K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation

Producción CientíficaK+ channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. Purpose: To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion . Methods: Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K+ channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro. Results: Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84±4 % vs. 70±5 % in BPN, p<0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18± 6 % vs. 58±20 % with vehicle, p<0.05). Conclusions: Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.La versión original del artículo contiene un error. El gráfico de la página 505 es incorrecto. La corrección del mismo se encuentra en el segundo fichero "Erratum to: K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation".Ministerio de Economía, Industria y Competitividad (project RD12/0042/0006)Fondo de Investigación en Salud - Instituto Carlos III (project PI11/00225)VALTEC 09-1-0042Ministerio de Ciencia, Innovación y Universidades (grant BFU2010-15898)Junta de Castilla y León (grant VA094A11-2

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Mutations in NR2E3, a gene encoding an orphan nuclear transcription factor, cause two retinal dystrophies with a distinct phenotype, but the precise role of NR2E3 in rod and cone transcriptional networks remains unclear. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wildtype and two different Nr2e3 mouse models that show phenotypes similar to patients carrying NR2E3 mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones co-expressing both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant and includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how different mutations in NR2E3 lead to distinct visual disorders in humans

Positron emission tomography of the airway distribution of intranasal challenge solutions

Abstract of: Scientific Sessions: 2007 AAAAI Annual Meeting, February 23-27, San Diego, CAIntranasal administration is one of the main routes of allergen challenge in mouse models of airway disease. Although it is widely used, it is not well established the amount of allergen that reaches the lung or is lost to the gastrointestinal tract. The local distribution of the challenge solution within the airways is also unknown. The aim of this study was to assess the distribution immediately after intranasal delivery using a Positron Emission Tomography scanner (PET)FIS 01/0598 and Foundation SEAICPublicad

Land-use change and windstorms legacies drove the recolonization dynamics of laurel forests in Tenerife, Canary islands

Laurel forests are quite relevant for biodiversity conservation and are among the island ecosystems most severely damaged by human activities. In the past, Canary laurel forests have been greatly altered by logging, livestock and agriculture. The remains of laurel forests are currently protected in the Canary Islands (Spain). However, we miss basic information needed for their restoration and adaptive management, such as tree longevity, growth potential and responsiveness to natural and anthropogenic disturbances. Using dendrochronological methods, we studied how forest dynamic is related to land-use change and windstorms in two well-preserved laurel forests on Tenerife Island. Wood cores were collected from over 80 trees per stand at three stands per forest. We used ring-width series to estimate tree ages and calculate annual basal area increments (BAI), cumulative diameter increases, and changes indicative of released and suppressed growth. Twelve tree species were found in all stands, with Laurus novocanariensis, Ilex canariensis and Morella faya being the most common species. Although some individuals were over 100 years old, 61.8%–88.9% of the trees per stand established between 1940 and 1970, coinciding with a post-war period of land abandonment, rural exodus and the onset of a tourism economy. Some trees have shown growth rates larger than 1 ​cm diameter per year and most species have had increasing BAI trends over the past decades. Strong growth releases occurred after windstorms at both sites, but the effects of windstorms were site-dependent, with the 1958 storm affecting mainly the eastern tip of the island (Anaga massif) and the 1991 storm the western tip (Teno massif). Given the great ability of laurel forest trees to establish after land use cessation and to increase growth after local disturbances such as windstorms, passive restoration may be sufficient to regenerate this habitat in currently degraded areas.12 página

Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.

The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks

Gold Binding by Native and Chemically Modified Hops Biomasses

Heavy metals from mining, smelting operations and other industrial processing facilities pollute wastewaters worldwide. Extraction of metals from industrial effluents has been widely studied due to the economic advantages and the relative ease of technical implementation. Consequently, the search for new and improved methodologies for the recovery of gold has increased. In this particular research, the use of cone hops biomass (Humulus lupulus) was investigated as a new option for gold recovery. The results showed that the gold binding to native hops biomass was pH dependent from pH 2 to pH 6, with a maximum percentage binding at pH 3. Time dependency studies demonstrated that Au(III) binding to native and modified cone hops biomasses was found to be time independent at pH 2 while at pH 5, it was time dependent. Capacity experiments demonstrated that at pH 2, esterified hops biomass bound 33.4 mg Au/g of biomass, while native and hydrolyzed hops biomasses bound 28.2 and 12.0 mg Au/g of biomass, respectively. However, at pH 5 the binding capacities were 38.9, 37.8 and 11.4 mg of Au per gram of native, esterified and hydrolyzed hops biomasses, respectively

Differential contribution of the two major polygalacturonases from Penicillium digitatum to virulence towards citrus fruit

The fungus Penicillium digitatum is the causal agent of the citrus green mould, the major postharvest diseases of citrus fruit. Lesions on the surface of infected fruits first appear as soft areas around the inoculation site, due to maceration of fruit. The macerating activity has been associated with pectinases secreted by the fungus during infection. In order to evaluate the contribution to virulence and macerating activity of the two major polygalacturonases (PGs) secreted by P. digitatum, we have obtained and characterized mutants lacking either pg1 or pg2, the genes encoding PG1 and PG2, respectively. Disease incidence of deletants in either gene was not different from that of the parental strain or ectopic transformants. However, disease progressed more slowly in deletants, especially in those lacking the pg2 gene. The lesions originated by the Δpg2 deletants were not as soft and the pH was not as acid as those originated by either the wild type strain or the ectopic transformants. Total PG activity in the macerated tissue was also lower in fruits infected with the Δpg2 deletants. Interestingly, the macerated tissue of oranges infected with Δpg2 deletants showed around 50% reduction in galacturonic acid content with respect to lesions caused by any other strain.The technical assistance of Ana Izquierdo is gratefully acknowledged. LG-C's research is funded in part by the Spanish Ministry of Economy, Industry and Competitiveness (AGL2011-30519-C03-01 and AGL2014-55802-R) and the Generalitat Valenciana (PROMETEOII/2014/027). ML-P was supported by a “Formación de Personal Investigador” scholarship (BES-2006-12983). Authors want to thank the technical assistance of S. Dashevskaya and the financial support by AGL2011-30519-CO3-03 from the “Ministerio de Economía y Competitividad” (MINECO, Spain), and the CERCA Programme/Generalitat de Catalunya

Nanoencapsulated Clove Oil Applied as an Anesthetic at Slaughtering Decreases Stress, Extends the Freshness, and Lengthens Shelf Life of Cultured Fish

In the aquaculture industry, fish are stunned using a wide range of methods, but all of them trigger stress responses and affect the fish flesh quality. Chilled water is considered one of the most efficient methods, but even this is not a stress‐free experience for the fish. Anesthetics included in the ice slurry or in water could decrease this stress and delay the loss of flesh quality. In this work, we analyze the effect of clove oil (CO) nanoencapsulated in β‐cyclodextrins (β‐CD) (CO + β‐CD), incorporated in the stunning bath, on the stress response and the organoleptic attributes of fresh marine and freshwater fish from four economically important fish species: Atlantic salmon, European seabass, Nile tilapia, and Rainbow trout. CO + β‐CD reduces the time required to induce anesthesia, independently of water salinity, habitat or water temperature. The plasmatic glucose and cortisol levels decreased in all four species, although the concentrations of CO varied between species. Moreover, plasmatic lactate level differed between the marine and freshwater fish. The use of CO + β‐CD extended the shelf life of fish from all the species studied (by 3–7 days). In conclusion, using CO encapsulated in β‐CD for anesthetizing fish can be regarded as an improved fish‐stunning technique that reduces the anesthesia‐induction time, decreases the stress response, and extends the shelf life of fresh fish.Versión del edito

Urinary transferrin pre-emptively identifies the risk of renal damage posed by subclinical tubular alterations

Nephrotoxicity is an important limitation to the clinical use of many drugs and contrast media. Drug nephrotoxicity occurs in acute, subacute and chronic manifestations ranging from glomerular, tubular, vascular and immunological phenotypes to acute kidney injury. Pre-emptive risk assessment of drug nephrotoxicity poses an urgent need of precision medicine to optimize pharmacological therapies and interventional procedures involving nephrotoxic products in a preventive and personalized manner. Biomarkers of risk have been identified in animal models, and risk scores have been proposed, whose clinical use is abated by their reduced applicability to specific etiological models or clinical circumstances. However, our present data suggest that the urinary level of transferrin may be indicative of risk of renal damage, where risk is induced by subclinical tubular alterations regardless of etiology. In fact, urinary transferrin pre-emptively correlates with the subsequent renal damage in animal models in which risk has been induced by drugs and toxins affecting the renal tubules (i.e. cisplatin, gentamicin and uranyl nitrate); whereas transferrin shows no relation with the risk posed by a drug affecting renal hemodynamics (i.e. cyclosporine A). Our experiments also show that transferrin increases in the urine in the risk state (i.e. prior to the damage) precisely as a consequence of reduced tubular reabsorption. Finally, urinary transferrin pre-emptively identifies subpopulations of oncological and cardiac patients at risk of nephrotoxicity. In perspective, urinary transferrin might be further explored as a wider biomarker of an important mechanism of predisposition to renal damage induced by insults causing subclinical tubular alterations.Research from the authors’ laboratory supporting part of the information incorporated into this article was funded by grants from Instituto de Salud Carlos III (PI14/01776, DT15S/00166, PI15/01055 and PI17/01979, and Retic RD016/0009/0025, REDINREN), Ministerio de Economía y Competitividad (IPT-2012-0779-010000), Junta de Castilla y León (Consejería de Sanidad, BIO/SA20/14, BIO/SA66/15; and Consejería de Educación, SA359U14), and FEDER funds