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Mechanisms and consequences of hepatic regulation of mTORC1 by metformin
Evolution by Any Other Name: Antibiotic Resistance and Avoidance of the E-Word
The word "evolution" is rarely used in papers from medical journals describing antimicrobial resistance, which may directly impact public perception of the importance of evolutionary biology in our everyday lives
Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility
Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain MTIP, and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC) and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion
Global hepatitis C elimination: an investment framework
WHO has set global targets for the elimination of hepatitis B and hepatitis C as a public health threat by 2030. However, investment in elimination programmes remains low. To help drive political commitment and catalyse domestic and international financing, we have developed a global investment framework for the elimination of hepatitis B and hepatitis C. The global investment framework presented in this Health Policy paper outlines national and international activities that will enable reductions in hepatitis C incidence and mortality, and identifies potential sources of funding and tools to help countries build the economic case for investing in national elimination activities. The goal of this framework is to provide a way for countries, particularly those with minimal resources, to gain the substantial economic benefit and cost savings that come from investing in hepatitis C elimination
Tentative Evidence for Water Vapor in the Atmosphere of the Neptune-Size Exoplanet HD 106315 c
We present a transmission spectrum for the Neptune-size exoplanet HD 106315 c from optical to infrared wavelengths based on transit observations from the Hubble Space Telescope/Wide Field Camera 3, K2, and Spitzer. The spectrum shows tentative evidence for a water absorption feature in the 1.1−1.7μm wavelength range with a small amplitude of 30 ppm (corresponding to just 0.8±0.04 atmospheric scale heights). Based on an atmospheric retrieval analysis, the presence of water vapor is tentatively favored with a Bayes factor of 1.7 - 2.6 (depending on prior assumptions). The spectrum is most consistent with either enhanced metallicity, high altitude condensates, or both. Cloud-free solar composition atmospheres are ruled out at >5σ confidence. We compare the spectrum to grids of cloudy and hazy forward models and find that the spectrum is fit well by models with moderate cloud lofting or haze formation efficiency, over a wide range of metallicities (1−100× solar). We combine the constraints on the envelope composition with an interior structure model and estimate that the core mass fraction is ≳0.3. With a bulk composition reminiscent of that of Neptune and an orbital distance of 0.15 AU, HD 106315 c hints that planets may form out of broadly similar material and arrive at vastly different orbits later in their evolution
Tentative Evidence for Water Vapor in the Atmosphere of the Neptune-Size Exoplanet HD 106315 c
We present a transmission spectrum for the Neptune-size exoplanet HD 106315 c
from optical to infrared wavelengths based on transit observations from the
Hubble Space Telescope/Wide Field Camera 3, K2, and Spitzer. The spectrum shows
tentative evidence for a water absorption feature in the m
wavelength range with a small amplitude of 30 ppm (corresponding to just atmospheric scale heights). Based on an atmospheric retrieval
analysis, the presence of water vapor is tentatively favored with a Bayes
factor of 1.7 - 2.6 (depending on prior assumptions). The spectrum is most
consistent with either enhanced metallicity, high altitude condensates, or
both. Cloud-free solar composition atmospheres are ruled out at
confidence. We compare the spectrum to grids of cloudy and hazy forward models
and find that the spectrum is fit well by models with moderate cloud lofting or
haze formation efficiency, over a wide range of metallicities (
solar). We combine the constraints on the envelope composition with an interior
structure model and estimate that the core mass fraction is . With
a bulk composition reminiscent of that of Neptune and an orbital distance of
0.15 AU, HD 106315 c hints that planets may form out of broadly similar
material and arrive at vastly different orbits later in their evolution.Comment: Submitted to AAS journals; 19 pages, 12 figure
Innovative strategies for the elimination of viral hepatitis at a national level: a country case series
Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints
Transmission Spectroscopy for the Warm Sub-Neptune HD 3167c: Evidence for Molecular Absorption and a Possible High-metallicity Atmosphere
We present a transmission spectrum for the warm (500−600 K) sub-Neptune HD 3167c obtained using the Hubble Space Telescope Wide Field Camera 3 infrared spectrograph. We combine these data, which span the 1.125–1.643 μm wavelength range, with broadband transit measurements made using Kepler/K2 (0.6–0.9 μm) and Spitzer/IRAC (4–5 μm). We find evidence for absorption by at least one of H₂O, HCN, CO₂, and CH₄ (Bayes factor 7.4; 2.5σ significance), although the data precision does not allow us to unambiguously discriminate between these molecules. The transmission spectrum rules out cloud-free hydrogen-dominated atmospheres with metallicities ≤100× solar at >5.8σ confidence. In contrast, good agreement with the data is obtained for cloud-free models assuming metallicities >700× solar. However, for retrieval analyses that include the effect of clouds, a much broader range of metallicities (including subsolar) is consistent with the data, due to the degeneracy with cloud-top pressure. Self-consistent chemistry models that account for photochemistry and vertical mixing are presented for the atmosphere of HD 3167c. The predictions of these models are broadly consistent with our abundance constraints, although this is primarily due to the large uncertainties on the latter. Interior structure models suggest that the core mass fraction is >40%, independent of a rock or water core composition, and independent of atmospheric envelope metallicity up to 1000× solar. We also report abundance measurements for 15 elements in the host star, showing that it has a very nearly solar composition
Neuroliberalism:Cognition, context, and the geographical bounding of rationality
Focusing on the rise of the behavioural sciences within the design and implementation of public policy, this paper introduces the concept of neuroliberalism and suggests that it could offer a creative context within which to interpret related governmental developments. Understanding neuroliberaism as a system of government that targets the more-than rational aspects of human behaviour, this paper considers the particular contribution that geographical theories of context and spatial representation can make to a critical analysis of this evolving governmental project.authorsversionPeer reviewe
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