The role of KCNQ channels in the thalamus

Der ventrobasale thalamische Komplex (VB) spielt eine entscheidende Rolle bei der somatosensorischen Informationsverarbeitung und ist insbesondere wichtig für die diskriminativen und räumlichen Aspekte der akuten Schmerzverarbeitung. Wir schlagen einen neuen antinozizeptiven Mechanismus vor, der auf der Aktivierung von KCNQ-Kanälen in diesem Hirngebiet beruht. Die Wirkung von Retigabin, einem K+-Kanalöffner, beruht auf der spezifischen Aktivierung von KCNQ-Kanälen, welche den M-Strom (IM) herbeiführt. Dies gilt im Besonderen für die Untereinheiten KCNQ2 und KCNQ3, die durch Retigabin aktiviert und durch den spezifischen KCNQ-Kanalblocker XE991 inhibiert werden. In vitro induziert die Applikation von Retigabin eine Hyperpolarisation des Membranruhepotentials, die mit der Verringerung tonischer Aktivität und einer Förderung von Salvenaktivität einhergeht. Dies führt in vivo zu einer Schmerzhemmung. The thalamic ventrobasal complex (VB) plays a crucial role in somatosensory information processing, and it is particularly important for the discriminative and spatial aspects of acute pain processing. We propose a new antinociceptive mechanism based on the activation of KCNQ channels in the brain. Here, the channels formed by the co-assembly of the subunits KCNQ2 and KCNQ3 mediates the M current (IM). In vitro, the application of the specific opener retigabine induced hyperpolarization of the resting membrane potential, associated with the reduction in tonic activity and promotion of burst-like activity. This shift in the firing pattern is associated to reduction of pain sensation at supraspinal level. Thus, the possible role of thalamic KCNQ channels in pain sensation was the tested in an animal model of acute pain, suggesting a novel target for pain therapy

Neuroprotective role of lactate in a human in vitro model of the ischemic penumbra

In patients suffering from cerebral ischemic stroke, there is an urgent need for treatments to protect stressed yet viable brain cells. Recently, treatment strategies that induce neuronal activity have been shown to be neuroprotective. Here, we hypothesized that neuronal activation might maintain or trigger the astrocyte-to-neuron lactate shuttle (ANLS), whereby lactate is released from astrocytes to support the energy requirements of ATP-starved hypoxic neurons, and this leads to the observed neuroprotection. We tested this by using a human cell based in vitro model of the ischemic penumbra and investigating whether lactate might be neuroprotective in this setting. We found that lactate transporters are involved in the neuroprotective effect mediated by neuronal activation. Furthermore, we showed that lactate exogenously administered before hypoxia correlated with neuroprotection in our cellular model. In addition, stimulation of astrocyte with consequent endogenous production of lactate resulted in neuroprotection. To conclude, here we presented evidence that lactate transport into neurons contributes to neuroprotection during hypoxia providing a potential basis for therapeutic approaches in ischemic stroke.</p

Spatial correlations in attribute communities

Community detection is an important tool for exploring and classifying the properties of large complex networks and should be of great help for spatial networks. Indeed, in addition to their location, nodes in spatial networks can have attributes such as the language for individuals, or any other socio-economical feature that we would like to identify in communities. We discuss in this paper a crucial aspect which was not considered in previous studies which is the possible existence of correlations between space and attributes. Introducing a simple toy model in which both space and node attributes are considered, we discuss the effect of space-attribute correlations on the results of various community detection methods proposed for spatial networks in this paper and in previous studies. When space is irrelevant, our model is equivalent to the stochastic block model which has been shown to display a detectability-non detectability transition. In the regime where space dominates the link formation process, most methods can fail to recover the communities, an effect which is particularly marked when space-attributes correlations are strong. In this latter case, community detection methods which remove the spatial component of the network can miss a large part of the community structure and can lead to incorrect results.Comment: 10 pages and 7 figure

A MECHATRONIC TOOL FOR REVEALING INVERSE RELATIONSHIPS AMONG HEART’S STROKE VOLUME AND HEAD’S LINEAR ACCELERATION INDUCED BY MOORED BOATS ROLLING IN ELDERLY SAILORS WITH UNCHANGED BODY SIZES: A NON-DRUG ANTI-HYPERTENSIVE ADVANTAGE?

Three aged and skilled sailors, being in a good condition of cardio metabolic compensation, took a seven days coastal sailing cruise. They daily underwent a cardiodynamic assessment by a impedance cardigraphy tool while staying seated on the moored boat. They showed a statistically significant inverse linear regression of beat-to-beat left ventricular stroke volume (LSV) versus the component of the head acceleration along the spatial X-axis, positioning the subject’s head so that the X-axis lay along the nose-ocipital direction. In fact, the temporally corresponding values of LSV inversely changed of about 11 ml on average, with an interindividual difference ranging from a minimum of about 6 ml to a maximum of about 14 ml, for each unitary head acceleration change. Since the reduction of left ventricular stroke volume may be due to the already observed vestibulo-sympathetic reflex from which limbs muscle vasodilation may occur, and considering that LSV falling induces a reduction in arterial blood pressure, it is hypothesized that the slow rolling of moored boat might also act as a non-invasive arterial blood pressure attenuator effect

Inference of hidden structures in complex physical systems by multi-scale clustering

We survey the application of a relatively new branch of statistical physics--"community detection"-- to data mining. In particular, we focus on the diagnosis of materials and automated image segmentation. Community detection describes the quest of partitioning a complex system involving many elements into optimally decoupled subsets or communities of such elements. We review a multiresolution variant which is used to ascertain structures at different spatial and temporal scales. Significant patterns are obtained by examining the correlations between different independent solvers. Similar to other combinatorial optimization problems in the NP complexity class, community detection exhibits several phases. Typically, illuminating orders are revealed by choosing parameters that lead to extremal information theory correlations.Comment: 25 pages, 16 Figures; a review of earlier work

FUNKCIONALNO MESO PERADI OBOGAĆENO BIOLOŠKI AKTIVNIM TVARIMA IZ NEUTRALNIH EKSTRAKATA DOBIVENIH OD SMREKOVIH IGLICA

Neutral extractives of spruce needles were produced from forestry by-products: the green biomass of spruce needles. The extractes of spruce needles extract con¬tains a significant amount of natural biologically active substances. In the course of our investigations, the evaluation of biologically active substances obtained from neutral extracts of spruce needles was carried out to assess their effect on quality of broiler chicken meat. The feeding trial was conducted with broiler chickens of the cross ROOS – 308 by adding neutral extract of spruce needles in the form of loose powder to the com¬position of broiler chicken diet. It was found that the loose powder feed additives containing neutral extract of spruce needles (0.05% and 0.10% in pure substance) used to supplement the broiler feed improved the quality of poultry meat. The feed additives containing biologically active substances from spruce needles neutral ex¬tract involved in metabolic processes of the broiler chicken organism, increased the n – 3 polyunsaturated fatty acids (DHA) content in meat by 0.59 – 1.05% and the carotenoids’ content in liver by 1.46 – 1.70 mg kg -1, at the same time positively reducing the cholesterol level in meat by 17.18 – 26.16 mg 100 g-1 in comparison with the control group.Neutralni ekstrakti smrekovih iglica proizvedeni su iz smrekovih popratnih proizvoda, zelene biomase smrekovih iglica. Ekstrakti smrekovih iglica sadrže značajnu količinu prirodnih, biološki aktivnih tvari. U tijeku naših istraživanja procijenjene su biološki aktivne tvari dobivene iz neutralnih ekstrakata smrekovih iglica radi ocjene njihovog djelovanja na kakvoću mesa pilića brojlera. Proveden je pokus hranidbe brojlera križanaca Ross-308 dodavanjem neutralnih ekstrakata smrekovih iglica u obliku rasutog praška u smjesu za njihove obroke. Pokazalo se da je rasuti prašak kao dodatak hrani brojlera koji je sadržavao neutralne ekstrakte smrekovih iglica (0,05% i 0,10% čiste tvari) poboljšao kakvoću mesa pilića. Dodaci hrani koji sadrže biološki aktivne tvari iz neutralnog ekstrakta smrekovih iglica uključeni u metaboličke procese brojlera povećali su sadržaj n-3 polinezasićenih masnih kiselina (DHA) u mesu za 0,59-1,05% (P<0,05) i sadržaj karotenoida u jetri za 0,46-1,70 mgkg.-1(P<0,05) te u isto vrijeme pozitivno smanjili razinu kolesterola u mesu za 17,18-26,16 mg.100g-1(P<0,05) u usporedbi s kontrolnom skupinom

Demand-driven sustainable tourism? A choice modelling analysis

This paper studies the preferences of tourists visiting Sardinia (Italy), using a choice modelling approach. The focus is on the evaluation of specific ‘demand-enhancing effects’ which, according to economic theory, provide a basis for implementing sustainable tourism policies. Multinomial logit estimates reveal that strong negative effects result from the congestion of tourist attractions and the transformation of coastal environments, though tourists clearly gain utility from the other components of a tourism destination. The extent of the effects related to environmental preservation seems to support planning tourism development policies that will not have strong irreversible effects on coastal areas

NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.</p