Several experiments have highlighted the complexity of stress interactions involved in plant response. The impact in field conditions of combined environmental constraints on the mechanisms involved ...in plant photosynthetic response, however, remains understudied. In a long‐term field study performed in a managed grassland, we investigated the photosynthetic apparatus response of the perennial ryegrass (Lolium perenne L.) to environmental constraints and its ability to recover and acclimatize. Frequent field measurements of chlorophyll a fluorescence (ChlF) were made in order to determine the photosynthetic performance response of a population of L. perenne. Strong midday declines in the maximum quantum yield of primary photochemistry (FVFM) were observed in summer, when a combination of heat and high light intensity increased photosynthetic inhibition. During this period, increase in photosystem I (PSI) activity efficiency was also recorded, suggesting an increase in the photochemical pathway for de‐excitation in summer. Strong climatic events (e.g. heat waves) were shown to reduce electron transport between photosystem II (PSII) and PSI. This reduction might have preserved the PSI from photo‐oxidation. Periods of low soil moisture and high levels of sun irradiance increased PSII sensitivity to heat stress, suggesting increased susceptibility to combined environmental constraints. Despite the multiple inhibitions of photosynthetic functionality in summer, the L. perenne population showed increased PSII tolerance to environmental stresses in August. This might have been a response to earlier environmental constraints. It could also be linked to the selection and/or emergence of well‐adapted individuals.
Bdelloid rotifers are micro-invertebrates distributed worldwide, from temperate latitudes to the most extreme areas of the planet like Antarctica or the Atacama Desert. They have colonized any ...habitat where liquid water is temporarily available, including terrestrial environments such as soils, mosses, and lichens, tolerating desiccation and other types of stress such as high doses of ionizing radiation (IR). It was hypothesized that bdelloid desiccation and radiation resistance may be attributed to their potential ability to repair DNA double-strand breaks (DSBs). Here, these properties are investigated and compared among nine bdelloid species collected from both mild and harsh habitats, addressing the correlation between the ability of bdelloid rotifers to survive desiccation and their capacity to repair massive DNA breakage in a phylogenetically explicit context. Our research includes both specimens isolated from habitats that experience frequent desiccation (at least 1 time per generation), and individuals sampled from habitats that rarely or never experienced desiccation.
Our analysis reveals that DNA repair prevails in somatic cells of both desiccation-tolerant and desiccation-sensitive bdelloid species after exposure to X-ray radiation. Species belonging to both categories are able to withstand high doses of ionizing radiation, up to 1000 Gy, without experiencing any negative effects on their survival. However, the fertility of two desiccation-sensitive species, Rotaria macrura and Rotaria rotatoria, was more severely impacted by low doses of radiation than that of desiccation-resistant species. Surprisingly, the radioresistance of desiccation-resistant species is not related to features of their original habitat. Indeed, bdelloids isolated from Atacama Desert or Antarctica were not characterized by a higher radioresistance than species found in more temperate environments.
Tolerance to desiccation and radiation are supported as ancestral features of bdelloid rotifers, with a group of species of the genus Rotaria having lost this trait after colonizing permanent water habitats. Together, our results provide a comprehensive overview of the evolution of desiccation and radiation resistance among bdelloid rotifers.
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Paclitaxel (PTX)-loaded polymeric micelles (M-PTX) have been shown to enhance the blood flow and oxygenation of tumors 24h after treatment. We hypothesized that these changes in the ...tumor microenvironment could lead to an enhancement of the EPR (enhanced permeability and retention) effect. M-PTX, administered 24h before analysis, increased the accumulation of macromolecules, nanoparticles and polymeric micelles in tumors. This increased EPR effect could be linked to normalization of the tumor vasculature and decreased interstitial fluid pressure. M-PTX used as a pre-treatment allowed a more effective delivery of three nanomedicines into tumors: polymeric micelles, liposomes and nanoparticles. These experiments demonstrate an enhanced EPR effect after M-PTX treatment, which lead to better availability and enhanced efficacy of a subsequent treatment with nanomedicines.
Medication Event Monitoring System (MEMS®) is considered the gold standard for the evaluation of medication adherence, yet few studies have applied this method, especially over long periods of time.
...To investigate medication adherence patterns in a sample of post-discharge patients with schizophrenia monitored with MEMS caps during a six-month period.
Adherence to antipsychotics was prospectively investigated using MEMS among 68 patients with schizophrenia. Treatment initiation, implementation or whether or not the patient takes his dosing regimen as prescribed, persistence or the length of time between initiation and discontinuation, and treatment discontinuation were used to describe adherence. Persistence over time was described using Kaplan-Meier curves.
After discharge 16% of the patients never initiated treatment. On average 37.3% of patients adhered to treatment in the first 6months. However, a strong decrease in adherence was observed over time (p<0.0001), primarily due by treatment non-persistence. Only half of the patients were persistent at 6weeks, persistence further dropped to 19.0% after 6months. Among persistent patients, implementation was consistent over time with 87.8% of patients taking their medication as prescribed on any given day.
Dosing profile analysis provides further evidence for the magnitude of non-adherence with antipsychotic prescriptions among post-discharge patients with schizophrenia. Using the high precision of MEMS®, dosing profiles may provide a better understanding of non-adherence patterns and help clinicians determine optimal individualized strategies.
Developing reliable methodologies for detecting and quantifying allergens in processed food commodities is crucial to support food business operators in allergen risk assessment and properly ...implementing precautionary allergen labels whenever required to safeguard the health of allergic consumers. Multiple Mass Spectrometry (MS) methods have been developed so far and applied for single and multi-allergen detection in foods, generating a heterogeneous literature on this topic, with little attention paid to the extraction and the digestion steps, crucial in delivering accurate allergen measurements.
This investigation carried out within an international consortium specifically built up to convey a prototype MS based reference method, reports on the first part of the method development, namely the optimization of the sample preparation protocol for six allergens detection (cow's milk, hen's egg, soy, peanut, hazelnut, and almond) in chocolate. The latter was chosen as model complex food matrix, having a high lipid and polyphenol content.
Different steps of the sample preparation protocol have been taken into consideration: (i) sampling, (ii) composition of the extraction buffer, (iii) protein purification, (iv) protein enzymatic digestion, (v) peptide purification and pre-concentration, and some experiments were carried out by two independent laboratories and two different MS platforms to provide a first assessment of the robustness of the method under development. Fifty target peptides were monitored in multiple reaction monitoring mode and validated in different laboratories to trace the six allergenic ingredients in the incurred chocolate and the best performing protocol for sample preparation was identified. This work paves the way of the forthcoming full analytical validation of a prototype reference method for MS-based allergen quantification.
•Development of a sample prep protocol for allergen detection in chocolate.•Optimization of factors influencing allergen recovery by Mass spectrometry.•Validation of peptide markers tracing for milk, egg, soy, peanut, hazelnut, almond in chocolate.
•Chocolate and broth powder were incurred with six allergenic ingredients (milk, egg, peanut, soybean, hazelnut, and almond).•Discovery analyses were carried out by HR-MS/MS analysis on both incurred ...matrices.•Different conditions for sample preparation were tested and a single best protocol was identified.•A list of potential markers for all ingredients was collected in both matrices with some shared options.•DIA analysis allowed identifying a preliminary set of reliable transitions according to their sensitivity.
Peptide marker identification is an important step in development of a mass spectrometry method for multiple allergen detection, since specificity, robustness and sensitivity of the overall analytical method will depend on the reliability of the proteotypic peptides. As part of the development of a multi-analyte reference method, discovery analysis of two incurred food matrices has been undertaken to select the most reliable peptide markers. Six allergenic ingredients (milk, egg, peanut, soybean, hazelnut, and almond) were incurred into either chocolate or broth powder matrix. Different conditions of protein extraction and purification were tested and the tryptic peptide pools were analysed by untargeted high resolution tandem mass spectrometry and the resulting fragmentation spectra were processed via a commercial software for sequence identification. The analysis performed on incurred foods provides both a prototype effective and straightforward sample preparation protocol and delivers reliable peptides to be included in a standardized selected reaction monitoring method.
Biomarkers and novel therapeutic targets are urgently needed in colorectal cancer (CRC). The pseudo tyrosine kinase receptor 7 (PTK7) is involved in planar cell polarity and it is deregulated in ...various malignancies, including CRC. Yet, little is known about its protein expression in human CRC, or about a possible correlation of its expression with clinical endpoints. Using a clinically annotated Tissue MicroArray (TMA) produced from from 192 consecutive CRC patients treated by initial surgery, we examined PTK7 expression by immunohistochemistry in tumoral tissue and matched normal mucosae, and correlated its expression with clinico-pathological features and patient outcome. PTK7 depletion by specific shRNA in HCT116 and HCT15 CRC cell lines was found to affect cell proliferation, resistance to drugs and cell migration. Tumor growth and metastatic phenotype were investigated in vivo using a xenograft mouse model of CRC cells with modulated expression of PTK7 levels. PTK7 was significantly up-regulated in CRC tissue as compared to matched healthy mucosae, and significant overexpression was found in 34% of patients. PTK7 overexpression was significantly associated with a reduced metastasis-free survival in non-metastatic patients. In HCT116 and HCT15 cells, shRNA PTK7 reduced migration but did not affect cell proliferation and resistance to drugs. In a xenograft mouse of HCT15 cells, downregulation of PTK7 led to reduced tumor growth, whereas its overexpression in PTK7-negative cancer cells led to increased metastatic events. PTK7 expression thus represents a potential prognostic biomarker and a novel therapeutic target in CRC.
With climate projections questioning the future survival of stony corals and their dominance as tropical reef builders, it is critical to understand the adaptive capacity of corals to ongoing climate ...change. Biological mediation of the carbonate chemistry of the coral calcifying fluid is a fundamental component for assessing the response of corals to global threats. The Tara Pacific expedition (2016-2018) provided an opportunity to investigate calcification patterns in extant corals throughout the Pacific Ocean. Cores from colonies of the massive Porites and Diploastrea genera were collected from different environments to assess calcification parameters of long-lived reef-building corals. At the basin scale of the Pacific Ocean, we show that both genera systematically up-regulate their calcifying fluid pH and dissolved inorganic carbon to achieve efficient skeletal precipitation. However, while Porites corals increase the aragonite saturation state of the calcifying fluid (Ω
) at higher temperatures to enhance their calcification capacity, Diploastrea show a steady homeostatic Ω
across the Pacific temperature gradient. Thus, the extent to which Diploastrea responds to ocean warming and/or acidification is unclear, and it deserves further attention whether this is beneficial or detrimental to future survival of this coral genus.
Combining measurements of impaired lung mechanics (inspiratory constraints) with an index of increased respiratory stimuli to metabolic demand (poor ventilatory efficiency) might enhance the ability ...of cardiopulmonary exercise testing (CPET) in exposing a mechanistic role for ventilation on exertional dyspnea in COPD. In addition to the standard approach to suggest ventilatory limitation to exercise - a low breathing reserve (1−(peak ventilation (V̇E)/maximal voluntary ventilation × 100 < 20%) - we assessed the presence of critical inspiratory constraints (end-inspiratory lung volume (EILV)/total lung capacity (TLC) ≥ 0.9) and ventilatory inefficiency (V̇E/CO
2
output (V̇CO
2
) nadir > 34) in 288 patients with mild to very severe COPD (FEV
1
ranging from 18 to 121% predicted). We found that ∼50% of the patients with preserved breathing reserve developed critical inspiratory constraints. A low breathing reserve was weakly related to a lower peak O
2
uptake (V̇O
2
) and/or a higher dyspnea burden; for instance, patients with low breathing reserve but without critical inspiratory constraints had similar dyspnea and peak V̇O
2
than those with preserved breathing reserve (p > 0.05). In contrast, critical inspiratory constraints and ventilatory inefficiency were strongly associated with a negative outcome (likelihood ratio = 42.3 and 47.7, respectively; p < 0.001). A multiple logistic regression analysis revealed that only EILV/TLC ≥ 0.9 and V̇E/V̇CO
2
nadir >34 predicted a severely reduced peak V̇O
2
due to a high dyspnea burden (p < 0.001). Measurements of dynamic mechanical constraints and ventilatory inefficiency during incremental CPET are key to determine the impact of COPD on dyspnea and exercise tolerance across the spectrum of disease severity.
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