Phenomenology of the nMSSM from colliders to cosmology

Low energy supersymmetric models provide a solution to the hierarchy problem and also have the necessary ingredients to solve two of the most outstanding issues in cosmology: the origin of dark matter and baryonic matter. One of the most attractive features of this framework is that the relevant physical processes are related to interactions at the weak scale and therefore may be tested in collider experiments in the near future. This is true for the Minimal Supersymmetric Standard Model (MSSM) as well as for its extension with the addition of one singlet chiral superfield, the so-called nMSSM. It has been recently shown that within the nMSSM an elegant solution to both the problem of baryogenesis and dark matter may be found, that relies mostly on the mixing of the singlet sector with the Higgs sector of the theory. In this work we review the nMSSM model constraints from cosmology and present the associated collider phenomenology at the LHC and the ILC. We show that the ILC will efficiently probe the neutralino, chargino and Higgs sectors, allowing to confront cosmological observations with computations based on collider measurements. We also investigate the prospects for a direct detection of dark matter and the constraints imposed by the current bounds of the electron electric dipole moment in this model.Comment: 44 pp, 10 figures; Fig.9 replaced; discussion on CP violation extended and references added; few minor additions in text about details of the cut

Neutrino Oscillations and Collider Test of the R-parity Violating Minimal Supergravity Model

We study the R-parity violating minimal supergravity models accounting for the observed neutrino masses and mixing, which can be tested in future collider experiments. The bi-large mixing can be explained by allowing five dominant tri-linear couplings $\lambda'_{1,2,3}$ and $\lambda_{1,2}$. The desired ratio of the atmospheric and solar neutrino mass-squared differences can be obtained in a very limited parameter space where the tree-level contribution is tuned to be suppressed. In this allowed region, we quantify the correlation between the three neutrino mixing angles and the tri-linear R-parity violating couplings. Qualitatively, the relations $| \lambda'_1 | < | \lambda'_2| \sim | \lambda'_3|$, and $|\lambda_1| \sim |\lambda_2|$ are required by the large atmospheric neutrino mixing angle $\theta_{23}$ and the small angle $\theta_{13}$, and the large solar neutrino mixing angle $\theta_{12}$, respectively. Such a prediction on the couplings can be tested in the next linear colliders by observing the branching ratios of the lightest supersymmetric particle (LSP). For the stau or the neutralino LSP, the ratio $|\lambda_1|^2: |\lambda_2|^2: |\lambda_1|^2 + |\lambda_2|^2$ can be measured by establishing $Br(e\nu): Br(\mu\nu) : Br(\tau\nu)$ or $Br(\nu e^\pm \tau^\mp ): Br(\nu\mu^\pm\tau^\mp) : Br(\nu\tau^\pm\tau^\mp)$, respectively. The information on the couplings $\lambda'_i$ can be drawn by measuring $Br(l_i t \bar{b}) \propto |\lambda'_i|^2$ if the neutralino LSP is heavier than the top quark.Comment: RevTex, 25 pages, 8 eps figure

Differential orientation effect in the neural response to interacting biological motion of two agents

<p>Abstract</p> <p>Background</p> <p>A recent behavioral study demonstrated that the meaningful interaction of two agents enhances the detection sensitivity of biological motion (BM), however, it remains unclear when and how the 'interaction' information of two agents is represented in our neural system. To clarify this point, we used magnetoencephalography and introduced a novel experimental technique to extract a neuromagnetic response relating to two-agent BM perception. We then investigated how this response was modulated by the interaction of two agents. In the present experiment, we presented two kinds of visual stimuli (interacting and non-interacting BM) with two orientations (upright and inverted).</p> <p>Results</p> <p>We found a neuromagnetic response in the bilateral occipitotemporal region, on average 300 – 400 ms after the onset of a two-agent BM stimulus. This result showed that interhemispheric differences were apparent for the peak amplitudes. For the left hemisphere, the orientation effect was manifest when the two agents were made to interact, and the interaction effect was manifest when the stimulus was inverted. In the right hemisphere, the main effects of both orientation and interaction were significant, suggesting that the peak amplitude was attenuated when the visual stimulus was inverted or made to interact.</p> <p>Conclusion</p> <p>These results demonstrate that the 'interaction' information of two agents can affect the neural activities in the bilateral occipitotemporal region, on average 300 – 400 ms after the onset of a two-agent BM stimulus, however, the modulation was different between hemispheres: the left hemisphere is more concerned with dynamics, whereas the right hemisphere is more concerned with form information.</p

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

PurposeErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.MethodsMI was induced in pigs by a 90&nbsp;min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6&nbsp;weeks post-MI. Histopathology was performed 6&nbsp;weeks post-MI.ResultsAt week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p &lt; 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.ConclusionOur findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF

Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

Mechanisms underlying age-dependent changes of dendritic spines on striatal medium spiny neurons are poorly understood. Spinophilin is an F-actin- and protein phosphatase 1 (PP1)-binding protein that targets PP1 to multiple downstream effectors to modulate dendritic spine morphology and function. We found that calcium/calmodulin-dependent protein kinase II (CaMKII) directly and indirectly associates with N- and C-terminal domains of spinophilin, but F-actin can displace CaMKII from the N-terminal domain. Spinophilin co-localizes PP1 with CaMKII on the F-actin cytoskeleton in heterologous cells, and spinophilin co-localizes with synaptic CaMKII in neuronal cultures. Thr286 autophosphorylation enhances the binding of CaMKII to spinophilin in vitro and in vivo. Although there is no change in total levels of Thr286 autophosphorylation, maturation from postnatal day 21 into adulthood robustly enhances the levels of CaMKII that co-immunoprecipitate with spinophilin from mouse striatal extracts. Moreover, N- and C-terminal domain fragments of spinophilin bind more CaMKII from adult vs. postnatal day 21 striatal lysates. Total levels of other proteins that interact with C-terminal domains of spinophilin decrease during maturation, perhaps reducing competition for CaMKII binding to the C-terminal domain. In contrast, total levels of α-internexin and binding of α-internexin to the spinophilin N-terminal domain increases with maturation, perhaps bridging an indirect interaction with CaMKII. Moreover, there is an increase in the levels of myosin Va, α-internexin, spinophilin, and PP1 in striatal CaMKII immune complexes isolated from adult and aged mice compared to those from postnatal day 21. These changes in spinophilin/CaMKII interactomes may contribute to changes in striatal dendritic spine density, morphology, and function during normal postnatal maturation and aging

Methods used to evaluate the en dehors or turnout of dancers and classical ballet dancers: a literature review

A técnica do ballet clássico exige a realização máxima do en dehors ou turnout, caracterizado pela rotação externa de membros inferiores. Considerando a sua importância, diversos protocolos para a sua avaliação e mensuração têm sido propostos. O objetivo desta revisão foi investigar sistematicamente quais os métodos utilizados para avaliar o turnout de bailarinos clássicos e/ou praticantes de ballet clássico existentes atualmente. A busca foi feita nas bases de dados Scopus, Science Direct e PubMed, no mês de fevereiro de 2016, e os artigos encontrados deveriam: estar redigidos na língua inglesa, avaliar bailarinos clássicos ou dançarinos que praticassem ballet clássico e mensurar o en dehors ou turnout. Foram encontrados 593 artigos, dos quais 25 foram pré-selecionados para esta revisão, apresentando quinze diferentes métodos e instrumentos de mensuração do turnout: cinemetria; inclinômetro; turnout protactor ou transferidor para medir o turnout; goniômetro; Dupuis Tropometer; transferidor original; fotos dos sujeitos; discos rotacionais; teste de flexibilidade de Nicholas; flexímetro; desenho clínico dos pés; sujeito sobre um pedaço de papel ou solo ou quadro branco; ressonância magnética; filmagem do sujeito executando sequência de passos; Dasco Pro Angle Finder. Esta revisão apresenta forte evidência para afirmar que não há, até o presente momento, um método ou instrumento padrão-ouro para mensuração do turnout de bailarinos, de modo que esta costuma ser adaptada e escolhida de acordo com o objetivo de cada estudo.La técnica del ballet clásico exige la realización máxima del en dehors o turnout, caracterizado por la rotación externa de miembros inferiores. Considerando su importancia, varios protocolos para su evaluación y medición han sido propuestos. El objetivo de esta revisión ha sido investigar sistemáticamente los métodos utilizados para evaluar el turnout de bailarines clásicos y/o practicantes de ballet clásico existentes actualmente. Se hizo la búsqueda en las bases de datos Scopus, Science Direct y PubMed, en el mes de febrero de 2016, y los artículos encontrados deberían: estar redactados en la lengua inglesa, evaluar bailarines clásicos o bailarines que practicaran ballet clásico y medir el en dehors o turnout. Se encontraron 593 artículos, de los cuales se preseleccionaron 25 para esta revisión, presentándose 15 diferentes métodos e instrumentos de medición del turnout: cinemetría; inclinómetro; turnout protactor o transferidor para medir el turnout; goniómetro; Dupuis Tropometer; transferidor original; fotos de los sujetos; discos rotacionales; prueba de flexibilidad de Nicholas; flexímetro; diseño clínico de los pies; sujeto sobre un pedazo de papel o suelo o cuadro blanco; resonancia magnética; filmación del sujeto ejecutando secuencia de pasos; Daco Pro Angle Finder. Esta revisión presenta una fuerte evidencia para afirmar que no hay, hasta el momento, un método o instrumento estándar-oro para la medición del turnout de bailarines, de modo que ésta suele ser adaptada y elegida de acuerdo con el objetivo de cada estudio.The classical ballet technique requires the maximum en dehors or turnout, which is the lower limbs external rotation. Considering its importance, several evaluation and measurement protocols have been proposed. This review aims to investigate systematically which methods were used to assess the classical dancers’ or classical ballet practitioners’ turnout. A systematic search was made in the Scopus, Science Direct, and PubMed databases in February 2016 for studies written in English that evaluated classical dancers or ballerinas, and the en dehors or turnout was measured. We found 593 articles, of which 25 were pre-selected for this review, featuring fifteen different methods and instruments for measuring turnout: kinemetry; inclinometer; Turnout Protractor, or protractor to measure the turnout; goniometer; dupuis tropometer; original protractor; subjects photos; rotational discs; Nicholas flexibility test; fleximeter; clinical drawing of the feet; subject standing on a piece of paper, or soil, or whiteboard; magnetic resonance; filming the subject during a sequence of dance steps; Dasco pro angle finder. This review rovides convincing evidence that there is not a method or gold-standard instrument for measuring dancers’ turnout, therefore such measurement is usually adapted and chosen according to each study objectives

piggyBac is an effective tool for functional analysis of the Plasmodium falciparum genome

<p>Abstract</p> <p>Background</p> <p>Much of the <it>Plasmodium falciparum </it>genome encodes hypothetical proteins with limited homology to other organisms. A lack of robust tools for genetic manipulation of the parasite limits functional analysis of these hypothetical proteins and other aspects of the <it>Plasmodium </it>genome. Transposon mutagenesis has been used widely to identify gene functions in many organisms and would be extremely valuable for functional analysis of the <it>Plasmodium </it>genome.</p> <p>Results</p> <p>In this study, we investigated the lepidopteran transposon, <it>piggyBac</it>, as a molecular genetic tool for functional characterization of the <it>Plasmodium falciparum </it>genome. Through multiple transfections, we generated 177 unique <it>P. falciparum </it>mutant clones with mostly single <it>piggyBac </it>insertions in their genomes. Analysis of <it>piggyBac </it>insertion sites revealed random insertions into the <it>P. falciparum </it>genome, in regards to gene expression in parasite life cycle stages and functional categories. We further explored the possibility of forward genetic studies in <it>P. falciparum </it>with a phenotypic screen for attenuated growth, which identified several parasite genes and pathways critical for intra-erythrocytic development.</p> <p>Conclusion</p> <p>Our results clearly demonstrate that <it>piggyBac </it>is a novel, indispensable tool for forward functional genomics in <it>P. falciparum </it>that will help better understand parasite biology and accelerate drug and vaccine development.</p

Relationship between Regulatory T Cells and Immune Activation in Human Immunodeficiency Virus-Infected Patients Interrupting Antiretroviral Therapy

Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r = −0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p = 0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p = 0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI

Phylogenomic analysis of the Chlamydomonas genome unmasks proteins potentially involved in photosynthetic function and regulation

Chlamydomonas reinhardtii, a unicellular green alga, has been exploited as a reference organism for identifying proteins and activities associated with the photosynthetic apparatus and the functioning of chloroplasts. Recently, the full genome sequence of Chlamydomonas was generated and a set of gene models, representing all genes on the genome, was developed. Using these gene models, and gene models developed for the genomes of other organisms, a phylogenomic, comparative analysis was performed to identify proteins encoded on the Chlamydomonas genome which were likely involved in chloroplast functions (or specifically associated with the green algal lineage); this set of proteins has been designated the GreenCut. Further analyses of those GreenCut proteins with uncharacterized functions and the generation of mutant strains aberrant for these proteins are beginning to unmask new layers of functionality/regulation that are integrated into the workings of the photosynthetic apparatus