Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy.
View Article and Find Full Text PDFPrecise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits - Equalizers - that buffer copy-number variation at the single-cell level.
View Article and Find Full Text PDFRelapse during abstinence in cocaine use disorder (CUD) is often hastened by high impulsivity (predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and high cue reactivity (e.g., attentional bias towards drug reward stimuli).
View Article and Find Full Text PDFA non-synonymous single nucleotide polymorphism of the human serotonin 5-HT receptor (5-HTR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HTR pharmacology at a cellular and systems level. We hypothesized that the Cys23Ser alters 5-HTR intracellular signaling via changes in subcellular localization in vitro. Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
View Article and Find Full Text PDFImpulsivity is a multifaceted behavioral manifestation with implications in several neuropsychiatric disorders. Glutamate neurotransmission through the N-methyl-D-aspartate receptors (NMDARs) in the medial prefrontal cortex (mPFC), an important brain region in decision-making and goal-directed behaviors, plays a key role in motor impulsivity. We discovered that inherent motor impulsivity predicted responsiveness to D-cycloserine (DCS), a partial NMDAR agonist, which prompted the hypothesis that inherent motor impulsivity is associated with the pattern of expression of cortical NMDAR subunits (GluN1, GluN2A, GluN2B), specifically the protein levels and synaptosomal trafficking of the NMDAR subunits.
View Article and Find Full Text PDFBackground And Aims: Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation that is elevated in patients with inflammatory bowel disease. However, the correlation between FLA levels and serological markers of disease activity has not been previously reported, to our knowledge. In the present study we evaluated the ability of FLA levels to reflect disease activity in pediatric patients with inflammatory bowel disease.
View Article and Find Full Text PDFJ Public Health Manag Pract
February 2005
The objective of this study was to assess compliance with Boston's 100% smoke-free bar regulation within the first 3 months of implementation. An observational survey was conducted of a random sample of 102 bars in Boston before and after the smoking ban went into effect. Forty bars were observed both pre- and postban, serving as a true comparison group; 62 additional bars were observed postban only.
View Article and Find Full Text PDFThis project examined whether smokers differentially responded to messages about oral health that emphasized either the benefits of quitting smoking or the risks of continued smoking. Messages concerning oral health and smoking were developed to emphasize the benefits of quitting smoking (gain-framed) or the costs of continued smoking (loss-framed). These messages were embedded in recruitment brochures for smoking cessation trials, which were placed in twenty dental office waiting rooms for a six-month period.
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