1,352 research outputs found
Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity
Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice
Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli
We have designed an experimental/computational framework for studying complex phenotypes in bacteria.Our framework relies on whole-genome fitness profiling coupled with a module-level analysis to discover pathways that directly affect fitness.As a proof-of-principle, we studied ethanol tolerance in Escherichia coli and we identified key pathways that contribute to this phenotype.We then validated our findings through genetic manipulations, gene-expression profiling, metabolite-level measurements, and stable-isotope labeling
From Local to Global Dilemmas in Social Networks
Social networks affect in such a fundamental way the dynamics of the population they support that the global, population-wide behavior that one observes often bears no relation to the individual processes it stems from. Up to now, linking the global networked dynamics to such individual mechanisms has remained elusive. Here we study the evolution of cooperation in networked populations and let individuals interact via a 2-person Prisoner's Dilemma â a characteristic defection dominant social dilemma of cooperation. We show how homogeneous networks transform a Prisoner's Dilemma into a population-wide evolutionary dynamics that promotes the coexistence between cooperators and defectors, while heterogeneous networks promote their coordination. To this end, we define a dynamic variable that allows us to track the self-organization of cooperators when co-evolving with defectors in networked populations. Using the same variable, we show how the global dynamics â and effective dilemma â co-evolves with the motifs of cooperators in the population, the overall emergence of cooperation depending sensitively on this co-evolution
Multiple factors influence compliance with colorectal cancer staging recommendations: an exploratory study
<p>Abstract</p> <p>Background</p> <p>For patients with colorectal cancer (CRC) retrieval by surgeons, and assessment by pathologists of at least 12 lymph nodes (LNs) predicts the need for adjuvant treatment and improved survival. Different interventions (educational presentation, engaging clinical opinion leaders, performance data sent to hospital executives) to improve compliance with this practice had variable results. This exploratory study examined factors hypothesized to have influenced the outcome of those interventions.</p> <p>Methods</p> <p>Semi-structured interviews were conducted with 26 surgeons and pathologists at eleven hospitals. Clinicians were identified by intervention organizers, public licensing body database, and referral from interviewees. An interview guide incorporating open-ended questions was pilot-tested on one surgeon and pathologist. A single investigator conducted all interviews by phone. Transcripts were analyzed independently by two investigators using a grounded approach,ho then compared findings to resolve differences.</p> <p>Results</p> <p>Improvements in LN staging practice may have occurred largely due to educational presentations that created awareness, and self-initiated changes undertaken by pathologists. Executives that received performance data may not have shared this with staff, and opinion leaders engaged to promote compliance may not have fulfilled their roles. Barriers to change that are potentially amenable to quality improvement included perceptions about the practice (perceived lack of evidence for the need to examine at least 12 LNs) and associated responsibilities (blaming other profession), technical issues (need for pathology assistants, better clearing solutions and laboratory facilities), and a lack of organizational support for multidisciplinary interaction (little communication between surgeons and pathologists) or quality improvement (no change leaders or capacity for monitoring).</p> <p>Conclusion</p> <p>Use of an exploratory approach provided an in-depth view of the way that numerous factors amenable to quality improvement influenced the adoption of new CRC LN staging recommendations. Continued interventions targeting physicians and executives, in the absence of a receptive organizational infrastructure, may be fruitless. Individualized rather than regional or punitive performance data, coupled with increased organizational capacity for change may stimulate greater surgical and organizational response to quality improvement. Descriptive or experimental studies are needed to test these hypotheses.</p
The pseudogap: friend or foe of high Tc?
Although nineteen years have passed since the discovery of high temperature
superconductivity, there is still no consensus on its physical origin. This is
in large part because of a lack of understanding of the state of matter out of
which the superconductivity arises. In optimally and underdoped materials, this
state exhibits a pseudogap at temperatures large compared to the
superconducting transition temperature. Although discovered only three years
after the pioneering work of Bednorz and Muller, the physical origin of this
pseudogap behavior and whether it constitutes a distinct phase of matter is
still shrouded in mystery. In the summer of 2004, a band of physicists gathered
for five weeks at the Aspen Center for Physics to discuss the pseudogap. In
this perspective, we would like to summarize some of the results presented
there and discuss its importance in the context of strongly correlated electron
systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in
Physic
Youth in the Netherlands Study (JOiN): study design
Background: Adolescence is a critical developmental period regarding exposure to substances. Therefore, it is important to be able to identify those adolescents who are most vulnerable to substance abuse in the (near) future. The JOiN study was specifically designed to examine two endophenotypes of adolescent substance use in a normal risk (NR) and high risk (HR) sample of adolescents: (1) behavioural disinhibition, and (2) individual differences in stress sensitivity. Methods: The NR adolescents were part of a longitudinal general population study at the Erasmus Medical Center in Rotterdam, the Netherlands of children and adolescents initially aged 6 to 18 years old. Three assessment waves have been nearly completed, and data are available of N = 711 participants for stress sensitivity measures, and of a subsample of N = 110 for electroencephalography (EEG) measures. Added to this study, HR adolescents who had at least one parent with a substance use disorder and who were treated by an outpatient clinic of a primary addiction care provider were approached via their parent(s). In total, N = 83 adolescents formed this HR sample. NR and HR adolescents participated in standardized stress procedure and EEG procedures in our laboratory. Questionnaires were filled out on background variables, behavioural and emotional problems, and substance use, and a diagnostic interview was conducted with adolescents and parents to assess psychopathology symptoms. DNA was collected through saliva or blood samples. Discussion: The design of the JOiN study is optimal for examining the predictive role of endophenotypes of adolescent substance use. The combination of different methods, i.e. stress physiology, electrophysiology, genetics, and questionnaire data from several informants on a range of behaviours and environmental factors enables the investigation of the multifactorial nature of adolescent substance use
Heterogeneous Aspirations Promote Cooperation in the Prisoner's Dilemma Game
To be the fittest is central to proliferation in evolutionary games. Individuals
thus adopt the strategies of better performing players in the hope of successful
reproduction. In structured populations the array of those that are eligible to
act as strategy sources is bounded to the immediate neighbors of each
individual. But which one of these strategy sources should potentially be
copied? Previous research dealt with this question either by selecting the
fittest or by selecting one player uniformly at random. Here we introduce a
parameter that interpolates between these two extreme options.
Setting equal to zero returns the random selection of the
opponent, while positive favor the fitter
players. In addition, we divide the population into two groups. Players from
group select their opponents as dictated by the parameter
, while players from group
do so randomly irrespective of
. We denote the fraction of players contained in groups
and by
and , respectively. The
two parameters and
allow us to analyze in detail how aspirations in the
context of the prisoner's dilemma game influence the evolution of
cooperation. We find that for sufficiently positive values of
there exist a robust intermediate
for which cooperation thrives best. The robustness of
this observation is tested against different levels of uncertainty in the
strategy adoption process and for different
interaction networks. We also provide complete phase diagrams depicting the
dependence of the impact of and
for different values of , and contrast the
validity of our conclusions by means of an alternative model where individual
aspiration levels are subject to evolution as well. Our study indicates that
heterogeneity in aspirations may be key for the sustainability of cooperation in
structured populations
Control of multi-joint arm movements for the manipulation of touch in keystroke by expert pianists
Descriptive Epidemiology of Serious Work-Related Injuries in British Columbia, Canada
OBJECTIVE: This study examined the rates and distribution of serious work-related injuries by demographic, work and injury characteristics in British Columbia, Canada from 2002-2008, using population-based data. METHODS: Claims for workers with a serious injury were extracted from workers' compensation data. Serious injuries were defined by long duration, high cost, serious medical diagnosis, or fatality. Workforce estimates were used to calculate stratum-specific rates. Rate-ratios (RR) and 95% CIs were calculated using negative binomial regression for the comparison of rates, adjusting for gender, age and occupation. RESULTS: Women had a lower overall serious injury rate compared to men (RR: 0.93, 95% CI: 0.87-0.99). The 35-44 age group had the highest overall rate compared to the youngest age group. The rate for severe strains/sprains was similarly high for men and women in the 35-44 age group, although there was a differential pattern by gender for other injury types: the rate of fracture was similar across age groups for men, but increased with age for women (RR: 2.7, 95% CI: 2.2-3.3); and the rate of severe falls increased with age for men and women, with a larger three-fold increase for older women (men: RR: 1.8, 95% CI: 1.7-2.1; women: RR: 3.2, 95% CI: 2.7-3.7). CONCLUSIONS: The risk of serious injuries is higher among specific age groups with different patterns emerging for men and women. Variations persisted within similar injury types and occupation groups in our adjusted models. These results provide evidence for the burden of serious injuries and a basis for future analytic research. Given projected demographic shifts and increasing workforce participation of older workers, intervention programs should be carefully implemented with consideration to demographic groups at risk for serious injuries in the workplace
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