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Sökning: WFRF:(Chen Shih Shih)

  • Resultat 1-10 av 72
  • [1]234567...8Nästa
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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)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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2.
  • Chen, Ji, et al. (författare)
  • The trans-ancestral genomic architecture of glycemic traits
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:6, s. 840-860
  • Tidskriftsartikel (refereegranskat)abstract
    • Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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3.
  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)
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4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 45:11, s. 1345-1345
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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5.
  • Doi, Yasuo, et al. (författare)
  • The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
  • 2020
  • Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 899:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present new observations of the active star formation region NGC 1333 in the Perseus molecular cloud complex from the James Clerk Maxwell Telescope B-Fields In Star-forming Region Observations (BISTRO) survey with the POL-2 instrument. The BISTRO data cover the entire NGC 1333 complex (∼1.5 pc ? 2 pc) at 0.02 pc resolution and spatially resolve the polarized emission from individual filamentary structures for the first time. The inferred magnetic field structure is complex as a whole, with each individual filament aligned at different position angles relative to the local field orientation. We combine the BISTRO data with low- and high- resolution data derived from Planck and interferometers to study the multiscale magnetic field structure in this region. The magnetic field morphology drastically changes below a scale of ∼1 pc and remains continuous from the scales of filaments (∼0.1 pc) to that of protostellar envelopes (∼0.005 pc or ∼1000 au). Finally, we construct simple models in which we assume that the magnetic field is always perpendicular to the long axis of the filaments. We demonstrate that the observed variation of the relative orientation between the filament axes and the magnetic field angles are well reproduced by this model, taking into account the projection effects of the magnetic field and filaments relative to the plane of the sky. These projection effects may explain the apparent complexity of the magnetic field structure observed at the resolution of BISTRO data toward the filament network.
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6.
  • Eswaraiah, Chakali, et al. (författare)
  • The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
  • 2021
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 912:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.
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7.
  • Hua, Kuo-Tai, et al. (författare)
  • N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
  • 2011
  • Ingår i: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
  • Tidskriftsartikel (refereegranskat)abstract
    • N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
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8.
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9.
  • Ngoc, Nguyen Bich, et al. (författare)
  • Observations of Magnetic Fields Surrounding LkH alpha 101 Taken by the BISTRO Survey with JCMT-POL-2
  • 2021
  • Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 908:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the first high spatial resolution measurement of magnetic fields surrounding LkH alpha 101, part of the Auriga-California molecular cloud. The observations were taken with the POL-2 polarimeter on the James Clerk Maxwell Telescope within the framework of the B-fields In Star-forming Region Observations (BISTRO) survey. Observed polarization of thermal dust emission at 850 mu m is found to be mostly associated with the redshifted gas component of the cloud. The magnetic field displays a relatively complex morphology. Two variants of the Davis-Chandrasekhar-Fermi method, unsharp masking and structure function, are used to calculate the strength of magnetic fields in the plane of the sky, yielding a similar result of B-POS similar to 115 mu G. The mass-to-magnetic-flux ratio in critical value units, lambda similar to 0.3, is the smallest among the values obtained for other regions surveyed by POL-2. This implies that the LkH alpha 101 region is subcritical, and the magnetic field is strong enough to prevent gravitational collapse. The inferred delta B/B-0 similar to 0.3 implies that the large-scale component of the magnetic field dominates the turbulent one. The variation of the polarization fraction with total emission intensity can be fitted by a power law with an index of alpha = 0.82 0.03, which lies in the range previously reported for molecular clouds. We find that the polarization fraction decreases rapidly with proximity to the only early B star (LkH alpha 101) in the region. Magnetic field tangling and the joint effect of grain alignment and rotational disruption by radiative torques can potentially explain such a decreasing trend.
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10.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 45:11, s. 1274-1274
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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