TRPC Channels in the SOCE Scenario

Transient receptor potential (TRP) proteins form non-selective Ca2+ permeable channels that contribute to the modulation of a number of physiological functions in a variety of cell types. Since the identification of TRP proteins in Drosophila, it is well known that these channels are activated by stimuli that induce PIP2 hydrolysis. The canonical TRP (TRPC) channels have long been suggested to be constituents of the store-operated Ca2+ (SOC) channels; however, none of the TRPC channels generate Ca2+ currents that resemble ICRAC. STIM1 and Orai1 have been identified as the components of the Ca2+ release-activated Ca2+ (CRAC) channels and there is a body of evidence supporting that STIM1 is able to gate Orai1 and TRPC1 in order to mediate non-selective cation currents named ISOC. STIM1 has been found to interact to and activate Orai1 and TRPC1 by different mechanisms and the involvement of TRPC1 in store-operated Ca2+ entry requires both STIM1 and Orai1. In addition to the participation of TRPC1 in the ISOC currents, TRPC1 and other TRPC proteins might play a relevant role modulating Orai1 channel function. This review summarizes the functional role of TRPC channels in the STIM1–Orai1 scenario.Junta de Extremadura Consejería de Economía e Infraestructura-FEDER Grant IB16046 y GR18061Junta de Extremadura TA18011 y TA18054Ministerio de Ciencia, Innovación y Universidade

EFHB is a Novel Cytosolic Ca2+ Sensor That Modulates STIM1-SARAF Interaction

Background/aims: STIM1 and Orai1 are the key components of store-operated Ca2+ entry (SOCE). Among the proteins involved in the regulation of SOCE, SARAF prevents spontaneous activation of SOCE and modulates STIM1 function. Methods: Cytosolic Ca2+ mobilization was estimated in fura-2-loaded cells using an epifluorescence inverted microscope. STIM1 interaction with Orai1, EFHB (EF-hand domain family member B, also known as CFAP21) and SARAF was detected by immunoprecipitation followed by Western blotting using specific antibodies. The involvement of EFHB in the translocation of NFAT to the nucleus was detected by confocal microscopy. Results: Here, we report the identification of EFHB as a new SOCE regulator. EFHB interacts with STIM1 upon store depletion and dissociates through a Ca2+-dependent mechanism. RNAi-mediated silencing as well as overexpression studies revealed that EFHB plays a relevant role in the interaction of STIM1 and Orai1 upon store depletion, the activation of SOCE and NFAT translocation from the cytosol to the nucleus. Silencing EFHB expression abolished the dissociation of SARAF from STIM1, which indicates that EFHB might play an important role in the dynamic interaction between both proteins, which is relevant for the activation of Orai1 channels upon Ca2+ store depletion and their subsequent modulation via slow Ca2+-dependent inactivation. Conclusion: Our results indicate that EFHB is a new SOCE regulator that modulates STIM1-SARAF interaction.MINECO BFU2013-45564-C2-1-P/2-P, BFU2016-74932-C2-1-P/2-P, BFU2016-74932-C2-1-PJunta de Extremadura-FEDER (Fondo Europeo de Desarrollo Regional Grants) IB16046, GR18061Junta de Extremadura-FEDER European Union (EU) IB16046Ministerio Economía y Competitividad, España IJCI-2015-25665MINECO Grant BFU2016-74932-C2-1-

Altered protein expression and protein nitration pattern during d-galactosamine-induced cell death in human hepatocytes: a proteomic analysis

BACKGROUND/AIMS: Hepatic injury by d-galactosamine (d-GalN) is a suitable experimental model of hepatocellular injury. The induction of oxidative and nitrosative stress participates during d-GalN-induced cell death in cultured rat hepatocytes. This study aimed to identify protein expression changes during the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes. METHODS: A proteomic approach was used to identify the proteins involved and those altered by tyrosine nitration. A high dose of d-GalN (40 mM) was used to induce apoptosis and necrosis in primary culture of human hepatocytes. Cellular lysates prepared at different times after addition of d-GalN were separated by two-dimensional electrophoresis. Gel spots with an altered expression and those matching nitrotyrosine-immunopositive proteins were excised and analyzed by mass spectrometry. RESULTS: d-GalN treatment upregulated microsomal cytochrome b5, fatty acid binding protein and manganese superoxide dismutase, and enhanced annexin degradation. d-GalN increased tyrosine nitration of four cytosolic (Hsc70, Hsp70, annexin A4 and carbonyl reductase) and three mitochondrial (glycine amidinotransferase, ATP synthase beta chain, and thiosulfate sulfurtransferase) proteins in human hepatocytes. CONCLUSIONS: The results provide evidences that oxidative stress and nitric oxide-derived reactive oxygen intermediates induce specific alterations in protein expression that may be critical for the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes

Seasonal and Spatial Patterns in Salinity, Nutrients, and Chlorophyll α in the Alvarado Lagoonal System, Veracruz, Mexico

Ten monthly collections, distributed among three seasons, were taken from July 2000 to June 2001 in the Alvarado lagoonal system, Veracruz, Mexico. Variables measured in situ included dissolved oxygen, salinity, and water temperature. Water samples were collected to determine concentrations of ammonium, nitrates, nitrites, orthophosphates, total phosphorus and chlorophyll α. Collections representing the rainy season were taken in September and October, those for the nortes season were taken in November, December, and January, and dry season collections were taken during February, March, May June, and July. There was seasonal and spatial variation in nutrient concentrations, and they were related to the discharge of the rivers; concentrations increased during the rainy and nortes seasons. Other factors affecting water quality included the constant discharge of organic materials into the system, resuspension of sediments during the nortes season and the biological activity within the system that assimilated the nutrients in the water. The Alvarado lagoonal system has three separate zones based on physicochemical characteristics; Camaronera Lagoon, Buen Pais Lagoon and the urban zone of Alvarado Lagoon, and the river zone in Alvarado Lagoon

Selecting patterns and features for between- and within-crop-row weed mapping using UAV-imagery

This paper approaches the problem of weed mapping for precision agriculture, using imagery provided by Unmanned Aerial Vehicles (UAVs) from sunflower and maize crops. Precision agriculture referred to weed control is mainly based on the design of early post-emergence site-specific control treatments according to weed coverage, where one of the most important challenges is the spectral similarity of crop and weed pixels in early growth stages. Our work tackles this problem in the context of object-based image analysis (OBIA) by means of supervised machine learning methods combined with pattern and feature selection techniques, devising a strategy for alleviating the user intervention in the system while not compromising the accuracy. This work firstly proposes a method for choosing a set of training patterns via clustering techniques so as to consider a representative set of the whole field data spectrum for the classification method. Furthermore, a feature selection method is used to obtain the best discriminating features from a set of several statistics and measures of different nature. Results from this research show that the proposed method for pattern selection is suitable and leads to the construction of robust sets of data. The exploitation of different statistical, spatial and texture metrics represents a new avenue with huge potential for between and within crop-row weed mapping via UAV-imagery and shows good synergy when complemented with OBIA. Finally, there are some measures (specially those linked to vegetation indexes) that are of great influence for weed mapping in both sunflower and maize crops

Spatial and temporal patterns of Holocene precipitation change in the Iberian Peninsula

Precipitation is a key climate parameter of vegetation and ecosystems in the Iberian Peninsula. Here, we use a regional pollen-climate calibration model and fossil pollen data from eight sites from the Atlantic coast to southern Spain to provide quantitative reconstructions of annual precipitation trends and excursions and their regional patterns for the last 11 700 years. The Early Holocene (11 700 to 11 000 cal. a BP) was characterized by high precipitation values followed by a slowly declining trend until about 9000 cal. a BP in the south and about 8000 cal. a BP in the north. From 8000 to 6000 cal. a BP the reconstructed precipitation values are the highest in most records, especially in those located in the Mediterranean climatic region in the southern part of the peninsula, with maximum values nearly 100% higher than the modern reconstructed values. The results suggest a declining precipitation during the Late Holocene in the south, with a positive excursion at around 2500 cal. a BP, while in the north precipitation remained high until 500 cal. a BP. However, the Late Holocene climate reconstructions in the Iberian Peninsula are biased by intensifying human impact on vegetation. The statistical time series analyses using SiZer technique do not indicate any statistically significant high-frequency drought events in the region. In general, our results suggest regional differences in the precipitation patterns between the northern and southern parts of the peninsula, with a more distinct Middle Holocene period of high humidity in the south.Peer reviewe

Spatial and temporal patterns of Holocene precipitation change in the Iberian Peninsula

Precipitation is a key climate parameter of vegetation and ecosystems in the Iberian Peninsula. Here, we use a regional pollen-climate calibration model and fossil pollen data from eight sites from the Atlantic coast to southern Spain to provide quantitative reconstructions of annual precipitation trends and excursions and their regional patterns for the last 11 700 years. The Early Holocene (11 700 to 11 000 cal. a BP) was characterized by high precipitation values followed by a slowly declining trend until about 9000 cal. a BP in the south and about 8000 cal. a BP in the north. From 8000 to 6000 cal. a BP the reconstructed precipitation values are the highest in most records, especially in those located in the Mediterranean climatic region in the southern part of the peninsula, with maximum values nearly 100% higher than the modern reconstructed values. The results suggest a declining precipitation during the Late Holocene in the south, with a positive excursion at around 2500 cal. a BP, while in the north precipitation remained high until 500 cal. a BP. However, the Late Holocene climate reconstructions in the Iberian Peninsula are biased by intensifying human impact on vegetation. The statistical time series analyses using SiZer technique do not indicate any statistically significant high-frequency drought events in the region. In general, our results suggest regional differences in the precipitation patterns between the northern and southern parts of the peninsula, with a more distinct Middle Holocene period of high humidity in the south.Peer reviewe

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

Background In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. Objectives The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action. Methods Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1Δi12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. Results In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1Δi12 mice show increased cardiac hypertrophy and declined contractility. Conclusions The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches

Imaging land subsidence in the Guadalentín River Basin (SE Spain) using Advanced Differential SAR Interferometry

Aquifer overexploitation can lead to the irreversible loss of groundwater storage caused by the compaction or consolidation of unconsolidated fine-grained sediments resulting in land subsidence. Advanced Differential SAR Interferometry (A-DINSAR) is particularly efficient to monitor progressive ground movements, making it an appropriate method to study depleting aquifers undergoing overexploitation and land subsidence. The Guadalentín River Basin (Murcia, Spain) is a widely recognized subsiding area that exhibits the highest rates of groundwater-related land subsidence recorded in Europe (>10 cm/yr). The basin covers an extension of more than 500 km2 and is underlain by an overexploited aquifer-system formed by two contiguous hydraulically connected units (Alto Guadalentín and Bajo Guadalentín). Although during the last years the piezometric levels have partially stabilized, the ongoing aquifer-system deformation is evident and significant, as revealed by the A-DInSAR analysis presented. In this work, we submit the first vertical and horizontal (E-W) decomposition results of the LOS velocity and displacement time series of the whole Guadalentín Basin obtained from two datasets of Sentinel-1 SAR acquisitions in ascending and descending modes. The images cover the period from 2015 to 2021 and they were processed using the Parallel Small BAseline Subset (P-SBAS) implemented by CNRIREA in the Geohazards Exploitation Platform (GEP) on-demand web tool, which is funded by the European Space Agency. The output ascending and descending measurement points of P-SBAS lie on the same regular grid, which is particularly suited for the geometrical decomposition. Time series displacements are compared to a permanent GNSS station located in the Bajo Guadalentín basin.This study has received funding in framework of the RESERVOIR project (Sustainable groundwater RESources managEment by integrating eaRth observation deriVed monitoring and flOw modelIng Results), funded by the Partnership for Research and Innovation in the Mediterranean Area (PRIMA) programme supported by the European Union (Grant Agreement 1924; https://reservoir-prima.org/). The study has also been supported by the Grant FPU19/03929 (funded by MCIN/AEI/10.13039/501100011033 and by “FSE invests in your future”); the Project CGL2017-83931-C3-3-P (funded by MCIN/ AEI/10.13039/501100011033 and by “ERDF A way of making Europe”); the ESA-MOST China DRAGON-5 Project (ref. 59339) and the SARAI Project PID2020-116540RB-C22 (funded by MCIN/AEI/10.13039/501100011033). Copernicus Sentinel-1 IW SAR data were provided and processed in ESA’s Geohazards Exploitation Platform (GEP), in the framework of the GEP Early Adopters Programme

Spanish multicenter real – life registry of retrievable vena cava filters (REFiVeC)

Background The treatment of venous thromboembolic disease the treatment of choice is systemic anticoagulation. However, the interruption of the inferior vena cava with filters has been recommended when anticoagulation fails or there is a contraindication. Due to the rising inferior vena cava filter (IVCF) complications, physicians are encouraged to retrieve them when there is no longer recommended. In daily practice, it may be a difficult close follow-up of these patients. In this study, the primary objective was to evaluate the IVCF retrieval rate of all implanted filters in a Spanish registry. Secondary objectives were to analyze the causes of failed retrieval, procedure-related complications, and outcomes at a 12-month follow-up. Results Three hundred fifty-six vena cava filters were implanted in 355 patients. The types of filter were: Gunther Tulip (Cook Medical) 160 (44.9%), Optease (Cordis) 77 (21.6%), Celect (Cook Medical) 49 (13, 7%), Aegisy (Lifetech Scientific) 33 (9.2%), Option ELITE (Argon Medical devices) 16 (4.4%), Denali filter (BD Bard) 11 (3.08%), ALN filter (ALN) 10 (2.8%). Removal was achieved in 274/356 (76,9%). eighty-two (23,1%) IVCF were not retrieved due to the following: 41 (11,5%) patients required ongoing filtration, 24 IVCF (6,7%) patients died before retrieval, and 17 (4,7%) impossibility of retrieval because of a tilted and embedded filter apex. There were no major complications observed. Conclusions The global retrieval rate of IVCF was achieved in 76.9%, and the adjusted retrieval rate was of 94.15% with no major complications. IVCF tilting was associated with failure of filter removal in less than 5% of cases. This study demonstrates that the retrieval procedure of IVCF is controlled by the clinician and not by the interventional radiologist