Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Subgingival Microbiome Colonization and Cytokine Production during Early Dental Implant Healing

Little is known about longitudinal development of the peri-implant subgingival microbiome and cytokine production as a new sulcus forms after dental implant placement. Therefore, the purpose of this observational study was to evaluate simultaneous longitudinal changes in the oral microbiome and cytokine production in the developing peri-implant sulcus compared to control natural teeth. Four and 12 weeks after implant placement and abutment connection, a dental implant and a natural tooth were sampled in 25 patients for subgingival plaque and gingival crevicular fluid (GCF [around teeth] and peri-implant crevicular fluid [PICF] around implants). DNA from plaque samples was extracted and sequenced using Illumina-based 16S rRNA sequencing. GCF and PICF samples were analyzed using a customized Milliplex human cytokine and chemokine magnetic bead panel. Beta diversity analysis revealed that natural teeth and implants had similar subgingival microbiomes, while teeth had greater alpha diversity than implants. At the genus level, however, few differences were noted between teeth and dental implants over 12 weeks. Specifically, Actinomyces and Selenomonas were significantly elevated around teeth versus dental implants at both 4 weeks and 12 weeks, while Corynebacterium and Campylobacter were significantly elevated only at 4 weeks around teeth. The only difference between PICF and GCF biomarkers was significantly elevated granulocyte-macrophage colony-stimulating factor levels around teeth versus dental implants at the 4-week visit. The subgingival microbiome and cytokine production were similar between teeth and implants during early healing, suggesting that these profiles are driven by the patient following dental implant placement and are not determined by anatomical niche

Experimental Evidence for Adaptation to Species-Specific Gut Microbiota in House Mice

The gut microbial communities of mammals have codiversified with host species, and changes in the gut microbiota can have profound effects on host fitness. Therefore, the gut microbiota may drive adaptation in mammalian species, but this possibility is underexplored. Here, we show that the gut microbiota has codiversified with mice in the genus Mus over the past 6 million years, and we present experimental evidence that the gut microbiota has driven adaptive evolution of the house mouse, Mus musculus domesticus. Phylogenetic analyses of metagenomeassembled bacterial genomic sequences revealed that gut bacterial lineages have been retained within and diversified alongside Mus species over evolutionary time. Transplantation of gut microbiotas from various Mus species into germfree M. m. domesticus showed that foreign gut microbiotas slowed growth rate and upregulated macrophage inflammatory protein in hosts. These results suggest adaptation by M. m. domesticus to its gut microbiota since it diverged from other Mus species

Step-Indexed Normalization for a Language with General Recursion

The Trellys project has produced several designs for practical dependently typed languages. These languages are broken into two fragments-a_logical_fragment where every term normalizes and which is consistent when interpreted as a logic, and a_programmatic_fragment with general recursion and other convenient but unsound features. In this paper, we present a small example language in this style. Our design allows the programmer to explicitly mention and pass information between the two fragments. We show that this feature substantially complicates the metatheory and present a new technique, combining the traditional Girard-Tait method with step-indexed logical relations, which we use to show normalization for the logical fragment.Comment: In Proceedings MSFP 2012, arXiv:1202.240

\u3ci\u3eIn Vivo\u3c/i\u3e Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract

\u3ci\u3eIn Vivo\u3c/i\u3e Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract

Reduced cardiovascular morbidity in patients with hemophilia:results of a 5-year multinational prospective study

Hemophilia is a congenital bleeding disorder caused by low levels of clotting factor VIII or IX. The life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased; in retrospective studies, there are conflicting data regarding if, despite this increase, the incidence is still lower than in the general population. We prospectively compared the incidence of CVD in PWH vs the predicted incidence. This prospective, multicenter, observational study included adult PWH (aged &gt;30 years) from The Netherlands and United Kingdom. They were followed up for a 5-year period, and CVD incidence was compared with a predicted event rate based on the QRISK2-2011 CVD risk model. The primary end point was the observed fatal and nonfatal CVD incidence after 5 years compared with the estimated events and in relation to severity of hemophilia. The study included 709 patients, of whom 687 (96.9%) completed 5 years' follow-up or reached an end point. For 108 patients, the QRISK score could not be calculated at inclusion. For the remaining 579, fewer CVD events were observed than predicted: 9 vs 24 (relative risk, 0.38; 95% confidence interval, 0.18-0.80; P 5 .01), corresponding with an absolute risk reduction of 2.4%. Severe hemophilia treated on demand had the highest risk reduction. There was no statistically significant relation between severity of hemophilia and incidence of CVD. In hemophilia, a lower-than-predicted CVD incidence was found, supporting the theory that hemophilia protects against CVD. The study is registered at www.clinicaltrials.gov as #NCT01303900.</p

The Impact of a Dedicated Research Education Month for Anesthesiology Residents

An educational intervention was implemented at the University of Michigan starting in 2008, in which anesthesiology interns complete a dedicated month-long didactic rotation in evidence-based medicine (EBM) and research methodology. We sought to assess its utility. Scores on a validated EBM test before and after the rotation were compared and assessed for significance of improvement. A survey was also given to gauge satisfaction with the quality of the rotation and self-reported improvement in understanding of EBM topics. Fourteen consecutive interns completed the research rotation during the study period. One hundred percent completed both the pre- and postrotation test. The mean pretest score was 7.78 ± 2.46 (median = 7.5, 0–15 scale, and interquartile range 7.0–10.0) and the mean posttest score was 10.00 ± 2.35 (median = 9.5, interquartile range 8.0–12.3), which represented a statistically significant increase (P=0.011, Wilcoxon signed-rank test). All fourteen of the residents “agreed” or “strongly agreed” that they would recommend the course to future interns and that the course increased their ability to critically review the literature. Our findings demonstrate that this can be an effective means of improving understanding of EBM topics and anesthesiology research

Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly

The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system is not a major contributor to these processes. In conclusion, this study established a measurable effect of colonization history on gut microbiota assembly in a model in which host and environmental factors were strictly controlled, illuminating a potential cause for the high levels of unexplained individuality in host-associated microbial communities. Supplemental figures attached below

Adverse adult consequences of different alcohol use patterns in adolescence: An integrative analysis of data to age 30 years from four Australasian cohorts

BACKGROUND AND AIMS: Studies have linked adolescent alcohol use with adverse consequences in adulthood; yet it is unclear how strong the associations are and to what extent they may be due to confounding. Our aim was to estimate the strength of association between different patterns of adolescent drinking and longer-term psychosocial harms taking into account individual, family, and peer factors. DESIGN: Participant-level data were integrated from four long running longitudinal studies: Australian Temperament Project; Christchurch Health and Development Study; Mater Hospital and University of Queensland Study of Pregnancy; Victorian Adolescent Health Cohort Study. SETTING: Australia and New Zealand. PARTICIPANTS: Participants were assessed on multiple occasions between ages 13 and 30 years (from 1991-2012). Number of participants varied (up to N=9453) by analysis. MEASUREMENTS: Three patterns of alcohol use (frequent, heavy episodic, and problem drinking) were assessed prior to age 17. Thirty outcomes were assessed to age 30 spanning substance use and related problems, antisocial behavior, sexual risk-taking, accidents, socioeconomic functioning, mental health, and partner relationships. FINDINGS: After covariate adjustment, weekly drinking prior to age 17 was associated with a two to three-fold increase in the odds of binge drinking (OR: 2.14; 95%CI: 1.57-2.90), drink driving (OR: 2.78; 95%CI: 1.84-4.19), alcohol-related problems (OR: 3.04; 95%CI: 1.90-4.84), and alcohol dependence (OR: 3.30; 95%CI: 1.69-6.47) in adulthood. Frequency of drinking accounted for a greater proportion of the rate of most adverse outcomes than the other measures of alcohol use. Associations between frequent, heavy episodic, and problem drinking in adolescence and most non-alcohol outcomes were largely explained by shared risk factors for adolescent alcohol use and poor psychosocial functioning. CONCLUSIONS: Frequency of adolescent drinking predicts substance use problems in adulthood as much as, and possibly more than, heavy episodic and problem drinking independent of individual, family and peer predictors of those outcomes