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Neurons exhibit a striking degree of functional diversity, each one tuned to the needs of the circuitry in which it is embedded. A fundamental functional dichotomy occurs in activity patterns, with some neurons firing at a relatively constant “tonic” rate, while others fire in bursts, a “phasic” pattern. Synapses formed by tonic versus phasic neurons are also functionally differentiated, yet the bases of their distinctive properties remain enigmatic. A major challenge toward illuminating the synaptic differences between tonic and phasic neurons is the difficulty in isolating their physiological properties. At the Drosophila neuromuscular junction, most muscle fibers are coinnervated by two motor neurons: the tonic “MN-Ib” and phasic “MN-Is.” Here, we used selective expression of a newly developed botulinum neurotoxin transgene to silence tonic or phasic motor neurons in Drosophila larvae of either sex. This approach highlighted major differences in their neurotransmitter release properties, including probability, short-term plasticity, and vesicle pools. Furthermore, Ca21 imaging demonstrated ;2-fold greater Ca21 influx at phasic neuron release sites relative to tonic, along with an enhanced synaptic vesicle coupling. Finally, confocal and super-resolution imaging revealed that phasic neuron release sites are organized in a more compact arrangement, with enhanced stoichiometry of voltage-gated Ca21 channels relative to other active zone scaffolds. These data suggest that distinctions in active zone nano-architecture and Ca21 influx collaborate to differentially tune glutamate release at tonic versus phasic synaptic subtypes. [ABSTRACT FROM AUTHOR]

Objective: Somatosensory feedback from upper airway structures is essential for swallowing and airway defense but little is known about the identities and distributions of human upper airway neurons. Furthermore, whether sensory innervation modifies with aging is unknown. In this study, we quantify neuronal and chemosensory cell density in upper airway structures and correlate with age. Methods: Participants underwent biopsies from base of tongue, lateral and midline pharyngeal wall, epiglottis, and arytenoids (N = 25 13 female/12 male; 20–80 years, mean 51.4 years without clinical diagnosis of dysphagia or clinical indication for biopsy). Tissue sections were labeled with antibodies for all neurons, myelinated neurons, and chemosensory cells. Densities of lamina propria innervation, epithelial innervation, solitary chemosensory cells, and taste buds were calculated and correlated with age. Results: Arytenoid had the highest density of innervation and chemosensory cells across all measures compared to other sites. Taste buds were frequently observed in arytenoid and epiglottis. Base of tongue, lateral pharynx, and midline posterior pharynx had minimal innervation and few chemosensory cells. Epithelial innervation was present primarily in close proximity to chemosensory cells and taste buds. Overall innervation and myelinated fibers in the arytenoid lamina propria decline with aging. Conclusion: Findings establish the architecture of healthy adult sensory innervation and demonstrate the varied distribution of laryngopharyngeal innervation, necessary steps toward understanding the sensory basis for swallowing and airway defense. We also document age‐related decline in arytenoid innervation density. These findings suggest that sensory afferent denervation of the upper airway may be a contributing factor to presbyphagia. Level of Evidence: NA Laryngoscope, 133:773–784, 2023 [ABSTRACT FROM AUTHOR]

To investigate the role of participant level of effort (LoE) on outcome in post-acute brain injury rehabilitation with the hypothesis that greater effort is associated with more positive outcomes. Observational cohort study. Comprehensive integrated rehabilitation program for brain injury within a skilled nursing facility. Consecutive admissions with acquired brain injury (N=101). Individualized interdisciplinary brain injury rehabilitation; therapist rating of participant LoE with Acquired Brain Injury LoE Scale (ABI-LoES) during physical therapy, occupational therapy, and speech and language pathology sessions. Mayo-Portland Adaptability Inventory, fourth edition (MPAI-4); Supervision Rating Scale (SRS). Linear regression showed that discharge MPAI-4 Total T scores were significantly associated with mean ABI-LoES rating, admission MPAI-4 Total T scores, age at admission, and days from injury but not with standard deviation of ABI-LoES rating, sex, injury type, length of stay, or treatment before or during the COVID-19 pandemic. Discharge SRS scores were significantly associated with mean ABI-LoES rating, admission SRS scores, and age. A 1-unit increase in mean ABI-LoES rating was associated with 5.1-unit lower discharge MPAI-4 Total T scores and 1.5 lower discharge SRS scores, after controlling for other variables. Logistic regression showed that the odds of achieving a minimal clinically important difference on the MPAI-4 were 8.34 times higher with each 1-unit increase in mean ABI-LoES rating after controlling for other variables. Admission MPAI-4 was negatively associated with mean ABI-LoES rating (β=−0.07, t =−8.85, P <.0001). After controlling for nonmodifiable variables, average ABI-LoES rating is positively associated with outcome. Initial level of disability is negatively associated with mean ABI-LoES rating. [ABSTRACT FROM AUTHOR]

Background: Disorders of airway protection (cough and swallowing) are pervasive in Parkinson's disease (PD) resulting in a high incidence of aspiration pneumonia and death. However, there are no randomized controlled trials comparing strength and skill‐based approaches to improve airway protection in PD. Objectives: The aim of this study was to compare expiratory muscle strength training (EMST) and sensorimotor training for airway protection (smTAP) to improve cough‐related outcomes in people with PD. Methods: Participants with PD and dysphagia were recruited for this prospective phase II randomized‐blinded controlled clinical trial. Participants completed baseline assessment, 5 weeks of EMST or smTAP, and a post‐training assessment. Primary outcome measures included maximum expiratory pressure (MEP) and voluntary cough peak expiratory flow rate (PEFR). Mixed effects models were used to assess the effects of EMST and smTAP on outcomes. Results: A total of 65 participants received either EMST (n = 34) or smTAP (n = 31). MEP improved from pre‐ to post‐treatment for smTAP (P < 0.001, d = 0.19) and EMST (P < 0.001, d = 0.53). Voluntary PEFR increased from pre‐ to post‐treatment for smTAP (P < 0.001, d = 0.19) and EMST (P < 0.001, d = 0.06). Moreover, reflex cough PEFR (P < 0.001, d = 0.64), reflex cough expired volume (P < 0.001, d = 0.74), and urge to cough (P = 0.018, OR = 2.70) improved for the smTAP group but not for the EMST group. Conclusions: This clinical trial confirmed the efficacy of smTAP to improve reflex and voluntary cough function, above and beyond EMST, the current gold standard. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Melt extrusion pretreatment of poly(ethylene terephthalate) (PET) prior to enzymatic depolymerization with an unpurified leaf branch compost cutinase enzyme cocktail is explored to ascertain the efficiency gained by different processing methods on the enzymatic depolymerization of PET. Specific surface area (SSA) is investigated as a key factor in reducing depolymerization time. Higher SSA substrates (>5.6 mm2 mg−1) show higher depolymerization rates (≈0.88 g L−1 terephthalic acid [TPA] per day) and no induction phase, while lower SSA substrates (≈4.3, 4.4, and 5.6 mm2 mg−1) show, after an initial induction phase, similar depolymerization rates (≈0.46, 0.45, and 0.44 g L−1 TPA per day) despite increases in SSA of up to 30%. The mechanism of enzymatic depolymerization manifests in the appearance of anisotropic pitting. Longer incubation time used to overcome the induction phase in low SSA substrates allows for nearly full recovery of monomeric products, but manual pregrinding of extruded PET sharply increases SSA, depolymerization rate, and substrate crystallinity which may decrease the maximum recycled yield of the product materials. An estimate of the energy cost of increasing SSA is made and its effects on material properties are discussed. This work highlights key material structure and pretreatment aspects influencing the enzymatic recycling of PET. [ABSTRACT FROM AUTHOR]

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-[alpha] and ROS in a Rac1-dependent manner. TNF-[alpha] was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease. macrophages doi: 10.1152/ajplung.90590.2008.