| 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. |
- Fujita, S., et al.
(författare)
-
Spatial and temporal variability of snow accumulation rate on the East Antarctic ice divide between Dome Fuji and EPICA DML
- 2011
-
Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 5:4, s. 1057-1081
-
Tidskriftsartikel (refereegranskat)abstract
- To better understand the spatio-temporal variability of the glaciological environment in Dronning Maud Land (DML), East Antarctica, a 2800-km-long Japanese-Swedish traverse was carried out. The route includes ice divides between two ice-coring sites at Dome Fuji and EPICA DML. We determined the surface mass balance (SMB) averaged over various time scales in the late Holocene based on studies of snow pits and firn cores, in addition to radar data. We find that the large-scale distribution of the SMB depends on the surface elevation and continentality, and that the SMB differs between the windward and leeward sides of ice divides for strong-wind events. We suggest that the SMB is highly influenced by interactions between the large-scale surface topography of ice divides and the wind field of strong-wind events that are often associated with high-precipitation events. Local variations in the SMB are governed by the local surface topography, which is influenced by the bedrock topography. In the eastern part of DML, the accumulation rate in the second half of the 20th century is found to be higher by similar to 15% than averages over longer periods of 722 a or 7.9 ka before AD 2008. A similar increasing trend has been reported for many inland plateau sites in Antarctica with the exception of several sites on the leeward side of the ice divides.
|
|
| 3. |
- Abramowski, A., et al.
(författare)
-
Revisiting the Westerlund 2 field with the HESS telescope array
- 2011
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A46-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. Previous observations with the HESS telescope array revealed the existence of extended very-high-energy (VHE; E > 100 GeV) gamma-ray emission, HESS J1023-575, coincident with the young stellar cluster Westerlund 2. At the time of discovery, the origin of the observed emission was not unambiguously identified, and follow-up observations have been performed to further investigate the nature of this gamma-ray source. Methods. The Carina region towards the open cluster Westerlund 2 has been re-observed, increasing the total exposure to 45.9 h. The combined dataset includes 33 h of new data and now permits a search for energy-dependent morphology and detailed spectroscopy. Results. A new, hard spectrum VHE gamma-ray source, HESS J1026-582, was discovered with a statistical significance of 7 sigma. It is positionally coincident with the Fermi LAT pulsar PSRJ1028-5819. The positional coincidence and radio/gamma-ray characteristics of the LAT pulsar favors a scenario where the TeV emission originates from a pulsar wind nebula. The nature of HESS J1023-575 is discussed in light of the deep HESS observations and recent multi-wavelength discoveries, including the Fermi LAT pulsar PSRJ1022-5746 and giant molecular clouds in the region. Despite the improved VHE dataset, a clear identification of the object responsible for the VHE emission from HESS J1023-575 is not yet possible, and contribution from the nearby high-energy pulsar and/or the open cluster remains a possibility.
|
|
| 4. |
|
|
| 5. |
- Dagnelund, Daniel, 1980-, et al.
(författare)
-
Evidence for a phosphorus-related interfacial defect complex at a GaP/GaNP heterojunction
- 2010
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : The American Physical Society. - 1098-0121 .- 1550-235X. ; 81, s. 115334-
-
Tidskriftsartikel (refereegranskat)abstract
- Optically detected magnetic resonance (ODMR) studies of molecular beam epitaxial GaNP/GaP structures reveal presence of a P-related complex defect, evident from its resolved hyperfine interaction between an unpaired electronic spin (S=1/2) and a nuclear spin (I = ½) of a 31P atom. The principal axis of the defect is concluded to be along a <111> crystallographic direction from angular dependence of the ODMR spectrum, restricting the P atom (either a PGa antisite or a Pi interstitial) and its partner in the complex defect to be oriented along this direction. The principal values of the electronic g-tensor and hyperfine interaction tensor are determined as: g┴=2.013, g║=2.002, and A┴=130´10-4 cm-1, A║=330´10-4 cm-1, respectively. The interface nature of the defect is clearly manifested by the absence of the ODMR lines originating from two out of four equivalent <111> orientations. Defect formation is shown to be facilitated by nitrogen ion bombardment under non-equilibrium growth conditions and the defect is thermally stable upon post-growth thermal annealing.
|
|
| 6. |
- Dagnelund, Daniel, et al.
(författare)
-
Phosphorus-related interfacial defect complex at a GaP/GaNP heterojunction
- 2010
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For full exploration of dilute nitrides in device applications, a better understanding and control of defects located at interfaces involving e.g. Ga(In)NP are required. In this work we report on the first identification of a point defect situated at an interface between two semiconductors: GaNP and GaP. The defect is concluded to be a complex involving a P antisite or a P interstitial in its core, partnered with a neighboring impurity/defect aligned along a <111> direction, from detailed angular dependence studies of the optically detected magnetic resonance (ODMR) spectra at both X- and Q-band microwave frequencies. The principal g and A values, g┴=2.013, g║=2.002, A┴=130x10-4 cm-1 and A║=330x10-4 cm-1, are obtained from a spin Hamiltonian analysis. The interface nature of the defect is clearly evident from the absence of the ODMR lines originating from two out of four equivalent <111> orientations. Defect formation is shown to be facilitated by severe nitrogen ion bombardment under non-equilibrium growth conditions during solid-source molecular beam epitaxy and the defect is thermally stable upon post-growth thermal annealing.
|
|
| 7. |
- Ellinor, Patrick T., et al.
(författare)
-
Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
-
Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
|
|
| 8. |
- Kaur, H., et al.
(författare)
-
Differential Role of HAMP-like Linkers in Regulating the Functionality of the Group III Histidine Kinase DhNik1p
- 2014
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:29, s. 20245-20258
-
Tidskriftsartikel (refereegranskat)abstract
- Nik1 orthologs are sensor kinases that function upstream of the high osmolarity glycerol/p38 MAPK pathway in fungi. They contain a poly-HAMP module at their N terminus, which plays a pivotal role in osmosensing as well as fungal death upon exposure to fludioxonil. DhNik1p is a typical member of this class that contains five HAMP domains and four HAMP-like linkers. We investigated the contribution of each of the HAMP-like linker regions to the functionality of DhNik1p and found that the HAMP4b linker was essential as its deletion resulted in the complete loss of activity. Replacement of this linker with flexible peptide sequences did not restore DhNik1p activity. Thus, the HAMP-like sequence and possibly structural features of this linker region are indispensable for the kinase activity of DhNik1p. To gain insight into the global shape of the poly-HAMP module in DhNik1p (HAMP1-5), multi-angle laser light and small angle x-ray scattering studies were carried out. Those data demonstrate that the maltose-binding protein-tagged HAMP1-5 protein exist as a dimer in solution with an elongated shape of maximum linear dimension similar to 365 angstrom. Placement of a sequence similarity based model of the HAMP1-5 protein inside experimental data-based models showed how two chains of HAMP1-5 are entwined on each other and the overall structure retained a periodicity. Normal mode analysis of the structural model is consistent with the H4b linker being a key to native-like collective motion in the protein. Overall, our shape-function studies reveal how different elements in the HAMP1-5 structure mediate its function.
|
|
| 9. |
- Padamsee, Mahajabeen, et al.
(författare)
-
The genome of the xerotolerant mold Wallemia sebi reveals adaptations to osmotic stress and suggests cryptic sexual reproduction
- 2012
-
Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1087-1845 .- 1096-0937. ; 49:3, s. 217-226
-
Tidskriftsartikel (refereegranskat)abstract
- Wallemia (Wallemiales, Wallemiomycetes) is a genus of xerophilic Fungi of uncertain phylogenetic position within Basidiomycota. Most commonly found as food contaminants, species of Wallemia have also been isolated from hypersaline environments. The ability to tolerate environments with reduced water activity is rare in Basidiomycota. We sequenced the genome of W. sebi in order to understand its adaptations for surviving in osmotically challenging environments, and we performed phylogenomic and ultrastructural analyses to address its systematic placement and reproductive biology. W. sebi has a compact genome (9.8Mb), with few repeats and the largest fraction of genes with functional domains compared with other Basidiomycota. We applied several approaches to searching for osmotic stress-related proteins. In silico analyses identified 93 putative osmotic stress proteins; homology searches showed the HOG (High Osmolarity Glycerol) pathway to be mostly conserved. Despite the seemingly reduced genome, several gene family expansions and a high number of transporters (549) were found that also provide clues to the ability of W. sebi to colonize harsh environments. Phylogenetic analyses of a 71-protein dataset support the position of Wallemia as the earliest diverging lineage of Agaricomycotina, which is confirmed by septal pore ultrastructure that shows the septal pore apparatus as a variant of the Tremella-type. Mating type gene homologs were identified although we found no evidence of meiosis during conidiogenesis, suggesting there may be aspects of the life cycle of W. sebi that remain cryptic.
|
|
