| 1. |
- Chen, Xin, 1980, et al.
(författare)
-
Dataset for suppressors of amyloid-beta toxicity and their functions in recombinant protein production in yeast
- 2022
-
Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 42
-
Tidskriftsartikel (refereegranskat)abstract
- The production of recombinant proteins at high levels often induces stress-related phenotypes by protein misfolding or aggregation. These are similar to those of the yeast Alzheimer's disease (AD) model in which amyloid-beta peptides (A beta 42) were accumulated [1,2] . We have previously identified suppressors of A beta 42 cytotoxicity via the genome-wide synthetic genetic array (SGA) [3] and here we use them as metabolic engineering targets to evaluate their potentiality on recombinant protein production in yeast Saccharomyces cerevisiae. In order to investigate the mechanisms linking the genetic modifications to the improved recombinant protein production, we perform systems biology approaches (transcriptomics and proteomics) on the resulting strain and intermediate strains. The RNAseq data are preprocessed by the nf-core/RNAseq pipeline and analyzed using the Platform for Integrative Analysis of Omics (PIANO) package [4] . The quantitative proteome is analyzed on an Orbitrap Fusion Lumos mass spectrometer interfaced with an Easy-nLC1200 liquid chromatography (LC) system. LC-MS data files are processed by Proteome Discoverer version 2.4 with Mascot 2.5.1 as a database search engine. The original data presented in this work can be found in the research paper titled "Suppressors of Amyloid-beta Toxicity Improve Recombinant Protein Produc-tion in yeast by Reducing Oxidative Stress and Tuning Cellu-lar Metabolism", by Chen et al. [5] . (C) 2022 The Author(s). Published by Elsevier Inc.
|
|
| 2. |
- Chen, Xin, 1980, et al.
(författare)
-
Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
- 2022
-
Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 72, s. 311-324
-
Tidskriftsartikel (refereegranskat)abstract
- High-level production of recombinant proteins in industrial microorganisms is often limited by the formation of misfolded proteins or protein aggregates, which consequently induce cellular stress responses. We hypothesized that in a yeast Alzheimer's disease (AD) model overexpression of amyloid-β peptides (Aβ42), one of the main peptides relevant for AD pathologies, induces similar phenotypes of cellular stress. Using this humanized AD model, we previously identified suppressors of Aβ42 cytotoxicity. Here we hypothesize that these suppressors could be used as metabolic engineering targets to alleviate cellular stress and improve recombinant protein production in the yeast Saccharomyces cerevisiae. Forty-six candidate genes were individually deleted and twenty were individually overexpressed. The positive targets that increased recombinant α-amylase production were further combined leading to an 18.7-fold increased recombinant protein production. These target genes are involved in multiple cellular networks including RNA processing, transcription, ER-mitochondrial complex, and protein unfolding. By using transcriptomics and proteomics analyses, combined with reverse metabolic engineering, we showed that reduced oxidative stress, increased membrane lipid biosynthesis and repressed arginine and sulfur amino acid biosynthesis are significant pathways for increased recombinant protein production. Our findings provide new insights towards developing synthetic yeast cell factories for biosynthesis of valuable proteins.
|
|
| 3. |
- Lakshmana, Tilak Rajesh, 1980, et al.
(författare)
-
Partial joint processing for frequency selective channels
- 2010
-
Ingår i: IEEE Vehicular Technology Conference. - 1550-2252. - 9781424435746
-
Konferensbidrag (refereegranskat)abstract
- In this paper, we consider a static cluster of base stations where joint processing is allowed in the downlink. The partial joint processing scheme is a user-centric approach where subclusters or active sets of base stations are dynamically defined for each user in the cluster. In frequency selective channels, the definition of the subclusters or active set thresholding of base stations can be frequency adaptive (per resource block) or non-adaptive (averaged over all the resource blocks). Frequency adaptive thresholding improves the average sum-rate of the cluster, but at the cost of an increased user data interbase information exchange with respect to the non-adaptive frequency thresholding case. On the other hand, the channel state information available at the transmitter side to design the beamforming matrix is very limited and rank deficiency problems arise for low values of active set thresholding and users located close to the base station. To solve this problem, an algorithm is proposed that defines a cooperation area over the cluster where the partial joint processing scheme can be performed, frequency adaptive or non-adaptive, for a given active set threshold value.
|
|
| 4. |
|
|
| 5. |
- Busayavalasa, Kiran, et al.
(författare)
-
The Nup155-mediated organisation of inner nuclear membrane proteins is independent of Nup155 anchoring to the metazoan nuclear pore complex
- 2012
-
Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 125:18, s. 4214-4218
-
Tidskriftsartikel (refereegranskat)abstract
- The nuclear envelope (NE), an important barrier between the nucleus and the cytoplasm, is composed of three structures: the outer nuclear membrane, which is continuous with the ER, the inner nuclear membrane (INM), which interfaces with chromatin, and nuclear pore complexes (NPCs), which are essential for the exchange of macromolecules between the two compartments. The NPC protein Nup155 has an evolutionarily conserved role in the metazoan NE formation; but the in vivo analysis of Nup155 has been severely hampered by the essential function of this protein in cell viability. Here, we take advantage of the hypomorphicity of RNAi systems and use a combination of protein binding and rescue assays to map the interaction sites of two neighbouring NPC proteins Nup93 and Nup53 on Nup155, and to define the requirements of these interactions in INM protein organization. We show that different parts of Drosophila Nup155 have distinct functions: the Nup155 beta-propeller anchors the protein to the NPC, whereas the alpha-solenoid part of Nup155 is essential for the correct localisation of INM proteins lamin-B receptor (LBR) and otefin. Using chromatin extracts from semisynchronized cells, we also provide evidence that the Nup155 alpha-solenoid has a chromatin-binding activity that is stronger at the end of mitosis. Our results argue that the role of Nup155 in INM protein localisation is not mediated through the NPC anchoring activity of the protein and suggest that regions other than Nup155 beta-propeller are necessary for the targeting of proteins to the INM.
|
|
| 6. |
- Chen, Xin, 1980, et al.
(författare)
-
Amyloid-beta peptide-induced cytotoxicity and mitochondrial dysfunction in yeast
- 2015
-
Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 15:6
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by deposits of amyloid-beta(A beta) peptides. However, the underlying molecular mechanisms of neuron cell dysfunction and cell death in AD still remain poorly understood. Yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. Thanks to relatively simple and quick genetic and environmental manipulations, the large knowledge base and data collections, this organism has become a valuable tool to unravel fundamental intracellular mechanisms underlying neurodegeneration. In this study, we have used yeast as a model system to study the effects of intracellular A beta peptides and we found that cells constitutively producing native A beta directed to the secretory pathway exhibited a lower growth rate, lower biomass yield, lower respiratory rate, increased oxidative stress, hallmarks of mitochondrial dysfunction and ubiquitin-proteasome system dysfunction. These findings are relevant for better understanding the role of A beta in cell stress and cell damage.
|
|
| 7. |
- Chen, Xin, 1980, et al.
(författare)
-
FMN reduces Amyloid-beta toxicity in yeast by regulating redox status and cellular metabolism
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is defined by progressive neurodegeneration, with oligomerization and aggregation of amyloid-beta peptides (A beta) playing a pivotal role in its pathogenesis. In recent years, the yeast Saccharomyces cerevisiae has been successfully used to clarify the roles of different human proteins involved in neurodegeneration. Here, we report a genome-wide synthetic genetic interaction array to identify toxicity modifiers of A beta 42, using yeast as the model organism. We find that FMN1, the gene encoding riboflavin kinase, and its metabolic product flavin mononucleotide (FMN) reduce A beta 42 toxicity. Classic experimental analyses combined with RNAseq show the effects of FMN supplementation to include reducing misfolded protein load, altering cellular metabolism, increasing NADH/(NADH+NAD(+)) and NADPH/(NADPH+NADP(+)) ratios and increasing resistance to oxidative stress. Additionally, FMN supplementation modifies Htt103QP toxicity and alpha-synuclein toxicity in the humanized yeast. Our findings offer insights for reducing cytotoxicity of A beta 42, and potentially other misfolded proteins, via FMN-dependent cellular pathways.Saccharomyces cerevisiae is a model organism to study proteins involved in neurodegeneration. Here, the authors performed a yeast genome-wide synthetic genetic interaction array (SGA) to screen for toxicity modifiers of A beta 42 and identify riboflavin kinase and its metabolic product flavin mononucleotide as modulators that alleviate cellular A beta 42 toxicity, which is supported by further experimental analyses.
|
|
| 8. |
- Chen, Xin, 1980, et al.
(författare)
-
Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response
- 2023
-
Ingår i: Advanced Functional Materials. - 1616-3028 .- 1616-301X. ; 33:45
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, with the aggregation of misfolded amyloid-β (Aβ) peptides in the brain being one of its histopathological hallmarks. Recently, graphene oxide (GO) nanoflakes have attracted significant attention in biomedical areas due to their capacity of suppressing Aβ aggregation in vitro. The mechanism of this beneficial effect has not been fully understood in vivo. Herein, the impact of GO on intracellular Aβ42 aggregates and cytotoxicity is investigated using yeast Saccharomyces cerevisiae as the model organism. This study finds that GO nanoflakes can effectively penetrate yeast cells and reduce Aβ42 toxicity. Combination of proteomics data and follow-up experiments show that GO treatment alters cellular metabolism to increases cellular resistance to misfolded protein stress and oxidative stress, and reduces amounts of intracellular Aβ42 oligomers. Additionally, GO treatment also reduces HTT103QP toxicity in the Huntington's disease (HD) yeast model. The findings offer insights for rationally designing GO nanoflakes-based therapies for attenuating cytotoxicity of Aβ42, and potentially of other misfolded proteins involved in neurodegenerative pathology.
|
|
| 9. |
- Chen, Xin, 1980, et al.
(författare)
-
Improved resource allocation strategy in SU-CoMP network
- 2011
-
Ingår i: The Journal of China Universities of Posts and Telecommunications. - 2210-5123. ; 18:4, s. 7-12
-
Tidskriftsartikel (refereegranskat)abstract
- Coordinated Multi-Point transmission and reception (CoMP) for single user, named as SU-CoMP, is considered as an efficient approach tomitigate inter-cell interference in Orthogonal Frequency Division Multiple Access (OFDMA) systems. Two prevalent approaches in SU-CoMP areCoordinated Scheduling (CS) and Joint Processing (JP). Although JP in SU-CoMP has been proved to achieve a great link performanceimprovement for the cell-edge user, efficient Resource Allocation (RA) on the system level is quite needed. However, so far limited work has beendone considering JP, and most existing schemes achieved the improvement of cell-edge performance at cost of the cell-average performancedegradation compared to the single cell RA. In this paper, a two-phase strategy is proposed for SU-CoMP networks. CS and JP are combined toimprove both cell-edge and cell-average performance. Compared to the single cell RA, simulation results demonstrate that, the proposed strategyleads to both higher cell-average and cell-edge throughput.
|
|
| 10. |
- Chen, Xin, 1980, et al.
(författare)
-
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-beta (A beta) Toxicity in Yeast
- 2017
-
Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-beta peptides (A beta) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of A beta associated with AD are A beta 40 and A beta 42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either A beta 40 or A beta 42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth. Reduced growth rates and biomass yields were observed upon A beta 42 expression, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondria' functionality and ATP generation in A beta 42 expressing cells, which matched with observed aberrant mitochondria' structures. Genome-wide expression level analysis showed that A beta 42 expression triggered strong ER stress and unfolded protein responses. Equivalent expression of A beta 40, however, induced only mild ER stress, which resulted in hardly affected physiology. Using AD yeast models in well controlled cultures strengthened our understanding on how cells translate different A beta toxicity signals into particular cell fate programs, and further enhance their potential as a discovery platform to identify possible therapies.
|
|
