukemia

Despite the success of imatinib mesylate (IM) in the early chronic phase of chronic myeloid leukemia (CML), patients are resistant to IM and other kinase inhibitors in the later stages of CML. Our findings indicate that inhibition of Janus kinase 2 (Jak2) in Bcr–Abl+ cells overcomes IM resistance although the precise mechanism of Jak2 action is unknown. Knocking down Jak2 in Bcr–Abl+ cells reduced levels of the Bcr–Abl protein and also the phosphorylation of Tyr177 of Bcr–Abl, and Jak2 overexpression rescued these knockdown effects. Treatment of Bcr–Abl+ cells with Jak2 inhibitors for 4–6 h but not with IM also reduced Bcr–Abl protein and pTyr177 levels. In vitro kinase experiments performed with recombinant Jak2 showed that Jak2 readily phosphorylated Tyr177 of Bcr–Abl (a Jak2 consensus site, YvnV) whereas c-Abl did not. Importantly, Jak2 inhibition decreased pTyr177 Bcr–Abl in immune complexes but did not reduce levels of Bcr–Abl, suggesting that the reduction of Bcr–Abl by Jak2 inhibition is a separate event from phosphorylation of Tyr177. Jak2 inhibition by chemical inhibitors (TG101209/WP1193) and Jak2 knockdown diminished the activation of Ras, PI-3 kinase pathways and reduced levels of pTyrSTAT5. These findings suggest that Bcr–Abl stability and oncogenic signaling in CML cells are under the control of Jak2

Icaritin Shows Potent Anti-Leukemia Activity on Chronic Myeloid Leukemia In Vitro and In Vivo by Regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT Signalings

PURPOSE: To explore the effects of Icaritin on chronic myeloid leukemia (CML) cells and underlying mechanisms. METHOD: CML cells were incubated with various concentration of Icaritin for 48 hours, the cell proliferation was analyzed by MTT and the apoptosis was assessed with Annexin V and Hoechst 33258 staining. Cell hemoglobinization was determined. Western blotting was used to evaluate the expressions of MAPK/ERK/JNK signal pathway and Jak-2/Phorpho-Stat3/Phorsph-Akt network-related protein. NOD-SCID nude mice were applied to demonstrate the anti-leukemia effect of Icaritin in vivo. RESULTS: Icaritin potently inhibited proliferation of K562 cells (IC50 was 8 µM) and primary CML cells (IC50 was 13.4 µM for CML-CP and 18 µM for CML-BC), induced CML cells apoptosis and promoted the erythroid differentiation of K562 cells with time-dependent manner. Furthermore, Icaritin was able to suppress the growth of primary CD34+ leukemia cells (CML) and Imatinib-resistant cells, and to induce apoptosis. In mouse leukemia model, Icaritin could prolong lifespan of NOD-SCID nude mice inoculated with K562 cells as effective as Imatinib without suppression of bone marrow. Icaritin could up-regulate phospho-JNK or phospho-C-Jun and down-regulate phospho-ERK, phospho-P-38, Jak-2, phospho-Stat3 and phospho-Akt expression with dose- or time-dependent manner. Icaritin had no influence both on c-Abl and phospho-c-Abl protein expression and mRNA levels of Bcr/Abl. CONCLUSION: Icaritin from Chinese herb medicine may be a potential anti-CML agent with low adverse effect. The mechanism of anti-leukemia for Icaritin is involved in the regulation of Bcr/Abl downstream signaling. Icaritin may be useful for an alternative therapeutic choice of Imatinib-resistant forms of CML