| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
|
|
| 3. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 4. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 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.
|
|
| 5. |
- Zhang, Huai, et al.
(författare)
-
A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
-
Ingår i: Hepatology international. - 1936-0541.
-
Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
|
|
| 6. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
|
|
| 7. |
- Zhang, Guojie, et al.
(författare)
-
Comparative genomics reveals insights into avian genome evolution and adaptation
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1311-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
|
|
| 8. |
- Zhang, Li, et al.
(författare)
-
Characterization of anti-BCG benz[α]anthraquinones and new siderophores from a Xinjiang desert-isolated rare actinomycete Nocardia sp. XJ31
- 2020
-
Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 104:19, s. 8267-8278
-
Tidskriftsartikel (refereegranskat)abstract
- The current global demand for novel anti-TB drugs has drawn urgent attention on the discovery of natural product compounds with anti-TB activity. Lots of efforts have emphasized on environmental samples from unexplored or underexplored natural habits and identified numerous rare actinomycete taxa producing structurally diverse bioactive natural products. Herein, we report a survey of the rare actinobacteria diversity in Xinjiang region together with the discovery of anti-TB active natural products from these strains. We have collected 17 soil samples at different sites with different environmental conditions, from which 39 rare actinobacteria were identified by using a selective isolation strategy with 5 media variations. Among those isolated strains, XJ31 was identified as a new Nocardia sp. based on 16S rRNA gene analysis. Through one strain-many compounds (OSMAC) strategy combined with anti-Bacillus Calmette-Guérin bioassay-guided isolation, two groups of compounds were identified. They were twelve siderophores (nocardimicins, 1-12) and two anthraquinones (brasiliquinones, 13 and 14) and ten of them were identified as new compounds. The structures of the purified compounds were elucidated using HR-ESI-MS, 1D NMR, and 2D NMR techniques. The anti-TB bioassays revealed that the two benz[α]anthraquinones have potent activity against BCG (MICs = 25 μM), which can be used as a promising start point for further anti-TB drug development.
|
|
| 9. |
- Mahajan, Anubha, et al.
(författare)
-
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
|
|
| 10. |
- Reimers, Jeffrey R., et al.
(författare)
-
Challenges facing an understanding of the nature of low-energy excited states in photosynthesis
- 2016
-
Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1857:9, s. 1627-1640
-
Forskningsöversikt (refereegranskat)abstract
- While the majority of the photochemical states and pathways related to the biological capture of solar energy are now well understood and provide paradigms for artificial device design, additional low-energy states have been discovered in many systems with obscure origins and significance. However, as low-energy states are naively expected to be critical to function, these observations pose important challenges. A review of known properties of low energy states covering eight photochemical systems, and options for their interpretation, are presented. A concerted experimental and theoretical research strategy is suggested and outlined, this being aimed at providing a fully comprehensive understanding.
|
|
| 11. |
- Wei, Xiao-Ping, et al.
(författare)
-
Investigations on electronic, Fermi surface, Curie temperature and optical properties of Zr2CoAl
- 2017
-
Ingår i: Journal of Solid State Chemistry. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0022-4596 .- 1095-726X. ; 247, s. 97-104
-
Tidskriftsartikel (refereegranskat)abstract
- Using full-potential local-orbital minimum-basis along with spin-polarized relativistic Korringa-Kohn-Rostoker methods, we study the electronic, Fermi surface, Curie temperature and optical properties of Zr2CoAl alloy. The alloy with Li2AgSb and Cu2MnAl structures are compared in terms of magnetic properties, and the electronic structures in two structures are also discussed. According to the calculated electronic states, it finds that the Zr2CoAl with Li2AgSb structure is half-metallic ferromagnet with an integral magnetic moment of 2.00 mu(beta), meanwhile we also notice the d-d and p-d hybridizations are responsible for the formation of minority-spin gap, furthermore, the fat-bands are applied to discuss the mixture between d and p electrons in the vicinity of the Fermi level. The Fermi surfaces related to the valence bands are constructed, and it is found that the spin-up valence bands 26, 27 and 28 across the Fermi energy dominate the nature of electrons. By mapping the system onto a Heisenberg Hamiltonian, we obtain the exchange coupling parameters, and observe that the Zr(A)-Co(C) and Zr(A)-Zr(B) interactions provide a major contribution for exchange interactions. Based on the calculated exchange coupling parameters, the Curie temperature is estimated to be 287.86 K at equilibrium, and also the dependence of Curie temperature on lattice constant related to the tunable Curie temperature in Zr2CoAl alloy is studied. Finally, we report the optical properties of Zr2CoAl alloy, and present the photon energy dependence of the absorption, the optical conductivity and the loss function.
|
|
| 12. |
- Zhang, Yue-Jiao, et al.
(författare)
-
Probing the Electronic Structure of Heterogeneous Metal Interfaces by Transition Metal Shelled Gold Nanoparticle-Enhanced Raman Spectroscopy
- 2016
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:37, s. 20684-20691
-
Tidskriftsartikel (refereegranskat)abstract
- In heterogeneous catalysis, characterization of heterogeneous metal interfaces of bimetallic catalysts is a crucial step to elucidate the catalytic performance and is a key to develop advanced catalysts. However, analytical techniques such as X-ray photoelectron spectroscopy can only work in vacuum conditions and are difficult to use for in situ analysis. Here, we present efficient and convenient core-shell nano particle-enhanced Raman spectroscopy to explore the in situ electronic structures of heterogeneous interfaces (Au@Pd and Au@Pt core-shell NPs) by varying the shell thickness. The experimental observations reported here clearly show that Pd donates electrons to Au, while Pt accepts electrons from Au at the heterogeneous interfaces. This conclusion gains further support from ex situ X-ray photoelectron spectroscopy results. The Au core greatly affects the electronic structures of both the Pd and Pt shells as well as catalytic behaviors. Finally, the as prepared core-shell nanoparticles were used to demonstrate their improved catalytic properties in real electrocatalytic systems such as methanol oxidation and oxygen reduction reactions.
|
|
| 13. |
- Cheng, Shi-Ping, et al.
(författare)
-
Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
-
Ingår i: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
|
|
| 14. |
- Hu, Honglin, et al.
(författare)
-
Self-Configuration and Self-Optimization for LTE Networks
- 2010
-
Ingår i: IEEE Communications Magazine. - 0163-6804 .- 1558-1896. ; 48:2, s. 94-100
-
Tidskriftsartikel (refereegranskat)abstract
- With the rapid growth of mobile communications, deployment and maintenance of cellular mobile networks are becoming more and more complex, time consuming, and expensive. In order to meet the requirements of network operators and service providers, the telecommunication industry and international standardization bodies have recently paid intensive attention to the research and development of self-organizing networks. In this article we first introduce both the market and technological perspectives for SONs. Then we focus on the self-configuration procedure and illustrate a self-booting mechanism for a newly added evolved NodeB without a dedicated backhaul interface. Finally, mobility load balancing as one of the most important self-optimization issues for Long Term Evolution networks is discussed, and a distributed MLB algorithm with low handover cost is proposed and evaluated.
|
|
| 15. |
- Li-Juan, Zhang, et al.
(författare)
-
A novel water layer structure inside nanobubbles at room temperature
- 2014
-
Ingår i: NUCL SCI TECH. - 1001-8042. ; 25:6, s. 060503-
-
Tidskriftsartikel (refereegranskat)abstract
- Molecularly thin water layer, with a hydrogen bonding network different from those in bulk water and ice, has unique properties and is generally involved in many important processes such as wetting, erosion, atmosphere chemical reaction, protein folding and biomolecular interaction. Here, we report a new water layer structure at room temperature, which is found inside nanobubbles by using synchrotron based scanning transmission soft X-ray microscopy (STXM). The three peaks 535.0, 536.8 and 540.9 eV at O K edge inside the nanobubbles show a novel characteristics of very thin water layers, which has never been observed before.
|
|
| 16. |
- Liu, Lu-Chuan, et al.
(författare)
-
Improved Spatial Resolution Achieved by Chromatic Intensity Interferometry
- 2021
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 127:10
-
Tidskriftsartikel (refereegranskat)abstract
- Interferometers are widely used in imaging technologies to achieve enhanced spatial resolution, but require that the incoming photons be indistinguishable. In previous work, we built and analyzed color erasure detectors, which expand the scope of intensity interferometry to accommodate sources of different colors. Here we demonstrate experimentally how color erasure detectors can achieve improved spatial resolution in an imaging task, well beyond the diffraction limit. Utilizing two 10.9-mm- aperture telescopes and a 0.8 m baseline, we measure the distance between a 1063.6 and a 1064.4 nm source separated by 4.2 mm at a distance of 1.43 km, which surpasses the diffraction limit of a single telescope by about 40 times. Moreover, chromatic intensity interferometry allows us to recover the phase of the Fourier transform of the imaged objects-a quantity that is, in the presence of modest noise, inaccessible to conventional intensity interferometry.
|
|
| 17. |
- Movérare-Skrtic, Sofia, et al.
(författare)
-
Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.
- 2014
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 20:11, s. 1279-88
-
Tidskriftsartikel (refereegranskat)abstract
- The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.
|
|
| 18. |
- Shi, Ying, et al.
(författare)
-
Effects of low-molecular-weight polyols on the hydration status of the light-harvesting complex 2 from Rhodobacter sphaeroides 2.4.1
- 2021
-
Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 20:5, s. 627-637
-
Tidskriftsartikel (refereegranskat)abstract
- Low-molecular-weight (MW) polyols are organic osmolytes influencing water activity. We have investigated the effects of polyol molecules (glycerol and sorbitol) on the optical and triplet excitation dynamics of light-harvesting complex 2 (LH2) from Rhodobacter (Rba.) sphaeroides in buffer-detergent solutions. The resonance Raman spectroscopy demonstrated that, on increasing glycerol and sorbitol volume fractions ranging from 0 to 80% (v/v) (accompanied by the decreasing water activities), the planar and all-trans conformation of carotenoids (Crts) remained unchanged, and the bacteriochlorophyll a (BChl) Qy absorption intensity decreased. The B850 fluorescence amplitude elevated in the 20–80% v/v sorbitol and 20–40% v/v glycerol solution, but decreased in 80% v/v glycerol solution. The change of 3[Crt*–BChl] interaction bands caused by 3Crt*–BChl interaction had no obvious correlation with water activities against polyol volume fractions, which are rationalized by the water activity sensitive of C- and N-termini of protein which binding with BChls. The results suggest that Rba. sphaeroides LH2 is more sensitive to low-molecular-weight polyols compared with that of the thermophiles purple bacterium Thermochromatium (Tch.) tepidum we had investigated before. Graphic abstract: [Figure not available: see fulltext.]
|
|
| 19. |
- Wang, Mo-Jin, et al.
(författare)
-
The prognostic factors and multiple biomarkers in young patients with colorectal cancer
- 2015
-
Ingår i: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:10645
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.
|
|
| 20. |
- Wei, Jian-Feng, et al.
(författare)
-
Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility
- 2008
-
Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 217:2, s. 544-557
-
Tidskriftsartikel (refereegranskat)abstract
- Focal adhesion kinase (FAK) plays key roles in cell adhesion and migration. We now report that the delayed rectifier Kv2.1 potassium channel, through its LD-like motif in N-terminus, may interact with FAK and enhance phosphorylation of FAK(397) and FAK(576/577) Overlapping distribution of Kv2.1 and FAK was observed on soma and proximal dendrites of cortical neurons. FAK expression promotes a polarized membrane distribution of the Kv2.1 channel. In Kv2.1-transfected CHO cells, formation of the Kv2.1-FAK complex was stimulated by fibronectin/integrin and inhibited by the K channel blocker tetraethylammonium (TEA). FAK phosphorylation was minimized by shRNA knockdown of the Kv2.1 channel, point mutations of the N-terminus, and TEA, respectively. Cell migration morphology was altered by Kv2.1 knockdown or TEA, hindering cell migration activity. In wound healing tests in vitro and a traumatic injury animal model, Kv2.1 expression and co-localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility.
|
|
| 21. |
- Xing, Li-Da, et al.
(författare)
-
Asianopodus-type footprints from the Hekou Group of Honggu District, Lanzhou City, Gansu, China and the “heel” of large theropod tracks
- 2014
-
Ingår i: Palaeoworld. - : Elsevier BV. - 1871-174X .- 1875-5887. ; 23:3-4, s. 304-313
-
Tidskriftsartikel (refereegranskat)abstract
- An increasing number of dinosaur tracksites have been reported from the Cretaceous Hekou Group deposits of the Lanzhou-Minhe Basin in theGansu Province region. These include small sites such as the Huazhuang tracksite, from the Honggu District reported here, the Zhongpu tracksitewith multiple track levels but few well-preserved tracks, other small tracksites currently under investigation, and the large and diverse LiujixiaNational Dinosaur Geopark site at Yanguoxia, where intensive study is ongoing. Collectively these sites reveal that ichnofaunas in the HekouGroup are widespread and diverse. The Huazhuang tracksite yields a small assemblage of moderately well-preserved theropod tracks assigned toAsianopodus. This is the first report of Asianopodus from the Hekou Group. Huazhuang Asianopodus belongs to the Eubrontes morphotype. Thelarge theropod tracks from Lanzhou-Minhe Basin were left by large theropod trackmakers with the same general foot morphology. The specimensare described in detail and compared with other theropod track morphotypes from the Lower Cretaceous of China and elsewhere. In general,although the metatarsophalangeal pads of some Jurassic Eubrontes-type tracks are aligned with the axis of digit III, this feature appears mostcommon in the Early Cretaceous theropod (Eubrontes-type) tracks.
|
|
| 22. |
- Xu, An, et al.
(författare)
-
Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
|
|
| 23. |
- Yuan, Jin-Na, et al.
(författare)
-
Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes
- 2021
-
Ingår i: World Journal of Pediatrics. - : Zhejiang University Press. - 1708-8569 .- 1867-0687. ; 17:1, s. 99-105
-
Tidskriftsartikel (refereegranskat)abstract
- Background No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population. Methods Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes. Results Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged >= 11 years. Conclusions Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.
|
|
| 24. |
- Zhang, Jian, et al.
(författare)
-
Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and-2 Influenza A Neuraminidases, Including a Drug-Resistant Variant
- 2018
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:14, s. 6379-6397
-
Tidskriftsartikel (refereegranskat)abstract
- On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.
|
|
| 25. |
- Zhang, Kai Xin, et al.
(författare)
-
Substrate-thickness dependence of negative-index metamaterials at optical frequencies
- 2024
-
Ingår i: Applied Physics Letters. - 0003-6951 .- 1077-3118. ; 124:10
-
Tidskriftsartikel (refereegranskat)abstract
- Optical metamaterials have attracted intensive attention in recent years for their broad applications in superlenses, electromagnetic cloaking, and bio-sensing. Negative refractive index (NRI) metal-dielectric-metal fishnet metamaterials (MMs) are typically used for beyond-diffraction-limit imaging. However, there are few reports about the substrate-thickness dependence of NRI, which strongly affects the practical application. In our study, it is demonstrated that the membrane-based NRI MMs with a more negative index work better than the bulk substrate-based counterparts. In addition, a regular periodic vibration of NRI with the thickness of the membrane substrate was theoretically studied. The destructive interference of the thin film can explain this phenomenon. Furthermore, the proposed explanation was further proved by substituting the dielectric spacer with a larger permittivity. Therefore, an NRI structure on a membrane substrate with constructive interference can be a good choice in ultra-compact photoelectronic devices. This study can be a guide to the practical application of ultracompact NRI devices.
|
|
| 26. |
- Zhang, Mei, et al.
(författare)
-
Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement
- 2012
-
Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 3:4, s. 317-321
-
Tidskriftsartikel (refereegranskat)abstract
- A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel and potent complement inhibitors through structural modification of the original compound from high-throughput screening. Various analogues (7 and 13-15) were synthesized and identified as complement inhibitors, with the introduction of a five- or six-carbon chain (7c, 7d, 7k, 7I, and 7o) greatly improving their activity. Optimized compound 7I has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7I inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
|
|
| 27. |
- Zhang, Wei, et al.
(författare)
-
Synthesis and characterization of some new mononuclear ruthenium complexes containing 4-(un) substituted dipyridylpyrazole ligands
- 2008
-
Ingår i: Polyhedron. - : Elsevier BV. - 0277-5387 .- 1873-3719. ; 27:4, s. 1168-1176
-
Tidskriftsartikel (refereegranskat)abstract
- A mononuclear ruthenium complex [Ru(bpy)(2)(bpp)](PF6) (1) and its halogenated and nitro derivatives [Ru(bpy)(2)(Xbpp)](PF6) (bpy = 2,2'-bipyridine; bpp = 3,5-bis(2-pyridyl)pyrazole; X = Cl, 2; X = Br, 3; X = I, 4; X = NO2, 5) have been synthesized and characterized by H-1 NMR, C-13 NMR, HRMS, elemental analysis. Complexes 2-5 have been further confirmed by X-ray diffraction. Their UV-Vis and emission spectroscopies, electrochemical measurements and acid-base properties are described. The results presented here reveal that the introduction of Cl, Br, I and NO2 groups to the coordinated bpp(-) ligand makes the absorption and emission maxima of the parent complex 1 blue-shifted, the oxidation potential of the Ru-II/Ru-III couple increased and the pK(a) value decreased obviously. In addition, significant quenching of the emission by these groups is also observed.
|
|
