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Antimicrobials are widely used worldwide in food animal production for controlling and preventing disease and for improving feed conversion efficiency and growth promotion. Inappropriate use of antimicrobials in animal agriculture has the potential to promote antimicrobial resistance, which represents a threat to human, animal, and environmental health. State and municipal policies in the United States have recently been implemented to improve antimicrobial use and reporting in this sector. This study analyzed the implementation of two state-level policies (California (CA) and Maryland (MD)) and a city-level policy in San Francisco (SF), California that aimed to reduce the use of antimicrobials in food-animals and increase transparency of antimicrobial use. A qualitative analysis was based on in-depth interviews with key informants (KIs) (n = 19) who had direct experience implementing or working in the context of these sub-national policies. Interviews were recorded and transcriptions were analyzed independently by two researchers using a three-stage, grounded theory coding procedure. This study identified four major findings, including 1) vague language on antimicrobial use within policies reduces policy effectiveness; 2) the lack of reporting by producers challenges the ability to evaluate the impact of the policies on actual use; 3) diverse stakeholders need to be involved in order to develop a more effective policy; and 4) funding should be linked to the policy to provide for reporting and data analysis. This analysis provides insights on the successes and failures of existing policies and serves to inform future sub-national policies aiming to improve the judicious use of antimicrobials in food-animals. 

Chronic hyperglycemia in type II diabetes results in impaired autophagy function, accumulation of protein aggregates, and neurodegeneration. However, little is known about how to preserve autophagy function under hyperglycemic conditions. In this study, we tested whether progranulin (PGRN), a neurotrophic factor required for proper lysosome function, can restore autophagy function in neurons under high-glucose stress. We cultured primary cortical neurons derived from E18 Sprague-Dawley rat pups to maturity at 10 days in vitro (DIV) before incubation in high glucose medium and PGRN for 24-72 h before testing for autophagy flux, protein turnover, and mitochondrial function. We found that although PGRN by itself did not upregulate autophagy, it attenuated impairments in autophagy seen under high-glucose conditions. Additionally, buildup of the autophagosome marker light chain 3B (LC3B) and lysosome marker lysosome-associated membrane protein 2A (LAMP2A) changed in both neurons and astrocytes, indicating a possible role for glia in autophagy flux. Protein turnover, assessed by remaining advanced glycation end-product levels after a 6-h incubation, was preserved with PGRN treatment. Mitochondrial activity differed by complex, although PGRN appeared to increase overall activity in high glucose. We also found that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3β (GSK3β), kinases implicated in autophagy function, increased with PGRN treatment under stress. Together, our data suggest that PGRN prevents hyperglycemia-induced decreases in autophagy by increasing autophagy flux via increased ERK1/2 kinase activity in primary rat cortical neurons. 

Abstract Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi 2,3 , we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue 4 , we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders. 

Abstract For insect species in temperate environments, seasonal timing is often governed by the regulation of diapause, a complex developmental programme that allows insects to weather unfavourable conditions and synchronize their life cycles with available resources. Diapause development consists of a series of distinct phases including initiation, maintenance, termination and post‐diapause development. The evolution of insect seasonal timing depends in part on how these phases of diapause development and post‐diapause development interact to affect variation in phenology. Here, we dissect the physiological basis of a recently evolved phenological shift inRhagoletis pomonella(Diptera: Tephritidae), a model system for ecological divergence. A recently derived population ofR. pomonellashifted from specializing on native hawthorn fruit to earlier fruiting introduced apples, resulting in a 3–4 week shift in adult emergence timing. We tracked metabolic rates of individual flies across post‐winter development to test which phases of development may act either independently or in combination to contribute to this recently evolved divergence in timing. Apple and hawthorn flies differed in a number of facets of their post‐winter developmental trajectories. However, divergent adaptation in adult emergence phenology in these flies was due almost entirely to the end of the pupal diapause maintenance phase, with post‐diapause development having a very small effect. The relatively simple underpinnings of variation in adult emergence phenology suggest that further adaptation to seasonal change in these flies for this trait might be largely due to the timing of diapause termination unhindered by strong covariance among different components of post‐diapause development. 

Abstract Here, an unobtrusive, adhesive‐integrated electrode array for continuous monitoring of stomach electric activity is introduced. This patient‐friendly, disposable peel‐and‐stick adhesive device represents an important advancement over existing arrays that require placement of each electrode individually and are thus also labor intensive and are in general more rigid and cumbersome. In comparison to other silver–silver chloride electrodes, this skin conformal array does not require gel and thus can withstand low impedance over the duration of long recordings. Interfacing these electrodes with miniaturized electronic recording and wireless telemetry systems has the potential to enable scalable population health opportunities to perform objective gastrointestinal assessment and optimization of treatment regimens.