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We present a search for new physics in events with two high p(T) leptons of the same electric charge, using data with an integrated luminosity of 6.1 fb(-1). The observed data are consistent with standard model predictions. We set 95% C.L. lower limits on the mass of doubly charged scalars decaying to like-sign dileptons, m(H)++ > 190-245 GeV/c(2), assuming 100% BR to ee, mu mu or e mu

Natural killer T cells (NKT cells) recognize glycolipid antigens presented by CD1d. These cells express an evolutionarily conserved, invariant T cell antigen receptor (TCR), but the forces that drive TCR conservation have remained uncertain. Here we show that NKT cells recognized diacylglycerol-containing glycolipids from Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, and group B Streptococcus, which causes neonatal sepsis and meningitis. Furthermore, CD1d-dependent responses by NKT cells were required for activation and host protection. The glycolipid response was dependent on vaccenic acid, which is present in low concentrations in mammalian cells. Our results show how microbial lipids position the sugar for recognition by the invariant TCR and, most notably, extend the range of microbes recognized by this conserved TCR to several clinically important bacteria.

The fission yeast Schizosaccharomyces pombe is a rod-shaped cell that grows by linear extension at the cell tips, with a nearly constant width throughout the cell cycle. This simple geometry makes it an ideal system for studying the control of cellular dimensions. In this study, we carried out a near-genome-wide screen for mutants wider than wild-type cells. We found 11 deletion mutants that were wider; seven of the deleted genes are implicated in the control of the small GTPase Cdc42, including the Cdc42 guanine nucleotide exchange factor (GEF) Scd1 and the Cdc42 GTPase-activating protein (GAP) Rga4. Deletions of rga4 and scd1 had additive effects on cell width, and the proteins localized independently of one another, with Rga4 located at the cell sides and Scd1 at the cell tips. Activated Cdc42 localization is altered in rga4 Delta, scd1 Delta, and scd2 Delta mutants. Delocalization and ectopic retargeting experiments showed that the localizations of Rga4 and Scd1 are crucial for their roles in determining cell width. We propose that the GAP Rga4 and the GEF Scd1 establish a gradient of activated Cdc42 within the cellular tip plasma membrane, and it is this gradient that determines cell growth-zone size and normal cell width.

A detailed understanding of how activation of innate immunity can be exploited to generate more effective vaccines is critically required. However, little is known about how to target adjuvants to generate safer and better vaccines. In this study, we describe an adjuvant that, through complement activation and binding to follicular dendritic cells (FDC), dramatically enhances germinal center (GC) formation, which results in greatly augmented Ab responses. The nontoxic CTA1-DD adjuvant hosts the ADP-ribosylating CTA1 subunit from cholera toxin and a dimer of the D fragment from Staphylococcus aureus protein A. We found that T cell-dependent, but not -independent, responses were augmented by CTA1-DD. GC reactions and serum Ab titers were both enhanced in a dose-dependent manner. This effect required complement activation, a property of the DD moiety. Deposition of CTA1-DD to the FDC network appeared to occur via the conduit system and was dependent on complement receptors on the FDC. Hence, Cr2(-/-) mice failed to augment GC reactions and exhibited dramatically reduced Ab responses, whereas Ribi adjuvant demonstrated unperturbed adjuvant function in these mice. Noteworthy, the adjuvant effect on priming of specific CD4 T cells was found to be intact in Cr2(-/-) mice, demonstrating that the CTA1-DD host both complement-dependent and -independent adjuvant properties. This is the first demonstration, to our knowledge, of an adjuvant that directly activates complement, enabling binding of the adjuvant to the FDC, which subsequently strongly promoted the GC reaction, leading to augmented serum Ab titers and long-term memory development. The Journal of Immunology, 2011, 187: 3641-3652.

A measurement of the top-quark mass is presented using Tevatron data from proton-antiproton collisions at center-of-mass energy root s = 1.96 TeV collected with the CDF II detector. Events are selected from a sample of candidates for production of t (t) over bar pairs that decay into the lepton + jets channel. The top-quark mass is measured with an unbinned maximum likelihood method where the event probability density functions are calculated using signal and background matrix elements, as well as a set of parametrized jet-to-parton transfer functions. The likelihood function is maximized with respect to the top-quark mass, the signal fraction in the sample, and a correction to the jet energy scale (JES) calibration of the calorimeter jets. The simultaneous measurement of the JES correction (Delta(JES)) amounts to an additional in situ jet energy calibration based on the known mass of the hadronically decaying W boson. Using the data sample of 578 lepton + jets candidate events, corresponding to 3.2 fb(-1) of integrated luminosity, the top-quark mass is measured to be m(t) = 172.4 +/- 1.4(stat + Delta(JES)) +/- 1.3(syst) GeV/c(2).

This paper reports a search for nonstandard model topquark resonances, Z', decaying to t (t) over bar -> W(+)bW(-)(b) over bar, where both W decay to quarks. We examine the top-antitop quark invariant mass spectrum for the presence of narrow resonant states. The search uses a data sample of p (p) over bar collisions at a center of mass energy of 1.96 TeV collected by the CDF II detector at the Fermilab Tevatron, with an integrated luminosity of 2.8 fb(-1). No evidence for top-antitop quark resonant production is found. We place upper limits on the production cross section times branching ratio for a specific topcolor assisted technicolor model in which the Z' has a width of Gamma(Z') = 0.012M(Z'). Within this model, we exclude a Z' boson with masses below 805 GeV/c(2) at the 95% confidence level.

CK2 is a heterotetrameric ubiquitous kinase consisting of two catalytic subunits and two regulatory subunits. The two catalytic subunits, alpha and alpha', are highly homologous but differ in their C-terminal regions. It is not known whether CK2 alpha and alpha' have distinctive substrate specificity, since no alpha- or alpha'-specific substrate has been identified. Thus, it is assumed that the two kinase isoforms overlap in their substrate specificity. CK2 protein levels and activity were found to be elevated in the brain when compared to other organs. Here we have studied the protein levels of CK2 alpha and alpha' isoforms in nine major brain regions. We found that both, CK2 alpha and alpha', are expressed in all brain regions tested. Whereas CK2 alpha levels do not vary strongly across the regions, CK2 alpha' levels are slightly higher in the cortex and hippocampus than in other regions. Furthermore, we show that CK2 alpha protein levels in the striatum are relatively high when compared to CK2 alpha'. The approximate stoichiometry ratio of CK2 alpha:CK2 alpha' is 8:1. Therefore, one can consider that CK2 alpha levels are predominant in comparison to CK2 alpha' levels throughout the mammalian brain.

The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus. Using a position-specific scoring matrix, we identified evolutionary-conserved putative GREs from a microarray based set of hippocampal target genes. Using chromatin immunoprecipitation, we were able to confirm GR binding to 15 out of a selection of 32 predicted sites (47%). The majority of these 15 GREs are previously undescribed and thus represent novel GREs that bind GR and therefore may be functional in the rat hippocampus. GRE nucleotide composition was not predictive for binding of GR to a GRE. Asearch for conserved flanking sequences that may predict GR-GRE interaction resulted in the identification of GC-box associated motifs, such as Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the hippocampus. This enrichment was not present around nonbinding GRE sequences nor around proven GR-binding sites from a mesenchymal stem-like cell dataset that we analyzed. GC-binding transcription factors therefore may be unique partners for DNA-bound GR and may in part explain cell-specific transcriptional regulation by glucocorticoids in the context of the hippocampus. (Endocrinology 152: 3749-3757, 2011)

Trypanosome brucei undergoes major biochemical and morphological changes during its development from the bloodstream form in the mammalian host to the procyclic form in the midgut of its insect host. The underlying regulation of gene expression, however, is poorly understood. More than 60% of the predicted genes remain annotated as hypothetical, and the 5' and 3' untranslated regions important for regulation of gene expression are unknown for >90% of the genes. In this review, we compare the data from four recently published high-throughput RNA sequencing studies in light of the different experimental setups and discuss how these data can enhance genome annotation and give insights into the regulation of gene expression in T. brucei.