In situ multi-frequency measurements of magnetic susceptibility as an indicator of planetary regolith maturity

Space weathering is now generally accepted to modify the optical and magnetic properties of airless planetary regoliths such as those on the Moon and Mercury. Under micrometeorite and ion bombardment, ferrous iron in such surfaces is reduced to metallic iron spheres, found in amorphous coatings on almost all exposed regolith grains. The size and number distribution of these particles and their location in the regolith all determine the nature and extent of the optical and magnetic changes. These parameters in turn reflect the formation mechanisms, temperatures, and durations involved in the evolution of the regolith. Studying them in situ is of intrinsic value to understanding the weathering process, and useful for determining the maturity of the regolith and providing supporting data for interpreting remotely sensed mineralogy. Fine-grained metallic iron has a number of properties that make it amenable to magnetic techniques, of which magnetic susceptibility is the simplest and most robust. The magnetic properties of the lunar regolith and laboratory regolith analogues are therefore reviewed and the theoretical basis for the frequency dependence of magnetic susceptibility presented. Proposed here is then an instrument concept using multi-frequency measurements of magnetic susceptibility to confirm the presence of fine grained magnetic material and attempt to infer its quantity and size distribution. Such an instrument would be invaluable on a future mission to an asteroid, the Moon, Mercury or other airless rocky Solar System body

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture

On the application of magnetic methods for the characterisation of space weathering products

Space weathering is now commonly accepted to modify the optical and magnetic properties of airless body regoliths throughout the Solar System. Although the precise formation processes are not well understood, the presence of ubiquitous sub-microscopic metallic iron (SMFe) grains in lunar soils and corresponding spectral analyses have explained both the unique optical and magnetic properties of such soils. More recently, a variety of ion irradiation, laser melting and vaporisation and impact experiments have been shown to reproduce these effects in the laboratory. Such experiments are crucial to the study of the formation of SMFe under controlled conditions. To date, more emphasis has been placed on optical analyses of laboratory samples, as these address directly the mineralogical interpretation of remote sensing data. However, the magnetic analyses performed on the Apollo and Luna samples have provided useful qualitative and quantitative evaluation of regolith metallic iron content. These techniques are reviewed here, demonstrated on pulsed laser irradiated olivine powder, and their utility for determining the quantity and size distribution of this metallic iron discussed. Ferromagnetic resonance, multi- frequency magnetic susceptibility, vibrating sample magnetometry and thermomagnetic measurements were carried out. Each showed trends expected for the conversion of paramagnetic Fe2+ in olivine to fine-grained Fe0, with some grains in the superparamagnetic size range. Although evidence for super- paramagnetic iron was found, the quantity of sub-microscopic metallic iron produced in these experiments proved insufficient to make conclusive measurements of either the quantity or size distribution of this iron. Improvements to both the experimental and analytical procedures are discussed to better enable such measurements in the future

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

Evidence for the formation of comet 67P/Churyumov-Gerasimenko through gravitational collapse of a bound clump of pebbles

The processes that led to the formation of the planetary bodies in the Solar System are still not fully understood. Using the results obtained with the comprehensive suite of instruments on-board ESA’s Rosetta mission, we present evidence that comet 67P/Churyumov-Gerasimenko likely formed through the gentle gravitational collapse of a bound clump of mm-sized dust aggregates (“pebbles”), intermixed with microscopic ice particles. This formation scenario leads to a cometary make-up that is simultaneously compatible with the global porosity, homogeneity, tensile strength, thermal inertia, vertical temperature profiles, sizes and porosities of emitted dust, and the steep increase in water-vapour production rate with decreasing heliocentric distance, measured by the instruments on-board the Rosetta spacecraft and the Philae lander. Our findings suggest that the pebbles observed to be abundant in protoplanetary discs around young stars provide the building material for comets and other minor bodies

The KIC 8462852 light curve from 2015.75 to 2018.18 shows a variable secular decline

The star KIC 8462852 (Boyajian's Star) displays both fast dips of up to 20% on time scales of days, plus long-term secular fading by up to 19% on time scales from a year to a century. We report on CCD photometry of KIC 8462852 from 2015.75 to 2018.18, with 19,176 images making for 1,866 nightly magnitudes in BVRI. Our light curves show a continuing secular decline (by 0.023±0.003 mags in the B-band) with three superposed dips with duration 120-180 days. This demonstrates that there is a continuum of dip durations from a day to a century, so that the secular fading is seen to be by the same physical mechanism as the short-duration Kepler dips. The BVRI light curves all have the same shape, with the slopes and amplitudes for VRI being systematically smaller than in the B-band by factors of 0.77±0.05, 0.50±0.05, and 0.31±0.05. We rule out any hypothesis involving occultation of the primary star by any star, planet, solid body, or optically thick cloud. But these ratios are the same as that expected for ordinary extinction by dust clouds. This chromatic extinction implies dust particle sizes going down to ˜0.1 micron, suggesting that this dust will be rapidly blown away by stellar radiation pressure, so the dust clouds must have formed within months. The modern infrared observations were taken at a time when there was at least 12.4%±1.3% dust coverage (as part of the secular dimming), and this is consistent with dimming originating in circumstellar dust

The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1

Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype

Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae

Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3–4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role

Pellino-1 Regulates the Responses of the Airway to Viral Infection

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1-/- mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses.</p