Switching the Post-translational Modification of Translation Elongation Factor EF-P

Tripeptides with two consecutive prolines are the shortest and most frequent sequences causing ribosome stalling. The bacterial translation elongation factor P (EF-P) relieves this arrest, allowing protein biosynthesis to continue. A seven amino acids long loop between beta-strands β3/β4 is crucial for EF-P function and modified at its tip by lysylation of lysine or rhamnosylation of arginine. Phylogenetic analyses unveiled an invariant proline in the -2 position of the modification site in EF-Ps that utilize lysine modifications such as Escherichia coli. Bacteria with the arginine modification like Pseudomonas putida on the contrary have selected against it. Focusing on the EF- Ps from these two model organisms we demonstrate the importance of the β3/β4 loop composition for functionalization by chemically distinct modifications. Ultimately, we show that only two amino acid changes in E. coli EF-P are needed for switching the modification strategy from lysylation to rhamnosylation

Switching the Post-translational Modification of Translation Elongation Factor EF-P

Tripeptides with two consecutive prolines are the shortest and most frequent sequences causing ribosome stalling. The bacterial translation elongation factor P (EF-P) relieves this arrest, allowing protein biosynthesis to continue. A seven amino acids long loop between beta-strands β3/β4 is crucial for EF-P function and modified at its tip by lysylation of lysine or rhamnosylation of arginine. Phylogenetic analyses unveiled an invariant proline in the -2 position of the modification site in EF-Ps that utilize lysine modifications such as Escherichia coli. Bacteria with the arginine modification like Pseudomonas putida on the contrary have selected against it. Focusing on the EF-Ps from these two model organisms we demonstrate the importance of the β3/β4 loop composition for functionalization by chemically distinct modifications. Ultimately, we show that only two amino acid changes in E. coli EF-P are needed for switching the modification strategy from lysylation to rhamnosylation

Super Resolution Mapping of Scatterometer Ocean Surface Wind Speed Using Generative Adversarial Network: Experiments in the Southern China Sea

This paper designed a Generative Adversarial Network (GAN)-based super-resolution framework for scatterometer ocean surface wind speed (OSWS) mapping. An improved GAN, WSGAN, was well-trained to generate high-resolution OSWS (~1/64 km) from low-resolution OSWS (~12.5 km) retrieved from scatterometer observations. The generator of GAN incorporated Synthetic Aperture Radar (SAR) information in the training phase. Therefore, the pre-trained model could reconstruct high-resolution OSWS with historical local spatial and texture information. The training experiments were executed in the South China Sea using the OSWS generated from the Advanced SCATterometer (ASCAT) scatterometer and Sentinel-1 SAR OSWS set. Several GAN-based methods were compared, and WSGAN performed the best in most sea states, enabling more detail mining with fewer checkerboard artifacts at a scale factor of eight. The model reaches an overall root mean square error (RMSE) of 0.81 m/s and an overall mean absolute error (MAE) of 0.68 m/s in the collocation region of ASCAT and Sentinel-1. The model also exhibits excellent generalization capability in another scatterometer with an overall RMSE of 1.11 m/s. This study benefits high-resolution OSWS users when no SAR observation is available

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent

Petroleum Charging History of the Paleogene Sandstone Reservoirs in the Huangtong Sag of the Fushan Depression, South China Sea

The Paleogene sandstone reservoir in the Huangtong Sag of the Fushan Depression is one of the most commercially prolific oil accumulations in the Beibuwan Basin, South China Sea. In this study, twenty-seven crude oil samples from four oilfields in the sag were geochemically analyzed and classified into three oil groups. Oils in the Meitai and Hongguang oilfields show similar geochemical characteristics, with relatively abundant C30 4α-methyl-24-ethylcholestanes and low contents of oleanane and C19+20 tricyclic terpanes (TT), and therefore may be derived from the same source kitchen. Oils from the Yong’an oilfield have a greater proportion of oleanane and C19+20 TT compounds. Oils from the Chaoyang oilfield have intermediate contents of these biomarkers and proportionate values of other related parameters. The unimodal distribution pattern of homogenization temperatures of fluid inclusions found in all the Paleogene reservoirs indicates a single episode of charging. Combining this understanding with the reconstruction of stratigraphy-burial and geothermal histories by 1-D basin modeling, the petroleum charging time was determined to be between 8–2 Ma (the end of the middle Miocene to the early Pliocene). Hydrocarbon migration orientation and charging pathways were traced using molecular indicators (4-/1-methyldibenzothiophene and 1-/4-methodibenzofuran). In the Chaoyang oilfield, the values of these geochemical parameters decreased with decreasing burial depth, indicating vertical oil migration along faults, which are plentiful in the sag. Sandstone bodies with deeper burial depths may therefore be the most promising exploration targets in the Chaoyang area. The Yong’an oils generally migrate from the northwest toward the southeast, suggesting that the source kitchen for the Yong’an oilfield is in the northwest. By similar inference, the hydrocarbon source kitchen for the Hongguang-Meitai area is likely to be on the north side of the Hongguang-Meitai area. By tracing these hydrocarbon charging pathways, the northwest of the Yong’an area and the northern part of the Hongguang-Meitai area are identified as the most promising areas for exploration

Geological conditions and the main controlling factors for the tight oil accumulation in Liushagang Formation of Fushan Depression, Beibuwan Basin

Unravelling the accumulation conditions and their controlling factors for the tight oil in the Liushagang Formation, Fushan Depression, Beibuwan Basin, is critical for the further evaluation of the tight oil distribution and the favorable exploration area.Based on comprehensive analysis of seismic, well logging, core and lab tests in this study, the effective source rocks, favorable reservoir, and the source-reservoir matching relations were investigated.It can be proposed that the high-quality source rocks were formed in Huangtong, Bailian two sub-sags during the maximum lake flooding periods in Liushagang depositional stage and were characterized as high organic content and moderate degree of thermal evolution, and thus they provide the material basis for the formation of tight oil; due to the influence of multi-source supply, tight sandstones penetrated into these two sub-sags and they were widely distributed with superimposed source-reservoir assemblages. The development of dissolution pores and structural fractures was favorable for the migration and enrichment of tight oil; the tectonic conditions of the sag were relatively stable and no major fault system was active when the main sources entered peak oil window, and thus the relatively stable tectonic environment enabled the formation and preservation of tight oil accumulations.Therefore, the Liushagang Formation of the Fushan Depression have favorable geological conditions for the formation of tight oil, which mainly distribute in the lower L1 submember and L2 member vertically and Huangtong and Bailian sub-sags horizontally.The distribution of high-quality source rocks, the distribution of "sweet point" reservoirs being rich in dissolution pores and favorable superimposed source-reservoir assemblages are the three main controlling factors for the formation and distribution of tight oil in Liushagang Formation of Fushan Depression, Beibuwan Basin

Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects. Hence, an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences. However, it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods. To solve this issue, we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets: (1) rare germline variants from clinical relevant sequence variants (ClinVar), (2) rare somatic variants from Catalogue Of Somatic Mutations In Cancer (COSMIC), (3) common regulatory variants from curated expression quantitative trait locus (eQTL) data, and (4) disease-associated common variants from curated genome-wide association studies (GWAS). All 24 tested methods performed differently under various conditions, indicating varying strengths and weaknesses under different scenarios. Importantly, the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve (AUROC) of 0.4481–0.8033 and poor for rare somatic variants from COSMIC (AUROC = 0.4984–0.7131), common regulatory variants from curated eQTL data (AUROC = 0.4837–0.6472), and disease-associated common variants from curated GWAS (AUROC = 0.4766–0.5188). We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder, and found that the combined annotation-dependent depletion (CADD) and context-dependent tolerance score (CDTS) methods showed better performance. Summarily, we assessed the performance of 24 computational methods under diverse scenarios, providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants