| 1. |
- Backofen, Rolf, et al.
(author)
-
Requirements and specification of bioinformatics use cases
- 2005
-
Reports (other academic/artistic)abstract
- This deliverable specifies use cases based on bioinformatics research carried out by members ofA2. The use cases involve the use of rules to reason over ontologies and pathways (Dresden,Edinburgh, Paris, Linköping) and rules to specify workflows to integrate bioinformatics data (Lisbon, Skövde, Jena, Bucharest). The use cases are designed as a reference point to foster the take up of A2 use cases by I-work packages. Most notably, many of the use cases specify the need for querying and reactivity with languages like Xcerpt (I4), Erus (I5) and Prova (I5). The use cases range from basic research applications to fully deployed software with an international user base.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Backofen, Rolf, et al.
(author)
-
Usage of bioinformatics tools and identification of information sources
- 2005
-
Reports (other academic/artistic)abstract
- Bioinformatics is an important application area for semantic web technologies as much of the data is online and accessible in XML format, as some sites already support web services, and as ontologies are widely used to annotate data. In this deliverable, we give a survey over 18 of the most important bioinformatics resources and discuss their availability and accessibility, which are two of the main criteria for these resources to act as bases for later demonstrators.
|
|
| 6. |
|
|
| 7. |
- Gross, Angelina S., et al.
(author)
-
Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK
- 2019
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 294:32, s. 12020-12039
-
Journal article (peer-reviewed)abstract
- Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1(S/A)) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1(S/A) cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1(S/A). Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging.
|
|
| 8. |
- Gross, Angelina S., et al.
(author)
-
Acetyl-CoA carboxylase 1–dependent lipogenesis promotes autophagy downstream of AMPK
- 2019
-
In: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 294:32, s. 12020-12039
-
Journal article (peer-reviewed)abstract
- Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1S/A) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1S/A cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1S/A. Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging.
|
|
| 9. |
- Mitzner, Rolf, et al.
(author)
-
L-Edge X-ray Absorption Spectroscopy of Dilute Systems Relevant to Metalloproteins Using an X-ray Free-Electron Laser
- 2013
-
In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:21, s. 3641-3647
-
Journal article (peer-reviewed)abstract
- L-edge spectroscopy of 3d transition metals provides important electronic structure information and has been used in many fields. However, the use of this method for studying dilute aqueous systems, such as metalloenzymes, has not been prevalent because of severe radiation damage and the lack of suitable detection systems. Here we present spectra from a dilute Mn aqueous solution using a high-transmission zone-plate spectrometer at the Linac Coherent Light Source (LCLS). The spectrometer has been optimized for discriminating the Mn L-edge signal from the overwhelming 0 K-edge background that arises from water and protein itself, and the ultrashort LCLS X-ray pulses can outrun X-ray induced damage. We show that the deviations of the partial-fluorescence yield-detected spectra from the true absorption can be well modeled using the state-dependence of the fluorescence yield, and discuss implications for the application of our concept to biological samples.
|
|
| 10. |
- Palmio, Johanna, et al.
(author)
-
Hereditary myopathy with early respiratory failure: occurrence in various populations
- 2014
-
In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 85:3, s. 345-353
-
Journal article (peer-reviewed)abstract
- Objective Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort. Methods DNA samples of all currently known families with HMERF without molecular genetic cause were obtained from 12 families in seven different countries. Clinical, histopathological and muscle imaging data were collected and five biopsy samples made available for further immunohistochemical studies. Genotyping, exome sequencing and Sanger sequencing were used to identify and confirm sequence variations. Results All patients with clinical diagnosis of HMERF were genetically solved by five different titin mutations identified. One mutation has been reported while four are novel, all located exclusively in the FN3 119 domain (A150) of A-band titin. One of the new mutations showed semirecessive inheritance pattern with subclinical myopathy in the heterozygous parents. Typical clinical features were respiratory failure at mid-adulthood in an ambulant patient with very variable degree of muscle weakness. Cytoplasmic bodies were retrospectively observed in all muscle biopsy samples and these were reactive for myofibrillar proteins but not for titin. Conclusions We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.
|
|
