Several major invasive bacterial pathogens are encapsulated. Expression of a polysaccharide capsule is essential for survival in the blood, and thus for virulence, but also is a target for host antibodies and the basis for effective vaccines. Encapsulated species typically exhibit antigenic variation and express one of a number of immunochemically distinct capsular polysaccharides that define serotypes. We provide the sequences of the capsular biosynthetic genes of all 90 serotypes of Streptococcus pneumoniae and relate these to the known polysaccharide structures and patterns of immunological reactivity of typing sera, thereby providing the most complete understanding of the genetics and origins of bacterial polysaccharide diversity, laying the foundations for molecular serotyping. This is the first time, to our knowledge, that a complete repertoire of capsular biosynthetic genes has been available, enabling a holistic analysis of a bacterial polysaccharide biosynthesis system. Remarkably, the total size of alternative coding DNA at this one locus exceeds 1.8 Mbp, almost equivalent to the entire S. pneumoniae chromosomal complement.
A significant proportion of mammalian genes are not represented in the genomes of Drosophila, Caenorhabditis or Saccharomyces, and many of these are assumed to have been vertebrate innovations. To test this assumption, we conducted a preliminary EST project on the anthozoan cnidarian, Acropora millepora, a basal metazoan. More than 10% of the Acropora ESTs with strong metazoan matches to the databases had clear human homologs but were not represented in the Drosophila or Caenorhabditis genomes; this category includes a surprising diversity of transcription factors and metabolic proteins that were previously assumed to be restricted to vertebrates. Consistent with higher rates of divergence in the model invertebrates, three-way comparisons show that most Acropora ESTs match human sequences much more strongly than they do any Drosophila or Caenorhabditis sequence. Gene loss has thus been much more extensive in the model invertebrate lineages than previously assumed and, as a consequence, some genes formerly thought to be vertebrate inventions must have been present in the common metazoan ancestor. The complexity of the Acropora genome is paradoxical, given that this organism contains apparently few tissue types and the simplest extant nervous system consisting of a morphologically homogeneous nerve net.
As the closest outgroup to the Bilateria, the Phylum Cnidaria is likely to be critical to understanding the origins and evolution of body axes. Proteins of the decapentaplegic (DPP)͞bone morphogenetic protein (BMP) 2͞4 subfamily are central to the specification of the dorsoventral (D͞V) axis in bilateral animals, albeit with an axis inversion between arthropods and chordates. We show that a dpp͞BMP2͞4 ortholog (bmp2͞4-Am) is present in the reef-building scleractinian coral, Acropora millepora (Class Anthozoa) and that it is capable of causing phenotypic effects in Drosophila that mimic those of the endogenous dpp gene. We also show that, during coral embryonic development, bmp2͞4-Am expression is localized in an ectodermal region adjacent to the blastopore. Thus, a representative of the DPP͞BMP2͞4 subfamily of ligands was present in the common ancestor of diploblastic and triploblastic animals where it was probably expressed in a localized fashion during development. A localized source of DPP͞BMP2͞4 may have already been used in axis formation in this ancestor, or it may have provided a means by which an axis could evolve in triploblastic animals.
This paper critically explores the research and development of ‘digital phenotyping’, which broadly refers to the idea that digital data can measure and predict people’s mental health as well as their potential risk for mental ill health. Despite increasing research and efforts to digitally track and predict ill mental health, there has been little sociological and critical engagement with this field. This paper aims to fill this gap by introducing digital phenotyping to the social sciences. We explore the origins of digital phenotyping, the concept of the digital phenotype and its potential for benefit, linking these to broader developments within the field of ‘mental health sensing’. We then critically discuss the technology, offering three critiques. First, that there may be assumptions of normality and bias present in the use of algorithms; second, we critique the idea that digital data can act as a proxy for social life; and third that the often biological language employed in this field risks reifying mental health problems. Our aim is not to discredit the scientific work in this area, but rather to call for scientists to remain reflexive in their work, and for more social science engagement in this area.
The relative newness of 'impact' as a criterion for research assessment has meant that there is yet to be an empirical study examining the process of its evaluation. This article is part of a broader study which is exploring the panel-based peer and end-user review process for societal impact evaluation using the UK's national research assessment exercise, the Research Excellence Framework (REF) 2014, as a case study. In particular, this article explores the different perceptions REF2014 evaluators had regarding societal impact, preceding their evaluation of this measure as part of REF2014. Data are drawn from 62 interviews with evaluators from the health-related Panel A and its subpanels, prior to the REF2014 exercise taking place. We show how going into the REF exercise, evaluators from Panel A had different perceptions about how to characterize impact and how to define impact realization in terms of research outcomes and the research process. We conclude by discussing the implications of our findings for future impact evaluation frameworks, as well as postulating a series of hypotheses about the ways in which evaluators' different perceptions going into an impact assessment could potentially influence the evaluation of impact submissions. Using REF2014 as a case study, these hypotheses will be tested in interviews with REF2014 evaluators post-assessment.
BackgroundThis paper proposes a refocusing of consent for clinical genetic testing, moving away from an emphasis on autonomy and information provision, towards an emphasis on the virtues of healthcare professionals seeking consent, and the relationships they construct with their patients.MethodsWe draw on focus groups with UK healthcare professionals working in the field of clinical genetics, as well as in-depth interviews with patients who have sought genetic testing in the UK’s National Health Service (data collected 2013–2015). We explore two aspects of consent: first, how healthcare professionals consider the act of ‘consenting’ patients; and second how these professional accounts, along with the accounts of patients, deepen our understanding of the consent process.ResultsOur findings suggest that while healthcare professionals working in genetic medicine put much effort into ensuring patients’ understanding about their impending genetic test, they acknowledge, and we show, that patients can still leave genetic consultations relatively uninformed. Moreover, we show how placing emphasis on the informational aspect of genetic testing is not always reflective of, or valuable to, patients’ decision-making. Rather, decision-making is socially contextualised – also based on factors outside of information provision.ConclusionsA more collaborative on-going consent process, grounded in virtue ethics and values of honesty, openness and trustworthiness, is proposed.
Escherichia coli O157, Salmonella enterica O30, and Citrobacter freundii F90 have identical O-antigen structures, as do E. coli O55 and S. enterica O50. The O-antigen gene cluster sequences for E. coli O157 and E. coli O55 have been published, and the genes necessary for O-antigen biosynthesis have been identified, although transferase genes for glycosidic linkages are only generic and have not been allocated to specific linkages. We determined sequences for S. enterica O30 and C. freundii F90 O-antigen gene clusters and compared them to the sequence of the previously described E. coli O157 cluster. We also determined the sequence of the S. enterica O50 O-antigen gene cluster and compared it to the sequence of the previously described E. coli O55 cluster. For both the S. enterica O30-C. freundii F90-E. coli O157 group and the S. enterica O50-E. coli O55 group of O antigens, the gene clusters have identical or nearly identical organizations. The two sets of gene clusters had comparable overall levels of similarity in their genes, which were lower than the levels determined for housekeeping genes for these species, which were 55 to 65% for the genes encoding glycosyltransferases and O-antigen processing proteins and 75 to 93% for the nucleotide-sugar pathway genes. Nonetheless, the similarity of the levels of divergence in the five gene clusters required us to consider the possibility that the parent gene cluster for each structure was in the common ancestor of the species and that divergence is faster than expected for the common ancestor hypothesis. We propose that the identical O-antigen gene clusters originated from a common ancestor, and we discuss some possible explanations for the increased rate of divergence that is seen in these genes.
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