Reversal of the adipostat control of torpor during migration in hummingbirds

Many small endotherms use torpor to reduce metabolic rate and manage daily energy balance. However, the physiological 'rules' that govern torpor use are unclear. We tracked torpor use and body composition in ruby-throated hummingbirds (Archilochus colubris), a long-distance migrant, throughout the summer using respirometry and quantitative magnetic resonance. During the mid-summer, birds entered torpor at consistently low fat stores (~5% of body mass), and torpor duration was negatively related to evening fat load. Remarkably, this energy-emergency strategy was abandoned in the late summer when birds accumulated fat for migration. During the migration period, birds were more likely to enter torpor on nights when they had higher fat stores, and fat gain was positively correlated with the amount of torpor used. These findings demonstrate the versatility of torpor throughout the annual cycle and suggest a fundamental change in physiological feedback between adiposity and torpor during migration. Moreover, this study highlights the underappreciated importance of facultative heterothermy in migratory ecology.

Influence of Hospital Outdoor Space on Physiological Electroencephalography (EEG) Feedback of Staff

Objectives: To investigate the differences and relationships between different outdoor spaces of hospitals on the physiological electroencephalography (EEG) feedback (PEEGF) of staff. Background: Relieving the pressure of hospital staff is essential, and several studies have revealed that even short-term exposure to outdoor space has a decompression effect. Yet, the focus is scarcely centered on the differences and influential relationships between the PEEGF from different outdoor spaces where the staff spend time, particularly in large-scale hospitals in China. Methods: EEG measurement equipment was utilized to obtain the value of β wave (vβw) that represents the stress and anxiety of staff in three different outdoor spaces: open, traffic, and rest. On the basis of EEG data, correlation analysis was conducted in accordance with the proportion of space elements. Results: The proportion of natural elements, such as landscape ( r = −.800** p=.005) and waterscape ( r = −.782* p=.013), were negatively correlated with the vβw produced by staff, while the proportion of hard paving was positive ( r = .817** p=.004) with more vβw produced by staff. In other words, the percentage of landscape and waterscape can reduce stress, while hard paving has the opposite effect. Further, there was a difference in the amount of vβw generated between nurses and administrators in the open space at the entrance of the main building ( p = .043). Conclusions: The present study revealed the influence of different outdoor space elements of the hospital on the physiological feedback of staff, demonstrated the practical necessity of evidence-based design, and proposed relevant optimization suggestions.

A Biological Circuit Involving Mef2c, Mef2d, and Hdac9 Controls the Immunosuppressive Functions of CD4+Foxp3+ T-Regulatory Cells

The Mads/Mef2 (Mef2a/b/c/d) family of transcription factors (TFs) regulates differentiation of muscle cells, neurons and hematopoietic cells. By functioning in physiological feedback loops, Mef2 TFs promote the transcription of their repressor, Hdac9, thereby providing temporal control of Mef2-driven differentiation. Disruption of this feedback is associated with the development of various pathologic states, including cancer. Beside their direct involvement in oncogenesis, Mef2 TFs indirectly control tumor progression by regulating antitumor immunity. We recently reported that in CD4+CD25+Foxp3+ T-regulatory (Treg) cells, Mef2d is required for the acquisition of an effector Treg (eTreg) phenotype and for the activation of an epigenetic program that suppresses the anti-tumor immune responses of conventional T and B cells. We now report that as with Mef2d, the deletion of Mef2c in Tregs switches off the expression of Il10 and Icos and leads to enhanced antitumor immunity in syngeneic models of lung cancer. Mechanistically, Mef2c does not directly bind the regulatory elements of Icos and Il10, but its loss-of-function in Tregs induces the expression of the transcriptional repressor, Hdac9. As a consequence, Mef2d, the more abundant member of the Mef2 family, is converted by Hdac9 into a transcriptional repressor on these loci. This leads to the impairment of Treg suppressive properties in vivo and to enhanced anti-cancer immunity. These data further highlight the central role played by the Mef2/Hdac9 axis in the regulation of CD4+Foxp3+ Treg function and adds a new level of complexity to the analysis and study of Treg biology.

Reversal of the adipostat control of torpor during migration in hummingbirds

Many small endotherms use torpor to reduce metabolic rate and manage daily energy balance. However, the physiological 'rules' that govern torpor use are unclear. We tracked torpor use and body composition in ruby-throated hummingbirds (Archilochus colubris), a long-distance migrant, throughout the summer using respirometry and quantitative magnetic resonance. During the mid-summer, birds entered torpor at consistently low fat stores (~5% of body mass), and torpor duration was negatively related to evening fat load. Remarkably, this energy-emergency strategy was abandoned in the late summer when birds accumulated fat for migration. Migrating birds were more likely to enter torpor on nights when they had higher fat stores, and fat gain was positively correlated with the amount of torpor used. These findings demonstrate the versatility of torpor throughout the annual cycle and suggest a fundamental change in physiological feedback between adiposity and torpor during migration. Moreover, this study highlights the underappreciated importance of facultative heterothermy in migratory ecology.

A digital lifestyle behaviour change intervention for the prevention of type 2 diabetes: a qualitative study exploring intuitive engagement with real-time glucose and physical activity feedback

Background Mobile health technologies have advanced to now allow monitoring of the acute physiological responses to lifestyle behaviours. Our aim was to explore how people engaged with real-time feedback on their physical activity and glucose levels over several weeks. Methods Semi-structured interviews with 26 participants (61.5% female, 56.6 years) at moderate-to-high risk of developing type 2 diabetes were conducted. Interviews were completed after participants took part in an intervention comprising a flash glucose monitor (Freestyle Libre) and a physical activity monitor (Fitbit Charge 2). Purposive sampling ensured representation of ages, genders and group allocations. Results Inductive thematic analysis revealed how individuals intuitively used, interpreted and acted on feedback from wearable technologies. Six key themes emerged: triggers of engagement with the technologies, links between behaviour and health, lack of confidence, changes to movement behaviours, changes to diet and barriers to lifestyle behaviour change. Conclusions Our findings demonstrate that accessing behavioural and physiological feedback can increase self-awareness of how lifestyle impacts short-term health. Some participants noticed a link between the feedback presented by the two devices and changed their behaviour but many did not. Training and educational support, as well as efforts to optimize how feedback is presented to users, are needed to sustain engagement and behaviour change. Extensions of this work to involve people with diabetes are also warranted to explore whether behavioural and physiological feedback in parallel can encourage better diabetes self-management. Trial registration ISRCTN Registry, ISRCTN17545949, 12/05/2017, prospectively registered.

Minimal biophysical model of combined antibiotic action

Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.

Minimal biophysical model of combined antibiotic action

Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics, but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We systematically refine the model by including direct physical interactions of different drugs on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions derived using entropy maximization. It further makes parameter-free predictions for combined drug effects on cells carrying resistance genes and for drugs that mimic poor nutrient environments. We show experimentally that resistance genes can drastically alter drug interactions in notable agreement with our theoretical predictions. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.

miR-467 regulates inflammation and blood insulin and glucose

Obesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycemia, in regulating inflammation and blood glucose handling.We previously demonstrated that miR-467a-5p is induced by hyperglycemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57/BL6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1−/− (and other unknown transcripts) are targeted by miR-467 to regulate inflammation.miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.