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

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

\ua9 2023, Springer Nature Limited. The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: s41531-023-00526-9 npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below

Delocalizing Communities: Changing Forms of Community Engagement in Natural Resources Governance

Across both the developing and developed worlds, community engagement has become a key strategy for natural resource management. However, a growing number of studies, report that community-based approaches are experiencing formidable challenges, with limited outcomes in terms of livelihoods, decentralization and sustainability. Yet, policies continue to focus attention unduly on "community participation", ignoring the ways in which the "community" is itself embedded in a wider social system. Recent studies have shown that local communities are more complex than previously assumed, with local community actions being heavily shaped by wider social and environmental contexts. Yet, scholarly research tends to focus on reporting such cross-scalar dynamics, with little explanation of how and why they occur. This paper advances a framework to understand how local communities interact with the wider world, through what we term "delocalization of communities" in natural resource management. Using Bourdieu's theory of social field, we present an approach to analyze various trajectories of delocalization involving the exchange of, and struggle for, a variety of resources valued in specific fields of natural resource governance.We extend the work of several researchers who have been critical of the conventional view of the community, and argue that a new model of delocalized "community" needs to be envisaged, one that emphasizes the interactions among actors within and between spatial scales and levels of political organization. While such a cross-scalar view is not novel, we deepen social field approach to assess how cross-scalar processes unfold in the course of "delocalization" of communities in the context of rapid social and environmental change. We draw on evidence from five different case studies from three continents that demonstrate specific aspects of the delocalization phenomenon.The cases selected are from Australia, Indonesia, Mexico, Nepal, and Papua New Guinea. We demonstrate through these cases that increasingly diverse interests in natural resources such as forests have served to delocalize communities beyond "local" domains. We conclude that local community is not a localized entity, and there are multiple cross-scale networks which need to be recognized, as these have profound implications in community-based natural resource management. In such situations, open and exploratory approaches - moving away from blueprint interventions - are required to facilitate context-specific fields and spheres of local democracy, nurturing diverse, flexible, and networked models of community participation, along with the recognition of political and economic influence coming from the wider domain

Agricultural innovation and adaptation to climate change: empirical evidence from diverse agro-ecologies in South Asia

While impacts of climate change on agricultural systems have been widely researched, there is still limited understanding of what agricultural innovations have evolved over time in response to both climatic and non-climatic drivers. Although there has been some progress in formulating national adaptation policies and strategic planning in different countries of South Asia, research to identify local-level adaptive strategies and practices is still limited. Through eight case studies and a survey of 300 households in 15 locations in India, Nepal and Bangladesh, this paper generates empirical evidence on emerging agricultural innovations in contrasting socio-economic, geographical and agro-ecological contexts. The study demonstrates that several farm practices (innovations) have emerged in response to multiple drivers over time, with various forms of institutional and policy support, including incentives to reduce risks in the adoption of innovative practice. It further shows that there is still limited attempt to systematically mainstream adaptation innovations into local, regional and national government structures, policies and planning processes. The paper shows that the process of farm-level adaptation through innovation adoption forms an important avenue for agricultural adaptation in South Asia. A key implication of this finding is that there is a need for stronger collaborations between research institutions, extension systems, civil society and the private sector actors to enhance emerging adaptive innovations at the farm level