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| 3. |
- 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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- Willander, Magnus, et al.
(författare)
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Zinc oxide nanorod based photonic devices : recent progress in growth, light emitting diodes and lasers
- 2009
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Ingår i: NANOTECHNOLOGY. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 20:33, s. 332001-
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Forskningsöversikt (refereegranskat)abstract
- Zinc oxide (ZnO), with its excellent luminescent properties and the ease of growth of its nanostructures, holds promise for the development of photonic devices. The recent advances in growth of ZnO nanorods are discussed. Results from both low temperature and high temperature growth approaches are presented. The techniques which are presented include metal-organic chemical vapour deposition (MOCVD), vapour phase epitaxy (VPE), pulse laser deposition (PLD), vapour-liquid-solid (VLS), aqueous chemical growth (ACG) and finally the electrodeposition technique as an example of a selective growth approach. Results from structural as well as optical properties of a variety of ZnO nanorods are shown and analysed using different techniques, including high resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), photoluminescence (PL) and cathodoluminescence (CL), for both room temperature and for low temperature performance. These results indicate that the grown ZnO nanorods possess reproducible and interesting optical properties. Results on obtaining p-type doping in ZnO micro- and nanorods are also demonstrated using PLD. Three independent indications were found for p-type conducting, phosphorus-doped ZnO nanorods: first, acceptor-related CL peaks, second, opposite transfer characteristics of back-gate field effect transistors using undoped and phosphorus doped wire channels, and finally, rectifying I-V characteristics of ZnO: P nanowire/ZnO:Ga p-n junctions. Then light emitting diodes (LEDs) based on n-ZnO nanorods combined with different technologies (hybrid technologies) are suggested and the recent electrical, as well as electro-optical, characteristics of these LEDs are shown and discussed. The hybrid LEDs reviewed and discussed here are mainly presented for two groups: those based on n-ZnO nanorods and p-type crystalline substrates, and those based on n-ZnO nanorods and p-type amorphous substrates. Promising electroluminescence characteristics aimed at the development of white LEDs are demonstrated. Although some of the presented LEDs show visible emission for applied biases in excess of 10 V, optimized structures are expected to provide the same emission at much lower voltage. Finally, lasing from ZnO nanorods is briefly reviewed. An example of a recent whispering gallery mode (WGM) lasing from ZnO is demonstrated as a way to enhance the stimulated emission from small size structures.
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| 7. |
- Schneider, E, et al.
(författare)
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CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5911-
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.
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| 8. |
- Vitova, T., et al.
(författare)
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High energy resolution x-ray absorption spectroscopy study of uranium in varying valence states
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 82:23, s. 235118-
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Tidskriftsartikel (refereegranskat)abstract
- A high energy resolution x-ray absorption near-edge structure (XANES) spectroscopy study on U4+ (UO2), U5+ ([UO2Py5][KI2Py2]), and U6+ [UO2(NO3)(2)(H2O)(6)] demonstrates the potential of this experimental technique for qualitative/semiqualitative and quantitative actinide speciation investigations. We observe a pre-edge feature with quadrupole nature in a U L-3 edge partial fluorescence yield-XANES spectrum. This feature is a tool for characterizing the participation of 5f orbitals in U-O bonding. The feature origin is explained by performing calculations with the finite difference method near-edge structure code based on the multiple-scattering theory and the finite difference method.
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| 9. |
- Abudu, YP, et al.
(författare)
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SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components
- 2021
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 220:8
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Tidskriftsartikel (refereegranskat)abstract
- Mitophagy is the degradation of surplus or damaged mitochondria by autophagy. In addition to programmed and stress-induced mitophagy, basal mitophagy processes exert organelle quality control. Here, we show that the sorting and assembly machinery (SAM) complex protein SAMM50 interacts directly with ATG8 family proteins and p62/SQSTM1 to act as a receptor for a basal mitophagy of components of the SAM and mitochondrial contact site and cristae organizing system (MICOS) complexes. SAMM50 regulates mitochondrial architecture by controlling formation and assembly of the MICOS complex decisive for normal cristae morphology and exerts quality control of MICOS components. To this end, SAMM50 recruits ATG8 family proteins through a canonical LIR motif and interacts with p62/SQSTM1 to mediate basal mitophagy of SAM and MICOS components. Upon metabolic switch to oxidative phosphorylation, SAMM50 and p62 cooperate to mediate efficient mitophagy.
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| 10. |
- Gorman, Jeffrey, et al.
(författare)
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Deoxyribonucleic Acid Encoded and Size-Defined π-Stacking of Perylene Diimides
- 2022
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:1, s. 368-376
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Tidskriftsartikel (refereegranskat)abstract
- Natural photosystems use protein scaffolds to control intermolecular interactions that enable exciton flow, charge generation, and long-range charge separation. In contrast, there is limited structural control in current organic electronic devices such as OLEDs and solar cells. We report here the DNA-encoded assembly of pi-conjugated perylene diimides (PDIs) with deterministic control over the number of electronically coupled molecules. The PDIs are integrated within DNA chains using phosphoramidite coupling chemistry, allowing selection of the DNA sequence to either side, and specification of intermolecular DNA hybridization. In this way, we have developed a "toolbox" for construction of any stacking sequence of these semiconducting molecules. We have discovered that we need to use a full hierarchy of interactions: DNA guides the semiconductors into specified close proximity, hydrophobic-hydrophilic differentiation drives aggregation of the semiconductor moieties, and local geometry and electrostatic interactions define intermolecular positioning. As a result, the PDIs pack to give substantial intermolecular pi wave function overlap, leading to an evolution of singlet excited states from localized excitons in the PDI monomer to excimers with wave functions delocalized over all five PDIs in the pentamer. This is accompanied by a change in the dominant triplet forming mechanism from localized spin-orbit charge transfer mediated intersystem crossing for the monomer toward a delocalized excimer process for the pentamer. Our modular DNA-based assembly reveals real opportunities for the rapid development of bespoke semiconductor architectures with molecule-by-molecule precision.
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| 11. |
- Hermans, Martijn, et al.
(författare)
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Impact of natural re-oxygenation on the sediment dynamics of manganese, iron and phosphorus in a euxinic Baltic Sea basin
- 2019
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533. ; 246, s. 174-196
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Tidskriftsartikel (refereegranskat)abstract
- The Baltic Sea is characterized by the largest area of hypoxic (oxygen (O2) < 2 mg L−1) bottom waters in the world’s ocean induced by human activities. Natural ventilation of these O2-depleted waters largely depends on episodic Major Baltic Inflows from the adjacent North Sea. In 2014 and 2015, two such inflows led to a strong rise in O2 and decline in phosphate (HPO42−) in waters below 125 m depth in the Eastern Gotland Basin. This provided the opportunity to assess the impact of such re-oxygenation events on the cycles of manganese (Mn), iron (Fe) and phosphorus (P) in the sediment for the first time. We demonstrate that the re-oxygenation induced the activity of sulphur (S)-oxidising bacteria, known as Beggiatoaceae in the surface sediment where a thin oxic and suboxic layer developed. At the two deepest sites, strong enrichments of total Mn and to a lesser extent Fe oxides and P were observed in this surface layer. A combination of sequential sediment extractions and synchrotron-based X-ray spectroscopy revealed evidence for the abundant presence of P-bearing rhodochrosite and Mn(II) phosphates. In contrast to what is typically assumed, the formation of Fe oxides in the surface sediment was limited. We attribute this lack of Fe oxide formation to the high flux of reductants, such as sulphide, from deeper sediments which allows Fe(II) in the form of FeS to be preserved and restricts the penetration of O2 into the sediment. We estimate that enhanced P sequestration in surface sediments accounts for only ∼5% of water column HPO42− removal in the Eastern Gotland Basin linked to the recent inflows. The remaining HPO42− was transported to adjacent areas in the Baltic Sea. Our results highlight that the benthic O2 demand arising from the accumulation of organic-rich sediments over several decades, the legacy of hypoxia, has major implications for the biogeochemical response of euxinic basins to re-oxygenation. In particular, P sequestration in the sediment in association with Fe oxides is limited. This implies that artificial ventilation projects that aim at removing water column HPO42− and thereby improving water quality in the Baltic Sea will likely not have the desired effect.
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| 12. |
- Orsborne, Sarah R.E., et al.
(författare)
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Photogeneration of Spin Quintet Triplet-Triplet Excitations in DNA-Assembled Pentacene Stacks
- 2023
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 145:9, s. 5431-5438
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Tidskriftsartikel (refereegranskat)abstract
- Singlet fission (SF), an exciton-doubling process observed in certain molecular semiconductors where two triplet excitons are generated from one singlet exciton, requires correctly tuned intermolecular coupling to allow separation of the two triplets to different molecular units. We explore this using DNA-encoded assembly of SF-capable pentacenes into discrete π-stacked constructs of defined size and geometry. Precise structural control is achieved via a combination of the DNA duplex formation between complementary single-stranded DNA and the local molecular geometry that directs the SF chromophores into a stable and predictable slip-stacked configuration, as confirmed by molecular dynamics (MD) modeling. Transient electron spin resonance spectroscopy revealed that within these DNA-assembled pentacene stacks, SF evolves via a bound triplet pair quintet state, which subsequently converts into free triplets. SF evolution via a long-lived quintet state sets specific requirements on intermolecular coupling, rendering the quintet spectrum and its zero-field-splitting parameters highly sensitive to intermolecular geometry. We have found that the experimental spectra and zero-field-splitting parameters are consistent with a slight systematic strain relative to the MD-optimized geometry. Thus, the transient electron spin resonance analysis is a powerful tool to test and refine the MD-derived structure models. DNA-encoded assembly of coupled semiconductor molecules allows controlled construction of electronically functional structures, but brings with it significant dynamic and polar disorders. Our findings here of efficient SF through quintet states demonstrate that these conditions still allow efficient and controlled semiconductor operation and point toward future opportunities for constructing functional optoelectronic systems.
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| 13. |
- Vallée, Tanja C, et al.
(författare)
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Wiskott-Aldrich Syndrome: A study on 577 patients defining the genotype as a predictive biomarker for disease severity.
- 2024
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 143:24, s. 2504-2516
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Tidskriftsartikel (refereegranskat)abstract
- WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
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