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| 2. |
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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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| 5. |
- Kristanl, Matej, et al.
(författare)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 6. |
- Chen, Chi-Kuan, et al.
(författare)
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Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment
- 2014
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Ingår i: Hepatology. - Hoboken : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 59:3, s. 974-985
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects.CONCLUSION: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer.
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| 7. |
- Ariyawansa, Hiran A., et al.
(författare)
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Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
- 2015
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
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Tidskriftsartikel (refereegranskat)abstract
- This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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| 8. |
- Hua, Kuo-Tai, et al.
(författare)
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N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
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Ingår i: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
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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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| 9. |
- Arzoumanian, Doris, et al.
(författare)
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Dust polarized emission observations of NGC 6334: BISTRO reveals the details of the complex but organized magnetic field structure of the high-mass star-forming hub-filament network
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 647
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Tidskriftsartikel (refereegranskat)abstract
- Context. Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained. Aims. We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation. Methods. We present new observations of the dust polarized emission at 850 μm toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the James Clerk Maxwell Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (PI), the polarization fraction (PF), and the plane-of-The-sky B-field angle (χB_POS) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and χBPOS along the ridge crest and compared them with the results obtained from simulated filaments. Results. The observations span 3 orders of magnitude in Stokes I and PI and 2 orders of magnitude in PF (from 0.2 to 20%). A large scatter in PI and PF is observed for a given value of I. Our analyses show a complex B-field structure when observed over the whole region ( 10 pc); however, at smaller scales (1 pc), χBPOS varies coherently along the crests of the filament network. The observed power spectrum of χBPOS can be well represented with a power law function with a slope of-1.33 ± 0.23, which is 20% shallower than that of I. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments, χBPOS rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in PF toward the high-column density (NH2 â 1023 cm-2) star cluster-forming hubs. These latter large PF values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure. Conclusions. These observational results reveal for the first time the characteristics of the small-scale (down to 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
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| 10. |
- Ching, Tao-Chung, et al.
(författare)
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The JCMT BISTRO-2 Survey: Magnetic Fields of the Massive DR21 Filament
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:2
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Tidskriftsartikel (refereegranskat)abstract
- We present 850 mu m dust polarization observations of the massive DR21 filament from the B-fields In STar-forming Region Observations (BISTRO) survey, using the POL-2 polarimeter and the SCUBA-2 camera on the James Clerk Maxwell Telescope. We detect ordered magnetic fields perpendicular to the parsec-scale ridge of the DR21 main filament. In the subfilaments, the magnetic fields are mainly parallel to the filamentary structures and smoothly connect to the magnetic fields of the main filament. We compare the POL-2 and Planck dust polarization observations to study the magnetic field structures of the DR21 filament on 0.1-10 pc scales. The magnetic fields revealed in the Planck data are well-aligned with those of the POL-2 data, indicating a smooth variation of magnetic fields from large to small scales. The plane-of-sky magnetic field strengths derived from angular dispersion functions of dust polarization are 0.6-1.0 mG in the DR21 filament and similar to 0.1 mG in the surrounding ambient gas. The mass-to-flux ratios are found to be magnetically supercritical in the filament and slightly subcritical to nearly critical in the ambient gas. The alignment between column density structures and magnetic fields changes from random alignment in the low-density ambient gas probed by Planck to mostly perpendicular in the high-density main filament probed by James Clerk Maxwell Telescope. The magnetic field structures of the DR21 filament are in agreement with MHD simulations of a strongly magnetized medium, suggesting that magnetic fields play an important role in shaping the DR21 main filament and subfilaments.
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| 11. |
- Doi, Yasuo, et al.
(författare)
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The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 899:1
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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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| 12. |
- Eswaraiah, Chakali, et al.
(författare)
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The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 912:2
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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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| 13. |
- Karoly, Janik, et al.
(författare)
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The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43
- 2023
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 952:1
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of polarized dust emission at 850 mu m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (N-H2 similar to 10(22) - 10(23) cm(-2)) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to similar to 160 +/- 30 mu G in the main starless core and up to similar to 90 +/- 40 mu G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvenic. We also present a new method of data reduction for these denser but fainter objects like starless cores.
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| 14. |
- Kwon, Woojin, et al.
(författare)
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B-fields in Star-forming Region Observations (BISTRO): Magnetic Fields in the Filamentary Structures of Serpens Main
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 926:2
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Tidskriftsartikel (refereegranskat)abstract
- We present 850 mu m polarimetric observations toward the Serpens Main molecular cloud obtained using the POL-2 polarimeter on the James Clerk Maxwell Telescope as part of the B-fields In STar-forming Region Observations survey. These observations probe the magnetic field morphology of the Serpens Main molecular cloud on about 6000 au scales, which consists of cores and six filaments with different physical properties such as density and star formation activity. Using the histogram of relative orientation (HRO) technique, we find that magnetic fields are parallel to filaments in less-dense filamentary structures where NH2 < 0.93 x 10(22) cm(-2) (magnetic fields perpendicular to density gradients), while they are perpendicular to filaments (magnetic fields parallel to density gradients) in dense filamentary structures with star formation activity. Moreover, applying the HRO technique to denser core regions, we find that magnetic field orientations change to become perpendicular to density gradients again at NH2 approximate to 4.6 x 10(22) NH2 approximate to 16 x 10(22) cm(-2), magnetic fields change back to being parallel to density gradients once again, which can be understood to be due to magnetic fields being dragged in by infalling material. In addition, we estimate the magnetic field strengths of the filaments (B-POS = 60-300 mu G)) using the Davis-Chandrasekhar-Fermi method and discuss whether the filaments are gravitationally unstable based on magnetic field and turbulence energy densities.
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| 15. |
- Lyo, A-Ran, et al.
(författare)
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The JCMT BISTRO Survey: An 850/450 mu m Polarization Study of NGC 2071IR in Orion B
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 918:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of simultaneous 450 mu m and 850 mu m polarization observations toward the massive star-forming region NGC 2071IR, a target of the BISTRO (B-fields in STar-forming Region Observations) Survey, using the POL-2 polarimeter and SCUBA-2 camera mounted on the James Clerk Maxwell Telescope. We find a pinched magnetic field morphology in the central dense core region, which could be due to a rotating toroidal disklike structure and a bipolar outflow originating from the central young stellar object IRS 3. Using the modified Davis-Chandrasekhar-Fermi method, we obtain a plane-of-sky magnetic field strength of 563 +/- 421 mu G in the central similar to 0.12 pc region from 850 mu m polarization data. The corresponding magnetic energy density of 2.04 x 10(-8) erg cm(-3) is comparable to the turbulent and gravitational energy densities in the region. We find that the magnetic field direction is very well aligned with the whole of the IRS 3 bipolar outflow structure. We find that the median value of polarization fractions is 3.0% at 450 mu m in the central 3 ' region, which is larger than the median value of 1.2% at 850 mu m. The trend could be due to the better alignment of warmer dust in the strong radiation environment. We also find that polarization fractions decrease with intensity at both wavelengths, with slopes, determined by fitting a Rician noise model of 0.59 +/- 0.03 at 450 mu m and 0.36 +/- 0.04 at 850 mu m, respectively. We think that the shallow slope at 850 mu m is due to grain alignment at the center being assisted by strong radiation from the central young stellar objects.
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| 16. |
- Ngoc, Nguyen Bich, et al.
(författare)
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Observations of Magnetic Fields Surrounding LkH alpha 101 Taken by the BISTRO Survey with JCMT-POL-2
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 908:1
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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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| 17. |
- Tahani, Mehrnoosh, et al.
(författare)
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JCMT BISTRO Observations: Magnetic Field Morphology of Bubbles Associated with NGC 6334
- 2023
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- We study the Hii regions associated with the NGC 6334 molecular cloud observed in the submillimeter and taken as part of the B-fields In STar-forming Region Observations Survey. In particular, we investigate the polarization patterns and magnetic field morphologies associated with these Hii regions. Through polarization pattern and pressure calculation analyses, several of these bubbles indicate that the gas and magnetic field lines have been pushed away from the bubble, toward an almost tangential (to the bubble) magnetic field morphology. In the densest part of NGC 6334, where the magnetic field morphology is similar to an hourglass, the polarization observations do not exhibit observable impact from Hii regions. We detect two nested radial polarization patterns in a bubble to the south of NGC 6334 that correspond to the previously observed bipolar structure in this bubble. Finally, using the results of this study, we present steps (incorporating computer vision; circular Hough transform) that can be used in future studies to identify bubbles that have physically impacted magnetic field lines.
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| 18. |
- Chen, Min-Wei, et al.
(författare)
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H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:20, s. 7830-7840
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Tidskriftsartikel (refereegranskat)abstract
- G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression.
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| 19. |
- Chen, Yujie, et al.
(författare)
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A gradient-distributed liquid-metal hydrogel capable of tunable actuation
- 2021
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 421, s. 127762-
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Tidskriftsartikel (refereegranskat)abstract
- Although thermoresponsive hydrogels have numerous applications that range from soft robots, biomedical engineering, and actuators to sensors for artificial muscles, the existing hydrogel actuators undergo only unidirectional deformation under a single thermal stimulus and suffer from slow actuation and unstable interfacial adhesion in multiple layers. Herein, hydrogels containing gradient-distributed polydopamine-coated eutectic gallium-indium (PDA-EGaIn) nanodroplets in a poly(N-isopropylacrylamide) (PNIPAM) matrix and thus featuring a gradient distribution of thermal conductivity and an increased barrier towards water loss are shown to be capable of a rapid and tuneable thermoresponse. Notably, whereas hydrogels with a low content of PDAEGaIn undergo rapid one-way bending under a single thermal (45 degrees C) stimulus, those with a high content of PDAEGaIn undergo sequential bidirectional (bending) actuation. The ability of these hydrogels to undergo fast and tuneable actuation under a single thermal stimulus makes them suitable for use in grab-release instruments and soft robots.
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| 20. |
- Chen, Zhen, et al.
(författare)
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Multifunctional conductive hydrogels and their applications as smart wearable devices
- 2021
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 9:11, s. 2561-2583
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Forskningsöversikt (refereegranskat)abstract
- Recently, hydrogekbased conductive materials and their applications as smart wearable devices have been paid tremendous attention due to their high stretchability, flexibility, and excellent biocompatibility. Compared with single functional conductive hydrogels, multifunctional conductive hydrogels are more advantageous to match various demands for practical applications. This review focuses on multifunctional conductive hydrogels applied for smart wearable devices. Representative strategies for conduction of hydrogels are discussed firstly: (1) electronic conduction based on the conductive fillers and (2) ionic conduction based on charged ions. Then, the common and intensive research on multiple functionahties of conductive hydrogels, such as mechanical properties, conductive and sensory properties, anti-freezing and moisturizing properties, and adhesion and self-healing properties is presented. The applications of multifunctional conductive hydrogels such as in human motion sensors, sensory skins, and personal healthcare diagnosis are provided in the third part. Finally, we offer our perspective on open challenges and future areas of interest for multifunctional conductive hydrogels used as smart wearable devices.
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| 21. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 22. |
- Hwang, Jihye, et al.
(författare)
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The JCMT BISTRO Survey: A Spiral Magnetic Field in a Hub-filament Structure, Monoceros R2
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:1
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Tidskriftsartikel (refereegranskat)abstract
- We present and analyze observations of polarized dust emission at 850 μm toward the central 1 × 1 pc hub-filament structure of Monoceros R2 (Mon R2). The data are obtained with SCUBA-2/POL-2 on the James Clerk Maxwell Telescope (JCMT) as part of the B-fields in Star-forming Region Observations survey. The orientations of the magnetic field follow the spiral structure of Mon R2, which are well described by an axisymmetric magnetic field model. We estimate the turbulent component of the magnetic field using the angle difference between our observations and the best-fit model of the underlying large-scale mean magnetic field. This estimate is used to calculate the magnetic field strength using the Davis–Chandrasekhar–Fermi method, for which we also obtain the distribution of volume density and velocity dispersion using a column density map derived from Herschel data and the C18O (J = 3 - 2) data taken with HARP on the JCMT, respectively. We make maps of magnetic field strengths and mass-to-flux ratios, finding that magnetic field strengths vary from 0.02 to 3.64 mG with a mean value of 1.0 ± 0.06 mG, and the mean critical mass-to-flux ratio is 0.47 ± 0.02. Additionally, the mean Alfvén Mach number is 0.35 ± 0.01. This suggests that, in Mon R2, the magnetic fields provide resistance against large-scale gravitational collapse, and the magnetic pressure exceeds the turbulent pressure. We also investigate the properties of each filament in Mon R2. Most of the filaments are aligned along the magnetic field direction and are magnetically subcritical.
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| 23. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
-
Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 24. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 25. |
- Chen, Yujie, et al.
(författare)
-
Shape-Memory Polymeric Artificial Muscles : Mechanisms, Applications and Challenges
- 2020
-
Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:18
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Forskningsöversikt (refereegranskat)abstract
- Shape-memory materials are smart materials that can remember an original shape and return to their unique state from a deformed secondary shape in the presence of an appropriate stimulus. This property allows these materials to be used as shape-memory artificial muscles, which form a subclass of artificial muscles. The shape-memory artificial muscles are fabricated from shape-memory polymers (SMPs) by twist insertion, shape fixation via T(m)or T-g, or by liquid crystal elastomers (LCEs). The prepared SMP artificial muscles can be used in a wide range of applications, from biomimetic and soft robotics to actuators, because they can be operated without sophisticated linkage design and can achieve complex final shapes. Recently, significant achievements have been made in fabrication, modelling, and manipulation of SMP-based artificial muscles. This paper presents a review of the recent progress in shape-memory polymer-based artificial muscles. Here we focus on the mechanisms of SMPs, applications of SMPs as artificial muscles, and the challenges they face concerning actuation. While shape-memory behavior has been demonstrated in several stimulated environments, our focus is on thermal-, photo-, and electrical-actuated SMP artificial muscles.
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| 26. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 27. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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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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| 28. |
- Lai, Kuei-Hung, et al.
(författare)
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Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Two new scalarane sesterterpenoids, 12 beta-(3'beta-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12 beta-(3'beta-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 mu g/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase II alpha expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70(S6k), NF kappa B, Raf-1, p-GSK3 beta, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.
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| 29. |
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| 30. |
- Chen, Chi-Hua, et al.
(författare)
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Leveraging genome characteristics to improve gene discovery for putamen subcortical brain structure
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Discovering genetic variants associated with human brain structures is an on-going effort. The ENIGMA consortium conducted genome-wide association studies (GWAS) with standard multi-study analytical methodology and identified several significant single nucleotide polymorphisms (SNPs). Here we employ a novel analytical approach that incorporates functional genome annotations (e.g., exon or 5′UTR), total linkage disequilibrium (LD) scores and heterozygosity to construct enrichment scores for improved identification of relevant SNPs. The method provides increased power to detect associated SNPs by estimating stratum-specific false discovery rate (FDR), where strata are classified according to enrichment scores. Applying this approach to the GWAS summary statistics of putamen volume in the ENIGMA cohort, a total of 15 independent significant SNPs were identified (conditional FDR < 0.05). In contrast, 4 SNPs were found based on standard GWAS analysis (P < 5 × 10−8). These 11 novel loci include GATAD2B, ASCC3, DSCAML1, and HELZ, which are previously implicated in various neural related phenotypes. The current findings demonstrate the boost in power with the annotation-informed FDR method, and provide insight into the genetic architecture of the putamen.
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| 31. |
- Chi, Chaodan, et al.
(författare)
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Si-based InGaAs photodetectors on heterogeneous integrated substrate
- 2021
-
Ingår i: Science China: Physics, Mechanics and Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 64:6
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, InGaAs p-i-n photodetectors (PDs) on an InP/SiO2/Si (InPOI) substrate fabricated by ion-slicing technology are demonstrated and compared with the identical device on a commercial InP substrate. The quality of epitaxial layers on the InPOI substrate is similar to that on the InP substrate. The photo responsivities of both devices measured at 1.55 µm are comparable, which are about 0.808–0.828 A W−1. Although the dark current of PD on the InPOI substrate is twice as high as that of PD on the InP substrate at 300 K, the peak detectivities of both PDs are comparable. In general, the overall performance of the InPOI-based PD is comparable to the InP-based PD, demonstrating that the ion-slicing technology is a promising route to enable the high-quality Si-based InP platform for the full photonic integration on a Si substrate.
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| 32. |
- Chien, Ming-Hsien, et al.
(författare)
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Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway.
- 2009
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 30:12, s. 2005-13
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF)-C is recognized as a tumor lymphangiogenic factor based on the effects of activated VEGF-R3 on lymphatic endothelial cells. Many tumor cells express VEGF-R3 but the function of this receptor in tumor cells is largely unknown. It has been reported that the VEGF-C/VEGF-R3 axis is activated in subsets of leukemia patients. Herein, we have shown that VEGF-C induces angiogenic activity in the tube formation assay invitro and Matrigel plug assay in vivo by upregulating an angiogenic factor, cyclooxygenase-2 (COX-2), through VEGF-R3 in the human acute myeloid leukemia (AML) cell line, THP-1. COX-2 induction by VEGF-C was also observed in other VEGF-R3(+) human AML cell lines (U937 and HL60). Moreover, immunohistochemical analysis of bone marrow specimens of 37 patients diagnosed with AML revealed that VEGF-C expression in specimens was associated with the expression of COX-2 (P < 0.001). The manner by which signaling pathways transduced by VEGF-C is responsible for COX-2 upregulation was further investigated. Blocking the p42/44 mitogen-activated protein kinase (MAPK) pathway with the MAPK kinase inhibitor, PD 98059, failed to inhibit VEGF-C-mediated COX-2 expression. However, VEGF-C-induced COX-2 upregulation was effectively abolished by overexpression of dominant-negative c-Jun N-terminal kinase (JNK) or treatment with the JNK inhibitor, SP 600125. VEGF-C induced JNK-dependent nuclear translocation of c-Jun. Furthermore, chromatin immunoprecipitation and reporter assays revealed that VEGF-C enhanced c-Jun binding to the cyclic adenosine 3',5'-monophosphate-response element of the COX-2 promoter and induced COX-2 expression. In sum, the data herein highlight the pathogenic role of VEGF-C in leukemia via regulation of angiogenesis through upregulation of COX-2.
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| 33. |
- Kauppi, Karolina, et al.
(författare)
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Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease
- 2018
-
Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Improved prediction of progression to Alzheimer's Disease (AD) among older individuals with mild cognitive impairment (MCI) is of high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age of AD onset above and beyond APOE. Here, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to further explore the potential clinical utility of PHS for predicting AD development in older adults with MCI. We examined the predictive value of PHS alone and in combination with baseline structural magnetic resonance imaging (MRI) data on performance on the Mini-Mental State Exam (MMSE). In survival analyses, PHS significantly predicted time to progression from MCI to AD over 120 months (p = 1.07e-5), and PHS was significantly more predictive than APOE alone (p = 0.015). Combining PHS with baseline brain atrophy score and/or MMSE score significantly improved prediction compared to models without PHS (three-factor model p = 4.28e-17). Prediction model accuracies, sensitivities and area under the curve were also improved by including PHS in the model, compared to only using atrophy score and MMSE. Further, using linear mixed-effect modeling, PHS improved the prediction of change in the Clinical Dementia Rating—Sum of Boxes (CDR-SB) score and MMSE over 36 months in patients with MCI at baseline, beyond both APOE and baseline levels of brain atrophy. These results illustrate the potential clinical utility of PHS for assessment of risk for AD progression among individuals with MCI both alone, or in conjunction with clinical measures of prodromal disease including measures of cognitive function and regional brain atrophy.
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| 34. |
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| 35. |
- Kauppi, Karolina, et al.
(författare)
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Revisiting Antipsychotic Drug Actions Through Gene Networks Associated With Schizophrenia
- 2018
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Ingår i: American Journal of Psychiatry. - : AMER PSYCHIATRIC PUBLISHING, INC. - 0002-953X .- 1535-7228. ; 175:7, s. 674-682
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel "druggable" pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated, but specific genes and pathways constituting this overlap are undetermined. Risk genes of polygenic disorders do not operate in isolation but in combination with other genes through protein-protein interactions among gene product.Method: The protein interactome was used to map antipsychotic drug targets (N=88) to networks of schizophrenia risk genes (N=328).Results: Schizophrenia risk genes were significantly localized in the interactome, forming a distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH, and HCN families were not connected to existing antipsychotics but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia, such as cognitive or negative symptoms.Conclusions: The network medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multitarget antischizophrenia drugs. This approach is transferable to other diseases.
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| 36. |
- Koch, Elise, et al.
(författare)
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Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia
- 2023
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified 12 drug repurposing candidates, most of which have anti-inflammatory and neuroprotective effects. Sex-stratified analyses showed that out of these 12 drugs, four were identified in females only, three were identified in males only, and five were identified in both sexes. Based on our bioinformatics analyses of disease genetics, we suggest 12 candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options.
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| 37. |
- Koch, Elise, et al.
(författare)
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Interactome overlap between schizophrenia and cognition
- 2020
-
Ingår i: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509. ; 222, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairments constitute a core feature of schizophrenia, and a genetic overlap between schizophrenia and cognitive functioning in healthy individuals has been identified. However, due to the high polygenicity and complex genetic architecture of both traits, overlapping biological pathways have not yet been identified between schizophrenia and normal cognitive ability. Network medicine offers a framework to study underlying biological pathways through protein-protein interactions among risk genes. Here, established network-based methods were used to characterize the biological relatedness of schizophrenia and cognition by examining the genetic link between schizophrenia risk genes and genes associated with cognitive performance in healthy individuals, through the protein interactome. First, network separation showed a profound interactome overlap between schizophrenia risk genes and genes associated with cognitive performance (S-AB = -0.22, z-score = -6.80, p= 5.38e-12). To characterize this overlap, network propagation was thereafter used to identify schizophrenia risk genes that are close to cognition-associated genes in the interactome network space (n = 140, of which 54 were part of the direct genetic overlap). Schizophrenia risk genes close to cognition were enriched for pathways including long-termpotentiation and Alzheimer's disease, and included genes with a role in neurotransmitter systems important for cognitive functioning, such as glutamate and dopamine. These results pinpoint a subset of schizophrenia risk genes that are of particular interest for further examination in schizophrenia patient groups, of which some are druggable genes with potential as candidate targets for cognitive enhancing drugs.
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| 38. |
- Lo, Min-Tzu, et al.
(författare)
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Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 152-156
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Tidskriftsartikel (refereegranskat)abstract
- Personality is influenced by genetic and environmental factors(1) and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci(2,3), significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132-260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422-18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit- hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion-introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).
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| 39. |
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| 40. |
- Lo, Min-Tzu, et al.
(författare)
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Identification of genetic heterogeneity of Alzheimer's disease across age
- 2019
-
Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 84, s. 243.e1-243.e9
-
Tidskriftsartikel (refereegranskat)abstract
- The risk of APOE for Alzheimer's disease (AD) is modified by age. Beyond APOE, the polygenic architecture may also be heterogeneous across age. We aim to investigate age-related genetic heterogeneity of AD and identify genomic loci with differential effects across age. Stratified gene-based genome-wide association studies and polygenic variation analyses were performed in the younger (60-79 years, N = 14,895) and older (>= 80 years, N = 6559) age-at-onset groups using Alzheimer's Disease Genetics Consortium data. We showed a moderate genetic correlation (r(g) = 0.64) between the two age groups, supporting genetic heterogeneity. Heritability explained by variants on chromosome 19 (harboring APOE) was significantly larger in younger than in older onset group (p < 0.05). APOE region, BIN1, OR2S2, MS4A4E, and PICALM were identified at the gene-based genome-wide significance (p < 2.73 x 10(-6)) with larger effects at younger age (except MS4A4E). For the novel gene OR2S2, we further performed leave-one-out analyses, which showed consistent effects across subsamples. Our results suggest using genetically more homogeneous individuals may help detect additional susceptible loci. Published by Elsevier Inc.
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| 41. |
- Lo, Min-Tzu, et al.
(författare)
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Modeling prior information of common genetic variants improves gene discovery for neuroticism
- 2017
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Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:22, s. 4530-4539
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Tidskriftsartikel (refereegranskat)abstract
- Neuroticism reflects emotional instability, and is related to various mental and physical health issues. However, the majority of genetic variants associated with neuroticism remain unclear. Inconsistent genetic variants identified by different genome-wide association studies (GWAS) may be attributable to low statistical power. We proposed a novel framework to improve the power for gene discovery by incorporating prior information of single nucleotide polymorphisms (SNPs) and combining two relevant existing tools, relative enrichment score (RES) and conditional false discovery rate (FDR). Here, SNP's conditional FDR was estimated given its RES based on SNP prior information including linkage disequilibrium (LD)-weighted genic annotation scores, total LD scores and heterozygosity. A known significant locus in chromosome 8p was excluded before estimating FDR due to long-range LD structure. Only one significant LD-independent SNP was detected by analyses of unconditional FDR and traditional GWAS in the discovery sample (N = 59 225), and notably four additional SNPs by conditional FDR. Three of the five SNPs, all identified by conditional FDR, were replicated (P < 0.05) in an independent sample (N = 170 911). These three SNPs are located in intronic regions of CADM2, LINGO2 and EP300 which have been reported to be associated with autism, Parkinson's disease and schizophrenia, respectively. Our approach using a combination of RES and conditional FDR improved power of traditional GWAS for gene discovery providing a useful framework for the analysis of GWAS summary statistics by utilizing SNP prior information, and helping to elucidate the links between neuroticism and complex diseases from a genetic perspective.
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| 42. |
- Sanyal, Nilotpal, et al.
(författare)
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GWASinlps : non-local prior based iterative SNP selection tool for genome-wide association studies
- 2019
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Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811. ; 35:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Multiple marker analysis of the genome-wide association study (GWAS) data has gained ample attention in recent years. However, because of the ultra high-dimensionality of GWAS data, such analysis is challenging. Frequently used penalized regression methods often lead to large number of false positives, whereas Bayesian methods are computationally very expensive. Motivated to ameliorate these issues simultaneously, we consider the novel approach of using non-local priors in an iterative variable selection framework.Results: We develop a variable selection method, named, iterative non-local prior based selection for GWAS, or GWASinlps, that combines, in an iterative variable selection framework, the computational efficiency of the screen-and-select approach based on some association learning and the parsimonious uncertainty quantification provided by the use of non-local priors. The hallmark of our method is the introduction of 'structured screen-and-select' strategy, that considers hierarchical screening, which is not only based on response-predictor associations, but also based on response-response associations and concatenates variable selection within that hierarchy. Extensive simulation studies with single nucleotide polymorphisms having realistic linkage disequilibrium structures demonstrate the advantages of our computationally efficient method compared to several frequentist and Bayesian variable selection methods, in terms of true positive rate, false discovery rate, mean squared error and effect size estimation error. Further, we provide empirical power analysis useful for study design. Finally, a real GWAS data application was considered with human height as phenotype.
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| 43. |
- Smeland, Olav B., et al.
(författare)
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Shared genetic variants between schizophrenia and general cognitive function indicate common molecular genetic mechanisms
- 2017
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Ingår i: European Neuropsychopharmacology. - : ELSEVIER SCIENCE BV. - 0924-977X .- 1873-7862. ; 27, s. S410-S410
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Schizophrenia (SCZ) is a severe mental disorder characterized by widespread cognitive impairments including deficits in learning, memory, processing speed, attention and executive functioning. Although cognitive deficits are a strong predictor of functional outcome in SCZ, current treatment strategies largely fail to ameliorate these impairments. Thus, in order to develop more efficient treatment strategies in SCZ, a better understanding of the pathogenesis of these cognitive deficits is needed. Given that both SCZ and cognitive ability are substantially heritable, we here aimed to determine whether SCZ share genetic influences with general cognitive function (COG), a phenotype that captures the shared variation in performance across several cognitive domains. Methods: We analyzed GWAS results in the form of summary statistics (p-values and z-scores) from SCZ (the Psychiatric Genomics Consortium; n=82 315) and COG (CHARGE Consortium; n=53 949). We applied a conditional false discovery rate (FDR) framework. By leveraging SNP-associations in a secondary trait (SCZ or COG), the conditional FDR approach increases power to detect loci in the primary trait (COG or SCZ), regardless of the directions of allelic effects of the risk loci. We then applied the conjunction FDR to identify shared loci between the phenotypes. The conjunction FDR is defined as the maximum of the conditional FDRs for both directions, and we used an overall FDR threshold of 0.05. Results: To visualize pleiotropic enrichment, we constructed conditional Q-Q plots which indicate substantial polygenetic overlap between SCZ and COG. For progressively stringent p-value thresholds for SCZ SNPs, we found approximately 150-fold enrichment for COG. For progressively stringent p-value thresholds for COG SNPs, we found approximately 100-fold enrichment for SCZ. We then used the conjunction FDR and identified fourteen independent loci shared between SCZ and COG. The majority of the shared loci show inverse associations in SCZ and COG, in line with the observed cognitive dysfunction in SCZ. Discussion: Our preliminary findings indicate shared molecular genetic mechanisms between SCZ and COG, which may provide important new insights into the pathogenesis of cognitive dysfunction in SCZ.
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| 44. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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