Publications by authors named "Mark Kirk"

Polyphenisms occur when phenotypic plasticity produces morphologically distinct phenotypes from the same genotype. Plasticity is maintained through fitness trade-offs which are conferred to different phenotypes under specific environmental contexts. Predicting the impacts of contemporary climate change on phenotypic plasticity is critical for climate-sensitive animals like amphibians, but elucidating the selective pressures maintaining polyphenisms requires a framework to control for all mechanistic drivers of plasticity.

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Fitness trade-offs are a foundation of ecological and evolutionary theory because trade-offs can explain life history variation, phenotypic plasticity, and the existence of polyphenisms. Using a 32-year mark-recapture dataset on lifetime fitness for 1093 adult Arizona tiger salamanders (Ambystoma mavortium nebulosum) from a high elevation, polyphenic population, we evaluated the extent to which two life history morphs (aquatic paedomorphs vs. terrestrial metamorphs) exhibited fitness trade-offs in breeding and body condition with respect to environmental variation (e.

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Studies predicting how the distribution of aquatic organisms will shift with climate change often use projected increases in air temperature or water temperature. However, the assumed correlations between water temperature change and air temperature change can be problematic, especially for mountainous, high elevation streams. Using stream fish assemblage data from 1,442 surveys across a mountain-plains gradient (Wyoming, USA; 1990-2018), we compared the responsiveness of thermal guilds, native status groups, and assemblage structure to projected climate warming from generalized air temperature models and stream-specific water temperature models.

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Monitoring long-term changes in aquatic biodiversity requires the effective use of historical data that were collected with different methods and varying levels of effort. Aggregating data into different spatial scales can control for such differences and provide a robust framework for monitoring distribution trends. We used a quantitative, multi-scale assessment to evaluate the potential drivers of distribution change for 60 fish species at three spatial scales, using 503 unique sampling events conducted between 1931 and 2019 in a stream biodiversity hotspot (French Creek, Pennsylvania, U.

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There is considerable variation among studies that evaluate how amphibian populations respond to global climate change. We used 23 years of annual survey data to test whether changes in climate have caused predictable shifts in the phenology and population characteristics of adult spotted salamanders (Ambystoma maculatum) during spring breeding migrations. Although we observed year-to-year correlation between seasonal climate variables and salamander population characteristics, there have not been long-term, directional shifts in phenological or population characteristics.

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Having sufficient medical countermeasures (MCMs) available for the treatment of acetylcholinesterase-inhibiting nerve agent poisoned patients following a mass chemical exposure is a challenge for communities. After stockpiles containing auto-injectors are exhausted, communities need to be aware of alternative pharmaceutical options. The Department of Homeland Security Chemical Defense Program convened a federal interagency working group consisting of first responders, clinicians, and experts from the fields of medical toxicology, pharmacology, and emergency management.

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A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes.

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Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM-derived cancer stem cells (GSCs).

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Most approaches toward chemical and radiological/nuclear (CRN) incidents focus on the clinical skills of the first receiver. These skills are certainly important and are addressed throughout this article. Management skills are often overlooked.

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Article Synopsis
  • The central nervous system is prone to neurodegenerative disorders like Alzheimer's, which lead to significant loss of nerve cells.
  • Stem cells can transform into various cell types, making them potential candidates for treating these disorders, although clinical success is still lacking.
  • A key challenge in applying stem cell therapy in clinical settings is the immune response that occurs after transplanting stem cells.
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Decontaminating patients who have been exposed to hazardous chemicals can directly benefit the patients' health by saving lives and reducing the severity of toxicity. While the importance of decontaminating patients to prevent the spread of contamination has long been recognized, its role in improving patient health outcomes has not been as widely appreciated. Acute chemical toxicity may manifest rapidly-often minutes to hours after exposure.

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DNA modifications, such as methylation and hydroxymethylation, are pivotal players in modulating gene expression, genomic imprinting, X-chromosome inactivation, and silencing repetitive sequences during embryonic development. Aberrant DNA modifications lead to embryonic and postnatal abnormalities and serious human diseases, such as cancer. Comprehensive genome-wide DNA methylation and hydroxymethylation studies provide a way to thoroughly understand normal development and to identify potential epigenetic mutations in human diseases.

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Background: Case-based discussion (CBD) is an established method for active learning in medical education. High-fidelity simulation has emerged as an important new educational technology. There is limited data from direct comparisons of these modalities.

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The majority of meningiomas are benign tumors associated with favorable outcomes; however, the less common aggressive variants with unfavorable outcomes often recur and may be due to subpopulations of less-differentiated cells residing within the tumor. These subpopulations of tumor cells have tumor-initiating properties and may be isolated from heterogeneous tumors when sorted or cultured in defined medium. We report the isolation and characterization of a population of tumor-initiating cells derived from an atypical meningioma.

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Background: Neurogenesis, the production of neural cell-types from neural stem cells (NSCs), occurs during development as well as within select regions of the adult brain. NSCs in the adult subependymal zone (SEZ) exist in a well-categorized niche microenvironment established by surrounding cells and their molecular products. The components of this niche maintain the NSCs and their definitive properties, including the ability to self-renew and multipotency (neuronal and glial differentiation).

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Drug-induced prolongation of the QT interval is frequently encountered after medication overdose. Such toxicity can result in degeneration to torsades de pointes (TdP) and require overdrive pacing. We present 3 cases in which intentional medication overdose resulted in QTc prolongation with subsequent degeneration to TdP.

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A central issue in stem cell biology is the determination of function and activity of differentiated stem cells, features that define the true phenotype of mature cell types. Commonly, physiological mechanisms are used to determine the functionality of mature cell types, including those of the nervous system. Calcium imaging provides an indirect method of determining the physiological activities of a mature cell.

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The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors.

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Recent advances in our understanding of lysosomal storage disorders (LSDs) may lead to new therapies to treat the neuronal ceroid-lipofuscinoses (NCLs). In this review, enzyme replacement therapy, gene therapy, cell-mediated therapy and pharmaceutical treatments are considered across the LSDs and extended to therapies for the NCLs. It is likely that a combination of approaches will produce the most beneficial clinical outcome for treatment of pathologies displayed by the NCLs.

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Recent studies show that adult neural tissues can harbor stem cells within unique niches. In the mammalian central nervous system, neural stem cell (NSC) niches have been identified in the dentate gyrus and the subventricular zone (SVZ). Stem cells in the well-characterized SVZ exist in a microenvironment established by surrounding cells and tissue components, including transit-amplifying cells, neuroblasts, ependymal cells, blood vessels, and a basal lamina.

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In the early part of chemical terrorism or hazardous materials events, protective actions and patient care require empirical decisions because reliable and accurate information may not be readily available. It has become increasingly important to identify reliable information resources that are the most likely to be accessed for information during these events. We sought to identify information resources that volunteer Emergency Medical Services (EMS) providers would use during a suspected chemical exposure.

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There is well-founded concern that a chemical or radioactive agent will at some point be used as a weapon of terror. There are several antidotes that, if used correctly in a timely fashion, can help lessen the harm caused by these agents. This article is meant to introduce the clinician to several such agents, along with the antidotes useful in the management of exposure to these.

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An accident or a deliberate terrorism attack releasing hazardous chemicals will create chaos, confusion, and seeming unpredictability that complicates the emergency response. Clinicians are challenged to urgently treat patients needing care, even before a chemical is confirmed. Emergency response planning that focuses on preparing for predictable challenges to the health care system and applies basic toxicologic principles to clinical decision-making can bring a sense of order to the chaos and provide medical care that will be best for the most victims of an incident.

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