The effective Lagrangian of dark energy from observations

Using observational data on the expansion rate of the universe (H(z)) we constrain the effective Lagrangian of the current accelerated expansion. Our results show that the effective potential is consistent with being flat i.e., a cosmological constant; it is also consistent with the field moving along an almost flat potential like a pseudo-Goldstone boson. We show that the potential of dark energy does not deviate from a constant at more than 6% over the redshift range 0 < z < 1. The data can be described by just a constant term in the Lagrangian and do not require any extra parameters; therefore there is no evidence for augmenting the number of parameters of the LCDM paradigm. We also find that the data justify the effective theory approach to describe accelerated expansion and that the allowed parameters range satisfy the expected hierarchy. Future data, both from cosmic chronometers and baryonic acoustic oscillations, that can measure H(z) at the % level, could greatly improve constraints on the flatness of the potential or shed some light on possible mechanisms driving the accelerated expansion. Besides the above result, it is shown that the effective Lagrangian of accelerated expansion can be constrained from cosmological observations in a model-independent way and that direct measurements of the expansion rate H(z) are most useful to do so.Comment: 9 pages, 3 figures, JCAP submitted. This paper presents a reconstruction of the dark energy potential. It is a companion to Moresco et al. 2012a, which presents new H(z) results and Moresco et al. 2012b, which provides cosmological parameter constraint

Two inhibitors of yeast plasma membrane ATPase 1 (ScPma1p): toward the development of novel antifungal therapies

Given that many antifungal medications are susceptible to evolved resistance, there is a need for novel drugs with unique mechanisms of action. Inhibiting the essential proton pump Pma1p, a P-type ATPase, is a potentially effective therapeutic approach that is orthogonal to existing treatments. We identify NSC11668 and hitachimycin as structurally distinct antifungals that inhibit yeast ScPma1p. These compounds provide new opportunities for drug discovery aimed at this important target

Differing marine animal biomass shifts under 21st century climate change between Canada's three ocean

Identificadors digitals: Digital object identifier for the 'European Research Council' (http://dx.doi.org/10.13039/501100000781) and Digital object identifier for 'Horizon 2020' (http://dx.doi.org/10.13039/501100007601)Unidad de excelencia María de Maeztu CEX2019-000940-MUnder climate change, species composition and abundances in high-latitude waters are expected to substantially reconfigure with consequences for trophic relationships and ecosystem services. Outcomes are challenging to project at national scales, despite their importance for management decisions. Using an ensemble of six global marine ecosystem models we analyzed marine ecosystem responses to climate change from 1971 to 2099 in Canada's Exclusive Economic Zone (EEZ) under four standardized emissions scenarios. By 2099, under business-as-usual emissions (RCP8.5) projected marine animal biomass declined by an average of −7.7% (±29.5%) within the Canadian EEZ, dominated by declines in the Pacific (−24% ± 24.5%) and Atlantic (−25.5% ± 9.5%) areas; these were partially compensated by increases in the Canadian Arctic (+26.2% ± 38.4%). Lower emissions scenarios projected successively smaller biomass changes, highlighting the benefits of stronger mitigation targets. Individual model projections were most consistent in the Atlantic and Pacific, but highly variable in the Arctic due to model uncertainties in polar regions. Different trajectories of future marine biomass changes will require regional-specific responses in conservation and management strategies, such as adaptive planning of marine protected areas and species-specific management plans, to enhance resilience and rebuilding of Canada's marine ecosystems and commercial fish stocks

On the Importance of Electroweak Corrections for Majorana Dark Matter Indirect Detection

Recent analyses have shown that the inclusion of electroweak corrections can alter significantly the energy spectra of Standard Model particles originated from dark matter annihilations. We investigate the important situation where the radiation of electroweak gauge bosons has a substantial influence: a Majorana dark matter particle annihilating into two light fermions. This process is in p-wave and hence suppressed by the small value of the relative velocity of the annihilating particles. The inclusion of electroweak radiation eludes this suppression and opens up a potentially sizeable s-wave contribution to the annihilation cross section. We study this effect in detail and explore its impact on the fluxes of stable particles resulting from the dark matter annihilations, which are relevant for dark matter indirect searches. We also discuss the effective field theory approach, pointing out that the opening of the s-wave is missed at the level of dimension-six operators and only encoded by higher orders.Comment: 25 pages, 6 figures. Minor corrections to match version published in JCA

Quarkonium Photoproduction at Next-to-leading Order

We present the calculation of O(as^2 aem) corrections to heavy-quarkonium total photoproduction cross-sections. Results are given for the colour-octet component of S and P waves. The calculation is performed using covariant projectors in dimensional regularization. A phenomenological study of the results, including a discussion of the high-energy behaviour of the cross sections, is presented. For gamma-p energies up to few hundred GeV the NLO corrections significantly reduce the scale dependence of the production rates relative to the Born-level results. Large small-x corrections arise at higher energies, making the predictions strongly dependent on the shape of the gluon density and on the choice of factorization scale.Comment: 32 pages, Latex, epsfig, 13 figure

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase

Summary2-Oxoglutarate-dependent dioxygenases, including the EglN prolyl hydroxylases that regulate HIF, can be inhibited with drug-like molecules. EglN2 is estrogen inducible in breast carcinoma cells and the lone Drosophila EglN interacts genetically with Cyclin D1. Although EglN2 is a nonessential gene, we found that EglN2 inactivation decreases Cyclin D1 levels and suppresses mammary gland proliferation in vivo. Regulation of Cyclin D1 is a specific attribute of EglN2 among the EglN proteins and is HIF independent. Loss of EglN2 catalytic activity inhibits estrogen-dependent breast cancer tumorigenesis and can be rescued by exogenous Cyclin D1. EglN2 depletion also impairs the fitness of lung, brain, and hematopoietic cancer lines. These findings support the exploration of EglN2 inhibitors as therapeutics for estrogen-dependent breast cancer and other malignancies

Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration