Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10–300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion

A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

Multivariate and network meta-analysis of multiple outcomes and multiple treatments: rationale, concepts, and examples

Organisations such as the National Institute for Health and Care Excellence require the synthesis of evidence from existing studies to inform their decisions—for example, about the best available treatments with respect to multiple efficacy and safety outcomes. However, relevant studies may not provide direct evidence about all the treatments or outcomes of interest. Multivariate and network meta-analysis methods provide a framework to address this, using correlated or indirect evidence from such studies alongside any direct evidence. In this article, the authors describe the key concepts and assumptions of these methods, outline how correlated and indirect evidence arises, and illustrate the contribution of such evidence in real clinical examples involving multiple outcomes and multiple treatment

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

GJ 3236: a new bright, very low-mass eclipsing binary system discovered by the MEarth observatory

We report the detection of eclipses in GJ 3236, a bright (I = 11.6) very low mass binary system with an orbital period of 0.77 days. Analysis of light- and radial velocity curves of the system yielded component masses of 0.38 +/- 0.02 and 0.28 +/- 0.02 Msol. The central values for the stellar radii are larger than the theoretical models predict for these masses, in agreement with the results for existing eclipsing binaries, although the present 5% observational uncertainties limit the significance of the larger radii to approximately 1 sigma. Degeneracies in the light curve models resulting from the unknown configuration of surface spots on the components of GJ 3236 currently dominate the uncertainties in the radii, and could be reduced by obtaining precise, multi-band photometry covering the full orbital period. The system appears to be tidally synchronized and shows signs of high activity levels as expected for such a short orbital period, evidenced by strong Halpha emission lines in the spectra of both components. These observations probe an important region of mass-radius parameter space around the predicted transition to fully-convective stellar interiors, where there are a limited number of precise measurements available in the literature.Comment: 14 pages, 5 figures, 10 tables, emulateapj format. Accepted for publication in Ap

Digital Accessibility in the Hospitality and Tourism Industry: Legal and Ethical Considerations

Federal law requires accessibility for public sector websites. What about the web pages and apps of hotels, restaurants, and tourism providers? The Americans with Disabilities Act may cover private sector websites if they are considered a place of public accommodation, but the law is unclear. This Article will provide an overview of the legal responsibilities of operators to provide accessibility to persons with disabilities, discuss the World Wide Web Consortium’s guidelines for web accessibility, and argue that the hospitality and tourism industry has a unique ethical obligation to fill in the gap where the legal system has failed this population

Next Generation Very Large Array Memo No. 9 Science Working Group 4: Time Domain, Fundamental Physics, and Cosmology

We report here on key science topics for the Next Generation Very Large Array in the areas of time domain, fundamental physics, and cosmology. Key science cases considered are pulsars in orbit around the Galactic Center massive black hole, Sagittarius A*, electromagnetic counterparts to gravitational waves, and astrometric cosmology. These areas all have the potential for ground-breaking and transformative discovery. Numerous other topics were discussed during the preparation of this report and some of those discussions are summarized here, as well. There is no doubt that further investigation of the science case will reveal rich and compelling opportunities