scholarly journals Systematic Analysis and Prediction ofIn SituCross Talk of O-GlcNAcylation and Phosphorylation

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Heming Yao ◽  
Ao Li ◽  
Minghui Wang

Reversible posttranslational modification (PTM) plays a very important role in biological process by changing properties of proteins. As many proteins are multiply modified by PTMs, cross talk of PTMs is becoming an intriguing topic and draws much attention. Currently, lots of evidences suggest that the PTMs work together to accomplish a specific biological function. However, both the general principles and underlying mechanism of PTM crosstalk are elusive. In this study, by using large-scale datasets we performed evolutionary conservation analysis, gene ontology enrichment, motif extraction of proteins with cross talk of O-GlcNAcylation and phosphorylation cooccurring on the same residue. We found that proteins within situO-GlcNAc/Phos cross talk were significantly enriched in some specific gene ontology terms and no obvious evolutionary pressure was observed. Moreover, 3 functional motifs associated with O-GlcNAc/Phos sites were extracted. We further used sequence features and GO features to predict O-GlcNAc/Phos cross talk sites based on phosphorylated sites and O-GlcNAcylated sites separately by the use of SVM model. The AUC of classifier based on phosphorylated sites is 0.896 and the other classifier based on GlcNAcylated sites is 0.843. Both classifiers achieved a relatively better performance compared with other existing methods.


2020 ◽  
Author(s):  
Birgit H M Meldal ◽  
Carles Pons ◽  
Livia Perfetto ◽  
Noemi Del-Toro ◽  
Edith Wong ◽  
...  

AbstractThe EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data is freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members.



2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.



2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e16-e16
Author(s):  
Ahmed Moussa ◽  
Audrey Larone-Juneau ◽  
Laura Fazilleau ◽  
Marie-Eve Rochon ◽  
Justine Giroux ◽  
...  

Abstract BACKGROUND Transitions to new healthcare environments can negatively impact patient care and threaten patient safety. Immersive in situ simulation conducted in newly constructed single family room (SFR) Neonatal Intensive Care Units (NICUs) prior to occupancy, has been shown to be effective in testing new environments and identifying latent safety threats (LSTs). These simulations overlay human factors to identify LSTs as new and existing process and systems are implemented in the new environment OBJECTIVES We aimed to demonstrate that large-scale, immersive, in situ simulation prior to the transition to a new SFR NICU improves: 1) systems readiness, 2) staff preparedness, 3) patient safety, 4) staff comfort with simulation, and 5) staff attitude towards culture change. DESIGN/METHODS Multidisciplinary teams of neonatal healthcare providers (HCP) and parents of former NICU patients participated in large-scale, immersive in-situ simulations conducted in the new NICU prior to occupancy. One eighth of the NICU was outfitted with equipment and mannequins and staff performed in their native roles. Multidisciplinary debriefings, which included parents, were conducted immediately after simulations to identify LSTs. Through an iterative process issues were resolved and additional simulations conducted. Debriefings were documented and debriefing transcripts transcribed and LSTs classified using qualitative methods. To assess systems readiness and staff preparedness for transition into the new NICU, HCPs completed surveys prior to transition, post-simulation and post-transition. Systems readiness and staff preparedness were rated on a 5-point Likert scale. Average survey responses were analyzed using dependent samples t-tests and repeated measures ANOVAs. RESULTS One hundred eight HCPs and 24 parents participated in six half-day simulation sessions. A total of 75 LSTs were identified and were categorized into eight themes: 1) work organization, 2) orientation and parent wayfinding, 3) communication devices/systems, 4) nursing and resuscitation equipment, 5) ergonomics, 6) parent comfort; 7) work processes, and 8) interdepartmental interactions. Prior to the transition to the new NICU, 76% of the LSTs were resolved. Survey response rate was 31%, 16%, 7% for baseline, post-simulation and post-move surveys, respectively. System readiness at baseline was 1.3/5,. Post-simulation systems readiness was 3.5/5 (p = 0.0001) and post-transition was 3.9/5 (p = 0.02). Staff preparedness at baseline was 1.4/5. Staff preparedness post-simulation was 3.3/5 (p = 0.006) and post-transition was 3.9/5 (p = 0.03). CONCLUSION Large-scale, immersive in situ simulation is a feasible and effective methodology for identifying LSTs, improving systems readiness and staff preparedness in a new SFR NICU prior to occupancy. However, to optimize patient safety, identified LSTs must be mitigated prior to occupancy. Coordinating large-scale simulations is worth the time and cost investment necessary to optimize systems and ensure patient safety prior to transition to a new SFR NICU.





2021 ◽  
Vol 13 (2) ◽  
pp. 228
Author(s):  
Jian Kang ◽  
Rui Jin ◽  
Xin Li ◽  
Yang Zhang

In recent decades, microwave remote sensing (RS) has been used to measure soil moisture (SM). Long-term and large-scale RS SM datasets derived from various microwave sensors have been used in environmental fields. Understanding the accuracies of RS SM products is essential for their proper applications. However, due to the mismatched spatial scale between the ground-based and RS observations, the truth at the pixel scale may not be accurately represented by ground-based observations, especially when the spatial density of in situ measurements is low. Because ground-based observations are often sparsely distributed, temporal upscaling was adopted to transform a few in situ measurements into SM values at a pixel scale of 1 km by introducing the temperature vegetation dryness index (TVDI) related to SM. The upscaled SM showed high consistency with in situ SM observations and could accurately capture rainfall events. The upscaled SM was considered as the reference data to evaluate RS SM products at different spatial scales. In regard to the validation results, in addition to the correlation coefficient (R) of the Soil Moisture Active Passive (SMAP) SM being slightly lower than that of the Climate Change Initiative (CCI) SM, SMAP had the best performance in terms of the root-mean-square error (RMSE), unbiased RMSE and bias, followed by the CCI. The Soil Moisture and Ocean Salinity (SMOS) products were in worse agreement with the upscaled SM and were inferior to the R value of the X-band SM of the Advanced Microwave Scanning Radiometer 2 (AMSR2). In conclusion, in the study area, the SMAP and CCI SM are more reliable, although both products were underestimated by 0.060 cm3 cm−3 and 0.077 cm3 cm−3, respectively. If the biases are corrected, then the improved SMAP with an RMSE of 0.043 cm3 cm−3 and the CCI with an RMSE of 0.039 cm3 cm−3 will hopefully reach the application requirement for an accuracy with an RMSE less than 0.040 cm3 cm−3.



2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Sungmin O. ◽  
Rene Orth

AbstractWhile soil moisture information is essential for a wide range of hydrologic and climate applications, spatially-continuous soil moisture data is only available from satellite observations or model simulations. Here we present a global, long-term dataset of soil moisture derived through machine learning trained with in-situ measurements, SoMo.ml. We train a Long Short-Term Memory (LSTM) model to extrapolate daily soil moisture dynamics in space and in time, based on in-situ data collected from more than 1,000 stations across the globe. SoMo.ml provides multi-layer soil moisture data (0–10 cm, 10–30 cm, and 30–50 cm) at 0.25° spatial and daily temporal resolution over the period 2000–2019. The performance of the resulting dataset is evaluated through cross validation and inter-comparison with existing soil moisture datasets. SoMo.ml performs especially well in terms of temporal dynamics, making it particularly useful for applications requiring time-varying soil moisture, such as anomaly detection and memory analyses. SoMo.ml complements the existing suite of modelled and satellite-based datasets given its distinct derivation, to support large-scale hydrological, meteorological, and ecological analyses.



Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.



2021 ◽  
Vol 13 (7) ◽  
pp. 1335
Author(s):  
Ronald Souza ◽  
Luciano Pezzi ◽  
Sebastiaan Swart ◽  
Fabrício Oliveira ◽  
Marcelo Santini

The Brazil–Malvinas Confluence (BMC) is one of the most dynamical regions of the global ocean. Its variability is dominated by the mesoscale, mainly expressed by the presence of meanders and eddies, which are understood to be local regulators of air-sea interaction processes. The objective of this work is to study the local modulation of air-sea interaction variables by the presence of either a warm (ED1) and a cold core (ED2) eddy, present in the BMC, during September to November 2013. The translation and lifespans of both eddies were determined using satellite-derived sea level anomaly (SLA) data. Time series of satellite-derived surface wind data, as well as these and other meteorological variables, retrieved from ERA5 reanalysis at the eddies’ successive positions in time, allowed us to investigate the temporal modulation of the lower atmosphere by the eddies’ presence along their translation and lifespan. The reanalysis data indicate a mean increase of 78% in sensible and 55% in latent heat fluxes along the warm eddy trajectory in comparison to the surrounding ocean of the study region. Over the cold core eddy, on the other hand, we noticed a mean reduction of 49% and 25% in sensible and latent heat fluxes, respectively, compared to the adjacent ocean. Additionally, a field campaign observed both eddies and the lower atmosphere from ship-borne observations before, during and after crossing both eddies in the study region during October 2013. The presence of the eddies was imprinted on several surface meteorological variables depending on the sea surface temperature (SST) in the eddy cores. In situ oceanographic and meteorological data, together with high frequency micrometeorological data, were also used here to demonstrate that the local, rather than the large scale forcing of the eddies on the atmosphere above, is, as expected, the principal driver of air-sea interaction when transient atmospheric systems are stable (not actively varying) in the study region. We also make use of the in situ data to show the differences (biases) between bulk heat flux estimates (used on atmospheric reanalysis products) and eddy covariance measurements (taken as “sea truth”) of both sensible and latent heat fluxes. The findings demonstrate the importance of short-term changes (minutes to hours) in both the atmosphere and the ocean in contributing to these biases. We conclude by emphasizing the importance of the mesoscale oceanographic structures in the BMC on impacting local air-sea heat fluxes and the marine atmospheric boundary layer stability, especially under large scale, high-pressure atmospheric conditions.



2004 ◽  
Vol 261-263 ◽  
pp. 1097-1102 ◽  
Author(s):  
Jian Liu ◽  
Xia Ting Feng ◽  
Xiu Li Ding ◽  
Huo Ming Zhou

The time-dependent behavior of rock mass, which is generally governed by joints and shearing zones, is of great significance for engineering design and prediction of long-term deformation and stability. In situ creep test is a more effective method than laboratory test in characterizing the creep behavior of rock mass with joint or shearing zone due to the complexity of field conditions. A series of in situ creep tests on granite with joint at the shiplock area of the Three-Gorges Project and basalt with shearing zone at the right abutment of the Xiluodu Project were performed in this study. Based on the test results, the stress-displacement-time responses of the joints and basalt are analyzed, and their time-dependent constitutive model and model coefficients are given, which is crucial for the design to prevent the creep deformations of rock masses from causing the failure of the operation of the shiplock gate at the Three-Gorges Project and long-term stability of the Xiluodu arc dam.



2021 ◽  
Author(s):  
Xiao-Ya Zhai ◽  
Yifan Zhao ◽  
Guo-Ying Zhang ◽  
Bing-Yu Wang ◽  
Qi-Yun Mao

In the work, a direct Z-scheme AgBr/α-Ag2WO4 heterojunction was prepared by in-situ anion exchange at room temperature. The construction strategy is energy- and time-saving for large scale synthesis. The α-Ag2WO4...



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