Artificial Multienzyme Scaffolds: Pursuing in Vitro Substrate Channeling with an Overview of Current Progress

Artificial multienzyme scaffolds are being developed for in vitro cascaded biocatalytic activity and, in particular, accessing substrate channeling. This review covers progress in this field over t..

Research on Race/Ethnicity and Health Care Discrimination: Where We Are and Where We Need to Go

https://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.2012.30070

Rlpy: A Value-Function-Based Reinforcement Learning Framework for Education and Research

RLPy is an object-oriented reinforcement learning software package with a focus on valuefunction-based methods using linear function approximation and discrete actions. The framework was designed for both educational and research purposes. It provides a rich library of fine-grained, easily exchangeable components for learning agents (e.g., policies or representations of value functions), facilitating recently increased specialization in reinforcement learning. RLPy is written in Python to allow fast prototyping, but is also suitable for large-scale experiments through its built-in support for optimized numerical libraries and parallelization. Code profiling, domain visualizations, and data analysis are integrated in a self-contained package available under the Modified BSD License at http://github.com/rlpy/rlpy. All of these properties allow users to compare various reinforcement learning algorithms with little effort

Constitutive alzheimer\u27s-type tau epitopes in a neuritogenic rat CNS cell line

Paired helical filaments (PHFs) of Alzheimer\u27s disease (AD) largely comprise hyperphosphorylated forms of the cytoskeletal protein tau. AD-type tau phosphoepitopes, detected by various monoclonal antibodies, are absent from normal adult neurons, but recent studies have shown that their expression may contribute to neuritogenesis and axon differentiation in the developing nervous system. Therefore, we have examined a brain nerve cell line that is spontaneously neuritogenic for possible expression of AD-type tau epitopes. The neuritogenic rat brain cell line B103 was found to constitutively produce two AD-related epitopes of tau, detected by cellular immunofluorescence studies with the PHF-1 and Alz-50 monoclonal antibodies. Biochemical studies showed that the antibodies bound to proteins within the molecular weight range expected for phosphorylated tau isoforms. Further verification was established by use of tau antisense oligomers, which eliminated cellular immunofluorescence due to the AD-related monoclonals and polyclonal anti-tau but did not eliminate fluorescence due to anti-tubulin. Cells treated with tau antisense were not neurite-free. Neurites that remained, however, were abnormal, generally short and wavy in appearance. Cellular distribution of the tau epitopes was found to be particularly interesting. Alz-50 recognized only cytoplasmic tau whereas PHF-1 recognized nuclear tau as well as cytoplasmic. Thus, the two epitopes are morphologically segregated within the cell. Because subcellular segregation of tau is compromised in Alzheimer\u27s disease, mechanisms that segregate AD-type phosphotau epitopes in B103 cells may have relevance to this neurodegenerative disorder

Multiscaffold DNA Origami Nanoparticle Waveguides

DNA origami templated self-assembly has shown its potential in creating rationally designed nanophotonic devices in a parallel and repeatable manner. In this investigation, we employ a multiscaffold DNA origami approach to fabricate linear waveguides of 10 nm diameter gold nanoparticles. This approach provides independent control over nanoparticle separation and spatial arrangement. The waveguides were characterized using atomic force microscopy and far-field polarization spectroscopy. This work provides a path toward large-scale plasmonic circuitry

Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.

Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4-S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels. © 2018 Wang et al

Spontaneous self-affirmation is associated with psychological well-being: evidence from a US national adult survey sample

Emerging evidence suggests that individuals spontaneously self-affirm, by reflecting on values and strengths, in response to daily threats. We examined the prevalence and demographic and well-being correlates of spontaneous self-affirmation in the general population. Participants (n = 3185) completed the cross-sectional, nationally representative 2013 Health Information National Trends Survey (HINTS 4, Cycle 3), and answered questions about spontaneous self-affirmation, demographic factors, well-being, and affect. The majority of the population reported spontaneously self-affirming. Black and Hispanic respondents reported engaging in more spontaneous self-affirmation. Engaging in spontaneous self-affirmation was related to greater happiness, hopefulness, optimism, subjective health, and personal health efficacy, and less anger and sadness