Gene expression network analysis reveals new transcriptional regulators as novel factors in human ischemic cardiomyopathy

BACKGROUND: Ischemic cardiomyopathy (ICM) is characterized by transcriptomic changes that alter cellular processes leading to decreased cardiac output. Because the molecular network of ICM is largely unknown, the aim of this study was to characterize the role of new transcriptional regulators in the molecular mechanisms underlying the responses to ischemia. METHODS: Myocardial tissue explants from ICM patients and control (CNT) subjects were analyzed by RNA-Sequencing (RNA-Seq) and quantitative Real-Time PCR. RESULTS: Enrichment analysis of the ICM transcriptomic profile allowed the characterization of novel master regulators. We found that the expression of the transcriptional regulators SP100 (-1.5-fold, p < 0.05), CITED2 (-3.8-fold, p < 0.05), CEBPD (-4.9-fold, p < 0.05) and BCL3 (-3.3-fold, p < 0.05) were lower in ICM than in CNT. To gain insights into the molecular network defined by the transcription factors, we identified CEBPD, BCL3, and HIF1A target genes in the RNA-Seq datasets. We further characterized the biological processes of the target genes by gene ontology annotation. Our results suggest that CEBPD-inducible genes with roles in the inhibition of apoptosis are downregulated and that BCL3-repressible genes are involved in the regulation of cellular metabolism in ICM. Moreover, our results suggest that CITED2 downregulation causes increased expression of HIF1A target genes. Functional analysis of HIF1A target genes revealed that hypoxic and stress response genes are activated in ICM. Finally, we found a significant correlation between the mRNA levels of BCL3 and the mRNA levels of both CEBPD (r = 0.73, p < 0.001) and CITED2 (r = 0.56, p < 0.05). Interestingly, CITED2 mRNA levels are directly related to ejection fraction (EF) (r = 0.54, p < 0.05). CONCLUSIONS: Our data indicate that changes in the expression of SP100, CITED2, CEBPD, and BCL3 affect their transcription regulatory networks, which subsequently alter a number of biological processes in ICM patients. The relationship between CITED2 mRNA levels and EF emphasizes the importance of this transcription factor in ICM. Moreover, our findings identify new mechanisms used to interpret gene expression changes in ICM and provide valuable resources for further investigation of the molecular basis of human cardiac ischemic response.National Institute of Health "Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III"European Commissio

ATP synthase subunit alpha and LV mass in ischaemic human hearts

Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D‐DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = −0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology‐specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions

Relationship of Weather Types on the Seasonal and Spatial Variability of Rainfall, Runoff, and Sediment Yield in the Western Mediterranean Basin

Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations.Spanish Government (Ministry of Economy and Competitiveness, MINECO) and FEDER Projects: CGL2014 52135-C3-3-R, ESP2017-89463-C3-3-R, CGL2014-59946-R, CGL2015-65569-R, CGL2015-64284-C2-2-R, CGL2015-64284-C2-1-R, CGL2016-78075-P, GL2008-02879/BTE, LEDDRA 243857, RECARE-FP7, CGL2017-83866-C3-1-R, and PCIN-2017-061/AEI. Dhais Peña-Angulo received a “Juan de la Cierva” postdoctoral contract (FJCI-2017-33652 Spanish Ministry of Economy and Competitiveness, MEC). Ana Lucia acknowledge the "Brigitte-Schlieben-Lange-Programm". The “Geoenvironmental Processes and Global Change” (E02_17R) was financed by the Aragón Government and the European Social Fund. José Andrés López-Tarazón acknowledges the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUS- Fluvial Dynamics Research Group). Artemi Cerdà thank the funding of the OCDE TAD/CRP JA00088807. José Martínez-Fernandez acknowledges the project Unidad de Excelencia CLU-2018-04 co-funded by FEDER and Castilla y León Government. Ane Zabaleta is supported by the Hydro-Environmental Processes consolidated research group (IT1029-16, Basque Government). This paper has the benefit of the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306)

Relationship of Weather Types on the Seasonal and Spatial Variability of Rainfall, Runoff, and Sediment Yield in the Western Mediterranean Basin

Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations

Modelling the impact of climate change on sediment yield in a highly erodible Mediterranean catchment

The assessment of climate change impacts on the sediment cycle is currently a primary concern for environmental policy analysts in Mediterranean areas. Nevertheless, quantitative assessment of climate change impacts is still a complex task. The aim of this study was to implement a sediment model by taking advantage of sediment proxy information provided by reservoir bottom deposits and to use it for climate change assessment in a Mediterranean catchment. The sediment model was utilised in a catchment that drains into a large reservoir. The depositional history of the reservoir was reconstructed and used for sediment sub-model implementation. The model results were compared with gauged suspended sediment data in order to verify model robustness. Then, the model was coupled with future precipitation and temperature scenarios obtained from climate models. Climatological model outputs for two emission scenarios (A2 and B2) were simulated and the results compared with a reference scenario. Model results showed a general decrease in soil moisture and water discharge. Large floods, which are responsible for the majority of sediment mobilisation, also showed a general decrease. Sediment yield showed a clear reduction under the A2 scenario but increased under the B2 scenario. The computed specific sediment yield for the control period was 6.33 Mg ha(-1) year(-1), while for the A2 and B2 scenarios, it was 3.62 and 7.04 Mg ha(-1) year(-1), respectively. Furthermore, sediment transport showed an increase in its time compression, i.e. a stronger dependence of total sediment yield from the largest event contributions. This study shows a methodology for implementing a distributed sediment model by exploiting reservoir sedimentation volumes. This methodology can be applied to a wide range of catchments, given the high availability of reservoir sedimentation data. Moreover, this study showed how such a model can be used in the framework of a climate change study, providing a measure of the impact of climate change on soil erosion and sediment yields.This study was funded by the Spanish Ministry of Economy and Competitiveness through the research projects SCARCE-CONSOLIDER (ref. CSD2009-00065) and ECOTETIS (ref. CGL2011-28776-C02-01). Suspended sediment records of the Isabena river and bathymetrical surveys were carried out within the framework of the project "Sediment export from large semi-arid catchments: measurements and modelling (SESAM), funded by the German Science Foundation (Deutsche Forschungsgemeinschaft, DFG). The authors wish to thank the EbroWater Authorities for permission to install the measuring equipment at the Capella gauging station and or providing hydrological data. Both observed and modelled precipitation and temperature data were provided by the Spanish Meteorological Agency (AEMET). Some of the reservoir bathymetric survey reports were provided by Rafael Cobo Rayan (CEH-CEDEX, National Center for Hydrological Studies).Bussi, G.; Francés, F.; Horel, E.; López Tarazón, JA.; Batalla, R. (2014). Modelling the impact of climate change on sediment yield in a highly erodible Mediterranean catchment. Journal of Soils and Sediments. 14(12):1921-1937. doi:10.1007/s11368-014-0956-7S192119371412Alatorre LC, Beguería S, García-Ruiz JM (2010) Regional scale modeling of hillslope sediment delivery: a case study in the Barasona Reservoir watershed (Spain) using WATEM/SEDEM. J Hydrol 391:109–123Alpert P, Ben-Gai T, Baharad A, Benjamini Y, Yekutieli D, Colacino M, Diodato L, Ramis C, Homar V, Romero R, Michaelides S, Manes A (2002) The paradoxical increase of Mediterranean extreme daily rainfall in spite of decrease in total values. Geophys Res Lett 29(11):1536Andrés-Doménech I, Múnera JC, Francés F, Marco JB (2010) Coupling urban event-based and catchment continuous modelling for combined sewer overflow river impact assessment. Hydrol Earth Syst Sci 14:2057–2072Avendaño Salas C, Cobo Rayán R (1998) Seguimiento de los sólidos en suspensión durante el vaciado del embalse de Joaquín Costa. Limnética 14:113–120Avendaño Salas С, Sanz Montero ME, Cobo Rayán R, Gómez Montaña JL (1997) Sediment yield at Spanish reservoirs and its relationship with the drainage basin area. In: Proceedings of the 19th Symposium of Large Dams, Florence. ICOLD (International Committee on Large Dams), pp 863–874Baade J, Franz S, Reichel A (2012) Reservoir siltation and sediment yield in the Kruger National Park, South Africa: a first assessment. Land Degrad Dev 23:586–600Bangash RF, Passuello A, Sanchez-Canales M, Terrado M, López A, Elorza FJ, Ziv G, Acuña V, Schuhmacher M (2013) Ecosystem services in Mediterranean river basin: climate change impact on water provisioning and erosion control. Sci Total Environ 458-460C:246–255Beguería S, López-Moreno JI, Lorente L, Seeger M, García-Ruiz JM (2003) Assessing the effect of climate oscillations and land-use changes on streamflow in the central Spanish Pyrenees. Ambio 32:283–286Blöschl G (2001) Scaling in hydrology. Hydrol Process 15:709–711Brune GM (1953) Trap efficiency of reservoirs. Trans AGU 34:407–418Bussi G, Rodríguez-Lloveras X, Francés F, Benito G, Sánchez-Moya Y, Sopeña A (2013) Sediment yield model implementation based on check dam infill stratigraphy in a semiarid Mediterranean catchment. Hydrol Earth Syst Sci 17:3339–3354Bussi G, Francés F, Montoya JJ, Julien PY (2014), Distributed sediment yield modelling: importance of initial sediment conditions, Environ Model Softw 58:58–70Cerdà A (1998) Effect of climate on surface flow along a climatological gradient in Israel: a field rainfall simulation approach. J Arid Environ 38:145–159Cerdà A, Brazier R, Nearing M, de Vente J (2013) Scales and erosion. Catena 102:1–2Christensen JH, Carter TR, Rummukainen M, Amanatidis G (2007) Evaluating the performance and utility of regional climate models: the PRUDENCE project. Clim Chang 81(S1):1–6Coulthard TJ, Ramirez J, Fowler HJ, Glenis V (2012) Using the UKCP09 probabilistic scenarios to model the amplified impact of climate change on drainage basin sediment yield. Hydrol Earth Syst Sci 16:4401–4416Cowpertwait P, Ocio D, Collazos G, de Cos O, Stocker C (2013) Regionalised spatiotemporal rainfall and temperature models for flood studies in the Basque Country, Spain. Hydrol Earth Syst Sci 17:479–494Cusack S, Slingo A, Edwards JM, Wild M (1998) The radiative impact of a simple aerosol climatology on the Hadley Centre atmospheric GCM. Quat J R Meteorol Soc 124:2517–2526De Vente J, Poesen J, Verstraeten G (2005) The application of semi-quantitative methods and reservoir sedimentation rates for the prediction of basin sediment yield in Spain. J Hydrol 305:63–86De Vente J, Poesen J, Verstraeten G, Van Rompaey A, Govers G (2008) Spatially distributed modelling of soil erosion and sediment yield at regional scales in Spain. Glob Planet Chang 60:393–415Déqué M (2007) Frequency of precipitation and temperature extremes over France in an anthropogenic scenario: model results and statistical correction according to observed values. Glob Planet Chang 57:16–26Déqué M, Dreveton C, Braun A, Cariolle D (1994) The ARPEGE/IFS atmosphere model: a contribution to the French community climate modelling. Clim Dyn 10:249–266Duck R, McManus J (1993) Sedimentation in natural and artificial impoundments: an indicator of evolving climate land use and dynamic conditions. In: McManus J, Duck R (eds) Geomorphology and sedimentology of lakes and reservoirs. Wiley and Sons, ChichesterEngelund F, Hansen E (1967) A monograph on sediment transport in alluvial streams. Monogr Denmark Tech Univ Hydraul Lab, Teknisk Forlag, CopenhagenESDB2 (2004) The European Soil Database distribution version 2.0. European Commission and the European Soil Bureau Network Office for Official Publications of the European Communities. LuxembourgEuropean Environment Agency (2007) CLC2006 technical guidelines EEA technical report no. 17/2007. European Environment Agency, Copenhagen, DenmarkFrancés F, Vélez JI, Vélez JJ (2007) Split-parameter structure for the automatic calibration of distributed hydrological models. J Hydrol 332:226–240Foster IDL, Rowntree KM, Boardman J, Mighall TM (2012) Changing sediment yield and sediment dynamics in the Karoo uplands, South Africa; post-European impacts. Land Degrad Dev 23:508–522González-Hidalgo JC, Batalla RJ, Cerdà A, de Luis M (2010) Contribution of the largest events to suspended sediment transport across the USA. Land Degrad Dev 21:83–91González-Hidalgo JC, Batalla RJ, Cerdà A (2013) Catchment size and contribution of the largest daily events to suspended sediment load on a continental scale. Catena 102:40–45Herrera S, Gutiérrez JM, Ancell R, Pons MR, Frías MD, Fernández J (2010) Development and analysis of a 50-year high-resolution daily gridded precipitation dataset over Spain (Spain02). Int J Climatol 32:74–85Haregeweyn N, Poesen J, Verstraeten G, Govers G, de Vente J, Nyssen J, Deckers J, Moeyersons J (2013) Assessing the performance of a spatially distributed soil erosion and sediment delivery model (WATEM/SEDEM) in northern Ethiopia. Land Degrad Dev 24:188–204IGME (1994) Mapa geológico de la península ibérica Baleares y Canarias. Instituto Tecnológico Geominero de España, MadridJohnson B, Julien P, Molnar DK, Watson CC (2000) The two-dimensional upland erosion model CASC2D-SED. J Am Water Resour Assoc 36:31–42Jolly JP (1982) A proposed method for accurately calculating sediment yields from reservoir deposition volumes. In: Proceedings of the Exeter Symposium "Recent developments in the explanation and prediction of erosion and sediment yield". Ed. D. E. Walling.  IAHS Publ No 37, IAHS Press, Wallingford, UKJulien P (1995) Erosion and sedimentation. Cambridge University Press, CambridgeKilinc M, Richardson EV (1973) Mechanics of soil erosion from overland flow generated by simulated rainfall. Colorado State University Hydrology Papers, ColoradoLane EW, Koelzer VA (1943) Density of sediments deposited in reservoirs. Rep No 9 of a Study of Methods Used in Measurement and Analysis of Sediment Loads in Streams, Engineering District, St. Paul, MN, USA, District Sub-Office Univ. of Iowa, USALavee HA, Imeson C, Sarah P (1998) The impact of climate change on geomorphology and desertification along a Mediterranean-arid transect. Land Degrad Dev 9:407–422Le Roux JS, Roos ZN (1982) The rate of soil erosion in the Wuras Dam catchment calculated from sediments trapped in the dam. Z Geomorphol Suppl 26:315–329López-Moreno JI, Goyette S, Beniston M (2009) Impact of climate change on snowpack in the Pyrenees: horizontal spatial variability and vertical gradients. J Hydrol 374:384–396López-Tarazón JA, Batalla RJ, Vericat D, Francke T (2009) Suspended sediment transport in a highly erodible catchment: the River Isábena (Southern Pyrenees). Geomorphology 109:210–221López-Tarazón JA, Batalla RJ, Vericat D, Francke T (2012) The sediment budget of a highly dynamic mesoscale catchment: the River Isábena. Geomorphology 138:15–28. doi: 10.1016/jgeomorph201108020López-Vicente M, Navas A, Machín J (2008) Modelling soil detachment rates in rainfed agrosystems in the south-central Pyrenees. Agric Water Manag 95:1079–1089Mamede GL (2008) Reservoir sedimentation in dryland catchments: modelling and management. PhD dissertation, University of Potsdam, UniversitätsbibliothekMiddelkoop H, Daamen K, Gellens D, Grabs W, Kwadijk JCJ, Lang H, Parmet BWAH, Schädler B, Schulla J, Wilke K (2001) Impact of climate change on hydrological regimes and water resources management in the Rhine Basin. Clim Chang 49:105–128Miller CR (1953) Determination of the unit weight of sediment for use in sediment volume computations. Bureau of Reclamation Memorandum Denver, Colorado, USMilly PCD, Dunne KA, Vecchia AV (2005) Global pattern of trends in streamflow and water availability in a changing climate. Nature 438:347–350Moriasi DN, Arnold JG, Van Liew MW, Bingner RL, Harme RD, Veith TL (2007) Model evaluation guidelines for systematic quantification of accuracy in watershed simulations. Trans ASAE 50:885–900Mouri G, Golosov V, Chalov S, Takizawa S, Oguma K, Yoshimura K, Shiiba M, Hori T, Oki T (2013) Assessment of potential suspended sediment yield in Japan in the 21st century with reference to the general circulation model climate change scenarios. Glob Planet Chang 102:1–9Mullan D, Favis-Mortlock D, Fealy R (2012) Addressing key limitations associated with modelling soil erosion under the impacts of future climate change. Agric For Meteorol 156:18–30Müller EN, Francke T (2008) SESAM DATA SESAM: sediment export from semi-arid catchments—measurement and modelling (2005–2008). Potsdam, GermanyNadal-Romero E, Lasanta T, Gonzalez-Hidalgo JC, de Luis M, García-Ruiz JM (2012) The effect of intense rainstorm events on the suspended sediment response under various land uses: the Aísa valley experimental station. Cuad Investig Geogr 38:27–47Nakicenovic N, Swart R (2000) Special report on emissions scenarios. Cambridge University Press, CambridgeNearing MA, Pruski FF, O’Neill MR (2004) Expected climate change impacts on soil erosion rates: a review. J Soil Water Conserv (USA) 59:43–50Nearing MA, Jetten V, Baffaut C, Cerdan O, Couturier A, Hernandez M, Le Bissonnais Y, Nichols MH, Nunes JP, Renschler CS, Souchère V, van Oost K (2005) Modeling response of soil erosion and runoff to changes in precipitation and cover. Catena 61:131–154Nunes JP, Seixas J, Pacheco NR (2008) Vulnerability of water resources vegetation productivity and soil erosion to climate change in Mediterranean watersheds. Hydrol Process 22:3115–3134Olive LJ, Rieger WA (1988) An examination of the role of sampling strategies in the study of suspended sediment transport. In Sediment Budgets. IAHS Publ 174, IAHS Press, Wallingford, UK, pp 259–267Peizhen Z, Molnar P, Downs WR (2001) Increased sedimentation rates and grain sizes 2–4 Myr ago due to the influence of climate change on erosion rates. Nature 410:891–897Pope VD, Gallani ML, Rowntree PR, Stratton RA (2000) The impact of new physical parametrizations in the Hadley Centre climate model: HadAM3. Clim Dyn 16:123–146Pruski FF, Nearing MA (2002) Climate-induced changes in erosion during the 21st century for eight US locations. Water Resour Res 38:34–1–34–11Raclot D, Albergel J (2006) Runoff and water erosion modelling using WEPP on a Mediterranean cultivated catchment. Phys Chem Earth Parts A/B/C 31:1038–1047Regüés D, Nadal-Romero E (2013) Uncertainty in the evaluation of sediment yield from badland areas: suspended sediment transport estimated in the Araguás catchment (central Spanish Pyrenees). Catena 106:93–100Salazar S, Francés F, Komma J, Blume T, Francke T, Bronstert A, Blöschl G (2013) A comparative analysis of the effectiveness of flood management measures based on the concept of “retaining water in the landscape” in different European hydro-climatic regions. Nat Hazards Earth Syst Sci 12(11):3287–3306Sanz Montero ME, Cobo Rayán R, Avendaño Salas C, Gómez Montaña JL (1996) Influence of the drainage basin area on the sediment yield to Spanish reservoirs. In: Proceedings of the First European Conference and Trace Exposition on Control ErosionSeibert J, McDonnell JJ (2002) On the dialog between experimentalist and modeler in catchment hydrology: use of soft data for multicriteria model calibration. Water Resour Res 38(11):23–1–23–14Serrano-Muela P, Nadal-Romero E, Lana-Renault N, González-Hidalgo JC, López-Moreno J I, Beguería S, Sanjuan Y, García-Ruiz JM (2013) An exceptional rainfall event in the Central Western Pyrenees: spatial patterns in discharge and impact. Land Degrad Dev, Online ver. doi: 10.1002/ldr.2221Srinivasan R, Ramanarayanan TS, Arnold JG, Bednarz ST (1998) Large area hydrologic modeling and assessment part II: model application. J Am Water Resour Assoc 34(1):91–101Valero-Garcés BL, Navas A, Machı́n J, Walling D (1999) Sediment sources and siltation in mountain reservoirs: a case study from the Central Spanish Pyrenees. Geomorphology 28:23–41Van Rompaey A, Verstraeten G, Van Oost K, Govers G, Poesen J (2001) Modelling mean annual sediment yield using a distributed approach. Earth Surf Proc Land 26:1221–1236Van Rompaey A, Vieillefont V, Jones RJA, Montanarella L, Verstraeten G, Bazzoffi P, Dostal T, Krasa J, de Vente J, Poesen J (2003) Validation of soil erosion estimates at European scale. European Soil Bureau Research Report No13 EUR 20827 EN Office for Official Publications of the European Communities, LuxembourgVerstraeten G, Poesen J, de Vente J, Koninckx X (2003) Sediment yield variability in Spain: a quantitative and semiqualitative analysis using reservoir sedimentation rates. Geomorphology 50:327–348Walling DE, Fang D (2003) Recent trends in the suspended sediment loads of the world’s rivers. Glob Planet Chang 39:111–126Webb BW, Foster IDL, Gurnell A (1995) Hydrology water quality and sediment behaviour. In: Foster IDL, Gurnell A, Webb BW (eds) Sediment and water quality in river catchments. Wiley, Chichester, pp 1–30Wilby RL, Hay LE, Leavesley GH (1999) A comparison of downscaled and raw GCM output: implications for climate change scenarios in the San Juan River basin Colorado. J Hydrol 225:67–91Zhao G, Mu X, Wen Z, Wang F, Gao P (2013) Soil erosion, conservation and eco-environment changes in the Loess Plateau of China. Land Degrad Dev 24:499–51

Protein inhibitor of NOS1 plays a central role in the regulation of NOS1 activity in human dilated hearts

An essential factor for the production of nitric oxide by nitric oxide synthase 1 (NOS1), major modulator of cardiac function, is the cofactor tetrahydrobiopterin (BH4). BH4 is regulated by GTP cyclohydrolase 1, the rate-limiting enzyme in BH4 biosynthesis which catalyses the formation of dihydroneopterin 3′triphosfate from GTP, producing BH4 after two further steps catalyzed by 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. However, there are other essential factors involved in the regulation of NOS1 activity, such as protein inhibitor of NOS1 (PIN), calmodulin, heat shock protein 90, and NOS interacting protein. All these molecules have never been analysed in human non-ischemic dilated hearts (DCM). In this study we demonstrated that the upregulation of cardiac NOS1 is not accompanied by increased NOS1 activity in DCM, partly due to the elevated PIN levels and not because of alterations in biopterin biosynthesis. Notably, the PIN concentration was significantly associated with impaired ventricular function, highlighting the importance of this NOS1 activity inhibitor in Ca2+ homeostasis. These results take a central role in the current list of targets for future studies focused on the complex cardiac dysfunction processes through more efficient harnessing of NOS1 signalling

Human ischemic cardiomyopathy shows cardiac Nos1 translocation and its increased levels are related to left ventricular performance

The role of nitric oxide synthase 1 (NOS1) as a major modulator of cardiac function has been extensively studied in experimental models; however, its role in human ischemic cardiomyopathy (ICM) has never been analysed. Thus, the objectives of this work are to study NOS1 and NOS-related counterparts involved in regulating physiological function of myocyte, to analyze NOS1 localisation, activity, dimerisation, and its relationship with systolic function in ICM. The study has been carried out on left ventricular tissue obtained from explanted human hearts. Here we demonstrate that the upregulation of cardiac NOS1 is not accompanied by an increase in NOS activity, due in part to the alterations found in molecules involved in the regulation of its activity. We observed partial translocation of NOS1 to the sarcolemma in ischemic hearts, and a direct relationship between its protein levels and systolic ventricular function. Our findings indicate that NOS1 may be significant in the pathophysiology of human ischemic heart disease with a preservative role in maintaining myocardial homeostasis

Protein inhibitor of NOS1 plays a central role in the regulation of NOS1 activity in human dilated hearts

An essential factor for the production of nitric oxide by nitric oxide synthase 1 (NOS1), major modulator of cardiac function, is the cofactor tetrahydrobiopterin (BH4). BH4 is regulated by GTP cyclohydrolase 1, the rate-limiting enzyme in BH4 biosynthesis which catalyses the formation of dihydroneopterin 3′triphosfate from GTP, producing BH4 after two further steps catalyzed by 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. However, there are other essential factors involved in the regulation of NOS1 activity, such as protein inhibitor of NOS1 (PIN), calmodulin, heat shock protein 90, and NOS interacting protein. All these molecules have never been analysed in human non-ischemic dilated hearts (DCM). In this study we demonstrated that the upregulation of cardiac NOS1 is not accompanied by increased NOS1 activity in DCM, partly due to the elevated PIN levels and not because of alterations in biopterin biosynthesis. Notably, the PIN concentration was significantly associated with impaired ventricular function, highlighting the importance of this NOS1 activity inhibitor in Ca2+ homeostasis. These results take a central role in the current list of targets for future studies focused on the complex cardiac dysfunction processes through more efficient harnessing of NOS1 signalling