Institution
University of Santiago de Compostela
Education•Santiago de Compostela, Spain•
About: University of Santiago de Compostela is a education organization based out in Santiago de Compostela, Spain. It is known for research contribution in the topics: Population & Boundary value problem. The organization has 18141 authors who have published 39676 publications receiving 986578 citations. The organization is also known as: USC & Universidad de Santiago de Compostela.
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TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
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.
For example, 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 versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase 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. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
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. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. 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 assays, we hope to encourage technical innovation in the field.
5,187 citations
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented 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.
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.
4,316 citations
TL;DR: The random forest is clearly the best family of classifiers (3 out of 5 bests classifiers are RF), followed by SVM (4 classifiers in the top-10), neural networks and boosting ensembles (5 and 3 members in theTop-20, respectively).
Abstract: We evaluate 179 classifiers arising from 17 families (discriminant analysis, Bayesian, neural networks, support vector machines, decision trees, rule-based classifiers, boosting, bagging, stacking, random forests and other ensembles, generalized linear models, nearest-neighbors, partial least squares and principal component regression, logistic and multinomial regression, multiple adaptive regression splines and other methods), implemented in Weka, R (with and without the caret package), C and Matlab, including all the relevant classifiers available today. We use 121 data sets, which represent the whole UCI data base (excluding the large-scale problems) and other own real problems, in order to achieve significant conclusions about the classifier behavior, not dependent on the data set collection. The classifiers most likely to be the bests are the random forest (RF) versions, the best of which (implemented in R and accessed via caret) achieves 94.1% of the maximum accuracy overcoming 90% in the 84.3% of the data sets. However, the difference is not statistically significant with the second best, the SVM with Gaussian kernel implemented in C using LibSVM, which achieves 92.3% of the maximum accuracy. A few models are clearly better than the remaining ones: random forest, SVM with Gaussian and polynomial kernels, extreme learning machine with Gaussian kernel, C5.0 and avNNet (a committee of multi-layer perceptrons implemented in R with the caret package). The random forest is clearly the best family of classifiers (3 out of 5 bests classifiers are RF), followed by SVM (4 classifiers in the top-10), neural networks and boosting ensembles (5 and 3 members in the top-20, respectively).
2,616 citations
TL;DR: In this paper, a unified framework for the assessment of beta diversity, disentangling the contribution of spatial turnover and nestedness to beta-diversity patterns, is provided, which is crucial for our understanding of central biogeographic, ecological and conservation issues.
Abstract: Aim Beta diversity (variation of the species composition of assemblages) may reflect two different phenomena, spatial species turnover and nestedness of assemblages, which result from two antithetic processes, namely species replacement and species loss, respectively. The aim of this paper is to provide a unified framework for the assessment of beta diversity, disentangling the contribution of spatial turnover and nestedness to beta-diversity patterns.
Innovation I derive an additive partitioning of beta diversity that provides the two separate components of spatial turnover and nestedness underlying the total amount of beta diversity. I propose two families of measures of beta diversity for pairwise and multiple-site situations. Each family comprises one measure accounting for all aspects of beta diversity, which is additively decomposed into two measures accounting for the pure spatial turnover and nestedness components, respectively. Finally, I provide a case study using European longhorn beetles to exemplify the relevance of disentangling spatial turnover and nestedness patterns.
Main conclusion Assigning the different beta-diversity patterns to their respective biological phenomena is essential for analysing the causality of the processes underlying biodiversity. Thus, the differentiation of the spatial turnover and nestedness components of beta diversity is crucial for our understanding of central biogeographic, ecological and conservation issues.
2,364 citations
TL;DR: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva).
Abstract: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.
2,286 citations
Authors
Showing all 18379 results
Name | H-index | Papers | Citations |
---|---|---|---|
Donald G. Truhlar | 165 | 1518 | 157965 |
Gavin Davies | 159 | 2036 | 149835 |
Hector F. DeLuca | 133 | 1303 | 69395 |
Luis M. Liz-Marzán | 132 | 616 | 61684 |
Peter Hansen | 128 | 1271 | 86210 |
Leon O. Chua | 122 | 824 | 71612 |
Kyriacos C. Nicolaou | 120 | 1350 | 68945 |
Bernd W. Scheithauer | 119 | 729 | 55985 |
Joakim Nystrand | 117 | 658 | 50146 |
C. Patrignani | 117 | 1754 | 110008 |
Hongbo Zhu | 116 | 573 | 57329 |
Richard Vidal | 113 | 685 | 61464 |
Fergus J. Couch | 110 | 557 | 54485 |
Heino Falcke | 110 | 999 | 50297 |
D. Domínguez Vázquez | 106 | 435 | 46081 |