Multimessenger astronomy, combining gravitational-wave (GW) and electromagnetic-wave (EM) observations, has a huge impact on physics, astrophysics, and cosmology. However, the majority of sources ...detected with currently running ground-based GW observatories are binary black hole (BBH) mergers, which disappointingly were expected to have no EM counterparts. In this Letter, we propose that if a BBH merger happens in a gaseous disk around a supermassive black hole, the merger can be accompanied by a transient radio flare like a fast radio burst (FRB). We argue that the total mass and the effective spin derived from GW detection can be used to distinguish such a source from other channels of BBH mergers. If this prediction is confirmed with future observations, multimessenger astronomy can be greatly improved. The mystery of the origin of FRBs could also be revealed partially.
The Wufeng organic-rich shale is widespread in the Upper Yangtze platform, and it is one of the most advantageous shale gas producers in China. Its deposition commenced with the onset of the Boda ...warming event in the late Katian and terminated at the Hirnantian glacial maximum. The depositional mechanism of the Wufeng Formation was poorly understood owing to its relatively thin thickness, being interpreted as the result of organic matter (OM) accumulation in a shelf setting under anoxic conditions. This study integrated detailed geochemical analyses based on the core samples from three boreholes which are located in the outer-, middle- and inner-shelf of the Upper Yangtze platform, in order to investigate the depositional environments during the deposition of the Wufeng Formation. Geochemical redox proxies (Mo-EF, U-EF, and V/Cr) and productivity proxies (P, Baxs, Sixs) indicate that the deposition of the Wufeng Formation was associated with four intervals (WF1 to WF4), each characterized by its unique geochemical features related to sea-level fluctuations. Black siliceous mudstones deposited during WF1 and WF2 are relatively organic-lean due to low productivity, less favorable preservation conditions, and terrestrial dilution. Whereas black siliceous mudstone deposited during WF3 and WF4 is organic-rich due to high paleoproductivity and conducive preservation conditions. The geochemical proxies (Cd/Mo, Co x Mn) associated with the modern upwelling settings were replicated in the Wufeng Formation, revealing that the outer-shelf of the Upper Yangtze platform was dominated by persistent upwelling. The upwelling-driven primary productivity is considered as the first-order control for the OM enrichment at the outer-shelf of the Upper Yangtze platform. Seasonal upwelling may influence the middle-shelf of the Upper Yangtze Platform, where both primary productivity and preservation played essential roles in the OM accumulation. In contrast, the OM accumulation at the inner-shelf was fundamentally driven by good preservation conditions.
•Four deposition intervals were identified in the Wufeng Formation.•An ancient upwelling system was verified in the Upper Yangtze platform.•OM accumulation is primarily driven by upwelling at out-shelf.•OM accumulation is fundamentally driven by preservation conditions at inner-shelf.
Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin‐binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical ...heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available D‐glucosamine, diacetone α‐D‐glucose, and penta‐O‐acetyl‐D‐glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one‐pot reactions that considerably reduce the synthetic effort and improve the yield.
Working against the clot: The synthetic anticoagulant fondaparinux, a pentasaccharide based on the antithrombin‐binding domain of heparin, was prepared in a concise and efficient manner in the shortest route reported to date. The application of one‐pot strategies, the use of common intermediates, and the efficient preparation of monosaccharide building blocks from commercial sources are key features of this approach.
In the Big Data environment, aims of enterprises investing in Big Data are to gain Big Data information (BDI). To study the decision-making issues of BDI investment and its effects on supply chain ...coordination, a supply chain with one retailer and one manufacturer was chosen. Meanwhile, considering a company owned the internal BDI and the external BDI, the market demand function was revised and four decision models were proposed from a new perspective. Then, the effects of BDI investment on supply chain members’ benefits under the four models were analyzed and an effectively coordination tactic was presented for achieving supply chain coordination. Results indicated when the investment cost could face a certain threshold, the retailer or the manufacturer investing in BDI could increase its benefits. Meanwhile, there existed “positive externalities” for other supply chain members. In addition, after supply chain members investing in BDI together, revenue-sharing contract could coordinate the supply chain effectively. This article provided a theoretical guidance or a decision basis for companies investing in BDI, meanwhile, it had reference values for supply chain coordination after investing in BDI.
All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing déstabilisation of iron-sulfur (Fe-S) clusters and generating Fenton ...chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.
Identifying the clinical implications and modifiable and unmodifiable factors of aging requires the measurement of biological age (BA) and age gap. Leveraging the biomedical traits involved with ...physical measures, biochemical assays, genomic data, and cognitive functions from the healthy participants in the UK Biobank, we establish an integrative BA model consisting of multi‐dimensional indicators. Accelerated aging (age gap >3.2 years) at baseline is associated incident circulatory diseases, related chronic disorders, all‐cause, and cause‐specific mortality. We identify 35 modifiable factors for age gap (p < 4.81 × 10−4), where pulmonary functions, body mass, hand grip strength, basal metabolic rate, estimated glomerular filtration rate, and C‐reactive protein show the most significant associations. Genetic analyses replicate the possible associations between age gap and health‐related outcomes and further identify CST3 as an essential gene for biological aging, which is highly expressed in the brain and is associated with immune and metabolic traits. Our study profiles the landscape of biological aging and provides insights into the preventive strategies and therapeutic targets for aging.
The study included 59,316 healthy participants in the UK Biobank and considered 8276 phenotypes for developing biological age model. LightGBM algorithm was conducted to identify the most important predictors for biological age and build the model and the top 20 predictors were selected. We tested the longitudinal associations of age gap with 70 common health‐related outcomes, all‐cause mortality and cause‐specific mortality, and the genetic correlations of age gap with common health‐related outcomes. We identified 34 modifiable factors and 9 genomic risk loci for age gap and profiled the pleiotropy of rs3761280 in the UK Biobank.
Treatment with β2-agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2-agonists is caused by ...changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty-four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2-receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.
Nineteen new quinoline derivatives were prepared via the Mannich reaction and evaluated for their antibacterial activities against both Gram-positive (G⁺) and Gram-negative (G
) bacteria, taking ...compound
as the lead. Among the target compounds, quinolone coupled hybrid
exerted the potential effect against most of the tested G⁺ and G
strains with MIC values of 0.125⁻8 μg/mL, much better than those of
. Molecular-docking assay showed that compound
might target both bacterial LptA and Top IV proteins, thereby displaying a broad-spectrum antibacterial effect. This hybridization strategy was an efficient way to promote the antibacterial activity of this kind, and compound
was selected for the further investigation, with an advantage of a dual-target mechanism of action.
Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified ...bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult.
Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPβ for methylated motifs and the preference of c-Myc for unmethylated E-box motifs.
Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications.
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