Physiology最新文献

Bees are the most important insect pollinators of the crops humans grow, and Apis mellifera, the Western honey bee, is the most commonly managed species for this purpose. In addition to providing agricultural services, the complex biology of honey bees has been the subject of scientific study since the 18th century, and the intricate behaviors of honey bees and ants, fellow hymenopterans, inspired much sociobiological inquest. Unfortunately, honey bees are constantly exposed to parasites, pathogens, and xenobiotics, all of which pose threats to their health. Despite our curiosity about and dependence on honey bees, defining the molecular mechanisms underlying their interactions with biotic and abiotic stressors has been challenging. The very aspects of their physiology and behavior that make them so important to agriculture also make them challenging to study, relative to canonical model organisms. However, because we rely on A. mellifera so much for pollination, we must continue our efforts to understand what ails them. Here, we review major advancements in our knowledge of honey bee physiology, focusing on immunity and detoxification, and highlight some challenges that remain.

Cystic fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it was discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells. Despite the great strides that have been made in understanding the role of CFTR in the airway epithelium, the role of CFTR in the endothelium remains unclear. Considering that the airway epithelium and endothelium work in tandem to allow gas exchange, it becomes very crucial to understand how a defective CFTR protein can impact the pulmonary vasculature and overall lung function. Fortunately, more recent research has been dedicated to elucidating the role of CFTR in the endothelium. As a result, several vascular dysfunctions associated with CF disease have come to light. Here, we summarize the current knowledge on pulmonary vascular dysfunctions in CF and discuss applicable therapies.

Whether it is the dramatic suffocating sensation from a heat wave in the summer or the positive reinforcement arising from a hot drink on a cold day; we can certainly agree that our thermal environment underlies our daily rhythms of sensation. Extensive research has focused on deciphering the central circuits responsible for conveying the impact of thermogenesis on mammalian behavior. Here, we revise the recent literature responsible for defining the behavioral correlates that arise from thermogenic fluctuations in mammals. We transition from the physiological significance of thermosensation to the circuitry responsible for the autonomic or behavioral responses associated with it. Subsequently, we delve into the positive and negative valence encoded by thermoregulatory processes. Importantly, we emphasize the crucial junctures where reward, pain, and thermoregulation intersect, unveiling a complex interplay within these neural circuits. Finally, we briefly outline fundamental questions that are pending to be addressed in the field. Fully deciphering the thermoregulatory circuitry in mammals will have far-reaching medical implications. For instance, it may lead to the identification of novel targets to overcome thermal pain or allow the maintenance of our core temperature in prolonged surgeries.

Astrocytes are no longer considered as passive support cells. In the hypothalamus, these glial cells actively participate in the control of appetite, energy expenditure, and the processes leading to obesity and its secondary complications. Here we briefly review studies supporting this conclusion and the advances made in understanding the underlying mechanisms.

The prevalence of obesity continues to rise in both adolescents and adults, in parallel obesity is strongly associated with the increased incidence of type 2 diabetes, heart failure, certain types of cancer, and all-cause mortality. In relation to obesity, many pharmacological approaches of the past have tried and failed to combat the rising obesity epidemic, particularly due to insufficient efficacy or unacceptable side effects. However, while the history of antiobesity medication is plagued by failures and disappointments, we have witnessed over the last 10 years substantial progress, particularly in regard to biochemically optimized agonists at the receptor for glucagon-like peptide-1 (GLP-1R) and unimolecular coagonists at the receptors for GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP). Although the GIP receptor:GLP-1R coagonists are being heralded as premier pharmacological tools for the treatment of obesity and diabetes, uncertainty remains as to why these drugs testify superiority over best-in-class GLP-1R monoagonists. Particularly with regard to GIP, there remains great uncertainty if and how GIP acts on systems metabolism and if the GIP system should be activated or inhibited to improve metabolic outcome in adjunct to GLP-1R agonism. In this review, we summarize recent advances in GLP-1- and GIP-based pharmacology and discuss recent findings and open questions related to how the GIP system affects systemic energy and glucose metabolism.

The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many patients with diabetes. However, there is still a negative perception of ketone bodies stemming from ketoacidosis. Originally, ketone bodies were thought of as a vital source of energy during fasting and exercise. Furthermore, in recent years, research on calorie restriction and its potential impact on extending healthy lifespans, as well as studies on ketone bodies, have gradually led to a reevaluation of the significance of ketone bodies in promoting longevity. Thus, in this review, we discuss the emerging and hidden roles of ketone bodies in various organs, including the heart, kidneys, skeletal muscles, and brain, as well as their potential impact on malignancies and lifespan.

Circadian rhythms in physiology and behavior sync organisms to external environmental cycles. Here, circadian oscillation in intracellular chloride in central pacemaker neurons of the fly, Drosophila melanogaster, is reviewed. Intracellular chloride links SLC12 cation-coupled chloride transporter function with kinase signaling and the regulation of inwardly rectifying potassium channels.

The application of single-cell molecular profiling coupled with spatial technologies has enabled charting of cellular heterogeneity in reference tissues and in disease. This new wave of molecular data has highlighted the expected diversity of single-cell dynamics upon shared external queues and spatial organizations. However, little is known about the relationship between single-cell heterogeneity and the emergence and maintenance of robust multicellular processes in developed tissues and its role in (patho)physiology. Here, we present emerging computational modeling strategies that use increasingly available large-scale cross-condition single-cell and spatial datasets to study multicellular organization in tissues and complement cell taxonomies. This perspective should enable us to better understand how cells within tissues collectively process information and adapt synchronized responses in disease contexts and to bridge the gap between structural changes and functions in tissues.