| 1. |
- 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.
|
|
| 2. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 3. |
- Adare, A., et al.
(författare)
-
Cross section and transverse single-spin asymmetry of eta mesons in p up arrow plus p collisions at root s=200 GeV at forward rapidity
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:7
-
Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the cross section and transverse single-spin asymmetry (AN) for. mesons at large pseudorapidity from root s = 200 GeV p up arrow + p collisions. The measured cross section for 0.5 < p(T) < 5.0 GeV/c and 3.0 < vertical bar eta vertical bar < 3.8 is well described by a next-to-leading-order perturbative-quantum-chromodynamics calculation. The asymmetries A(N) have been measured as a function of Feynman-x (x(F)) from 0.2 < vertical bar x(F)vertical bar < 0.7, as well as transverse momentum (p(T)) from 1.0 < p(T) < 4.5 GeV/c. The asymmetry averaged over positive x(F) is < A(N)> = 0.061 +/- 0.014. The results are consistent with prior transverse single-spin measurements of forward eta and pi(0) mesons at various energies in overlapping x(F) ranges. Comparison of different particle species can help to determine the origin of the large observed asymmetries in p up arrow + p collisions.
|
|
| 4. |
- Adare, A., et al.
(författare)
-
Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
|
|
| 5. |
- Adare, A., et al.
(författare)
-
Measurement of K-S(0) and K*(0) in p plus p, d plus Au, and Cu plus Cu collisions at root s(NN)=200 GeV
- 2014
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K-S(0) and K*(0) meson production at midrapidity in p + p, d + Au, and Cu + Cu collisions at root s(NN) = 200 GeV. The K-S(0) and K*(0) mesons are reconstructed via their K-S(0) -> pi(0)(-> gamma gamma) pi(0)(-> gamma gamma) and K*(0) -> K-+/-pi(-/+) decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K-S(0) and K*(0) mesons in d + Au and Cu + Cu collisions at different centralities. In the d + Au collisions, the nuclear modification factor of K-S(0) and K*(0) mesons is almost constant as a function of transverse momentum and is consistent with unity, showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu + Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p + p yield scaled by the number of binary nucleon-nucleon collisions in the Cu + Cu system. In the p(T) range 2-5 GeV/c, the strange mesons (K-S(0), K*(0)) similarly to the phi meson with hidden strangeness, showan intermediate suppression between the more suppressed light quark mesons (pi(0)) and the nonsuppressed baryons (p, (p) over bar). At higher transverse momentum, p(T) > 5 GeV/c, production of all particles is similarly suppressed by a factor of approximate to 2.
|
|
| 6. |
- Karlsson-Lindahl, Linda, 1972, et al.
(författare)
-
Heparanase affects food intake and regulates energy balance in mice.
- 2012
-
Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
|
|
| 7. |
- Kongstad Rasmussen, Ole, et al.
(författare)
-
Ventricular repolarization sequences on the epicardium and endocardium. Monophasic action potential mapping in healthy pigs
- 2012
-
Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 45:1, s. 49-56
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate repolarization sequence, monophasic action potentials were recorded from a mean of 153 +/- 54 left and right ventricular epicardial and endocardial sites in 10 pigs using the CARTO mapping system (Biosense Webster, Waterloo, Belgium). The activation time and end-of-repolarization (EOR) time were measured and 3-dimensional maps of activation and repolarization sequences constructed. Results: In 8 of 9 pigs, both the activation and EOR times appeared first in the septum and last in the latero-basal areas on the endocardium, not on the epicardium. The EOR followed the activation sequence, both on the epicardium (in 8/9 pigs) and endocardium (in 8/8 pigs). The maximal EOR differences were 84 +/- 20 ms, whereas the local EOR differences between paired sites against each other on the tell ventricular epicardium and endocardium were 11 +/- 9 ms in the apex and 12 +/- 12 ms in the anterior wall. Conclusion: The EOR follows the activation sequence both on the epicardium and endocardium. The apico-basal gradients are predominant repolarization gradients, as compared with the epicardial-endocardial gradients. (C) 2012 Elsevier Inc. All rights reserved.
|
|
| 8. |
- Li-xia, Huang, et al.
(författare)
-
Adaptive bands filter bank optimized by genetic algorithm for robust speech recognition system
- 2011
-
Ingår i: Journal of Central South University of Technology. - : Springer Verlag (Germany). - 1005-9784 .- 1993-0666 .- 2095-2899 .- 2227-5223. ; 18:5, s. 1595-1601
-
Tidskriftsartikel (refereegranskat)abstract
- Perceptual auditory filter banks such as Bark-scale filter bank are widely used as front-end processing in speech recognition systems. However, the problem of the design of optimized filter banks that provide higher accuracy in recognition tasks is still open. Owing to spectral analysis in feature extraction, an adaptive bands filter bank (ABFB) is presented. The design adopts flexible bandwidths and center frequencies for the frequency responses of the filters and utilizes genetic algorithm (GA) to optimize the design parameters. The optimization process is realized by combining the front-end filter bank with the back-end recognition network in the performance evaluation loop. The deployment of ABFB together with zero-crossing peak amplitude (ZCPA) feature as a front process for radial basis function (RBF) system shows significant improvement in robustness compared with the Bark-scale filter bank. In ABFB, several sub-bands are still more concentrated toward lower frequency but their exact locations are determined by the performance rather than the perceptual criteria. For the ease of optimization, only symmetrical bands are considered here, which still provide satisfactory results.
|
|
| 9. |
- Liu, Hairong, et al.
(författare)
-
Theoretical investigation on guiding IR light in hollow-core metallic fiber with corrugated inner surface
- 2010
-
Ingår i: Optics Express. - 1094-4087. ; 18:21, s. 21959-21964
-
Tidskriftsartikel (refereegranskat)abstract
- Hollow metallic fibers (HMFs) are in general lossy primarily owing to the fact that the guided transverse-magnetic (TM) light sustains a relatively high propagation loss. In this paper, we propose a type of practical hollow-core metallic fiber (HMF) with longitudinally corrugated inner surface for transmitting infrared (IR) light. Simulation results show that the loss of the fundamental TM mode can be easily reduced by 50 similar to 100 times compared to a HMF without surface corrugation. In contrast to the traditional HMF with a dielectric coating, it is shown that the loss of the fundamental TM mode in the proposed HMF is relatively insensitive to the corrugation layer thickness or equivalently the operating frequency.
|
|
| 10. |
- Liu, Hairong, et al.
(författare)
-
Theoretical investigation on guiding IR light in hollow-core metallic fiber with corrugated inner surface
- 2010
-
Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 18:21, s. 21959-21964
-
Tidskriftsartikel (refereegranskat)abstract
- Hollow metallic fibers (HMFs) are in general lossy primarily owing to the fact that the guided transverse-magnetic (TM) light sustains a relatively high propagation loss. In this paper, we propose a type of practical hollow-core metallic fiber (HMF) with longitudinally corrugated inner surface for transmitting infrared (IR) light. Simulation results show that the loss of the fundamental TM mode can be easily reduced by 50~100 times compared to a HMF without surface corrugation. In contrast to the traditional HMF with a dielectric coating, it is shown that the loss of the fundamental TM mode in the proposed HMF is relatively insensitive to the corrugation layer thickness or equivalently the operating frequency.
|
|
