Activity

Overall, the results indicate that this attempted transition is complex, challenging, and unique and largely influenced by self-confidence. Addressing the individual factors impacting on athletes’ self-confidence appears critical to enhancing swimmers’ transitional experiences at the highest level.

Mutations in KCNC1 can cause severe neurological dysfunction, including intellectual disability, epilepsy, and ataxia. The Arg320His variant, which occurs in the voltage-sensing domain of the channel, causes a highly penetrant and specific form of progressive myoclonus epilepsy with severe ataxia, designated myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK). KCNC1 encodes the voltage-gated potassium channel K

3.1, a channel that is important for enabling high-frequency firing in interneurons, raising the possibility that MEAK is associated with reduced interneuronal function.

To determine how this variant triggers MEAK, we expressed K

3.1b

in cortical interneurons in vitro and investigated the effects on neuronal function and morphology. buy FX11 We also performed electrophysiological recordings of oocytes expressing K

3.1b to determine whether the mutation introduces gating pore currents.

Expression of the K

3.1b

variant profoundly reduced excitability of mature cortical interneurons, and cells expressing these channels were unable to support high-frequency firing. The mutant channel also had an unexpected effect on morphology, severely impairing neurite development and interneuron viability, an effect that could not be rescued by blocking K

3 channels. Oocyte recordings confirmed that in the adult K

3.1b isoform, R320H confers a dominant negative loss-of-function effect by slowing channel activation, but does not introduce potentially toxic gating pore currents.

Overall, our data suggest that, in addition to the regulation of high-frequency firing, K

3.1 channels play a hitherto unrecognized role in neuronal development. MEAK may be described as a developmental dendritopathy.

Overall, our data suggest that, in addition to the regulation of high-frequency firing, KV 3.1 channels play a hitherto unrecognized role in neuronal development. MEAK may be described as a developmental dendritopathy.

Existing therapeutic approaches to treat cholangiocarcinoma (CCA) have limited effectiveness, prompting further study to develop therapies for CCA. We report a mechanistic role for the heparan sulfate editing enzyme sulfatase 2 (SULF2) in CCA pathogenesis.

In silico analysis revealed elevated SULF2 expression in human CCA samples, occurring partly through gain of SULF2 copy number. We examined the effects of knockdown or overexpression of SULF2 on tumor growth, chemoresistance, and signaling pathway activity in human CCA cell lines in vitro. Up-regulation of SULF2 in CCA leads to increased platelet-derived growth factor receptor beta (PDGFRβ)-Yes-associated protein (YAP) signaling activity, promoting tumor growth and chemotherapy resistance. To explore the utility of targeting SULF2 in the tumor microenvironment for CCA treatment, we tested an anti-SULF2 mouse monoclonal antibody, 5D5, in a mouse CCA xenograft model. Targeting SULF2 by monoclonal antibody 5D5 inhibited PDGFRβ-YAP signaling and tumor growth in the mouse xenograft model.

These results suggest that SULF2 monoclonal antibody 5D5 or related agents may be potentially promising therapeutic agents in CCA.

These results suggest that SULF2 monoclonal antibody 5D5 or related agents may be potentially promising therapeutic agents in CCA.As post-secondary education migrates online, developing and evaluating new avenues for assessment in anatomy is paramount. Three-dimensional (3D) visualization technology is one area with the potential to augment or even replace resource-intensive cadaver use in anatomical education. This manuscript details the development of a smartphone application, entitled “Virtual Reality Bell-Ringer (VRBR),” capable of displaying monoscopic two-dimensional (2D) or stereoscopic 3D images with the use of an inexpensive cardboard headset for use in spot examinations. Cadaveric image use, creation, and pinning processes are explained, and the source code is provided. To validate this tool, this paper compares traditional laboratory-based spot examination assessment stations against those administered using the VRBR application to test anatomical knowledge. Participants (undergraduate, n = 38; graduate, n = 13) completed three spot examinations specific to their level of study, one in each of the modalities (2D, 3D, laboratory) as well as a mental rotation test (MRT), Stereo Fly stereotest, and cybersickness survey. Repeated measures ANCOVA suggested participants performed significantly better on laboratory and 3D stations compared to 2D stations. Moderate to severe cybersickness symptoms were reported by 63% of participants in at least one category while using the VRBR application. Highest reported symptoms included eye strain, general discomfort, difficulty focusing, and difficulty concentrating. Overall, the VRBR application is a promising tool for its portability, affordability, and accessibility. Due to reported cybersickness and other technical limitations, the use of VRBR as an alternative to cadaveric specimens presents several challenges when testing anatomy knowledge that must be addressed before widespread adoption.The liver is the primary organ responsible for drug detoxification. Drug-induced liver injury (DILI) is a leading cause of attrition during drug development and is one of the main reasons that drugs are withdrawn from the market. Hence, the prevention of DILI plays a central role in the overall drug-discovery process. Most of the liver’s energy supply comes in the form of adenosine triphosphate (ATP), which is largely generated by mitochondria. This article describes the evaluation of drug-induced mitochondrial dysfunction using the Seahorse Extracellular Flux Analyzer (Agilent). The described protocols detail the accurate measurement of ATP production rate in HepG2 cells after exposure to a panel of potentially toxic compounds. This assay measures changes in extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) as indicators of glycolysis and mitochondrial respiration-the two major energy-generating pathways in a cell. This assay provides a useful model to predict mitochondrial dysfunction-mediated DILI.