| 1. |
- Chung, Sunjae, et al.
(författare)
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Investigation of superlattices based on ferromagnetic semiconductor GaMnAs by planar Hall effect
- 2012
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 111:7, s. 07D310-1-07D310-3
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Tidskriftsartikel (refereegranskat)abstract
- Two ferromagnetic semiconductor GaMnAs-based superlattices (SLs) were investigated by measuring the planar Hall effect (PHE) with the external magnetic field applied in the plane of the sample. The two GaMnAs/GaAs SLs differed only by the Be doping of the nonmagnetic GaAs spacer layers. Both SLs showed a typical two-step transition behavior in PHE field scans at 4.0 K, essentially the same as that normally observed on single GaMnAs ferromagnetic layers with two in-plane magnetic easy axes. As the temperature increased to 30 K, the behaviors of the PHE changed differently in the two SL samples. The PHE in the undoped SL can be described simply by the temperature dependence of the magnetic anisotropy within the film plane of a GaMnAs film. However, the Be-doped SL revealed a completely different behavior, showing a transition of magnetization with a negative coercive field. The observation of this feature in a ferromagnetic multilayer indicates the presence of spontaneous anti-parallel interlayer exchange coupling between the GaMnAs magnetic layers.
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| 2. |
- Kim, D., et al.
(författare)
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Predicting unintended effects of drugs based on off-target tissue effects
- 2016
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 469:3, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- Unintended effects of drugs can be caused by various mechanisms. Conventional analysis of unintended effects has focused on the target proteins of drugs. However, an interaction with off-target tissues of a drug might be one of the unintended effect-related mechanisms. We propose two processes to predict a drug’s unintended effects by off-target tissue effects: 1) identification of a drug’s off-target tissue and; 2) tissue protein - symptom relation identification (tissue protein - symptom matrix). Using this method, we predicted that 1,177 (10.7%) side-effects were related to off-target tissue effects in 11,041 known side-effects. Off-target tissues and unintended effects of successful repositioning drugs were also predicted. The effectiveness of relations of the proposed tissue protein - symptom matrix were evaluated by using the literature mining method. We predicted unintended effects of drugs as well as those effect-related off-target tissues. By using our prediction, we are able to reduce drug side-effects on off-target tissues and provide a chance to identify new indications of drugs of interest.
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| 3. |
- Lee, Sunjae, et al.
(författare)
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Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis
- 2016
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:12, s. 5529-5539
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the underlying molecular mechanisms. As a major cause for development of HCC is fatty liver disease, we here investigated anomalies in regulation of lipid metabolism in the liver. We applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of metabolism. Using transcriptomics data of HCC patients, we identified significant dysregulated expressions of lipid-regulated genes, across many different lipid metabolic pathways. Our findings, however, show that viral hepatitis causes HCC by a distinct mechanism, less likely involving lipid anomalies. Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies.
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| 4. |
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| 5. |
- Lee, Sanghoon, et al.
(författare)
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Magnetotransport properties of ferromagnetic semiconductor GaMnAs-based superlattices
- 2012
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Ingår i: Current applied physics. - : Elsevier BV. - 1567-1739 .- 1878-1675. ; 12:SUPPL. 2, s. S31-S36
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Tidskriftsartikel (refereegranskat)abstract
- Two series of GaMnAs/GaAs superlattices (SSs) comprised of ferromagnetic semiconductor GaMnAs layers and non-magnetic GaAs spacers were investigated by the electronic transport measurements with an external magnetic field applied in the plane of the sample. The two SL series consisted of specimens that were structurally the same, but the GaAs spacers layers of one series were doped by Be, while in the second series the spacers were undoped. Although in field scans taken at 4 K all SLs showed a typical anisotropic magnetoresistance (MR) behavior dominated by magnetic anisotropy, similar to that normally observed in single GaMnAs ferromagnetic layers grown on GaAs (001) substrates, some of the SLs showed signatures of interaction between the GaMnAs layers in the form of broadening of the MR hysteresis. The effect of inter-layer exchange coupling (IEC) between the GaMnAs magnetic layers became clear in the MR data taken at 30 K, where the strength of the magnetic anisotropy was reduced to the level of the inter-layer interaction. Specifically, MR measurements on two of the Be-doped SLs (BD2 and BD3) exhibited conspicuously large values of resistance at zero field, along with transitions of magnetization with negative coercive fields. The observation of these features in GaMnAs/GaAs SLs indicates the presence of spontaneous antiferromagnetic (AFM) inter-layer exchange coupling (IEC) between the GaMnAs magnetic layers. The study further revealed that the IEC in the GaMnAs multilayers strongly depended on the properties of the non-magnetic GaAs spacers, such as their thickness and the density of carriers in the layers. Importantly, these IEC effects occurred on a longer range than that expected from current theoretical studies.
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| 6. |
- Lee, SangWook, et al.
(författare)
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Network analyses identify liver-specific targets for treating liver diseases
- 2017
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.
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| 7. |
- Song, Byong-Sop, et al.
(författare)
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Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Mitochondria are involved in cancer energy metabolism, although the mechanisms underlying the involvement of mitoribosomal dysfunction in hepatocellular carcinoma (HCC) remain poorly understood. Here, we investigated the effects of mitoribosomal impairment-mediated alterations on the immunometabolic characteristics of liver cancer.Methods We used a mouse model of HCC, liver tissues from patients with HCC, and datasets from The Cancer Genome Atlas (TCGA) to elucidate the relationship between mitoribosomal proteins (MRPs) and HCC. In a mouse model, we selectively disrupted expression of the mitochondrial ribosomal protein CR6-interacting factor 1 (CRIF1) in hepatocytes to determine the impact of hepatocyte-specific impairment of mitoribosomal function on liver cancer progression. The metabolism and immunophenotype of liver cancer was assessed by glucose flux assays and flow cytometry, respectively.Results Single-cell RNA-seq analysis of tumor tissue and TCGA HCC transcriptome analysis identified mitochondrial defects associated with high-MRP expression and poor survival outcomes. In the mouse model, hepatocyte-specific disruption of the mitochondrial ribosomal protein CRIF1 revealed the impact of mitoribosomal dysfunction on liver cancer progression. Crif1 deficiency promoted programmed cell death protein 1 expression by immune cells in the hepatic tumor microenvironment. A [U-13C6]-glucose tracer demonstrated enhanced glucose entry into the tricarboxylic acid cycle and lactate production in mice with mitoribosomal defects during cancer progression. Mice with hepatic mitoribosomal defects also exhibited enhanced progression of liver cancer accompanied by highly exhausted tumor-infiltrating T cells. Crif1 deficiency induced an environment unfavorable to T cells, leading to exhaustion of T cells via elevation of reactive oxygen species and lactate production.Conclusions Hepatic mitoribosomal defects promote glucose partitioning toward glycolytic flux and lactate synthesis, leading to T cell exhaustion and cancer progression. Overall, the results suggest a distinct role for mitoribosomes in regulating the immunometabolic microenvironment during HCC progression.
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| 8. |
- Uhlén, Mathias, et al.
(författare)
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A pathology atlas of the human cancer transcriptome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 357:6352, s. 660-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.
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| 9. |
- Zhang, Cheng, et al.
(författare)
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Investigating the Combinatory Effects of Biological Networks on Gene Co-expression
- 2016
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Ingår i: Frontiers in Physiology. - : Frontiers Media. - 1664-042X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Co-expressed genes often share similar functions, and gene co-expression networks have been widely used in studying the functionality of gene modules. Previous analysis indicated that genes are more likely to be co-expressed if they are either regulated by the same transcription factors, forming protein complexes or sharing similar topological properties in protein-protein interaction networks. Here, we reconstructed transcriptional regulatory and protein-protein networks for Saccharornyces cerevisiae using well-established databases, and we evaluated their co-expression activities using publically available gene expression data. Based on our network-dependent analysis, we found that genes that were co-regulated in the transcription regulatory networks and shared similar neighbors in the protein-protein networks were more likely to be co-expressed. Moreover, their biological functions were closely related.
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| 10. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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