30 research outputs found
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
High Temperature Oxidation and Corrosion Properties of High Entropy Superalloys
The present work investigates the high temperature oxidation and corrosion behaviour of high entropy superalloys (HESA). A high content of various solutes in HESA leads to formation of complex oxides, however the Cr and Al activities of HESA are sufficient to promote protective chromia or alumina formation on the surface. By comparing the oxidation and corrosion resistances of a Ni-based superalloy—CM247LC, Al2O3-forming HESA can possess comparable oxidation resistance at 1100 °C, and Cr2O3-forming HESA can exhibit superior resistance against hot corrosion at 900 °C. This work has demonstrated the potential of HESA to maintain surface stability in oxidizing and corrosive environments
Aluminizing for enhanced oxidation resistance of ductile refractory high-entropy alloys
Refractory high-entropy alloys (RHEAs) emerge as promising candidate materials for ultrahigh-temperature applications. One critical issue to solve for RHEAs is their balanced oxidation resistance and mechanical properties, mainly room-temperature ductility for the latter. Recently, it was found that existing ductile RHEAs are subject to catastrophic accelerated oxidation, also known as pesting. In this work, both alloying and surface coating, are applied to enhance the oxidation resistance of ductile RHEAs, with the focus on surface coating using the pack cementation method and more specifically, aluminizing. The oxidation resistance of two RHEAs, Hf0.5Nb0.5Ta0.5Ti1.5Zr, one recently identified ductile RHEA which pests in the temperature range of 600–1000 \ub0C, and Al0.5Cr0.25Nb0.5Ta0.5Ti1.5, the newly designed ductile RHEA which does not pest but embrittles after oxidation, are studied after aluminizing at 900 \ub0C using three different pack components. Aluminizing, if using the appropriate pack cementation parameters, can avoid pesting in Hf0.5Nb0.5Ta0.5Ti1.5Zr and alleviate the oxidation induced embrittlement in Al0.5Cr0.25Nb0.5Ta0.5Ti1.5, and holds the promise for further improving the RHEAs as potential ultrahigh-temperature materials
THREE NEWLY RECORDED GENERA AND SPECIES OF GOBIID FISHES (TELEOSTEI: GOBIIDAE) FROM THE DONGSHA ATOLL (PRATAS ISLANDS), SOUTH CHINA SEA
ABSTRACT Three newly recorded gobiid genera of coral-reef gobies have been collected and examined by scuba diving in the Dongsha Atoll, also known as the Pratas Islands, South China Sea. They are Fei
THREE NEWLY RECORDED GENERA AND SPECIES OF GOBIID FISHES (TELEOSTEI: GOBIIDAE) FROM THE DONGSHA ATOLL (PRATAS ISLANDS), SOUTH CHINA SEA
ABSTRACT Three newly recorded gobiid genera of coral-reef gobies have been collected and examined by scuba diving in the Dongsha Atoll, also known as the Pratas Islands, South China Sea. They are Fei