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Biology subjects

Good, C.

Publications and source records attributed to Good, C..

4 recordsLinked to original sources

Focused ultrasound to the bilateral thalamus causally modulates human cognitive attention in a frequency- and intensity-dependent manner

The centromedian nucleus of the thalamus (CMT) is a core arousal center with potential for enhancing cognitive attention. While emergent focused ultrasound can reach this area, the stimulation paradigms which may enhance function in humans remain unknown. Here we performed bilateral stimulation of the CMT using a novel ultrasound neuromodulation wearable device using 3 distinct pulse frequencies. We found that a brief 25Hz stimulation enhanced reaction time in a in a directed attention Oddball task for at least 40 minutes. Pre-post task electrocortical EEG revealed a correlation between reaction time and the prevalence of arousal related alpha and theta cortical activity. Examination of dose dependence revealed bidirectional modulation of arousal state, with lower intensities preferentially enhancing cognitive function. Pre- and post-MRI scans showed no neuroradiological changes due to stimulation. Collectively, these findings demonstrate that targeted LIFU stimulation of the CMT can safely enhance cognitive function in healthy individuals with carefully designed parameters.

neuroscience↗

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics monitoring in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally specific drug delivery while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRABNE and GRABDA, and neuropeptide sensors. We demonstrate the performance this platform for investigating neuropharmacological mechanisms in vivo and characterize its efficacy in probing precise mechanistic actions of neuroactive compounds across several rapidly evolving neuroscience domains.

neuroscience↗

Development and comparison of Loop-Mediated Isothermal Amplification with Quantitative PCR for the specific detection of Saprolegnia spp.

Saprolegniasis is an important disease in freshwater aquaculture, and is associated with oomycete pathogens in the genus Saprolegnia. Early detection of significant levels of Saprolegnia spp. pathogens would allow informed decisions for treatment which could significantly reduce losses. This study is the first to report the development of loop-mediated isothermal amplification (LAMP) for the detection of Saprolegnia spp. and compares it with quantitative PCR (qPCR). The developed protocols targeted the internal transcribed spacer (ITS) region of ribosomal DNA and the cytochrome C oxidase subunit 1 (CoxI) gene and was shown to be specific only to Saprolegnia genus. This LAMP method can detect as low as 10 fg of S. salmonis DNA while the qPCR method has a detection limit of 2 pg of S. salmonis DNA, indicating the superior sensitivity of LAMP compared to qPCR. When applied to detect the pathogen in water samples, both methods could detect the pathogen when only one zoospore of Saprolegnia was present. We propose LAMP as a quick (about 20-60 minutes) and sensitive molecular diagnostic tool for the detection of Saprolegnia spp. suitable for on-site applications.

molecular biology↗

Type III interferon signaling restricts Enterovirus 71 infection of goblet cells

Recent worldwide outbreaks of enterovirus (EV71) have caused major epidemics of hand, foot, and mouth disease (HFMD) with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but very little is known about the mechanisms it utilizes to cross the human gastrointestinal (GI) tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the GI epithelium from the apical surface, where it preferentially infects goblet cells. Unlike echovirus 11 (E11), an enterovirus that infects enterocytes, EV71 infection did not alter epithelial barrier function, but did reduce the expression of a goblet cell-derived mucin, suggesting it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III IFNs, which potently restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.

microbiology↗