Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to ...characterize the sex differences in gut microbiota, and to explore the impact of depletion of gonadal hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbiota, as consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbiota, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk.
Water scarcity in arid and semiarid regions poses problems for agricultural systems, awakening special interest in the development of deficit irrigation strategies to improve water conservation. ...Toward this purpose, farmers and technicians must monitor soil water and soluble nutrient contents in real time using simple, rapid and economical techniques through time and space. Thus, this study aimed to achieve the following: (i) create a model that predicts water and soluble nutrient contents in soil profiles using electrical resistivity tomography (ERT); and (ii) apply the model to different woody crops under different irrigation regimes (full irrigation and regulated deficit irrigation (RDI)) to assess the efficiency of the model. Simple nonlinear regression analysis was carried out on water content and on different ion contents using electrical resistivity data as the dependent variable. A predictive model for soil water content was calibrated and validated with the datasets based on exponential decay of a three-parameter equation. Nonetheless, no accurate model was achieved to predict any soluble nutrient. Electrical resistivity images were replaced by soil water images after application of the predictive model for all studied crops. They showed that under RDI situations, soil profiles became drier at depth while plant roots seemed to uptake more water, contributing to reductions in soil water content by the creation of desiccation bulbs. Therefore, the use of ERT combined with application of the validated predictive model could be a sustainable strategy to monitor soil water evolution in soil profiles under irrigated fields, facilitating land irrigation management.
The aim of this work was to evaluate the effects on the chemical, physic-chemical, technological, and sensory properties of beef burger when replacing different quantities of fat (50 and 100%) with ...different levels of oil-in-water-gelled emulsion elaborated with walnut oil and cocoa bean shell flour (GECW). The chemical composition of the samples was affected by the fat replacement. The reformulation increased the moisture and ash content while the fat and protein content decreased with respect to the control sample. The linolenic and linolenic acid content of the beef burgers increased as the GECW replacement was augmented. The polyunsaturated fatty/saturated fatty acid ratio increased in both raw and cooked burgers, whereas the atherogenicity index and thrombogenicity index were reduced in both raw and cooked burgers with respect to the control sample. The use of GECW as a fat replacer was found to be effective in improving the cooking loss. Similarly, there were positive effects on reductions in the diameter and the increases in the thickness of the beef burgers. Regarding lipid stability, in both the raw and cooked burgers, the reformulation increased the 2-thiobarbituric acid reactive substance (TBARs) values with respect to the control sample. In both types of reformulated burgers, three bound polyphenols (mainly catechin and epicatechin) and two free polyphenols were identified, as were methylxanthines theobromine and caffeine. The sensory properties for the control and partial pork backfat replacement treatments were similar, while the sample with the total pork backfat replacement treatment showed the lowest scores. The blend of cocoa bean shell flour and walnut oil could be used as new ingredients for the development of beef burgers with a healthier nutritional profile without demeriting their sensory or cooking characteristics and physic-chemical properties.
The Internet of Things (IoT) and edge computing are starting to go hand in hand. By providing cloud services close to end-users, edge paradigms enhance the functionality of IoT deployments, and ...facilitate the creation of novel services such as augmented systems. Furthermore, the very nature of these paradigms also enables the creation of a proactive defense architecture, an immune system, which allows authorized immune cells (e.g., virtual machines) to traverse edge nodes and analyze the security and consistency of the underlying IoT infrastructure. In this paper, we analyze the requirements for the development of an immune system for the IoT, and propose a security architecture that satisfies these requirements. We also describe how such a system can be instantiated in edge computing infrastructures using existing technologies. Finally, we explore the potential application of immune systems to other scenarios and purposes.
Identifying novel breast cancer biomarkers will improve patient stratification, enhance therapeutic outcomes, and help develop non-invasive diagnostics. We compared the proteomic profiles of ...whole-cell and exosomal samples of representative breast cancer cell subtypes to evaluate the potential of extracellular vesicles as non-invasive disease biomarkers in liquid biopsies. Overall, differentially-expressed proteins in whole-cell and exosome samples (which included markers for invasion, metastasis, angiogenesis, and drug resistance) effectively discriminated subtypes; furthermore, our results confirmed that the proteomic profile of exosomes reflects breast cancer cell-of-origin, which underscores their potential as disease biomarkers. Our study will contribute to identifying biomarkers that support breast cancer patient stratification and developing novel therapeutic strategies. We include an open, interactive web tool to explore the data as a molecular resource that can explain the role of these protein signatures in breast cancer classification.
Graphical Abstract
(
A
) We quantified proteomic profiles of breast cancer cells (BCCs) and breast cancer-derived exosomes (BCDEs) samples from four breast cancer cell lines representative of common breast cancer subtypes – Her2-positive (Her2, MDA-MB-453), Luminal A (LA, MCF7), Luminal B (LB, ZR-75), and triple-negative (TN, MDA-MB-231). (
B
) We independently performed four comparisons for BCCs and BCDEs, comparing each cell line against the remaining three. (
C
) We identified differentially-expressed proteins (DEPs) for BCCs and BCDEs, defined protein signatures, and functionally analyzed resulting networks. Through pathway inference analysis (PIA), we identified Kyoto Encyclopedia of genes and genomes (KEGG) subpaths and biological Gene Ontology (GO) terms that displayed differential activation. (
D
) We validated our proteomic signature using the Cancer Genome Atlas (TCGA) and the Cancer Proteome Atlas (TCPA) databases, verified that differentially-activated pathways in BCDEs caused a corresponding response in receptor cells, and confirmed that the BCDE proteomic signature reflects their cell-of-origin and identifies candidate disease biomarkers in liquid biopsies
•Resistance-to-Time-to-Digital conversion.•Direct Interface Circuits between Programmable Digital Device and Resistive Sensors.•Fast, low-power reading of resistive sensors.•High-accuracy electronic ...circuits for the readout of resistive sensors.
Direct Interface Circuits (DICs) are simple circuits used in readouts for all types of sensors. For resistive sensors, all DICs perform a resistance-to-time-to-digital conversion using just the sensor, some calibration resistors, one or two capacitors, and a Digital Processor. These circuits require a variable number of charging and discharging cycles of a capacitor to estimate the sensor resistance, Rx, increasing both acquisition time and power consumption. This paper presents two resistive DICs capable of estimating Rx by means of a single charging-discharging process, simplifying the readout process. Furthermore, this is achieved without increasing hardware requirements. Only two time measurements are used to obtain Rx. Despite the simplicity of the new circuits, the experimental results show that relative errors of estimating Rx can be below 0.8 %, and this in a wide range of resistances of over 40 dB. Moreover, acquisition time and energy consumption can be reduced by up to 75 %.
Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an ...anomalous regulation of resting intracellular Casup.2+ (Casup.2+ sub.i ) in vascular smooth muscle cells (VSMCs) from a mouse (mdx) model of DMD. We investigated the effect of hypoxia on Casup.2+ sub.i in isolated and quiescent VSMCs from C57BL/10SnJ (WT) and C57BL/10ScSn-Dmd (mdx) male mice. Casup.2+ sub.i was measured using Casup.2+ -selective microelectrodes under normoxic conditions (95% air, 5% COsub.2 ) and after hypoxia (glucose-free solution aerated with 95% N2-5% COsub.2 for 30 min). Casup.2+ sub.i in mdx VSMCs was significantly elevated compared to WT under normoxia. Hypoxia-induced Casup.2+ sub.i overload, which was significantly greater in mdx than in WT VSMCs. A low Casup.2+ solution caused a reduction in Casup.2+ sub.i and prevented Casup.2+ sub.i overload secondary to hypoxia. Nifedipine (10 µM), a Casup.2+ channel blocker, did not modify resting Casup.2+ sub.i in VSMCs but partially prevented the hypoxia-induced elevation of Casup.2+ sub.i in both genotypes. SAR7334 (1 µM), an antagonist of TRPC3 and TRPC6, reduced the basal and Casup.2+ sub.i overload caused by hypoxia. Cell viability, assessed by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced in mdx compared to WT VSMCs. Pretreatment with SAR7341 increases cell viability in normoxic mdx (p < 0.001) and during hypoxia in WT and mdx VSMCs. These results provide evidence that the lack of dystrophin makes VSMCs more susceptible to hypoxia-induced Casup.2+ sub.i overload, which appears to be mediated by increased Casup.2+ entry through L-type Casup.2+ and TRPC channels.
Robust fuzzy clustering of multivariate time series is addressed when the clustering purpose is grouping together series generated from similar stochastic processes. Robustness to the presence of ...anomalous series is attained by considering three well-known robust versions of a fuzzy C-means model based on a spectral dissimilarity measure with high discriminatory power. The dissimilarity measure compares principal component scores obtained from estimates of quantile cross-spectral densities, and the robust techniques follow the so-called metric, noise and trimmed approaches. The metric approach incorporates in the objective function a distance aimed at neutralizing the effect of the outliers, the noise approach builds an artificial cluster expected to contain the outlying series, and the trimmed approach removes the most atypical series in the dataset. As result, the proposed clustering methods take advantage of both the robust nature of these techniques and the capability of the quantile cross-spectral density to identify complex dependence structures. An extensive simulation study including multivariate linear, nonlinear and GARCH processes shows that the algorithms are substantially effective in coping with the presence of outlying series, clearly outperforming other alternative procedures. Two specific applications regarding financial and environmental series illustrate the usefulness of the presented methods.
Organic fertilizers may differ greatly in composition and as a result there may also be differences in nitrogen oxides emissions following their application to soils. The aim of this study was to ...evaluate the influence of mineral and organic N fertilizers on the nitrification and denitrification processes, and consequently on N
2O and NO emissions. Therefore, a field experiment was carried out on an irrigated sandy loam soil under Mediterranean conditions during the maize (
Zea mays L.) growing season. Untreated pig slurry (UPS) both with and without the nitrification inhibitor dicyandiamide (UPS
+
DCD), digested thin pig slurry fraction (DTP), composted solid fraction of slurry mixed with urea (CPS
+
U) and composted municipal solid waste mixed with urea (MSW
+
U) were applied at a rate of 175
kg available N
ha
−1. Their emissions were compared with those from urea (U) and a control treatment to which no nitrogen fertilization was administered (Control). Accumulated nitrous oxide losses during the crop season ranged from 6.0 to 9.3
kg N
2O-N
ha
−1 for the Control and CPS
+
U, respectively, whereas nitric oxide losses ranged from 0.01 to 0.23
kg NO-N
ha
−1, for the Control and U, respectively. The use of digested slurries mitigated N
2O emission by 25% in relation to untreated pig slurry, but NO emissions were similar for both treatments. Dicyandiamide reduced N
2O and NO emissions by 64 and 78% with respect to slurry without the inhibitor. An indirect effect of DCD on denitrification was also observed, with a reduction of 32% in denitrification with respect to the slurry without the inhibitor. In this case, the greatest reduction in denitrification losses occurred during the irrigation period. Composts mixed with urea reduced NO emissions by 56% (CPS
+
U) and 85% (MSW
+
U) in relation to the urea treatment, but its effect on N
2O depended on the type of compost involved: CPS
+
U increased N
2O emission by 27%, whereas MSW
+
U reduced it by 55% in relation to urea. Denitrification was the most important process responsible for N
2O emissions when organic fertilizers were applied to the soil, while nitrification was the most important for the inorganic fertilizer. The C:N ratio of fertilizers was a good predictor of their NO emissions, denitrification losses and N
2O/N
2 ratio. On the other hand, added soluble N was a good predictor for cumulative N
2O emissions during the period before irrigation. This work shows that an appropriate selection of organic fertilizers based on their composition could be used to mitigate emissions of the atmospheric pollutants NO and N
2O in comparison with urea.
Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson's disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation ...of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson's disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4-10 Hz) activity (mean peak: 6.71 Hz) that was generated 2-8 mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0-2 mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4-7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5-10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson's disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with l-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson's disease, specifically engaging different anatomo-functional territories.
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