Mechanisms Responsible for omega-Pore Currents in Ca-v Calcium Channel Voltage-Sensing Domains

Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in CaV1.1 and CaV1.3 Ca2+ channels bearing several S4 charge mutations. Our modeling predicts that mutations of CaV1.1-R1 (R528H/G, R897S) or CaV1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of CaV1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. Functional characterization validates the modeling prediction showing that CaV1.3-R990H channels conduct ω-currents at hyperpolarizing potentials, but not upon membrane depolarization compared with wild-type channels

Water as a solvent of election for obtaining oleuropein-rich extracts from olive (Olea europaea) leaves

Leaves from Olea europaea represent one of the main by-products of the olive oil industry, containing a plethora of bioactive compounds with several promising activities for human health. An organic solvent-free extraction method was developed for the recovery of olive leaf phenols, which obtained an extract containing oleuropein in high amounts. A comparison of various extraction media is reported, together with the total phenolic content, DPPH (2,2-Diphenyl-1-picrylhydrazyl) content, ORAC (oxygen radical absorbance capacity), and polyphenol oxidase activity of the corresponding extracts. The polyphenol profiles and content of the most representative extracts have also been studied. Extraction solvent and temperature significantly influenced the phenolic content and antioxidant activity of the extracts, with hot water representing the solvent of election for the extraction of bioactive compounds from this matrix. All the extracts obtained showed reasonably high total phenol content (TPC) and good DPPH radical scavenging activity; among them, the water extract is characterized by desirable traits and could be used for many industrial applications and human consumption

miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer

This work is licensed under a Creative Commons Attribution 4.0 International License.Elevated prostaglandin E2 (PGE2) levels are observed in colorectal cancer (CRC) patients, and this increase is associated with poor prognosis. Increased synthesis of PGE2 in CRC has been shown to occur through COX-2-dependent mechanisms; however, loss of the PGE2-catabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, HPGD), in colonic tumors contributes to increased prostaglandin levels and poor patient survival. While loss of 15-PGDH can occur through transcriptional mechanisms, we demonstrate that 15-PGDH can be additionally regulated by a miRNA-mediated mechanism. We show that 15-PGDH and miR-21 are inversely correlated in CRC patients, with increased miR-21 levels associating with low 15-PGDH expression. 15-PGDH can be directly regulated by miR-21 through distinct sites in its 3′ untranslated region (3′UTR), and miR-21 expression in CRC cells attenuates 15-PGDH and promotes increased PGE2 levels. Additionally, epithelial growth factor (EGF) signaling suppresses 15-PGDH expression while simultaneously enhancing miR-21 levels. miR-21 inhibition represses CRC cell proliferation, which is enhanced with EGF receptor (EGFR) inhibition. These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE2.NIH R01 CA134609NIH R01 AR069044NIH/NCI Cancer Center Support Grant (P30 CA168524)New Jersey Commission on Cancer ResearchAmerican Heart Association (15GRNT23240019

Efecto del riego y la poda en el contenido de componentes menores y ácidos grasos del aceite de oliva virgen varietal Farga

The effect of different irrigation and pruning strategies on the amount of substances related to the oxidative stability of virgin olive oils of the variety Farga (polyphenols, chlorophylls, carotenoids and fatty acids), was analyzed. Four treatments were used: T100%SP (irrigation supplying 100% of the plants’ evaporative transpiration demand (Etc) during the entire cycle, without winter pruning); T50%SP (irrigation supplying 50% of the plants’ Etc from pit hardening to harvest, without winter pruning); T100%CP (irrigation supplying 100%, with pruning) and T50%CP (irrigation supplying 50%, with pruning). The plants’ hydric status was monitored through the stem hydric potential (SHP) at noon, and the soil moisture content and the photosynthetically active incident radiation within the tree branches were determined. The olive sampling was taken from pre-ripening to full maturity. The oil was extracted from the olives by grinding them in a laboratory screw type mill with thermo-kneading. The separation of solid and liquid phases was performed using a hand press and decanter to remove the oil. Chlorophylls and carotenoids (absorbance at 670 nm and 472 nm) and total polyphenols (at 725 nm), were determined by spectrophotometry on the mechanically extracted oil. Fatty acids were determined by capillary gas chromatography (CGC). Oil yield data show no statistical differences between deficit irrigation covering 50% of the ETc and the control treatment, both in plants with or without pruning. The contents of polyphenols, chlorophylls and carotenoids in the oils decrease with fruit ripening, regardless of the initial content and treatment. Deficit irrigation treatments (T 50%) have higher contents of polyphenols (except for pre-envero sampling), chlorophylls and carotenoids. There are no statistically significant differences between treatments with and without pruning.Se analizó el efecto de distintas estrategias de riego y poda, sobre el contenido de componentes vinculados a la estabilidad oxidativa de los aceites de oliva vírgenes (polifenoles, clorofilas y carotenoides), variedad Farga. Se aplicaron cuatro tratamientos: T100%SP (riego equivalente al 100% de la demanda evapotranspiratoria (Etc) del cultivo durante todo el ciclo y sin poda invernal); T50%SP (riego que equivalente al 50% de la Etc desde endurecimiento de carozo hasta cosecha y sin poda); T100%CP (riego 100% y con poda); T50%CP (riego deficitario y con poda). Se monitoreó el estado hídrico de las plantas a través del potencial hídrico del tallo a mediodía (PHT), el contenido de humedad del suelo y la radiación fotosintéticamente activa incidente en el interior de la copa de los olivos. El muestreo de aceitunas se extendió desde pre-envero hasta maduración completa. El aceite se extrajo en laboratorio por molienda de las aceitunas con molino de tornillo, termo-amasado, separación de fases sólida y líquida con una prensa manual y decantación para separar el aceite. Sobre el aceite extraído por métodos mecánicos se determinó: perfil de ácidos grasos, clorofilas y carotenoides (espectrofotometría a 670 nm y 472 nm), polifenoles totales (absorbancia a 725 nm) y ácidos grasos por cromatografía gaseosa capilar (CGC). Los datos de rendimiento graso (lipogénesis) expuestos muestran que no hay diferencias estadísticas entre un riego deficitario que cubre 50% de la Etc y el tratamiento control, tanto en plantas con poda o sin ella. El contenido de polifenoles, clorofilas y carotenoides en los aceites desciende a medida que avanza el estado de madurez de los frutos, independientemente del contenido inicial y el tratamiento. Los tratamientos con riego deficitario (T50%) presentan contenidos más elevados de polifenoles (excepto para el muestreo de pre-envero), clorofilas y de carotenoides. No se observan diferencias estadísticamente significativas entre los tratamientos con y sin poda

Th17-related cytokines: new players in the control of chronic intestinal inflammation

Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man, are thought to be caused by an excessive and poorly controlled immune response that is directed against components of the normal microflora. The exact sequence of events by which this pathological process is triggered and maintained is not fully understood, but studies in experimental models of IBD and data emerging from recent clinical trials indicate that T cell-derived cytokines are crucial mediators of the tissue damage. Although CD and UC have been traditionally considered two typical examples of T helper (Th)1 or Th2-associated disease respectively, it is now known that CD- and UC-related inflammation is also marked by enhanced production of cytokines made by a distinct subset of Th cells, termed Th17 cells. Th17 cytokines can have both tissue-protective and inflammatory effects in the gut and there is evidence that Th17 cells can alter their cytokine program according to the stimuli received and convert into Th1-producing cells. These novel findings have contributed to advancing our understanding of mechanisms of gut tissue damage and open new avenues for development of therapeutic strategies in IBD

Synergistic use of Lagrangian dispersion and radiative transfer modelling with satellite and surface remote sensing measurements for the investigation of volcanic plumes: the Mount Etna eruption of 25–27 October 2013

Abstract. In this paper we combine SO2 and ash plume dispersion modelling with satellite and surface remote sensing observations to study the regional influence of a relatively weak volcanic eruption from Mount Etna on the optical and micro-physical properties of Mediterranean aerosols. We analyse the Mount Etna eruption episode of 25–27 October 2013. The evolution of the plume along the trajectory is investigated by means of the FLEXible PARTicle Lagrangian dispersion (FLEXPART) model. The satellite data set includes true colour images, retrieved values of volcanic SO2 and ash, estimates of SO2 and ash emission rates derived from MODIS (MODerate resolution Imaging Spectroradiometer) observations and estimates of cloud top pressure from SEVIRI (Spinning Enhanced Visible and InfraRed Imager). Surface remote sensing measurements of aerosol and SO2 made at the ENEA Station for Climate Observations (35.52° N, 12.63° E; 50 m a.s.l.) on the island of Lampedusa are used in the analysis. The combination of these different data sets suggests that SO2 and ash, despite the initial injection at about 7.0 km altitude, reached altitudes around 10–12 km and influenced the column average aerosol particle size distribution at a distance of more than 350 km downwind. This study indicates that even a relatively weak volcanic eruption may produce an observable effect on the aerosol properties at the regional scale. The impact of secondary sulfate particles on the aerosol size distribution at Lampedusa is discussed and estimates of the clear-sky direct aerosol radiative forcing are derived. Daily shortwave radiative forcing efficiencies, i.e. radiative forcing per unit AOD (aerosol optical depth), are calculated with the LibRadtran model. They are estimated between −39 and −48 W m−2 AOD−1 at the top of the atmosphere and between −66 and −49 W m−2 AOD−1 at the surface, with the variability in the estimates mainly depending on the aerosol single scattering albedo. These results suggest that sulfate particles played a large role in the transported plume composition and radiative forcing, while the contribution by ash particles was small in the volcanic plume arriving at Lampedusa during this event

Wet Angrites? A D/H and Pb-Pb Study of Silicates and Phosphates

No abstract availabl