| 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. |
- Wijesooriya, K, et al.
(författare)
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Polarization measurements in high-energy deuteron photodisintegration
- 2001
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 86:14, s. 2975-2979
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the recoil proton polarization for the d(γ⃗,p⃗)n reaction at θc.m. = 90° for photon energies up to 2.4 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. The induced polarization py vanishes above 1 GeV, contrary to meson-baryon model expectations, in which resonances lead to large polarizations. However, the polarization transfer Cx does not vanish above 1 GeV, inconsistent with hadron helicity conservation. Thus, we show that the scaling behavior observed in the d(γ,p)ncross sections is not a result of perturbative QCD. These data should provide important tests of new nonperturbative calculations in the intermediate energy regime.
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| 3. |
- Alffenaar, J. W. C., et al.
(författare)
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Clinical standards for the dosing and management of TB drugs
- 2022
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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| 4. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 5. |
- Schulte, EC, et al.
(författare)
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High energy angular distribution measurements of the exclusive deuteron photodisintegration reaction
- 2002
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Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813 .- 1089-490X. ; 66:4
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Tidskriftsartikel (refereegranskat)abstract
- The first complete measurements of the angular distributions of the two-body deuteron photodisintegration differential cross section at photon energies above 1.6 GeV were performed at the Thomas Jefferson National Accelerator Facility. The results show a persistent forward-backward asymmetry up to E-gamma=2.4 GeV, the highest-energy measured in this experiment. The Hard Rescattering and the Quark-Gluon string models are in fair agreement with the results.
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| 6. |
- Berlow, E.L., et al.
(författare)
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Interaction strengths in food webs : Issues and opportunities
- 2004
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 73:3, s. 585-598
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Forskningsöversikt (refereegranskat)abstract
- 1. Recent efforts to understand how the patterning of interaction strength affects both structure and dynamics in food webs have highlighted several obstacles to productive synthesis. Issues arise with respect to goals and driving questions, methods and approaches, and placing results in the context of broader ecological theory. 2. Much confusion stems from lack of clarity about whether the questions posed relate to community-level patterns or to species dynamics, and to what authors actually mean by the term 'interaction strength'. Here, we describe the various ways in which this term has been applied and discuss the implications of loose terminology and definition for the development of this field. 3. Of particular concern is the clear gap between theoretical and empirical investigations of interaction strengths and food web dynamics. The ecological community urgently needs to explore new ways to estimate biologically reasonable model coefficients from empirical data, such as foraging rates, body size, metabolic rate, biomass distribution and other species traits. 4. Combining numerical and analytical modelling approaches should allow exploration of the conditions under which different interaction strengths metrics are interchangeable with regard to relative magnitude, system responses, and species identity. 5. Finally, the prime focus on predator-prey links in much of the research to date on interaction strengths in food webs has meant that the potential significance of nontrophic interactions, such as competition, facilitation and biotic disturbance, has been largely ignored by the food web community. Such interactions may be important dynamically and should be routinely included in future food web research programmes.
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| 7. |
- Pearson Johansson, Joel, et al.
(författare)
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Near-infrared Supernova Ia Distances : Host Galaxy Extinction and Mass-step Corrections Revisited
- 2021
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Ingår i: Astrophysical Journal. - : IOP Publishing Ltd. - 0004-637X .- 1538-4357. ; 923:2
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Tidskriftsartikel (refereegranskat)abstract
- We present optical and near-infrared (NIR, Y-, J-, H-band) observations of 42 Type Ia supernovae (SNe Ia) discovered by the untargeted intermediate Palomar Transient Factory survey. This new data set covers a broad range of redshifts and host galaxy stellar masses, compared to previous SN Ia efforts in the NIR. We construct a sample, using also literature data at optical and NIR wavelengths, to examine claimed correlations between the host stellar masses and the Hubble diagram residuals. The SN magnitudes are corrected for host galaxy extinction using either a global total-to-selective extinction ratio, R-V = 2.0, for all SNe, or a best-fit R-V for each SN individually. Unlike previous studies that were based on a narrower range in host stellar mass, we do not find evidence for a "mass step," between the color- and stretch-corrected peak J and H magnitudes for galaxies below and above log(M-*/M-circle dot) = 10. However, the mass step remains significant (3 sigma) at optical wavelengths (g, r, i) when using a global R-V, but vanishes when each SN is corrected using their individual best-fit R-V. Our study confirms the benefits of the NIR SN Ia distance estimates, as these are largely exempted from the empirical corrections dominating the systematic uncertainties in the optical.
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