| 1. |
|
|
| 2. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 4. |
- Chandrasekaran, Abinaya, et al.
(författare)
-
Astrocytic reactivity triggered by defective autophagy and metabolic failure causes neurotoxicity in frontotemporal dementia type 3
- 2021
-
Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; , s. 2736-2751
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and the endolysosomal pathway in neurons. To dissect the astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) and confirmed our findings in CHMP2B mutant mice. Our data provide mechanistic insights into how defective autophagy causes perturbed mitochondrial dynamics with impaired glycolysis, increased reactive oxygen species, and elongated mitochondrial morphology, indicating increased mitochondrial fusion in FTD3 astrocytes. This shift in astrocyte homeostasis triggers a reactive astrocyte phenotype and increased release of toxic cytokines, which accumulate in nuclear factor kappa b (NF-κB) pathway activation with increased production of CHF, LCN2, and C3 causing neurodegeneration.
|
|
| 5. |
- Demichev, Vadim, et al.
(författare)
-
A time-resolved proteomic and prognostic map of COVID-19
- 2021
-
Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
|
|
| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 7. |
- Hering, Lars, et al.
(författare)
-
Opsins in Onychophora (Velvet Worms) Suggest a Single Origin and Subsequent Diversification of Visual Pigments in Arthropods
- 2012
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 29:11, s. 3451-3458
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple visual pigments, prerequisites for color vision, are found in arthropods, but the evolutionary origin of their diversity remains obscure. In this study, we explore the opsin genes in five distantly related species of Onychophora, using deep transcriptome sequencing and screening approaches. Surprisingly, our data reveal the presence of only one opsin gene (onychopsin) in each onychophoran species, and our behavioral experiments indicate a maximum sensitivity of onychopsin to blue-green light. In our phylogenetic analyses, the onychopsins represent the sister group to the monophyletic clade of visual r-opsins of arthropods. These results concur with phylogenomic support for the sister-group status of the Onychophora and Arthropoda and provide evidence for monochromatic vision in velvet worms and in the last common ancestor of Onychophora and Arthropoda. We conclude that the diversification of visual pigments and color vision evolved in arthropods, along with the evolution of compound eyes-one of the most sophisticated visual systems known.
|
|
| 8. |
- Kleeman, Sam O, et al.
(författare)
-
Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.
- 2023
-
Ingår i: Cell genomics. - 2666-979X. ; 3:8
-
Tidskriftsartikel (refereegranskat)abstract
- Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.
|
|
| 9. |
|
|
| 10. |
- Martini, Paul, et al.
(författare)
-
Splashing of Large Helium Nanodroplets upon Surface Collisions
- 2021
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 127:26
-
Tidskriftsartikel (refereegranskat)abstract
- In the present work we observe that helium nanodroplets colliding with surfaces can exhibit splashing in a way that is analogous to classical liquids. We use transmission electron microscopy and mass spectrometry to demonstrate that neutral and ionic dopants embedded in the droplets are efficiently backscattered in such events. High abundances of weakly bound He-tagged ions of both polarities indicate a gentle extraction mechanism of these ions from the droplets upon collision with a solid surface. This backscattering process is observed for dopant particles with masses up to 400 kilodaltons, indicating an unexpected mechanism that effectively lowers deposition rates of nanoparticles formed in helium droplets.
|
|
