Antioxidant and drought-acclimation responses in UV-B-exposed transgenic Nicotiana tabacum displaying constitutive overproduction of H2O2.

Hydrogen peroxide (H2O2) is an important molecule that regulates antioxidant responses that are crucial for plant stress resistance. Exposure to low levels of ultraviolet-B radiation (UV-B, 280-315 nm) can also activate antioxidant defenses and acclimation responses. However, how H2O2 and UV-B interact to promote stress acclimation remains poorly understood. In this work, a transgenic model of Nicotiana tabacum cv Xanthi nc, with elevated Mn-superoxide dismutase (Mn-SOD) activity, was used to study the interaction between the constitutive overproduction of H2O2 and a 14-day UV-B treatment (1.75 kJ m-2 d-1 biologically effective UV-B). Subsequently, these plants were subjected to a 7-day moderate drought treatment to evaluate the impact on drought resistance of H2O2- and UV-dependent stimulation of the plants' antioxidant system. The UV-B treatment enhanced H2O2 levels and altered the antioxidant status by increasing the epidermal flavonol index, Trolox Equivalent Antioxidant Capacity, and catalase, peroxidase and phenylalanine ammonia lyase activities in the leaves. UV-B also retarded growth and suppressed acclimation responses in highly H2O2-overproducing transgenic plants. Plants not exposed to UV-B had a higher drought resistance in the form of higher relative water content of leaves. Our data associate the interaction between Mn-SOD transgene overexpression and the UV-B treatment with a stress response. Finally, we propose a hormetic biphasic drought resistance response curve as a function of leaf H2O2 content in N. tabacum cv Xanthi.

Characterization of the Key Compounds of Bell Pepper by Spectrophotometry and Gas Chromatography on the Effects of Induced Stress on the Concentration of Secondary Metabolite.

Sweet peppers are consumed worldwide, and traditional uses have sparked interest in their applications as dietary antioxidants, which can be enhanced in plants using elicitors. These are endowed with phytochemicals with potential health benefits such as antioxidants, bioavailability, and bioaccessibility. The trend in metabolomics shows us chemical fingerprints linking metabolomics, innovative analytical form, and bioinformatics tools. The objective was to evaluate the impact of multiple stress interactions, elicitor concentrations, and electrical conductivity on the concentration of secondary metabolites to relate their response to metabolic pathways through the foliar application of a cocktail of said elicitors in pepper crops under greenhouse conditions. The extracts were analyzed by spectrophotometry and gas chromatography, and it was shown that the PCA analysis identified phenolic compounds and low molecular weight metabolites, confirming this as a metabolomic fingerprint in the hierarchical analysis. These compounds were also integrated by simultaneous gene and metabolite simulants to obtain effect information on different metabolic pathways. Showing changes in metabolite levels at T6 (36 mM H2O2 and 3.6 dS/m) and T7 (0.1 mM SA and 3.6 dS/m) but showing statistically significant changes at T5 (3.6 dS/m) and T8 (0.1 mM SA, 36 mM H2O2, and 3.6 dS/m) compared to T1 (32 dS/m) or control. Six pathways changed significantly (p < 0.05) in stress-induced treatments: aminoacyl t-RNA and valine-leucine-isoleucine biosynthesis, and alanine-aspartate-glutamate metabolism, glycoxylate-dicarboxylate cycle, arginine-proline, and citrate. This research provided a complete profile for the characterization of metabolomic fingerprint of bell pepper under multiple stress conditions.

Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion.

Rearrangements involving the neurotrophic receptor tyrosine kinase (NTRK) gene family have been reported in diverse tumor types, and NTRK-targeted therapies have recently been approved. In this article, we report a case of a 26-year-old man with an NTRK2-rearranged isocitrate dehydrogenase-wild-type glioblastoma who showed a robust but temporary response to the NTRK inhibitor larotrectinib. Rebiopsy after disease progression showed elimination of the NTRK2-rearranged tumor cell clones, with secondary emergence of a PDGFRA-amplified subclone. Retrospective examination of the initial biopsy material confirmed rare cells harboring PDGFRA amplification. Although mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma has been previously described, mosaicism involving a fusion gene driver event has not. This case highlights the potential efficacy of NTRK-targeted treatment in glioblastoma and the implications of molecular heterogeneity in the setting of targeted therapy. KEY POINTS: This case highlights the efficacy of the NTRK inhibitor larotrectinib in treating NTRK-rearranged glioblastoma. This is the first case to demonstrate mosaicism in glioblastoma involving both a fusion gene and amplification for receptor tyrosine kinases. Intratumoral heterogeneity in glioblastoma has significant implications for tumor resistance to targeted therapies.

Ultraviolet-B exposure and exogenous hydrogen peroxide application lead to cross-tolerance toward drought in Nicotiana tabacum L.

Acclimation of plants to water deficit involves biochemical and physiological adjustments. Here, we studied how ultraviolet (UV)-B exposure and exogenously applied hydrogen peroxide (H2 O2 ) potentiates drought tolerance in tobacco (Nicotiana tabacum L. cv. xanthi nc). Separate and combined applications for 14 days of 1.75 kJ m-2  day-1 UV-B radiation and 0.2 mM H2 O2 were assessed. Both factors, individually and combined, resulted in inhibition of growth. Furthermore, the combined treatment led to the most compacted plants. UV-B- and UV-B + H2 O2 -treated plants increased total antioxidant capacity and foliar epidermal flavonol index. H2 O2 - and UV-B + H2 O2 -pre-treated plants showed cross-tolerance to a subsequent 7-day moderate drought treatment, which was assessed as the absence of negative impact on growth, leaf wilting, and leaf relative water content. Plant responses to the pre-treatment were notably different: (1) H2 O2 increased the activity of catalase (EC 1.11.1.6), phenylalanine ammonia lyase (EC 4.3.1.5), and peroxidase activities (EC 1.11.1.7), and (2) the combined treatment induced epidermal flavonols which were key to drought tolerance. We report synergistic effects of UV-B and H2 O2 on transcription accumulation of UV RESISTANCE LOCUS 8, NAC DOMAIN PROTEIN 13 (NAC13), and BRI1-EMS-SUPPRESSOR 1 (BES1). Our data demonstrate a pre-treatment-dependent response to drought for NAC13, BES1, and CHALCONE SYNTHASE transcript accumulation. This study highlights the potential of combining UV-B and H2 O2 to improve drought tolerance which could become a useful tool to reduce water use.

Accuracy of MRI T2*-weighted sequences (GRE-EPI) compared to CTA for detection of anterior circulation large vessel thrombus.

PURPOSE: Rapid detection of vessel occlusion is pivotal to the management of patients with acute stroke. Magnetic resonance (MR) T2*-weighted (W) sequence has proven its capability to detect intravascular thrombi, but its diagnostic value compared to computed tomography angiography (CTA) is not well established. We aimed to determine the diagnostic performance of fast 1.5-T MR T2*W sequences compared to CTA for the detection of intra-arterial thrombi in patients with acute stroke. METHODS: About 71 consecutive patients with known middle cerebral artery (MCA) territory stroke were identified. Patients with CTA and MR imaging within 12 h of symptom onset were included in the study. Two investigators reviewed the DWI and T2*W sequences for the presence of infarction and susceptibility vessel sign (SVS). A comparison to the corresponding internal carotid artery (ICA) and M1 and M2 segments of the MCA findings on CTA was made. RESULTS: Of the 51 patients included in our study, CTA thrombi were identified 84% patients (43/51). Of these, 77% (33/43) presented a corresponding SVS on T2*W. A total of 29 CTA thrombi were identified in the M1 segment, and of these, 22 patients had a corresponding SVS. Of the patients without M1 thrombus on CTA, no M1-SVS was detected on T2*W sequences. We found an accuracy of 92%, sensitivity of 85%, specificity of 100%, PPV 100%, and NPV of 86% for M1 occlusion. The Kappa coefficient was 0.79. CONCLUSION: Fast T2*W sequences demonstrated very good diagnostic performance and inter-reader agreement for detecting SVS in the M1 segment in patients with acute ischemic stroke.

Methodological consensus on clinical proton MRS of the brain: Review and recommendations.

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

Imaging in neurointerventional stroke treatment: review of the recent trials and what your neurointerventionalist wants to know from emergency radiologists.

Stroke is one of the leading causes of death and disability worldwide. Standard treatment for stroke is intravenous (IV) injection of tissue plasminogen activator (t-PA) rapidly after symptom onset. However, there are limitations of IV t-PA treatment, such as a short time window for administration and risk for hemorrhage. Recent trials have demonstrated the benefit of endovascular treatment when added to standard treatment to improve outcomes for patients. Advanced imaging was utilized in some trials to identify patients with proximal intracranial occlusion to target for endovascular reperfusion therapy, and to exclude patients with large infarct cores or poor collateral circulation who would not be expected to benefit from intervention. This article summarizes the use of imaging in recent stroke trials in details, provides a stroke imaging protocol, and provides tips which radiologists should know to help their neurointerventionalists.

Timbe (Acaciella angustissima) Pods Extracts Reduce the Levels of Glucose, Insulin and Improved Physiological Parameters, Hypolipidemic Effect, Oxidative Stress and Renal Damage in Streptozotocin-Induced Diabetic Rats.

In Mexico one in 14 deaths are caused by diabetes mellitus (DM) or by the macro and microvascular disorders derived from it. A continuous hyperglycemic state is characteristic of DM, resulting from a sustained state of insulin resistance and/or a dysfunction of ß-pancreatic cells. Acaciella angustissima is a little studied species showing a significant antioxidant activity that can be used as treatment of this disease or preventive against the complications. The objective of this study was to explore the effect of oral administration of A. angustissima methanol extract on physiological parameters of streptozotocin-induced diabetic rats. The results indicated a significant reduction in blood glucose levels, an increase in serum insulin concentration, a decrease in lipid levels and an improvement in the parameters of kidney damage by applying a concentration of 100 mg/Kg B.W. However, glucose uptake activity was not observed in the adipocyte assay. Moreover, the extract of A. angustissima displayed potential for the complementary treatment of diabetes and its complications likely due to the presence of bioactive compounds such as protocatechuic acid. This study demonstrated that methanol extract of Acacciella angustissima has an antidiabetic effect by reducing the levels of glucose, insulin and improved physiological parameters, hypolipidemic effect, oxidative stress and renal damage in diabetic rats.

FPGA-based smart sensor for drought stress detection in tomato plants using novel physiological variables and discrete wavelet transform.

Soil drought represents one of the most dangerous stresses for plants. It impacts the yield and quality of crops, and if it remains undetected for a long time, the entire crop could be lost. However, for some plants a certain amount of drought stress improves specific characteristics. In such cases, a device capable of detecting and quantifying the impact of drought stress in plants is desirable. This article focuses on testing if the monitoring of physiological process through a gas exchange methodology provides enough information to detect drought stress conditions in plants. The experiment consists of using a set of smart sensors based on Field Programmable Gate Arrays (FPGAs) to monitor a group of plants under controlled drought conditions. The main objective was to use different digital signal processing techniques such as the Discrete Wavelet Transform (DWT) to explore the response of plant physiological processes to drought. Also, an index-based methodology was utilized to compensate the spatial variation inside the greenhouse. As a result, differences between treatments were determined to be independent of climate variations inside the greenhouse. Finally, after using the DWT as digital filter, results demonstrated that the proposed system is capable to reject high frequency noise and to detect drought conditions.

An analysis of electrical impedance measurements applied for plant N status estimation in lettuce (Lactuca sativa).

Nitrogen plays a key role in crop yields. Hence, farmers may apply excessive N fertilizers to crop fields, inducing environmental pollution. Crop N monitoring methods have been developed to improve N fertilizer management, most of them based on leaf or canopy optical-property measurements. However, sensitivity to environmental interference remains an important drawback. Electrical impedance has been applied to determine the physiological and nutritional status of plant tissue, but no studies related to plant-N contents are reported. The objective of this article is to analyze how the electrical impedance response of plants is affected by their N status. Four sets of lettuce (Lactuca sativa L.) with a different N-source concentrations per set were used. Total nitrogen and electrical impedance spectra (in a 1 to 100 kHz frequency range) were measured five times per set, three times every other day. Minimum phase angles of impedance spectra were detected and analyzed, together with the frequency value in which they occurred, and their magnitude at that frequency. High and positive correlation was observed between plant N content and frequency values at minimum phase angle with no significant variations detected between days of measurement. These results suggest that electrical impedance can be sensitive to plant N status.

A non-digestible fraction of the common bean (Phaseolus vulgaris L.) induces cell cycle arrest and apoptosis during early carcinogenesis.

We have previously demonstrated that the non-digestible fraction (NDF) from common cooked beans (P. vulgaris L., cv Negro 8025) inhibits azoxymethane (AOM)-induced colon cancer and influences the expression of genes involved in the induction of apoptosis and cell cycle arrest through the action of butyrate. The objective of this study was to identify cell cycle alterations and morphological changes induced by treatment with AOM and to examine the formation of colonic aberrant crypt foci (ACF) in male Sprague Dawley rats fed with these beans. Rats were fed control diets upon arrival and were randomly placed into four groups after one week of acclimatization: control, NDF (intragastric administration), NDF + AOM and AOM. Rats treated with NDF + AOM exhibited a significantly lower number of total colonic ACF with a notable increase in the number of cells present in the G1 phase (83.14%); a decreased proliferation index was observed in the NDF + AOM group when compared to AOM group. NDF + AOM also displayed a higher number of apoptotic cells compared to AOM group. NDF of cooked common beans inhibited colon carcinogenesis at an early stage by inducing cell cycle arrest of colon cells and morphological changes linked to apoptosis, thus confirming previous results obtained with gene expression studies.

Vasa vasorum enhancement on computerized tomographic angiography correlates with symptomatic patients with 50% to 70% carotid artery stenosis.

BACKGROUND AND PURPOSE: Significant stenosis of the internal carotid artery (ICA) is an established stroke risk factor. Recent evidence suggests that features within the atherosclerotic plaque also have prognostic value. The purpose of this study was to correlate the enhancement of the vasa vasorum (VV) overlying the carotid artery plaque with acute neurological symptoms in patients with 50% to 70% ICA stenosis. METHODS: We conducted a 4-year retrospective computerized tomographic angiographic review to identify patients with 50% to 70% stenosis of the ICA. Three types of plaques were identified: enhancing VV, calcified, and nonenhancing-noncalcified. Medical records were reviewed for cardiovascular risk factors and neurological status, and imaging was reviewed for signs of a recent stroke. RESULTS: We identified a total of 428 patients with 50% to 70% ICA stenosis: 103 (24.1%) had enhancing VV, 202 (47.2%) calcified, and 123 (28.7%) nonenhancing-noncalcified arteries; 97 were symptomatic and 331 asymptomatic. Thirty-three (34%) symptomatic subjects demonstrated enhancing VV, 42 (20%) had calcified arterial plaques, and 22 (17%) had nonenhancing-noncalcified arterial plaques. Fisher exact tests revealed that the proportion of symptomatic individuals with enhancing VV plaque was double that of the other groups combined (P=0.015; odds ratio, 1.92; 95% confidence interval, 1.17-3.16). Regression analyses confirmed this association as independent from other known cardiovascular risk factors. CONCLUSIONS: In patients with 50% to 70% ICA stenosis, VV enhancement recognized on computed tomographic angiography is strongly associated with acute neurological symptoms compared with calcified and nonenhancing-noncalcified arterial plaques. This finding may aid in the identification of patients at increased risk for ischemic stroke within populations with the same degree of stenosis.

A review of methods for sensing the nitrogen status in plants: advantages, disadvantages and recent advances.

Nitrogen (N) plays a key role in the plant life cycle. It is the main plant mineral nutrient needed for chlorophyll production and other plant cell components (proteins, nucleic acids, amino acids). Crop yield is affected by plant N status. Thus, the optimization of nitrogen fertilization has become the object of intense research due to its environmental and economic impact. This article focuses on reviewing current methods and techniques used to determine plant N status. Kjeldahl digestion and Dumas combustion have been used as reference methods for N determination in plants, but they are destructive and time consuming. By using spectroradiometers, reflectometers, imagery from satellite sensors and digital cameras, optical properties have been measured to estimate N in plants, such as crop canopy reflectance, leaf transmittance, chlorophyll and polyphenol fluorescence. High correlation has been found between optical parameters and plant N status, and those techniques are not destructive. However, some drawbacks include chlorophyll saturation, atmospheric and soil interference, and the high cost of instruments. Electrical properties of plant tissue have been used to estimate quality in fruits, and water content in plants, as well as nutrient deficiency, which suggests that they have potential for use in plant N determination.

Agriculture and bioactives: achieving both crop yield and phytochemicals.

Plants are fundamental elements of the human diet, either as direct sources of nutrients or indirectly as feed for animals. During the past few years, the main goal of agriculture has been to increase yield in order to provide the food that is needed by a growing world population. As important as yield, but commonly forgotten in conventional agriculture, is to keep and, if it is possible, to increase the phytochemical content due to their health implications. Nowadays, it is necessary to go beyond this, reconciling yield and phytochemicals that, at first glance, might seem in conflict. This can be accomplished through reviewing food requirements, plant consumption with health implications, and farming methods. The aim of this work is to show how both yield and phytochemicals converge into a new vision of agricultural management in a framework of integrated agricultural practices.

Oxidative and molecular responses in Capsicum annuum L. after hydrogen peroxide, salicylic acid and chitosan foliar applications.

Hydrogen peroxide (H2O2) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response can also be generated with the application of elicitors, stable molecules that induce the activation of transduction cascades and hormonal pathways, which trigger induced resistance to environmental stress. In this work, we evaluated the endogenous H2O2 production caused by salicylic acid (SA), chitosan (QN), and H2O2 elicitors in Capsicum annuum L. Hydrogen peroxide production after elicitation, catalase (CAT) and phenylalanine ammonia lyase (PAL) activities, as well as gene expression analysis of cat1, pal, and pathogenesis-related protein 1 (pr1) were determined. Our results displayed that 6.7 and 10 mM SA concentrations, and, 14 and 18 mM H2O2 concentrations, induced an endogenous H2O2 and gene expression. QN treatments induced the same responses in lesser proportion than the other two elicitors. Endogenous H2O2 production monitored during several days, showed results that could be an indicator for determining application opportunity uses in agriculture for maintaining plant alert systems against a stress.

Flaxseed (Linum usitatissimum L.) and its total non-digestible fraction influence the expression of genes involved in azoxymethane-induced colon cancer in rats.

The influence of flaxseed (Linum usitatissimum L.) and its total non-digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM)-induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50 ± 3.5) compared with the AOM treatment (34.00 ± 11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl-2, bax and caspase-3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21-independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF + AOM group exhibited the expression of caspase-3, decreased bcl-2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed.

Tackling prediction uncertainty in machine learning for healthcare.

Predictive machine-learning systems often do not convey the degree of confidence in the correctness of their outputs. To prevent unsafe prediction failures from machine-learning models, the users of the systems should be aware of the general accuracy of the model and understand the degree of confidence in each individual prediction. In this Perspective, we convey the need of prediction-uncertainty metrics in healthcare applications, with a focus on radiology. We outline the sources of prediction uncertainty, discuss how to implement prediction-uncertainty metrics in applications that require zero tolerance to errors and in applications that are error-tolerant, and provide a concise framework for understanding prediction uncertainty in healthcare contexts. For machine-learning-enabled automation to substantially impact healthcare, machine-learning models with zero tolerance for false-positive or false-negative errors must be developed intentionally.

Head CT deep learning model is highly accurate for early infarct estimation.

Non-contrast head CT (NCCT) is extremely insensitive for early (< 3-6 h) acute infarct identification. We developed a deep learning model that detects and delineates suspected early acute infarcts on NCCT, using diffusion MRI as ground truth (3566 NCCT/MRI training patient pairs). The model substantially outperformed 3 expert neuroradiologists on a test set of 150 CT scans of patients who were potential candidates for thrombectomy (60 stroke-negative, 90 stroke-positive middle cerebral artery territory only infarcts), with sensitivity 96% (specificity 72%) for the model versus 61-66% (specificity 90-92%) for the experts; model infarct volume estimates also strongly correlated with those of diffusion MRI (r2 > 0.98). When this 150 CT test set was expanded to include a total of 364 CT scans with a more heterogeneous distribution of infarct locations (94 stroke-negative, 270 stroke-positive mixed territory infarcts), model sensitivity was 97%, specificity 99%, for detection of infarcts larger than the 70 mL volume threshold used for patient selection in several major randomized controlled trials of thrombectomy treatment.

Plant hormesis: Revising of the concepts of biostimulation, elicitation and their application in a sustainable agricultural production.

Current research in basic and applied knowledge of plant science has aimed to unravel the role of the interaction between environmental factors and the genome in the physiology of plants to confer the ability to overcome challenges in a climate change scenario. Evidence shows that factors causing environmental stress (stressors), whether of biological, chemical, or physical origin, induce eustressing or distressing effects in plants depending on the dose. The latter suggests the induction of the "hormesis" phenomenon. Sustainable crop production requires a better understanding of hormesis, its basic concepts, and the input variables to make its management feasible. This implies that acknowledging hormesis in plant research could allow specifying beneficial effects to effectively manage environmental stressors according to cultivation goals. Several factors have been useful in this regard, which at low doses show beneficial eustressing effects (biostimulant/elicitor), while at higher doses, they show distressing toxic effects. These insights highlight biostimulants/elicitors as tools to be included in integrated crop management strategies for reaching sustainability in plant science and agricultural studies. In addition, compelling evidence on the inheritance of elicited traits in plants unfolds the possibility of implementing stressors as a tool in plant breeding.