246 research outputs found
Redefining Performance Evaluation Tools for Real-Time QRS Complex Classification Systems
International audienceIn a heartbeat classification procedure, the detection of QRS complex waveforms is necessary. In many studies, this heartbeat extraction function is not considered: the inputs of the classifier are assumed to be correctly identified. This paper aims to redefine classical performance evaluation tools in entire QRS complex classification systems and to evaluate the effects induced by QRS detection errors on the performance of a heartbeat classification processing (normal vs abnormal). Performance statistics are given and discussed considering the MIT/BIH database records that are replayed on a real-time classification system imposed of the classical detector proposed by Hamilton & Tompkins, followed by a neural network classifier. This study shows that a classification accuracy of 96.72% falls to 94.90% when a drop of 1.78% error rate is introduced in the detector quality. This corresponds an increase of about 50% bad classifications
Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment
In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes
Modelled subglacial floods and tunnel valleys control the life cycle of transitory ice streams
Ice streams are corridors of fast-flowing ice that
control mass transfers from continental ice sheets to oceans.
Their flow speeds are known to accelerate and decelerate,
their activity can switch on and off, and even their locations
can shift entirely. Our analogue physical experiments reveal
that a life cycle incorporating evolving subglacial meltwater
routing and bed erosion can govern this complex transitory
behaviour. The modelled ice streams switch on and accelerate
when subglacial water pockets drain as marginal outburst
floods (basal decoupling). Then they decelerate when the lubricating
water drainage system spontaneously organizes itself
into channels that create tunnel valleys (partial basal recoupling).
The ice streams surge or jump in location when
these water drainage systems maintain low discharge but they
ultimately switch off when tunnel valleys have expanded to
develop efficient drainage systems. Beyond reconciling previously
disconnected observations of modern and ancient ice
streams into a single life cycle, the modelling suggests that
tunnel valley development may be crucial in stabilizing portions
of ice sheets during periods of climate change
Photoswitchable diacylglycerols enable optical control of protein kinase C.
Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling
Membrane Potential-Dependent Inactivation of Voltage-Gated Ion Channels in α-Cells Inhibits Glucagon Secretion From Human Islets
OBJECTIVE: To document the properties of the voltage-gated ion channels in human pancreatic alpha-cells and their role in glucagon release. RESEARCH DESIGN AND METHODS: Glucagon release was measured from intact islets. [Ca(2+)](i) was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated alpha-cells identified by immunocytochemistry. RESULT: Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl(2). Glucose remained inhibitory in the presence of ZnCl(2) and after blockade of type-2 somatostatin receptors. Human alpha-cells are electrically active at 1 mmol/l glucose. Inhibition of K(ATP)-channels with tolbutamide depolarized alpha-cells by 10 mV and reduced the action potential amplitude. Human alpha-cells contain heteropodatoxin-sensitive A-type K(+)-channels, stromatoxin-sensitive delayed rectifying K(+)-channels, tetrodotoxin-sensitive Na(+)-currents, and low-threshold T-type, isradipine-sensitive L-type, and omega-agatoxin-sensitive P/Q-type Ca(2+)-channels. Glucagon secretion at 1 mmol/l glucose was inhibited by 40-70% by tetrodotoxin, heteropodatoxin-2, stromatoxin, omega-agatoxin, and isradipine. The [Ca(2+)](i) oscillations depend principally on Ca(2+)-influx via L-type Ca(2+)-channels. Capacitance measurements revealed a rapid (<50 ms) component of exocytosis. Exocytosis was negligible at voltages below -20 mV and peaked at 0 mV. Blocking P/Q-type Ca(2+)-currents abolished depolarization-evoked exocytosis. CONCLUSIONS: Human alpha-cells are electrically excitable, and blockade of any ion channel involved in action potential depolarization or repolarization results in inhibition of glucagon secretion. We propose that voltage-dependent inactivation of these channels underlies the inhibition of glucagon secretion by tolbutamide and glucose
Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function
OBJECTIVE— Somatostatin (SST) is secreted by islet δ-cells and by extraislet neuroendocrine cells. SST receptors have been identified on α- and β-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating α- and β-cell function. However, the specific intraislet function of δ-cell SST remains uncertain. We have used Sst−/− mice to investigate the role of δ-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo
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