The rockefeller university

Stromatolites can grow under the influence of microbial processes, but it is often unclear whether and how the macroscopic morphology of these rocks records biological processes. Conical stromatolites, which formed in the absence of sedimentation, provide a comparatively simple record of the interplay between microbial growth and lithification. Here, we show that the dynamics shaping conical stromatolites result from diffusive gradients within the overlying microbial mat. These gradients cause minerals to precipitate faster in regions of high curvature, resulting in measurable properties of the shapes of stromatolite laminas. This model allows us to estimate the thickness of ancient stromatolite-forming mats to be approximately 1 mm, consistent with modern systems. Proceeding from the assumption that the ubiquitous process of diffusion is recorded in the translating form of a stromatolite, we derive the shape of a diffusion-driven stromatolite. The conical morphology-a distinctive feature of stromatolites growing in the absence of sedimentation-arises from these dynamics. This form is quantitatively consistent with the shape of conical stromatolites that grew for more than 2.9 x 10(9) yrs of Earth history.

A search for a Higgs boson decaying into a Z boson and a photon is described. The analysis is performed using proton-proton collision datasets recorded by the CMS detector at the LHC. Events were collected at center-of-mass energies of 7 TeV and 8 TeV, corresponding to integrated luminosities of 5.0 fb(-1) and 19.6 fb(-1), respectively. The selected events are required to have opposite-sign electron or muon pairs. No excess above standard model predictions has been found in the 120-160 GeV mass range and the first limits on the Higgs boson production cross section times the H -> Z gamma branching fraction at the LHC have been derived. The observed at 95% confidence level limits are between about 4 and 25 times the standard model cross section times the branching fraction. For a standard model Higgs boson mass of 125 GeV the expected limit at the 95% confidence level is 10 and the observed limit is 9.5. Models predicting the Higgs boson production cross section times the H -> Z gamma branching fraction to be larger than one order of magnitude of the standard model prediction are excluded for most of the 125-157 GeV mass range. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.

Searches for anomalous top quark-antiquark production are presented, based on pp collisions at root s = 8 TeV. The data, corresponding to an integrated luminosity of 19.7 fb(-1), were collected with the CMS detector at the LHC. The observed t (t) over bar invariant mass spectrum is found to be compatible with the standard model prediction. Limits on the production cross section times branching fraction probe, for the first time, a region of parameter space for certain models of new physics not yet constrained by precision measurements.

Significant efforts have been made to identify HIV-1 neutralizing antibodies because they are considered to be critical to the design of an effective HIV-1 vaccine. Although soluble HIV-1 envelope proteins can be used for this purpose, these reagents differ from membrane-anchored HIV-1 envelope spike in a number of important ways and display only a subset of its native epitopes. Consistent with this, some broadly neutralizing antibodies preferentially bind cell surface-expressed HIV-1 envelope, but not the soluble protein. Here we report the details of a new method for isolating anti-HIV-1 specific B cells based on capturing cells that produce antibodies to cell surface-expressed gp160 Delta c(BaL). While this method is far less efficient than sorting with soluble envelope proteins, it isolated broadly neutralizing anti-HIV-1 antibodies that bind cell surface-expressed gp160 Delta c(BaL) but not soluble envelope proteins. Published by Elsevier B.V.

Purpose: Human endogenous retroviruses (HERV) encode 8% of the human genome. While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic association has yet been established. We studied the expression and immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation to the clinical course of prostate cancer. Experimental Design: In vitro expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues, microarrays, and cell lines, and effects of demethylation and androgen stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG-HERV-K and other self-antigens by ELISA and seromics (protein array profiling). Results: GAG-HERV-K expression was most frequent in prostate tissues and regulated both by demethylation of the promoter region and by androgen stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in a subset of patients with prostate cancer (33 of 483, 6.8%) but rarely in male healthy donors (1 of 55, 1.8%). Autoantibodies to GAG-HERV-K occurred more frequently in patients with advanced prostate cancer (29 of 191 in stage III-IV, 21.0%) than in early prostate cancer (4 of 292 in stages I-II, 1.4%). Presence of GAG-HERV-K serum antibody was correlated with worse survival of patients with prostate cancer, with a trend for faster biochemical recurrence in patients with antibodies to GAG-HERV-K. Conclusions: Preferential expression of GAG-HERV-K ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies observed in patients with advanced prostate cancer make this protein one of the first bona fide retroviral cancer antigens in humans, with potential as a biomarker for progression and biochemical recurrence rate of prostate cancer. (C) 2013 AACR.

Approximately 90% of patients with isolated agammaglob ulinemia and failure of B cell development have mutations in genes required for signaling through the pre-B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agatnmaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue-specific heteroclimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors.

Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fc gamma receptor Fc gamma RIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally deleted for Fc gamma RIIB on defined cellular populations or mutated in specific signaling components, we now demonstrate that different agonistic antiTNFR antibodies have specific requirements for Fc gamma RIIB expression on defined cellular populations and function in trans in the absence of Fc gamma RIIB signaling components, thus supporting a general mechanism of FcRIIB cross-linking in vivo for the activities of these antibodies.

Combination therapy may improve the outcome of Streptococcus pneumoniae-induced bacteraemia. Here we tested the combination of two antipneumococcal agents, daptomycin and Cpl-1 (the pneumococcal Cp-1 bacteriophage lysin), in a mouse model of pneumococcal bacteraemia. Mice were challenged intraperitoneally (i.p.) with 10(6) CFU of the extremely virulent serotype 2 S. pneumoniae D39 isolate. Subtherapeutic doses of daptomycin (0.4 mg/kg) and Cpl-1 (0.4 mg/kg and 1 mg/kg) were administrated i.p. either alone or in combination by a single bolus injection 1 h after bacterial challenge. Survival rates of animals were followed over a period of 7 days. Daptomycin (0.4 mg/kg) in combination with Cpl-1 (0.4 mg/kg) significantly increased the percentage of surviving mice at Day 7 (80%) compared with the untreated control (0%) and daptomycin or Cpl-1 monotherapy (35% and 0%, respectively). Whilst increasing the concentration of Cpl-1 to 1.0 mg/kg did not improve survival when injected alone, its combination with 0.4 mg/kg daptomycin further increased the survival rate to 95%. Thus, it was found that the combination of daptomycin with Cpl-1 was synergistic and bactericidal against S. pneumoniae in a mouse model of pneumococcal bacteraemia. To our knowledge, this is the first report of synergism between daptomycin and a phage lysin demonstrated in vivo. Such a combination could represent an interesting alternative therapy for the treatment of pneumococcal bacteraemia/sepsis and possibly other severe pneumococcal infections. (c) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Results are reported from a search for non-standard-model Higgs boson decays to pairs of new light bosons, each of which decays into the mu(+)mu(-) final state. The new bosons may be produced either promptly or via a decay chain. The data set corresponds to an integrated luminosity of 5.3 fb(-1) of proton-proton collisions at root s = 7 TeV, recorded by the CMS experiment at the LHC in 2011. Such Higgs boson decays are predicted in several scenarios of new physics, including supersymmetric models with extended Higgs sectors or hidden valleys. Thus, the results of the search are relevant for establishing whether the new particle observed in Higgs boson searches at the LHC has the properties expected for a standard model Higgs boson. No excess of events is observed with respect to the yields expected from standard model processes. A model-independent upper limit of 0.86 +/- 0.06 fb on the product of the cross section times branching fraction times acceptance is obtained. The results, which are applicable to a broad spectrum of new physics scenarios, are compared with the predictions of two benchmark models as functions of a Higgs boson mass larger than 86 GeV/c(2) and of a new light boson mass within the range 0.25-3.55 GeV/c(2). (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.

We present a measurement of the top-quark pair production cross section in proton-antiproton collisions at root s = 1.96 TeV. The data were collected at the Fermilab Tevatron by the CDF II detector and correspond to an integrated luminosity of 8.8 fb(-1), representing the complete CDF Run II data set. We select events consistent with the production of top-quark pairs by requiring the presence of two reconstructed leptons, an imbalance in the total event transverse momentum, and jets. At least one jet is required to be identified as consistent with the fragmentation of a bottom quark using a secondary-vertex-finding algorithm. The 246 candidate events are estimated to have a signal purity of 91%. We measure a cross section of sigma(t (t) over bar) = 7.09 +/- 0.84 pb, assuming a top-quark mass of 172.5 GeV/c(2). The results are consistent with the standard model as predicted by next-to-leading-order calculations.