Major cereal yields are expected to decline significantly in coming years due to the effects of climate change temperature rise. Agroforestry systems have been recognized as a useful land management ...strategy that could mitigate these effects through the shelter provided by trees, but it is unclear how shade affects cereal production. Most cereal species and cultivars have been selected for full light conditions, making it necessary to determine those able to acclimate to low irradiance environments and the traits that drive this acclimation. A greenhouse experiment was conducted in central Spain to assess the photosynthetic response, leaf morphology and grain yield of nine cultivars of winter wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) at three levels of photosynthetic active radiation (100%, 90% and 50%). Cultivars were selected according to three different precocity categories and were widely used in the studied area. The main objective was to assess whether the species and cultivars could acclimate to partial shade through physiological and morphological acclimations and thus increase their grain yield for cultivation in agroforestry systems. Both species increased grain yield by 19% in shade conditions. However, they used different acclimation strategies. Barley mostly performed a physiological acclimation, while wheat had a major morphological adjustment under shaded environment. Barley had lower dark respiration (42%), lower light compensation point (73%) and higher maximum quantum yield (48%) than wheat in full light conditions, revealing that it was a more shade-tolerant species than wheat. In addition, to acclimate to low irradiance conditions, barley showed a 21% reduction of the carotenoids/chlorophyll ratio in the lowest irradiance level compared to 100% light availability and adjusted the chlorophyll a/b ratio, photosystem II quantum efficiency, electron transport rate and non-photochemical quenching to shade conditions. On the other hand, wheat showed a 48% increase in single leaf area in the 50% irradiance level than in full light to maximize light capture. Our results showed that current commercialized wheat and barley cultivars had sufficient plasticity for adaptation to shade, supporting tree presence as a tool to reduce the negative effects of climate change.
Due to their capability to transport chemicals or proteins into target cells, cell‐penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting ...properties, arginine‐rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic lateral sclerosis (ALS) as a model of an arginine‐rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA‐ and DNA‐binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids, such as RNA transcription, translation, splicing and degradation, or DNA replication and repair, is impaired by the presence of the CPPs. Interestingly, the effects of (PR)n are fully mimicked by protamine, a small arginine‐rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA‐ and DNA‐binding factors from chromatin and mRNA accounts for the toxicity of arginine‐rich CPPs, including those that have been recently associated with the onset of ALS.
Synopsis
Arginine‐rich cell penetrating peptides (CPPs) can target therapeutic agents into cells, but often exhibit toxicity. Here, this is shown to originate from a generalized coating of cellular nucleic acids, affecting the physiological interactions with their binding factors.
Arginine‐rich CPPs coat cellular nucleic acids, leading to a generalized displacement of DNA‐ and RNA‐binding factors from chromatin and mRNA.
The impact of ALS‐associated (PR)20 peptides on translation is due to interactions with mRNA that prevent the assembly of 80S ribosomes.
The effects of arginine‐rich CPPs are recapitulated by protamine, the protein with the highest percentage of arginine within the animal proteome.
Non‐coding oligonucleotides and heparin alleviate the cellular effects of arginine‐rich peptides.
The toxic side effects of basic peptides used as pharmaceutic delivery tools, originates from their protamine‐like coating of nucleic acids.
To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS).
We include 1045 consecutive patients who ...fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models.
After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease.
Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.
Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall ...survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4).
The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection.
We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma.
NCT02614534 ( clinicaltrial.gov ) Nov-2015.
The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In ...this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.
Several types of mixed recycled aggregates (MRA) from construction and demolition waste (C&DW) treatment plants in Córdoba and Malaga, Spain, and a sample of natural aggregate (NA) were studied to ...evaluate the viability of their use in the construction of road layers. The physicochemical properties, mechanical behavior and environmental impact of all samples were determined. The life cycle analysis of road sections manufactured with the materials studied was also determined. All samples of MRA showed a mechanical behavior suitable for use in the formation of road layers. In addition, it was determined that these materials, when they come from C&DW with selective collection at origin, cause less environmental impact than the impact caused by the use of natural aggregates in the formation of road layers.
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•Four types of MRA of different qualities according to the production system were studied.•New leaching limits impact for Mixed Recycled Aggregates (MRA) is proposed.•Higher MRA rates could be used without causing environmental problems.•The mechanical behavior of MRA is similar to that of natural aggregate.
The microRNAs (miRNAs) are a class of small, 20-22 nucleotides in length, endogenously expressed noncoding RNAs that regulate multiple targets posttranscriptionally. Interestingly, miRNAs have ...emerged as regulators of most physiological and pathological processes, including metastatic tumor progression, in part by controlling a reversible process called epithelial-to-mesenchymal transition (EMT). The activation of EMT increases the migratory and invasive properties fundamental for tumor cell spread while activation of the reverse mesenchymal-to-epithelial transition is required for metastasis outgrowth. The EMT triggering leads to the activation of a core of transcription factors (EMT-TFs) - SNAIL1/SNAIL2, bHLH (E47, E2-2, and TWIST1/TWIST2), and ZEB1/ZEB2 - that act as E-cadherin repressors and, ultimately, coordinate EMT. Recent evidence indicates that several miRNAs regulate the expression of EMT-TFs or EMT-activating signaling pathways. Interestingly, some miRNAs and EMT-TFs form tightly interconnected negative feedback loops that control epithelial cell plasticity, providing self-reinforcing signals and robustness to maintain the epithelial or mesenchymal cell status. Among the most significant feedback loops, we focus on the ZEB/miR-200 and the SNAIL1/miR-34 networks that hold a clear impact in the regulation of the epithelial-mesenchymal state. Recent insights into the p53 modulation of the EMT-TF/miRNA loops and epigenetic regulatory mechanisms in the context of metastasis dissemination will also be discussed. Understanding the regulation of EMT by miRNAs opens new avenues for the diagnosis and prognosis of tumors and identifies potential therapeutic targets that might help to negatively impact on metastasis dissemination and increasing patient survival.
The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no ...depressive disorder (nonD). Factors related to subD were identified.
PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL.
The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ± 12.8 vs 11.6 ± 10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ± 0.5 vs 4 ± 0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ± 32 vs 29.1 ± 25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011–1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045–1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007–1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983–0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086–1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058–1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone.
SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.
•Subthreshold depression (SubD) is a frequent problem in patients with PD and is near to triple prevalent than in controls.•Health-related and global perceived quality of life (QoL) are worse in subD than in non-depressed (nonD) PD patients.•A greater non-motor symptoms burden is associated with subthreshold depression in PD.•Specifically, fatigue, sleep problems, and neuropsychiatric symptoms seems to be related to subD in PD.•All this suggests that detection of subD in PD could be an important factor in clinical practice.
Milpa is a traditional polyculture production system mainly composed of corn, beans and pumpkin, together with other edible plants. It represents an important food and nutrients supply, but also ...bioactive compounds source, such as phenols, anthocyanins, phytosterols, phytates, resistant starch, peptides, among others compounds that confer multiple health benefits. Therefore, the aim of this work was to gather the scientific evidence on the health effects of the bioactive compounds found in the plants that belong to the milpa. Although there are few studies that report the interaction between different biomolecules and crops in combination, as in meant to be at regular eating; evidence, here summarized, suggests that consumption of milpa vegetables has an active effect of biomolecules from these crops was found active, mainly on chronic non-communicable diseases. Thus, the main objective of this study was to summarize the scientific evidence on bioactive compounds found in the plants grown as part of the milpa and their health-related benefits.
•Most of the C stock was contained in SOC, followed by aboveground biomass.•50% of SOC was in the uppermost soil layer (0–25cm).•SOC is a more sensitive pool to management techniques.•Grazing and ...legume sowing are suitable techniques for optimising SOC and tree growth.
Recent studies in temperate regions have shown that agroforestry systems, especially silvopastoral systems, have greater carbon (C) sequestration potential than monocropping systems or pastures, or even forest plantations. In Europe, there is growing interest in establishing high quality wood plantations with intensive management comprising irrigation, fertilisation and chemical weed control to reduce rotation length. However, these operations can have major environmental impacts similar to the effects of intensive agriculture, such as impoverishment of soil C. The aim of this study is to identify optimum management practices for intensive systems of quality wood production to optimise soil C stock and plantation productivity. An experiment was conducted in Extremadura, mid-west Spain, from 2011 to 2014, in a 13-year-old hybrid walnut (Juglans major×regia mj 209xra) plantation with a density of 333 trees ha−1. Two essays were established: one with three techniques to control competition from herbaceous strata beneath trees – mowing, ploughing and sheep grazing (1 sheep ha−1) – and the other to test implementation of legumes (mixture of Trifolium michelanium and Ornithopus compressus complemented by the same quantities of phosphorous and potassium as mineral treatment) as an alternative to traditional mineral fertilisation (40kgNha−1, 40kg P2O5 ha−1 and 50kg K2O ha−1). The C stock estimate was based on soil organic carbon (SOC) and aboveground (tree trunks and branches) and belowground biomass (tree and pasture roots). Most of the C stock was contained in SOC, at 50% in the uppermost soil layer (0–25cm), followed by aboveground biomass. The response of SOC in each treatment was higher than the other parameters analysed, suggesting that SOC is a more sensitive pool to management techniques. Grazing as control of herbaceous vegetation and legume implementation as nitrogen supply are suitable techniques for optimising soil C stocks and also achieve adequate tree growth in the longer term.
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