Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKI include inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of ...interest to develop therapeutic approaches for improving the microvascular damage in septic-AKI. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone. Thus, the aim of this study was to evaluate the protective effects of EPO on microvascular injury in a murine model of endotoxemic AKI.
Male Balb/c mice were divided into four groups: control, LPS (8 mg/kg, ip.), EPO (3000 IU / kg, sc.) and LPS + EPO. A time course study (0–48 h) was designed. Experiments include, among others, immunohistochemistry and Western blottings of hypoxia-inducible transcription factor (HIF-1α), erythropoietin receptor (EPO-R), vascular endothelial growth factor system (VEGF/VEGFR-2), platelet and endothelial adhesion molecule-1 (PeCAM-1), inducible nitric oxide synthase (iNOS) and phosphorylated nuclear factor kappa B p65 (NF-κB).
Data showed that EPO attenuates renal microvascular damage during septic-AKI progression through a) the decrease of HIF-1 alpha, iNOS, and NF-κB and b) the enhancement of EPO-R, PeCAM-1, VEGF, and VEGFR-2 expression.
In summary, EPO renoprotection involves the attenuation of septic-induced renal hypoxia and inflammation as well as ameliorates the endotoxemic microvascular injury.
Aim: To identify periodontal bacterial DNA (PBDNA) by PCR in subgingival dental plaque (SDP), serum and synovial fluid (SF) of rheumatoid arthritis (RA) with periodontal disease (PD) patients and to ...explore the possible PBDNA transport pathways from mouth to joints.
Methods: This cross‐sectional prolective study involved 19 subjects with RA and PD. Informed consent, health and dental questionnaires were obtained. SDP, SF and serum samples were obtained, and leucocytes were isolated from blood. DNA was extracted and PCR assays to detect main PD species were carried out. Cultures on agar plates and broth, from each sample, were performed.
Results: Hundred percentage of patients showed PBDNA in SDP and SF and 83.5% in serum. Prevotella intermedia (89.4% and 73.6%) and Porphyromonas gingivalis (57.8% and 42.1%) were the species most frequently detected in SDP and SF, respectively. In SDP, 4.05 different bacterial species were found followed by 1.19 in serum and 2.26 in SF. Culture onto agar plates and broth did not show any bacterial growth, leucocytes were not positive to PBDNA by PCR.
Conclusion: This study suggests that PBDNA could have a role on the RA aetiology. The possible pathway of transport of PBDNA from mouth to joints could be via the free form of DNA.
With the ever-increasing world population, an extra 1.5 billion mouths need to be fed by 2050 with continuously dwindling arable land. Hence, it is imperative that extra food come from the marginal ...lands that are expected to be unsuitable for growing major staple crops under the adverse climate change scenario. Crop diversity provides right alternatives for marginal environments to improve food, feed, and nutritional security. Well-adapted and climate-resilient crops will be the best fit for such a scenario to produce seed and biomass. The minor millets are known for their high nutritional profile and better resilience for several abiotic stresses that make them the suitable crops for arid and salt-affected soils and poor-quality waters. Finger millet (
) and foxtail millet (
), also considered as orphan crops, are highly tolerant grass crop species that grow well in marginal and degraded lands of Africa and Asia with better nutritional profile. Another category of grains, called pseudo-cereals, is considered as rich foods because of their protein quality and content, high mineral content, and healthy and balance food quality. Quinoa (
), amaranth (
sp.), and buckwheat (
) fall under this category. Nevertheless, both minor millets and pseudo-cereals are morphologically different, although similar for micronutrient bioavailability, and their grains are gluten-free. The cultivation of these millets can make dry lands productive and ensure future food as well as nutritional security. Although the natural nutrient profile of these crop plant species is remarkably good, little development has occurred in advances in molecular genetics and breeding efforts to improve the bioavailability of nutrients. Recent advances in NGS have enabled the genome and transcriptome sequencing of these millets and pseudo-cereals for the faster development of molecular markers and application in molecular breeding. Genomic information on finger millet (1,196 Mb with 85,243 genes);
, a model small millet (well-annotated draft genome of 420 Mb with 38,801 protein-coding genes); amaranth (466 Mb genome and 23,059 protein-coding genes); buckwheat (genome size of 1.12 Gb with 35,816 annotated genes); and quinoa (genome size of 1.5 Gb containing 54,438 protein-coding genes) could pave the way for the genetic improvement of these grains. These genomic resources are an important first step toward genetic improvement of these crops. This review highlights the current advances and available resources on genomics to improve nutrient bioavailability in these five suitable crops for the sustained healthy livelihood.
Over the last two decades, academic debates around neoliberalism in Latin America have shifted from evaluations of the drawbacks and virtues of the application of neoliberal policies for achieving ...socioeconomic development, towards discussions imagining and implementing alternatives. After thirty years of neoliberal reform, even neoliberal advocates have increasingly recognised the pernicious effects that the process of neoliberalization have had on people's lives. The fleeting left and centre‐left moment brought renewed hopes and expectations of a post‐neoliberal future. However, post‐neoliberal states could not solve the contradictions of neoliberalism and told us much about its resilience and adaptability. This article offers an overview of the dynamics of neoliberalism's resilience and contestation in Latin America as treated by extant literature as a way to account for the politics of neoliberalism in the region, its rise and its current status.
Satellite precipitation products are becoming increasingly useful to complement rain gauge networks in regions where these are too sparse to capture spatial precipitation patterns, such as in the ...Tropical Andes. The Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (TPR) was active for 17 years (1998–2014) and has generated one of the longest single‐sensor, high‐resolution, and high‐accuracy rainfall records. In this study, high‐resolution (5 km) gridded mean monthly climatological precipitation is derived from the raw orbital TPR data (TRMM 2A25) and merged with 723 rain gauges using multiple satellite‐gauge (S‐G) merging approaches. The resulting precipitation products are evaluated by cross validation and catchment water balances (runoff ratios) for 50 catchments across the Tropical Andes. Results show that the TPR captures major synoptic and seasonal precipitation patterns and also accurately defines orographic gradients but underestimates absolute monthly rainfall rates. The S‐G merged products presented in this study constitute an improved source of climatological rainfall data, outperforming the gridded TPR product as well as a rain gauge‐only product based on ordinary Kriging. Among the S‐G merging methods, performance of inverse distance interpolation of satellite‐gauge residuals was similar to that of geostatistical methods, which were more sensitive to gauge network density. High uncertainty and low performance of the merged precipitation products predominantly affected regions with low and intermittent precipitation regimes (e.g., Peruvian Pacific coast) and is likely linked to the low TPR sampling frequency. All S‐G merged products presented in this study are available in the public domain.
Key Points
High‐resolution (5 km) monthly precipitation climatologies derived from TRMM Precipitation Radar
Comparative evaluation of statistical and geostatistical satellite‐gauge rainfall merging methods
Simple interpolation of TPR‐gauge residuals performs comparably to Kriging‐based merging methods
An extensive evaluation of nine global-scale high-resolution satellite-based rainfall (SBR) products is performed using aminimum of 6 years (within the period of 2000–13) of reference rainfall data ...derived from rain gauge networks in nine mountainous regions across the globe. The SBR products are compared to a recently released global reanalysis dataset from the European Centre for Medium-Range Weather Forecasts (ECMWF). The study areas include the eastern Italian Alps, the Swiss Alps, the western Black Sea of Turkey, the French Cévennes, the Peruvian Andes, the Colombian Andes, the Himalayas over Nepal, the Blue Nile in East Africa, Taiwan, and the U.S. Rocky Mountains. Evaluation is performed at annual, monthly, and daily time scales and 0.25° spatial resolution. The SBR datasets are based on the following retrieval algorithms: Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis (TMPA), the NOAA/Climate Prediction Center morphing technique (CMORPH), Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN), and Global Satellite Mapping of Precipitation (GSMaP). SBR products are categorized into those that include gauge adjustment versus unadjusted. Results show that performance of SBR is highly dependent on the rainfall variability. Many SBR products usually underestimate wet season and overestimate dry season precipitation. The performance of gauge adjustment to the SBR products varies by region and depends greatly on the representativeness of the rain gauge network.
Opa1 participates in inner mitochondrial membrane fusion and cristae morphogenesis. Here, we show that muscle‐specific Opa1 ablation causes reduced muscle fiber size, dysfunctional mitochondria, ...enhanced Fgf21, and muscle inflammation characterized by NF‐κB activation, and enhanced expression of pro‐inflammatory genes. Chronic sodium salicylate treatment ameliorated muscle alterations and reduced the muscle expression of Fgf21. Muscle inflammation was an early event during the progression of the disease and occurred before macrophage infiltration, indicating that it is a primary response to Opa1 deficiency. Moreover, Opa1 repression in muscle cells also resulted in NF‐κB activation and inflammation in the absence of necrosis and/or apoptosis, thereby revealing that the activation is a cell‐autonomous process and independent of cell death. The effects of Opa1 deficiency on the expression NF‐κB target genes and inflammation were absent upon mitochondrial DNA depletion. Under Opa1 deficiency, blockage or repression of TLR9 prevented NF‐κB activation and inflammation. Taken together, our results reveal that Opa1 deficiency in muscle causes initial mitochondrial alterations that lead to TLR9 activation, and inflammation, which contributes to enhanced Fgf21 expression and to growth impairment.
Synopsis
Mitochondrial DNA stress caused by Opa1 deficiency in skeletal muscle leads to inflammation via TLR9 activation, which contributes to enhanced Fgf21 expression and systemic growth impairment.
Skeletal muscle‐specific Opa1 ablation causes mitochondrial inflammatory myopathy.
Opa1 deficiency results in reduced muscle mass, mitochondrial dysfunction and enhanced Fgf21 expression.
Opa1 deficiency‐dependent inflammation results in severe growth defects.
Inflammation is a primary cell‐autonomous response of muscle cells to Opa1 deficiency, leading to NF‐κB activation.
Opa1 deficiency activates TLR9 by a mechanism that requires mitochondrial DNA.
Mitochondrial DNA stress caused by Opa1 deficiency in skeletal muscle leads to inflammation via TLR9 activation, which contributes to enhanced Fgf21 expression and systemic growth impairment.
The great success of the Tropical Rainfall Measuring Mission (TRMM) and its successor Global Precipitation Measurement (GPM) has accelerated the development of global high-resolution satellite-based ...precipitation products (SPP). However, the quantitative accuracy of SPPs has to be evaluated before using these datasets in water resource applications. This study evaluates the following GPM-era and TRMM-era SPPs based on two years (2014–2015) of reference daily precipitation data from rain gauge networks in ten mountainous regions: Integrated Multi-SatellitE Retrievals for GPM (IMERG, version 05B and version 06B), National Oceanic and Atmospheric Administration (NOAA)/Climate Prediction Center Morphing Method (CMORPH), Global Satellite Mapping of Precipitation (GSMaP), and Multi-Source Weighted-Ensemble Precipitation (MSWEP), which represents a global precipitation data-blending product. The evaluation is performed at daily and annual temporal scales, and at 0.1 deg grid resolution. It is shown that GSMaPV07 surpass the performance of IMERGV06B Final for almost all regions in terms of systematic and random error metrics. The new orographic rainfall classification in the GSMaPV07 algorithm is able to improve the detection of orographic rainfall, the rainfall amounts, and error metrics. Moreover, IMERGV05B showed significantly better performance, capturing the lighter and heavier precipitation values compared to IMERGV06B for almost all regions due to changes conducted to the morphing, where motion vectors are derived using total column water vapor for IMERGV06B.
A decade of genetic association studies in multiple organisms suggests that most complex traits are polygenic; that is, they have a genetic architecture determined by numerous loci, each with small ...effect‐size. Thus, determining the degree of polygenicity and its variation across traits, environments and time is crucial to understand the genetic basis of phenotypic variation. We applied multilocus approaches to estimate the degree of polygenicity of fitness‐related traits in a long‐lived plant (Pinus pinaster Ait., maritime pine) and to analyse this variation across environments and years. We evaluated five categories of fitness‐related traits (survival, height, phenology, functional, and biotic‐stress response) in a clonal common‐garden network planted in contrasted environments (over 20,500 trees). Most of the analysed traits showed evidence of local adaptation based on Qst–Fst comparisons. We further observed a remarkably stable degree of polygenicity, averaging 6% (range of 0%–27%), across traits, environments and years. We detected evidence of negative selection, which could explain, at least partially, the high degree of polygenicity. Because polygenic adaptation can occur rapidly, our results suggest that current predictions on the capacity of natural forest tree populations to adapt to new environments should be revised, especially in the current context of climate change.
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. ...Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.
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