Medium chain fatty acids are commonly consumed as part of diets for endurance sports and as medical treatment in ketogenic diets where these diets regulate energy metabolism and increase adenosine levels. However, the role of the equilibrative nucleoside transporter 1 (ENT1), which is responsible for adenosine transport across membranes in this process, is not well understood. Here, we investigate ENT1 activity in controlling the effects of two dietary medium chain fatty acids (decanoic and octanoic acid), employing the tractable model system We show that genetic ablation of three ENT1 orthologues unexpectedly improves cell proliferation specifically following decanoic acid treatment.
View Article and Find Full Text PDFMacropinocytosis is a broadly conserved endocytic process discovered nearly 100 years ago, yet still poorly understood. It is prominent in cancer cell feeding, immune surveillance, uptake of RNA vaccines and as an invasion route for pathogens. Macropinocytic cells extend large cups or flaps from their plasma membrane to engulf droplets of medium and trap them in micron-sized vesicles.
View Article and Find Full Text PDFNeurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the specialized apparatus characterizing the neuronal presynapse must form de novo. How the components for presynaptic neurotransmission are transported and assembled is poorly understood.
View Article and Find Full Text PDFIntimate associations between fungi and intracellular bacterial endosymbionts are becoming increasingly well understood. Phylogenetic analyses demonstrate that bacterial endosymbionts of Mucoromycota fungi are related either to free-living Burkholderia or Mollicutes species. The so-called Burkholderia-related endosymbionts or BRE comprise Mycoavidus, Mycetohabitans and Candidatus Glomeribacter gigasporarum.
View Article and Find Full Text PDFBackground: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria.
View Article and Find Full Text PDFPhosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity.
View Article and Find Full Text PDFMacropinocytosis is a conserved endocytic process by which cells engulf droplets of medium into micron-sized vesicles. We use light-sheet microscopy to define an underlying set of principles by which macropinocytic cups are shaped and closed in Dictyostelium amoebae. Cups form around domains of PIP3 stretching almost to their lip and are supported by a specialized F-actin scaffold from lip to base.
View Article and Find Full Text PDFBackground: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival.
Methods: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016.
The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the amoeba , we find that cells lacking Katnip (Katanin interacting protein) have a general defect in lysosomal delivery and although they make autophagosomes and phagosomes correctly, cells are then unable to digest them. Katnip is largely unstudied yet highly conserved across evolution.
View Article and Find Full Text PDFSignificance: Traditional pathology workflow suffers from limitations including biopsy invasiveness, small fraction of large tissue samples being analyzed, and complex and time-consuming processing.
Aim: We address limitations of conventional pathology workflow through development of a laser microbiopsy device for minimally invasive harvest of sub-microliter tissue volumes. Laser microbiopsy combined with rapid diagnostic methods, such as virtual hematoxylin and eosin (H&E) imaging has potential to provide rapid minimally invasive tissue diagnosis.
Background: The Children's Oncology Group Long-Term Follow-Up Guidelines provide exposure-based risks and recommendations for late effects screening of survivors of childhood cancer. Passport for Care (PFC) is a web-based clinical decision support tool for generating a personalized survivorship care plan (SCP) derived from the Guidelines and user-entered exposures. We assessed PFC clinician user practices and perceptions of PFC impact on clinic workflow, guidelines application, and survivor shared decision-making.
View Article and Find Full Text PDFMacropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in the endo-lysosomal system. They use macropinocytosis for feeding, maintaining a high rate of fluid uptake that makes assay and experimentation easy.
View Article and Find Full Text PDFOpportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood.
View Article and Find Full Text PDFObjectives: Emergency department (ED) visits by children with solid organ transplants have increased significantly. Our objectives were to describe the common complaints, diagnosis, types, and rates of serious bacterial infection (SBI) in children with renal transplant (RT) who present to the hospital.
Methods: We conducted a retrospective study from 2012 to 2016 of RT children up to 18 years who presented to the ED or were directly admitted.
This study aimed at answering three research questions: (1) Under the experimental conditions studied, what is the dominant mechanism of Holmium:YAG lithotripsy with or without pulse modulation? (2) Under what circumstances can laser pulse modulation increase crater volume of stone ablation per joule of emitted radiant energy? (3) Are BegoStone phantoms a suitable model for laser lithotripsy studies? The research questions were addressed by ablation experiments with BegoStone phantoms and native stones. Experiments were performed under three stone conditions: dry stones in air, hydrated stones in air, and hydrated stones in water. Single pulses with and without pulse modulation were applied.
View Article and Find Full Text PDFThe social amoeba provides an excellent model for research across a broad range of disciplines within biology. The organism diverged from the plant, yeast, fungi and animal kingdoms around 1 billion years ago but retains common aspects found in these kingdoms. has a low level of genetic complexity and provides a range of molecular, cellular, biochemical and developmental biology experimental techniques, enabling multidisciplinary studies to be carried out in a wide range of areas, leading to research breakthroughs.
View Article and Find Full Text PDFJ Cell Biol
September 2021
In this issue, Le et al. (2021. J.
View Article and Find Full Text PDFChild welfare workers aim to promote the well-being and safety of children and are the link between the child welfare system and families. Families served by the child welfare system should expect similar service based on clinical factors, not based on their caseworker's characteristics. Using secondary data analyses of the most recent Canadian Incidence Study of Reported Child Abuse and Neglect (CIS-2008) and multilevel modeling, this study examines whether child welfare worker characteristics, such as education level and field, age, and experience predict their perception of the risk of future maltreatment.
View Article and Find Full Text PDFJ Paediatr Child Health
October 2021
In 2019 we started a new annual meeting, aimed at bringing together researchers from across the United Kingdom studying cellular microbiology and the cell biology of host-pathogen interactions. In contrast to large glamourous meetings, featuring the great and the good from across the world, we wanted to create a forum for early career researchers to present their work and enjoy lively discussion. In particular, we hope that focussing on making the meeting accessible, affordable, and informal would help integrate and build the U.
View Article and Find Full Text PDFEngulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown.
View Article and Find Full Text PDFPurpose: Early animal studies suggest that parotid gland (PG) toxicity prediction could be improved by an accurate estimation of the radiation dose to sub-regions of the PG. Translation to clinical investigation requires voxel-level dose accumulation in this organ that responds volumetrically throughout treatment. To date, deformable image registration (DIR) has been evaluated for the PG using only surface alignment.
View Article and Find Full Text PDFTwo decades ago, McKenzie's meta-analysis of literature provided six fundamental elements of adventure education programme design still used to guide research and practice today. While the value of McKenzie's early work should not be underestimated, adventure education has undergone considerable changes. Adventurous activities are now available in urban and indoor contexts and used to facilitate a growing health and wellbeing agenda.
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