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Features of People ≥ A decade old enough along with Dissipate Intrinsic Pontine Glioma: A Report from your International DIPG Registry.
Liquid-liquid phase separation (LLPS) of proteins and nucleic acids to form membraneless cellular compartments is considered to be involved in various biological functions. The RNA-binding protein fused in sarcoma (FUS) undergoes LLPS in vivo and in vitro. Here, we investigated the effects of pressure and temperature on the LLPS of FUS by high-pressure microscopy and high-pressure UV/vis spectroscopy. The phase-separated condensate of FUS was obliterated with increasing pressure but was observed again at a higher pressure. We generated a pressure-temperature phase diagram that describes the phase separation of FUS and provides a general understanding of the thermodynamic properties of self-assembly and phase separation of proteins. FUS has two types of condensed phases, observed at low pressure (LP-LLPS) and high pressure (HP-LLPS). The HP-LLPS state was more condensed and exhibited lower susceptibility to dissolution by 1,6-hexanediol and karyopherin-β2 than the LP-LLPS state. Moreover, molecular dynamic simulations revealed that electrostatic interactions were destabilized, whereas cation-π, π-π, and hydrophobic interactions were stabilized in HP-LLPS. When cation-π, π-π, and hydrophobic interactions were transiently stabilized in the cellular environment, the phase transition to HP-LLPS occurred; this might be correlated to the aberrant enrichment of cytoplasmic ribonucleoprotein granules, leading to amyotrophic lateral sclerosis.Resonant stimulated X-ray Raman spectroscopy of the bimetallic [MnIIIMnIV(μ-O)2(μ-OAC)(tacn)2]2+ manganese complex is investigated in a simulation study. Essential biological processes, including water oxidation in photosynthesis, involve charge transfer between manganese sites of different oxidation states. We study a prototypical binuclear mixed-valence transition-metal complex with two Mn atoms in different oxidation states surrounded by ligand structures and employ a pump-probe sequence of resonant X-ray Raman excitations to follow the charge transfer occurring in the molecule. This allows us to generate and monitor valence-electron wave packets at selected regions in the molecule by exploiting element-specific core-excited states. NMSP937 A two-color protocol is presented, with pump and probe pulses tuned to the Mn and N K-edges. A natural orbital decomposition allows the visualization of the electron dynamics underlying the signal.Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]nonane skeleton. Inspired by Sawamura's works, we generated the bicyclic backbone through a Conia-ene-derived 7-exo-dig cyclization from an enantiomerically enriched TIPS-based silyl enol ether. The reaction, catalyzed by a sensitive gold(I) complex, was efficiently performed on a large scale by glovebox free techniques. Furthermore, the shape of this system was exploited for subsequent installation of all of the stereogenic centers.Poly(3-hexylthiophene) (P3HT) is a well-studied benchmark system for semiconducting polymers used in optoelectronic devices. In these materials, aggregation can improve charge transport efficiency or enhance emission yields depending on the interchain packing. This may be inferred from the absorption and emission spectra when analyzed using exciton coupling models such as the well-known H- and J-coupling model of Kasha. The more recently developed weakly coupled H-aggregate (WCH) model quantifies the degree of disorder via the ratio of the electronic origin intensity to that of the first vibronic band. Here, the underlying assumptions of this approach are tested experimentally for P3HT aggregates formed by solvent poisoning using bulk and single-molecule-based spectroscopic techniques. Specifically, we show that the contribution of residual monomeric chains to the aggregate spectrum must be accounted for to properly assign the spectra as H- or J-type. A modification of the WCH model is introduced to account for multiple emissive species.Novel, linker-free, BODIPY-carbohydrate derivatives containing sugar residues at positions C2 and C6 are efficiently obtained by, hitherto unreported, Ferrier-type C-glycosylation of 8-aryl-1,3,5,7-tetramethyl BODIPYs with commercially available tri-O-acetyl-d-glucal followed by saponification. This transformation, which involves the electrophilic aromatic substitution (SEAr) of the dipyrrin framework with an allylic oxocarbenium ion, provides easy access to BODIPY-carbohydrate hybrids with excellent photophysical properties and a weaker tendency to aggregate in concentrated water solutions.The thermal dissociation reactions of C2F4 and C2F6 were studied in shock waves over the temperature range 1000-4000 K using UV absorption spectroscopy. Absorption cross sections of C2F4, CF2, CF, and C2 were derived and related to quantum-chemically modeled oscillator strengths. After confirming earlier results for the dissociation rates of C2F4, CF3, and CF2, the kinetics of secondary reactions were investigated. For example, the reaction CF2 + CF2 → CF + CF3 was identified. Its rate constant of 1010 cm3 mol-1 s-1 near 2400 K is markedly larger than the limiting high-pressure rate constant of the dimerization CF2 + CF2 → C2F4, suggesting that the reaction follows a different path. When the measurements of the thermal dissociation CF2 (+Ar) → CF + F (+Ar) are extended to temperatures above 2500 K, the formation of C2 radicals was shown to involve the reaction CF + CF → C2F + F (modeled rate constant 8.0 × 1012 (T/3500 K)1.0 exp(-4400 K/T) cm3 mol-1 s-1) and the subsequent dissociation C2F (+Ar) → C2 + F + (Ar) (modeled limiting low-pressure rate constant 3.
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