K. Seidel, J. Vinet, W. F. A. den Dunnen, E. R. Brunt, M. Meister, A. Boncoraglio, M. P. Zijlstra, H. W. G. M. Boddeke, U. Rüb, H. H. Kampinga and S. Carra (2012) Neuropathology and Applied ...Neurobiology38, 39–53
The HSPB8‐BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases
Aims: HSPB8 is a small heat shock protein that forms a complex with the co‐chaperone BAG3. Overexpression of the HSPB8‐BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation‐prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8‐BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate‐prone protein‐mediated toxicity. Here we analysed HSPB8‐BAG3 expression levels in post‐mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Methods: Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post‐mortem brain tissues, respectively. Results: In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8‐BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates. Conclusions: We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis.
Highlights • TAE as add-on to percutaneous RFA is feasible, safe, and very effective. • State-of-the-art embolization materials include tightly-size-calibrated microspheres. • MWA, cryoablation and ...IRE are TA systems beyond RFA. • Visible beads rank among the most promising innovative embolization materials. • Software-based solutions will be increasingly important for treatment guidance.
Results of a search for new physics in final states with an energetic jet and large missing transverse momentum are reported. The search uses proton-proton collision data corresponding to an ...integrated luminosity of 139 fb−1 at a center-of-mass energy of 13 TeV collected in the period 2015–2018 with the ATLAS detector at the Large Hadron Collider. Compared to previous publications, in addition to an increase of almost a factor of four in the data size, the analysis implements a number of improvements in the signal selection and the background determination leading to enhanced sensitivity. Events are required to have at least one jet with transverse momentum above 150 GeV and no reconstructed leptons (e , μ or τ) or photons. Several signal regions are considered with increasing requirements on the missing transverse momentum starting at 200 GeV. Overall agreement is observed between the number of events in data and the Standard Model predictions. Model-independent 95% confidence-level limits on visible cross sections for new processes are obtained in the range between 736 fb and 0.3 fb. Results are also translated into improved exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, supersymmetric particles in several compressed scenarios, axionlike particles, and new scalar particles in dark-energy-inspired models. In addition, the data are translated into bounds on the invisible branching ratio of the Higgs boson.
We report on experiments in which we study cavitation resulting from electrons in liquid helium. Electrons are introduced into the liquid by a radioactive source. After an electron comes to rest in ...the liquid, it forces open a small cavity referred to as an electron bubble. To study cavitation, a sound pulse is generated by means of a hemispherical piezoelectric transducer producing a large-amplitude pressure oscillation at the acoustic focus. If an electron is in the vicinity of the focus and the negative-going pressure swing exceeds a critical value, a cavitation bubble is produced which can be detected by light scattering. Two distinct critical pressures
P
el
and
P
rare
have been measured. The first corresponds to cavitation resulting from the application of a reduced pressure to liquid containing an electron which has already formed an electron bubble. The second is the critical pressure needed to lead to cavitation when an electron enters the liquid at a time and place where there is already a reduced pressure. We have measured these two pressures as a function of temperature and consider possible explanations for the difference between them. In addition to these clearly seen cavitation thresholds, there are some cavitation events that have been detected with a threshold that is at an even smaller negative pressure than
P
el
and
P
rare
.
Aerosol aerodynamic particle size is known to affect deposition patterns of inhaled aerosol particles, as well as the virulence of inhaled bioaerosol particles. While a significant amount of work has ...been performed to describe the deposition of aerosol particles in the human respiratory tract, only a limited amount of work has been performed to describe the deposition of aerosol particles in the respiratory tract of nonhuman primates, an animal model commonly utilized in pharmacological and toxicological studies, especially in the biodefense field. In this study, anesthetized rhesus macaques inhaled radiolabeled aerosols with MMADs of 1.7, 3.6, 7.4 and 11.8 µm to characterize regional deposition patterns. The results demonstrate that the regional deposition pattern shifts as particle size increases, with greater deposition in more proximal regions of the respiratory tract and decreased deposition in the pulmonary region. The results of this study extend the findings of previous studies which demonstrated a similar shift in the deposition pattern as a function of particle size by providing greater resolution of deposition patterns. These data on regional deposition patterns provide a starting point to begin to explore potential mechanisms responsible for the differences in virulence of infectious bioaerosols as a function of particle size and deposition pattern reported in previous studies. Additionally, the data are useful to assess the performance of various deposition models that have been published in the literature.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with inborn errors of immunity or DNA repair defects are at significant risk of developing malignancy and this complication of their underlying condition represents a substantial cause of ...morbidity and mortality. Whilst this risk is increasingly well-recognized, our understanding of the causative mechanisms remains incomplete. Diagnosing cancer is challenging in the presence of underlying co-morbidities and frequently other inflammatory and lymphoproliferative processes. We lack a structured approach to management despite recognizing the competing challenges of poor response to therapy and increased risk of toxicity. Finally, clinicians need guidance on how to screen for malignancy in many of these predisposing immunodeficiencies. In order to begin to address these challenges, we brought together representatives of European Immunology and Pediatric Haemato-Oncology to define the current state of our knowledge and identify priorities for clinical and research development. We propose key developmental priorities which our two communities will need to work together to address, collaborating with colleagues around the world.
A search for charginos and neutralinos at the Large Hadron Collider using fully hadronic final states and missing transverse momentum is reported. Pair-produced charginos or neutralinos are explored, ...each decaying into a high-pT Standard Model weak boson. Fully hadronic final states are studied to exploit the advantage of the large branching ratio, and the efficient rejection of backgrounds by identifying the high-pT bosons using large-radius jets and jet substructure information. An integrated luminosity of 139 fb−1 of proton-proton collision data collected by the ATLAS detector at a center-of-mass energy of 13 TeV is used. No significant excess is found beyond the Standard Model expectation. Exclusion limits at the 95% confidence level are set on wino or higgsino production with various assumptions about the decay branching ratios and the type of lightest supersymmetric particle. A wino (higgsino) mass up to 1060 (900) GeV is excluded when the lightest supersymmetry particle mass is below 400 (240) GeV and the mass splitting is larger than 400 (450) GeV. The sensitivity to high-mass winos and higgsinos is significantly extended relative to previous LHC searches using other final states.
Euclid preparation Bodendorf, C.; Grupp, F.; Hormuth, F. ...
Astronomy and astrophysics (Berlin),
06/2022, Letnik:
662
Journal Article
Recenzirano
Odprti dostop
Euclid
will be the first space mission to survey most of the extragalactic sky in the 0.95–2.02 µm range, to a 5
σ
point-source median depth of 24.4 AB mag. This unique photometric dataset will find ...wide use beyond
Euclid’s
core science. In this paper, we present accurate computations of the Euclid
Y
E
,
J
E
, and
H
E
passbands used by the Near-Infrared Spectrometer and Photometer (NISP), and the associated photometric system. We pay particular attention to passband variations in the field of view, accounting for, among other factors, spatially variable filter transmission and variations in the angle of incidence on the filter substrate using optical ray tracing. The response curves’ cut-on and cut-off wavelengths – and their variation in the field of view – are determined with ~0.8 nm accuracy, essential for the photometric redshift accuracy required by
Euclid.
After computing the photometric zero points in the AB mag system, we present linear transformations from and to common ground-based near-infrared photometric systems, for normal stars, red and brown dwarfs, and galaxies separately. A
Python
tool to compute accurate magnitudes for arbitrary passbands and spectral energy distributions is provided. We discuss various factors, from space weathering to material outgassing, that may slowly alter
Euclid
’s spectral response. At the absolute flux scale, the
Euclid
in-flight calibration program connects the NISP photometric system to
Hubble
Space Telescope spectrophotometric white dwarf standards; at the relative flux scale, the chromatic evolution of the response is tracked at the milli-mag level. In this way, we establish an accurate photometric system that is fully controlled throughout
Euclid’s
lifetime.
CLTA4 is relevant for FOXP3+Treg cells, and the link between skewed X chromosome inactivation (XCI) and autoimmunity is recognized. The observation of immune dysregulation polyendocrinopathy ...enteropathy X-linked syndrome and multiorgan endocrine autoimmune phenomena in various members of one family, associated with a CTLA4 polymorphism and skewed XCI, provides an in vivo model of how mechanisms of immune dysregulation may cooperate.
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