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- 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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| 5. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 6. |
- Hamer, Henrike M., et al.
(författare)
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Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission
- 2010
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Ingår i: Clinical Nutrition. - Amsterdam, Netherlands : Elsevier. - 0261-5614 .- 1532-1983. ; 29:6, s. 738-744
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Butyrate, produced by colonic fermentation of dietary fibers is often hypothesized to beneficially affect colonic health. This study aims to assess the effects of butyrate on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress.Methods: Thirty-five patients with ulcerative colitis in clinical remission daily administered 60 ml rectal enemas containing WO mM sodium butyrate (n = 17) or saline (n = 18) during 20 days (NCT00696098). Before and after the intervention feces, blood and colonic mucosal biopsies were obtained. Parameters of antioxidant defense and oxidative damage, myeloperoxidase, several cytokines, fecal calprotectin and CRP were determined.Results: Butyrate enemas induced minor effects on colonic inflammation and oxidative stress. Only a significant increase of the colonic IL-10/IL-12 ratio was found within butyrate-treated patients (p = 0.02), and colonic concentrations of CCL5 were increased after butyrate compared to placebo treatment (p = 0.03). Although in general butyrate did not affect colonic glutathione levels, the effects of butyrate enemas on total colonic glutathione appeared to be dependent on the level of inflammation.Conclusion: Although UC patients in remission were characterized by low-grade oxidative stress and inflammation, rectal butyrate enemas showed only minor effects on inflammatory and oxidative stress parameters.
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| 7. |
- van Valen, E., et al.
(författare)
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Chronic solvent-induced encephalopathy: European consensus of neuropsychological characteristics, assessment, and guidelines for diagnostics
- 2012
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X. ; 33:4, s. 710-726
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The presence of neuropsychological impairment is a hallmark of chronic solvent-induced encephalopathy (CSE), and using clinical neuropsychological procedures to generate a valid assessment of the condition is crucial for its diagnosis. The goals of this consensus document are to provide updated knowledge of the neuropsychological characteristics of CSE and to provide internationally acceptable guidelines for using neuropsychological assessments in the process of diagnosing patients who are suspected of having CSE. Materials and methods: A European working group that was composed of experts in the field of the clinical diagnosis of CSE met at several round-table meetings and prepared this report. The first section of the consensus paper addresses a review of the relevant literature that was published between 1985 and March 2012. The second section addresses recommendations for the clinical neuropsychological assessment of patients who are suspected of having CSE. Results: The literature review indicates that the most common neuropsychological impairments in CSE patients are within the domains of attention, particularly the speed of information processing, memory, and motor performance. It appears that the influence of CSE on memory processes mainly involves immediate recall and generally involves verbal, visual and visuospatial material. In the second section, six recommendations are presented regarding important functional domains for the neuropsychological diagnostic process of CSE that relate to the evaluation of neuropsychological impairment, the assessment and evaluation of symptoms, differential diagnostic considerations, the reliability and validity of neuropsychological test results, and the retesting of patients. Discussion and conclusions: These recommendations will contribute to the improvement of the process for accurately diagnosing CSE, better counselling for CSE patients, the comparability of epidemiological data between countries, and finally, by raising awareness, these recommendations will contribute to combating the adverse health effects of occupational exposure to solvents. (C) 2012 Elsevier Inc. All rights reserved.
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- Ringholm, M., et al.
(författare)
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Analytic cubic and quartic force fields using density-functional theory
- 2014
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 140:3, s. 034103-
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Tidskriftsartikel (refereegranskat)abstract
- We present the first analytic implementation of cubic and quartic force constants at the level of Kohn-Sham density-functional theory. The implementation is based on an open-ended formalism for the evaluation of energy derivatives in an atomic-orbital basis. The implementation relies on the availability of open-ended codes for evaluation of one- and two-electron integrals differentiated with respect to nuclear displacements as well as automatic differentiation of the exchange-correlation kernels. We use generalized second-order vibrational perturbation theory to calculate the fundamental frequencies of methane, ethane, benzene, and aniline, comparing B3LYP, BLYP, and Hartree-Fock results. The Hartree-Fock anharmonic corrections agree well with the B3LYP corrections when calculated at the B3LYP geometry and from B3LYP normal coordinates, suggesting that the inclusion of electron correlation is not essential for the reliable calculation of cubic and quartic force constants.
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