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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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- Bercic, L., et al.
(author)
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Whistler instability driven by the sunward electron deficit in the solar wind High-cadence Solar Orbiter observations
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Journal article (peer-reviewed)abstract
- Context. Solar wind electrons play an important role in the energy balance of the solar wind acceleration by carrying energy into interplanetary space in the form of electron heat flux. The heat flux is stored in the complex electron velocity distribution functions (VDFs) shaped by expansion, Coulomb collisions, and field-particle interactions. Aims. We investigate how the suprathermal electron deficit in the anti-strahl direction, which was recently discovered in the near-Sun solar wind, drives a kinetic instability and creates whistler waves with wave vectors that are quasi-parallel to the direction of the background magnetic field.Methods. We combined high-cadence measurements of electron pitch-angle distribution functions and electromagnetic waves provided by Solar Orbiter during its first orbit. Our case study is based on a burst-mode data interval from the Electrostatic Analyser System (SWA-EAS) at a distance of 112 R-S (0.52 au) from the Sun, during which several whistler wave packets were detected by Solar Orbiter's Radio and Plasma Waves (RPW) instrument.Results. The sunward deficit creates kinetic conditions under which the quasi-parallel whistler wave becomes unstable. We directly test our predictions for the existence of these waves through solar wind observations. We find whistler waves that are quasi-parallel and almost circularly polarised, propagating away from the Sun, coinciding with a pronounced sunward deficit in the electron VDF. The cyclotron-resonance condition is fulfilled for electrons moving in the direction opposite to the direction of wave propagation, with energies corresponding to those associated with the sunward deficit.Conclusions. We conclude that the sunward deficit acts as a source of quasi-parallel whistler waves in the solar wind. The quasilinear diffusion of the resonant electrons tends to fill the deficit, leading to a reduction in the total electron heat flux.
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10. |
- Coll, M., et al.
(author)
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Towards Oxide Electronics: a Roadmap
- 2019
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In: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 482, s. 1-93
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Journal article (peer-reviewed)abstract
- At the end of a rush lasting over half a century, in which CMOS technology has been experiencing a constant and breathtaking increase of device speed and density, Moore’s law is approaching the insurmountable barrier given by the ultimate atomic nature of matter. A major challenge for 21st century scientists is finding novel strategies, concepts and materials for replacing silicon-based CMOS semiconductor technologies and guaranteeing a continued and steady technological progress in next decades. Among the materials classes candidate to contribute to this momentous challenge, oxide films and heterostructures are a particularly appealing hunting ground. The vastity, intended in pure chemical terms, of this class of compounds, the complexity of their correlated behaviour, and the wealth of functional properties they display, has already made these systems the subject of choice, worldwide, of a strongly networked, dynamic and interdisciplinary research community. Oxide science and technology has been the target of a wide four-year project, named Towards Oxide-Based Electronics (TO-BE), that has been recently running in Europe and has involved as participants several hundred scientists from 29 EU countries. In this review and perspective paper, published as a final deliverable of the TO-BE Action, the opportunities of oxides as future electronic materials for Information and Communication Technologies ICT and Energy are discussed. The paper is organized as a set of contributions, all selected and ordered as individual building blocks of a wider general scheme. After a brief preface by the editors and an introductory contribution, two sections follow. The first is mainly devoted to providing a perspective on the latest theoretical and experimental methods that are employed to investigate oxides and to produce oxide-based films, heterostructures and devices. In the second, all contributions are dedicated to different specific fields of applications of oxide thin films and heterostructures, in sectors as data storage and computing, optics and plasmonics, magnonics, energy conversion and harvesting, and power electronics.
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- Louarn, P., et al.
(author)
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Multiscale views of an Alfvenic slow solar wind : 3D velocity distribution functions observed by the Proton-Alpha Sensor of Solar Orbiter
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Journal article (peer-reviewed)abstract
- Context. The Alfvenic slow solar wind is of particular interest, as it is often characterized by intense magnetic turbulence, complex proton 3D velocity distribution functions (VDF), and an ensuing richness of kinetic and dynamic processes.Aims. We take advantage of the fast time cadence of measurements taken by the Proton-Alpha Sensor (PAS) on board Solar Orbiter to analyze the kinetic properties of the proton population, the variability of their VDFs, and the possible link with propagating magnetic structures. We also study the magnetic (B) and velocity (V) correlation that characterizes this type of wind down to the ion gyroperiod.Methods. We analyzed the VDFs measured by PAS, a novelty that take advantages of the capability of 3D measurements at a 4 Hz cadence. In addition, we considered MAG observations.Results. We first show that there is a remarkable correlation between the B and V components observed down to timescales approaching the ion gyrofrequency. This concerns a wide variety of fluctuations, such as waves, isolated peaks, and discontinuities. The great variability of the proton VDFs is also documented. The juxtaposition of a core and a field-aligned beam is the norm but the relative density of the beam, drift speed, and temperatures can considerably change on scales as short as as a few seconds. The characteristics of the core are comparatively more stable. These variations in the beam characteristics mostly explain the variations in the total parallel temperature and, therefore, in the total anisotropy of the proton VDFs. Two magnetic structures that are associated with significant changes in the shape of VDFs, one corresponding to relaxation of total anisotropy and the other to its strong increase, are analyzed here. Our statistical analysis shows a clear link between total anisotropy (and, thus, beam characteristics) and the direction of B with respect to the Parker spiral. In the present case, flux tubes aligned with Parker spiral contain an average proton VDF with a much more developed beam (thus, with larger total anisotropy) than those that are inclined, perpendicular, or even reverse with regard to the outward direction.Conclusions. These observations document the variability of the proton VDF shape in relation to the propagation of magnetic structures. This is a key area of interest for understanding of the effect of turbulence on solar wind dynamics.
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- Maurichi, A, et al.
(author)
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Reply to E. Hindié
- 2020
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 38:27, s. 3238-
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Journal article (other academic/artistic)
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17. |
- Monakhov, E., et al.
(author)
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Boron-enhanced diffusion in excimer laser annealed Si
- 2004
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In: Materials Science & Engineering. - : Elsevier BV. - 0921-5107 .- 1873-4944. ; 114-15, s. 114-117
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Journal article (peer-reviewed)abstract
- The effect of excimer laser annealing (ELA) and rapid thermal annealing (RTA) on B redistribution in B-implanted Si has been studied by secondary ion mass spectrometry (SIMS) and spreading resistance probe (SRP). B has been implanted with an energy of 1 keV and a dose of 10(16) cm(-2) forming a distribution with a width of 20-30nm and a peak concentration of similar to5 x 10(21) cm(-3). It has been found that ELA with 10 pulses of the energy density of 850 mJ/cm(2) results in a uniform B distribution over the ELA-molten region with an abrupt profile edge. SRP measurements demonstrate good activation of the implanted B after ELA, with the concentration of the activated fraction (similar to10(21) cm(-3)) exceeding the solid solubility level. RTA (30 s at 1100degreesC) of the as-implanted and ELA-treated samples leads to a diffusion of B with diffusivities exceeding the equilibrium one and the enhancement is similar for both of the samples. It is also found that RTA decreases the activated B in the ELA-treated sample to the solid solubility limit (2 x 10(20) cm(-3)). The similarity of the B diffusivity for the as-implanted and ELA-treated samples suggests that the enhancement of the B diffusivity is due to the so-called boron-enhanced diffusion (BED). Possible mechanisms of BED are discussed.
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18. |
- Monakhov, E. V., et al.
(author)
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Boron distribution in silicon after excimer laser annealing with multiple pulses
- 2005
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In: Materials Science & Engineering. - : Elsevier BV. - 0921-5107 .- 1873-4944. ; 124, s. 228-231
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Journal article (peer-reviewed)abstract
- We have studied B re-distribution in Si after excimer laser annealing (ELA) with multiple laser pulses. B was implanted using both B and BF2 ions with energies from 1 to 20 keV and doses of 1 x 10(14) and 1 x 10(15) cm(-2). ELA with the number of pulses from 1 to 100 was performed in vacuum with the sample kept at room temperature and 450 degrees C. Independently of the implantation parameters and the ELA conditions used, a peak in the B concentration is observed near the maximum melting depth after 10 pulses of ELA. A detailed study has revealed that B accumulates at the maximum melt depth gradually with the number of ELA pulses. An increase in the carrier concentration at the maximum melt depth is observed after ELA with 100 pulses. No structural defects have been detected by transmission electron microscopy in the region of the B accumulation.
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19. |
- Monakhov, E. V., et al.
(author)
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Boron distribution in silicon after multiple pulse excimer laser annealing
- 2005
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:8
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Journal article (peer-reviewed)abstract
- We have studied B redistribution in Si after excimer laser annealing (ELA) with multiple laser pulses. B was implanted with energies of 1 and 10 keV and doses of 1x10(14) and 1x10(15) cm(-2). ELA with the number of pulses from 1 to 100 was performed at room temperature and 450 degrees C in vacuum. Irrespective of the implantation parameters and the ELA conditions used, a pile-up in the B concentration is observed near the maximum melting depth after ten pulses of ELA. Moreover, a detailed study has revealed that B accumulates at the maximum melt depth gradually with the number of ELA pulses. Besides, an increase in the carrier concentration is observed at the maximum melt depth, suggesting electrical activity of the accumulated B. Formation of Si-B complexes and vacancy accumulation during multiple ELA are discussed as possible mechanisms for the B build-up.
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20. |
- Monakhov, E. V., et al.
(author)
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Enhanced boron diffusion in excimer laser preannealed Si
- 2005
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 86:15
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Journal article (peer-reviewed)abstract
- We have investigated boron diffusion during rapid thermal annealing in Si implanted with boron using an energy of 1 keV and a dose of 1 x 10(16) cm(-2). Two types of samples have been studied: As-implanted and pretreated with excimer laser annealing. For both types an enhanced diffusion of boron has been observed with an enhancement by a factor of 3-5 over the standard diffusion. It is suggested that the high concentration of implanted boron is a dominant factor for the diffusion enhancement as compared to the effect of implantation-induced damage. The data indicate that the proximity of the surface can also affect the boron diffusion enhancement.
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21. |
- Monakhov, E. V., et al.
(author)
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Excimer laser annealing of B and BF2 implanted Si
- 2005
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In: Materials Science & Engineering. - : Elsevier BV. - 0921-5107 .- 1873-4944. ; 124, s. 232-234
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Journal article (peer-reviewed)abstract
- We have performed a comparative study of B re-distribution and electrical activation after excimer laser annealing (ELA) of B and BF2 implanted Si. Chemical B concentration and electrical activation profiles were measured by secondary ion mass spectrometry (SIMS) and spreading resistance profiling (SRP), respectively. SIMS data demonstrate that the presence of F does not influence significantly the re-distribution of B during ELA. A dramatic contrast, however, can be observed in the electrical activation of the dopant in the B and BF2 implanted samples. While almost 100% electrical activation of B occurs in the B implanted samples, only 20-50% of the dopant can be activated by ELA in the BF2 implanted sample. Possible mechanisms causing the deactivation of B in the BF2 implanted samples after ELA are discussed.
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22. |
- Monakhov, E. V., et al.
(author)
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Excimer laser annealing of shallow As and B doped layers
- 2004
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In: Materials Science & Engineering. - : Elsevier BV. - 0921-5107 .- 1873-4944. ; 114-15, s. 352-357
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Journal article (peer-reviewed)abstract
- Excimer laser annealing (ELA) of As-, B- and BF2-implanted Si has been studied by secondary ion mass spectrometry (SIMS), spreading resistance probe (SRP) and transmission electron microscopy (TEM). The implantations have been performed in the energy range from I to 30 keV with doses of 10(15)-10(16) cm(-2). ELA has been carried out with the energy densities in the range of 600-1200 mJ/cm(2) and the number of laser pulses from 1 to 10. It is shown that ELA results in a more uniform dopant distribution over the doped region with a more abrupt profile edge as compared to those after rapid thermal annealing (RTA). Besides, in contrast to RTA, ELA demonstrates a highly confined annealing effect, where the distribution of dopants below the melting region is not affected. SRP measurements demonstrate almost complete activation of the implanted dopants after ELA, and TEM does not reveal extended defects in the ELA-treated samples. The depth of the doped layers, abruptness of the profiles and the total doping dose as a function of ELA energy density and number of laser pulses are investigated. Computer simulations of ELA show a good agreement with the experimental data.
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23. |
- Monakhov, E. V., et al.
(author)
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The effect of excimer laser pretreatment on diffusion and activation of boron implanted in silicon
- 2005
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:19
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Journal article (peer-reviewed)abstract
- We have investigated the effect of excimer laser annealing (ELA) on transient enhanced diffusion (TED) and activation of boron implanted in Si during subsequent rapid thermal annealing (RTA). It is observed that ELA with partial melting of the implanted region causes reduction of TED in the region that remains solid during ELA, where the diffusion length of boron is reduced by a factor of similar to 4 as compared to the as-implanted sample. This is attributed to several mechanisms such as liquid-state annealing of a fraction of the implantation induced defects, introduction of excess vacancies during ELA, and solid-state annealing of the defects beyond the maximum melting depth by the heat wave propagating into the Si wafer. The ELA pretreatment provides a substantially improved electrical activation of boron during subsequent RTA.
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24. |
- Nunes, S. C., et al.
(author)
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Sol-gel-derived potassium-based di-ureasils for "smart windows''
- 2007
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In: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 1364-5501 .- 0959-9428. ; 17:40, s. 4239-4248
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Journal article (peer-reviewed)abstract
- Sol-gel-derived KCF3SO3-doped di-urea cross-linked poly(oxyethylene) (POE)/siloxane (di-ureasil) ormolytes with infinity > n >= 1 (n is the number of oxyethylene units per K+ ion) have been analysed. Samples with n. 40 are thermally stable up to 310 degrees C. At n >= 100, POE crystallites are present. At n = 5, a crystalline POE-KCF3SO3 complex with stoichiometry 1 : 1 is formed. In the xerogel with n = 1 this complex coexists with free salt. The highest ionic conductivity is reached at n = 20. The redox stability domain of this material spans 5.0 V. "Free'' anions and weakly coordinated CF3SO3- ions appear to be the main charge carriers at n = 20. The K+ ions interact with the urea carbonyl oxygen atoms at all salt concentrations. Complexation of the cations by POE occurs at n
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25. |
- Xia, L, et al.
(author)
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Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis
- 2020
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:10, s. 889-
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Journal article (peer-reviewed)abstract
- Chronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, we investigated the role of autophagy in experimental endotoxin-induced pancreatic injury and aimed to identify LPS in human CP tissue. Pancreatic Atg7-deficient mice were injected with a single sub-lethal dose of LPS. Expression of autophagy, apoptosis, necroptosis, and inflammatory markers was determined 3 and 24 h later utilizing immunoblotting and immunofluorescence. The presence of LPS in pancreatic tissue from mice and from patients and healthy controls was determined using immunohistochemistry, immunoblots, and chromogenic assay. Mice lacking pancreatic autophagy exhibited local signs of inflammation and were particularly sensitive to the toxic effect of LPS injection as compared to control mice. In response to LPS, Atg7Δpan mice exhibited enhanced vacuolization of pancreatic acinar cells, increase in TLR4 expression coupled to enhanced expression of NF-κΒ, JNK, and pro-inflammatory cytokines by acinar cells and enhanced infiltration by myeloid cells (but not Atg7F/F controls). Cell death was enhanced in Atg7Δpan pancreata, but only necroptosis and trypsin activation was further amplified following LPS injection along with elevated pancreatic LPS. The presence of LPS was identified in the pancreata from all 14 CP patients examined but was absent in the pancreata from all 10 normal controls. Altogether, these results support a potential role for metabolic endotoxemia in the pathogenesis of CP. Moreover, the evidence also supports the notion that autophagy plays a major cytoprotective and anti-inflammatory role in the pancreas, and blunting metabolic endotoxemia-induced CP.
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26. |
- Zhou, XD, et al.
(author)
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RIP3 attenuates the pancreatic damage induced by deletion of ATG7
- 2017
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8:7, s. e2918-
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Journal article (peer-reviewed)abstract
- Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion.
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27. |
- Zhou, XD, et al.
(author)
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The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis
- 2017
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In: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 3, s. 17027-
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Journal article (peer-reviewed)abstract
- The functional relationship between bile acid (BA) and autophagy has not been evaluated in the context of pancreatitis. Here we investigated whether BA and their nuclear farnesoid X receptor (FXR) modulate autophagy and the development of pancreatitis. FXR expression, autophagy, apoptosis and necroptosis were determined in human chronic pancreatitis (CP) tissue in vivo and in pancreatic cells lines in vitro by means of real-time PCR, immunoblots and immunofluorescence. Pancreatic cell lines exposed to the most abundant BAs glycochenodeoxycholate (GCDC) and taurocholic acid (TCA) increased the expression of nuclear FXR and diminished that of the essential autophagy-related protein ATG7. BA was also elevated in pancreatic tissues from CP patients, correlating with elevated FXR and curtailed ATG7 expression with locally reduced autophagic activity. This was accompanied by an increased manifestation of CP hallmarks including apoptosis, necroptosis, inflammation and fibrosis. The present results suggest a cascade of events in which local accumulation of BA signals via FXR to suppress autophagy in pancreatic acinar cells, thereby unleashing acinar cell apoptosis and necroptosis. Thus, BA may cause CP by suppressing autophagy and exacerbating acinar cell apoptosis and necroptosis.
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