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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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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| 10. |
- Andrade, EB, et al.
(författare)
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A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3138-
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Tidskriftsartikel (refereegranskat)abstract
- Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.
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| 11. |
- Welsh, Joshua A., et al.
(författare)
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
- 2024
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Ingår i: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
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| 12. |
- Anghinolfi, F., et al.
(författare)
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Hadron beam test of a scintillating fibre tracker system for elastic scattering and luminosity measurement in ATLAS
- 2007
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- A scintillating fibre tracker is proposed to measure elastic proton scattering at very small angles in the ATLAS experiment at CERN. The tracker will be located in so-called Roman Pot units at a distance of 240 m on each side of the ATLAS interaction point. An initial validation of the design choices was achieved in a beam test at DESY in a relatively low energy electron beam and using slow off-the-shelf electronics. Here we report on the results from a second beam test experiment carried out at CERN, where new detector prototypes were tested in a high energy hadron beam, using the first version of the custom designed front-end electronics. With a spatial resolution of 25 mu m an adequate tracking performance was obtained, under conditions which are similar to the situation at the LHC. In addition, the alignment method using so-called overlap detectors was studied and shown to have the expected precision.
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| 13. |
- Mapelli, A., et al.
(författare)
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Development of a detector (ALFA) to measure the absolute LHC luminosity at ATLAS
- 2008
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Ingår i: Astroparticle, Particle and Space Physics, Detectors and Medical Physics Applications - Proceedings of the 10th Conference. - 9812819088 - 9789812819086 ; , s. 984-988
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Konferensbidrag (refereegranskat)abstract
- The ATLAS collaboration plans to determine the absolute luminosity of the CERN LHC at Interaction Point 1 by measuring the trajectory of protons elastically scattered at very small angles (μrad). A scintillating fibre tracker system called ALFA (Absolute Luminosity For ATLAS) is proposed for this measurement. Detector modules will be placed above and below the LHC beam axis in roman pot units at a distance of 240 m on cach side of the ATLAS interaction point. They allow the detectors to approach the beam axis to millimeter distance. Overlap detectors also based on the scintillating fibre technology, will measure the precise relative position of the two detector modules, Results obtained during beam tests at DESY and at CERN validate the detectors design and demonstrate the achievable resolution. We also report about radiation hardness studies of the scintillating fibres to estimate the lifetime of the ALFA system at different operating conditions of the LHC.
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| 14. |
- Rayasam, A., et al.
(författare)
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Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis
- 2021
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- Stroke is among the top ten causes of death in children but has received disproportionally little attention. Cerebral arteriopathies account for up to 80% of childhood arterial ischemic stroke (CAIS) cases and are strongly predictive of CAIS recurrence and poorer outcomes. The underlying mechanisms of sensitization of neurovasculature by viral infection are undefined. In the first age-appropriate model for childhood arteriopathy-by administration of viral mimetic TLR3-agonist Polyinosinic:polycytidylic acid (Poly-IC) in juvenile mice-we identified a key role of the TLR3-neutrophil axis in disrupting the structural-functional integrity of the blood-brain barrier (BBB) and distorting the developing neurovascular architecture and vascular networks. First, using an array of in-vivo/post-vivo vascular imaging, genetic, enzymatic and pharmacological approaches, we report marked Poly-IC-mediated extravascular leakage of albumin (66kDa) and of a small molecule DiI (similar to 934Da) and disrupted tight junctions. Poly-IC also enhanced the neuroinflammatory milieu, promoted neutrophil recruitment, profoundly upregulated neutrophil elastase (NE), and induced neutrophil extracellular trap formation (NETosis). Finally, we show that functional BBB disturbances, NETosis and neuroinflammation are markedly attenuated by pharmacological inhibition of NE (Sivelestat). Altogether, these data reveal NE/NETosis as a novel therapeutic target for viral-induced cerebral arteriopathies in children.
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| 15. |
- Chumak, Tetyana, 1982, et al.
(författare)
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Maternal n-3 Polyunsaturated Fatty Acid Enriched Diet Commands Fatty Acid Composition in Postnatal Brain and Protects from Neonatal Arterial Focal Stroke
- 2022
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 13:3, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- The fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA). In adult animals, n-3 PUFA ameliorates stroke-mediated brain injury, but the modulatory effects of different PUFA content in maternal diet on focal arterial stroke in neonates are unknown. This study explored effects of maternal n-3 or n-6 enriched PUFA diets on neonatal stroke outcomes. Pregnant mice were assigned three isocaloric diets until offspring reached postnatal day (P) 10-13: standard, long-chain n-3 PUFA (n-3) or n-6 PUFA (n-6) enriched. Fatty acid profiles in plasma and brain of mothers and pups were determined by gas chromatography-mass spectrometry and cytokines/chemokines by multiplex protein analysis. Transient middle cerebral artery occlusion (tMCAO) was induced in P9-10 pups and cytokine and chemokine accumulation, caspase-3 and calpain-dependent spectrin cleavage and brain infarct volume were analyzed. The n-3 diet uniquely altered brain lipid profile in naive pups. In contrast, cytokine and chemokine levels did not differ between n-3 and n-6 diet in naive pups. tMCAO triggered accumulation of inflammatory cytokines and caspase-3-dependent and -independent cell death in ischemic-reperfused regions in pups regardless of diet, but magnitude of neuroinflammation and caspase-3 activation were attenuated in pups on n-3 diet, leading to protection against neonatal stroke. In conclusion, maternal/postnatal n-3 enriched diet markedly rearranges neonatal brain lipid composition and modulates the response to ischemia. While standard diet is sufficient to maintain low levels of inflammatory cytokines and chemokines under physiological conditions, n-3 PUFA enriched diet, but not standard diet, attenuates increases of inflammatory cytokines and chemokines in ischemic-reperfused regions and protects from neonatal stroke.
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| 16. |
- Hou, Qichao, et al.
(författare)
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Different Doping Behaviors of Silicon in Zinc Blende and Wurtzite GaAs Nanowires : Implications for Crystal-Phase Device Design
- 2023
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Ingår i: ACS Applied Nano Materials. - 2574-0970. ; 6:13, s. 11465-11471
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Tidskriftsartikel (refereegranskat)abstract
- Crystal-phase engineering between zinc blende (ZB) and wurtzite (WZ) structures is becoming an important method in designing unique optoelectronic and electronic semiconductor devices. Doping to engineer their electric properties is thus of critical importance, but a direct experimental comparison in doping these two crystal structures is still missing. Nanowires (NWs) allow the coexistence of both structures due to their special growth mode. The differences in dopant incorporation between the two phases are studied here in GaAs NW shells that are coherently grown around the NWs, hence maintaining the crystal structure of the core. The Si dopant is observed to have a higher incorporation efficiency into the WZ structure due to a 2 times lower incorporation energy compared with that of the ZB structure. Besides, it can also be predicted that Si is more inclined toward Ga sites in both structures. Indeed, the As-site doping energy of the WZ structure is several orders of magnitude higher than that of Ga sites, allowing a lower doping compensation effect. This work provides useful information for doping control and hence designing crystal-phase devices.
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| 17. |
- Rayasam, A., et al.
(författare)
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Scavenger receptor CD36 governs recruitment of myeloid cells to the blood-CSF barrier after stroke in neonatal mice
- 2022
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Ischemic stroke induces the activation and recruitment of peripheral leukocytes to the injured brain. These cells can infiltrate the brain through multiple routes, either by penetrating blood-brain barrier or via blood-CSF barriers at the meninges or the choroid plexus (CP). We previously showed that myeloid cell trafficking via the CP occurs early after neonatal arterial stroke and modulates injury. CD36 is a receptor that mediates function of endothelial cells and cells of the monocyte lineage under various neurodegenerative conditions and can influence brain injury after neonatal stroke. Here we asked whether CD36 impacts injury by altering leukocyte trafficking through the CP in neonatal mice subjected to transient middle cerebral artery occlusion (tMCAO). Methods In neonatal mice with intact or globally disrupted CD36 signalling (CD36 KO), we characterized the phenotypes of myeloid cells by flow cytometry and the underlying gene expression signatures in the CPs contralateral and ipsilateral to tMCAO by RNA sequencing analyses, focussing on early post-reperfusion time window. Results Flow cytometry in the isolated CPs revealed that CD36 mediates stepwise recruitment of myeloid cells to the CP ipsilateral to tMCAO early after reperfusion, with a predominant increase first in inflammatory monocyte subsets and neutrophils followed by patrolling monocytes. RNA sequencing analyses demonstrated marked changes in gene expression in the CP ipsilateral compared to the CP contralateral to tMCAO in wild type mice. Changes were further modified by lack of CD36, including distinction in several clusters of genes involved in inflammatory, metabolic and extracellular matrix signalling in the CP ipsilateral to tMCAO. Conclusion Altogether, our data suggest cooperation between blood-CSF-brain interface via the CP through CD36-mediated signalling following neonatal stroke with a key role for inflammatory monocytes and neutrophils.
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