| 1. |
- 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.
|
|
| 2. |
- Davies, Neil, et al.
(författare)
-
The founding charter of the Genomic Observatories Network
- 2014
-
Ingår i: GigaScience. - 2047-217X. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
|
|
| 3. |
|
|
| 4. |
- Camacho Dejay, Rafael, et al.
(författare)
-
Polarization Imaging of Emissive Charge Transfer States in Polymer/Fullerene Blends
- 2014
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 26:23, s. 6695-6704
-
Tidskriftsartikel (refereegranskat)abstract
- Photoexcitation of conjugated polymerfullerene blends results in population of a local charge transfer (CT) state at the interface between the two materials. The competition between recombination and dissociation of this interfacial state limits the generation of fully separated free charges. Therefore, a detailed understanding of the CT states is critical for building a comprehensive picture of the organic solar cells operation. We applied a new fluorescence microscopy method called two-dimensional polarization imaging to gain insight into the orientation of the transition dipole moments of the CT states, and the associated excitation energy transfer processes in TQ1:PCBM blend films. The polymer phase was oriented mechanically to relate the polymer dipole moment orientation to that of the CT states. CT state formation was observed to be much faster than energy transfer in the polymer phase. However, after being formed an emissive CT state does not exchange excitation energy with other CT states, suggesting that they are spatially and/or energetically isolated. We found that the quantum yield of the CT emission is smaller for CT states spatially located in the highly oriented polymer domains, which is interpreted as the result of enhanced CT state dissociation in highly ordered structures.
|
|
| 5. |
- Davies, N., et al.
(författare)
-
Report of the 14th Genomic Standards Consortium Meeting, Oxford, UK, September 17-21, 2012
- 2014
-
Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 9:3, s. 1236-1250
-
Tidskriftsartikel (refereegranskat)abstract
- This report summarizes the proceedings of the 14th workshop of the Genomic Standards Consortium (GSC) held at the University of Oxford in September 2012. The primary goal of the workshop was to work towards the launch of the Genomic Observatories (GOs) Network under the GSC. For the first time, it brought together potential GOs sites, GSC members, and a range of interested partner organizations. It thus represented the first meeting of the GOs Network (GOs1). Key outcomes include the formation of a core group of “champions” ready to take the GOs Network forward, as well as the formation of working groups. The workshop also served as the first meeting of a wide range of participants in the Ocean Sampling Day (OSD) initiative, a first GOs action. Three projects with complementary interests – COST Action ES1103, MG4U and Micro B3 – organized joint sessions at the workshop. A two-day GSC Hackathon followed the main three days of meetings.
|
|
| 6. |
- Godoy, Patricio, et al.
(författare)
-
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
-
Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
-
Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
|
|
| 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. |
- Klein, Jan Philipp, et al.
(författare)
-
The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention
- 2013
-
Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundDepressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression.Methods/DesignThis study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments.DiscussionThe study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry.
|
|
| 9. |
- Lazaridis, Iosif, et al.
(författare)
-
Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
-
Tidskriftsartikel (refereegranskat)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
|
|
| 10. |
- Merdasa, Aboma, et al.
(författare)
-
Single Levy States-Disorder Induced Energy Funnels in Molecular Aggregates
- 2014
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 14:12, s. 6774-6781
-
Tidskriftsartikel (refereegranskat)abstract
- Using fluorescence super-resolution microscopy we studied simultaneous spectral, spatial localization, and blinking behavior of individual 1D J-aggregates. Excitons migrating 100 nm are funneled to a trap appearing as an additional red-shifted blinking fluorescence band. We propose that the trap is a Frenkel exciton state formed much below the main exciton band edge due to an environmentally induced heavy-tailed Levy disorder. This points to disorder engineering as a new avenue in controlling light-harvesting in molecular ensembles.
|
|
