| 1. |
- 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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| 2. |
- Wang, Zhaoming, et al.
(författare)
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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
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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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.
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| 3. |
- QingMiao, Hu, et al.
(författare)
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Composition dependent elastic modulus and phase stability of Ni2MnGa based ferromagnetic shape memory alloys
- 2012
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Ingår i: SCI CHINA TECHNOL SC. - : Springer Science and Business Media LLC. - 1674-7321 .- 1869-1900. ; 55:2, s. 295-305
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Tidskriftsartikel (refereegranskat)abstract
- Ni2MnGa based ferromagnetic alloys are ideal candidates for applications such as actuators, magnetic refrigerators or magnetostrictive transducers due to their attractive properties such as magnetic field induced shape memory effect and large magnetocaloric effect. The properties of these alloys (e.g., the martensitic transformation temperature T (M) ) sensitively depend on the composition. Understanding the composition dependence of these properties so as to design the alloy as desired is one of the main research topics in this area. In recent years, we have investigated the composition dependent elastic modulus and phase stability of Ni2MnGa-based alloys by using a first-principles method, in hope of clarifying their connection to the properties of these alloys. In this article, we review the main results of our investigations. We show that the tetragonal shear modulus C' is a better predictor of the composition dependent T (M) than the number of valence electrons per atom (e/a) since the general T (M) similar to C' correlation works for some of the alloys for which the T (M) similar to e/a correlation fails, although there exist several cases for which both the general T (M) similar to C' and T (M)similar to e/a correlations break down. Employing the experimentally determined modulation function, the complex 5-layer modulated (5M) structure of the martensite of Ni2MnGa and the Al-doping effect on it are studied. We find that the shuffle and shear of the 5M structure are linearly coupled. The relative stability of the austenite and the martensites is examined by comparing their total energies. The non-modulated martensite beta aEuro(3)aEuro(2) with the tetragonality of the unit cell c/a > 1 is shown to be globally stable whereas the 5M martensite with c/a < 1 is metastable. The critical Al atomic fraction over which the martensitic transformation between the 5M martensite and austenite cannot occur is predicted to be 0.26, in reasonable agreement with experimental findings.
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| 4. |
- Li, Chun-Mei, et al.
(författare)
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First-principles investigation of the composition dependent properties of Ni2+xMn1-xGa shape-memory alloys
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 82:2, s. 024201-1-024201-9
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Tidskriftsartikel (refereegranskat)abstract
- The composition dependent lattice parameter, phase stability, elastic moduli, and magnetic transition temperature of the Ni2+xMn1-xGa shape-memory alloys are studied by using the first-principles exact muffin-tin orbital method in combination with the coherent potential approximation. The lattice parameter and tetragonal shear modulus of the cubic L-21 austenite phase decreases linearly with increasing concentration x of excess Ni atoms. The heats of formation of both cubic L-21 and tetragonal beta''' phases and their difference increase with x, indicating decreasing stability of the cubic and tetragonal phases and increasing driving force for the L-21 to beta''' martensitic transition. Investigating the electronic density of states, we find that the Ni-induced decreasing phase stability can mainly be ascribed to the weakening of the covalent bonding between minority spin states of Ni and Ga. Using the computed parameters, the composition dependence of the martensitic transition temperature is discussed. The theoretical Curie temperature, estimated from the Heisenberg model in combination with the mean-field approximation, is larger for the beta''' phase than for the L-21 phase. For both phases, the Curie temperature decreases nearly linearly with increasing x.
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| 5. |
- Li, Chun-Mei, et al.
(författare)
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Role of magnetic and atomic ordering in the martensitic transformation of Ni-Mn-In from a first-principles study
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 86:21, s. 214205-
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Tidskriftsartikel (refereegranskat)abstract
- The composition-dependent lattice parameters, crystal structure, elastic properties, magnetic moment, and electronic structure of Ni2Mn1+xIn1-x (0 <= x <= 0.6) are studied by using first-principles calculations. It is shown that the martensitic phase transition (MPT) from cubic L2(1) to tetragonal L1(0) accompanies theMn(Mn)-Mn-In ferromagnetic (FM) to antiferromagnetic (AFM) transition, at around the critical composition x = 0.32, in agreement with the experimental measurement. The Mn-In atomic disorder leads to decreasing stability of the martensite relative to the austenite, which depresses the MPT. The shear elastic constant C' of the parent phase first decreases slightly with increasing x and then remains almost unchanged above x = 0.32, indicating C' alone cannot account for the increase of the MPT temperature with x. The total magnetic moments for the L2(1) phase are in good agreement with those determined by experiments, whereas for the L1(0) phase they are slightly larger than the experimental data due to the possibleMn-In atomic disorder in the sample. The calculated density of states demonstrate that the covalent bonding between the minority spin states of Ni and In plays an important role in both the magnetic and structural stability.
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| 6. |
- Li, Chun-Mei, et al.
(författare)
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Site preference and elastic properties of Fe-, Co-, and Cu- doped Ni(2)MnGa shape memory alloys from first principles
- 2011
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:2, s. 024206-
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Tidskriftsartikel (refereegranskat)abstract
- The site preference and elastic properties of Fe-, Co-, and Cu-doped Ni(2)MnGa alloys are investigated by using the first-principles exact muffin-tin orbital method in combination with coherent-potential approximation. It is shown that Fe atom prefers to occupy the Mn and Ni sublattices even in Ga-deficient alloys; Co has strong tendency to occupy the Ni sublattice in all types of alloys; Cu atoms always occupy the sublattice of the host elements in deficiency. For most of the alloys with stable site occupations, both the electron density n and the shear modulus C' can be considered as predictors of the composition dependence of the martensitic transition temperature T(M) of the alloys. The physics underlying the composition-dependent C' are discussed based on the calculated density of states.
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| 7. |
- Li, Chun-Mei, et al.
(författare)
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Temperature dependence of elastic properties of Ni(2+x)Mn(1-x)Ga and Ni(2)Mn(Ga(1-x)Al(x)) from first principles
- 2011
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:17, s. 174117-
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Tidskriftsartikel (refereegranskat)abstract
- The temperature dependence of the elastic properties of Ni(2+x)Mn(1-x)Ga and Ni(2)Mn(Ga(1-x)Al(x)) (x = 0.0, 0.1, and 0.2) random alloys are investigated by using the first-principles exact muffin-tin orbitals method. At 0 K, the calculated equilibrium parameters in both cubic L2(1) and nonmodulated tetragonal beta'''-Ni(2)MnGa are in good agreement with the available experimental data and other theoretical results. Separating the thermal effects into single electron excitation, volume expansion, phonon smearing, and magnetic terms, we find that phonon smearing gives the dominating positive tetragonal elastic constant (C') versus temperature (T) slope for the cubic phase. For Ni(2+x)Mn(1-x)Ga, the competition between the negative alloying effect (partial derivative C'/partial derivative x < 0) and the positive temperature effect (partial derivative C'/partial derivative T > 0) leads to nearly constant C'[x, T(M)(x)] at the martensitic transition temperature T(M)(x). For Ni(2)Mn(Ga(1-x)Al(x)), where both partial derivative C'/partial derivative x and partial derivative C'/partial derivative T are positive, however, due to the significantly decrease of T(M)(x), the critical C'[x, T(M)(x)] slightly decreases with Al doping. Furthermore, it is demonstrated that both the composition and the temperature dependence of C' are indispensable to get a reasonable theoretical T(M)(x).
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| 8. |
- Li, Chun-Xia, et al.
(författare)
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Lattice parameters and relative stability of alpha '' phase in binary titanium alloys from first-principles calculations
- 2013
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Ingår i: Solid State Communications. - : Elsevier BV. - 0038-1098 .- 1879-2766. ; 159, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- The crystallographic structure and stability of the alpha" phase relative to the alpha and beta phases in Ti-x M (M=Ta, Nb, V, Mo) alloys are investigated by using the first-principles exact muffin-tin orbital method in combination with the coherent potential approximation. We show that, with increasing concentration of the alloying elements, the structure of the orthorhombic-alpha'' phase evolutes from the hcp-alpha to the bcc-beta phase, i.e., the lattice parameters b/a and c/a as well as the basal shuffle y decreases from those corresponding to the alpha phase to those of the beta phase. The compositional alpha/alpha" and alpha"/beta phase boundaries are determined by comparing the total energies of the phases. The predicted alpha/alpha" phase boundaries are about 10.2, 10.5, 11.5, 4.5 at% for Ti-V, Ti-Nb, Ti-Ta, and Ti-Mo, respectively, in reasonable agreement with experiments. The alpha"/beta phase boundaries are higher than the experimental values, possibly due to the absence of temperature effect in the first-principles calculations. Analyzing the electronic density of states, we propose that the stability of the alpha" phase is controlled by the compromise between the strength of the covalent and metallic bonds.
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| 9. |
- Luo, Hu-Bin, et al.
(författare)
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Magnetic properties and temperature-dependent half-metallicity of Co2Mn(Ga(1-x)Z(x)) (Z = Si, Ge, Sn) from first-principles calculation
- 2013
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 25:15, s. 156003-
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Tidskriftsartikel (refereegranskat)abstract
- Using the first-principles exact muffin-tin orbitals method in combination with the coherent potential approximation, we investigated the magnetic properties, exchange interactions, and temperature-dependent half-metallicity of the Co2Mn(Ga(1-x)Z(x)) (Z = Si, Ge, Sn) alloys. The total magnetic moment follows perfectly a previously proposed Slater-Pauling relation, i.e., mu(0) = N-t - 24, with N-t being the number of valence electrons. The Co-Mn and Co1-Co2 (inter-sublattice) interactions are dominated by direct exchange, whereas the Co1-Co1 (intra-sublattice) interaction is characterized by superexchange. The Mn-Mn exchange interaction in Co2MnGa is of long-ranged RKKY-type. However, the Mn-Mn exchange interactions in Co(2)MnZ are relatively localized and can be attributed to superexchange. The Co-Mn, Co1-Co2 and Co1-Co1 total exchange interactions increase with x, whereas the Mn-Mn total exchange interactions show convex behavior. The calculated Curie temperature (T-C) increases with x. The ability of Z to enhance T-C follows the sequence of Si > Ge > Sn, in agreement with the experimental findings. The temperature dependence of the spin polarization at the Fermi level [P(T)] is investigated based on the disordered local moment model. P(T) drops abruptly at temperatures much lower than T-C. At temperatures higher than 200 K, the composition with higher TC generally corresponds to larger P(T).
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| 10. |
- Luo, Hu-Bin, et al.
(författare)
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Phase stability of Ni-2(Mn1-xFex)Ga : A first-principles study
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 86:2, s. 024427-
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Tidskriftsartikel (refereegranskat)abstract
- Ni-2(Mn1-xFex)Ga ferromagnetic shape memory alloy shows unusual composition-dependent martensitic transformation temperature (T-M), namely, T-M decreases with increasing e/a ratio. In hope of understanding this unusual behavior, we investigated the composition dependence of the heat of formation (H-f) and shear elastic modulus (C') of the cubic austenite as well as the stability of the five-layer modulated (5M) tetragonal martensite relative to the austenite, using first-principles exact muffin-tin orbital method in combination with coherent potential approximation. Our calculations demonstrated that H-f of the austenite increases with the Fe content x. C' increases slightly with x up to 0.05 but decreases thereafter. The composition dependence of both H-f and C' cannot fully account for the trend of T-M against x although such correlations have been proposed in literature for other Ni-Mn-Ga based alloys. The structure of 5M martensite phase of Ni-2(Mn1-xFex)Ga with 0 < x < 0.2 is determined by optimizing both the shear (changing c/a) and wavelike shuffle of atoms in (110) planes along [1 (1) over bar0] direction adopting the experimentally determined modulation function. The energy difference Delta E-AM between the austenite and 5M phases decreases with increasing x up to 0.05, following the lower Delta E-AM corresponding to lower T-M rule. However, with x larger than 0.05, Delta E-AM increases, against the experimental T-M similar to x behavior. We propose that, if taking the temperature effect and the spin-orbital coupling into account, the Delta E-AM similar to x curve might be altered and may explain the unusual composition dependence of Ni-2(Mn1-xFex)Ga.
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