Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic.... Show morePositive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18-22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium "Positive-Strand RNA Viruses" to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium. Show less
The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering... Show moreThe ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium "Organoids as Tools for Fundamental Discovery and Translation". Show less
Ruitenberg, M.F.L.; Koppelmans, V.; Seidler, R.D.; Schomaker, J. 2022
With limited resources, exploring new opportunities is crucial for survival. Exploring novel options, however, comes at the cost of uncertainty. Therefore, there is a trade-off between exploiting... Show moreWith limited resources, exploring new opportunities is crucial for survival. Exploring novel options, however, comes at the cost of uncertainty. Therefore, there is a trade-off between exploiting options with a known beneficial outcome and exploring novel options with a potentially higher gain. Computational models have suggested that novelty may promote exploratory behavior by inducing a so-called novelty bonus through reward-related processes. So far, few studies have provided behavioral evidence for such a novelty bonus. In this study, we aimed to investigate whether spatial novelty can stimulate exploratory behavior (Experiment 1), and whether age, novelty-seeking, and reduced action radius or social interactions due to COVID-19 restrictions influenced the exploration–exploitation trade-off (Experiment 2). In both experiments, we employed a novel paradigm in which participants made binary decisions between food items, while on rare trials, a surprise option was presented. Results from Experiment 1 are in line with a novelty bonus, with spatial novelty promoting exploratory behavior. In Experiment 2, we found that exploratory behavior declined with age, high novelty seekers made more exploratory choices than low novelty seekers, and participants with a smaller action radius made fewer exploratory choices. These findings are consistent with previous findings in animals and predictions from computational models. Show less
Kruijf, E.J.F.M. de; Fibbe, W.E.; Pel, M. van 2020
Peripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell... Show morePeripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell transplantation. The use of mobilized HSPCs has several advantages over traditional bone marrow-derived HSPCs, including a less invasive harvesting process for the donor, higher HSPC yields, and faster hematopoietic reconstitution in the recipient. For years, the mechanisms by which cytokines and other agents mobilize HSPCs from the bone marrow were not fully understood. The field of stem cell mobilization research has advanced significantly over the past decade, with major breakthroughs in the elucidation of the complex mechanisms that underlie stem cell mobilization. In this review, we provide an overview of the events that underlie HSPC mobilization and address the relevant cellular and molecular components of the bone marrow niche. Furthermore, current and future mobilizing agents will be discussed. Show less
Son, D. van; Rover, M. de; Blasio, F.M. de; Does, W. van der; Barry, R.J.; Putman, P. 2019
The ratio between frontal resting‐state electroencephalography (EEG) theta and beta frequency power (theta/beta ratio, TBR) is negatively related to cognitive control. It is unknown which... Show moreThe ratio between frontal resting‐state electroencephalography (EEG) theta and beta frequency power (theta/beta ratio, TBR) is negatively related to cognitive control. It is unknown which psychological processes during resting state account for this. Increased theta and reduced beta power are observed during mind wandering (MW), and MW is related to decreased connectivity in the executive control network (ECN) and increased connectivity in the default mode network (DMN). The goal of this study was to test if MW‐related fluctuations in TBR covary with such functional variation in ECN and DMN connectivity and if this functional variation is related to resting‐state TBR. Data were analyzed for 26 participants who performed a 40‐min breath‐counting task and reported the occurrence of MW episodes while EEG was measured and again during magnetic resonance imaging. Frontal TBR was higher during MW than controlled thought and this was marginally related to resting‐state TBR. DMN connectivity was higher and ECN connectivity was lower during MW. Greater ECN connectivity during focus than MW was correlated to lower TBR during focus than MW. These results provide the first evidence of the neural correlates of TBR and its functional dynamics and further establish TBR's usefulness for the study of executive control, in normal and potentially abnormal psychology. Show less
Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for... Show moreSm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection. Show less
This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye... Show moreThis paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB). Show less
Autoantibodies against muscle-specific kinase (MuSK), a protein essential for clustering of acetylcholine receptors at the neuromuscular junction (NMJ), are detected in the serum of a proportion of... Show moreAutoantibodies against muscle-specific kinase (MuSK), a protein essential for clustering of acetylcholine receptors at the neuromuscular junction (NMJ), are detected in the serum of a proportion of myasthenia gravis (MG) patients. In most MuSK MG patients the anti-MuSK activity resides in the IgG4 subclass, a minor IgG component without very well-defined, but presumably anti-inflammatory, roles in immunity. In recent years, several animal model studies showed that anti-MuSK autoantibodies can cause muscle weakness by directly affecting NMJ function and, therefore, are likely not simply bystander disease markers in MuSK MG patients. In passive transfer mice, we recently provided proof that MuSK MG patient IgG4 is severely myasthenogenic, causing functional defects at NMJs. Against the clinical, serological, and pharmacological background of MuSK MG, here we discuss the MuSK MG animal models generated by our laboratory and others that have been instrumental in elucidating the etiological and pathophysiological roles of anti-MuSK antibodies. Show less
