Fuchs' problem for indecomposable abelian groups

More than 50 years ago, Laszlo Fuchs asked which abelian groups can be the group of units of a commutative ring. Though progress has been made, the question remains open. We provide an answer to this question in the case of indecomposable abelian groups by classifying the indecomposable abelian groups that are realizable as the group of units of a ring of any given characteristic.Comment: 10 pages, accepted for publication in Journal of Algebr

Characterizations of Mersenne and 2-rooted primes

We give several characterizations of Mersenne primes (Theorem 1.1) and of primes for which 2 is a primitive root (Theorem 1.2). These characterizations involve group algebras, circulant matrices, binomial coefficients, and bipartite graphs.Comment: 19 pages, final version, to appear in Finite Fields and their Application

Fuchs' problem for endomorphisms of abelian groups

L\'{a}szl\'{o} Fuchs posed the following question: which abelian groups arise as the group of units in a ring? In this paper, we investigate a related question: for such realizable groups $G$, when is there a ring $R$ with unit group $G$ such that every group endomorphism of $G$ is induced by a ring endomorphism of $R$? We answer this question for four common classes of groups: torsion-free abelian groups, groups of odd order, torsion abelian groups, and finitely generated abelian groups.Comment: 13 pages, Accepted for publication in the Journal of Algebr

Spatio-temporal regulation of Wnt and retinoic acid signaling by tbx16/spadetail during zebrafish mesoderm differentiation

<p>Abstract</p> <p>Background</p> <p>A complex network of signaling pathways and transcription factors regulates vertebrate mesoderm development. Zebrafish mutants provide a powerful tool for examining the roles of individual genes in such a network. <it>spadetail (spt) </it>is a mutant with a lesion in <it>tbx16</it>, a T-box transcription factor involved in mesoderm development; the mutant phenotype includes disrupted primitive red blood cell formation as well as disrupted somitogenesis. Despite much recent progress, the downstream targets of <it>tbx16 </it>remain incompletely understood. The current study was carried out to test whether any of the five major signaling pathways are regulated by <it>tbx16 </it>during two specific stages of mesoderm development: primitive red blood cell formation in the intermediate mesoderm and somite formation in the tail paraxial mesoderm. This test was performed using Gene Set Enrichment Analysis, which identifies coordinated changes in expression among <it>a priori </it>sets of genes associated with biological features or processes.</p> <p>Results</p> <p>Our Gene Set Enrichment Analysis results identify Wnt and retinoic acid signaling as likely downstream targets of <it>tbx16 </it>in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation. In addition, such results identify retinoic acid signaling as a downstream target of <it>tbx16 </it>in the developing zebrafish posterior somites. Finally, using candidate gene identification and <it>in situ </it>hybridization, we provide expression domain information for 25 additional genes downstream of <it>tbx16 </it>that are outside of both pathways; 23 were previously unknown downstream targets of <it>tbx16</it>, and seven had previously uncharacterized expression in zebrafish.</p> <p>Conclusions</p> <p>Our results suggest that (1) <it>tbx16 </it>regulates Wnt signaling in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation, and (2) <it>tbx16 </it>regulates retinoic acid signaling at two distinct embryonic locations and developmental stages, which may imply ongoing spatio-temporal regulation throughout mesoderm development.</p

Amino acid sequence of the active site of human serum cholinesterase from usual, atypical, and atypical-silent genotypes

Active-site tryptic peptides were isolated from three genetic types of human serum cholinesterase. The active-site peptide was identified by labeling the active-site serine with [ 3 H] diisopropylfluorophosphate. Peptides were purified by high-performance liquid chromatography. Amino acid composition and sequence analysis showed that the peptide from the usual genotype contained 29 residues with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser-Val-Ser-Leu-His-Leu-Leu-Ser-Pro-Gly-Ser-His-Ser-Leu-Phe-Thr-Arg. The active-site serine was the eighth residue from the N- terminal. The peptide containing the active-site serine from the atypical genotype contained 22 residues with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser-Val-Ser-Leu-His-Leu-Leu-Ser-Pro-Gly. The peptide from the atypical-silent genotype contained eight residues with the sequence Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser. Thus, the sequences of the atypical and atypical-silent active-site peptides were identical to the corresponding portions of the usual peptide.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44153/1/10528_2004_Article_BF00499101.pd

Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis

DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b–/– lymphomas, but not in Dnmt3b–/– pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b–/– lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies

Immunological comparison of the usual and atypical human serum cholinesterase phenotypes

Antiserum prepared against highly purified usual human serum cholinesterase (the most common phenotype) cross-reacted identically with the atypical serum cholinesterase. The level of circulating atypical enzyme protein, determined immunologically, was about 30% lower when the enzyme came from an atypical rather than a usual phenotype, and the level of enzyme activity measured enzymatically at V max with either o -nitrophenylbutyrate or benzoylcholine as substrate showed approximately the same degree of reduction. The average specific activity (activity at V max per microgram of enzyme protein) in sera from 28 usual and 20 atypical individuals did not differ significantly. These findings suggest that the atypical enzyme not only has altered catalytic properties ( K ) m but also might be synthesized more slowly, or cleared in vivo more rapidly, than the usual enzyme.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44145/1/10528_2004_Article_BF00498901.pd

Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties.Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection