5,989 research outputs found

    Mitochondria: It is all about energy

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    Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases

    The place where curses are manufactured : four poets of the Vietnam War

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    The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences

    Imagination as Thought in Aristotle\u27s De Anima

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    Aristotle appears to indicate in various passages in the De Anima that imagination is a kind of thought, and my thesis attempts to make some sense out of this claim. I examine three possible interpretations of the claim that imagination is a kind of thought and eliminate two of them. The first states that Aristotle only calls imagination a kind of thought in a superficial “in name only” sense. The second, more radical interpretation, identifies images as the most basic kind of thoughts. My final chapter defends a more moderate position—inspired by Avempace and the early Averroes—which steers between the superficial and radical interpretations, by construing the formal content of images as a sort of quasi-corporeal substrate for the generation of learned thoughts

    RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes

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    MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy. HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD). PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies. In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD. To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells. To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression. In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies

    Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention

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    a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by ..

    The Adirondack Chronology

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    The Adirondack Chronology is intended to be a useful resource for researchers and others interested in the Adirondacks and Adirondack history.https://digitalworks.union.edu/arlpublications/1000/thumbnail.jp

    SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS

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    In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures

    Validation of a Novel Screening Tool for Obstructive Sleep Apnoea in Bariatric Surgery Candidates

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    Undiagnosed obstructive sleep apnoea (OSA) is increasingly recognised as a serious post-operative risk with bariatric surgery. Demand for pre-operative screening for OSA in bariatric surgery candidates is rising and there is a need for simple, cost-effective screening methods to mitigate the stain on Sleep Services. WatchPAT is a relatively new device, which uses peripheral arterial tonometry rather than airflow to estimate the apnoea hypopnoea index (AHI). While WatchPAT use is increasing in the general sleep clinic population it has not yet been validated in patients with a BMI >35, i.e. the target population in bariatric surgery. The studies described in this thesis aim to validate WatchPAT against the clinical gold-standard in patients on the bariatric pathway and to assess patient acceptability of WatchPAT. 28 bariatric surgery candidates (22 female/6 male, mean ± SD age 44.1 ± 11.6 years, BMI 45.7 ± 7.5 kg/m2) wore WatchPAT 300 and Embletta MPR simultaneously for one night and the outcome measure, AHI was compared in the two devices. AHI was higher in WatchPAT than Embletta (Median (range) 23.5 (3.9-70.6) versus 11.7 (0.7-46.5) events per hour; z=-4.623, p=0.000). There was a strong positive correlation between WatchPAT and Embletta AHI measurements (r=0.849; p=0.000). Bland Altman plots revealed a systematic bias; differences diverging at higher AHI values. ROC plots were constructed for a range of AHI cut-offs; AUC was highest for an AHI ≄20 (0.986), ≄15 (0.947) and AHI ≄30 (0.979), while for AHI ≄5 the AUC was 0.850. 97% of respondents reported that WatchPAT would be acceptable to them if introduced into the bariatric surgery pathway. These results are similar to those in the non-bariatric sleep clinic population and suggest that WatchPAT may suitable for use in bariatric surgery patients requiring screening for OSA though further larger scale studies are needed to confirm these findings before incorporating into clinical guidelines

    Review on biomedical sensors, technologies, and algorithms for diagnosis of sleep-disordered breathing: Comprehensive survey

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    This paper provides a comprehensive review of available technologies for measurements of vital physiology related parameters that cause sleep disordered breathing (SDB). SDB is a chronic disease that may lead to several health problems and increase the risk of high blood pressure and even heart attack. Therefore, the diagnosis of SDB at an early stage is very important. The essential primary step before diagnosis is measurement. Vital health parameters related to SBD might be measured through invasive or non-invasive methods. Nowadays, with respect to increase in aging population, improvement in home health management systems is needed more than even a decade ago. Moreover, traditional health parameter measurement techniques such as polysomnography are not comfortable and introduce additional costs to the consumers. Therefore, in modern advanced self-health management devices, electronics and communication science are combined to provide appliances that can be used for SDB diagnosis, by monitoring a patient's physiological parameters with more comfort and accuracy. Additionally, development in machine learning algorithms provides accurate methods of analysing measured signals. This paper provides a comprehensive review of measurement approaches, data transmission, and communication networks, alongside machine learning algorithms for sleep stage classification, to diagnose SDB
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