Astrocytes and Inflammatory Processes in Alzheimer’s Disease

A significant increase in inflammation has been shown to be a crucial factor in the progression of the Alzheimer’s disease (AD). Moreover, inflammatory signals are already present in mild cognitive impairment (MCI) patients before they develop AD. The amyloid hypothesis argues that in AD, there is an increase in oxidative stress caused by the accumulation of β-amyloid (Aβ) and that its elimination should be a priority. Also, hyperphosphorylation of the protein TAU occurs, which is characteristic of this disease. In AD oxidative stress processes occur and also inflammation. The basal chronic inflammation produces a cascade of cellular, such as astrocytes and microglial cells, and molecular processes in AD patients. We here have tried to explore the action of the inflammatory process and its implication in the neurodegenerative process of the AD. We can see that the role of Aβ is only one component that gives rise to inflammation, probably mediated by activation of microglia and astrocytes with the goal of getting rid of these brain waste products. In fact, it is related to a greater degree with the progression of the disease and worsening of the symptoms with the increase of phosphorylated TAU in different parts of the brain

Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin

Purpose:The goal of this study was to determine the effects of vasopressin and the selective V2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses.Methods:Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V,-receptor antagonist d(CH2)5Tyr(Me)AVP (10−6 mol/L), the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10−6 mol/L), indomethacin (10−6 mol/L), or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10−4 mol/L).Results:In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing-half-maximal contractions (EC50) of 3.44 × 10−8 mol/L. The vasopressin V1-receptor antagonist (10−6 mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V1-antagonist (10−6 mol/L), vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10−6 mol/L) and unaffected by the V1-V2-receptor antagonist (10−6 mol/L) or by L-NAME (10−4 mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME.Conclusions:These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant Prostaglandins, probably derived from endothelial cells, and is independent of V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating Prostaglandins from the endothelial cells

Speeding Up Active Mesh Segmentation by Local Termination of Nodes

This article outlines a procedure for speeding up segmentation of images using active mesh systems. Active meshes and other deformable models are very popular in image segmentation due to their ability to capture weak or missing boundary information; however, where strong edges exist, computations are still done after mesh nodes have settled on the boundary. This can lead to extra computational time whilst the system continues to deform completed regions of the mesh. We propose a local termination procedure, reducing these unnecessary computations and speeding up segmentation time with minimal loss of quality

Material multimedia para aumentar el rendimiento académico de los trabajos en grupo

[EN] Multimedia can be considered a useful tool for improving the learning. In this study we analyze the marks that students get in a group activity with and without the use of a multimedia material made by teachers. The scores are obtained using a rubric previously tested for this activity and the results show an increase in the final qualification for student groups who used the multimedia material. We also analyze the scores by units following the rubric and we note that scores increase 4.0 points for a maximum of 10 in the methodology unit. Moreover, we collect the opinion of our students about the multimedia material and how it helped them to better understand the work they had to do in the activity group. Teachers give their opinion too. In conclusion, this multimedia material is a good tool to guide group activity and get higher marks[ES] El uso de materiales multimedia puede favorecer el proceso de aprendizaje. En este estudio se analizan las calificaciones obtenidas en una actividad grupal con y sin ayuda de un material multimedia elaborado por los profesores de la asignatura. Las calificaciones se obtienen con una rúbrica adecuada para evaluar la actividad de grupo y muestran un incremento de la nota final para los equipos de estudiantes que tuvieron a su disposición el material multimedia. Se realiza un análisis de las calificaciones desglosando los distintos apartados de la rúbrica y se aprecia que el apartado de metodología es el más sensible al material multimedia, incrementando la calificación en 4.0 puntos sobre 10. Se recoge la opinión de los alumnos y del equipo docente en la dinámica de la actividad grupal con y sin el material multimedia y se concluye que dicho material supone una buena guía para orientar a los alumnos en la actividad por equipos.Mauricio, M.; Valles, S.; Vila, J.; Aldasoro, M.; Serna, E. (2017). Material multimedia para aumentar el rendimiento académico de los trabajos en grupo. En In-Red 2017. III Congreso Nacional de innovación educativa y de docencia en red. Editorial Universitat Politècnica de València. 178-184. https://doi.org/10.4995/INRED2017.2017.6846OCS17818

Hiperestentsioa: kontinenteen apurketa ulertzeko eredu berri bat

Kontinenteen apurketa luzaroan ikertu den prozesu geologikoa da. Rifting deritzon prozesu horrek milioika urte irauten ditu, eta kontinente-ertzetan, mendikateetan eta bestelako ingurune geologikoetan topatzen dira fenomeno tektoniko horren aztarnak. Plaka tektonikoen banaketaren interpretazioa, ordea, eboluzionatuz doa ikertzaileen ulermenaren eta aurrerapen teknologikoen arabera. Hiperestentsioaren ideia da interpretazio horren azken berrikuntza. Ideia hori litosfera kontinentalaren deformazio polifasikoan barneratzen da, litosferaren muturreko luzapenean oinarrituz, hain zuzen. Ertz egonkorretan eta gerriko orogenikoetan identifikaturiko egitura geologiko eta eremu estruktural bereizgarriek ahalbidetzen dute fenomeno horren bilakaeraren nolakotasuna definitzea. Magman txiroak bezala ezagutzen diren ertz egonkorretako eremu horiek dira hurbileko domeinua, necking domeinua, urruneko domeinua edo hiperluzatua eta kanpoko domeinua. Domeinu horietako bakoitza riftingaren deformazio faseekin lotzen da; fase horiek litosfera kontinentalaren luzapena, mehetzea, mantuaren azaleratzea eta lurrazal ozeanikoaren zabaltzea dira. Esan bezala, iraganean hiperluzatutako arroetan ari da garatzen ikerketa, eta hipotesi horren bitartez ulertzen hasia da, honezkero, Euskokantauriar arroa (EKA) barneratzen duen Iberia eta Eurasia arteko Mesozoikoko rift-sistemaren garapena. Urteetan arroan bildutako datuek, behintzat, horretara bultzatzen dute. Pirinioen mendebaldean deskribaturiko mantuaren azaleratzeak eta arroan deskribaturiko hamaika prozesuk indartu dute Kretazeoko riftingean hiperestentsioak izan zezakeen garrantzia; azken horrek, gainera, garai hartako EKAren eboluzio geologikoaren paradigma argitu dezake.; Continental breakup is a geological process which has been deeply learnt. The keys of that tectonic phenomena, the so-called rifting process that lasts millions of years, can be found worldwide within rifted margins, mountain chains and other geological settings. However, the interpretation of tectonic plate rupture evolves while researcher´s comprehension and technology advance. Hyperextension is the last update within that interpretation. This revolutionary idea involves the extreme polyphasic extensional deformation of the continental lithosphere. Characteristic geological structures and structural domains identified within passive margins and orogenic belts, allow to define the evolution of this phenomena. Domains such as the proximal domain, necking domain, distal or hyperextended domain and outer domain are distinguishing features within magma poor rifted margins. These domains are linked to specific deformation phases during rifting, being stretching and thinning of continental lithosphere, mantle exhumation and oceanic crust spreading part of these process. As said, research is being carried out in hyperextended basins, and the evolution of the Iberia-Eurasia Mesozoic rift system, which involves the Basque-Cantabrian Basin (BCB), is already being understood within that hypothesis. Data collected over years in the BCB, at least, suggest that. Mantle exhumation described in the western Pyrenees and several processes linked to that within the BCB, reinforces the significance that hyperextension could have occurred during the Cretaceous rifting, shedding light to the paradigm concerning the evolution of the BCB

Why Did Red Ereño Limestone Go Red? Linking Scientific Knowledge and Geoheritage Story-Telling (Basque Country, Spain)

Red Ereño is a red-stained ornamental and construction limestone with characteristic white fossil shells. Although exploited since Roman times, marketed worldwide and that the rock itself and its outcrop areas have been included in geological heritage inventories, the origin of its characteristic reddish colour remained unresolved. The aim of this work is to deepen the scientific knowledge of Red Ereño as a basis for understanding the characteristics of this stone and to make this information available for geoconservation actions. The mineralogical and petrological study, mainly based on optical and electron microscopy, X-ray diffraction, and rock magnetism and paleomagnetic techniques, concluded that the red-staining mineral is pigmentary hematite. Moreover, the analysis stated that hematite precipitated after sedimentation but prior to burial diagenesis and before alpine inversion. Based on palaeomagnetic studies, it can be stated that mineralisation occurred during the Late Cretaceous. This work illustrates how scientific research on this potential heritage stone provides key information for geoconservation.This study has been carried out by the UPV/EHU Research Group IT-1678/22 (Government of the Basque Country) in the framework of the project US21/32 under the cooperation agreement between the University of the Basque Country UPV/EHU, Basque Energy Agency (EVE), and Provincial Council of Biscay (BFA). Authors also thank the support of the project PID2019-108753GB-C21 financed by State Research Agency (Spain) [AEI /https://doi.org/10.13039/501100011033]. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. UPV/EHU Research Group IT-1678/22 (Government of the Basque Country); UPV/EHU, EVE/EEE, DFB/BFA project US21/32

Cardiovascular Agents Affect the Tone of Pulmonary Arteries and Veins in Precision-Cut Lung Slices

Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins.Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins.Pulmonary veins responded stronger than arteries to α(1)-agonists (contraction) and β(2)-agonists (relaxation). Notably, inhibition of β(2)-adrenoceptors unmasked the α(1)-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V(1a) and AT(1) receptors, respectively, without affecting pulmonary arteries.Vasopressin and (nor)epinephrine in combination with β(2)-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT(1) receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α(1)-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not

The Neutrophil's Eye-View: Inference and Visualisation of the Chemoattractant Field Driving Cell Chemotaxis In Vivo

As we begin to understand the signals that drive chemotaxis in vivo, it is becoming clear that there is a complex interplay of chemotactic factors, which changes over time as the inflammatory response evolves. New animal models such as transgenic lines of zebrafish, which are near transparent and where the neutrophils express a green fluorescent protein, have the potential to greatly increase our understanding of the chemotactic process under conditions of wounding and infection from video microscopy data. Measurement of the chemoattractants over space (and their evolution over time) is a key objective for understanding the signals driving neutrophil chemotaxis. However, it is not possible to measure and visualise the most important contributors to in vivo chemotaxis, and in fact the understanding of the main contributors at any particular time is incomplete. The key insight that we make in this investigation is that the neutrophils themselves are sensing the underlying field that is driving their action and we can use the observations of neutrophil movement to infer the hidden net chemoattractant field by use of a novel computational framework. We apply the methodology to multiple in vivo neutrophil recruitment data sets to demonstrate this new technique and find that the method provides consistent estimates of the chemoattractant field across the majority of experiments. The framework that we derive represents an important new methodology for cell biologists investigating the signalling processes driving cell chemotaxis, which we label the neutrophils eye-view of the chemoattractant field

Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Molecular evolution of Adh and LEAFY and the phylogenetic utility of their introns in Pyrus (Rosaceae)

<p>Abstract</p> <p>Background</p> <p>The genus <it>Pyrus </it>belongs to the tribe Pyreae (the former subfamily Maloideae) of the family Rosaceae, and includes one of the most important commercial fruit crops, pear. The phylogeny of <it>Pyrus </it>has not been definitively reconstructed. In our previous efforts, the internal transcribed spacer region (ITS) revealed a poorly resolved phylogeny due to non-concerted evolution of nrDNA arrays. Therefore, introns of low copy nuclear genes (LCNG) are explored here for improved resolution. However, paralogs and lineage sorting are still two challenges for applying LCNGs in phylogenetic studies, and at least two independent nuclear loci should be compared. In this work the second intron of <it>LEAFY </it>and the alcohol dehydrogenase gene (<it>Adh</it>) were selected to investigate their molecular evolution and phylogenetic utility.</p> <p>Results</p> <p>DNA sequence analyses revealed a complex ortholog and paralog structure of <it>Adh </it>genes in <it>Pyrus </it>and <it>Malus</it>, the pears and apples. Comparisons between sequences from RT-PCR and genomic PCR indicate that some <it>Adh </it>homologs are putatively nonfunctional. A partial region of <it>Adh1 </it>was sequenced for 18 <it>Pyrus </it>species and three subparalogs representing <it>Adh1-1 </it>were identified. These led to poorly resolved phylogenies due to low sequence divergence and the inclusion of putative recombinants. For the second intron of <it>LEAFY</it>, multiple inparalogs were discovered for both <it>LFY1int2 </it>and <it>LFY2int2</it>. <it>LFY1int2 </it>is inadequate for phylogenetic analysis due to lineage sorting of two inparalogs. <it>LFY2int2-N</it>, however, showed a relatively high sequence divergence and led to the best-resolved phylogeny. This study documents the coexistence of outparalogs and inparalogs, and lineage sorting of these paralogs and orthologous copies. It reveals putative recombinants that can lead to incorrect phylogenetic inferences, and presents an improved phylogenetic resolution of <it>Pyrus </it>using <it>LFY2int2-N</it>.</p> <p>Conclusions</p> <p>Our study represents the first phylogenetic analyses based on LCNGs in <it>Pyrus</it>. Ancient and recent duplications lead to a complex structure of <it>Adh </it>outparalogs and inparalogs in <it>Pyrus </it>and <it>Malus</it>, resulting in neofunctionalization, nonfunctionalization and possible subfunctionalization. Among all investigated orthologs, <it>LFY2int2-N </it>is the best nuclear marker for phylogenetic reconstruction of <it>Pyrus </it>due to suitable sequence divergence and the absence of lineage sorting.</p