823 research outputs found
On -filtrations of Weyl modules
This paper considers Weyl modules for a simple, simply connected algebraic
group over an algebraically closed field of positive characteristic
. The main result proves, if (where is the Coxeter
number) and if the Lusztig character formula holds for all (irreducible modules
with) regular restricted highest weights, then any Weyl module
has a -filtration, namely, a filtration with
sections of the form
, where is
restricted and is arbitrary dominant. In case the highest weight
of the Weyl module is -regular, the
-filtration is compatible with the -radical series of the module. The
problem of showing that Weyl modules have -filtrations was first
proposed as a worthwhile ("w\"unschenswert") problem in Jantzen's 1980 Crelle
paper.Comment: Latest version corrects minor mistakes in previous versions. A
reference is made to Williamson's recent arXiv posting, providing some
relevant discussion in a footnote. [Comments on earlier versions: Previous v.
1 with minor errors and statements corrected. Improved organization. Should
replace v. 2 which is an older version (even older than v.1) and was
mistakenly posted.
Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A
Ubc13, a ubiquitin-conjugating enzyme (Ubc), requires the presence of a Ubc variant (Uev) for polyubiquitination. Uevs, although resembling Ubc in sequence and structure, lack the active site cysteine residue and are catalytically inactive. The yeast Uev (Mms2) incites noncanonical Lys63-linked polyubiquitination by Ubc13, whereas the increased diversity of Uevs in higher eukaryotes suggests an unexpected complication in ubiquitination. In this study, we demonstrate that divergent activities of mammalian Ubc13 rely on its pairing with either of two Uevs, Uev1A or Mms2. Structurally, we demonstrate that Mms2 and Uev1A differentially modulate the length of Ubc13-mediated Lys63-linked polyubiquitin chains. Functionally, we describe that Ubc13–Mms2 is required for DNA damage repair but not nuclear factor κB (NF-κB) activation, whereas Ubc13–Uev1A is involved in NF-κB activation but not DNA repair. Our finding suggests a novel regulatory mechanism in which different Uevs direct Ubcs to diverse cellular processes through physical interaction and alternative polyubiquitination
Glycoproteome remodeling and organelle-specific N-glycosylation accompany neutrophil granulopoiesis
Neutrophils store microbicidal glycoproteins in cytosolic granules to fight intruding pathogens, but their granule distribution and formation mechanism(s) during granulopoiesis remain unmapped. Herein, we comprehensively profile the neutrophil N-glycoproteome with spatiotemporal resolution by analyzing four key types of intracellular organelles isolated from blood-derived neutrophils and during their maturation from bone marrow–derived progenitors using a glycomics-guided glycoproteomics approach. Interestingly, the organelles of resting neutrophils exhibited distinctive glycophenotypes including, most strikingly, highly truncated N-glycans low in α2,6-sialylation and Lewis fucosylation decorating a diverse set of microbicidal proteins (e.g., myeloperoxidase, azurocidin, neutrophil elastase) in the azurophilic granules. Excitingly, proteomics and transcriptomics data from discrete myeloid progenitor stages revealed that profound glycoproteome remodeling underpins the promyelocytic-to-metamyelocyte transition and that the glycophenotypic differences are driven primarily by dynamic changes in protein expression and less by changes within the glycosylation machinery. Notable exceptions were the oligosaccharyltransferase subunits responsible for initiation of N-glycoprotein biosynthesis that were strongly expressed in early myeloid progenitors correlating with relatively high levels of glycosylation of the microbicidal proteins in the azurophilic granules. Our study provides spatiotemporal insights into the complex neutrophil N-glycoproteome featuring intriguing organelle-specific N-glycosylation patterns formed by dynamic glycoproteome remodeling during the early maturation stages of the myeloid progenitors
Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors
With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors
Early Universe Quantum Processes in BEC Collapse Experiments
We show that in the collapse of a Bose-Einstein condensate (BEC) {For an
excellent introduction to BEC theory, see C. Pethick and H. Smith,
Bose-Einstein condensation in dilute gases (Cambridge University Press,
Cambridge, England, 2002)} certain processes involved and mechanisms at work
share a common origin with corresponding quantum field processes in the early
universe such as particle creation, structure formation and spinodal
instability. Phenomena associated with the controlled BEC collapse observed in
the experiment of Donley et al E. Donley et. al., Nature 412, 295 (2001)(they
call it `Bose-Nova', see also J. Chin, J. Vogels and W. Ketterle, Phys. Rev.
Lett. 90, 160405 (2003)) such as the appearance of bursts and jets can be
explained as a consequence of the squeezing and amplification of quantum
fluctuations above the condensate by the dynamics of the condensate. Using the
physical insight gained in depicting these cosmological processes, our analysis
of the changing amplitude and particle contents of quantum excitations in these
BEC dynamics provides excellent quantitative fits with the experimental data on
the scaling behavior of the collapse time and the amount of particles emitted
in the jets. Because of the coherence properties of BEC and the high degree of
control and measurement precision in atomic and optical systems, we see great
potential in the design of tabletop experiments for testing out general ideas
and specific (quantum field) processes in the early universe, thus opening up
the possibility for implementing `laboratory cosmology'.Comment: 7 pages, 3 figures. Invited Talk presented at the Peyresq Meetings of
Gravitation and Cosmology, 200
Hyper-truncated Asn355- And Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase
Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products. Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive. To this end, we have characterised the structure–biosynthesis–activity relationship of neutrophil MPO (nMPO). Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans. Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation. Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer. Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation. We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis. While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations. Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO. Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition. Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity
Giant phonon anomalies and central peak due to charge density wave formation in YBaCuO
The electron-phonon interaction is a major factor influencing the competition
between collective instabilities in correlated-electron materials, but its role
in driving high-temperature superconductivity in the cuprates remains poorly
understood. We have used high-resolution inelastic x-ray scattering to monitor
low-energy phonons in YBaCuO (superconducting
K), which is close to a charge density wave (CDW) instability. Phonons in a
narrow range of momentum space around the CDW ordering vector exhibit extremely
large superconductivity-induced lineshape renormalizations. These results imply
that the electron-phonon interaction has sufficient strength to generate
various anomalies in electronic spectra, but does not contribute significantly
to Cooper pairing. In addition, a quasi-elastic "central peak" due to CDW
nanodomains is observed in a wide temperature range above and below ,
suggesting that the gradual onset of a spatially inhomogeneous CDW domain state
with decreasing temperature is a generic feature of the underdoped cuprates
MLN51 Stimulates the RNA-Helicase Activity of eIF4AIII
The core of the exon-junction complex consists of Y14, Magoh, MLN51 and eIF4AIII, a DEAD-box RNA helicase. MLN51 stimulates the ATPase activity of eIF4AIII, whilst the Y14-Magoh complex inhibits it. We show that the MLN51-dependent stimulation increases both the affinity of eIF4AIII for ATP and the rate of enzyme turnover; the K (M) is decreased by an order of magnitude and k (cat) increases 30 fold. Y14-Magoh do inhibit the MLN51-stimulated ATPase activity, but not back to background levels. The ATP-bound form of the eIF4AIII-MLN51 complex has a 100-fold higher affinity for RNA than the unbound form and ATP hydrolysis reduces this affinity. MLN51 stimulates the RNA-helicase activity of eIF4AIII, suggesting that this activity may be functionally important
Conceptualizing pathways linking women's empowerment and prematurity in developing countries.
BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed
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