Plasmodium vivax in Hematopoietic Niches: Hidden and Dangerous

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordEstimation of Plasmodium vivax biomass based on circulating biomarkers indicates the existence of a predominant biomass outside of the circulation that is not captured by peripheral parasitemia, in particular in patients with complicated outcomes. A series of recent studies have suggested that the hematopoietic niche of the bone marrow (BM) is a major reservoir for parasite replication and the development of transmission stages. However, significant knowledge gaps remain in our understanding of host–parasite interactions, pathophysiology, and the implications for treatment and diagnosis of such a reservoir. Here, we discuss the current status of this emerging research field in the context of P. vivax.National Institute of Allergy and Infectious Diseases of the National Institutes of HealthMedical Research Council (MRC)Royal SocietySao Paulo Research Foundatio

Predictive use of the Maximum Entropy Production principle for Past and Present Climates

In this paper, we show how the MEP hypothesis may be used to build simple climate models without representing explicitly the energy transport by the atmosphere. The purpose is twofold. First, we assess the performance of the MEP hypothesis by comparing a simple model with minimal input data to a complex, state-of-the-art General Circulation Model. Next, we show how to improve the realism of MEP climate models by including climate feedbacks, focusing on the case of the water-vapour feedback. We also discuss the dependence of the entropy production rate and predicted surface temperature on the resolution of the model

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Performance benchmarks for a next generation numerical dynamo model

Numerical simulations of the geodynamo have successfully represented many observable characteristics of the geomagnetic field, yielding insight into the fundamental processes that generate magnetic fields in the Earth's core. Because of limited spatial resolution, however, the diffusivities in numerical dynamo models are much larger than those in the Earth's core, and consequently, questions remain about how realistic these models are. The typical strategy used to address this issue has been to continue to increase the resolution of these quasi-laminar models with increasing computational resources, thus pushing them toward more realistic parameter regimes. We assess which methods are most promising for the next generation of supercomputers, which will offer access to O(106) processor cores for large problems. Here we report performance and accuracy benchmarks from 15 dynamo codes that employ a range of numerical and parallelization methods. Computational performance is assessed on the basis of weak and strong scaling behavior up to 16,384 processor cores. Extrapolations of our weak-scaling results indicate that dynamo codes that employ two-dimensional or three-dimensional domain decompositions can perform efficiently on up to ∼106 processor cores, paving the way for more realistic simulations in the next model generation

Biochemical Trade-Offs: Evidence for Ecologically Linked Secondary Metabolism of the Sponge Oscarella balibaloi

Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay) and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction) and abiotic (temperature) factors

Structure-based statistical analysis of transmembrane helices

Recent advances in determination of the high-resolution structure of membrane proteins now enable analysis of the main features of amino acids in transmembrane (TM) segments in comparison with amino acids in water-soluble helices. In this work, we conducted a large-scale analysis of the prevalent locations of amino acids by using a data set of 170 structures of integral membrane proteins obtained from the MPtopo database and 930 structures of water-soluble helical proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu, Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of helix. The distribution of amino acids along TM helices was also examined. As expected, hydrophobic and slightly polar amino acids are commonly found in the hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the interface regions. Charged amino acids are also statistically prevalent outside the hydrophobic core of the membrane, and whereas acidic amino acids are frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic amino acids cluster at the cytoplasmic interface. These results strongly support the experimentally demonstrated biased distribution of positively charged amino acids (that is, the so-called the positive-inside rule) with structural data

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons’ activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders

Stroke prevalence among the Spanish elderly: an analysis based on screening surveys

BACKGROUND: This study sought to describe stroke prevalence in Spanish elderly populations and compare it against that of other European countries. METHODS: We identified screening surveys -both published and unpublished- in Spanish populations, which fulfilled specific quality requirements and targeted prevalence of stroke in populations aged 70 years and over. Surveys covering seven geographically different populations with prevalence years in the period 1991–2002 were selected, and the respective authors were then asked to provide descriptions of the methodology and raw age-specific data by completing a questionnaire. In addition, five reported screening surveys in European populations furnished useful data for comparison purposes. Prevalence data were combined, using direct adjustment and logistic regression. RESULTS: The overall study population, resident in central and north-eastern Spain, totalled 10,647 persons and yielded 715 cases. Age-adjusted prevalences, using the European standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes. Prevalence was significantly lower in women, OR 0.79 95% CI 0.68–0.93, increased with age, particularly among women, and displayed a threefold spatial variation with statistically significant differences. Prevalences were highest, 8.7%, in suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish populations, statistically significant differences were seen in eight Italian populations, OR 1.39 95%CI (1.18–1.64), and in Kungsholmen, Sweden, OR 0.40 95%CI (0.27–0.58). CONCLUSION: Prevalence in central and north-eastern Spain is higher in males and in suburban areas, and displays a threefold geographic variation, with women constituting the majority of elderly stroke sufferers. Compared to reported European data, stroke prevalence in Spain can be said to be medium and presents similar age- and sex-specific traits