304 research outputs found
Mutation in triangulated categories and rigid Cohen-Macaulay modules
We introduce the notion of mutation of -cluster tilting subcategories in a
triangulated category with Auslander-Reiten-Serre duality. Using this idea, we
are able to obtain the complete classifications of rigid Cohen-Macaulay modules
over certain Veronese subrings.Comment: 52 pages. To appear in Invent. Mat
Signatures of Quark-Gluon-Plasma formation in high energy heavy-ion collisions: A critical review
A critical review on signatures of Quark-Gluon-Plasma formation is given and
the current (1998) experimental status is discussed. After giving an
introduction to the properties of QCD matter in both, equilibrium- and
non-equilibrium theories, we focus on observables which may yield experimental
evidence for QGP formation. For each individual observable the discussion is
divided into three sections: first the connection between the respective
observable and QGP formation in terms of the underlying theoretical concepts is
given, then the relevant experimental results are reviewed and finally the
current status concerning the interpretation of both, theory and experiment, is
discussed. A comprehensive summary including an outlook towards RHIC is given
in the final section.Comment: Topical review, submitted to Journal of Physics G: 68 pages,
including 39 figures (revised version: only minor modifications, some
references added
Factors that could explain the increasing prevalence of type 2 diabetes among adults in a Canadian province: a critical review and analysis
Abstract: Background: The prevalence of diabetes has increased since the last decade in New Brunswick. Identifying factors contributing to the increase in diabetes prevalence will help inform an action plan to manage the condition. The objective was to describe factors that could explain the increasing prevalence of type 2 diabetes in New Brunswick since 2001. Methods: A critical literature review was conducted to identify factors potentially responsible for an increase in prevalence of diabetes. Data from various sources were obtained to draw a repeated cross-sectional (2001–2014) description of these factors concurrently with changes in the prevalence of type 2 diabetes in New Brunswick. Linear regressions, Poisson regressions and Cochran Armitage analysis were used to describe relationships between these factors and time. Results: Factors identified in the review were summarized in five categories: individual-level risk factors, environmental risk factors, evolution of the disease, detection effect and global changes. The prevalence of type 2 diabetes has increased by 120% between 2001 and 2014. The prevalence of obesity, hypertension, prediabetes, alcohol consumption, immigration and urbanization increased during the study period and the consumption of fruits and vegetables decreased which could represent potential factors of the increasing prevalence of type 2 diabetes. Physical activity, smoking, socioeconomic status and education did not present trends that could explain the increasing prevalence of type 2 diabetes. During the study period, the mortality rate and the conversion rate from prediabetes to diabetes decreased and the incidence rate increased. Suggestion of a detection effect was also present as the number of people tested increased while the HbA1c and the age at detection decreased. Period and birth cohort effect were also noted through a rise in the prevalence of type 2 diabetes across all age groups, but greater increases were observed among the younger cohorts. Conclusions: This study presents a comprehensive overview of factors potentially responsible for population level changes in prevalence of type 2 diabetes. Recent increases in type 2 diabetes in New Brunswick may be attributable to a combination of some individual-level and environmental risk factors, the detection effect, the evolution of the disease and global changes
Origins of the Ambient Solar Wind: Implications for Space Weather
The Sun's outer atmosphere is heated to temperatures of millions of degrees,
and solar plasma flows out into interplanetary space at supersonic speeds. This
paper reviews our current understanding of these interrelated problems: coronal
heating and the acceleration of the ambient solar wind. We also discuss where
the community stands in its ability to forecast how variations in the solar
wind (i.e., fast and slow wind streams) impact the Earth. Although the last few
decades have seen significant progress in observations and modeling, we still
do not have a complete understanding of the relevant physical processes, nor do
we have a quantitatively precise census of which coronal structures contribute
to specific types of solar wind. Fast streams are known to be connected to the
central regions of large coronal holes. Slow streams, however, appear to come
from a wide range of sources, including streamers, pseudostreamers, coronal
loops, active regions, and coronal hole boundaries. Complicating our
understanding even more is the fact that processes such as turbulence,
stream-stream interactions, and Coulomb collisions can make it difficult to
unambiguously map a parcel measured at 1 AU back down to its coronal source. We
also review recent progress -- in theoretical modeling, observational data
analysis, and forecasting techniques that sit at the interface between data and
theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue
connected with a 2016 ISSI workshop on "The Scientific Foundations of Space
Weather." 44 pages, 9 figure
SUMOylation of DRIL1 Directs Its Transcriptional Activity Towards Leukocyte Lineage-Specific Genes
DRIL1 is an ARID family transcription factor that can immortalize primary mouse fibroblasts, bypass RASV12-induced cellular senescence and collaborate with RASV12 or MYC in mediating oncogenic transformation. It also activates immunoglobulin heavy chain transcription and engages in heterodimer formation with E2F to stimulate E2F-dependent transcription. Little, however, is known about the regulation of DRIL1 activity. Recently, DRIL1 was found to interact with the SUMO-conjugating enzyme Ubc9, but the functional relevance of this association has not been assessed. Here, we show that DRIL1 is sumoylated both in vitro and in vivo at lysine 398. Moreover, we provide evidence that PIASy functions as a specific SUMO E3-ligase for DRIL1 and promotes its sumoylation both in vitro and in vivo. Furthermore, consistent with the subnuclear localization of PIASy in the Matrix-Associated Region (MAR), SUMO-modified DRIL1 species are found exclusively in the MAR fraction. This post-translational modification interferes neither with the subcellular localization nor the DNA-binding activity of the protein. In contrast, DRIL1 sumoylation impairs its interaction with E2F1 in vitro and modifies its transcriptional activity in vivo, driving transcription of subset of genes regulating leukocyte fate. Taken together, these results identify sumoylation as a novel post-translational modification of DRIL1 that represents an important mechanism for targeting and modulating DRIL1 transcriptional activity
Human Polycomb 2 Protein Is a SUMO E3 Ligase and Alleviates Substrate-Induced Inhibition of Cystathionine β-Synthase Sumoylation
Human cystathionine β-synthase (CBS) catalyzes the first irreversible
step in the transsulfuration pathway and commits homocysteine to the synthesis
of cysteine. Mutations in CBS are the most common cause of severe hereditary
hyperhomocysteinemia. A yeast two-hybrid approach to screen for proteins that
interact with CBS had previously identified several components of the
sumoylation pathway and resulted in the demonstration that CBS is a substrate
for sumoylation. In this study, we demonstrate that sumoylation of CBS is
enhanced in the presence of human polycomb group protein 2 (hPc2), an
interacting partner that was identified in the initial yeast two-hybrid screen.
When the substrates for CBS, homocysteine and serine for cystathionine
generation and homocysteine and cysteine for H2S generation, are
added to the sumoylation mixture, they inhibit the sumoylation reaction, but
only in the absence of hPc2. Similarly, the product of the CBS reaction,
cystathionine, inhibits sumoylation in the absence of hPc2. Sumoylation in turn
decreases CBS activity by ∼28% in the absence of hPc2 and by
70% in its presence. Based on these results, we conclude that hPc2
serves as a SUMO E3 ligase for CBS, increasing the efficiency of sumoylation. We
also demonstrate that γ-cystathionase, the second enzyme in the
transsulfuration pathway is a substrate for sumoylation under in vitro
conditions. We speculate that the role of this modification may be for nuclear
localization of the cysteine-generating pathway under conditions where nuclear
glutathione demand is high
SUMO modification of PCNA is controlled by DNA
Post-translational modification by the ubiquitin-like protein SUMO is often regulated by cellular signals that restrict the modification to appropriate situations. Nevertheless, many SUMO-specific ligases do not exhibit much target specificity, and—compared with the diversity of sumoylation substrates—their number is limited. This raises the question of how SUMO conjugation is controlled in vivo. We report here an unexpected mechanism by which sumoylation of the replication clamp protein, PCNA, from budding yeast is effectively coupled to S phase. We find that loading of PCNA onto DNA is a prerequisite for sumoylation in vivo and greatly stimulates modification in vitro. To our surprise, however, DNA binding by the ligase Siz1, responsible for PCNA sumoylation, is not strictly required. Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated
Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells
available in PMC 2011 November 01.Cellular RNA levels are determined by the interplay of RNA production, processing and degradation. However, because most studies of RNA regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification and computational modeling to estimate RNA transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed RNA population to estimate temporally constant RNA processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation.Human Frontier Science Program (Strasbourg, France)Howard Hughes Medical InstituteBurroughs Wellcome Fund (Career Award at the Scientific Interface
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