3,035 research outputs found
Lactate Shuttles in Neuroenergetics—Homeostasis, Allostasis and Beyond
No full textUnderstanding brain energy metabolism—neuroenergetics—is becoming increasingly important as it can be identified repeatedly as the source of neurological perturbations. Within the scientific community we are seeing a shift in paradigms from the traditional neurocentric view to that of a more dynamic, integrated one where astrocytes are no longer considered as being just supportive, and activated microglia have a profound influence. Lactate is emerging as the “good guy,” contrasting its classical “bad guy” position in the now superseded medical literature. This review begins with the evolution of the concept of “lactate shuttles”; goes on to the recent shift in ideas regarding normal neuroenergetics (homeostasis)—specifically, the astrocyte–neuron lactate shuttle; and progresses to covering the metabolic implications whereby homeostasis is lost—a state of allostasis, and the function of microglia. The role of lactate, as a substrate and shuttle, is reviewed in light of allostatic stress, and beyond—in an acute state of allostatic stress in terms of physical brain trauma, and reflected upon with respect to persistent stress as allostatic overload—neurodegenerative diseases. Finally, the recently proposed astrocyte–microglia lactate shuttle is discussed in terms of chronic neuroinflammatory infectious diseases, using tuberculous meningitis as an example. The novelty extended by this review is that the directionality of lactate, as shuttles in the brain, in neuropathophysiological states is emerging as crucial in neuroenergetic
Author Reading: Mason Deaver
No full textAward-winning young adult author Mason Deaver is returning (virtually) to CWU to discuss their new book, The Ghosts We Keep.
This emotional, character-driven journey is about a nonbinary teenager grieving their first shattering loss and, moving forward, allowing that experience to be a guidepost for the relationships that are important to them...An unflinchingly honest story that doesn’t shy away from the complex emotions of grief but also offers a hopeful path forward for Liam and everyone else left behind in the wake of Ethan’s death. ~ Alaina Leary, Booklist
Brought to you by CWU Libraries and CWU Lion Rock Visiting Writers Series.https://digitalcommons.cwu.edu/libraryevents/1248/thumbnail.jp
An Agent-Based Spatially Explicit Epidemiological Model in MASON
No full textThis paper outlines the design and implementation of an agent-based epidemiological simulation system. The system was implemented in the MASON toolkit, a set of Java-based agent-simulation libraries. This epidemiological simulation system is robust and extensible for multiple applications, including classroom demonstrations of many types of epidemics and detailed numerical experimentation on a particular disease. The application has been made available as an applet on the MASON web site, and as source code on the author\'s web site.Epidemiology, Social Networks, Agent-Based Simulation, MASON Toolkit
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis
No full textBackground: In Africa, tuberculosis is generally regarded as persisting as one of the most devastating infectious diseases. The pediatric population is particularly vulnerable, with infection of the brain in the form of tuberculous meningitis (TBM) being the most severe manifestation. TBM is often difficult to diagnose in its early stages because of its non-specific clinical presentation. Of particular concern is that late diagnosis, and subsequent delayed treatment, leads to high risk of long-term neurological sequelae, and even death. Using advanced technology and scientific expertise, we are intent on further describing the biochemistry behind this devastating neuroinflammatory disease, with the goal of improving upon its early diagnosis.Method: We used the highly sensitive analytical platform of gas chromatography-mass spectrometry (GC-MS) to analyze amino acid profiles of cerebrospinal fluid (CSF) collected from a cohort of 33 South African pediatric TBM cases, compared to 34 controls.Results: Through the use of a stringent quality assurance procedure and various statistical techniques, we were able to confidently identify five amino acids as being significantly elevated in TBM cases, namely, alanine, asparagine, glycine, lysine, and proline. We found also in an earlier untargeted metabolomics investigation that alanine can be attributed to increased CSF lactate levels, and lysine as a marker of lipid peroxidation. Alanine, like glycine, is an inhibitory neurotransmitter in the brain. Asparagine, as with proline, is linked to the glutamate-glutamine cycle. Asparagine is associated with the removal of increased nitrites in the brain, whereas elevated proline coincides with the classic biochemical marker of increased CSF protein in TBM. All five discriminatory amino acids are linked to ammonia due to increased nitrites in TBM.Conclusion: A large amount of untapped biochemical information is present in CSF of TBM cases, of which amino acid profiling through GC-MS has potential in aiding in earlier diagnosis, and hence crucial earlier treatment
Miniaturized 1H-NMR method for analyzing limited-quantity samples applied to a mouse model of Leigh disease
No full textIntroduction
The analysis of limited-quantity samples remains a challenge associated with mouse models, especially for multi-platform metabolomics studies. Although inherently insensitive, the highly specific characteristics of nuclear magnetic resonance (NMR) spectroscopy make it an advantageous platform for global metabolite profiling, particularly in mitochondrial disease research.
Objectives
Show method equivalency between a well-established standard operating protocol (SOP) and our novel miniaturized 1H-NMR method.
Method
The miniaturized method was performed in a 2 mm NMR tube on a standard 500 MHz NMR spectrometer with a 5 mm triple-resonance inverse TXI probe at room temperature.
Results
Firstly, using synthetic urine spiked with low (50 µM), medium (250 µM) and high (500 µM) levels (n = 10) of nine standards, both the SOP and miniaturized method were shown to have acceptable precision (CV 0.95), except for taurine. Furthermore, statistical equivalence was shown using the two one-sided test. Secondly, pooled mouse quadriceps muscle extract was used to further confirm method equivalence (n = 3), as well as explore the analytical dynamics of this novel approach by analyzing more-concentrated versions of samples (up to 10× concentration) to expand identification of metabolites qualitatively, with quantitative linearity. Lastly, we demonstrate the new technique’s application in a pilot metabolomics study using minute soleus muscle tissue from a mouse model of Leigh syndrome using Ndufs4 KO mice.
Conclusion
We demonstrate method equivalency, supporting our novel miniaturized 1H-NMR method as a financially feasible alternative to cryoprobe technology—for limited-quantity biological samples in metabolomics studies that requires a volume one-tenth of the SO
Dark Commerce: How a New Illicit Economy Is Threatening Our Future
No full textA recording of a Mason Author Series talk by Louise Shelley, author of "Dark Commerce: How a New Illicit Economy Is Threatening Our Future" (Princeton University Press, 2018). Professor Shelley is the Omer L. and Nancy Hirst Professor of Public Policy, University Professor, and Director of the Terrorism, Transnational Crime and Corruption Center in the Schar School of Government at George Mason University
Tuberculous meningitis in infants and children: Insights from nuclear magnetic resonance metabolomics
No full textTuberculous meningitis (TBM) is a prevalent form of central nervous system tuberculosis (CNS-TB) and the most severe common form of bacterial meningitis in infants and children below the age of 13 years, especially in the Western Cape Province of South Africa. Research to identify markers for timely and accurate diagnosis and treatment outcomes remains high on the agenda for TBM, in respect of which the field of metabolomics is as yet largely unexploited. However, the national Department of Science and Technology (DST) recently established several biotechnology platforms at South African institutions, including one for metabolomics hosted at North-West University. We introduce this national platform for nuclear magnetic resonance (NMR) metabolomics by providing an overview of work on TBM. We focus on selected collaborative multidisciplinary approaches to this disease and conclude with the outcomes of an untargeted NMR metabolomics study of cerebrospinal fluid from TBM patients. This study enabled the formulation of a conceptual shuttle representing the unique metabolic plasticity of CNS metabolism towards the energy requirements for the microglia-driven neuroinflammatory responses, of which TBM is one example. From insights generated by this explorative NMR metabolomics investigation, we propose directions for future in-depth research strategies to address this devastating disease. In our view, the timely initiative of the DST, the operational expertise in metabolomics now available and the potential for involving national and international networks in this field of research offers remarkable opportunities for the future of metabolomics in South Africa and for an ever greater understanding of disease mechanisms
Oral history interview with Michael Mason
No full textMichael Mason, an author and journalist with roots in Tulsa, Oklahoma, describes his childhood in the 1970s and 1980s and the hard times that came along with being Hispanic in Tulsa during that time. Mason shares that reading became his escape and explains how that influenced his decision to major in English in college. He talks about his various jobs from advertising to being a psychological technician at a hospital. Mason discusses the creation of This Land, a website for high quality journalism. He also talks about the intricacies when writing about Oklahoma and how there are so many untold stories.The Deep Roots: Oklahoma Authors Collection is a series of interviews with authors who discuss their lives, work, and creative processes
(1)H NMR spectral identification of medication in cerebrospinal fluid of pediatric meningitis
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The Evolution of Courses in Evolutionary Medicine
No full textLOCATION: Dewberry Hall, Johnson Center (Ground Floor); Group B 4:45-5:15pm
Evolutionary perspectives on disease first began to be formally introduced in courses in the 1990s, with the publication of Why We Get Sick (Nesse and Williams, 1994), although medical anthropologists have been taking a biocultural approach towards studying health since at least the 1960s (meanthro.net) and biological anthropologists formalized paleopathology as a field in 1973 (paleopathologyassociation.wildapricot.org). The author began teaching an undergraduate course on evolutionary medicine, paleopathology, and demography in 2002. The course has evolved into two course that have been taught almost continuously in three different institutions (SUNY Potsdam, St. Lawrence University, and George Mason University). These courses are continually evolving. The author now teaches both classes at undergraduate and graduate levels, and they serve as electives for students in anthropology, health and nutrition programs. This poster visually shows the evolution of aspects of the course(s) over time.
 
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