Background
Alcohol use in pregnancy increases the risk of abnormal cardiac development, and excessive alcohol consumption in adults can induce cardiomyopathy, contractile dysfunction, and ...arrhythmias. Understanding molecular mechanisms underlying alcohol‐induced cardiac toxicity could provide guidance in the development of therapeutic strategies.
Methods
We have performed proteomic and bioinformatic analysis to examine protein alterations globally and quantitatively in cardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) treated with ethanol (EtOH). Proteins in both cell lysates and extracellular culture media were systematically quantitated.
Results
Treatment with EtOH caused severe detrimental effects on hiPSC‐CMs as indicated by significant cell death and deranged Ca2+ handling. Treatment of hiPSC‐CMs with EtOH significantly affected proteins responsible for stress response (e.g., GPX1 and HSPs), ion channel‐related proteins (e.g. ATP1A2), myofibril structure proteins (e.g., MYL2/3), and those involved in focal adhesion and extracellular matrix (e.g., ILK and PXN). Proteins involved in the TNF receptor‐associated factor 2 signaling (e.g., CPNE1 and TNIK) were also affected by EtOH treatment.
Conclusions
The observed changes in protein expression highlight the involvement of oxidative stress and dysregulation of Ca2+ handling and contraction while also implicating potential novel targets in alcohol‐induced cardiotoxicity. These findings facilitate further exploration of potential mechanisms, discovery of novel biomarkers, and development of targeted therapeutics against EtOH‐induced cardiotoxicity.
Treatment of human stem cell‐derived cardiomyocytes with ethanol results in cell death and abnormal Ca2+ handling. Proteomic profiling and bioinformatic analysis reveal that ethanol treatment affects the expression of proteins involved in oxidative stress, ion channels, myofibril structure, focal adhesion, extracellular matrix and TRAF2 signaling.
Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular ...change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to C(11)PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.
In this paper, advanced β-Ga2O3 TCAD simulation parameters and methodologies are presented by calibrating simulation setup to vertical junctionless multi-gate transistor experimental data. Through ...careful calibration, several important β-Ga2O3 device physics are identified. The effects of compensation doping and incomplete ionization of dopants are investigated. Electron Philips unified carrier mobility (PhuMob) model, which can capture the temperature effect, is used. We also show that interfacial traps possibly play no role on the non-ideal sub-threshold slope (SS) and short channel effect is the major cause of SS degradation. The breakdown mechanism of the junctionless Ga2O3 transistor is also discussed and is shown to be limited by channel punch-through in off-state. The calibrated models match experimental Capacitance-Voltage (CV) and Current-Voltage (IV) well and can be used to predict the electrical performance of novel β-Ga2O3 devices.
This work presents a physics of failure (POF) methodology coupling failure signatures with physico-chemical analyses. The aim is to work out electro-optical failure signatures located in packaged ...InGaN/GaN Multiple Quantum Wells Light Emitting Diodes (MQW LEDs). Electrical and optical characteristics performed after accelerated ageing tests (30
mA/85
°C/1500
h), confirm a 65% drop of optical power and an increase of one decade of leakage current spreading at the silicone oil/chip interfaces. Through measurements of silicone coating fluorescence emission spectra, we demonstrate that the polymer enlarges the LED emission spectrum and shifts central wavelength. This shift is related to silicone oil spectral instability and the central wavelength of packaged LED appears to be temperature insensitive. In this paper, we discriminate the degradation of bulk silicone oil responsible for optical losses from the polymer/chip interface inducing larger leakage current.
Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe
. The emission from GRBs comprises a short (typically tens of ...seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed
. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments
. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive
. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
•Cigarette smoke extract reduces division and increases apoptosis of Th1 effectors.•Cigarette smoke extract enhances Th1 cytokine production and T-bet expression.•Cigarette smoke extract mediates its ...impact directly on responding CD4 T cells.•Cigarette smoke extract drives terminal differentiation and restricts memory fate.
Although cigarette smoke is known to alter immune responses, whether and how CD4 T cells are affected is not well-described. We aimed to characterize how exposure to cigarette smoke extract impacts CD4 T cell effector generation in vitro under Th1-polarizing conditions. Our results demonstrate that cigarette smoke directly acts on CD4 T cells to impair effector expansion by decreasing division and increasing apoptosis. Furthermore, cigarette smoke enhances Th1-associated cytokine production and increases expression of the transcription factor T-bet, the master regulator of Th1 differentiation. Finally, we show that exposure to cigarette smoke extract during priming impairs the ability of effectors to form memory cells. Our findings thus demonstrate that cigarette smoke simultaneously enhances effector functions but promotes terminal differentiation of CD4 T cell effectors. This study may be relevant to understanding how smoking can both aggravate autoimmune symptoms and reduce vaccine efficacy.
En France, la gestion de la pêche en eau douce est généralement confiée aux associations de pêcheurs qui agissent sous le contrôle de l’Etat. Le Conseil Supérieur de la Pêche a développé une méthode ...synthétique d’élaboration de plans de gestion piscicole qui favorisent la reproduction naturelle et le maintien des populations sauvages. Ces plans s’appuient sur des opérations de protection des habitats et de restauration du milieu dont il convient d’évaluer la rentabilité sociale. Ce qui conduit à estimer la valeur du poisson sauvage (c’est à dire né dans le milieu naturel, de parents eux-mêmes sauvages). Cette valeur intègre deux composantes principales, une valeur d’usage qui dérive de la pratique de la pêche et une valeur de non-usage qui découle de son existence même et qui intéresse une population plus vaste que celle des seuls pêcheurs. Les bénéfices potentiels engendrés par la présence de poissons sauvages sont estimés par la méthode d’évaluation contingente. Les résultats empiriques sont basés sur un échantillon de 1 629 pêcheurs qui ont participé à une enquête postale. Le Consentement A Payer (CAP) pour le poisson sauvage est une fonction croissante du revenu, de la valeur du matériel et de la distance parcourue pour pêcher. De plus on note que les amateurs de brochets et de truites (espèces repères de l’étude) ainsi que ceux qui pêcheraient plus souvent s’il y avait du poisson sauvage ont, toutes choses égales, par ailleurs un CAP plus élevé. La valeur moyenne du CAP varie selon le modèle retenu de 50 F à 100 F par pêcheur et par an. Ce CAP correspond à un concept de valeur totale qui inclut une composante de valeur d’usage et de valeur de non-usage. Certains pêcheurs sont prêts à payer sans pour autant marquer une préférence pour la pêche au poisson sauvage. Leur CAP est associé à une valeur de non-usage et correspond à la valeur d’existence du poisson sauvage. Celle-ci est comprise entre 20 F et 50 F par pêcheur et par an. Un calcul simple montre que les bénéfices des pêcheurs sont du même ordre que les coûts de fonctionnement associés aux plans de gestion piscicole.
In France, angling societies are, under the supervision of the government, generally in charge of inland fisheries management. The National Council of Fishing has developed a series of guidelines to design management schemes which favour natural reproduction processes and the preservation of wild fish stocks. They rely on habitat protection and ecosystem restoration programmes involving public expenditures whose profitability has to be assessed. This leads to estimate the value of wild fish (born in the natural environment from parents wild fish themselves). This value integrates two main components, an use value which is derived from angling and a non use value which stems from the existence of wild fish and concerns a broader population than the anglers one. Potential benefits stemming from the existence of wild fish populations are estimated using the contingent valuation method. Empirical results are based on a sample of 1 629 anglers who participated in a mail survey. Willingness-To-Pay (WTP) for wild fish increases with income, cost of equipment and trip distance. Other things being equal, those preferring fish such as pike and trout (reference species of the study), and those preferring to angle wild fish are likely to pay an additional amount. Mean WTP ranges from FF 50 to FF 100 per year, depending on model specification. This money amount is associated with the concept of total value which includes a use and a non use component. Some anglers are willing to pay but are not interested in fishing wild fish. For these people, WTP states a non use value and is associated with the existence of wild fish. The corresponding amount is estimated to be between FF 20 and FF 50. A straightforward calculation shows that anglers’ potential benefits are of the same magnitude than the operating costs associated to management schemes.
An intrinsic gamma-ray burst afterglow
Long gamma-ray bursts (GRBs) are emitted by relativistic jets generated during the collapse of a massive star in a distant galaxy. The GRB itself lasts only a ...few seconds but is followed by an afterglow that can persist for hours or days. The H.E.S.S. Collaboration observed the afterglow of GRB 190829A, a nearby long GRB. The proximity of this burst allowed it to be detected at tera–electron volt energies that would otherwise be absorbed in the intergalactic medium. By analyzing the spectrum and light curve at x-ray and gamma-ray wavelengths, the authors show that the afterglow cannot be explained by standard models.
Science
, abe8560, this issue p.
1081
Observations of a nearby gamma-ray burst at tera–electron volt energies cannot be explained by standard models.
Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera–electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.
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