Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level.

‘A picture is worth a thousand words’ is an idiom from the English language (‘borrowed’ from on old Chinese proverb) that conveys the notion that a complex idea can be succinctly and fully described by a single image. Never has this expression been truer than in the clinical and pharmaceutical arenas. Enormous strides have been made by the scientific community in the evolving field of biomedical imaging with the aim of representing and/or quantifying aspects of disease and drug action by using tools such as radiography, MRI, PET, and ultrasound. Yet linking the phenotypical data generated by these systems to the genome is a challenging task. Identifying the link between the mechanism of disease or failed drug response to the genome of an individual is difficult, because central pieces of information are missing. However, imaging mass spectrometry (IMS) can overcome this issue. IMS aims to detect the molecular constituents of the tissue; these can then be correlated with genome-related characteristics, such as gene expression patterns and possible mutations, and ultimately provide a phenotypic molecular link to the complex disease biology. The big data technology of IMS can generate spatial information of thousands of metabolites and proteins from within a tissue, facilitating a deeper understanding of the connections between the genome, phenotypic characteristics and the biological response. It is a technology that has the potential to serve as a segue between gene expression and observed biological signal

A new purple sulfur bacterium from saline littoral sediments, Thiorhodotvibrio winogradskyi gen. nov. and sp. nov.

Two strains of a new purple sulfur bacterium were isolated in pure culture from the littoral sediment of a saline lake (Mahoney Lake, Canada) and a marine microbial mat from the North Sea island of Mellum, respectively. Single cells were vibrioid-to spirilloid-shaped and motile by means of single polar flagella. Intracellular photosynthetic membranes were of the vesicular type. As photosynthetic pigments, bacteriochlorophyll a and the carotenoids lycopene, rhodopin, anhydrorhodovibrin, rhodovibrin and spirilloxanthin were present. Hydrogen sulfide and elemental sulfur were used under anoxic conditions for phototrophic growth. In addition one strain (06511) used thiosulfate. Carbon dioxide, acetate and pyruvate were utilized by both strains as carbon sources. Depending on the strain propionate, succinate, fumarate, malate, tartrate, malonate, glycerol or peptone may additionally serve as carbon sources in the light. Optimum growth rates were obtained at pH 7.2, 33 °C, 50 mol m-2 s-1 intensity of daylight fluorescent tubes and a salinity of 2.2–3.2% NaCl. During growth on sulfide, up to ten small sulfur globules were formed inside the cells. The strains grew microaerophilic in the dark and exhibited high specific respiration rates. No vitamins were required for growth. The DNA base composition was 61.0–62.4 mol% G+C. The newly isolated bacterium belongs to the family chromatiaceae and is described as a member of a new genus and species, Thiorhodovibrio winogradskyi gen. nov. and sp. nov. with the type strain SSP1, DSM No. 6702

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Do you see what I see? Identification of child protection concerns by hospital staff and general dental practitioners

Aim An exploration of the threshold that dentists, doctors and nurses recognise for dental and child protection (CP) actions in sample clinical cases, and any differences between these professional groups. Method We present a cross-sectional survey of dentists, doctors and nurses (50 each), who regularly examine children, utilised five fictitious vignettes, combining an oral examination image and clinical history reflecting dental and CP issues. Demographics were collected, and each participant gave their likely action for the cases presented. Results Dentists were significantly better at answering the dental element than the doctors and nurses, (P <0.0001) with no significant difference between these two; only 8% of the latter had undergone any training in assessment of dental health. Although 90.6% of all professionals had undergone CP training, dentists were significantly less accurate at identifying the CP component than doctors and nurses, (P <0.0001) between whom there were no significant differences. Those with higher levels of CP training were most accurate at identifying correct CP actions. Conclusions CP training is effective at improving recognition of child maltreatment, although there remains a worrying lack of knowledge about thresholds for action among dentists. Doctors and nurses have minimal training in, or knowledge of, dental health in children, thus precluding appropriate onward referrals

Arbuscular mycorrhizal colonisation of roots of grass species differing in invasiveness

Recent research indicates that the soil microbial community, particularly arbuscular mycorrhizal fungi (AMF), can influence plant invasion in several ways. We tested if 1) invasive species are colonised by AMF to a lower degree than resident native species, and 2) AMF colonisation of native plants is lower in a community inhabited by an invasive species than in an uninvaded resident community. The two tests were run in semiarid temperate grasslands on grass (Poaceae) species, and the frequency and intensity of mycorrhizal colonisation, and the proportion of arbuscules and vesicles in plant roots have been measured. In the first test, grasses representing three classes of invasiveness were included: invasive species, resident species becoming abundant upon disturbance, and non-invasive native species. Each class contained one C3 and one C4 species. The AMF colonisation of the invasive Calamagrostis epigejos and Cynodon dactylon was consistently lower than that of the non-invasive native Chrysopogon gryllus and Bromus inermis, and contained fewer arbuscules than the post-disturbance dominant resident grasses Bothriochloa ischaemum and Brachypodium pinnatum. The C3 and C4 grasses behaved alike despite their displaced phenologies in these habitats. The second test compared AMF colonisation for sand grassland dominant grasses Festuca vaginata and Stipa borysthenica in stands invaded by either C. epigejos or C. dactylon, and in the uninvaded natural community. Resident grasses showed lower degree of AMF colonisation in the invaded stand compared to the uninvaded natural community with F. vaginata responding so to both invaders, while S. borysthenica responding to C. dactylon only. These results indicate that invasive grasses supposedly less reliant on AMF symbionts have the capacity of altering the soil mycorrhizal community in such a way that resident native species can establish a considerably reduced extent of the beneficial AMF associations, hence their growth, reproduction and ultimately abundance may decline. Accumulating evidence suggests that such indirect influences of invasive alien plants on resident native species mediated by AMF or other members of the soil biota is probably more the rule than the exception

Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF

The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX) complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range of techniques to reveal the sites for direct contact between RNA and ORF57 in the absence and presence of ALYREF. A binding site within ORF57 was characterized which recognizes specific viral mRNA motifs. When ALYREF is present, part of this ORF57 RNA binding site, composed of an a-helix, binds preferentially to ALYREF. This competitively displaces viral RNA from the a-helix, but contact with RNA is still maintained by a flanking region. At the same time, the flexible N-terminal domain of ALYREF comes into contact with the viral RNA, which becomes engaged in an extensive network of synergistic interactions with both ALYREF and ORF57. Transfer of RNA to ALYREF in the ternary complex, and involvement of individual ORF57 residues in RNA recognition, were confirmed by UV cross-linking and mutagenesis. The atomic-resolution structure of the ORF57-ALYREF interface was determined, which noticeably differed from the homologous ICP27-ALYREF structure. Together, the data provides the first site-specific description of how viral mRNA is locked by a herpes viral adaptor protein in complex with cellular ALYREF, giving herpesvirus access to the cellular mRNA export machinery. The NMR strategy used may be more generally applicable to the study of fuzzy protein-protein-RNA complexes which involve flexible polypeptide regions

Condition-specific or generic preference-based measures in oncology? A comparison of the EORTC-8D and the EQ-5D-3L.

PURPOSE: It has been argued that generic health-related quality of life measures are not sensitive to certain disease-specific improvements; condition-specific preference-based measures may offer a better alternative. This paper assesses the validity, responsiveness and sensitivity of a cancer-specific preference-based measure, the EORTC-8D, relative to the EQ-5D-3L. METHODS: A longitudinal prospective population-based cancer genomic cohort, Cancer 2015, was utilised in the analysis. EQ-5D-3L and the EORTC QLQ-C30 (which gives EORTC-8D values) were asked at baseline (diagnosis) and at various follow-up points (3 months, 6 months, 12 months). Baseline values were assessed for convergent validity, ceiling effects, agreement and sensitivity. Quality-adjusted life-years (QALYs) were estimated and similarly assessed. Multivariate regression analyses were employed to understand the determinants of the difference in QALYs. RESULTS: Complete case analysis of 1678 patients found that the EQ-5D-3L values at baseline were significantly lower than the EORTC-8D values (0.748 vs 0.829, p < 0.001). While the correlation between the instruments was high, agreement between the instruments was poor. The baseline health state values using both instruments were found to be sensitive to a number of patient and disease characteristics, and discrimination between disease states was found to be similar. Mean generic QALYs (estimated using the EQ-5D-3L) were significantly lower than condition-specific QALYs (estimated using the EORTC-8D) (0.860 vs 0.909, p < 0.001). The discriminatory power of both QALYs was similar. CONCLUSIONS: When comparing a generic and condition-specific preference-based instrument, divergences are apparent in both baseline health state values and in the estimated QALYs over time for cancer patients. The variability in sensitivity between the baseline values and the QALY estimations means researchers and decision makers are advised to be cautious if using the instruments interchangeably