Effects of selenium biofortification on crop nutritional quality

Selenium (Se) at very low doses has crucial functions in humans and animals. Since plants represent the main dietary source of this element, Se-containing crops may be used as a means to deliver Se to consumers (biofortification). Several strategies have been exploited to increase plant Se content. Selenium assimilation in plants affects both sulphur (S) and nitrogen (N) metabolic pathways, which is why recent research has also focused on the effect of Se fertilization on the production of S- and N- secondary metabolites with putative health benefits. In this review we discuss the function of Se in plant and human nutrition and the progress in the genetic engineering of Se metabolism to increase the levels and bioavailability of this element in food crops. Particular attention is paid to Se biofortification and the synthesis of compounds with beneficial effects on health

Exploring the importance of sulfate transporters and ATP sulphurylases for selenium hyperaccumulation\u2014a comparison of Stanleya pinnata and Brassica juncea (Brassicaceae)

Selenium (Se) hyperaccumulation, the capacity of some species to concentrate Se to levels upwards of 0.1% of dry weight, is an intriguing phenomenon that is only partially understood. Questions that remain to be answered are: do hyperaccumulators have one or more Se-specific transporters? How are these regulated by Se and sulfur (S)? In this study, hyperaccumulator Stanleya pinnata was compared with related non-hyperaccumulator Brassica juncea with respect to S-dependent selenate uptake and translocation, as well as for the expression levels of three sulfate/selenate transporters (Sultr) and three ATP sulphurylases (APS). Selenium accumulation went down ~10-fold with increasing sulfate supply in B. juncea, while S. pinnata only had a 2\u20133-fold difference in Se uptake between the highest (5 mM) and lowest sulfate (0 mM) treatments. The Se/S ratio was generally higher in the hyperaccumulator than the non-hyperaccumulator, and while tissue Se/S ratio in B. juncea largely reflected the ratio in the growth medium, S. pinnata enriched itself up to 5-fold with Se relative to S. The transcript levels of Sultr1;2 and 2;1 and APS1, 2, and 4 were generally much higher in S. pinnata than B. juncea, and the species showed differential transcript responses to S and Se supply. These results indicate that S. pinnata has at least one transporter with significant selenate specificity over sulfate. Also, the hyperaccumulator has elevated expression levels of several sulfate/selenate transporters and APS enzymes, which likely contribute to the Se hyperaccumulation and hypertolerance phenotype

Selenium Biofortification in Radish Enhances Nutritional Quality via Accumulation of Methyl-Selenocysteine and Promotion of Transcripts and Metabolites Related to Glucosinolates, Phenolics, and Amino Acids

Two selenium (Se) fertilization methods were tested for their effects on levels of anticarcinogenic selenocompounds in radish (Raphanus sativus), as well as other nutraceuticals. First, radish was grown on soil and foliar selenate applied 7d before harvest at 0, 5, 10 and 20 mg Se per plant. Selenium levels were up to 1,200 mg Se/kg DW in leaves and 120 mg Se/kg DW in roots. The thiols cysteine and glutathione were present at 2-3 fold higher levels in roots of Se treated plants, and total glucosinolate levels were 35% higher, due to increases in glucoraphanin. The only seleno-aminoacid detected in Se treated plants was Se-methyl-SeCys (100 mg/kg FW in leaves, 33 mg/kg FW in roots). The levels of phenolic aminoacids increased with selenate treatment, as did root total nitrogen and protein content, while the level of several polyphenols decreased. Second, radish was grown in hydroponics and supplied with 0, 5, 10, 20, or 40 \uf06dM selenate for one week. Selenate treatment led to a 20-30% increase in biomass. Selenium concentration was 242 mg Se/kg DW in leaves and 85 mg Se/kg DW in roots. Cysteine levels decreased with Se in leaves but increased in roots; glutatione levels decreased in both. Total glucosinolate levels in leaves decreased with Se treatment due to repression of genes involved in glucosinolates metabolism. Se-methyl-SeCys concentration ranged from 7-15 mg/kg FW. Aminoacid concentration increased with Se treatment in leaves but decreased in roots. Roots of Se treated plants contained elevated transcript levels of sulfate transporters (Sultr) and ATP sulfurylase, a key enzyme of S/Se assimilation. No effects on polyphenols were observed. In conclusion, Se biofortification of radish roots may be achieved via foliar spray or hydroponic supply. One to ten radishes could fulfill the daily human requirement (70 \uf06dg) after a single foliar spray of 5 mg selenate per plant or one week of 5-10 \uf06dM selenate supply in hydroponics. The radishes metabolized selenate to the anticarcinogenic compound Se-methyl-selenocysteine. Selenate treatment enhanced levels of other nutraceuticals in radish roots, including glucoraphanin. Therefore, Se biofortification can produce plants with superior health benefit

Drought stress in maize causes differential acclimation responses of glutathione and sulfur metabolism in leaves and roots

Background: Drought is the most important environmental stress that limits crop yield in a global warming world. Despite the compelling evidence of an important role of oxidized and reduced sulfur-containing compounds during the response of plants to drought stress (e.g. sulfate for stomata closure or glutathione for scavenging of reactive oxygen species), the assimilatory sulfate reduction pathway is almost not investigated at the molecular or at the whole plant level during drought. Results: In the present study, we elucidated the role of assimilatory sulfate reduction in roots and leaves of the staple crop maize after application of drought stress. The time-resolved dynamics of the adaption processes to the stress was analyzed in a physiological relevant situation –when prolonged drought caused significant oxidation stress but root growth should be maintained. The allocation of sulfate was significantly shifted to the roots upon drought and allowed for significant increase of thiols derived from sulfate assimilation in roots. This enabled roots to produce biomass, while leaf growth was stopped. Accumulation of harmful reactive oxygen species caused oxidation of the glutathione pool and decreased glutathione levels in leaves. Surprisingly, flux analysis using [35S]-sulfate demonstrated a significant down-regulation of sulfate assimilation and cysteine synthesis in leaves due to the substantial decrease of serine acetyltransferase activity. The insufficient cysteine supply caused depletion of glutathione pool in spite of significant transcriptional induction of glutathione synthesis limiting GSH1. Furthermore, drought impinges on transcription of membrane-localized sulfate transport systems in leaves and roots, which provides a potential molecular mechanism for the reallocation of sulfur upon prolonged water withdrawal. Conclusions: The study demonstrated a significant and organ-specific impact of drought upon sulfate assimilation. The sulfur metabolism related alterations at the transcriptional, metabolic and enzyme activity level are consistent with a promotion of root growth to search for water at the expense of leaf growth. The results provide evidence for the importance of antagonistic regulation of sulfur metabolism in leaves and roots to enable successful drought stress response at the whole plant level

Algorithms Aside: Recommendation as the Lens of Life

In this position paper, we take the experimental approach of putting algorithms aside, and reflect on what recommenders would be for people if they were not tied to technology. By looking at some of the shortcomings that current recommenders have fallen into and discussing their limitations from a human point of view, we ask the question: if freed from all limitations, what should, and what could, RecSys be? We then turn to the idea that life itself is the best recommender system, and that people themselves are the query. By looking at how life brings people in contact with options that suit their needs or match their preferences, we hope to shed further light on what current RecSys could be doing better. Finally, we look at the forms that RecSys could take in the future. By formulating our vision beyond the reach of usual considerations and current limitations, including business models, algorithms, data sets, and evaluation methodologies, we attempt to arrive at fresh conclusions that may inspire the next steps taken by the community of researchers working on RecSys

Metabolic and molecular rearrangements of Sauvignon Blanc (Vitis vinifera L.) berries in response to foliar applications of specific dry yeast

Dry yeast extracts (DYE) are applied to vineyards to improve aromatic and secondary metabolic compound content and wine quality; however, systematic information on the underpinning molecular mechanisms is lacking. This work aimed to unravel, through a systematic approach, the metabolic and molecular responses of Sauvignon Blanc berries to DYE treatments. To accomplish this, DYE spraying was performed in a commercial vineyard for two consecutive years. Berries were sampled at several time points after the treatment, and grapes were analyzed for sugars, acidity, free and bound aroma precursors, amino acids, and targeted and untargeted RNA-Seq transcriptional profiles. The results obtained indicated that the DYE treatment did not interfere with the technological ripening parameters of sugars and acidity. Some aroma precursors, including cys-3MH and GSH3MH, responsible for the typical aromatic nuances of Sauvignon Blanc, were stimulated by the treatment during both vintages. The levels of amino acids and the global RNA-seq transcriptional profiles indicated that DYE spraying upregulated ROS homeostatic and thermotolerance genes, as well as ethylene and jasmonic acid biosynthetic genes, and activated abiotic and biotic stress responses. Overall, the data suggested that the DYE reduced berry oxidative stress through the regulation of specific subsets of metabolic and hormonal pathway

Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer

BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study—IL PSO (Italian landscape psoriasis)

Background: Tildrakizumab is a humanized monoclonal antibody that binds selectively the p19 subunit of interleukin-23. It is approved for treatment of moderate– severe chronic plaque psoriasis. Objectives: We conducted a 52-week retrospective study to assess the effectiveness and safety of tildrakizumab in a real-life setting. Methods: Our retrospective study included 237 consecutive adults with moderateto-severe plaque psoriasis, enrolled in 10 different Italian centres, treated with tildrakizumab up to Week 52. Patient characteristics, comorbidities, previous treatmentsand the PASI (Psoriasis Area and Severity Index) score at each visit (baseline, Week 16, Week 28 and Week 52) were retrieved from the electronic medical records. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI with respect to baseline PASI were registered. Results: At Week 52, 90.91%, 73.55% and 58.68% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. An absolute PASI≤2 was reached by 85.95% at Week 52. Compared with Phase 3 clinical trials, we observed similar rates of PASI 75/90 responses and higher percentages of patients achieving PASI 100. Patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities were significantly more likely to achieve PASI 100 at Week 28 and PASI 90 at Week 52. The higher body mass index did not interfere with the odds of reaching PASI 75/90/100 at each time point. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment because of adverse events. Conclusion: Our data suggest that the efficacy of tildrakizumab for plaque psoriasis in ‘real-life’ clinical practice is comparable with Phase 3 clinical trials with higher percentages of patients achieving complete skin clearance (PASI 100) at Weeks 16, 28 and 52

Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC