35 research outputs found

    Chemically-Induced RAT Mesenchymal Stem Cells Adopt Molecular Properties of Neuronal-Like Cells but Do Not Have Basic Neuronal Functional Properties

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    Induction of adult rat bone marrow mesenchymal stem cells (MSC) by means of chemical compounds (β-mercaptoethanol, dimethyl sulfoxide and butylated hydroxyanizole) has been proposed to lead to neuronal transdifferentiation, and this protocol has been broadly used by several laboratories worldwide. Only a few hours of MSC chemical induction using this protocol is sufficient for the acquisition of neuronal-like morphology and neuronal protein expression. However, given that cell death is abundant, we hypothesize that, rather than true neuronal differentiation, this particular protocol leads to cellular toxic effects. We confirm that the induced cells with neuronal-like morphology positively stained for NF-200, S100, β-tubulin III, NSE and MAP-2 proteins. However, the morphological and molecular changes after chemical induction are also associated with an increase in the apoptosis of over 50% of the plated cells after 24 h. Moreover, increased intracellular cysteine after treatment indicates an impairment of redox circuitry during chemical induction, and in vitro electrophysiological recordings (patch-clamp) of the chemically induced MSC did not indicate neuronal properties as these cells do not exhibit Na+ or K+ currents and do not fire action potentials. Our findings suggest that a disruption of redox circuitry plays an important role in this specific chemical induction protocol, which might result in cytoskeletal alterations and loss of functional ion-gated channels followed by cell death. Despite the neuronal-like morphology and neural protein expression, induced rat bone marrow MSC do not have basic functional neuronal properties, although it is still plausible that other methods of induction and/or sources of MSC can achieve a successful neuronal differentiation in vitro

    Long-Range Temporal Correlations Reflect Treatment Response in the Electroencephalogram of Patients with Infantile Spasms

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    Infantile spasms syndrome is an epileptic encephalopathy in which prompt diagnosis and treatment initiation are critical to therapeutic response. Diagnosis of the disease heavily depends on the identification of characteristic electroencephalographic (EEG) patterns, including hypsarrhythmia. However, visual assessment of the presence and characteristics of hypsarrhythmia is challenging because multiple variants of the pattern exist, leading to poor inter-rater reliability. We investigated whether a quantitative measurement of the control of neural synchrony in the EEGs of infantile spasms patients could be used to reliably distinguish the presence of hypsarrhythmia and indicate successful treatment outcomes. We used autocorrelation and Detrended Fluctuation Analysis (DFA) to measure the strength of long-range temporal correlations in 21 infantile spasms patients before and after treatment and 21 control subjects. The strength of long-range temporal correlations was significantly lower in patients with hypsarrhythmia than control patients, indicating decreased control of neural synchrony. There was no difference between patients without hypsarrhythmia and control patients. Further, the presence of hypsarrhythmia could be classified based on the DFA exponent and intercept with 92% accuracy using a support vector machine. Successful treatment was marked by a larger increase in the DFA exponent compared to those in which spasms persisted. These results suggest that the strength of long-range temporal correlations is a marker of pathological cortical activity that correlates with treatment response. Combined with current clinical measures, this quantitative tool has the potential to aid objective identification of hypsarrhythmia and assessment of treatment efficacy to inform clinical decision-making

    Pandemic products and volatile chemical emissions

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    The recent pandemic (COVID-19) has seen a sweeping and surging use of products intended to clean and disinfect, such as air sprays, hand sanitizers, and surface cleaners, many of which contain fragrance. However, exposure to fragranced cleaning products has been associated with adverse effects on human health. Products can emit a range of volatile chemicals, including some classified as hazardous, but relatively few ingredients are disclosed to the public. Thus, relatively little is known about the specific emissions from these products. This study investigates the volatile organic compounds (VOCs) emitted from “pandemic products” that are being used frequently and extensively in society. In addition, among these emissions, this study identifies potentially hazardous compounds, compares so-called green and regular versions of products, and examines whether ingredients are disclosed to the public. Using gas chromatography/mass spectrometry, 26 commonly used pandemic products, including 13 regular and 13 so-called green versions, were analyzed for their volatile emissions. Product types included hand sanitizers, air disinfectants, multipurpose cleaners, and handwashing soap. All products were fragranced. The analyses found the products collectively emitted 399 VOCs with 127 VOCs classified as potentially hazardous. All products emitted potentially hazardous compounds. Comparing regular products and green products, no significant difference was found in the emissions of the most prevalent compounds. Further, among the 399 compounds emitted, only 4% of all VOCs and 11% of potentially hazardous VOCs were disclosed on any product label or safety data sheet. This study reveals that pandemic products can generate volatile emissions that could pose risks to health, that could be unrecognized, and that could be reduced, such as by using fragrance-free versions of products

    Numerical simulation of single-sided natural ventilation: ‎Impacts of balconies opening and depth scale on indoor ‎environment ‎

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    Heating Ventilation and Air Conditioning (HVAC), including, Mechanical ventilation (MV) in the building sector accounts for around 40% of electricity consumption and a large percentage of Greenhouse Gas (GHG) emissions. Natural ventilation (NV), as an alternative method, assist in decreasing energy consumption as well as harmful emissions. Balconies, a common architectural element in high rise residential buildings, could enhance NV and reduce reliance on mechanical ventilation in cooling dominant climates. Indoor air velocity (IAV) and distribution due to NV is less predictable than MV, and the impacts of balcony geometry on IAV and distribution profile have not yet been classified. This study, focusing on single-sided ventilation apartments, seeks to determine to what extent balcony depth and door opening area impacts on the indoor environment of the attached living area. For this, 3D – steady-state Computational Fluid Dynamics (CFD) simulations were conducted using ANSYS Fluent. The simulation results were validated against measured data in a full-scale experimental study in a residential building in subtropical Brisbane, Australia. Five different openings and nine depth scenarios were modelled, with results showing variances in indoor mean air velocity and temperature. The outcomes suggest that further research on the indoor distribution of temperature and air velocity may provide further clarity on the impact of balcony geometry on occupant comfort through NV

    Numerical simulation of single-sided natural ventilation: ‎Impacts of balconies opening and depth scale on indoor ‎environment ‎

    Get PDF
    Heating Ventilation and Air Conditioning (HVAC), including, Mechanical ventilation (MV) in the building sector accounts for around 40% of electricity consumption and a large percentage of Greenhouse Gas (GHG) emissions. Natural ventilation (NV), as an alternative method, assist in decreasing energy consumption as well as harmful emissions. Balconies, a common architectural element in high rise residential buildings, could enhance NV and reduce reliance on mechanical ventilation in cooling dominant climates. Indoor air velocity (IAV) and distribution due to NV is less predictable than MV, and the impacts of balcony geometry on IAV and distribution profile have not yet been classified. This study, focusing on single-sided ventilation apartments, seeks to determine to what extent balcony depth and door opening area impacts on the indoor environment of the attached living area. For this, 3D – steady-state Computational Fluid Dynamics (CFD) simulations were conducted using ANSYS Fluent. The simulation results were validated against measured data in a full-scale experimental study in a residential building in subtropical Brisbane, Australia. Five different openings and nine depth scenarios were modelled, with results showing variances in indoor mean air velocity and temperature. The outcomes suggest that further research on the indoor distribution of temperature and air velocity may provide further clarity on the impact of balcony geometry on occupant comfort through NV

    Bax/Bak-dependent release of DDP/TIMM8a promotes Drp-1-mediated mitochondrial fission and mitoptosis during programmed cell death.

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    SummaryMitochondrial morphology within cells is controlled by precisely regulated rates of fusion and fission [1–4]. During programmed cell death (PCD), mitochondria undergo extensive fragmentation [5–7] and ultimately caspase-independent elimination through a process known as mitoptosis [8]. Though this increased fragmentation is due to increased fission through the recruitment of the dynamin-like GTPase Drp1 to mitochondria [9, 10], as well as to a block in mitochondrial fusion [11, 12], cellular mechanisms underlying these processes remain unclear. Here, we describe a mechanism for the increased mitochondrial Drp1 levels and subsequent stimulation of mitochondrial fission seen during PCD. We observed Bax/Bak-mediated release of DDP/TIMM8a, a mitochondrial intermembrane space (IMS) protein [13, 14], into the cytoplasm, where it binds to and promotes the mitochondrial redistribution of Drp1, a mediator of mitochondrial fission. Using both loss- and gain-of-function assays, we also demonstrate that the Drp1- and DDP/TIMM8a-dependent mitochondrial fragmentation observed during PCD is an important step in mitoptosis, which in turn is involved in caspase-independent cell death. Thus, following Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP), IMS proteins released comprise not only apoptogenic factors such as cytochrome c involved in caspase activation [15, 16] but also DDP/TIMM8a, which activates Drp1-mediated fission to promote mitochondrial fragmentation and subsequently elimination during PCD
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