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Macrophages are mechanosensitive cells that can exquisitely fine-tune their function in response to their microenvironment. While macrophage polarization results in concomitant changes in cell morphology and epigenetic reprogramming, how biophysically-induced signaling cascades contribute to gene regulatory programs that drive polarization remains unknown. We reveal a cytoskeleton-dependent Src-H3 acetylation (H3Ac) axis responsible for inflammation-associated histone hyperacetylation. Inflammatory stimuli caused increases in traction forces, Src activity and H3Ac marks in macrophages, accompanied by reduced cell elongation and motility. These effects were curtailed following disruption of H3Ac-signaling through either micropattern-induced cell elongation or inhibition of H3Ac readers (BRD proteins) directly. Src activation relieves the suppression of p300 histone acetyltransferase (HAT) activity by PKCδ. Furthermore, while inhibition of Src reduced p300 HAT activity and H3Ac marks globally, local H3Ac levels within the Src promoter were increased, suggesting H3Ac regulates Src levels through feedback. Together, our study reveals an adhesome-to-epigenome regulatory nexus underlying macrophage mechanosensation, where Src modulates H3Ac-associated epigenetic signaling as a means of tuning inflammatory gene activity and macrophage fate decisions in response to microenvironmental cues.

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The integration of citizen scientists into ecological research is transforming how, where, and when data are collected, and expanding the potential scales of ecological studies. Citizen-science projects can provide numerous benefits for participants while educating and connecting professionals with lay audiences, potentially increasing the acceptance of conservation and management actions. However, for all the benefits, collection of citizen-science data is often biased towards areas that are easily accessible (e.g. developments and roadways), and thus data are usually affected by issues typical of opportunistic surveys (e.g. uneven sampling effort). These areas are usually illuminated by artificial light at night (ALAN), a dynamic sensory stimulus that alters the perceptual world for both humans and wildlife. Our goal was to test whether satellite-based measures of ALAN could improve our understanding of the detection process of citizen-scientist-reported sightings of a large mammal. We collected observations of American black bears Ursus americanus (n = 1,315) outside their primary range in Minnesota, USA, as part of a study to gauge population expansion. Participants from the public provided sighting locations of bears on a website. We used an occupancy modelling framework to determine how well ALAN accounted for observer metrics compared to other commonly used metrics (e.g. housing density). Citizen scientists reported 17% of bear sightings were under artificially lit conditions and monthly ALAN estimates did the best job accounting for spatial bias in detection of all observations, based on AIC values and effect sizes ( ß^  = 0.81, 0.71-0.90 95% CI). Bear detection increased with elevated illuminance; relative abundance was positively associated with natural cover, proximity to primary bear range and lower road density. Although the highest counts of bear sightings occurred in the highly illuminated suburbs of the Minneapolis-St. Paul metropolitan region, we estimated substantially higher bear abundance in another region with plentiful natural cover and low ALAN (up to ~375% increased predicted relative abundance) where observations were sparse. We demonstrate the importance of considering ALAN radiance when analysing citizen-scientist-collected data, and we highlight the ways that ALAN data provide a dynamic snapshot of human activity.

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Purpose: Goal Attainment Scaling (GAS) is used to assess functional gains in response to treatment. Specific characteristics of the functional goals set by individuals receiving botulinum toxin type A (BoNTA) injections for spasticity management are unknown. The primary objectives of this study were to describe the characteristics of the goals set by patients before receiving BoNTA injections using the International Classification of Functioning, Disability and Health (ICF) and to determine whether the pattern of spasticity distribution affected the goals set. Methods: A cross-sectional retrospective chart review was carried out in an outpatient spasticity-management clinic in Toronto. A total of 176 patients with a variety of neurological lesions attended the clinic to receive BoNTA injections and completed GAS from December 2012 to December 2013. The main outcome measures were the characteristics of the goals set by the participants on the basis of ICF categories (body functions and structures, activity and participation) and the spasticity distribution using Modified Ashworth Scale scores. Results: Of the patients, 73% set activity and participation goals, and 27% set body functions and structures goals (p<0.05). In the activity and participation category, 30% of patients set moving and walking goals, 28% set self-care and dressing goals, and 12% set changing and maintaining body position goals. In the body functions and structures category, 18% set neuromuscular and movement-related goals, and 8% set pain goals. The ICF goal categories were not related to the patterns of spasticity (upper limb vs. lower limb or unilateral vs. bilateral spasticity) or type of upper motor neuron (UMN) lesion (p>0.05). Conclusion: Our results show that patients receiving BoNTA treatment set a higher percentage of activity and participation goals than body functions and structures goals. Goal classification was not affected by type of spasticity distribution or type of UMN disorder.

Objectif : l'échelle de réalisation des objectifs (Goal Attainment Scaling ou GAS) est employée pour évaluer les gains fonctionnels en réponse à un traitement. On ne connaît pas les caractéristiques des objectifs fonctionnels établis par les personnes recevant des injections de toxine botulinique de type A (BoNTA) pour la prise en charge de la spasticité. Cette étude vise à décrire les caractéristiques des objectifs établis par les patients avant de recevoir des injections de BoNTA à l'aide de la Classification internationale du fonctionnement, du handicap et de la santé (CIF) et à déterminer si le modèle de distribution de la spasticité avait un effet sur les objectifs établis. Méthodologie : on a mené une revue rétrospective transversale des dossiers d'une clinique ambulatoire de prise en charge de la spasticité à Toronto. Au total, 176 patients ayant diverses lésions neurologiques sont venus à la clinique pour recevoir des injections de BoNTA et ont rempli la GAS entre décembre 2012 et décembre 2013. On a recensé les caractéristiques des objectifs en fonction des catégories de la CIF (fonctions organiques et structures anatomiques, activités et participation) et de la distribution de la spasticité à l'aide de l'échelle d'Ashworth modifiée. Résultats : de tous les patients, 73 % ont établi des objectifs liés aux activités et à la participation et 27 %, des objectifs liés aux fonctions organiques et aux structures anatomiques (p<0,05). Dans la catégorie des activités et de la participation, 30 % de tous les patients ont établi des objectifs par rapport à « marcher et se déplacer ¼, 28 % ont établi des objectifs par rapport aux « soins personnels ¼ et à « s'habiller ¼, et 12 %, par rapport à « modifier et maintenir sa position corporelle ¼. Dans la catégorie des fonctions organiques et des structures anatomiques, 18 % des participants ont établi des objectifs liés aux « fonctions de l'appareil locomoteur et au mouvement ¼ et 8 % ont établi des objectifs par rapport à la « douleur ¼. Les catégories d'objectifs de la CIF n'étaient pas liées aux modèles de spasticité (spasticité des membres supérieurs par rapport aux membres inférieurs ou spasticité unilatérale par rapport à bilatérale) ou au type de lésion des motoneurones supérieurs (p>0,05). Conclusion : nos résultats montrent que les patients qui reçoivent un traitement de BoNTA établissent un pourcentage plus élevé d'objectifs liés aux activités et à la participation qu'aux fonctions organiques et aux structures anatomiques. Le type de distribution de la spasticité ou le type de lésion des motoneurones n'a pas eu d'effet sur la classification des objectifs.