The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (DRP1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Dnm1l in adult AgRP neurons (Drp1 cKO) show decreased fasting- or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1 cKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and body-weight regulation.Animal behavior is regulated based on the values of future rewards. The phasic activity of midbrain dopamine neurons signals these values. Because reward values often change over time, even on a subsecond-by-subsecond basis, appropriate behavioral regulation requires continuous value monitoring. However, the phasic dopamine activity, which is sporadic and has a short duration, likely fails continuous monitoring. Here, we demonstrate a tonic firing mode of dopamine neurons that effectively tracks changing reward values. We recorded dopamine neuron activity in monkeys during a Pavlovian procedure in which the value of a cued reward gradually increased or decreased. Dopamine neurons tonically increased and decreased their activity as the reward value changed. This tonic activity was evoked more strongly by non-burst spikes than burst spikes producing a conventional phasic activity. Our findings suggest that dopamine neurons change their firing mode to effectively signal reward values in a given situation.TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic delay in peripheral nerve conduction causing significant motor deficits in mice, which is directly attributed to the absence of paranodal axoglial junctions. By contrast, paranodes in the central nervous system are unaltered in oligodendrocytes lacking TDP-43. Mechanistically, TDP-43 binds directly to Neurofascin mRNA, encoding the cell adhesion molecule essential for paranode assembly and maintenance. Loss of TDP-43 triggers the retention of a previously unidentified cryptic exon, which targets Neurofascin mRNA for nonsense-mediated decay. Thus, TDP-43 is required for neurofascin expression, proper assembly and maintenance of paranodes, and rapid saltatory conduction. Our findings provide a framework and mechanism for how Schwann cell-autonomous dysfunction in nerve conduction is directly caused by TDP-43 loss-of-function.The efficient knock-in of large DNA fragments to label endogenous proteins remains especially challenging in non-dividing cells such as neurons. We developed Targeted Knock-In with Two (TKIT) guides as a novel CRISPR/Cas9 based approach for efficient, and precise, genomic knock-in. Lotiglipron molecular weight Through targeting non-coding regions TKIT is resistant to INDEL mutations. We demonstrate TKIT labeling of endogenous synaptic proteins with various tags, with efficiencies up to 42% in mouse primary cultured neurons. Utilizing in utero electroporation or viral injections in mice TKIT can label AMPAR subunits with Super Ecliptic pHluorin, enabling visualization of endogenous AMPARs in vivo using two-photon microscopy. We further use TKIT to assess the mobility of endogenous AMPARs using fluorescence recovery after photobleaching. Finally, we show that TKIT can be used to tag AMPARs in rat neurons, demonstrating precise genome editing in another model organism and highlighting the broad potential of TKIT as a method to visualize endogenous proteins.General practice data provide important opportunities for both population health and within-practice initiatives to improve health. Despite its promise, a lack of accuracy affects the use of such data. The Sentinel Practices Data Sourcing (SPDS) project is a structured chronic disease surveillance and data quality improvement strategy in general practice. A mixed-methods approach was used to evaluate data quality improvement in 99 participating practices over 12 months. Quantitative data were obtained by measuring performance against 10 defined indicators, whereas 48 semi-structured interviews provided qualitative data. Aggregated scores demonstrated improvements in all indicators, ranging from minor to substantially significant improvements. Participants reported positively on levels of support provided, and acquisition of new knowledge and skills relating to data entry and cleansing. This evaluation provides evidence of the effectiveness of a structured approach to improve the quality of primary care data. Investing in this targeted intervention has the potential to create sustained improvements in data quality, which can drive clinical practice improvement.The extent to which oncology social workers (OSWs) are available and adapting to disruptions in service delivery throughout the COVID-19 pandemic is unknown.Objectives The purpose of this report is to outline the initial impact of COVID-19 on oncology social work practice during the first six months of the pandemic.Methods As part of a nationwide investigation of workforce conditions for OSWs, three professional organizations surveyed their members to assess the effects of COVID-19 on changes to work hours, employment status, work setting, pay, and mode for patient contact (e.g., telephone or videoconference).Findings Among 939 OSWs, 20% reported a reduction in work hours, and two-thirds indicated a temporary shift in work to home, with most patient contact occurring primarily via telephone or videoconference.Implications Results speak to the essential nature of oncology social work and the need for evidence to inform OSW training and advocacy efforts for however long the pandemic continues.