Disappearing cosmological constant in f(R) gravity

For higher-derivative f(R) gravity where R is the Ricci scalar, a class of models is proposed which produce viable cosmology different from the LambdaCDM one at recent times and satisfy cosmological, Solar system and laboratory tests. These models have both flat and de Sitter space-times as particular solutions in the absence of matter. Thus, a cosmological constant is zero in flat space-time, but appears effectively in a curved one for sufficiently large R. A 'smoking gun' for these models would be small discrepancy in values of the slope of the primordial perturbation power spectrum determined from galaxy surveys and CMB fluctuations. On the other hand, a new problem for dark energy models based on f(R) gravity is pointed which is connected with possible overproduction of new massive scalar particles (scalarons) arising in this theory in the very early Universe.Comment: 8 pages, footnote clarified, grammatical typo corrected, references added, final version to be published in JETP

Cosmology of a Scalar Field Coupled to Matter and an Isotropy-Violating Maxwell Field

Motivated by the couplings of the dilaton in four-dimensional effective actions, we investigate the cosmological consequences of a scalar field coupled both to matter and a Maxwell-type vector field. The vector field has a background isotropy-violating component. New anisotropic scaling solutions which can be responsible for the matter and dark energy dominated epochs are identified and explored. For a large parameter region the universe expands almost isotropically. Using that the CMB quadrupole is extremely sensitive to shear, we constrain the ratio of the matter coupling to the vector coupling to be less than 10^(-5). Moreover, we identify a large parameter region, corresponding to a strong vector coupling regime, yielding exciting and viable cosmologies close to the LCDM limit.Comment: Refs. added, some clarifications. Published in JHEP10(2012)06

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We reviewed a total of 102 tissue samples from patients in our tumour registry, with either primary or metastatic lung or colorectal adenocarcinoma. Tissue sections were stained for cytokeratin 7 and 20 and read as positive or negative for staining. Clinical and radiologic information was reviewed from computerised charts. The cytokeratin 7+/cytokeratin 20− pattern characterised 96% (29 out of 30) of primary and 95% (21 out of 22) of metastatic lung adenocarcinomas. All the primary (26), and 88% (21 out of 24) of metastatic colorectal adenocarcinomas stained cytokeratin 7−/cytokeratin 20+. Samples from a variety of metastatic sites were evaluated for cytokeratin 7 and 20 staining. Out of the 102 samples, in 95% (97 out of 102) of the cases, the cytokeratin 7 and cytokeratin 20 staining pattern characterised and differentiated between lung and colorectal adenocarcinoma. Primary and metastatic lung adenocarcinomas show a cytokeratin 7+/cytokeratin 20− staining pattern, while colorectal adenocarcinomas stain cytokeratin 7−/cytokeratin 20+. Cytokeratin staining is helpful in the diagnostic differentiation of metastatic lesions from these two common primaries, and assists in determining the site of origin of metastatic lesions

Inflation with stable anisotropic hair: is it cosmologically viable?

Recently an inflationary model with a vector field coupled to the inflaton was proposed and the phenomenology studied for the Bianchi type I spacetime. It was found that the model demonstrates a counter-example to the cosmic no-hair theorem since there exists a stable anisotropically inflationary fix-point. One of the great triumphs of inflation, however, is that it explains the observed flatness and isotropy of the universe today without requiring special initial conditions. Any acceptable model for inflation should thus explain these observations in a satisfactory way. To check whether the model meets this requirement, we introduce curvature to the background geometry and consider axisymmetric spacetimes of Bianchi type II,III and the Kantowski-Sachs metric. We show that the anisotropic Bianchi type I fix-point is an attractor for the entire family of such spacetimes. The model is predictive in the sense that the universe gets close to this fix-point after a few e-folds for a wide range of initial conditions. If inflation lasts for N e-folds, the curvature at the end of inflation is typically of order exp(-2N). The anisotropy in the expansion rate at the end of inflation, on the other hand, while being small on the one-percent level, is highly significant. We show that after the end of inflation there will be a period of isotropization lasting for about 2N/3 e-folds. After that the shear scales as the curvature and becomes dominant around N e-folds after the end of inflation. For plausible bounds on the reheat temperature the minimum number of e-folds during inflation, required for consistency with the isotropy of the supernova Ia data, lays in the interval (21,48). Thus the results obtained for our restricted class of spacetimes indicates that inflation with anisotropic hair is cosmologically viable.Comment: 25 pages, 3 figures; v2: Minor changes, refs added; v3: JHEP version (proof-reading corrections

Promoter regions of Plasmodium vivax are poorly or not recognized by Plasmodium falciparum

BACKGROUND: Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. METHODS: Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. RESULTS: Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT) in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN) in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. CONCLUSION: Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements

Deficiency of a Niemann-Pick, Type C1-related Protein in Toxoplasma Is Associated with Multiple Lipidoses and Increased Pathogenicity

Several proteins that play key roles in cholesterol synthesis, regulation, trafficking and signaling are united by sharing the phylogenetically conserved ‘sterol-sensing domain’ (SSD). The intracellular parasite Toxoplasma possesses at least one gene coding for a protein containing the canonical SSD. We investigated the role of this protein to provide information on lipid regulatory mechanisms in the parasite. The protein sequence predicts an uncharacterized Niemann-Pick, type C1-related protein (NPC1) with significant identity to human NPC1, and it contains many residues implicated in human NPC disease. We named this NPC1-related protein, TgNCR1. Mammalian NPC1 localizes to endo-lysosomes and promotes the movement of sterols and sphingolipids across the membranes of these organelles. Miscoding patient mutations in NPC1 cause overloading of these lipids in endo-lysosomes. TgNCR1, however, lacks endosomal targeting signals, and localizes to flattened vesicles beneath the plasma membrane of Toxoplasma. When expressed in mammalian NPC1 mutant cells and properly addressed to endo-lysosomes, TgNCR1 restores cholesterol and GM1 clearance from these organelles. To clarify the role of TgNCR1 in the parasite, we genetically disrupted NCR1; mutant parasites were viable. Quantitative lipidomic analyses on the ΔNCR1 strain reveal normal cholesterol levels but an overaccumulation of several species of cholesteryl esters, sphingomyelins and ceramides. ΔNCR1 parasites are also characterized by abundant storage lipid bodies and long membranous tubules derived from their parasitophorous vacuoles. Interestingly, these mutants can generate multiple daughters per single mother cell at high frequencies, allowing fast replication in vitro, and they are slightly more virulent in mice than the parental strain. These data suggest that the ΔNCR1 strain has lost the ability to control the intracellular levels of several lipids, which subsequently results in the stimulation of lipid storage, membrane biosynthesis and parasite division. Based on these observations, we ascribe a role for TgNCR1 in lipid homeostasis in Toxoplasma

Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites

Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications