Mining has proven to be a controversial form of resource development throughout the circumpolar north. This article compares two mining projects—the proposed Prosperity gold and copper mine in ...central British Columbia, Canada and the proposed Kallak iron ore mine in Norrbotten County in northern Sweden—that have endured long and protracted approval processes that have caused tensions and disputes between mining companies, Indigenous peoples, communities and state actors. In an effort understand the particular development paths taken by these two mining projects, this article examines the institutional determinants that structure relationships between industry, Indigenous communities and the state in Canada and Sweden. Using an historical institutionalist theoretical approach, the article focuses on the manner in which the structural features of the political systems and the environmental assessment and permitting processes in both countries have shaped the mine approval process. It also identifies particular critical junctures—important events and decisions that influenced the trajectory of the approval processes in profound and consequential ways. The article finds that institutional determinants, both historical and contemporary, have played a critical role in determining outcomes in both cases. In particular, it demonstrates the ways in which the structures of the Canadian and Swedish political systems have historically excluded Indigenous peoples from the decision-making process for resource development projects such as mines. It also shows how broader institutional contexts, as well as specific events and decisions, have complicated and politicized the mine approval processes, a situation that has heightened tensions on all sides.
The influenza virus polymerase transcribes and replicates the viral genome. The proper timing and balance of polymerase activity is important for successful replication. Genome replication is ...controlled in part by phosphorylation of NP that regulates assembly of the replication machinery. However, it remains unclear whether phosphorylation directly regulated polymerase activity. Here we identified polymerase phosphosites that control its function. Mutating phosphosites in the catalytic subunit PB1 altered polymerase activity and virus replication. Biochemical analyses revealed phosphorylation events that disrupted global polymerase function by blocking the NTP entry channel or preventing RNA binding. We also identified a regulatory site that split polymerase function by specifically suppressing transcription. These experiments show that host kinases phospho-regulate viral RNA synthesis directly by modulating polymerase activity and indirectly by controlling assembly of replication machinery. Further, they suggest polymerase phosphorylation may bias replication versus transcription at discrete times or locations during the infectious cycle.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A knowledge ecosystem is a collection of individuals and organizations who are involved in the creation, management and dissemination of knowledge, both in the form of research and lived experience ...and teaching. As is the case with ecosystems more generally, they thrive on variation and diversity, not only in the types of individuals and organizations involved but also in the roles that they play. For many decades, the northern knowledge ecosystem in Canada was dominated and controlled by Western scholarly approaches and researchers based in academic institutions outside the North. More recently, this research landscape has started to change, largely in response to the efforts of Indigenous peoples and northerners to realize greater self-determination and self-government. Not only have these changes led to the development of research and educational capacity in the North, but they have also changed the way that academic researchers engage in the research process. The keys to maintaining the future sustainability and health of the northern knowledge ecosystem will be encouraging diversity and balance in the research methodologies and approaches used to generate knowledge about the North and ensuring that the needs and priorities of northern and Indigenous peoples are recognized and addressed in the research process.
This Special Section explores the interplay between Indigenous peoples, industry, and the state in five proposed and active mining projects in Canada and Sweden. The overall aim is to identify ...factors shaping the quality of Indigenous community-industry-state interactions in mining and mine development. An ambition underlying the research is to develop knowledge to help manage mining related land-use conflicts in Sweden by drawing on Canadian comparisons and experience. This paper synthesizes the comparative research that has been conducted across jurisdictions in three Canadian provinces and Sweden. It focuses on the interplay between the properties of the governance system, the quality of interaction and governance outcomes. We combine institutional and interactive governance theory and use the concept of governability to assess how and why specific outcomes, such as mutually beneficial interaction, collaboration, or opposition, occurred. The analysis suggests there are measures that can be taken by the Swedish Government to improve the governability of mining related issues, by developing alternative, and more effective, avenues to recognize, and protect, Sámi rights and culture, to broaden the scope and increase the legitimacy and transparency of the EIAs, to raise the quality of interaction and consultation, and to develop tools to actively stimulate and support collaboration and partnerships on equal terms. Generally, we argue that Indigenous community responses to mining must be understood within a larger framework of Indigenous self-determination, in particular the communities’ own assessments of their opportunities to achieve their long-term objectives using alternative governing modes and types of interactions.
The protozoan pathogen Toxoplasma gondii has the unique ability to develop a chronic infection in the brain of its host by transitioning from the fast growing tachyzoite morphology to latent ...bradyzoite morphology. A hallmark of the bradyzoite is the development of neuronal cysts that are resilient against host immune response and current therapeutics. The bradyzoite parasites within the cyst have a carbohydrate and protein-rich wall and a slow-replication cycle, allowing them to remain hidden from the host. The intracellular, encysted lifestyle of T. gondii has made them recalcitrant to molecular analysis in vivo.
Here, we detail the results from transcriptional and proteomic analyses of bradyzoite-enriched fractions isolated from mouse brains infected with T. gondii over a time course of 21 to 150 days. The enrichment procedure afforded consistent identification of over 2000 parasitic peptides from the mixed-organism sample, representing 366 T. gondii proteins at 28, 90, and 120 day timepoints. Deep sequencing of transcripts expressed during these three timepoints revealed that a subpopulation of genes that are transcriptionally expressed at a high level. Approximately one-third of these transcripts are more enriched during bradyzoite conditions compared to tachyzoites and approximately half are expressed at similar levels during each phase. The T. gondii transcript which increased the most over the course of chronic infection, sporoAMA1, shows stage specific isoform expression of the gene.
We have expanded the transcriptional profile of in vivo bradyzoites to 120 days post-infection and provided the first in vivo proteomic profile of T. gondii bradyzoites. The RNA sequencing depth of in vivo bradyzoite T. gondii was over 250-fold greater than previous reports and allowed us to identify low level transcripts and a novel bradyzoite-specific isoform of sporoAMA1.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the past several decades, Manx Gaelic, the indigenous language of the Isle of Man, a small island in the British Isles, has undergone a profound process of revitalisation and reintegration into ...the life of the community. At the forefront of this revitalisation process has been a dedicated group of language activists who saved the language following the death of the last native speakers. More recently, however, the Isle of Man government has supported the revitalisation of Manx, mainly through education planning and support for cultural programming. This article examines the Select Committee on the Greater Use of Manx Gaelic, a committee of the island’s parliament, Tynwald, the internal and external contexts that shaped its deliberations and recommendations and the role it played in signalling a change in the attitude of the government towards Manx in the mid-1980s. The Select Committee highlights the important connection between the political (governance) and social (identity) dimensions of islandness in the revitalisation of an Indigenous language in a small island context.
The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here we apply quantitative proteomics of N-linked glycoproteins to reveal ...how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK, and AKT. We find that each oncogene has somewhat different surfaceomes, but the functions of these proteins are harmonized by common biological themes including up-regulation of nutrient transporters, down-regulation of adhesion molecules and tumor suppressing phosphatases, and alteration in immune modulators. Addition of a potent MEK inhibitor that blocks MAPK signaling brings each oncogene-induced surfaceome back to a common state reflecting the strong dependence of the oncogene on the MAPK pathway to propagate signaling. Cell surface protein capture is mediated by covalent tagging of surface glycans, yet current methods do not afford sequencing of intact glycopeptides. Thus, we complement the surfaceome data with whole cell glycoproteomics enabled by a recently developed technique called activated ion electron transfer dissociation (AI-ETD). We found massive oncogene-induced changes to the glycoproteome and differential increases in complex hybrid glycans, especially for KRAS and HER2 oncogenes. Overall, these studies provide a broad systems-level view of how specific driver oncogenes remodel the surfaceome and the glycoproteome in a cell autologous fashion, and suggest possible surface targets, and combinations thereof, for drug and biomarker discovery.
Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational ...modifications. Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5. Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra. Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues. Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da. Also, new is glycan “wildcard” search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans. Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications. We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
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•Filtering mass spectra by key peaks facilitates glycoproteomics search.•Glycan wildcard search finds unanticipated N-linked glycans.•User-defined diagnostic peaks for chemical biology.•Low-abundance O-linked glycosylation on neuropeptides derived from ProSAAS.
New features have been added to popular commercial software. The features are demonstrated on several publicly available data sets and are used to discover sulfated N-glycans on Fc gamma receptor IIIa, O-linked glycosylation on rat neuropeptides, and prenylated cysteines in human cells.
Russia’s invasion of Ukraine which commenced on 24 February 2022 represented just the latest, albeit most devastating, intervention in a neighbouring former Soviet state. This article considers the ...legal justifications for Russia’s actions and finds them to be far from satisfactory. The claims advanced by Russia closely mirror those made in respect of its prior interventions in the former Soviet space, underlining an attempt to distort some of the most fundamental norms of international law in order to afford an air of legitimacy to its actions. Although it is too soon to conclude with any certainty what the longer term implications of the recent conflict will be, both politically and legally, it is apparent that it can be seen as part of a wider policy objective on Russia’s part to maintain and/or reassert influence over its ‘near abroad’. While in some respects indicative of the possible emergence of a new ‘Cold War’, the international reaction to its intervention in Ukraine suggests that any intention to manipulate or reconstitute legal norms in support of its agenda is meeting with mass rejection.
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