Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This 'one bug-one drug' approach to antiviral drug development can be ...successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry.
Doppler spectroscopy was the first technique used to reveal the existence of extrasolar planetary systems hosted by solar-type stars. Radial-velocity surveys led to the detection of a rich population ...of super-Earths and Neptune-type planets. The numerous detected systems revealed a remarkable diversity. Combining Doppler measurements with photometric observations of planets transiting their host stars further provides access to the planet bulk density, a first step towards comparative exoplanetology. The development of new high-precision spectrographs and space-based facilities will ultimately lead us to characterize rocky planets in the habitable zone of our close stellar neighbours.
The interaction between peptides and biological membranes is of fundamental importance in the mechanism of numerous membrane-mediated cellular processes, including antimicrobial peptide action, ...hormone-receptor interactions, drug bioavailability across the blood-brain barrier, and viral fusion processes ....
A rocky planet transiting a nearby low-mass star Berta-Thompson, Zachory K; Irwin, Jonathan; Charbonneau, David ...
Nature (London),
11/2015, Letnik:
527, Številka:
7577
Journal Article, Web Resource
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M-dwarf stars--hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun--are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent ...results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.
Over the years, the scientific importance of nanoparticles for biomedical applications has increased. The high stability and biocompatibility, together with the low toxicity of the nanoparticles ...developed lead to their use as targeted drug delivery systems, bioimaging systems, and biosensors. The wide range of nanoparticles size, from 10 nm to 1 μm, as well as their optical properties, allow them to be studied using microscopy and spectroscopy techniques. In order to be effectively used, the physicochemical properties of nanoparticle formulations need to be taken into account, namely, particle size, surface charge distribution, surface derivatization and/or loading capacity, and related interactions. These properties need to be optimized considering the final nanoparticle intended biodistribution and target. In this review, we cover light scattering based techniques, namely dynamic light scattering and zeta-potential, used for the physicochemical characterization of nanoparticles. Dynamic light scattering is used to measure nanoparticles size, but also to evaluate their stability over time in suspension, at different pH and temperature conditions. Zeta-potential is used to characterize nanoparticles surface charge, obtaining information about their stability and surface interaction with other molecules. In this review, we focus on nanoparticle characterization and application in infection, cancer and cardiovascular diseases.
Nuclear movements are important for multiple cellular functions, and are driven by polarized forces generated by motor proteins and the cytoskeleton. During skeletal myofibre formation or ...regeneration, nuclei move from the centre to the periphery of the myofibre for proper muscle function. Centrally located nuclei are also found in different muscle disorders. Using theoretical and experimental approaches, we demonstrate that nuclear movement to the periphery of myofibres is mediated by centripetal forces around the nucleus. These forces arise from myofibril contraction and crosslinking that 'zip' around the nucleus in combination with tight regulation of nuclear stiffness by lamin A/C. In addition, an Arp2/3 complex containing Arpc5L together with γ-actin is required to organize desmin to crosslink myofibrils for nuclear movement. Our work reveals that centripetal forces exerted by myofibrils squeeze the nucleus to the periphery of myofibres.
Dengue, West Nile and Zika viruses are vector-borne flaviviruses responsible for numerous disease outbreaks in both Hemispheres. Despite relatively low mortality, infection may lead to potentially ...severe situations such as (depending on the virus): hypovolemic shock, encephalitis, acute flaccid paralysis, Guillain-Barré syndrome, congenital malformations (e.g., microcephaly) and, in some situations, death. Moreover, outbreaks also have major socioeconomic repercussions, especially in already vulnerable societies. Thus far, only generic symptoms relief is possible, as there are no specific treatments available yet. Dengvaxia was the world's first dengue vaccine. However, it is not fully effective. Prophylactic approaches against West Nile and Zika viruses are even more limited. Therefore, therapeutic strategies are required and will be discussed hereafter. We will first briefly present these viruses' epidemiology, life cycle and structure. Then, we introduce the clinical presentation, diagnosis approaches and available vaccines. Finally, we list and discuss promising compounds at discovery and preclinical development stages already deposited at the GlobalData database and divided into three main types, according to therapeutic molecule: antibody-based, peptide-based molecules and, other compounds. To conclude, we discuss and compare promising developments, useful for future therapies against these three flaviviruses of major concern to human health.
Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as ...25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses' entry into their target cells. We used atomic force microscopy to assess the effect of 25-hydroxycholesterol on different properties of supported lipid bilayers with controlled lipid compositions. In particular, we showed that 25-hydroxycholesterol inhibits the lipid-condensing effects of cholesterol, rendering the bilayers less rigid. This study indicates that the inclusion of 25-hydroxycholesterol in plasma membranes or the conversion of part of their cholesterol content into 25-hydroxycholesterol leads to morphological alterations of the sphingomyelin (SM)-enriched domains and promotes lipid packing inhomogeneities. These changes culminate in membrane stiffness variations.
Stars and planets both form by accreting material from a surrounding disk. Because they grow from the same material, theory predicts that there should be a relationship between their compositions. In ...this study, we search for a compositional link between rocky exoplanets and their host stars. We estimate the iron-mass fraction of rocky exoplanets from their masses and radii and compare it with the compositions of their host stars, which we assume reflect the compositions of the protoplanetary disks. We find a correlation (but not a 1:1 relationship) between these two quantities, with a slope of >4, which we interpret as being attributable to planet formation processes. Super-Earths and super-Mercuries appear to be distinct populations with differing compositions, implying differences in their formation processes.
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