Neuronal activity is an energy-intensive process that is largely sustained by instantaneous fuel utilization and ATP synthesis. However, how neurons couple ATP synthesis rate to fuel availability is largely unknown. Here, we demonstrate that the metabolic sensor enzyme O-linked N-acetyl glucosamine (O-GlcNAc) transferase regulates neuronal activity-driven mitochondrial bioenergetics in hippocampal and cortical neurons.
View Article and Find Full Text PDFThe healthcare crisis across unceded First Nations' territories in rural, remote and Indigenous communities in British Columbia (BC) is marked by persistent barriers to accessing care and support close to home. This commentary describes an exceptional story of how technology, trusted partnerships and relationships came together to create an innovative suite of virtual care programs called "Real-Time Virtual Support" (RTVS). We describe key approaches, learnings and future considerations to improve the equity of healthcare delivery for rural, remote and First Nations communities.
View Article and Find Full Text PDFEnergy metabolism supports neuronal function. While it is well established that changes in energy metabolism underpin brain plasticity and function, less is known about how individual neurons modulate their metabolic states to meet varying energy demands. This is because most approaches used to examine metabolism in living organisms lack the resolution to visualize energy metabolism within individual circuits, cells, or subcellular regions.
View Article and Find Full Text PDFRirA is a global iron regulator in diverse that belongs to the Rrf2 superfamily of transcriptional regulators, which can contain an iron-sulfur (Fe-S) cluster. Under iron-replete conditions, RirA contains a [4Fe-4S] cluster, enabling high-affinity binding to RirA-regulated operator sequences, thereby causing the repression of cellular iron uptake. Under iron deficiency, one of the cluster irons dissociates, generating an unstable [3Fe-4S] form that subsequently degrades to a [2Fe-2S] form and then to apo RirA, resulting in loss of high-affinity DNA-binding.
View Article and Find Full Text PDFEnergy metabolism supports neuronal function. While it is well established that changes in energy metabolism underpin brain plasticity and function, less is known about how individual neurons modulate their metabolic states to meet varying energy demands. This is because most approaches used to examine metabolism in living organisms lack the resolution to visualize energy metabolism within individual circuits, cells, or subcellular regions.
View Article and Find Full Text PDFThe combination of the ongoing violence perpetuated against Black, Brown, and Asian people, and the increased incidence of death of Black, Indigenous, people of color (BIPOC) and Asian Americans and Pacific Islanders (AAPI) at the start of the COVID-19 pandemic, elicited an important response from the field of social work across the nation. This article describes the efforts undertaken by a Social Work Department at a comprehensive cancer center in response to a call to develop antiracist practice. This article recounts the process of creating educational opportunities for oncology social workers to help them identify bias and racism in themselves and throughout the healthcare system, to embrace intentional antiracist practice, and to better advocate for BIPOC/AAPI patients and colleagues.
View Article and Find Full Text PDFNeuronal activity is an energy-intensive process that is largely sustained by instantaneous fuel utilization and ATP synthesis. However, how neurons couple ATP synthesis rate to fuel availability is largely unknown. Here, we demonstrate that the metabolic sensor enzyme O-GlcNAc transferase regulates neuronal activity-driven mitochondrial bioenergetics.
View Article and Find Full Text PDFObjective: The coronavirus disease 2019 pandemic accelerated the adoption of telehealth technologies. Persistent disparities in telecommunication devices, internet connectivity, and digital literacy, however, undermine the potential for telemedicine to reduce barriers to health care access. Health systems may have a role in addressing these structural inequities.
View Article and Find Full Text PDFCellular metabolism is regulated over space and time to ensure that energy production is efficiently matched with consumption. Fluorescent biosensors are useful tools for studying metabolism as they enable real-time detection of metabolite abundance with single-cell resolution. For monitoring glycolysis, the intermediate fructose 1,6-bisphosphate (FBP) is a particularly informative signal as its concentration is strongly correlated with flux through the whole pathway.
View Article and Find Full Text PDFMotivated by the growing importance of single fluorescent protein biosensors (SFPBs) in biological research and the difficulty in rationally engineering these tools, we sought to increase the rate at which SFPB designs can be optimized. SFPBs generally consist of three components: a circularly permuted fluorescent protein, a ligand-binding domain, and linkers connecting the two domains. In the absence of predictive methods for biosensor engineering, most designs combining these three components will fail to produce allosteric coupling between ligand binding and fluorescence emission.
View Article and Find Full Text PDFClin Soc Work J
February 2021
The COVID-19 pandemic necessitated an abrupt conclusion of field placement for social work interns at a comprehensive cancer center. In response to social distancing requirements, social workers, but not interns, were granted access to work remotely. Virtual programming became necessary to meet the interns' remaining educational requirements and provided an opportunity for proper termination from the program.
View Article and Find Full Text PDFBackground: Injuries are a major public health problem globally. With sound planning and organization, essential trauma care can be reliably provided with relatively low-cost equipment and supplies. However, availability of these resources requires an effective and efficient supply chain and good stock management practices.
View Article and Find Full Text PDFBackground: Gun violence (GV) is a complex public health issue, and the management of GV as a disease engages the surgeon in technical and nontechnical skills. The Anatomy of Gun Violence (AGV) curriculum was developed to teach surgical trainees these seemingly disparate skills, training residents to manage the multiple aspects of firearm injury.
Study Design: The AGV curriculum was delivered over 6 weeks in the 2017-2018 and 2018-2019 academic years (AY), and used multiple educational methods including didactic lectures, mock oral examinations, a Bleeding Control training session, a GV survivor's personal story, a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) training session, and the Surgery for Abdominal-thoracic ViolencE (SAVE) simulation lab.
The bacterial protein WhiD belongs to the Wbl family of iron-sulfur [Fe-S] proteins present only in the actinomycetes. In , it is required for the late stages of sporulation, but precisely how it functions is unknown. Here, we report results from and experiments with WhiD from (WhiD), which differs from WhiD (WhiD) only at the C terminus.
View Article and Find Full Text PDFRirA is a global regulator of iron homeostasis in and related α-proteobacteria. In its [4Fe-4S] cluster-bound form it represses iron uptake by binding to IRO Box sequences upstream of RirA-regulated genes. Under low iron and/or aerobic conditions, [4Fe-4S] RirA undergoes cluster conversion/degradation to apo-RirA, which can no longer bind IRO Box sequences.
View Article and Find Full Text PDFObjective: As part of a study exploring school food environments, this study aimed to understand youth perspectives of school food.
Design: Photovoice, a qualitative visual methodology, was used to engage participants through photo-taking, with goals of enabling reflection, promoting dialogue, and facilitating change.
Setting: Participants were recruited through 2 youth-focused community organizations in Nova Scotia, Canada.
Supporting the implementation of school food and nutrition policies (SFNPs) is an international priority to encourage healthier eating among children and youth. Such policies can improve equitable access, resources, and supports for healthy eating. However, despite the potential impact of SFNPs, several implementation barriers have been reported.
View Article and Find Full Text PDFBiol Methods Protoc
January 2019
The ability to specifically label the sulphide ions of protein-bound iron-sulphur (FeS) clusters with S isotope greatly facilitates structure-function studies. In particular, it provides insight when using either spectroscopic techniques that probe cluster-associated vibrations, or non-denaturing mass spectrometry, where the ∼+2 Da average increase per sulphide enables unambiguous assignment of the FeS cluster and, where relevant, its conversion/degradation products. Here, we employ a thermostable homologue of the -acetyl-l-serine sulfhydrylase CysK to generate S-substituted l-cysteine and subsequently use it as a substrate for the l-cysteine desulfurase NifS to gradually supply S for FeS cluster assembly in an otherwise standard cluster reconstitution protocol.
View Article and Find Full Text PDFFlow cytometry approaches combined with a genetically encoded targeted fluorescent biosensor are used to determine the subcellular compartmental availability of the oxidized form of nicotinamide adenine dinucleotide (NAD ). The availability of free NAD can affect the activities of NAD -consuming enzymes such as sirtuin, PARP/ARTD, and cyclic ADPR-hydrolase family members. Many methods for measuring the NAD available to these enzymes are limited because they cannot determine free NAD as it exists in various subcellular compartments distinctly from bound NAD or NADH.
View Article and Find Full Text PDFIntroduction: "See one, do one, teach one" has represented the model for surgical education for over a century, however recent changes in education have reduced autonomy in training. The goal of this study was to assess the impact of autonomy on learning a procedural skill.
Methods: Senior medical students were randomized and trained to performance a vascular anastomosis utilizing progressive autonomy vs.
Free nicotinamide adenine dinucleotide (NAD) serves as substrate for NAD-consuming enzymes. As such, the local concentration of free NAD can influence enzymatic activities. Here we describe methods for using a fluorescent, genetically-encoded sensor to measure subcellular NAD concentrations.
View Article and Find Full Text PDFObjective: Each July, surgical interns arrive to residency with variable skills, knowledge, and clinical experience. To standardize and improve intern preparation, the American College of Surgeons (ACS), Association of Program Directors in Surgery, and Association for Surgical Education developed a pilot Resident Prep Curriculum (RPC). To date, no studies have analyzed these efforts.
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