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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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.
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| 3. |
- Lee, Hyun-Seob, et al.
(author)
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Foxa2 and Nurr1 Synergistically Yield A9 Nigral Dopamine Neurons Exhibiting Improved Differentiation, Function, and Cell Survival
- 2010
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In: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:3, s. 501-512
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Journal article (peer-reviewed)abstract
- Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs derived from certain species such as mouse and human. We show here that Foxa2, a forkhead transcription factor whose role in midbrain DA neuron development was recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype acquisition, midbrain-specific gene expression, and neuronal maturation. Thus, the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully differentiated nigral (A9)-type midbrain neurons with clearly detectable DA neuronal activities. The effects of Foxa2 in DA neuron generation were observed regardless of the brain regions or species from which NPCs were derived. Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and reduced cell proliferation. Consistently, transplantation of NPCs transduced with Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but reduced number of proliferating cells, and significantly reversed motor deficits in a rat PD model. Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD. STEM CELLS 2010; 28: 501-512
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| 4. |
- An, Junghwa, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Journal article (peer-reviewed)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 5. |
- Mun, Seungsoo, et al.
(author)
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Reconfigurable dual-mode optical encryption enabled by block copolymer photonic crystal with micro-imprinted holographic metasurface
- 2023
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In: Materials Today. - : ELSEVIER SCI LTD. - 1369-7021 .- 1873-4103. ; 70, s. 44-56
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Journal article (peer-reviewed)abstract
- Dual-mode optical encryption based on holographic metasurfaces and color components is of great attraction because of their enhanced information security and storage; however, the realization of independently as well as reversibly encodable holographic metasurfaces and color components remains unreported. Herein, we present reconfigurable dual-mode encryptions of structural colors (SC) and holograms, achieved through stimuli-responsive block copolymer (BCP) photonic crystals (PCs) with micro-imprinted holographic metasurfaces. Holographic images appear when the micro-imprinted BCP PCs, consisting of self-assembled alternating lamellae of two dielectrics, are exposed to an incident laser. A characteristic SC develops in the visible range when the imprinted film is immersed in a liquid agent that can swell one of the dielectrics, allowing for dual-mode holographic and SC encodings in the solid and liquid states, respectively. The dual-mode optical encoding is reconfigured. The holographic image can be erased and replaced with another micropattern, while preserving the SC. Moreover, an SC, set by crosslinking of the swellable lamellae, is reset by chemical de-crosslinking and subsequent transient re-crosslinking, enabling the SC reconfigurability of the BCP PC film. A prototype of a high-security reconfigurable dual encryption has been developed, wherein true information is decrypted when holographic passwords are confirmed with full-color visible SC passwords.
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| 6. |
- Lee, Keum Hwa, et al.
(author)
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Consumption of Fish and omega-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies
- 2020
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In: ADVANCES IN NUTRITION. - : OXFORD UNIV PRESS. - 2161-8313 .- 2156-5376. ; 11:5, s. 1134-1149
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Research review (peer-reviewed)abstract
- Multiple studies have suggested that omega-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between omega-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or omega-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between omega-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta analyses by study design, we found weak associations between omega-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although omega-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between omega-3 fatty acid consumption and cancer risks.
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| 7. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 8. |
- Song, Byong-Sop, et al.
(author)
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Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion
- 2022
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In: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:5
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Journal article (peer-reviewed)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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| 9. |
- Björnsson, Bergthor, et al.
(author)
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Digital twins to personalize medicine
- 2020
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Research review (peer-reviewed)abstract
- Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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| 10. |
- Christian, Parul, et al.
(author)
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Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries
- 2013
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 42:5, s. 1340-1355
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Journal article (peer-reviewed)abstract
- BACKGROUND:Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30-40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain.METHODS:Using extant longitudinal birth cohorts (n = 19) with data on birthweight, gestational age and child anthropometry (12-60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth.RESULTS:We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5-3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively.CONCLUSIONS:This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.
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