1,736 research outputs found

    Mapping the mammalian ribosome quality control complex interactome using proximity labeling approaches.

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    Previous genetic and biochemical studies from Saccharomyces cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro, a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1. Surprisingly, validation studies revealed that a subset of substrates are ubiquitylated by Ltn1 in a regulatory manner that does not result in subsequent substrate degradation. We demonstrate that Ltn1 catalyzes the regulatory ubiquitylation of ribosomal protein S6 kinase 1 and 2 (RPS6KA1, RPS6KA3). Further, loss of Ltn1 function results in hyperactivation of RSK1/2 signaling without impacting RSK1/2 protein turnover. These results suggest that Ltn1-mediated RSK1/2 ubiquitylation is inhibitory and establishes a new role for Ltn1 in regulating mitogen-activated kinase signaling via regulatory RSK1/2 ubiquitylation. Taken together, our results suggest that mammalian RQC interactions are difficult to observe and may be more transient than the homologous complex in S. cerevisiae and that Ltn1 has RQC-independent functions

    An Examination of the Relationship Between Strategy and Human Resource Management Practices among Small Businesses

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    Although   it has been asserted  that an organization's  strategy  is, or should  be, a major determinant  of its human resource  management practices,  little empirical research has addressed this linkage in small businesses.  Therefore, we do not know whether managers of small firms have devoted resources to design, implement, and support  human resource management practices that are aligned with firm strategy. Accordingly, the purpose of this paper is to examine the nature and extent of the relationship, if any, between strategy and human resource management practices among small  businesses.   The results offer little evidence of a consistent relationship. This suggests that an opportunity to build future competitive advantage may be realized through strategically managing human resources

    Ocean defenders and human rights

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    Two pressing and overlapping marine policy issues are related to human rights in the ocean and the situation of ocean defenders. Human rights issues and violations are on the rise in the ocean due to the ongoing, rapid and unchecked escalation of anthropogenic activities in marine and coastal environments, which increasingly undermine the fundamental, civil and political, economic, social, cultural or environmental rights of individuals and groups. In this context, it is essential to recognize, support and safeguard the individuals, groups or communities who are mobilizing, advocating or taking action to protect the marine environment, coastal and oceanic territories, and associated human rights from existential threats. Yet, these ‘ocean defenders’ often face marginalization, intimidation, criminalization, threats, violence and murders. The failure to protect the human rights of coastal populations and ocean defenders needs to be urgently rectified by states, the private sector and civil society. We identify six specific areas of urgent action to protect human rights in and related to marine and coastal environments and to support and safeguard ocean defenders

    Ethical ecosurveillance: Mitigating the potential impacts on humans of widespread environmental monitoring

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    Ecosurveillance has proliferated in recent years, generating vast amounts of data on the natural environment. Ecosurveillance also has significant potential impacts on humans; therefore, researchers and policymakers need new conceptual tools to anticipate and mitigate any negative effects. Surveillance studies is an interdisciplinary field in the social sciences, providing a number of insights and practical lessons for predicting and managing the complex impacts (positive and negative, intended and unintended) of surveillance tools and practices. We draw on surveillance studies literature to propose two tools to guide designers and practitioners of ecosurveillance—a ‘red flag checklist’ to anticipate potential problems, and a ‘considerations guide’ to inform design decisions across a wide range of ecosurveillance systems. These tools will help ensure that the coming era of ecosurveillance is guided by responsible and ethical practices towards wildlife and humans alike, while also realizing the potential of these technologies for improving environmental outcomes.publishedVersio

    The human right to a clean, healthy and sustainable ocean

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    The United Nations General Assembly adopted a resolution in 2022 that formally recognizes that there is a universal human right to a clean, healthy and sustainable environment. Yet there is evidence that human rights impacts associated with the degradation of the ocean environment are accelerating. In this perspective, we highlight how the recognition of the human right to a healthy environment can catalyze ocean action and transform ocean governance. In particular, it can do so through 1) catalyzing marine protection and increasing accountability through clarifying state obligations, 2) improving the inclusiveness of ocean governance, including through prioritizing and empowering groups in situations of vulnerability, and 3) enhancing ocean economy practices through clarifying private sector responsibilities. To those ends, there is an urgent need to move from recognition to implementation in order to protect both current and future generations’ human right to a clean, healthy and sustainable ocean

    Observational learning of atypical biological kinematics in autism

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    Observing and voluntarily imitating the biological kinematics displayed by a model underpins the acquisition of new motor skills via sensorimotor processes linking perception with action. Differences in voluntary imitation in autism could be related to sensorimotor processing activity during action-observation of biological motion, as well as how sensorimotor integration processing occurs across imitation attempts. Using an observational practice protocol, which minimized the active contribution of the peripheral sensorimotor system, we examined the contribution of sensorimotor processing during action-observation. The data showed that autistic participants imitated both the temporal duration and atypical kinematic profile of the observed movement with a similar level of accuracy as neurotypical participants. These findings suggest the lower-level perception-action processes responsible for encoding biological kinematics during the action-observation phase of imitation are operational in autism. As there was no task-specific engagement of the peripheral sensorimotor system during observational practice, imitation difficulties in autism are most likely underpinned by sensorimotor integration issues related to the processing of efferent and (re)afferent sensorimotor information during trial-to-trial motor execution

    Equity trade-offs in conservation decision making

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    Conservation decisions increasingly involve multiple environmental and social objectives, which result in complex decision contexts with high potential for trade-offs. Improving social equity is one such objective that is often considered an enabler of successful outcomes and a virtuous ideal in itself. Despite its idealized importance in conservation policy, social equity is often highly simplified or ill-defined and is applied uncritically. What constitutes equitable outcomes and processes is highly normative and subject to ethical deliberation. Different ethical frameworks may lead to different conceptions of equity through alternative perspectives of what is good or right. This can lead to different and potentially conflicting equity objectives in practice. We promote a more transparent, nuanced, and pluralistic conceptualization of equity in conservation decision making that particularly recognizes where multidimensional equity objectives may conflict. To help identify and mitigate ethical conflicts and avoid cases of good intentions producing bad outcomes, we encourage a more analytical incorporation of equity into conservation decision making particularly during mechanistic integration of equity objectives. We recommend that in conservation planning motivations and objectives for equity be made explicit within the problem context, methods used to incorporate equity objectives be applied with respect to stated objectives, and, should objectives dictate, evaluation of equity outcomes and adaptation of strategies be employed during policy implementation

    Auxin fluxes through plasmodesmata modify root-tip auxin distribution

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    © 2020. Published by The Company of Biologists Ltd. Auxin is a key signal regulating plant growth and development. It is well established that auxin dynamics depend on the spatial distribution of efflux and influx carriers on the cell membranes. In this study, we employ a systems approach to characterise an alternative symplastic pathway for auxin mobilisation via plasmodesmata, which function as intercellular pores linking the cytoplasm of adjacent cells. To investigate the role of plasmodesmata in auxin patterning, we developed a multicellular model of the Arabidopsis root tip. We tested the model predictions using the DII-VENUS auxin response reporter, comparing the predicted and observed DII-VENUS distributions using genetic and chemical perturbations designed to affect both carrier-mediated and plasmodesmatal auxin fluxes. The model revealed that carrier-mediated transport alone cannot explain the experimentally determined auxin distribution in the root tip. In contrast, a composite model that incorporates both carrier-mediated and plasmodesmatal auxin fluxes re-capitulates the root-tip auxin distribution. We found that auxin fluxes through plasmodesmata enable auxin reflux and increase total root-tip auxin. We conclude that auxin fluxes through plasmodesmata modify the auxin distribution created by efflux and influx carriers
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