Institution
Casa Sollievo della Sofferenza
Healthcare•San Giovanni Rotondo, Italy•
About: Casa Sollievo della Sofferenza is a healthcare organization based out in San Giovanni Rotondo, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 2234 authors who have published 6183 publications receiving 239811 citations. The organization is also known as: Home for Relief of the Suffering.
Topics: Population, Cancer, Type 2 diabetes, Transplantation, Diabetes mellitus
Papers published on a yearly basis
Papers
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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
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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
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Wellcome Trust Sanger Institute1, Broad Institute2, University of Groningen3, University of Pittsburgh4, Cedars-Sinai Medical Center5, Yale University6, University of Cambridge7, University of Chicago8, Harvard University9, Katholieke Universiteit Leuven10, University of Liège11, King's College London12, Université de Montréal13, New Jersey Institute of Technology14, Cleveland Clinic15, Peninsula College of Medicine and Dentistry16, Université libre de Bruxelles17, Aarhus University18, University of Adelaide19, University of Kiel20, Flinders University21, McGill University22, Ludwig Maximilian University of Munich23, Charité24, Icahn School of Medicine at Mount Sinai25, University of Bonn26, Karolinska Institutet27, Torbay Hospital28, University of Auckland29, Christchurch Hospital30, Imperial College London31, Queen's University32, University of Oslo33, Lithuanian University of Health Sciences34, Emory University35, Casa Sollievo della Sofferenza36, Ghent University37, University of Western Australia38, University of Edinburgh39, Queensland Health40, Newcastle University41, University of Dundee42, University of Manchester43, University of Amsterdam44, University of Maribor45, Royal Hospital for Sick Children46, Guy's and St Thomas' NHS Foundation Trust47, QIMR Berghofer Medical Research Institute48, Norfolk and Norwich University Hospital49, Leiden University50, Technische Universität München51, University of Toronto52, University of Pennsylvania53, Johns Hopkins University54, University of Queensland55
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
Abstract: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
4,094 citations
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Jean-Charles Lambert1, Jean-Charles Lambert2, Jean-Charles Lambert3, Carla A. Ibrahim-Verbaas4 +212 more•Institutions (75)
TL;DR: In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
3,726 citations
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University of Washington1, National Institutes of Health2, Institute for Health Metrics and Evaluation3, Sapienza University of Rome4, Mayo Clinic5, FIU Herbert Wertheim College of Medicine6, Cincinnati Children's Hospital Medical Center7, Boston University8, Essentia Health9, University of Douala10, University of British Columbia11, Medical University of Graz12, Telethon Institute for Child Health Research13, University of Milan14, Cedars-Sinai Medical Center15, Johns Hopkins University16, University of California, San Diego17, University of Michigan18, University of Edinburgh19, University of Texas Southwestern Medical Center20, Queen Mary University of London21, University of Alabama at Birmingham22, Harvard University23, Tufts Medical Center24, All India Institute of Medical Sciences25, Northwestern University26, University of Kentucky27, Casa Sollievo della Sofferenza28, Columbia University29, Icahn School of Medicine at Mount Sinai30, University of Sydney31, University of Cape Town32, Federal University of Rio de Janeiro33, University of Ibadan34, Case Western Reserve University35, Stanford University36, Universidade Federal de Minas Gerais37, The George Institute for Global Health38, Uppsala University39, Dresden University of Technology40, King Fahd Medical City41, Tulane University42, Imperial College London43
TL;DR: CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high- income countries.
3,315 citations
Authors
Showing all 2237 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ralph B. D'Agostino | 226 | 1287 | 229636 |
Cisca Wijmenga | 136 | 668 | 86572 |
Massimo Mangino | 116 | 369 | 84902 |
Xavier Estivill | 110 | 673 | 59568 |
Andrea Natale | 106 | 945 | 52520 |
Stefano Pileri | 100 | 635 | 43369 |
Bruno Dallapiccola | 94 | 935 | 43208 |
Fortunato Ciardiello | 94 | 695 | 47352 |
F. Bianchi | 91 | 1370 | 40011 |
Paolo Gasparini | 91 | 431 | 36059 |
Joseph G. Gleeson | 86 | 307 | 23345 |
Mario Rizzetto | 79 | 470 | 33693 |
Giuseppe Leone | 74 | 654 | 21451 |
Maurizio Pompili | 74 | 783 | 20649 |
Massimo Rugge | 74 | 594 | 25624 |