Biomedical Ph.D. Students Enrolled in Two Elite Universities in the United Kingdom and the United States Report Adopting Multiple Learning Relationships

Objective: The ability to form multiple learning relationships is a key element of the doctoral learning environment in the biomedical sciences. Of these relationships, that between student and supervisor has long been viewed as key. There are, however, limited data to describe the student perspective on what makes this relationship valuable. In the present study, we discuss the findings of semi-structured interviews with biomedical Ph.D. students from the United Kingdom and the United States to: i) determine if the learning relationships identified in an Australian biomedical Ph.D. cohort are also important in a larger international student cohort; and ii) improve our understanding of student perceptions of value in their supervisory relationships. Study Design 32 students from two research intensive universities, one in the United Kingdom (n = 17), and one in the United States (n = 15) were recruited to participate in a semi-structured interview. Verbatim transcripts were transcribed, validated and analysed using a Miles and Huberman method for thematic analysis. Results: Students reported that relationships with other Ph.D. students, post-doctoral scientists and supervisors were all essential to their learning. Effective supervisory relationships were perceived as the primary source of high-level project guidance, intellectual support and confidence. Relationships with fellow students were viewed as essential for the provision of empathetic emotional support. Technical learning was facilitated, almost exclusively, by relationships with postdoctoral staff. Conclusions: These data make two important contributions to the scholarship of doctoral education in the biomedical sciences. Firstly, they provide further evidence for the importance of multiple learning relationships in the biomedical doctorate. Secondly, they clarify the form of a ‘valued’ supervisory relationship from a student perspective. We conclude that biomedical doctoral programs should be designed to contain a minimum level of formalised structure to promote the development of multiple learning relationships that are perceived as key to student learning

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions

Reply to Guy et al.: Support for a bottleneck in the 2011 Escherichia coli O104:H4 outbreak in Germany

In our paper (1), we analyzed isolates from the Escherichia coli O104:H4 outbreaks in Germany and France in May to July 2011. We concluded that, although the German outbreak was larger, the German isolates represent a clade within the greater diversity of the French outbreak. We proposed several hypotheses to explain these findings, including that the lineage leading to the German outbreak went through a narrow bottleneck that purged diversity. Guy et al. (2) report the genomes of eight additional E. coli O104:H4 isolates sampled from the German outbreak. By focusing on the numbers of SNPs in their samples, they suggest that the German outbreak is more diverse than we reported and is similar to the French outbreak. In fact, Guy et al.’s data (2) strongly support our conclusion that the German outbreak represents a clade within the diversity

Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi

INTRODUCTION: Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. MATERIALS AND METHODS: We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. RESULTS: Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. CONCLUSIONS: This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines

Patterns of Gene Flow Define Species of Thermophilic Archaea

A genomic view of speciation in Archaea shows higher rates of gene flow within coexisting microbial species than between them

Pneumococcal Capsular Polysaccharide Structure Predicts Serotype Prevalence

There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement

Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

Pneumococcal Serotypes and Mortality following Invasive Pneumococcal Disease: A Population-Based Cohort Study

Analyzing population-based data collected over 30 years in more than 18,000 patients with invasive pneumococcal infection, Zitta Harboe and colleagues find specific pneumococcal serotypes to be associated with increased mortality

Recombination and Population Structure in Salmonella enterica

Salmonella enterica is a bacterial pathogen that causes enteric fever and gastroenteritis in humans and animals. Although its population structure was long described as clonal, based on high linkage disequilibrium between loci typed by enzyme electrophoresis, recent examination of gene sequences has revealed that recombination plays an important evolutionary role. We sequenced around 10% of the core genome of 114 isolates of enterica using a resequencing microarray. Application of two different analysis methods (Structure and ClonalFrame) to our genomic data allowed us to define five clear lineages within S. enterica subspecies enterica, one of which is five times older than the other four and two thirds of the age of the whole subspecies. We show that some of these lineages display more evidence of recombination than others. We also demonstrate that some level of sexual isolation exists between the lineages, so that recombination has occurred predominantly between members of the same lineage. This pattern of recombination is compatible with expectations from the previously described ecological structuring of the enterica population as well as mechanistic barriers to recombination observed in laboratory experiments. In spite of their relatively low level of genetic differentiation, these lineages might therefore represent incipient species