Cross-Sectional Dating of Novel Haplotypes of HERV-K 113 and HERV-K 115 Indicate These Proviruses Originated in Africa before Homo sapiens

The human genome, human endogenous retroviruses (HERV), of which HERV-K113 and HERV-K115 are the only known full-length proviruses that are insertionally polymorphic. Although a handful of previously published papers have documented their prevalence in the global population; to date, there has been no report on their prevalence in the United States population. Here, we studied the geographic distribution of K113 and K115 among 156 HIV-1+ subjects from the United States, including African Americans, Hispanics, and Caucasians. In the individuals studied, we found higher insertion frequencies of K113 (21%) and K115 (35%) in African Americans compared with Caucasians (K113 9% and K115 6%) within the United States. We also report the presence of three single nucleotide polymorphism sites in the K113 5′ long terminal repeats (LTRs) and four in the K115 5′ LTR that together constituted four haplotypes for K113 and five haplotypes for K115. HERV insertion times can be estimated from the sequence differences between the 5′ and 3′ LTR of each insertion, but this dating method cannot be used with HERV-K115. We developed a method to estimate insertion times by applying coalescent inference to 5′ LTR sequences within our study population and validated this approach using an independent estimate derived from the genetic distance between K113 5′ and 3′ LTR sequences. Using our method, we estimated the insertion dates of K113 and K115 to be a minimum of 800,000 and 1.1 million years ago, respectively. Both these insertion dates predate the emergence of anatomically modern Homo sapiens

Resilience management during large-scale epidemic outbreaks

Assessing and managing the impact of large-scale epidemics considering only the individual risk and severity of the disease is exceedingly difficult and could be extremely expensive. Economic consequences, infrastructure and service disruption, as well as the recovery speed, are just a few of the many dimensions along which to quantify the effect of an epidemic on society's fabric. Here, we extend the concept of resilience to characterize epidemics in structured populations, by defining the system-wide critical functionality that combines an individual’s risk of getting the disease (disease attack rate) and the disruption to the system’s functionality (human mobility deterioration). By studying both conceptual and data-driven models, we show that the integrated consideration of individual risks and societal disruptions under resilience assessment framework provides an insightful picture of how an epidemic might impact society. In particular, containment interventions intended for a straightforward reduction of the risk may have net negative impact on the system by slowing down the recovery of basic societal functions. The presented study operationalizes the resilience framework, providing a more nuanced and comprehensive approach for optimizing containment schemes and mitigation policies in the case of epidemic outbreaks

Phylogeographic Analysis Elucidates the Influence of the Ice Ages on the Disjunct Distribution of Relict Dragonflies in Asia

Unusual biogeographic patterns of closely related groups reflect events in the past, and molecular analyses can help to elucidate these events. While ample research on the origin of disjunct distributions of different organism groups in the Western Paleartic has been conducted, such studies are rare for Eastern Palearctic organisms. In this paper we present a phylogeographic analysis of the disjunct distribution pattern of the extant species of the strongly cool-adapted Epiophlebia dragonflies from Asia. We investigated sequences of the usually more conserved 18 S rDNA and 28 S rDNA genes and the more variable sequences of ITS1, ITS2 and CO2 of all three currently recognised Epiophlebia species and of a sample of other odonatan species. In all genes investigated the degrees of similarity between species of Epiophlebia are very high and resemble those otherwise found between different populations of the same species in Odonata. This indicates that substantial gene transfer between these populations occurred in the comparatively recent past. Our analyses imply a wide distribution of the ancestor of extant Epiophlebia in Southeast Asia during the last ice age, when suitable habitats were more common. During the following warming phase, its range contracted, resulting in the current disjunct distribution. Given the strong sensitivity of these species to climatic parameters, the current trend to increasing global temperatures will further reduce acceptable habitats and seriously threaten the existences of these last representatives of an ancient group of Odonata

Chemical Defence in a Millipede: Evaluation and Characterization of Antimicrobial Activity of the Defensive Secretion from Pachyiulus hungaricus (Karsch, 1881) (Diplopoda, Julida, Julidae)

The chemical defence of the millipede Pachyiulus hungaricus is reported in the present paper, in which a chemical characterization is given and antimicrobial activity is determined. In total, independently of sex, 44 compounds were identified. All compounds belong to two groups: quinones and pentyl and hexyl esters of long-chain fatty acids. The relative abundances of quinones and non-quinones were 94.7% vs. 5.3% (males) and 87.3% vs. 12.7% (females), respectively. The two dominant quinones in both sexes were 2-methyl-1,4,-benzoquinone and 2-methoxy-3-methyl-1,4-benzoquinone. Antibacterial and antifungal activity of the defensive secretion was evaluated in vitro against seven bacterial strains and eight fungal species. With the aid of a dilution technique, the antimicrobial potential of the secretion and high sensitivity of all tested strains were confirmed. The lowest minimum concentrations of these compounds (0.20-0.25 mg/mL) were sufficient for inhibition of Aeromonas hydrophila, Listeria monocytogenes and Methicillin resistant Staphylococcus aureus (MRSA). The growth of eight tested fungal species was inhibited by slightly lower concentrations of the secretion, with Fusarium equisetias the most sensitive fungus and Aspergillus flavus as the most resistant. Values of MIC and MFC in the employed microdilution assay ranged from 0.10 to above 0.35 mg/m L. The given extract contains antimicrobial components potentially useful as therapeutic agents in the pharmaceutical and agricultural industries

Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases

OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies. METHODS: We meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases. RESULTS: Our analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study. CONCLUSIONS: We have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs