Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment

Acknowledgements The authors wish to thank Mark Stares, Richard Rance, and other members of the Wellcome Trust Sanger Institute’s 454 sequencing team for generating the 16S rRNA gene data. Lili Fox Vélez provided editorial support. Funding IA, JNP, and MP were partly supported by the NIH, grants R01-AI-100947 to MP, and R21-GM-107683 to Matthias Chung, subcontract to MP. JNP was partly supported by an NSF graduate fellowship number DGE750616. IA, JNP, BRL, OCS and MP were supported in part by the Bill and Melinda Gates Foundation, award number 42917 to OCS. JP and AWW received core funding support from The Wellcome Trust (grant number 098051). AWW, and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS).Peer reviewedPublisher PD

Lack of association between COMT gene and deficit/nondeficit schizophrenia

BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val(158)Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val(158)Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65). RESULTS: There was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases. CONCLUSION: Results from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia

Molecular Epidemiology of O139 Vibrio cholerae: Mutation, Lateral Gene Transfer, and Founder Flush

Vibrio cholerae in O-group 139 was first isolated in 1992 and by 1993 had been found throughout the Indian subcontinent. This epidemic expansion probably resulted from a single source after a lateral gene transfer (LGT) event that changed the serotype of an epidemic V. cholerae O1 El Tor strain to O139. However, some studies found substantial genetic diversity, perhaps caused by multiple origins. To further explore the relatedness of O139 strains, we analyzed nine sequenced loci from 96 isolates from patients at the Infectious Diseases Hospital, Calcutta, from 1992 to 2000. We found 64 novel alleles distributed among 51 sequence types. LGT events produced three times the number of nucleotide changes compared to mutation. In contrast to the traditional concept of epidemic spread of a homogeneous clone, the establishment of variant alleles generated by LGT during the rapid expansion of a clonal bacterial population may be a paradigm in infections and epidemics

Convergence towards a European strategic culture? A constructivist framework for explaining changing norms.

The article contributes to the debate about the emergence of a European strategic culture to underpin a European Security and Defence Policy. Noting both conceptual and empirical weaknesses in the literature, the article disaggregates the concept of strategic culture and focuses on four types of norms concerning the means and ends for the use of force. The study argues that national strategic cultures are less resistant to change than commonly thought and that they have been subject to three types of learning pressures since 1989: changing threat perceptions, institutional socialization, and mediatized crisis learning. The combined effect of these mechanisms would be a process of convergence with regard to strategic norms prevalent in current EU countries. If the outlined hypotheses can be substantiated by further research the implications for ESDP are positive, especially if the EU acts cautiously in those cases which involve norms that are not yet sufficiently shared across countries

Prevalence of classic, MLB-clade and VA-clade Astroviruses in Kenya and The Gambia.

BACKGROUND: Infectious diarrhea leads to significant mortality in children, with 40 % of these deaths occurring in Africa. Classic human astroviruses are a well-established etiology of diarrhea. In recent years, seven novel astroviruses have been discovered (MLB1, MLB2, MLB3, VA1/HMO-C, VA2/HMO-B, VA3/HMO-A, VA4); however, there have been few studies on their prevalence or potential association with diarrhea. METHODS: To investigate the prevalence and diversity of these classic and recently described astroviruses in a pediatric population, a case-control study was performed. Nine hundred and forty nine stools were previously collected from cases of moderate-to-severe diarrhea and matched controls of patients less than 5 years of age in Kenya and The Gambia. RT-PCR screening was performed using pan-astrovirus primers. RESULTS: Astroviruses were present in 9.9 % of all stool samples. MLB3 was the most common astrovirus with a prevalence of 2.6 %. Two subtypes of MLB3 were detected that varied based on location in Africa. In this case-control study, Astrovirus MLB1 was associated with diarrhea in Kenya, whereas Astrovirus MLB3 was associated with the control state in The Gambia. Classic human astrovirus was not associated with diarrhea in this study. Unexpectedly, astroviruses with high similarity to Canine Astrovirus and Avian Nephritis Virus 1 and 2 were also found in one case of diarrhea and two control stools respectively. CONCLUSIONS: Astroviruses including novel MLB- and VA-clade members are commonly found in pediatric stools in Kenya and The Gambia. The most recently discovered astrovirus, MLB3, was the most prevalent and was found more commonly in control stools in The Gambia, while astrovirus MLB1 was associated with diarrhea in Kenya. Furthermore, a distinct subtype of MLB3 was noted, as well as 3 unanticipated avian or canine astroviruses in the human stool samples. As a result of a broadly reactive PCR screen for astroviruses, new insight was gained regarding the epidemiology of astroviruses in Africa, where a large proportion of diarrheal morbidity and mortality occur

Seasonal Cholera from Multiple Small Outbreaks, Rural Bangladesh

Clinical and environmental Vibrio cholerae organisms collected from February 2004 through April 2005 were systematically isolated from 2 rural Bangladeshi locales. Their genetic relatedness was evaluated at 5 loci that contained a variable number of tandem repeats (VNTR). The observed minimal overlap in VNTR patterns between the 2 communities was consistent with sequential, small outbreaks from local sources

Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition

Acknowledgments This work was funded in part by the William and Melinda Gates Foundation, award 42917 to JPN and OCS; US National Institutes of Health grants 5R01HG005220 to HCB, 5R01HG004885 to MP; US National Science Foundation Graduate Research Fellowship award DGE0750616 to JNP; AWW and JP are funded by The Wellcome Trust (Grant No. WT098051).Peer reviewedPublisher PD

A framework for assessing 16S rRNA marker-gene survey data analysis methods using mixtures.

There are a variety of bioinformatic pipelines and downstream analysis methods for analyzing 16S rRNA marker-gene surveys. However, appropriate assessment datasets and metrics are needed as there is limited guidance to decide between available analysis methods. Mixtures of environmental samples are useful for assessing analysis methods as one can evaluate methods based on calculated expected values using unmixed sample measurements and the mixture design. Previous studies have used mixtures of environmental samples to assess other sequencing methods such as RNAseq. But no studies have used mixtures of environmental to assess 16S rRNA sequencing. We developed a framework for assessing 16S rRNA sequencing analysis methods which utilizes a novel two-sample titration mixture dataset and metrics to evaluate qualitative and quantitative characteristics of count tables. Our qualitative assessment evaluates feature presence/absence exploiting features only present in unmixed samples or titrations by testing if random sampling can account for their observed relative abundance. Our quantitative assessment evaluates feature relative and differential abundance by comparing observed and expected values. We demonstrated the framework by evaluating count tables generated with three commonly used bioinformatic pipelines: (i) DADA2 a sequence inference method, (ii) Mothur a de novo clustering method, and (iii) QIIME an open-reference clustering method. The qualitative assessment results indicated that the majority of Mothur and QIIME features only present in unmixed samples or titrations were accounted for by random sampling alone, but this was not the case for DADA2 features. Combined with count table sparsity (proportion of zero-valued cells in a count table), these results indicate DADA2 has a higher false-negative rate whereas Mothur and QIIME have higher false-positive rates. The quantitative assessment results indicated the observed relative abundance and differential abundance values were consistent with expected values for all three pipelines. We developed a novel framework for assessing 16S rRNA marker-gene survey methods and demonstrated the framework by evaluating count tables generated with three bioinformatic pipelines. This framework is a valuable community resource for assessing 16S rRNA marker-gene survey bioinformatic methods and will help scientists identify appropriate analysis methods for their marker-gene surveys.https://doi.org/10.1186/s40168-020-00812-

Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus USA300 Clone

An increase in SSTIs suggests that USA300 is becoming more virulent with a greater propensity to cause SSTIs

Microbiota that affect risk for shigellosis in children in low-income countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.publishedVersio