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In JoVE (1)
Other Publications (7)
Articles by Will Morgan in JoVE
JoVE Immunology and Infection
Using Eggs from Schistosoma mansoni as an In vivo Model of Helminth-induced Lung Inflammation
1Institute of Immunology, Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, 2Pathobiology, School of Veterinary Medicine, University of Pennsylvania
Schistosoma mansoni eggs are potent stimulators of the T helper type 2 (Th2) immune response, characteristic of parasite infection, asthma and allergic inflammation. This protocol utilizes S. mansoni egg injection to generate a CD4 Th2 cytokine-induced inflammatory response in the lung, characterized by lung granuloma formation around the egg, eosinophilia and macrophage alternative activation.
Other articles by Will Morgan on PubMed
What Sleep Characteristics Predict Cognitive Decline in the Elderly?
Sleep is critical for optimal cognitive function, but as we age both cognitive impairment and sleep problems increase. Longitudinal, population-based studies can be used to investigate temporal relationships between sleep and cognition.
In Vitro Studies on Odontogenic Tumors
Ameloblastomas are uncommon benign neoplasms of the jaws. They originate from dental epithelial cells, but they are not capable of mineralizing or forming enamel. The study of these tumors is limited to live tissue collected from patients during scheduled surgery. Ameloblastomas grow slowly in vivo and this property is translated to their behavior in vitro. Here, we describe the methods to culture ameloblastomas in organotypic cultures, as well as to isolate stem/progenitor cells from these tumors.
An Ultraviolet-optical Flare from the Tidal Disruption of a Helium-rich Stellar Core
The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.
No Association Between Conventional Brain MR Imaging and Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis
BACKGROUND AND PURPOSE:CCSVI has been reported to occur at high frequency in MS. Its significance in relation to MR imaging parameters also needs to be determined, both in patients with MS and HCs. Therefore, this study determined the associations of CCSVI and conventional MR imaging outcomes in patients with MS and in HCs.MATERIALS AND METHODS:T2, T1, and gadolinium lesion number, LV, and brain atrophy were assessed on 3T MR imaging in 301 subjects, of whom 162 had RRMS, 66 had secondary-progressive MS subtype, and 73 were HCs. CCSVI was assessed using extracranial and transcranial Doppler evaluation. The MR imaging measure differences were explored with 27 borderline cases for CCSVI, added to both the negative and positive CCSVI groups to assess sensitivity of the results of these cases.RESULTS:No significant differences between subjects with and without CCSVI were found in any of the individual diagnostic subgroups or MS disease subtypes for lesion burden and atrophy measures, independently of the CCSVI classification criteria used, except for a trend for higher T2 lesion number (irrespective of how borderline cases were classified) and lower brain volume (when borderline cases were included in the positive group) in patients with RRMS with CCSVI. No CCSVI or MR imaging differences were found between 26 HCs with, or 47 without, a familial relationship.CONCLUSIONS:CCSVI is not associated with more severe lesion burden or brain atrophy in patients with MS or in HCs.
Early Sucking and Swallowing Problems As Predictors of Neurodevelopmental Outcome in Children with Neonatal Brain Injury: a Systematic Review
Aim Early sucking and swallowing problems may be potential markers of neonatal brain injury and assist in identifying those infants at increased risk of adverse outcomes, but the relation between early sucking and swallowing problems and neonatal brain injury has not been established. The aim of the review was, therefore, to investigate the relation between early measures of sucking and swallowing and neurodevelopmental outcomes in infants diagnosed with neonatal brain injury and in infants born very preterm (<32wks) with very low birthweight (<1500g), at risk of neonatal brain injury. Method We conducted a systematic review of English-language articles using CINAHL, EMBASE, and MEDLINE OVID (from 1980 to May 2011). Additional studies were identified through manual searches of key journals and the works of expert authors. Extraction of data informed an assessment of the level of evidence and risk of bias for each study using a predefined set of quality indicators. Results A total of 394 abstracts were generated by the search but only nine studies met the inclusion criterion. Early sucking and swallowing problems were present in a consistent proportion of infants and were predictive of neurodevelopmental outcome in infancy in five of the six studies reviewed. Limitations The methodological quality of studies was variable in terms of research design, level of evidence (National Health and Medical Research Council levels II, III, and IV), populations studied, assessments used and the nature and timing of neurodevelopmental follow-up. Conclusions Based upon the results of this review, there is currently insufficient evidence to clearly determine the relation between early sucking and swallowing problems and neonatal brain injury. Although early sucking and swallowing problems may be related to later neurodevelopmental outcomes, further research is required to delineate their value in predicting later motor outcomes and to establish reliable measures of early sucking and swallowing function.
Vascular Development During Distraction Osteogenesis Proceeds by Sequential Intramuscular Arteriogenesis Followed by Intraosteal Angiogenesis
Vascular formation is intimately associated with bone formation during distraction osteogenesis (DO). While prior studies on this association have focused on vascular formation locally within the regenerate, we hypothesized that this vascular formation, as well as the resulting osteogenesis, relies heavily on the response of the vascular network in surrounding muscular compartments. To test this hypothesis, the spatiotemporal sequence of vascular formation was assessed in both muscular and osseous compartments in a murine model of DO and was compared to the progression of osteogenesis. Micro-computed tomography (μCT) scans were performed sequentially, before and after demineralization, on specimens containing contrast-enhanced vascular casts. Image registration and subtraction procedures were developed to examine the co-related, spatiotemporal patterns of vascular and osseous tissue formation. Immunohistochemistry was used to assess the contributory roles of arteriogenesis (formation of large vessels) and angiogenesis (formation of small vessels) to overall vessel formation. Mean vessel thickness showed an increasing trend during the period of active distraction (p=0.068), whereas vessel volume showed maximal increases during the consolidation period (p=0.009). The volume of mineralized tissue in the regenerate increased over time (p<0.039), was correlated with vessel volume (r=0.59; p=0.025), and occurred primarily during consolidation. Immunohistological data suggested that: 1) the period of active distraction was characterized primarily by arteriogenesis in the surrounding muscle; 2) during consolidation, angiogenesis predominated in the intraosteal region; and 3) vessel formation proceeded from the surrounding muscle into the regenerate. These data show that formation of vascular tissue occurs in both muscular and osseous compartments during DO and that periods of intense osteogenesis are concurrent with those of angiogenesis. The results further suggest the presence of morphogenetic factors that coordinate the development of vascular tissues from the intramuscular compartment into the regions of osseous regeneration.
Sustained Translational Repression by EIF2α-P Mediates Prion Neurodegeneration
The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the α-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2α-P levels are seen in patients with Alzheimer's, Parkinson's and prion diseases, but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2α-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2α-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2α-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2α-P dephosphorylation, increased eIF2α-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders.
