Mcdonaldenemark9156

This method is accurate and rapid because it does not require conformational sampling or iterative computation owing to the effective statistical treatment employed to derive the potential. The statistical potential describes specific protein atom-water interactions more accurately than conventional potentials by considering the dependence on the degree of solvent accessibility of protein atoms as well as on protein atom-water distances and orientations. The introduction of solvent accessibility allows effective consideration of competing nonspecific protein-water and intraprotein interactions. When tested on high-resolution protein crystal structures, this method could recover similar or larger fractions of crystallographic water 180 times faster than the sophisticated integral equation theory, 3D-RISM. A web service of this water prediction method is freely available at http//galaxy.seoklab.org/wkgb.The addition of particles during the sol-to-gel conversion process generally enhances the mechanical properties of the resulting hydrogels. However, the impact of the addition of porous particles during such a process remains an open question. Herein, we report hydrogel-to-elastomer conversions by natural porous particles called diatom frustule silica, namely, Melosira nummuloides. The surface pores provide mechanical interlocking points for polymers that are reinforced by gelation. The most critical aspect when choosing polymeric materials is the presence of water-resistant adhesion moieties, such as catechol, along a polymer chain, such as chitosan. Without catechol, no sol-to-gel conversion is observed; thus, no elastomeric hydrogel is produced. The resulting hybrid gel reveals reversible compressibility up to a 60% strain and high stretchability even up to ∼400% in area. Further, in vivo study demonstrates that the hybrid composite gel can be used as a therapeutic for pressure-induced ulcers. The synergy of chemical adhesion and physical chain entanglement via pores provides a way to fabricate a new class of 100% water-based elastomeric materials.Nanoscale transport of light through single molecule systems is of fundamental importance for light harvesting, nanophotonic circuits, and for understanding photosynthesis. Studies on organization of molecular entities for directional transfer of excitation energy have focused on energy transfer cascades via multiple small molecule dyes. Here, we investigate a single molecule conjugated polymer as a photonic wire. The phenylene-vinylene-based polymer is functionalized with multiple DNA strands and immobilized on DNA origami by hybridization to a track of single-stranded staples extending from the origami structure. Donor and acceptor fluorophores are placed at specific positions along the polymer which enables energy transfer from donor to polymer, through the polymer, and from polymer to acceptor. The structure is characterized by atomic force microscopy, and the energy transfer is studied by ensemble fluorescence spectroscopy and single molecule TIRF microscopy. It is found that the polymer photonic wire is capable of transferring light over distances of 24 nm. This demonstrates the potential residing in the use of conjugated polymers for nanophotonics.C-H-N-O system is central for organic chemistry and biochemistry and plays a major role in planetary science (dominating the composition of "ice giants" Uranus and Neptune). The inexhaustible chemical diversity of this system at normal conditions explains its role as the basis of all known life, but the chemistry of this system at high pressures and temperatures of planetary interiors is poorly known. Using ab initio evolutionary algorithm USPEX, we performed an extensive study of the phase diagram of the C-H-N-O system at pressures of 50, 200, and 400 GPa and temperatures up to 3000 K. Seven novel thermodynamically stable phases were predicted, including quaternary polymeric crystal C2H2N2O2 and several new N-O and H-N-O compounds. We describe the main patterns of changes in the chemistry of the C-H-N-O system under pressure and confirm that diamond should be formed at conditions of the middle-ice layers of Uranus and Neptune. We also provide the detailed CH4-NH3-H2O phase diagrams at high pressures, which are important for further improvement of the models of ice giants, and point out that current models are clearly deficient. In particular, in the existing models, Uranus and Neptune are assumed to have identical composition, nearly identical pressure-temperature profiles, and a single convecting middle layer ("mantle") made of a mixture of H2O/CH4/NH3 in the ratio of 56.532.511. Here, we provide new insights, shedding light into the difference of heat flows from Uranus and Neptune, which require them to have different compositions, pressure-temperature conditions, and a more complex internal structure.Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, can potentially cause lipid metabolism disorder; however, its biological effects on lipid homeostasis remain unknown. We investigated its ability to cause nonalcoholic fatty liver disease (NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0.02, 2.0 μM) for 2 weeks. Consequently, HFD-fed fish showed a higher measured concentration of TBPH than ND-fed fish. Further, TBPH-treated fish in the HFD group showed higher hepatic triglyceride levels and steatosis. In comparison to ND-fed fish, treating HFD-fed fish with TBPH led to an increase in the concentration of several proinflammatory markers (e.g., TNF-α, IL-6); TBPH exposure also caused oxidative stress. In addition, the mRNA levels of genes encoding peroxisome proliferator-activated receptors were increased, and the transcription of genes involved in lipid synthesis, transport, and oxidation was upregulated in both ND- and HFD-fed fish. Both the ND and HFD groups also showed demethylation of the peroxisome proliferator-activated receptor-γ coactivator 1-α gene promoter, accompanied by the upregulation of tet1 and tet2 transcription. To summarize, we found that TBPH amplified the disruption of lipid homeostasis in zebrafish, leading to the enhancement of diet-induced NAFLD progression.APOBEC3A (A3A) is a cytidine deaminase involved in innate immune response and is able to catalyze deamination on both DNA and RNA substrates. It was used in creating the CRISPR-mediated base editor, but has since been held back due to its dual activities. On the other hand, it has been a challenge to separate A3A's dual activities in order to enable it for single-base RNA editors. Here we developed the reporter system for C-to-U RNA editing and employed rational design for mutagenesis to differentiate deaminase activities on RNA and DNA substrates to obtain an RNA-specific editase. Generation and examination of 23 previous A3A mutants showed their deamination activity on RNA was mostly abolished when their activity on DNA was impaired, with the exception of mutant N57Q that displayed an inverse change. We designed new mutations on Loops 1 and 7 based on A3A's crystal structure and found mutants H29R and Y132G had differential effects on catalytic activity on RNA and DNA substrates. check details In order to engineer an A3A with RNA-specific deaminase activity, we combined Y132G with mutations in Loop 1 or helix 6 by rational design. Two multipoint mutants, Y132G/K30R and Y132G/G188A/R189A/L190A, were successful in retaining high deaminase activity on RNA substrate while eliminating deaminase activity on DNA. We, for the first time, created novel human A3A variants with RNA-specific cytidine deaminase activity, providing insight into A3A's mechanism on substrate recognition and a new addition of a toolset to the creation of a RNA-specific C-to-U base editor.

This study aimed to investigate the clinical characteristics of acute myeloid leukemia with myelodysplasia-related-changes (AML-MRC) according to the 2016 WHO classification and the preferred therapy of patients with AML-MRC and aged 60-75 years.

We retrospectively analyzed the differences of clinical data between 190 patients with AML-MRC and 667 patients with AML not otherwise specified (AML-NOS). And we compared different therapeutic regimens among patients with AML-MRC and aged 60-75 years.

Compared with AML-NOS, patients with AML-MRC had significantly different clinical characteristics as well as worse overall survival (OS) (9.2 vs 13.6 months; p<0.001) and complete remission (CR) rate (65.3% vs 76.2%; p=0.005). Multivariate analysis performed in the whole group (patients with AML-MRC and AML-NOS) showed that AML-MRC was the independent prognostic factor (p=0.002). Additional multivariate analysis performed in 190 patients with AML-MRC indicated that age (p<0.001) and LDH (p=0.031) were independent prognostic factors. Compared with IA/DA regimen [idarubin and cytarabine (IA) or daunorubicin and cytarabine (DA)], DAC+CAG regimen [decitabine and half-dose CAG regimen (cytarabine, aclarubicin and granulocyte colony-stimulating factor)] was associated with better OS (4.5 vs 6.2 months; p=0.021) in patients aged 60-75 years and categorized into unfavorable-risk group.

AML-MRC exhibited worse clinical outcome compared with AML-NOS. Compared with IA/DA regimen, DAC+CAG regimen was the optimal choice for patients with AML-MRC in unfavorable-risk group and aged 60-75 years.

AML-MRC exhibited worse clinical outcome compared with AML-NOS. Compared with IA/DA regimen, DAC+CAG regimen was the optimal choice for patients with AML-MRC in unfavorable-risk group and aged 60-75 years.

To identify the clinical significance of

and common cytogenetic abnormalities.

114 patients with newly diagnosed MM and

3 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed.

and other common mutations in MM patients were quantified by fluorescence in situ hybridization (FISH). Kaplan-Meier curves and Log-rank test were applied for survival analysis. Cox proportional hazard model for covariate analysis was used to determine the prognostic factors.

By extensive data analysis, we find

amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with

mutation has a modest impact on patient survival. Within these mutations, 1q21 amplification is associated with decreased CR (OR=4.209) and FGFR3 levels are positively correlated with patient progression-free and overall survival.

abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Further, 1q21 and FGFR3 mutations could potentially be used in combination with

status, to better predict patient survival and guide for selecting high-risk patients to advance patient treatment strategies.

TP53 abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Further, 1q21 and FGFR3 mutations could potentially be used in combination with TP53 status, to better predict patient survival and guide for selecting high-risk patients to advance patient treatment strategies.