1,729 research outputs found
Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis
Background: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. Results: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated β-galactosidase (SA-β-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. Conclusions: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis
Energy dependence of multiplicity fluctuations in heavy ion collisions
The energy dependence of multiplicity fluctuations was studied for the most central Pb+Pb collisions at 20A, 30A, 40A, 80A and 158A GeV by the NA49 experiment at the CERN SPS. The multiplicity distribution for negatively and positively charged hadrons is significantly narrower than Poisson one for all energies. No significant structure in energy dependence of the scaled variance of multiplicity fluctuations is observed. The measured scaled variance is lower than the one predicted by the grand-canonical formulation of the hadron-resonance gas model. The results for scaled variance are in approximate agreement with the string-hadronic model UrQMD
Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection
The molecular mechanisms that drive mucosal T helper type 2 (T[subscript H]2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T[subscript H]2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T[subscript H]2 responses
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector
A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13 TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
Методы и механизмы геттерирования кремниевых структур в производстве интегральных микросхем
Увеличение степени интеграции элементной базы предъявляет все более жесткие требования к уменьшению концентрации загрязняющих примесей и окислительных дефектов упаковки в исходных кремниевых пластинах с ее сохранением в технологическом цикле изготовления ИМС. Это обуславливает высокую актуальность применения геттерирования в современной технологии микроэлектроники. В статье рассмотрены существующие методы геттерирования кремниевых пластин и механизмы их протекания.Збільшення ступеня інтеграції елементної бази пред'являє все більш жорсткі вимоги до зменшення концентрації забруднюючих домішок та окислювальних дефектів упаковки у вихідних кремнієвих пластинах за її збереження у технологічному циклі виготовлення ІМС. Це обумовлює високу актуальність застосування гетерування в сучасній технології мікроелектроніки. Розглянуто існуючі методи гетерування кремнієвих пластин та розглянуто механізми їх перебігу.Increasing the degree of integration of hardware components imposes more stringent requirements for the reduction of the concentration of contaminants and oxidation stacking faults in the original silicon wafers with its preservation in the IC manufacturing process cycle. This causes high relevance of the application of gettering in modern microelectronic technology. The existing methods of silicon wafers gettering and the mechanisms of their occurrence are considered
Impulsivity as a vulnerability factor for poor addiction treatment outcomes: A review of neurocognitive findings among individuals with substance use disorders
The support of the Special Research Fund of Ghent University (Belgium) is gratefully acknowledged.With the current review, we explore the hypothesis that individual differences in neurocognitive aspects of impulsivity (i.e., cognitive and motor disinhibition, delay discounting and impulsive decision-making) among individuals with a substance use disorder are linked to unfavorable addiction treatment outcomes, including high drop-out rates and difficulties in achieving and maintaining abstinence. A systematic review of the literature was carried out using PubMed, PsycINFO and Web of Knowledge searches. Twenty-five unique empirical papers were identified and findings were considered in relation to the different impulsivity dimensions. Although conceptual/methodological heterogeneity and lack of replication are key limitations of studies in this area, findings speak for a prominent role of cognitive disinhibition, delay discounting and impulsive decision-making in the ability to successfully achieve and maintain abstinence during and following addiction treatment. In contrast, indices of motor disinhibition appear to be unrelated to abstinence levels. Whereas the relationship between impulsivity and treatment retention needs to be examined more extensively, preliminary evidence suggests that impulsive/risky decision-making is unrelated to premature treatment drop-out among individuals with a substance use disorder. The reviewed findings are discussed in terms of their clinical implications.Special Research Fund of Ghent University (Belgium
Fatty Acid and Peptide Profiles in Plasma Membrane and Membrane Rafts of PUFA Supplemented RAW264.7 Macrophages
The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers
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