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McHugh, M.

Publications and source records attributed to McHugh, M..

2 recordsLinked to original sources
bioRxiv2026

Single-chip End-to-End Ingestible Electronics for Gut Neurotransmitter Sensing

Neurotransmitters in the gut play a vital role in human health and neuroscience, and their real-time monitoring is essential for understanding underlying physiological mechanisms. However, bioelectronic systems capable of measuring neurotransmitters in vivo at the anatomical site of interest remain underdeveloped and largely depend on bulky, off-the-shelf electronic components, thereby constraining the development of systems that are both practical and minimally invasive. Here, we report a miniature ingestible pill that is capable of real-time in vivo sensing of two key neurotransmitters: serotonin (5-HT) and dopamine (DA). The system incorporates a fully printed three-electrode-based electrochemical sensor for neurotransmitter sensing and a custom application-specific integrated circuit (ASIC) that integrates all major functional blocks on a single chip, enabling a platform for fully wireless monitoring of gut neurotransmitters. The pill, measuring 5.8 mm in diameter and 19 mm in length, supports multiple electrochemical sensing techniques, including amperometry and voltammetry, with only 42 A of average current consumption. We demonstrate the ingestible platform through in vivo studies in rat animal models, enabling real-time monitoring of gut neurotransmitters.

bioengineering↗
bioRxiv2025

Positive allosteric modulation of emodepside sensitive Brugia malayi SLO-1F and Onchocerca volvulus SLO-1A potassium channels by GoSlo-SR-5-69

Human lymphatic filariasis and onchocerciasis are Neglected Tropical Diseases (NTDs), of major public health concern. Prophylaxis and treatment rely on anthelmintics that effectively eliminate migrating microfilariae but lack efficacy against adult filarial worms. To expedite the elimination of both diseases, the introduction of drugs with adulticidal activity is paramount. The broad-spectrum anthelmintic emodepside, a nematode selective SLO-1 K channel activator, has been considered a promising candidate for the treatment of onchocerciasis due to its macrofilaricidal activity against Onchocerca volvulus. Nevertheless, it is less effective against adult Brugia malayi, one of the causative agents of human lymphatic filariasis. Characterizing molecular and pharmacological disparities between highly conserved splice variant isoforms of B. malayi and O. volvulus SLO-1 K channels and identifying allosteric modulators that can increase emodepside potency on B. malayi SLO-1 K channels is necessary for therapeutic advance. In this study, we tested the effects of emodepside and the mammalian BK channel activator, GoSlo-SR-5-69 alone and in combination on Xenopus expressed B. malayi SLO-1F and O. volvulus SLO-1A channels. Additionally, binding poses of emodepside, and GoSlo-SR-5-69 were predicted on both channels using molecular docking. Ovo-SLO-1A was more sensitive to emodepside than Bma-SLO-1F. GoSlo-SR- 5-69 was a positive allosteric modulator, potentiating the effects of emodepside. Emodepside was docked at the S6 pocket below the selectivity filter for Bma-SLO-1F and Ovo-SLO-1A. The binding of emodepside in the S6 pocket indicated a stabilizing{pi} -{pi} interaction between F342 and the phenyl rings of emodepside which may contribute to the potency of emodepside on these filaria channels. Molecular docking suggested that GoSlo-SR-5-69 binds at the RCK1 pocket. This study reveals for the first time, allosteric modulation of filarial nematode SLO-1 K channels by a mammalian BK channel activator and highlights its ability to increase emodepside potency on the B. malayi SLO-1 K channel. Author SummaryB. malayi is one of the causative agents of lymphatic filariasis, while O. volvulus causes onchocerciasis. Elimination of adult B. malayi and O. volvulus is impeded by anthelmintics lacking adequate macrofilaricidal activity. The anthelmintic emodepside has microfilaricidal and macrofilaricidal activity. However, it exhibits poor efficacy against adult B. malayi in vivo. Here, we conducted a comparative pharmacological characterization of two closely related splice variants SLO-1 K channels of B. malayi and O. volvulus. Using voltage clamp, we tested the effects of emodepside and GoSlo-SR-5-69 independently and in combination on Xenopus expressed B. malayi SLO-1F and O. volvulus SLO-1A channels. Binding poses of emodepside, and GoSlo-SR-5-69 were predicted on both channels using molecular docking. We demonstrate that the O. volvulus SLO-1A receptor is more sensitive to emodepside than the B. malayi SLO-1F receptor. GoSlo-SR-5-69 is also a potentiator of emodepside responses. Homology modelling revealed that emodepside probably binds in the pore region of the B. malayi SLO-1F and O. volvulus SLO-1A channels, while GoSlo-SR-5-69 probably binds to the RCK1 domain of the channels. Our study provides new insights into similarities and differences shared between SLO-1 K channels of each species and reveals positive allosteric modulation by a mammalian SLO-1 K activator.

pathology↗