1,552 research outputs found

    Holographic current correlators at finite coupling and scattering off a supersymmetric plasma

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    By studying the effect of the order(\alpha'^3) string theory corrections to type IIB supergravity, including those corrections involving the Ramond-Ramond five-form field strength, we obtain the corrected equations of motion of an Abelian perturbation of the AdS_5-Schwarzschild black hole. We then use the gauge theory/string theory duality to examine the coupling-constant dependence of vector current correlators associated to a gauged U(1) sub-group of the global R-symmetry group of strongly-coupled N=4 supersymmetric Yang-Mills theory at finite temperature. The corrections induce a set of higher-derivative operators for the U(1) gauge field, but their effect is highly suppressed. We thus find that the order(\alpha'^3) corrections affect the vector correlators only indirectly, through the corrected metric. We apply our results to investigate scattering off a supersymmetric Yang-Mills plasma at low and high energy. In the latter regime, where Deep Inelastic Scattering is expected to occur, we find an enhancement of the plasma structure functions in comparison with the infinite 't Hooft coupling result.Comment: 38 pages, 6 figures, minor clarifications added, typos corrected, references adde

    NF-ÎșB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer

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    Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor ÎșB (NF-ÎșB) subunits, p65 and c-Rel, in Treg identity and function. In this report, we show that NF-ÎșB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors. Using mouse models, we demonstrate that melanoma growth is drastically reduced in mice lacking c-Rel, but not p65, in Tregs. Moreover, chemical inhibition of c-Rel function delayed melanoma growth by impairing aTreg-mediated immunosuppression and potentiated the effects of anti-PD-1 immunotherapy. Our studies therefore establish inhibition of NF-ÎșB c-Rel as a viable therapeutic approach for enhancing checkpoint-targeting immunotherapy protocols

    Plasma photoemission from string theory

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    Leading 't Hooft coupling corrections to the photoemission rate of the planar limit of a strongly-coupled {\cal {N}}=4 SYM plasma are investigated using the gauge/string duality. We consider the full order \alpha'^3 type IIB string theory corrections to the supergravity action, including higher order terms with the Ramond-Ramond five-form field strength. We extend our previous results presented in arXiv:1110.0526. Photoemission rates depend on the 't Hooft coupling, and their curves suggest an interpolating behaviour from strong towards weak coupling regimes. Their slopes at zero light-like momentum give the electrical conductivity as a function of the 't Hooft coupling, in full agreement with our previous results of arXiv:1108.6306. Furthermore, we also study the effect of corrections beyond the large N limit.Comment: 36 pages, 5 figures, paragraph added in the conclusions, references added, typos correcte

    Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos

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    <p>Abstract</p> <p>Background</p> <p>The use of genetically-encoded fluorescent proteins has revolutionized the fields of cell and developmental biology and in doing so redefined our understanding of the dynamic morphogenetic processes that shape the embryo. With the advent of more accessible and sophisticated imaging technologies as well as an abundance of fluorescent proteins with different spectral characteristics, the dynamic processes taking place <it>in situ </it>in living cells and tissues can now be probed. Photomodulatable fluorescent proteins are one of the emerging classes of genetically-encoded fluorescent proteins.</p> <p>Results</p> <p>We have compared PA-GFP, PS-CFP2, Kaede and KikGR four readily available and commonly used photomodulatable fluorescent proteins for use in ES cells and mice. Our results suggest that the green-to-red photoconvertible fluorescent protein, Kikume Green-Red (KikGR), is most suitable for cell labeling and lineage studies in ES cells and mice because it is developmentally neutral, bright and undergoes rapid and complete photoconversion. We have generated transgenic ES cell lines and strains of mice exhibiting robust widespread expression of KikGR. By efficient photoconversion of KikGR we labeled subpopulations of ES cells in culture, and groups of cells within <it>ex utero </it>cultured mouse embryos. Red fluorescent photoconverted cells and their progeny could be followed for extended periods of time.</p> <p>Conclusion</p> <p>Transgenic ES cells and mice exhibiting widespread readily detectable expression of KikGR are indistinguishable from their wild type counterparts and are amenable to efficient photoconversion. They represent novel tools for non-invasive selective labeling specific cell populations and live imaging cell dynamics and cell fate. Genetically-encoded photomodulatable proteins such as KikGR represent emergent attractive alternatives to commonly used vital dyes, tissue grafts and genetic methods for investigating dynamic behaviors of individual cells, collective cell dynamics and fate mapping applications.</p

    Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

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    The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the hostÂŽs cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, JesĂșs SebastiĂĄn. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; Argentin

    Lignin biomarkers as tracers of mercury sources in lakes water column

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    This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

    Prioritisation of Clinical Research by the Example of Type 2 Diabetes: A Caregiver-Survey on Perceived Relevance and Need for Evidence

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    BACKGROUND: The Cochrane Collaboration aims at providing the best available evidence for interventions in health care. We wished to examine to which extent treatments considered relevant by caregivers in type 2 diabetes are covered by Cochrane systematic reviews. METHODOLOGY/PRINCIPAL FINDINGS: 130 different interventions in type 2 diabetes were identified based on a review of clinical practice guidelines and expert opinion (Table S1). 459 members of the German Diabetes Society (diabetologists, general practitioners, diabetic nurses, nutritionists, podologists, others) were surveyed via e-mail-list to rank a) the perceived clinical relevance and b) the perceived need for evidence of interventions, based on an internet survey. In the Cochrane Library, there were, at the time of this evaluation, 56 reviews on interventions in diabetes. Generally, coverage of topics by Cochrane reviews reflected the perceived clinical relevance and perceived need for evidence. As an example, highly ranked treatments such as lifestyle changes or oral antidiabetics were well covered, while low rank treatments such as complementary approaches were not covered. Discrepancies occurred with new treatments such as amylin-analogues (low relevance, high need for evidence, review not yet completed) and interventions with immediate and dramatic effects such as treating hypoglycemia (high relevance, low need for evidence, no review). Also, there was a relative scarcity of reviews concerning specific problems, in particular, treatment of late diabetic complications. CONCLUSIONS/SIGNIFICANCE: For most interventions, perceived relevance and perceived need for evidence are reflected by the evidence already available. Prioritizing should aim at improving immediacy and consideration of the treatment of complications
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