On pp-filtrations of Weyl modules

This paper considers Weyl modules for a simple, simply connected algebraic group over an algebraically closed field $k$ of positive characteristic $p\not=2$. The main result proves, if $p\geq 2h-2$ (where $h$ is the Coxeter number) and if the Lusztig character formula holds for all (irreducible modules with) regular restricted highest weights, then any Weyl module $\Delta(\lambda)$ has a $\Delta^p$-filtration, namely, a filtration with sections of the form $\Delta^p(\mu_0+p\mu_1):=L(\mu_0)\otimes\Delta(\mu_1)^{[1]}$, where $\mu_0$ is restricted and $\mu_1$ is arbitrary dominant. In case the highest weight $\lambda$ of the Weyl module $\Delta(\lambda)$ is $p$-regular, the $p$-filtration is compatible with the $G_1$-radical series of the module. The problem of showing that Weyl modules have $\Delta^p$-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.

SARS-CoV-2 specific plasma cells acquire long-lived phenotypes in human bone marrowResearch in context

Summary: Background: SARS-CoV-2 specific antibody-secreting plasma cells (PC) mediating specific humoral immunity have been identified in the human bone marrow (BM) after COVID-19 or vaccination against SARS-CoV-2. However, it remained unclear whether or not they acquire phenotypes of human memory plasma cells. Methods: SARS-CoV-2-specific human bone marrow plasma cells (BMPC) were characterised by tetramer-based, antigen-specific flow cytometry and FluoroSpot assay. Findings: SARS-CoV-2 spike-S1-specific PC were detectable in all tested BM samples of previously vaccinated individuals, representing 0.22% of total BMPC. The majority of SARS-CoV-2-specific BMPC expressed IgG and their specificity for the spike S1 protein indicated emergence from a systemic vaccination response. Of note, one-fifth of SARS-CoV-2-specific BMPC showed the phenotype of memory plasma cells, i.e., downregulated CD19 and present or absent CD45 expression. Interpretation: Our data indicate the establishment of phenotypically diverse SARS-CoV-2-specific PC in the human BM after basic mRNA immunization, including the formation of memory phenotypes. These results suggest the induction of durable humoral immunity after basic mRNA vaccination against SARS-CoV-2. Funding: The study was supported by funding by the DFG grants TRR130 TP24, ME 3644/8-1, and the Berlin Senate. SR received funding from DFG SFB-1444 C01 Central Service Project

Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled γ-phosphate-linked GTP analogs

Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental activities of low molecular weight GTPases. We show that three guanosine 5′-triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5′-diphosphate with high intrinsic exchange rates in the presence of Mg(2+) ions, thereby acting as synthetic, low molecular weight guanine nucleotide exchange factors. The accompanying large fluorescence enhancements (as high as 12-fold), caused by a reduction in guanine quenching of the environmentally sensitive BODIPY dye fluorescence on protein binding, allow for real-time monitoring of this spontaneous nucleotide exchange in the visible spectrum with high signal-to-noise ratios. Binding affinities increased with longer aliphatic linkers connecting the nucleotide and BODIPY fluorophore and were in the 10–100 nM range. Steady-state and time-resolved fluorescence spectroscopy showed an inverse relationship between linker length and fluorescence enhancement factors and differences in protein-bound fluorophore mobilities, providing optimization criteria for future applications of such compounds as efficient elicitors and reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange, enabling rapid loading of GTPases with these probes. Differences in active site geometries, in the absence of Mg(2+), caused qualitatively different reporting of the bound state by the different analogs. The BODIPY analogs also prevented the interaction of Cdc42 with p21 activated kinase. Together, these results validate the use of these analogs as valuable tools for studying GTPase functions and for developing potent synthetic nucleotide exchange factors for this important class of signaling molecules