| 21. |
- Gógl, Gergö, et al.
(författare)
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Structural basis of Ribosomal S6 Kinase 1 (RSK1) inhibition by S100B Protein: modulation of the Extracellular Signal-regulated Kinase (ERK) signaling cascade in a calcium-dependent way.
- 2016
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 291:1, s. 11-27
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Tidskriftsartikel (refereegranskat)abstract
- Mitogen-activated protein kinases (MAPK) promote MAPK activated protein kinase (MAPKAPK) activation. In the MAPK pathway responsible to cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by calcium-binding S100 proteins in malignant melanomas. Here we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The calcium-dependent binding of S100B to the calcium/calmodulin dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent to the better known binding of calmodulin to CaMKII. Although S100B-RSK1 and the calmodulin-CAMKII system are clearly distinct functionally, they demonstrate how unrelated intracellular Ca(2+) binding proteins could influence the activity of CaMK domain containing protein kinases. Our crystallographic, small angle X-ray scattering (SAXS) and NMR analysis revealed that S100B forms a ″fuzzy″ complex with RSK1 peptide ligands. Based on fast-kinetics experiments we conclude that the binding involves both conformation selection and induced fit steps. Knowledge of the structural basis of this interaction could facilitate therapeutic targeting of melanomas.
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| 22. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 23. |
- Kovács, György, 1984-, et al.
(författare)
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Examining the Combination of Multi-Band Processing and Channel Dropout for Robust Speech Recognition
- 2019
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Ingår i: Proc. Interspeech 2019. - : The International Speech Communication Association (ISCA). ; , s. 421-425
-
Konferensbidrag (refereegranskat)abstract
- A pivotal question in Automatic Speech Recognition (ASR) is the robustness of the trained models. In this study, we investigate the combination of two methods commonly applied to increase the robustness of ASR systems. On the one hand, inspired by auditory experiments and signal processing considerations, multi-band band processing has been used for decades to improve the noise robustness of speech recognition. On the other hand, dropout is a commonly used regularization technique to prevent overfitting by keeping the model from becoming over-reliant on a small set of neurons. We hypothesize that the careful combination of the two approaches would lead to increased robustness, by preventing the resulting model from over-rely on any given band.To verify our hypothesis, we investigate various approaches for the combination of the two methods using the Aurora-4 corpus. The results obtained corroborate our initial assumption, and show that the proper combination of the two techniques leads to increased robustness, and to significantly lower word error rates (WERs). Furthermore, we find that the accuracy scores attained here compare favourably to those reported recently on the clean training scenario of the Aurora-4 corpus.
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| 24. |
- Kovacs, Krisztina, et al.
(författare)
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Trichoderma atroviride mutants with enhanced production of cellulase and beta-glucosidase on pretreated willow
- 2008
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Ingår i: Enzyme and Microbial Technology. - : Elsevier BV. - 0141-0229. ; 43:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Trichoderma atroviride mutants were developed by using N-methyl-N'-nitro-N-nitrosoguanidine (NTG) treatment and UV-Iight followed by a semiquantitative plate clearing assay on Walseth-cellulose/agar plates. The parent strain of the mutants was an isolate from the Amazonas basin (TUB F-1505), whose identity was established by ITS 1 and 2 and tef1 gene sequence analysis. Strain F-1505 proved to be the most promising extracellular cellulase producer among 150 wild-type Trichoderma in a screening program performed in shake flask fermentation on pretreated willow. Reducing sugar content, soluble protein, filter paper cellulase activity (FPA), beta-glucosidase activity and endoglucanase activity of the fermentation broths of the mutant strains were measured in both shake flask and lab-scale fermenters and compared with Trichoderma reesei Rut C30. Also, hydrolytic capacities of fermentation supernatants of T reesei Rut C30, the parent strain (F-1505) and the best mutants were compared on pretreated willow as carbon source and hydrolysis substrate. The T atroviride mutants produced high levels of extracellular cellulases as well as beta-glucosidase, rendering the need for beta-glucosidase supplementation in hydrolysis of cellulose or pretreated willow unnecessary. On the contrary, beta-glucosidase supplementations were essential in order to obtain good glucose yields for all other cellulase preparations tested.
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| 25. |
- Kovacs-Krausz, Zoltan, et al.
(författare)
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Revealing the band structure of ZrTe5 using multicarrier transport
- 2023
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 107:7
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Tidskriftsartikel (refereegranskat)abstract
- The layered material ZrTe5 appears to exhibit several exotic behaviors, which resulted in significant interest recently, although the exact properties are still highly debated. Among these we find a Dirac/Weyl semimetallic behavior, nontrivial spin textures revealed by low-temperature transport, and a potential weak or strong topological phase. The anomalous behavior of resistivity has been recently elucidated as originating from band shifting in the electronic structure. Our work examines magnetotransport behavior in ZrTe5 samples in the context of multicarrier transport. The results, in conjunction with ab initio band structure calculations, indicate that many of the transport features of ZrTe5 across the majority of the temperature range can be adequately explained by the semiclassical multicarrier transport model originating from a complex Fermi surface.
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| 26. |
- Kovács, Laszlo, et al.
(författare)
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Lack of the light-harvesting complex CP24 affects the structure and function of the grana membranes of higher plant chloroplasts.
- 2006
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Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 18:11, s. 3106-20
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Tidskriftsartikel (refereegranskat)abstract
- The photosystem II (PSII) light-harvesting antenna in higher plants contains a number of highly conserved gene products whose function is unknown. Arabidopsis thaliana plants depleted of one of these, the CP24 light-harvesting complex, have been analyzed. CP24-deficient plants showed a decrease in light-limited photosynthetic rate and growth, but the pigment and protein content of the thylakoid membranes were otherwise almost unchanged. However, there was a major change in the macroorganization of PSII within these membranes; electron microscopy and image analysis revealed the complete absence of the C2S2M2 light-harvesting complex II (LHCII)/PSII supercomplex predominant in wild-type plants. Instead, only C2S2 supercomplexes, which are deficient in the LHCIIb M-trimers, were found. Spectroscopic analysis confirmed the disruption of the wild-type macroorganization of PSII. It was found that the functions of the PSII antenna were disturbed: connectivity between PSII centers was reduced, and maximum photochemical yield was lowered; rapidly reversible nonphotochemical quenching was inhibited; and the state transitions were altered kinetically. CP24 is therefore an important factor in determining the structure and function of the PSII light-harvesting antenna, providing the linker for association of the M-trimer into the PSII complex, allowing a specific macroorganization that is necessary both for maximum quantum efficiency and for photoprotective dissipation of excess excitation energy.
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| 27. |
- Kovacs, T., et al.
(författare)
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Flow and turbulence in the discharge of radial pumping turbines : Influence of the turbine type
- 2001
-
Ingår i: Chemical Engineering & Technology. - 0930-7516 .- 1521-4125. ; 24:10, s. 1035-1044
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Tidskriftsartikel (refereegranskat)abstract
- Velocity measurements were made in the impeller discharge of 6SRGT- and Rushton-type impellers in a 0.6 m(3) tank using, constant temperature anemometry with a direction sensitive split-film probe. The reproducibility error of the measurement system was found to be greater than 5 % for all measured properties. The main flow and turbulent parameters measured at three agitation rates in the impeller discharge are compared for the two turbines with respect to both agitation rate and the measured power input. For comparison of the flow properties in the centerline of the two turbines having different diameter and blade height, a uniform representation was used treating the impeller stream as a special kind of free jet. Using this representation, we obtained similar results for both turbines on all measured parameters. The profile measurements showed a similar main flow field for both turbines, but significant differences were found in the axial distribution of turbulent kinetic energy and the energy dissipation rate.
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| 28. |
- Kovacs, T., et al.
(författare)
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Fourier spectrum to recover deterministic and stochastic behavior in stirred tanks
- 2001
-
Ingår i: AIChE Journal. - : Wiley. - 0001-1541 .- 1547-5905. ; 47:10, s. 2167-2176
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Tidskriftsartikel (refereegranskat)abstract
- Velocity data from the impeller region of Rushton and 6SRGT pilot-scale impellers were analyzed both in the frequency domain and with respect to periodicity. The four characteristic frequencies and their combination were detected from the Fourier spectrum, and the deterministic part of the signal was recovered by making the amplitude of the other frequencies zero. The deterministic part was then analyzed with tools from nonlinear theories. For the two turbine-types, the dynamics of the deterministic velocity parts were almost identical. The turbulent part of the signal could also be estimated in a similar manner.
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| 29. |
- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 30. |
- Lessmark, Anna, et al.
(författare)
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Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity
- 2022
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.
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