Molecular and phenotypic profiling from base to the crown in maritime pine wood-forming tissue

Research• Environmental, developmental and genetic factors affect variation in wood properties at the chemical, anatomical and physical levels. Here, the phenotypic variation observed along the tree stem was explored and the hypothesis tested that this variation could be the result of the differential expression of genes/proteins during wood formation. • Differentiating xylem samples of maritime pine (Pinus pinaster) were collected from the top (crown wood, CW) to the bottom (base wood, BW) of adult trees. These samples were characterized by Fourier transform infrared spectroscopy (FTIR) and analytical pyrolysis. Two main groups of samples, corresponding to CW and BW, could be distinguished from cell wall chemical composition. • A genomic approach, combining large-scale production of expressed sequence tags (ESTs), gene expression profiling and quantitative proteomics analysis, allowed identification of 262 unigenes (out of 3512) and 231 proteins (out of 1372 spots) that were differentially expressed along the stem. • A good relationship was found between functional categories from transcriptomic and proteomic data. A good fit between the molecular mechanisms involved in CW–BW formation and these two types of wood phenotypic differences was also observed. This work provides a list of candidate genes for wood properties that will be tested in forward genetic

Proximity Full-Text Search by Means of Additional Indexes with Multi-component Keys: In Pursuit of Optimal Performance

Full-text search engines are important tools for information retrieval. In a proximity full-text search, a document is relevant if it contains query terms near each other, especially if the query terms are frequently occurring words. For each word in a text, we use additional indexes to store information about nearby words that are at distances from the given word of less than or equal to the MaxDistance parameter. We showed that additional indexes with three-component keys can be used to improve the average query execution time by up to 94.7 times if the queries consist of high-frequency occurring words. In this paper, we present a new search algorithm with even more performance gains. We consider several strategies for selecting multi-component key indexes for a specific query and compare these strategies with the optimal strategy. We also present the results of search experiments, which show that three-component key indexes enable much faster searches in comparison with two-component key indexes. This is a pre-print of a contribution "Veretennikov A.B. (2019) Proximity Full-Text Search by Means of Additional Indexes with Multi-component Keys: In Pursuit of Optimal Performance." published in "Manolopoulos Y., Stupnikov S. (eds) Data Analytics and Management in Data Intensive Domains. DAMDID/RCDL 2018. Communications in Computer and Information Science, vol 1003" published by Springer, Cham. This book constitutes the refereed proceedings of the 20th International Conference on Data Analytics and Management in Data Intensive Domains, DAMDID/RCDL 2018, held in Moscow, Russia, in October 2018. The 9 revised full papers presented together with three invited papers were carefully reviewed and selected from 54 submissions. The final authenticated version is available online at https://doi.org/10.1007/978-3-030-23584-0_7.Comment: Revised paper of "Veretennikov A.B. Proximity full-text search with a response time guarantee by means of additional indexes with multi-component keys", Selected Papers of the XX International Conference on Data Analytics and Management in Data Intensive Domains (DAMDID/RCDL 2018), Moscow, Russia, October 9-12, 2018, http://ceur-ws.org/Vol-2277, http://ceur-ws.org/Vol-2277/paper23.pd

Proximity Full-Text Searches of Frequently Occurring Words with a Response Time Guarantee

Full-text search engines are important tools for information retrieval. In a proximity full-text search, a document is relevant if it contains query terms near each other, especially if the query terms are frequently occurring words. For each word in the text, we use additional indexes to store information about nearby words at distances from the given word of less than or equal to MaxDistance, which is a parameter. A search algorithm for the case when the query consists of high-frequently occurring words is discussed. In addition, we present results of experiments with different values of MaxDistance to evaluate the search speed dependence on the value of MaxDistance. These results show that the average time of the query execution with our indexes is 94.7–45.9 times (depending on the value of MaxDistance) less than that with standard inverted files when queries that contain high-frequently occurring words are evaluated. © Springer Nature Switzerland AG 2020

The Combined Dexamethasone/CRH Test (DEX/CRH Test) and Prediction of Acute Treatment Response in Major Depression

In this study the predictive value of the combined dexamethasone/CRH test (DEX/CRH test) for acute antidepressant response was investigated. In 114 depressed inpatients suffering from unipolar or bipolar depression (sample 1) the DEX/CRH test was performed at admission and shortly before discharge. During their stay in the hospital patients received different antidepressant treatment regimens. At admission, the rate of nonsuppression (basal cortisol levels >75.3 nmol/l) was 24.6% and was not related to the later therapeutic response. Moreover, 45 out of 114 (39.5%) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement. In a second sample, 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks. The DEX/CRH test was performed before, after 1 week, and after 5 weeks of pharmacotherapy. Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment, whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine. However, early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome. Taken together, performance of a single DEX/CRH test does not predict the therapeutic response. The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks. However, early improvement of HPA system dysfunction is not a sufficient condition for a favourable response. Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge, downregulation of HPA system function is not a necessary condition for acute clinical improvement either. Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression, although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response

Boolean versus ranked querying for biomedical systematic reviews

Background: The process of constructing a systematic review, a document that compiles the published evidence pertaining to a specified medical topic, is intensely time-consuming, often taking a team of researchers over a year, with the identification of relevant published research comprising a substantial portion of the effort. The standard paradigm for this information-seeking task is to use Boolean search; however, this leaves the user(s) the requirement of examining every returned result. Further, our experience is that effective Boolean queries for this specific task are extremely difficult to formulate and typically require multiple iterations of refinement before being finalized. Methods: We explore the effectiveness of using ranked retrieval as compared to Boolean querying for the purpose of constructing a systematic review. We conduct a series of experiments involving ranked retrieval, using queries defined methodologically, in an effort to understand the practicalities of incorporating ranked retrieval into the systematic search task. Results: Our results show that ranked retrieval by itself is not viable for this search task requiring high recall. However, we describe a refinement of the standard Boolean search process and show that ranking within a Boolean result set can improve the overall search performance by providing early indication of the quality of the results, thereby speeding up the iterative query-refinement process. Conclusions: Outcomes of experiments suggest that an interactive query-development process using a hybrid ranked and Boolean retrieval system has the potential for significant time-savings over the current search process in the systematic reviewing

Syndecan-4 Is Essential for Development of Concentric Myocardial Hypertrophy via Stretch-Induced Activation of the Calcineurin-NFAT Pathway

Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4−/− mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT) signaling pathway. Cardiomyocytes from syndecan-4−/−-NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold) compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function) activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179) in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had increased syndecan-4 levels with decreased pS179 which was associated with increased NFAT activation. In conclusion, our data show that syndecan-4 is essential for compensatory hypertrophy in the pressure overloaded heart. Specifically, syndecan-4 regulates stretch-induced activation of the calcineurin-NFAT pathway in cardiomyocytes. Thus, our data suggest that manipulation of syndecan-4 may provide an option for therapeutic modulation of calcineurin-NFAT signaling

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes