In vitro and in vivo activity of 3-alkoxy-1,2-dioxolanes against Schistosoma mansoni

Objectives Compounds characterized by a peroxidic skeleton are an interesting starting point for antischistosomal drug discovery. Previously a series of 3-alkoxy-1,2-dioxolanes, which are chemically stable cyclic peroxides, demonstrated significant in vitro activity against Plasmodium falciparum. We aimed to evaluate the potential of these compounds against Schistosoma mansoni and elucidate the roles of iron and peroxidic groups in activity. Methods Drugs were tested against juvenile and adult stages of S. mansoni in vitro and in vivo. Selected structures were assessed in vitro against schistosomes in the presence of additional iron sources. In addition, drugs were tested in vitro and in vivo against Echinostoma caproni, a non-blood-feeding intestinal fluke. Finally, the activity of non-peroxidic analogues was evaluated. Results Three dioxolanes displayed IC50s ≤20.1 μM against adult schistosomes and values as low as 4.2 μM against newly transformed schistosomula. Nonetheless, only moderate, non-significant worm burden reductions were observed after treatment of mice harbouring adult infections. Drugs lacked activity against juvenile schistosomes in vivo. Two selected dioxolanes showed in vitro activity against E. caproni down to concentrations of 5 mg/L, but none of the compounds revealed in vivo activity. All tested non-peroxidic analogues lacked activity in vitro against both parasites. Conclusions Selected dioxolanes presented interesting in vitro activity, but low in vivo activities have to be overcome to identify a lead candidate. Although the inactivity of non-peroxidic analogues underlines the necessity of a peroxide functional group, incubation of adult schistosomes with additional iron sources did not alter activity, supporting an iron-independent mode of activatio

Hypothesis Article Signatures of a Shadow Biosphere

Abstract Astrobiologists are aware that extraterrestrial life might differ from known life, and considerable thought has been given to possible signatures associated with weird forms of life on other planets. So far, however, very little attention has been paid to the possibility that our own planet might also host communities of weird life. If life arises readily in Earth-like conditions, as many astrobiologists contend, then it may well have formed many times on Earth itself, which raises the question whether one or more shadow biospheres have existed in the past or still exist today. In this paper, we discuss possible signatures of weird life and outline some simple strategies for seeking evidence of a shadow biosphere

Economic Impact of Cystic Echinococcosis in Peru

Cystic echinococcosis (CE), caused by infection with the larval stage of the cestode Echinococcus granulosus, constitutes an important public health problem in Peru. Despite its high prevalence in endemic communities no studies have attempted to estimate the economic impact of CE in Peruvian society. We used official and published sources of epidemiological and economic information to estimate direct and indirect costs associated with livestock production losses and human disease. We also used disability adjusted life years (DALYs) which is an overall measure of disease burden, expressed as number of years lost due to ill-health, disability or early death due to CE. We found that the total estimated cost of human CE in Peru was U.S.$2,420,348 per year. Total estimated livestock-associated costs due to CE ranged from U.S.$196,681 to U.S.$3,846,754. An estimated 1,139 DALYs were also lost due to surgical cases of CE which is comparable to DALY losses from Amebiasis or Malaria in Peru. This conservative assessment found significant economic losses caused by this CE in Peruvian society. The findings of this study are important as these data can serve to prioritize those areas that may need to be targeted in a control program

NEAs: Phase Angle Dependence of Asteroid Class and Diameter from Observational Studies

We will discuss the results of a planned observation campaign of Near Earth Asteroids (NEAs), 1999 CU3, 2002 GM2, 2002 FG7, and 3691 Bede with instruments on the United Kingdom Infrared Telescope (UKIRT) from 15-Mar-2015 to 28-April 2015 UT. We will study the phase-angle dependence of the reflectance and thermal emission spectra. Recent publications reveal that the assignment of the asteroid class from visible and near-IR spectroscopy can change with phase angle for NEAs with silicate-bearing minerals on their surfaces (S-class asteroids) (Thomas et al. 2014, Icarus 228, 217; Sanchez et al. 2012 Icarus 220, 36). Only three of the larger NEAs have been measured at a dozen phase angles and the trends are not all the same, so there is not yet enough information to create a phase-angle correction. Also, the phase angle effect is not characterized well for the thermal emission including determination of the albedo and the thermal emission. The few NEAs were selected for our study amongst many possible targets based on being able to observe them through a wide range of phase angles, ranging from less than about 10 degrees to greater than 45 degrees over the constrained date range. The orbits of NEAs often generate short observing windows at phase angles higher than 45 deg (i.e., whizzing by Earth and/or close to dawn or dusk). Ultimately, lowering the uncertainty of the translation of asteroid class to meteorite analog and of albedo and size determinations are amongst our science goals. On a few specific nights, we plan to observe the 0.75-2.5 micron spectra with IRTF+SpeX for comparison with UKIRT data including 5-20 micron with UKIRT+UIST/Michelle to determine as best as possible the albedos. To ensure correct phasing of spectroscopic data, we augment with TRAPPIST-telescope light curves and R-band guider image data. Our observations will contribute to understanding single epoch mid-IR and near-IR measurements to obtain albedo, size and IR beaming parameters (the outcomes of thermal models) and asteroid spectral class

What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach

Ambiguity surrounding the effect of external engagement on academic research has raised questions about what motivates researchers to collaborate with third parties. We argue that what matters for society is research that can be absorbed by users. We define openness as a willingness by researchers to make research more usable by external partners by responding to external influences in their own research practices. We ask what kinds of characteristics define those researchers who are more open to creating usable knowledge. Our empirical study analyses a sample of 1583 researchers working at the Spanish Council for Scientific Research (CSIC). Results demonstrate that it is personal factors (academic identity and past experience) that determine which researchers have open behaviours. The paper concludes that policies to encourage external engagement should focus on experiences which legitimate and validate knowledge produced through user encounters, both at the academic formation career stage as well as through providing ongoing opportunities to engage with third parties.The data used for this study comes from the IMPACTO project funded by the Spanish Council for Scientific Research - CSIC (Ref. 200410E639). The work also benefited from a mobility grant awarded by Eu-Spri Forum to Julia Olmos Penuela & Paul Benneworth for her visiting research to the Center of Higher Education Policy Studies. Finally, Julia Olmos Penuela also benefited from a post-doctoral grant funded by the Generalitat Valenciana (APOSTD-2014-A-006).Olmos-Peñuela, J.; Benneworth, P.; Castro-Martínez, E. (2015). What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach. 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Development of Atmospheric Tracer Methods To Measure Methane Emissions from Natural Gas Facilities and Urban Areas

A new, integrated methodology to locate and measure methane emissions from natural gas systems has been developed. Atmospheric methane sources are identified by elevated ambient CH4 concentrations measured with a mobile laser-based methane analyzer. The total methane emission rate from a source is obtained by simulating the source with a sulfur hexafluoride (SF6) tracer gas release and by measuring methane and tracer concentrations along downwind sampling paths using mobile, real-time analyzers. Combustion sources of methane are distinguished from noncombustion sources by concurrent ambient carbon dioxide measurements. Three variations on the tracer ratio method are described for application to (1) small underground vaults, (2) aboveground natural gas facilities, and (3) diffuse methane emissions from an entire town. Results from controlled releases and from replicate tests demonstrate that the tracer ratio approach can yield total emission rates to within approximately ±15%. The estimated accuracy of emission estimates for urban areas with a variety of diffuse emissions is ±50%. © 1995, American Chemical Society. All rights reserved

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead