The Th1 cell regulatory circuitry is largely conserved between human and mouse

Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We compared T-bet genomic targets between mouse and human CD4+ T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we found that the majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding was associated with differences in transcription factor–binding motifs and species-specific expression of associated genes. These results provide a genome-wide cross-species comparison of Th1 gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory and infectious diseases and cancer into human clinical trials

On Automorphisms and Focal Subgroups of Blocks

Given a p-block B of a finite group with defect group P and fusion system on P, we show that the rank of the group is invariant under stable equivalences of Morita type. The main ingredients are the construction, due to Broué and Puig, a theorem of Weiss on linear source modules, arguments of Hertweck and Kimmerle applying Weiss’ theorem to blocks, and connections with integrable derivations in the Hochschild cohomology of block algebras

Antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism

Pathogenic and mutualistic bacteria associated with eukaryotic hosts often lack distinctive genomic features, suggesting regular transitions between these lifestyles. Here we present evidence supporting a dynamic transition from plant pathogenicity to insect-defensive mutualism in symbiotic Burkholderia gladioli bacteria. In a group of herbivorous beetles, these symbionts protect the vulnerable egg stage against detrimental microbes. The production of a blend of antibiotics by B. gladioli, including toxoflavin, caryoynencin and two new antimicrobial compounds, the macrolide lagriene and the isothiocyanate sinapigladioside, likely mediate this defensive role. In addition to vertical transmission, these insect symbionts can be exchanged via the host plant and retain the ability to initiate systemic plant infection at the expense of the plant’s fitness. Our findings provide a paradigm for the transition between pathogenic and mutualistic lifestyles and shed light on the evolution and chemical ecology of this defensive mutualism

Torsion Units for a Ree group, Tits group and a Steinberg triality group

We investigate the Zassenhaus conjecture for the Steinberg triality group ${}^3D_4(2^3)$, Tits group ${}^2F_4(2)'$ and the Ree group ${}^2F_4(2)$. Consequently, we prove that the Prime Graph question is true for all three groups

The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus

The saprophytic fungus Aspergillus fumigatus is the most important air-borne fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a potential target for development of effective antifungal agents. A major role in maintaining cell wall integrity is played by the mitogen-activated protein kinase (MAPK) MpkA. To gain a comprehensive insight into this central signal transduction pathway, we performed a transcriptome analysis of the ΔmpkA mutant under standard and cell wall stress conditions. Besides genes involved in cell wall remodelling, protection against ROS and secondary metabolism such as gliotoxin, pyomelanin and pseurotin A, also genes involved in siderophore biosynthesis were regulated by MpkA. Consistently, northern and western blot analyses indicated that iron starvation triggers phosphorylation and thus activation of MpkA. Furthermore, localization studies indicated that MpkA accumulates in the nucleus under iron depletion. Hence, we report the first connection between a MAPK pathway and siderophore biosynthesis. The measurement of amino acid pools and of the pools of polyamines indicated that arginine was continuously converted into ornithine to fuel the siderophore pool in the ΔmpkA mutant strain. Based on our data, we propose that MpkA fine-tunes the balance between stress response and energy consuming cellular processes

T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer

The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA stability, and translation in a wide range of organisms. To provide a model system to explore the role of Dicer-generated RNAs in the differentiation of mammalian cells in vivo, we have generated a conditional Dicer allele. Deletion of Dicer at an early stage of T cell development compromised the survival of alphabeta lineage cells, whereas the numbers of gammadelta-expressing thymocytes were not affected. In developing thymocytes, Dicer was not required for the maintenance of transcriptional silencing at pericentromeric satellite sequences (constitutive heterochromatin), the maintenance of DNA methylation and X chromosome inactivation in female cells (facultative heterochromatin), and the stable shutdown of a developmentally regulated gene (developmentally regulated gene silencing). Most remarkably, given that one third of mammalian mRNAs are putative miRNA targets, Dicer seems to be dispensable for CD4/8 lineage commitment, a process in which epigenetic regulation of lineage choice has been well documented. Thus, although Dicer seems to be critical for the development of the early embryo, it may have limited impact on the implementation of some lineage-specific gene expression programs

Time evolution, cyclic solutions and geometric phases for the generalized time-dependent harmonic oscillator

The generalized time-dependent harmonic oscillator is studied. Though several approaches to the solution of this model have been available, yet a new approach is presented here, which is very suitable for the study of cyclic solutions and geometric phases. In this approach, finding the time evolution operator for the Schr\"odinger equation is reduced to solving an ordinary differential equation for a c-number vector which moves on a hyperboloid in a three-dimensional space. Cyclic solutions do not exist for all time intervals. A necessary and sufficient condition for the existence of cyclic solutions is given. There may exist some particular time interval in which all solutions with definite parity, or even all solutions, are cyclic. Criterions for the appearance of such cases are given. The known relation that the nonadiabatic geometric phase for a cyclic solution is proportional to the classical Hannay angle is reestablished. However, this is valid only for special cyclic solutions. For more general ones, the nonadiabatic geometric phase may contain an extra term. Several cases with relatively simple Hamiltonians are solved and discussed in detail. Cyclic solutions exist in most cases. The pattern of the motion, say, finite or infinite, can not be simply determined by the nature of the Hamiltonian (elliptic or hyperbolic, etc.). For a Hamiltonian with a definite nature, the motion can changes from one pattern to another, that is, some kind of phase transition may occur, if some parameter in the Hamiltonian goes through some critical value.Comment: revtex4, 28 pages, no figur