Predator-prey relationships among isolates of Salmonella enterica serovar typhimurium

Abstract only availableWhen two genetically related (but not identical) strains of Salmonella enterica serovar Typhimurium are grown together in the same culture, there is a tendency for competition to occur as nutrients deplete, possibly causing one strain to outgrow another. The Cancer Research Center has access to thousands of strains of Salmonella that have been sealed and stored under harsh environmental conditions for almost forty years. Our goal is to explore mutations that have arisen among these archived strains, and to test whether these mutations would provide a selective advantage over non-archived S. Typhimurium. We tested for selective advantages by competing different combinations of archived and non-archived strains in liquid media. This was done by selecting two different strains, preparing them in 1:100 ratios, and recording changes in population over a two to four week period. In every competition, the archival strain outgrew the non-archival when initially in minority. From our data, we can conclude that these archived strains must have gained some phenotypic qualities that provide additional fitness under environmental pressure. Further research might reveal information on specific phenotypic characteristics that our Salmonella strains may have utilized to survive under such nutrient-poor conditions.Life Sciences Undergraduate Research Opportunity Progra

Automated detection of breast cancer using SAXS data and wavelet features

The overarching goal of this project was to improve breast cancer screening protocols first by collecting small angle x-ray scattering (SAXS) images from breast biopsy tissue, and second, by applying pattern recognition techniques as a semi-automatic screen. Wavelet based features were generated from the SAXS image data. The features were supplied to a classifier, which sorted the images into distinct groups, such as “normal” and “tumor”. The main problem in the project was to find a set of features that provided sufficient separation for classification into groups of “normal” and “tumor.” In the original SAXS patterns, information useful for classification was obscured. The wavelet maps allowed new scale-based information to be uncovered from each SAXS pattern. The new information was subsequently used to define features that allowed for classification. Several calculations were tested to extract useful features from the wavelet decomposition maps. The wavelet map average intensity feature was selected as the most promising feature. The wavelet map intensity feature was improved by using pre-processing to remove the high central intensities from the SAXS patterns, and by using different wavelet bases for the wavelet decomposition. The investigation undertaken for this project showed very promising results. A classification rate of 100% was achieved for distinguishing between normal samples and tumor samples. The system also showed promising results when tested on unrelated MRI data. In the future, the semi-automatic pattern recognition tool developed for this project could be automated. With a larger set of data for training and testing, the tool could be improved upon and used to assist radiologists in the detection and classification of breast lesions

Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age

Neurotropism and blood-brain barrier involvement in COVID-19

The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists despite the progress of vaccination and increased natural immunity. SARS-CoV-2 is associated not only with pneumonia and acute respiratory distress, but also with many symptoms related to the central nervous system (CNS), including loss of the sense of taste and smell, headache, convulsions, visual disturbances, and impaired consciousness. In addition, the virus has been implicated in CNS diseases such as cerebral hemorrhage, cerebral infarction, and encephalitis. SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2), which is used by the virus as a cell entry receptor. Although the mechanism by which SARS-CoV-2 enters the brain is still unclear, the possibility of direct entry through the olfactory nerve tract and entry into the brain through the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) via blood circulation is indicated. The BBB likely serves as a site of entry for SARS-CoV-2 into the brain, and possibly contributes to the CNS symptoms of COVID-19 due to its dysfunction as a result of SARS-CoV-2 infection. The present review will focus on the effects of COVID-19 on the CNS, particularly on the BBB related cells involved

Lipopolysaccharide impairs amyloid β efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier

BACKGROUND: Defects in the low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein (Pgp) clearance of amyloid beta (Aβ) from brain are thought to contribute to Alzheimer\u27s disease (AD). We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS) results in impaired efflux of Aβ from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of Aβ clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood-brain barrier. METHODS: CD-1 mice aged between 6 and 8 weeks were treated with 3 intraperitoneal injections of 3 mg/kg LPS at 0, 6, and 24 hours and studied at 28 hours. 125I-Aβ1-42 or 125I-alpha-2-macroglobulin injected into the lateral ventricle of the brain (intracerebroventricular (ICV)) or into the jugular vein (intravenous (IV)) was used to quantify LRP-1-dependent partitioning between the brain vasculature and parenchyma and peripheral clearance, respectively. Disappearance of ICV-injected 14 C-inulin from brain was measured to quantify bulk flow of cerebrospinal fluid (CSF). Brain microvascular protein expression of LRP-1 and Pgp was measured by immunoblotting. Endothelial cell localization of LRP-1 was measured by immunofluorescence microscopy. Oxidative modifications to LRP-1 at the brain microvasculature were measured by immunoprecipitation of LRP-1 followed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine. RESULTS: We found that LPS: caused an LRP-1-dependent redistribution of ICV-injected Aβ from brain parenchyma to brain vasculature and decreased entry into blood; impaired peripheral clearance of IV-injected Aβ; inhibited reabsorption of CSF; did not significantly alter brain microvascular protein levels of LRP-1 or Pgp, or oxidative modifications to LRP-1; and downregulated LRP-1 protein levels and caused LRP-1 mislocalization in cultured brain endothelial cells. CONCLUSIONS: These results suggest that LRP-1 undergoes complex functional regulation following systemic inflammation which may depend on cell type, subcellular location, and post-translational modifications. Our findings that systemic inflammation causes deficits in both Aβ transport and bulk flow like those observed in AD indicate that inflammation could induce and promote the disease

The MoxFo initiative-Mechanisms of action: Biomarkers in multiple sclerosis exercise studies

background: as exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. however, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established.objective: establish recommendations for future mechanistic exercise studies in MS.Methods: In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research.results: we concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies.conclusion: the resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches

Pitavastatin Ameliorates Lipopolysaccharide-Induced Blood-Brain Barrier Dysfunction

Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood-brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/mL, 24 h) increased the permeability and lowered the transendothelial electrical resistance of the BBB, and the co-administration of PTV prevented these effects. LPS increased the release of interleukin-6, granulocyte colony-stimulating factor, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and regulated on activation, normal T-cell expressed and secreted from the BBB model. PTV inhibited the LPS-induced release of these cytokines. These results suggest that PTV can ameliorate LPS-induced BBB dysfunction, and these effects might be mediated through the inhibition of LPS-induced cytokine production. Clinically, therapeutic approaches using statins combined with novel strategies need to be designed. Our present finding sheds light on the pharmacological significance of statins in the treatment of central nervous system diseases

Cardiorespiratory Fitness and Attentional Control in the Aging Brain

A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness