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In this Letter, we present a precise measurement of the total ZZ production cross section in p (p) over bar collisions at root s 1: 96 TeV, using data collected with the CDF II detector corresponding to an integrated luminosity of approximately 6 fb(-1). The result is obtained by combining separate measurements in the four-charged (lll'l') and two-charged-lepton and two-neutral-lepton (llvv) decay modes of the Z boson pair. The combined measured cross section for p (p) over bar -> ZZ is 1.64(-0.38)(+0.11) pb. This is the most precise measurement of the ZZ production cross section in 1.96 TeV p (p) over bar collisions to date.

All mRNA molecules are subject to some degree of post-transcriptional gene regulation (PTGR) involving sequence-dependent modulation of splicing, cleavage and polyadenylation, editing, transport, stability, and translation. The recent introduction of deep-sequencing technologies enabled the development of new methods for broadly mapping interaction sites between RNA-binding proteins (RBPs) and their RNA target sites. In this article, we review crosslinking and immunoprecipitation (CLIP) methods adapted for large-scale identification of target RNA-binding sites and the respective RNA recognition elements. CLIP methods have the potential to detect hundreds of thousands of binding sites in single experiments although the separation of signal from noise can be challenging. As a consequence, each CLIP method has developed different strategies to distinguish true targets from background. We focus on photoactivatable ribonucleoside-enhanced CLIP, which relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise. The precise knowledge of the position and distribution of binding sites across mature and primary mRNA transcripts allows critical insights into cellular localization and regulatory function of the examined RBP. When coupled with other systems-wide approaches measuring transcript and protein abundance, the generation of high-resolution RBP-binding site maps across the transcriptome will broaden our understanding of PTGR and thereby lead to new strategies for therapeutic treatment of genetic diseases perturbing these processes. (C) 2011 John Wiley & Sons, Ltd.

Cadherin/catenin-based adhesions coordinate cellular growth, survival, migration, and differentiation within a tissue by mechanically anchoring cells to their neighbors. They also intersect with diverse signaling pathways in development and cancer. Although the adhesive functions of adherens junction proteins are well characterized, their contribution to other signaling pathways is less well understood. Here, we show that ablation of alpha-catenin in the epidermis selectively induces apoptosis in suprabasal differentiating keratinocytes while sparing basal cell progenitors. This protection from death is coupled to elevated focal adhesion signaling, faster migration, and an altered distribution of growth factor receptors. We show that simultaneous depletion of alpha-catenin and focal adhesion kinase or p21-activated kinase eliminates basal cell protection as well as the elevated migration and proliferation of cells. The increased dependency of cells upon matrix interactions for their survival when cell-cell adhesions are destabilized has important implications for cancer progression and metastasis.

Post-embryonic growth in plants depends on the continuous supply of undifferentiated cells within meristems. Proliferating cells maintain their competence for division by active repression of differentiation and the associated endocycle entry. We show by upregulation and downregulation of E2FA that it is required for maintaining proliferation, as well as for endocycle entry. While E2FB-RBR1 (retinoblastoma-related protein 1) complexes are reduced after sucrose addition or at elevated CYCD3;1 levels, E2FA maintains a stable complex with RBR1 in proliferating cells. Chromatin immunoprecipitation shows that RBR1 binds in the proximity of E2F promoter elements in CCS52A1 and CSS52A2 genes, central regulators for the switch from proliferation to endocycles. Overexpression of a truncated E2FA mutant (E2FA(Delta RB)) lacking the RBR1-binding domain interferes with RBR1 recruitment to promoters through E2FA, leading to decreased meristem size in roots, premature cell expansion and hyperactivated endocycle in leaves. E2F target genes, including CCS52A1 and CCS52A2, are upregulated in E2FADRB and e2fa knockout lines. These data suggest that E2FA in complex with RBR1 forms a repressor complex in proliferating cells to inhibit premature differentiation and endocycle entry. Thus, E2FA regulates organ growth via two distinct, sequentially operating pathways. The EMBO Journal (2012) 31, 1480-1493. doi:10.1038/emboj.2012.13; Published online 3 February 2012

Corynebacterium bovis is a common pathogen in athymic nude mouse colonies. Control and eradication of the organism are challenging because depopulation and restricted colony access are often not options within vivaria. We evaluated potential sources and dissemination routes of C. bovis in an enzootically infected colony. Immunocompetent mice and personnel were evaluated for their potential to carry C. bovis, and husbandry and sanitation methods were evaluated for their efficacy in preventing cross-contamination. C. bovis was detected in furred immunocompetent mice previously exposed to infected athymic nude mice and in the nasopharynx of humans. Microisolation cages were not effective in maintaining athymic nude mice C. bovis-free when they were housed in a room known to contain immunodeficient mice with C. bovis infections. A tunnel washer that provided >= 180 degrees F final rinse provided effective elimination of C. bovis from cage components. Passive and active air sampling techniques showed airborne dispersal of C. bovis despite the use of individually ventilated caging systems and stringent operational standards. Bacterial growth was not observed in settle plates placed inside autoclaved individually ventilated microisolation cages on various ventilated racks for 24-h periods. C. bovis aerosolization was shown to be a means of spread of the bacterium during cage-change procedures inside a class II type A2 biosafety cabinet. Our findings indicate that C. bovis can be a pervasive environmental contaminant in infected rodent holding rooms and successful eradication strategies must include environmental decontamination and attention to air quality.

A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model expectation is observed using a data sample collected in proton-proton collisions at root s = 7 TeV corresponding to an integrated luminosity of 2: 2 fb(-1). In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.

Axons travel to their targets in bundles or fascicles, but the molecules regulating fasciculation remain incompletely characterized. We found that Slit2 and its Robo receptors are expressed by motor axons, and that inactivation of Slit2 or Robo1 and Robo2 in mice caused axons to defasciculate prematurely at muscle targets. In vitro, Slit2 secreted by motoneurons regulated fasciculation through Robo1 and Robo2. These results support the idea that Slit2 promotes axon fasciculation via an autocrine and/or juxtaparacrine mechanism.

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in the tissues of humans and wildlife. It has been reported that gestational exposure to PFOS causes neonatal death of rats. However, the mechanism is still unclear. In this study, we investigated the effects of gestational PFOS exposure on the gene expression profiling of fetal rat lung at pseudoglandular stage. Adult Sprague Dawley dams were dosed orally from gestational day 12-18 with 0 (control), 5 mg/kg/day or 20 mg/kg/day PFOS. Animals were euthanized on day 18.5, fetal lung samples were collected for histochemical staining and RNA profiling analysis. PFOS did not cause apparent microscopic changes of fetal lungs. Gene expression profiling revealed that PFOS dose-dependently up-regulated the expression of 21 (5 mg/kg) and 43 (20 mg/kg) genes. These genes include five PPAR alpha target genes (Acot1, Hmgcs2, Fabp4, Fabp1 and Myh7), and 4 of them are involved in lipid metabolism. The other genes were primarily included in the categories of cytoskeletal structure (Tpm1, Tnnt2,Actn3, Myoz2,Tmod1, and Mfap5), extracellular matrix (Ckm, Lum, Tnnc1, Art3, Dcn, Col17a1, Aspn, Ctsk, Itm2a, Spock2 and Orm1), transporting (Cox8h, Cox6a2 and Scnn1a) and secreted proteins (Scgb3a1, Nppb and Spp1). Our study demonstrates that in utero PFOS exposure resulted in the alteration of a set of genes which are involved in significant cytoskeletal, extracellular matrix remodeling, lipid metabolism and secreted proteins in the fetal rat lung. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice.

Mites of 3 genera-Myobia, Myocoptes, and Radfordia-continue to plague laboratory mouse facilities, even with use of stringent biosecurity measures. Mites often spread before diagnosis, predominantly because of detection difficulty. Current detection methods have suboptimal sensitivity, are time-consuming, and are costly. A sensitive serodiagnostic technique would facilitate detection and ease workload. We evaluated whether total IgE increases could serve as a serodiagnostic marker to identify mite infestations. Variables affecting total IgE levels including infestation duration, sex, age, mite species, soiled-bedding exposure, and ivermectin treatment were investigated in Swiss Webster mice. Strain- and pinworm-associated effects were examined by using C57BL/6 mice and Swiss Webster mice dually infested with Syphacia obvelata and Aspiculuris tetraptera, respectively. Mite infestations led to significant increases in IgE levels within 2 to 4 wk. Total IgE threshold levels and corresponding sensitivity and specificity values were determined along the continuum of a receiver-operating characteristic curve. A threshold of 81 ng/mL was chosen for Swiss Webster mice; values above this point should trigger screening by a secondary, more specific method. Sex-associated differences were not significant. Age, strain, and infecting parasite caused variability in IgE responses. Mice exposed to soiled bedding showed a delayed yet significant increase in total IgE. Treatment with ivermectin reduced total IgE levels within 2 wk. Our data suggest that increases in total IgE in Swiss Webster and C57BL/6 mice warrant investigation, especially because mile infestations can rapidly elevate total IgE levels. We propose that using total IgE levels routinely in serologic panels will enhance biosecurity.