Search

Using a model of medroxyprogesterone acetate (MPA)-induced mouse mammary tumors that transit through different stages of hormone dependence, we previously reported that the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) pathway is critical for the growth of hormone-independent (HI) mammary carcinomas but not for the growth of hormone-dependent (HD) mammary carcinomas. The objective of this work was to explore whether the activation of the PI3K/AKT pathway is responsible for the changes in tumor phenotype and for the transition to autonomous growth. We found that the inhibition of the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway suppresses HI tumor growth. In addition, we were able to induce mammary tumors in mice in the absence of MPA by inoculating HD tumor cells expressing a constitutively active form of AKT1, myristoylated AKT1 (myrAKT1). These tumors were highly differentiated and displayed a ductal phenotype with laminin-1 and cytokeratin 8 expression patterns typical of HI tumors. Furthermore, myrAKT1 increased the tumor growth of IBH-6 and IBH-7 human breast cancer cell lines. In the estrogen-dependent IBH-7 cell line, myrAKT1 induced estrogen-independent growth accompanied by the expression of the adhesion markers focal adhesion kinase and E-cadherin. Finally, we found that cells expressing myrAKT1 exhibited increased phosphorylation of the progesterone receptor at Ser190 and Ser294 and of the estrogen receptor α at Ser118 and Ser167, independently of exogenous MPA or estrogen supply. Our results indicate that the activation of the PI3K/AKT/mTOR pathway promotes tissue architecture remodeling and the activation of steroid receptors. [ABSTRACT FROM AUTHOR]

A better understanding of the water and energy cycles at climate scale in the Third Pole Environment is essential for assessing and understanding the causes of changes in the cryosphere and hydrosphere in relation to changes of plateau atmosphere in the Asian monsoon system and for predicting the possible changes in water resources in South and East Asia. This paper reports the following results: (1) A platform of in situ observation stations is briefly described for quantifying the interactions in hydrosphere-pedosphere-atmosphere-cryosphere-biosphere over the Tibetan Plateau. (2) A multiyear in situ L-Band microwave radiometry of land surface processes is used to develop a new microwave radiative transfer modeling system. This new system improves the modeling of brightness temperature in both horizontal and vertical polarization. (3) A multiyear (2001–2018) monthly terrestrial actual evapotranspiration and its spatial distribution on the Tibetan Plateau is generated using the surface energy balance system (SEBS) forced by a combination of meteorological and satellite data. (4) A comparison of four large scale soil moisture products to in situ measurements is presented. (5) The trajectory of water vapor transport in the canyon area of Southeast Tibet in different seasons is analyzed, and (6) the vertical water vapor exchange between the upper troposphere and the lower stratosphere in different seasons is presented. [ABSTRACT FROM AUTHOR]

The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions – whether it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes. [ABSTRACT FROM AUTHOR]

Run of river (RoR) hydropower systems, despite being one of the most cost-effective and environmentally benign energy technologies, have the disadvantage that production is not constant because it is subject to a high variability in precipitation and snow cover. In addition, the management of RoR plants has to comply with some particular operating conditions, but also with some environmental flow requirements. This work presents the assessment of the main inputs included in a climate service, historical local data and the seasonal forecast of water inflow to RoR plants, which are used to predict the operability and the expected energy production. The analysis is presented through the application in a pilot RoR system located in the south of Spain, in a semi-arid Mediterranean area impacted by snow, where seasonal forecasting is especially challenging. The results show the high interannual variability of the operation in this kind of facilities. The outcomes indicate that seasonal climate forecast information would improve the prediction of observed river streamflow by 7.4% in reliability and 3.2% in sharpness compared to the current operational forecast based on historical data. The climate forecasts thus provide valuable information for the exploitation of available water resources, which generates a significant value for the operation of the plant and the energy production market. [ABSTRACT FROM AUTHOR]

Background: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). Methods: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). Results: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. Conclusion: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed. [ABSTRACT FROM AUTHOR]

The operation feasibility of small hydropower plants in mountainous sites is subjected to the run-of-river flow, which is also dependent on a high variability in precipitation and snow cover. Moreover, the management of this kind of system has to be performed with some particular operation conditions of the plant (e.g., turbine minimum and maximum discharge) but also some environmental flow requirements. In this context, a technological climate service is conceived in a tight connection with end users, perfectly answering the needs of the management of small hydropower systems in a pilot area, and providing a forecast of the river streamflow together with other operation data. This paper presents an overview of the service but also a set of lessons learnt related to the features, requirements, and considerations to bear in mind from the point of view of climate service developers. In addition, the outcomes give insight into how this kind of service could change the traditional management (normally based on past experience), providing a probability range of the future river flow based on future weather scenarios according to the range of future weather possibilities. This highlights the utility of the co-generation process to implement climate services for water and energy fields but also that seasonal climate forecasting could improve the business as usual of this kind of facility. [ABSTRACT FROM AUTHOR]

Annual grasslands are an essential component of oak savanna ecosystems as the primary source of fodder for livestock and wildlife. Drought resistance adaptation has led them to complete their life cycle before serious soil and plant water deficits develop, resulting in a close link between grass phenology and soil water dynamics. In this work, these links were explored using a combination of terrestrial photography, satellite imagery and hydrological ground measurements. We obtained key phenological parameters of the grass cycle from terrestrial camera data using the Green Chromatic Coordinate (GCCc) index. These parameters were compared with those provided by time-series of vegetation indices (VI) obtained from Sentinel-2 (S2) satellites and time-series of abiotic variables, which defined the hydrology of the system. The results showed that the phenological parameters estimated by the S2 Normalized Difference Vegetation Index (NDVI) (r = 0.83, p < 0.001) and soil moisture (SM) (r = 0.75, p < 0.001) presented the best agreement with ground-derived observations compared to those provided by other vegetation indices and abiotic variables. The study of NDVI and SM dynamics, that was extended over four growing seasons (July 2015–May 2019), showed that the seasonality of both variables was highly synchronized, with the best agreements at the beginning and at the end of the dry seasons. However, stage changes were estimated first by SM, followed by NDVI, with a delay of between 3 and 10 days. These results support the use of a multi-approach method to monitor the phenology and the influence of the soil moisture dynamic under the study conditions. [ABSTRACT FROM AUTHOR]

Objective: The study evaluated the anatomical and functional outcomes, as well as the safety data of laparoscopic sacrocolpopexy (LSC) for pelvic organ prolapse (POP) using a lightweight macroporous mesh. Methods: A multicentric observational study was developed including five expert centers between March 2011 and December 2019. Inclusion criteria were female patients with symptomatic ≥stage II POP (POP‐Q classification), who underwent a LSC. A lightweight and macroporous mesh device (Surelift Uplift) was used. Baseline anatomical positions were evaluated using POP‐Q stage. The anatomical outcomes and procedural complications were assessed during the postoperative period. Primary outcomes were anatomical success, defined as POP‐Q stage ≤I, and subjective success, defined as no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse. Results: A total of 325 LSCs were analyzed with a median patient age of 66 (interquartile range [IQR] 61–73). After a median follow‐up of 68 months (IQR 46.5–89), anatomical success was found in 88.9%, whereas subjective success was seen in 98.5% of the patients. Recurrent prolapse presented as cystocele (1.5%). Reported complications were bladder (4.6%) or rectum lesions (0.6%), de novo urinary incontinence (12.9%), and mesh extrusion (1.2%). Conclusions: LSC provides significant clinical improvement and excellent anatomical results, with a low risk of serious complications for women with ≥2 grade POP in a real clinical practice setting. [ABSTRACT FROM AUTHOR]

Climate change is increasing the vulnerability of Mediterranean coniferous plantations. Here, we integrate a Landsat time series with a physically-based distributed hydrological model (Watershed Integrated Management in Mediterranean Environments—WiMMed) to examine spatially-explicit relationships between the mortality processes of Pinus pinaster plantations and the hydrological regime, using different spectral indices of vegetation and machine learning algorithms. The Normalized Burn Ratio (NBR) and Moisture Stress Index (MSI) show the highest correlations with defoliation rates. Random Forest was the most accurate model (R2 = 0.79; RMSE = 0.059), showing a high model performance and prediction. Support vector machines and neural networks also demonstrated a high performance (R2 > 0.7). The main hydrological variables selected by the model to explain defoliation were potential evapotranspiration, winter precipitation and maximum summer temperature (lower Out-of-bag error). These results show the importance of hydrological variables involved in evaporation processes, and on the change in the spatial distribution of seasonal rainfall upon the defoliation processes of P. pinaster. These results underpin the importance of integrating temporal remote sensing data and hydrological models to analyze the drivers of forest defoliation and mortality processes in the Mediterranean climate. [ABSTRACT FROM AUTHOR]

Introduction: HIV worsens HCV‐related liver disease by accelerating fibrosis progression; however, progression rates are extremely variable among HIV/HCV‐coinfected individuals. NK cells are associated with modulation of liver fibrosis and are profoundly altered during HCV and HIV infections. CD4+ T‐cells modulate NK cell function, and are also affected by HIV infection. Here, we aim to characterize the association of hepatic fibrosis with both the phenotype and function of peripheral NK cells and their regulation by CD4+ T‐cells, in HIV/HCV‐coinfected individuals. Methods: Thirty‐four HIV/HCV‐coinfected individuals with minimal (n = 16) and advanced (n = 18) fibrosis (METAVIR F0/F1 and F4 scores respectively) and 20 healthy volunteers were enrolled. PBMC were obtained from peripheral blood samples and NK and CD4+ T‐cells were isolated and analysed. NK cell phenotype (CD25, CD69, Nkp46, NKG2D, PD‐1), degranulation (CD107a) and IFN‐γ and TNF‐α production, as well as CD4+ T‐cell activation (CD69, CD25 and CD38) were measured by flow cytometry. CD4+ T‐cell conditioned medium (CM) derived from F0/F1 or F4 individuals was assessed for IL‐2 levels by ELISA. Modulation of NK cell functionality by these CMs was also analysed. Results: When comparing to NK cells from individuals with minimal fibrosis, degranulation and cytokine secretion by NK cells from subjects with F4 scores was significantly impaired, while PD‐1 expression was augmented. On the one hand, neither the expression of activation markers nor IL‐2 secretion was distinctly induced in CD4+ T‐cells from subjects with F0/F1 or F4 METAVIR scores. Finally, NK cell degranulation and cytokine secretion were not differentially modulated by CD4+ T‐cell CM, whether CD4+ T‐cells derived from subjects with minimal or advanced fibrosis. Conclusions: Low levels of NK and CD4+ T‐cells in HIV/HCV‐coinfected individuals with advanced liver fibrosis have been previously described. Here, we show that advanced liver fibrosis in coinfected individuals is associated to a defective function of NK cells and an increased expression of the exhaustion/senescence marker PD‐1. This NK signature could not be attributed to changes in the ability of CD4+ T‐cells to modulate NK cell function. [ABSTRACT FROM AUTHOR]

A protocol for the covalent biofunctionalization of silicon-based biosensors using a UV light-induced thiol–ene coupling (TEC) reaction has been developed. This biofunctionalization approach has been used to immobilize half antibodies (hIgG), which have been obtained by means of a tris(2-carboxyethyl)phosphine (TCEP) reduction at the hinge region, to the surface of a vinyl-activated silicon-on-insulator (SOI) nanophotonic sensing chip. The response of the sensing structures within the nanophotonic chip was monitored in real time during the biofunctionalization process, which has allowed us to confirm that the bioconjugation of the thiol-terminated bioreceptors onto the vinyl-activated sensing surface is only initiated upon UV light photocatalysis. [ABSTRACT FROM AUTHOR]

Whereas short-term (10-15 days) weather and hydrological forecasts are already part of decision making processes at different levels in society, seasonal or decadal forecasts and future climate scenarios projections are not already involved in operational frameworks. Different reasons lie behind this fact, beyond the human perception of risks associated to the near-future being more relevant than those regarding far-future situations. On one hand, the uncertainty and, reversely, the skill of long-term forecasts and future projections are still low and far from those associated to short term forecasts in hydrology; on the other, most of the potential end-users of climate services that deal with long-term products lack of adequate knowledge to both understand key concepts involved in the climate projections and downscale these data sets to the local level, that is, the operational scale.Despite these weaknesses, it must be recognized that for decades the population in most of the countries have had access to everyday training to understand what is behind a weather forecast: this section in the TV news has been evolving with technology, but all of us learnt concepts such as cyclonic fronts, low and high pressure areas, probability of occurrence of precipitation, snow baseline, and a large etcetera. Nowadays, from the lay citizen who travels or not during the weekend to the operation of irrigation networks, dams, hydropower facilities, or alert systems, these forecasts constitute one of the most used open service in the world for decision-making. This level of training has resulted in a larger perception of confidence in population, which indirectly shows the need for i) training the receptor to adequately value information and ii) facilitating frequent contact with such information if awareness of the usefulness of a given service, and its products, is to be achieved.This work has been developed within the AQUACLEW project (www.aquaclew.eu) and shows the design of a game framework to co-develop climate services offering advanced information of future climate scenarios projections. The game was designed to both train potential end-users, and increase their valuing and awareness of the usefulness of such services, and acquire feedback on the products to be offered by the service. Concepts as models, skill, ensembles, end-members, uncertainty, scales, among others, were included in the game structure as part of the metadata associated to a given projected scenario. Gamers must make a decision on a selected situation in the future from a list by using some information that is sucessively provided in the game framework depending on their different chain of choices.The results include the analysis of the behaviour of different focus groups (potential end-users) in the game regarding the final decisions made in different situations as they increase their training, together with their perception of two key issues in climate services development: the value of the service, and the cost that it is worth assuming to access the products in each potential operational context. [ABSTRACT FROM AUTHOR]