Notes

E3 Ubiquitin Ligase SPL2 Is often a Lanthanide-Binding Necessary protein.
This method generates human cerebellar neurons useful for downstream applications, including gene expression, physiological, and morphological studies requiring 2D monolayer formats.Fast and precise measurements of live single-cell biophysical properties is significant in disease diagnosis, cytopathologic analysis, etc. Existing methods still suffer from unsatisfied measurement accuracy and low efficiency. We propose a computer vision method to track cell dielectrophoretic movements on a microchip, enabling efficient and accurate measurement of biophysical parameters of live single cells, including cell radius, cytoplasm conductivity, and cell-specific membrane capacitance, and in situ extraction of cell texture features. We propose a prediction-iteration method to optimize the cell parameter measurement, achieving high accuracy (less than 0.79% error) and high efficiency (less than 30 s). We further propose a hierarchical classifier based on a support vector machine and implement cell classification using acquired cell physical parameters and texture features, achieving high classification accuracies for identifying cell lines from different tissues, tumor and normal cells, different tumor cells, different leukemia cells, and tumor cells with different malignancies. The method is label-free and biocompatible, allowing further live cell studies on a chip, e.g., cell therapy, cell differentiation, etc.Black phosphorus (BP) has received increasing interest as a promising photocatalyst for water splitting. Nevertheless, exploring the underlying hydrogen evolution reaction (HER) mechanism and improving the water oxidizing ability remains an urgent task. Here, using first-principles calculations, we uncover the role of point defects in improving the HER activity of BP photocatalysts. We demonstrate that the defective phosphorene can be effectively activated by the photoinduced electrons under solar light, exhibiting high HER catalytic activity in a broad pH range (0-10). Besides, we propose that the direct Z-scheme in the defective BP/SnSe2 heterobilayer is quite feasible for photocatalytic overall water splitting. This mechanism could be further verified based on the excited state dynamics method. The role of point defects in the photocatalytic mechanism provides useful insights for the development of BP photocatalysts.Contezolid (MRX-I), a safer antibiotic of the oxazolidinone class, is a promising new antibiotic with potent activity against Mycobacterium tuberculosis (MTB) both in vitro and in vivo. To identify resistance mechanisms of contezolid in MTB, we isolated several in vitro spontaneous contezolid-resistant MTB mutants, which exhibited 16-fold increases in the MIC of contezolid compared with the parent strain but were still unexpectedly susceptible to linezolid. Whole-genome sequencing revealed that most of the contezolid-resistant mutants bore mutations in the mce3R gene, which encodes a transcriptional repressor. The mutations in mce3R led to markedly increased expression of a monooxygenase encoding gene Rv1936. We then characterized Rv1936 as a putative flavin-dependent monooxygenase that catalyzes the degradation of contezolid into its inactive 2,3-dihydropyridin-4-one (DHPO) ring-opened metabolites, thereby conferring drug resistance. While contezolid is an attractive drug candidate with potent antimycobacterial activity and low toxicity, the occurrence of mutations in Mce3R should be considered when designing combination therapy using contezolid for treating tuberculosis.Unicellular microalgae are of immense ecological importance with growing commercial potential in industries such as renewable energy, food, and pharmacology. Viral infections can have a profound impact on the growth and evolution of their hosts. However, very little is known of the diversity within, and the effect of, unicellular microalgal RNA viruses. In addition, identifying RNA viruses in these organisms that could have originated more than a billion years ago constitutes a robust data set to dissect molecular events and address fundamental questions in virus evolution. We assessed the diversity of RNA viruses in eight microalgal cultures, including representatives from the diatom, eustigmatophyte, dinoflagellate, red algae, and euglenid groups. Using metatranscriptomic sequencing combined with bioinformatic approaches optimized to detect highly divergent RNA viruses, we identified 10 RNA virus sequences, with nine constituting new viral species. Most of the newly identified RNA viruses belonged to the douencing, we aimed to reveal the RNA viruses present in cultures of eight microalgae species belonging to the diatom, dinoflagellate, eustigmatophyte, rhodophyte, and euglena major clades of algae. Protosappanin B Accordingly, we identified 10 new divergent RNA virus species belonging to RNA virus families as diverse as the double-stranded Totiviridae, Endornaviridae, and Partitiviridae and the single-stranded Marnaviridae. By expanding the known diversity of RNA viruses infecting unicellular eukaryotes, this study contributes to a better understanding of the early evolution of the virosphere and will inform the use of microalgae in industrial applications.The IL-15 superagonist N-803 has been shown to enhance the function of CD8 T cells and NK cells. We previously found that in a subset of vaccinated, ART-naive, SIV+ rhesus macaques, N-803 treatment led to a rapid but transient decline in plasma viremia that positively correlated with an increase in the frequency of CD8 T cells. Here, we tested the hypothesis that prophylactic vaccination was required for the N-803 mediated suppression of SIV plasma viremia. We either vaccinated rhesus macaques with a DNA prime/Ad5 boost regimen using vectors expressing SIVmac239 gag with or without a plasmid expressing IL-12 or left them unvaccinated. The animals were then intravenously infected with SIVmac239M. 6 months after infection, the animals were treated with N-803. We found no differences in the control of plasma viremia during N-803 treatment between vaccinated and unvaccinated macaques. Interestingly, when we divided the SIV+ animals based on their plasma viral load set-points prior to the N-803 treatment, N-803 inaneous controllers) compared to settings where HIV/SIV are not controlled, could impact the efficacy of N-803 utilization in the field of HIV cure.Together with inactivated influenza vaccines (IIV), live attenuated influenza vaccines (LAIV) are an important tool to prevent influenza A virus (IAV) illnesses in patients. LAIVs present the advantages to have a needle-free administration and to trigger a mucosal immune response. LAIV is approved for healthy 2- to 49-year old individuals. However, due to its replicative nature and higher rate of adverse events at-risk populations are excluded from the benefits of this vaccine. Using targeted mutagenesis, we modified the nonstructural protein 1 of the currently licensed LAIV in order to impair its ability to bind the host cellular protein CPSF30 and thus its ability to inhibit host mRNA poly-adenylation. We characterized our optimized LAIV (optiLAIV) in three different mouse models mimicking healthy and high-risk patients. Using a neonatal mouse model, we show faster clearance of our optimized vaccine compared to the licensed LAIV. Despite lower replication, optiLAIV equally protected mice against homosubtypiulations. We propose a strategy to improve LAIV safety and explore the possibility to expand its applications in children under 2-year old and immunocompromised patients. Using a neonatal mouse model, we show faster clearance of our optimized vaccine (optiLAIV) compared to the licensed LAIV. Despite lower replication, optiLAIV equally protected mice against influenza virus challenges. We confirmed the safer profile of optiLAIV in Stat1-/- mice (highly susceptible to viral infections) by showing no signs of morbidity compared to a 50% mortality rate from LAIV. OptiLAIV could expand the applications of the current LAIV and help mitigate the burden of IAV in susceptible populations.Iridoviruses are large DNA viruses which cause great economic losses to the aquaculture industry and serious threats to ecological diversity worldwide. Singapore grouper iridovirus (SGIV), a novel member of the genus Ranavirus, causes high mortality in grouper aquaculture. Previous work on genome annotation demonstrated that SGIV contained numerous uncharacterized or hypothetical open reading frames (ORFs), whose functions remained largely unknown. Here, we reported that the protein encoded by SGIV ORF131R (VP131) was localized predominantly within the endoplasmic reticulum (ER). Ectopic expression of GFP-VP131 significantly enhanced SGIV replication, while VP131 knockdown decreased viral infection in vitro, suggesting that VP131 functioned as a proviral factor during SGIV infection. Overexpression of GFP-VP131 inhibited the interferon (IFN)-1 promoter activity and mRNA level of IFN-related genes induced by poly(IC), Epinephelus coioides cyclic GMP/AMP synthase (EccGAS)/stimulator of IFN genes (EcSTING), TANKtion. However, viruses also distort the STING-TBK1 pathway to negatively regulate the IFN response and facilitate viral replication. Here, we reported that SGIV VP131 interacted with EcSTING within the ER and degraded EcSTING, leading to the suppression of IFN production and the promotion of SGIV infection. These results for the first time demonstrated that fish iridovirus evaded the host antiviral response via abrogating the STING-TBK1 signaling pathway.Both plants and their associated arbuscular mycorrhizal (AM) fungi require nitrogen (N) for their metabolism and growth. This can result in both positive and negative effects of AM symbiosis on plant N nutrition. Either way, the demand for and efficiency of uptake of mineral N from the soil by mycorrhizal plants are often higher than those of nonmycorrhizal plants. In consequence, the symbiosis of plants with AM fungi exerts important feedbacks on soil processes in general and N cycling in particular. Here, we investigated the role of the AM symbiosis in N uptake by Andropogon gerardii from an organic source (15N-labeled plant litter) that was provided beyond the direct reach of roots. In addition, we tested if pathways of 15N uptake from litter by mycorrhizal hyphae were affected by amendment with different synthetic nitrification inhibitors (dicyandiamide [DCD], nitrapyrin, or 3,4-dimethylpyrazole phosphate [DMPP]). We observed efficient acquisition of 15N by mycorrhizal plants through the mycorrhizal pathwfication and plant mineral nutrient acquisition, respectively, have often been studied in separation in the past. Here, we showed, using various biochemical and molecular approaches, that the fungi systematically suppress ammonia-oxidizing bacteria to an extent similar to that of some widely used synthetic nitrification inhibitors, whereas they have only a limited impact on abundance of ammonia-oxidizing archaea. Competition for free ammonium is a plausible explanation here, but it is also possible that the fungi produce some compounds acting as so-called biological nitrification inhibitors.
Although existing guidelines recommend commencing cannulation for extracorporeal cardiopulmonary resuscitation (ECPR) within 10-20 minutes of failed conventional resuscitation efforts for cardiac arrest, there is little supportive evidence. The present study aimed to determine the association of low-flow duration with survival-to-discharge rate in in-hospital cardiac arrest patients who received ECPR.

A nationwide retrospective cohort study analyzed a nationwide inpatient database in Japan. Low-flow duration was defined as the time interval from initiation of chest compression to termination of chest compression. We assessed the association between low-flow duration and survival-to-discharge rate by predicting estimates with covariate adjustment stratified by categories of low-flow duration.

More than 1,600 acute-care hospitals in Japan.

All in-hospital cardiac arrest patients greater than or equal to 18 years old who received ECPR during hospitalization from July 2010 to March 2018.

None.

Among 303,319 in-hospital cardiac arrest patients, 9,844 (3.
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