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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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| 3. |
- Muller, S, et al.
(author)
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Target 2035 - update on the quest for a probe for every protein
- 2022
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In: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 13:1, s. 13-21
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Journal article (other academic/artistic)abstract
- Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. Target 2035 aims to develop a pharmacological modulator for every protein in the human proteome to fill this gap.
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| 4. |
- Ackloo, S, et al.
(author)
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Target 2035 - an update on private sector contributions
- 2023
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In: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 14:6, s. 1002-1011
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Journal article (other academic/artistic)abstract
- Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein.
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| 5. |
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| 6. |
- Ferreira, J. J., et al.
(author)
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Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease
- 2013
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In: European Journal of Neurology. - : Wiley. - 1351-5101. ; 20:1, s. 5-15
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Journal article (peer-reviewed)abstract
- Objective: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. Methods: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. Results and Conclusions:: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.
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| 7. |
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| 8. |
- Wray, Selina, et al.
(author)
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Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Journal article (peer-reviewed)abstract
- Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
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| 9. |
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| 10. |
- Chiesa, Marco, 1987-, et al.
(author)
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The quest for resilient (static) forwarding tables
- 2016
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In: INFOCOM 2016 - The 35th Annual IEEE International Conference on Computer Communications, IEEE. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467399531
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Conference paper (peer-reviewed)abstract
- Fast Reroute (FRR) and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. We embark upon a systematic algorithmic study of the resiliency of immediate failover in a variety of models (with/without packet marking/duplication, etc.). We leverage our findings to devise new schemes for immediate failover and show, both theoretically and experimentally, that these outperform existing approaches.
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| 11. |
- Mullin, S., et al.
(author)
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Evolution and clustering of prodromal parkinsonian features in GBA1 carriers
- 2019
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 34:9, s. 1365-1373
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Journal article (peer-reviewed)abstract
- Background: Five to 25% of patients with PD carry glucocerebrosidase gene mutations, and 10% to 30% of glucocerebrosidase carriers will develop PD by age 80. Stratification of PD risk in glucocerebrosidase carriers provides an opportunity to target disease-modifying therapies. Objective: Cross-sectional and longitudinal survey of prodromal PD signs among glucocerebrosidase carriers. Design: Prospective assessment of 82 glucocerebrosidase mutation carriers and 35 controls over 4 to 5 years for prodromal clinical PD features. Results: At all time points, olfactory (measured using University of Pennsylvania Smell Identification Test) and cognitive (Montreal Cognitive Assessment) function and the International Parkinson and Movement Disorder Society UPDRS parts II and III scores were significantly worse amongst glucocerebrosidase mutation carriers. Progression to microsmia (odds ratio: 8.5; 95% confidence interval: 2.6–28.2; P < 0.05) and mild cognitive impairment (odds ratio: 4.2; 95% confidence interval: 1.1–16.6; P < 0.05) were more rapid compared to controls. Those with worse olfaction also had worse cognition (OR, 1.5; 95% CI: 0.0–2.8; P < 0.05) and depression (OR, 1.3; 95% CI: 0.6–2.8; P < 0.05). No participants reached the MDS prodromal PD diagnostic criteria before PD diagnosis. One participant developed PD. He did not fulfill the International Parkinson and Movement Disorder Society prodromal PD criteria before diagnosis. Conclusion: Assessment of individual and clustered PD prodromal features may serve as a useful tool to identify high-risk subjects for conversion to PD. As a result of the low conversion rate in our glucocerebrosidase mutation carriers to date, prospective validation is needed in larger cohorts to establish the profile of these features in PD convertors. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 13. |
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| 14. |
- Chiesa, Marco, 1987-, et al.
(author)
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On the resiliency of randomized routing against multiple edge failures
- 2016
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In: 43rd International Colloquium on Automata, Languages, and Programming, ICALP 2016. - : Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing. - 9783959770132
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Conference paper (peer-reviewed)abstract
- We study the Static-Routing-Resiliency problem, motivated by routing on the Internet: Given a graph G = (V, E), a unique destination vertex d, and an integer constant c > 0, does there exist a static and destination-based routing scheme such that the correct delivery of packets from any source s to the destination d is guaranteed so long as (1) no more than c edges fail and (2) there exists a physical path from s to d? We embark upon a study of this problem by relating the edge-connectivity of a graph, i.e., the minimum number of edges whose deletion partitions G, to its resiliency. Following the success of randomized routing algorithms in dealing with a variety of problems (e.g., Valiant load balancing in the network design problem), we embark upon a study of randomized routing algorithms for the Static-Routing-Resiliency problem. For any k-connected graph, we show a surprisingly simple randomized algorithm that has expected number of hops O(|V|k) if at most k-1 edges fail, which reduces to O(|V|) if only a fraction t of the links fail (where t < 1 is a constant). Furthermore, our algorithm is deterministic if the routing does not encounter any failed link.
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| 15. |
- Arrowsmith, CH, et al.
(author)
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The promise and peril of chemical probes
- 2015
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In: Nature chemical biology. - : Springer Science and Business Media LLC. - 1552-4469 .- 1552-4450. ; 11:8, s. 536-541
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Journal article (peer-reviewed)
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| 16. |
- Chiesa, Marco, 1987-, et al.
(author)
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On the Resiliency of Static Forwarding Tables
- 2017
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In: IEEE/ACM Transactions on Networking. - : Institute of Electrical and Electronics Engineers (IEEE). - 1063-6692 .- 1558-2566. ; 25:2, s. 1133-1146
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Journal article (peer-reviewed)abstract
- Fast reroute and other forms of immediate failover have long been used to recover from certain classes of failures without invoking the network control plane. While the set of such techniques is growing, the level of resiliency to failures that this approach can provide is not adequately understood. In this paper, we embarked upon a systematic algorithmic study of the resiliency of forwarding tables in a variety of models (i.e., deterministic/probabilistic routing, with packet-headerrewriting, with packet-duplication). Our results show that the resiliency of a routing scheme depends on the "connectivity" k of a network, i.e., the minimum number of link deletions that partition a network. We complement our theoretical result with extensive simulations. We show that resiliency to four simultaneous link failures, with limited path stretch, can be achieved without any packet modification/duplication or randomization. Furthermore, our routing schemes provide resiliency against k - 1 failures, with limited path stretch, by storing log(k) bits in the packet header, with limited packet duplication, or with randomized forwarding technique.
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