OsEUL lectin gene expression in rice : stress regulation, subcellular localization and tissue specificity

The Euonymus lectin (EUL) family is a unique group of carbohydrate-binding proteins that is omnipresent in plants. Sequences encoding EUL-related lectins have been retrieved from all completely sequenced plant genomes. The rice (Oryza sativa) genome contains 5 functional EUL genes referred to as OsEULS2, OsEULS3, OsEULD1a, OsEULD1b, and OsEULD2. In this study we focused on the tissue specific expression, stress inducibility and subcellular localization of the rice EULs. Even though the EUL domain sequence is highly conserved among the rice EULs (at least 80% sequence similarity) different biotic and abiotic stress treatments yielded unique responses for the different EULs. Transcript levels for OsEULs were differentially affected by drought and salt stress, ABA treatment, pathogen infection or insect infestation. Analysis of promoter activity revealed differential expression and tissue specificity for the 5 OsEUL genes, with most expression observed in the vascular system of roots and shoots, as well as in the root tips and seeds. At cell level, all OsEULs are located in the nucleus whereas OsEULD1b and OsEULD2 also locate to the cytoplasm. This paper contributes to the functional characterization of the EULs and provides insight in the biological importance of this family of proteins for rice

Effect of RIP overexpression on abiotic stress tolerance and development of rice

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic enzymes that can inhibit protein translation by depurinating rRNA. Most plant RIPs are synthesized with a leader sequence that sequesters the proteins to a cell compartment away from the host ribosomes. However, several rice RIPs lack these signal peptides suggesting they reside in the cytosol in close proximity to the plant ribosomes. This paper aims to elucidate the physiological function of two nucleocytoplasmic RIPs from rice, in particular, the type 1 RIP referred to as OsRIP1 and a presumed type 3 RIP called nuRIP. Transgenic rice lines overexpressing these RIPs were constructed and studied for developmental effects resulting from this overexpression under greenhouse conditions. In addition, the performance of transgenic seedlings in response to drought, salt, abscisic acid and methyl jasmonate treatment was investigated. Results suggest that both RIPs can affect methyl jasmonate mediated stress responses

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

Abstract Purpose To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential 18 F-FDG PETCT imaging. Materials and methods Prospective data (i.a. THUNDER trial) were used to train ( N =112, MAASTRO Clinic) and validate ( N =78, Universita Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUV max , SUV mean , metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. Results The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUV mean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. Conclusions The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy

'Rapid Learning health care in oncology' – An approach towards decision support systems enabling customised radiotherapy' ☆ ☆☆

AbstractPurposeAn overview of the Rapid Learning methodology, its results, and the potential impact on radiotherapy.Material and resultsRapid Learning methodology is divided into four phases. In the data phase, diverse data are collected about past patients, treatments used, and outcomes. Innovative information technologies that support semantic interoperability enable distributed learning and data sharing without additional burden on health care professionals and without the need for data to leave the hospital. In the knowledge phase, prediction models are developed for new data and treatment outcomes by applying machine learning methods to data. In the application phase, this knowledge is applied in clinical practice via novel decision support systems or via extensions of existing models such as Tumour Control Probability models. In the evaluation phase, the predictability of treatment outcomes allows the new knowledge to be evaluated by comparing predicted and actual outcomes.ConclusionPersonalised or tailored cancer therapy ensures not only that patients receive an optimal treatment, but also that the right resources are being used for the right patients. Rapid Learning approaches combined with evidence based medicine are expected to improve the predictability of outcome and radiotherapy is the ideal field to study the value of Rapid Learning. The next step will be to include patient preferences in the decision making

UR-CarA-Net: A Cascaded Framework with Uncertainty Regularization for Automated Segmentation of Carotid Arteries on Black Blood MR Images

We present a fully automated method for carotid artery (CA) outer wall segmentation in black blood MRI using partially annotated data and compare it to the state-of-the-art reference model. Our model was trained and tested on multicentric data of patients (106 and 23 patients, respectively) with a carotid plaque and was validated on different MR sequences (24 patients) as well as data that were acquired with MRI systems of a different vendor (34 patients). A 3D nnU-Net was trained on pre-contrast T1w turbo spin echo (TSE) MR images. A CA centerline sliding window approach was chosen to refine the nnU-Net segmentation using an additionally trained 2D U-Net to increase agreement with manual annotations. To improve segmentation performance in areas with semantically and visually challenging voxels, Monte-Carlo dropout was used. To increase generalizability, data were augmented with intensity transformations. Our method achieves state-of-the-art results yielding a Dice similarity coefficient (DSC) of 91.7% (interquartile range (IQR) 3.3%) and volumetric intraclass correlation (ICC) with ground truth of 0.90 on the development domain data and a DSC of 91.1% (IQR 7.2%) and volumetric ICC with ground truth of 0.83 on the external domain data outperforming top-ranked methods for open-source CA segmentation. The uncertainty-based approach increases the interpretability of the proposed method by providing an uncertainty map together with the segmentation

Social dimensions of fertility behavior and consumption patterns in the Anthropocene.

We consider two aspects of the human enterprise that profoundly affect the global environment: population and consumption. We show that fertility and consumption behavior harbor a class of externalities that have not been much noted in the literature. Both are driven in part by attitudes and preferences that are not egoistic but socially embedded; that is, each household's decisions are influenced by the decisions made by others. In a famous paper, Garrett Hardin [G. Hardin, Science 162, 1243-1248 (1968)] drew attention to overpopulation and concluded that the solution lay in people "abandoning the freedom to breed." That human attitudes and practices are socially embedded suggests that it is possible for people to reduce their fertility rates and consumption demands without experiencing a loss in wellbeing. We focus on fertility in sub-Saharan Africa and consumption in the rich world and argue that bottom-up social mechanisms rather than top-down government interventions are better placed to bring about those ecologically desirable changes

Role of D-type OsEUL lectins in plant development and abiotic stress response

The PhD aimed to gain more insight into the physiological role of several lectins from rice, especially the D-type OsEULs and their importance for the abiotic stress response, in particular drought stress response. Rice is the second most produced cereal and is a model for other important cereals. The Euonymus lectin (EUL) family is a unique group of carbohydrate-binding proteins that is omnipresent in plants, implying they fulfill an important biological role for the plant. The rice (Oryza sativa) genome contains 5 functional OsEUL genes referred to as OsEULS2, OsEULS3, OsEULD1a, OsEULD1b and OsEULD2. At the start of the PhD only a few scattered reports of proteomics data suggested that at least some of the OsEULs are stress-inducible proteins, especially the D-type OsEULs. First, a broad analysis of the five OsEULs was achieved by investigating the tissue-specific expression, the subcellular localization and the stress inducibility for each of the five OsEULs. Next, it was investigated, whether overexpression of one of the OsEUL genes affects the yield or growth traits of rice plants. After a first comparative analysis between the five OsEULs from rice, the research question focused more on the role of D-type OsEULs in root development and stress responses. The promoter activity of the D-type OsEUL genes was checked in roots of GUS reporter lines subjected to different abiotic treatments. Transgenic overexpression lines for OsEULD1a and OsEULD1b yielded longer roots and shoots, and these plants were more sensitive to salt stress and drought treatment compared to wild type plants. Also, OsEULD1a and OsEULD1b overexpression lines had longer meristematic zones with more meristematic cells compared to wild type plants. Furthermore, transcriptional analyses revealed that OsEULD1a inhibited the expression of the auxin biosynthesis gene OsYUCCA1 and the ABA biosynthesis gene NCED. Lastly, putative interaction partners for OsEULD1a were identified using GFP pull down assays and mass spectrometry

Modulation of cell death in the tumor microenvironment

The microenvironment of solid human tumors is characterized by heterogeneity in oxygenation. Hypoxia arises early in the process of tumor development because rapidly proliferating tumor cells outgrow the capacity of the host vasculature. Formation of solid tumors thus requires coordination of angiogenesis with continued tumor cell proliferation. However, despite such neovascularization, hypoxia is persistent and frequently found in tumors at the time of diagnosis. Tumors with low oxygenation have a poor prognosis, and strong evidence suggests this is because of the effects of hypoxia on malignant progression, angiogenesis, metastasis, and therapy resistance. The presence of viable hypoxic cells is likely a reflection of the development of hypoxia tolerance resulting from modulation of cell death in the microenvironment. This acquired feature has been explained on the basis of clonal selection-the hypoxic microenvironment selects cells capable of surviving in the absence of normal oxygen availability. However, the persistence and frequency of hypoxia in solid tumors raises a second potential explanation. We suggest that stable microregions of hypoxia may play a positive role in tumor growth. Although hypoxia inhibits cell proliferation and in tumor cells will eventually induce cell death, hypoxia also provides angiogenic and metastatic signals. The development of hypoxia tolerance will thus allow prolonged survival in the absence of oxygen and generation of a persistent angiogenic signal. We will discuss the concept of hypoxia tolerance and review mechanisms used by cancer cells to acquire this phenotype. The concept of hypoxia tolerance has important implications for current and future therapeutic approaches. Most therapeutic efforts to combat hypoxia have focused on targeting the presence of hypoxia itself. Our hypothesis predicts that targeting the biological responses to hypoxia and the pathways leading to hypoxia tolerance may also be attractive therapeutic strategies