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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Liu, Chun-Yan, et al.
(author)
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Massively Parallel Aligned Poly(vinylidene fluoride) Nanofibrils in All-Organic Dielectric Polymer Composite Films for Electric Energy Storage
- 2023
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In: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 56:4, s. 1481-1491
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Journal article (peer-reviewed)abstract
- It is a formidable challenge to combine the perform-ance advantages of linear and nonlinear polymer dielectrics for developing all-organic film capacitors with high energy density and low loss. In this work, massively parallel aligned poly(vinylidene fluoride) (PVDF) nanofibrils were in situ fabricated for the first time in the polyethylene (PE) matrix via a multistage stretching technology involving hot stretching and solid-state stretching at an elevated temperature. The largely enhanced interfacial area of PVDF nanofibrils could effectively induce interfacial polarization, imparting PE composite films with a high dielectric constant of 4.50. More interestingly, the nanoconfinement effect of PVDF nanofibrils greatly restricted the migration of free electrons and impurity ions, and an impressive breakdown strength of 624 MV m-1 was obtained. As a result, the as-prepared PE/PVDF composite films exhibited an attractive discharged energy density of as high as 6.4 J cm-3, which was more than 10 times of the conventional counterparts, and outperformed the current linear dielectric polymers. The ingenious structure design of in situ nonlinear dielectric nanofibrils provides a promising approach to maximize the advantageous polarizations and minimize the disadvantageous polarizations in the linear and nonlinear polymer dielectric blends, achieving all-organic polymer dielectric composite films with high energy density and low loss.
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4. |
- Zhang, Ya Hong, et al.
(author)
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AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
- 2024
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In: Matrix Biology. - 0945-053X. ; 129, s. 29-43
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Journal article (peer-reviewed)abstract
- As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AβPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AβPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.
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5. |
- Zhao, Xue-Ke, et al.
(author)
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Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Journal article (peer-reviewed)abstract
- The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
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- Zhu, Ao Shuang, et al.
(author)
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Different postprandial metabolic patterns after the consumption of fish oil and lard in healthy Chinese individuals
- 2017
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In: Nutrition Clinique et Metabolisme. - : Elsevier BV. - 0985-0562. ; 31:2, s. 134-139
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Journal article (peer-reviewed)abstract
- Aim: It is well known that nutritional intervention has positive effects on the secondary prevention of coronary heart disease. Different fat compositions of meals may alter postprandial plasma lipid patterns, which can further influence lipid metabolism in vivo. Methods: In the present study, we investigated postprandial plasma lipid parameters in twenty healthy volunteers after eating fat meals either with 80 gram lard or 80 gram fish oil. Blood samples were drawn at 0, 0.5, 1, 2, 3, 5 and 7. hours and plasma levels of total triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined. Results: It demonstrated that postprandial plasma concentrations of TG, TC and LDL-C were significantly lower whereas HDL-C was higher after eating fish oil compared to the consumption of lard. Moreover, comparing the individuals with or without dyslipidemic family history, the healthy individuals without family history of dyslipidemia after eating fish oil had even lower postprandial plasma TG and LDL-C (P <. 0.05) than the subjects with the family history. It is concluded that postprandial response following fish oil could be as a result of reduced TG, TC and LDL-C, and increased HDL-C. Conclusions: Postprandial responses following fish oil consumption may reduce TG, TC and LDL-C plasma levels, and increase HDL-C level. Individuals with dyslipidemic family history may have enhanced postprandial response than the individuals without dyslipidemic family history.
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7. |
- Ablikim, M., et al.
(author)
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Amplitude analysis of D0 → K -π+π+π-
- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 95:7
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Journal article (peer-reviewed)abstract
- We present an amplitude analysis of the decay D0 → K -π+π+π- based on a data sample of 2.93 fb−1 acquired by the BESIII detector at the ψ(3770) resonance. With a nearly background free sample of about 16000 events, we investigate the substructure of the decay and determine the relative fractions and the phases among the different intermediate processes. Our amplitude model includes the two-body decays D0 → ¯K*0ρ0, D0 → K−a+1(1260) and D0 → K−1(1270)π+, the three-body decays D0 →¯K*0π+π− and D0 → K−π+ρ0, as well as the four-body nonresonant decay D0 → K−π+π+π−. The dominant intermediate process is D0 → K−a+1(1260), accounting for a fit fraction of 54.6%.
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8. |
- Ablikim, M., et al.
(author)
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Amplitude analysis of the chi(c1) -> eta pi(+)pi(-) decays
- 2017
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:3
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Journal article (peer-reviewed)abstract
- Using 448.0 x 10(6) psi(3686) events collected with the BESIII detector, an amplitude analysis is performed for psi(3686) -> gamma chi(c1), chi(c1) ->eta pi(+)pi(-) decays. The most dominant two- body structure observed is a(0)(980)(+/-) pi(-/+); a(0)(980)(+/-) -> eta pi(+/-.) line shape is modeled using a dispersion relation, and a significant nonzero a(0) (980) coupling to the eta'pi channel is measured. We observe chi(c1) -> a(2)(1700)pi production for the first time, with a significance larger than 17 sigma. The production of mesons with exotic quantum numbers, J(PC) = 1(-+), is investigated, and upper limits for the branching fractions chi(c1) -> pi(1)(1400)(+/-)pi(-/+) , chi(c1) -> pi(1)(1600)(+/-)pi(-/+) and chi(c1) -> pi 1(2015)(+/-)pi(-/+) with subsequent pi(1)(X)(+/-) -> eta pi(+/-) decay, are determined.
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9. |
- Ablikim, M., et al.
(author)
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Amplitude analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot
- 2014
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In: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:5, s. 052001-
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Journal article (peer-reviewed)abstract
- We perform an analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot using a data set of 2.92 fb(-1) of e(+) e(-) collisions at the (3770) mass accumulated by the BESIII experiment, in which 166694 candidate events are selected with a background of 15.1%. The Dalitz plot is found to be well represented by a combination of six quasitwo- body decay channels [k(SP)(0)(+) (1450)(+,) ] plus a small nonresonant component. Using the fit fractions from this analysis, partial branching ratios are updated with higher precision than previous measurements.
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10. |
- Ablikim, M., et al.
(author)
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Amplitude Analysis of the Decays eta ' -> pi(+)pi(-)pi(0) and eta' -> pi(0)pi(0)pi(0)
- 2017
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 118:1
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Journal article (peer-reviewed)abstract
- Based on a sample of 1.31 x 10(9) J/Psi events collected with the BESIII detector, an amplitude analysis of the isospin-violating decays eta' -> pi(+)pi(-)pi(0) and eta' -> pi(0)pi(0)pi(0) is performed. A significant P-wave contribution from eta' -> rho(+/-)eta(-/+) is observed for the first time in eta' -> pi(+)pi(-)pi(0). The branching fraction is determined to be B(eta' -> rho(+/-)pi(-/+)) = (7.44 +/- 0.60 +/- 1.26 +/- 1.84) x 10(-4), where the first uncertainty is statistical, the second systematic, and the third model dependent. In addition to the nonresonant S-wave component, there is a significant sigma meson component. The branching fractions of the combined S-wave components are determined to be B(eta' -> pi(+)pi(-)pi(0))(S) = (37.63 +/- 0.77 +/- 2.22 +/- 4.48) x 10(-4) and B(eta' -> pi(0)pi(0)pi(0)) = (35.22 +/- 0.82 +/- 2.54) x 10(-4), respectively. The latter one is consistent with previous BESIII measurements.
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