97 research outputs found
Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple errorâcorrection procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons
A card game for the treatment of delusional ideas: A naturalistic pilot trial
BACKGROUND: "Michael's game" is a card game which aims at familiarizing healthcare professionals and patients with cognitive behavioral therapy of psychotic symptoms. This naturalistic study tests the feasibility and the impact of the intervention in various naturalistic settings. METHOD: Fifty five patients were recruited in seven centers. They were assessed in pre and post-test with the Peters Delusion Inventory â 21 items (PDI-21). RESULTS: Forty five patients completed the intervention significantly reducing their conviction and preoccupation scores on the PDI-21. CONCLUSION: This pilot study supports the feasibility and effectiveness of "Michael's game" in naturalistic setting. Additional studies could validate the game in a controlled fashion
Na+ imaging reveals little difference in action potentialâevoked Na+ influx between axon and soma
Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Neuroscience 13 (2010): 852-860, doi:10.1038/nn.2574.In cortical pyramidal neurons, the axon initial segment (AIS) plays a pivotal role in synaptic
integration. It has been asserted that this property reflects a high density of Na+ channels in AIS.
However, we here report that APâassociated Na+ flux, as measured by highâspeed fluorescence
Na+ imaging, is about 3 times larger in the rat AIS than in the soma. Spike evoked Na+ flux in
the AIS and the first node of Ranvier is about the same, and in the basal dendrites it is about 8
times lower. At near threshold voltages persistent Na+ conductance is almost entirely axonal.
Finally, we report that on a time scale of seconds, passive diffusion and not pumping is
responsible for maintaining transmembrane Na+ gradients in thin axons during high frequency
AP firing. In computer simulations, these data were consistent with the known features of AP
generation in these neurons.Supported by USâ
Israel BSF Grant (2003082), Grass Faculty Grant from the MBL, NIH Grant (NS16295),
Multiple Sclerosis Society Grant (PP1367), and a fellowship from the Gruss Lipper Foundation
Axons Amplify Somatic Incomplete Spikes into Uniform Amplitudes in Mouse Cortical Pyramidal Neurons
BACKGROUND: Action potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels. CONCLUSION/SIGNIFICANCE: An amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues
Coastal Upwelling Supplies Oxygen-Depleted Water to the Columbia River Estuary
Low dissolved oxygen (DO) is a common feature of many estuarine and shallow-water
environments, and is often attributed to anthropogenic nutrient enrichment from
terrestrial-fluvial pathways. However, recent events in the U.S. Pacific
Northwest have highlighted that wind-forced upwelling can cause naturally
occurring low DO water to move onto the continental shelf, leading to
mortalities of benthic fish and invertebrates. Coastal estuaries in the Pacific
Northwest are strongly linked to ocean forcings, and here we report observations
on the spatial and temporal patterns of oxygen concentration in the Columbia
River estuary. Hydrographic measurements were made from transect (spatial
survey) or anchor station (temporal survey) deployments over a variety of wind
stresses and tidal states during the upwelling seasons of 2006 through 2008.
During this period, biologically stressful levels of dissolved oxygen were
observed to enter the Columbia River estuary from oceanic sources, with minimum
values close to the hypoxic threshold of 2.0 mg Lâ1. Riverine
water was consistently normoxic. Upwelling wind stress controlled the timing and
magnitude of low DO events, while tidal-modulated estuarine circulation patterns
influenced the spatial extent and duration of exposure to low DO water. Strong
upwelling during neap tides produced the largest impact on the estuary. The
observed oxygen concentrations likely had deleterious behavioral and
physiological consequences for migrating juvenile salmon and benthic crabs.
Based on a wind-forced supply mechanism, low DO events are probably common to
the Columbia River and other regional estuaries and if conditions on the shelf
deteriorate further, as observations and models predict, Pacific Northwest
estuarine habitats could experience a decrease in environmental quality
Physical activity and colon cancer prevention: a meta-analysis
Although an inverse association between physical activity and risk of colon cancer is well established, a formal estimate of the magnitude of this risk reduction that includes recent studies is not available. This analysis examines the association by sex and study design, restricting analyses to studies where data for colon cancer alone were available. The authors reviewed published studies through June 2008 examining the association between physical activity and risk of colon cancer. Heterogeneity and publication bias were evaluated and random effects models used to estimate relative risks (RR). Differences by sex and study design were evaluated. A total of 52 studies were included. An inverse association between physical activity and colon cancer was found with an overall relative risk (RR) of 0.76 (95% confidence interval (CI): 0.72, 0.81). For men, the RR was 0.76 (95% CI: 0.71, 0.82); for women, this was little different, (RR=0.79, 95% CI: 0.71, 0.88). The findings from caseâcontrol studies were stronger (RR=0.69, 95% CI: 0.65, 0.74) than for cohort studies (RR=0.83, 95% CI: 0.78, 0.88). This study confirms previous studies reporting an inverse association between physical activity and colon cancer in both men and women, and provides quantitative estimates of the inverse association
Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials
The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37â42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Pathways of SME Internationalization: a bibliometric and systematic review
Business is dynamic and rapidly changing. Global markets were previously the playing field of multinational corporations (MNCs), while small and medium enterprises (SMEs) were local; however, the removal of imposed barriers, and recent technological advances in manufacturing, transportation and communications have indorsed SMEs and international entrepreneurs (IE) global access. SMEs and IEs are increasingly fueling economic growth and innovation and these trends are presenting both opportunities and challenges to both MNCs and SMEs in the global arena. This review systematically examines comparative SME and IE research, analyzing (after fine tuning) 762 articles published in leading journals from 1992 to September 2018. Our bibliometric and systematic review classifies SME and IE research findings into three echelons: (i) subjects; (ii) theories; and (iii) methods
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