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"Courtney, Michael"
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Working toward exposure thresholds for blast-induced traumatic brain injury: Thoracic and acceleration mechanisms
Research in blast-induced lung injury resulted in exposure thresholds that are useful in understanding and protecting humans from such injury. Because traumatic brain injury (TBI) due to blast exposure has become a prominent medical and military problem, similar thresholds should be identified that can put available research results in context and guide future research toward protecting war fighters as well as diagnosis and treatment. At least three mechanical mechanisms by which the blast wave may result in brain injury have been proposed—a thoracic mechanism, head acceleration, and direct cranial transmission. These mechanisms need not be mutually exclusive. In this study, likely regions of interest for the first two mechanisms based on blast characteristics (positive pulse duration and peak effective overpressure) are developed using available data from blast experiments and related studies, including behind-armor blunt trauma and ballistic pressure wave studies. These related studies are appropriate to include because blast-like pressure waves are produced that result in neurological effects like those caused by blast. Results suggest that injury thresholds for each mechanism are dependent on blast conditions, and that under some conditions, more than one mechanism may contribute. There is a subset of blast conditions likely to result in TBI due to head acceleration and/or a thoracic mechanism without concomitant lung injury. These results can be used to guide experimental designs and compare additional data as they become available. Additional data are needed before actual probabilities or severity of TBI for a given exposure can be described.
Journal Article
Nine Marvel super hero tales : featuring stories from Avengers, Spider-Man, Guardians of the Galaxy
A collection of action-packed tales featuring everyone's favorite superheroes.
BOOK
Resilient reporting
This book examines how election news reporting has changed over the last half century in Ireland by means of a unique dataset involving 25m words from newspapers as well as radio and television coverage. The authors examine reporting in terms of framing, tone and the distribution of coverage.They also focus on how the economy has affected election coverage as well as media reporting of leaders and personalities, gender and the effect of the commercial basis of media outlets. The findings - drawn from a machine learning computer system involving a huge content analysis study - will interest academics as well as politicians and policymakers internationally.
eBook
Blast-Associated Shock Waves Result in Increased Brain Vascular Leakage and Elevated ROS Levels in a Rat Model of Traumatic Brain Injury
Blast-associated shock wave-induced traumatic brain injury (bTBI) remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20-130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB) integrity following blast exposure. Reactive oxygen species (ROS) levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective therapeutic strategies that can prevent the resulting cascade of neurodegeneration.
Journal Article
The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline
Substantial progress in high-throughput metagenomic sequencing methodologies has enabled the characterisation of bacteria from various origins (for example gut and skin). However, the recently-discovered bacterial microbiota present within animal internal tissues has remained unexplored due to technical difficulties associated with these challenging samples.
We have optimized a specific 16S rDNA-targeted metagenomics sequencing (16S metabarcoding) pipeline based on the Illumina MiSeq technology for the analysis of bacterial DNA in human and animal tissues. This was successfully achieved in various mouse tissues despite the high abundance of eukaryotic DNA and PCR inhibitors in these samples. We extensively tested this pipeline on mock communities, negative controls, positive controls and tissues and demonstrated the presence of novel tissue specific bacterial DNA profiles in a variety of organs (including brain, muscle, adipose tissue, liver and heart).
The high throughput and excellent reproducibility of the method ensured exhaustive and precise coverage of the 16S rDNA bacterial variants present in mouse tissues. This optimized 16S metagenomic sequencing pipeline will allow the scientific community to catalogue the bacterial DNA profiles of different tissues and will provide a database to analyse host/bacterial interactions in relation to homeostasis and disease.
Journal Article
Resonance energy transfer sensitises and monitors in situ switching of LOV2-based optogenetic actuators
Engineered light-dependent switches provide uniquely powerful opportunities to investigate and control cell regulatory mechanisms. Existing tools offer high spatiotemporal resolution, reversibility and repeatability. Cellular optogenetics applications remain limited with diffusible targets as the response of the actuator is difficult to independently validate. Blue light levels commonly needed for actuation can be cytotoxic, precluding long-term experiments. We describe a simple approach overcoming these obstacles. Resonance energy transfer can be used to constitutively or dynamically modulate actuation sensitivity. This simultaneously offers on-line monitoring of light-dependent switching and precise quantification of activation-relaxation properties in intact living cells. Applying this approach to different LOV2-based switches reveals that flanking sequences can lead to relaxation times up to 11-fold faster than anticipated. In situ–measured parameter values guide the design of target-inhibiting actuation trains with minimal blue-light exposure, and context-based optimisation can increase sensitivity and experimental throughput a further 10-fold without loss of temporal precision.
Cellular optogenetics applications are limited by difficulties in quantification and blue light toxicity. Here the authors design LOV2-based switches that use resonance energy transfer to overcome these concerns.
Journal Article
Blood Microbiota Dysbiosis Is Associated with the Onset of Cardiovascular Events in a Large General Population: The D.E.S.I.R. Study
We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease.
D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35-0.70) whereas Pbac (1.56, 95%CI 1.12-2.15) was directly correlated.
Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease.
Journal Article
“Chickens in the Slaughterhouse” Police-Inflicted Trauma and Mental Health Consequences for an Urban African American LGBTQI+ Community
In this paper, we discuss qualitative findings drawn from a larger community-engaged project in a predominantly Black Midwestern city. Data collection for the project, which focused on the effects of policing on the city’s African American community, was carried out in collaboration with Black community organizations and an independent police oversight board. Using an intersectional queer politics lens, we present findings from a thematic analysis of field observations that focused on the city’s LGBTQI+ community. Major themes that emerged include the social context of Black LGBTQI+ oppression, the criminalization of the Black LGBTQI+ body, and mental health impact of policing experiences. Overall, we found that transgender and gender non-conforming experiences with police were particularly harmful. We conclude with insights into the strategies of resilience and resistance used by the community to navigate the impact police work has on their lived experience. Policy implications of our findings and the importance of queer politics to enable Black LGBTQI+ populations to access services and thrive, rather than survive are also addressed.
Journal Article
Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling
NMDA receptors (NMDAR) are glutamate-gated calcium channels that play pivotal roles in fundamental aspects of neuronal function. Dysregulated receptor function contributes to many disorders. Recruitment by NMDARs of calcium-dependent enzyme nNOS via PSD95 is seen as a key contributor to neuronal dysfunction. nNOS adaptor protein (NOS1AP), originally described as a competitor of PSD95:nNOS interaction, is regarded an inhibitor of NMDAR-driven nNOS function. In conditions of NMDAR hyperactivity such as excitotoxicity, one expects NOS1AP to be neuroprotective. Conditions of NMDAR hypoactivity, as thought to occur in schizophrenia, might be exacerbated by NOS1AP. Indeed GWAS have implicated NOS1AP and nNOS in schizophrenia. Several studies now indicate NOS1AP can mediate rather than inhibit NMDAR/nNOS-dependent responses, including excitotoxic signaling. Yet the concept of NOS1AP as an inhibitor of nNOS predominates in studies of human disease genetics. Here we review the experimental evidence to evaluate this apparent controversy, consider whether the known functions of NOS1AP might defend neurons against NMDAR dysregulation and highlight specific areas for future investigation to shed light on the functions of this adaptor protein.
Journal Article