Despite the diverse biological pathways known to be regulated by ubiquitylation, global identification of substrates that are targeted for ubiquitylation has remained a challenge. To globally ...characterize the human ubiquitin-modified proteome (ubiquitinome), we utilized a monoclonal antibody that recognizes diglycine (diGly)-containing isopeptides following trypsin digestion. We identify ∼19,000 diGly-modified lysine residues within ∼5000 proteins. Using quantitative proteomics we monitored temporal changes in diGly site abundance in response to both proteasomal and translational inhibition, indicating both a dependence on ongoing translation to observe alterations in site abundance and distinct dynamics of individual modified lysines in response to proteasome inhibition. Further, we demonstrate that quantitative diGly proteomics can be utilized to identify substrates for cullin-RING ubiquitin ligases. Interrogation of the ubiquitinome allows for not only a quantitative assessment of alterations in protein homeostasis fidelity, but also identification of substrates for individual ubiquitin pathway enzymes.
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► α-diGly was used to identify/quantify 19,000 ubiquitylation sites in 5,000 proteins ► Kinetics of ubiquitylation allows for classification of distinct substrate types ► Ubiquitinome formation largely requires ongoing protein synthesis ► diGly proteomics can be used to identify cullin-RING ligase substrates
There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of ...the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.
A growing literature explores abusive supervision, nonphysical forms of hostility perpetrated by managers against their direct reports. However, researchers have used different terminology to explore ...phenomena that overlap with abusive supervision, and extant research does not devolve from a unifying theoretical framework. These problems have the potential to undermine the development of knowledge in this important research domain. The author therefore provides a review of the literature that summarizes what is known about the antecedents and consequences of abusive supervision, provides the basis for an emergent model that integrates extant empirical work, and suggests directions for future research.
The Privacy Advocates Bennett, Colin J
2010, 20100813, 20080829, 2008, 2010-08-13, 2019-06-20
eBook
Today, personal information is captured, processed, and disseminated in a bewildering variety of ways, and through increasingly sophisticated, miniaturized, and distributed technologies: identity ...cards, biometrics, video surveillance, the use of cookies and spyware by Web sites, data mining and profiling, and many others. In The Privacy Advocates, Colin Bennett analyzes the people and groups around the world who have risen to challenge the most intrusive surveillance practices by both government and corporations. Bennett describes a network of self-identified privacy advocates who have emerged from civil society--without official sanction and with few resources, but surprisingly influential. A number of high-profile conflicts in recent years have brought this international advocacy movement more sharply into focus. Bennett is the first to examine privacy and surveillance not from a legal, political, or technical perspective but from the viewpoint of these independent activists who have found creative ways to affect policy and practice. Drawing on extensive interviews with key informants in the movement, he examines how they frame the issue and how they organize, who they are and what strategies they use. He also presents a series of case studies that illustrate how effective their efforts have been, including conflicts over key-escrow encryption (which allows the government to read encrypted messages), online advertising through third-party cookies that track users across different Web sites, and online authentication mechanisms such as the short-lived Microsoft Passport. Finally, Bennett considers how the loose coalitions of the privacy network could develop into a more cohesive international social movement.
Governance is one of the most important factors for ensuring effective environmental management and conservation actions. Yet, there is still a relative paucity of comprehensive and practicable ...guidance that can be used to frame the evaluation, design, and analysis of systems of environmental governance. This conceptual review and synthesis article seeks to addresses this problem through resituating the broad body of governance literature into a practical framework for environmental governance. Our framework builds on a rich history of governance scholarship to propose that environmental governance has four general aims or objectives – to be effective, to be equitable, to be responsive, and to be robust. Each of these four objectives need to be considered simultaneously across the institutional, structural, and procedural elements of environmental governance. Through a review of the literature, we developed a set of attributes for each of these objectives and relate these to the overall capacity, functioning, and performance of environmental governance. Our aim is to provide a practical and adaptable framework that can be applied to the design, evaluation, and analysis of environmental governance in different social and political contexts, to diverse environmental problems and modes of governance, and at a range of scales.
Highlights • Cortical disconnection may contribute to age-related cognitive decline. • Diffusion tensor imaging (DTI) can assess the integrity of neural connections. • Recent DTI research suggests ...age-related decline in cerebral white matter integrity. • White matter integrity effects may be either global (whole-brain) or tract-specific. • Testing alternative models will require multiple imaging modalities.
Background The need to observe roots in their natural undisturbed state within soil, both spatially and temporally, is a challenge that continues to occupy researchers studying the rhizosphere. Scope ...This paper reviews how over the last 30 years the application of X-ray Computed Tomography (CT) has demonstrated considerable promise for root visualisation studies. We describe how early CT work demonstrated that roots could be visualised within soils, but was limited by resolution (ca. 1 mm). Subsequent work, utilising newer micro CT scanners, has been able to achieve higher resolutions (ca. 50 μm) and enhance imaging capability in terms of detecting finer root material. However the overlap in the attenuation density of root material and soil pore space has been a major impediment to the uptake of the technology. We then outline how sophisticated image processing techniques, frequently based on object tracking methods, have demonstrated great promise in overcoming these obstacles. This, along with the concurrent advances in scan and reconstruction times, image quality and resolution (ca. 0.5 μm) have opened up new opportunities for the application of X-ray CT in experimental studies of root and soil interactions. Conclusions We conclude that CT is well placed to contribute significantly to unravelling the complex interactions between roots and soil.
Debate about what proportion of the Earth to protect often overshadows the question of how nature should be conserved and by whom. We present a systematic review and narrative synthesis of 169 ...publications investigating how different forms of governance influence conservation outcomes, paying particular attention to the role played by Indigenous peoples and local communities. We find a stark contrast between the outcomes produced by externally controlled conservation, and those produced by locally controlled efforts. Crucially, most studies presenting positive outcomes for both well-being and conservation come from cases where Indigenous peoples and local communities play a central role, such as when they have substantial influence over decision making or when local institutions regulating tenure form a recognized part of governance. In contrast, when interventions are controlled by external organizations and involve strategies to change local practices and supersede customary institutions, they tend to result in relatively ineffective conservation at the same time as producing negative social outcomes. Our findings suggest that equitable conservation, which empowers and supports the environmental stewardship of Indigenous peoples and local communities represents the primary pathway to effective long-term conservation of biodiversity, particularly when upheld in wider law and policy. Whether for protected areas in biodiversity hotspots or restoration of highly modified ecosystems, whether involving highly traditional or diverse and dynamic local communities, conservation can become more effective through an increased focus on governance type and quality, and fostering solutions that reinforce the role, capacity, and rights of Indigenous peoples and local communities. We detail how to enact progressive governance transitions through recommendations for conservation policy, with immediate relevance for how to achieve the next decade's conservation targets under the UN Convention on Biological Diversity.
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•A ‘second green revolution’ using crops with improved below-ground traits is needed.•Phenotyping plant roots poses practical and data challenges.•Technologies for 2D root phenotyping ...include rhizotrons, paper pouches, and plates.•MRI, PET and X-ray CT allow 3D and 4D root phenotyping in soil.•Non-invasive techniques for field phenotyping have recently advanced.•Deep machine learning techniques are transforming the root phenotyping landscape.
Major increases in crop yield are required to keep pace with population growth and climate change. Improvements to the architecture of crop roots promise to deliver increases in water and nutrient use efficiency but profiling the root phenome (i.e. its structure and function) represents a major bottleneck. We describe how advances in imaging and sensor technologies are making root phenomic studies possible. However, methodological advances in acquisition, handling and processing of the resulting ‘big-data’ is becoming increasingly important. Advances in automated image analysis approaches such as Deep Learning promise to transform the root phenotyping landscape. Collectively, these innovations are helping drive the selection of the next-generation of crops to deliver real world impact for ongoing global food security efforts.
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