Molecular genotyping of bacillus anthracis strains from Georgia and northeastern part of Turkey

Bacillus anthracis is the causal agent of anthrax and has a history of use as a biological weapon. Anthrax cases occur worldwide and the disease is endemic in certain regions. Here we describe a study of the genetic diversity of B. anthracis strains in two endemic areas: The country of Georgia and the Kars region of Turkey. Thirty Turkish isolates and thirty Georgian isolates were subjected to Single Nucleotide Polymorphism (SNP) sub typing, followed by higher-resolution genotyping using 25-loci variable-number tandem repeat analysis (MLVA-25). Canonical SNP typing indicated that Turkish strains belonged to both the A.Br.003 linage and the Australian 94 lineage. In light of a recent analysis that placed the majority of Georgian B. anthracis isolates in one phylogenetic group, we screened the Turkish strains using a previously developed Georgian SNP panel. Minimal diversity was observed among the Kars strains within the Georgian SNP lineage: all 30 of these strains grouped with A.Br.026, ten strains were derived from A.Br.028, and only two isolates belonged to A.Br.029. According to the results of MLVA-25 genotyping, all 30 Turkish strains belong to two clusters. Cluster A is more diverse than cluster B. Our results suggest that B. anthracis strains originating from Georgia and the northeastern part of Turkey are genetically interrelated, which could be explained by the geographic proximity of the countries

Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control

BACKGROUND: Release of gene-drive mutants to suppress Anopheles mosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element of Anopheles copulation being acoustic courtship. We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages. METHODS: Anopheles rely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of the doublesex gene (dsxF) on the wing beat frequency (WBF; measured as flight tone) of males (XY) and females (XX) in homozygous dsxF- mutants (dsxF-/-), heterozygous dsxF- carriers (dsxF+/-) and G3 dsxF+ controls (dsxF+/+). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. RESULTS: A previous study showed an altered phenotype only for dsxF-/- females, who appear intersex, suggesting that the female-specific dsxF allele is haplosufficient. We identified significant, dose-dependent increases in the WBF of both dsxF-/- and dsxF+/- females compared to dsxF+/+ females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of control dsxF+/+ females than to those of dsxF+/- and dsxF-/- females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls. CONCLUSIONS: A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm that dsxF disruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects of dsxF appear dose-dependent rather than haplosufficient

Local Delivery of Therapeutics to the Inner Ear: The State of the Science

BACKGROUND: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics. METHODS: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently. RESULTS: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker. CONCLUSION: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics

Early phase trials of novel hearing therapeutics: Avenues and opportunities

Novel hearing therapeutics are rapidly progressing along the innovation pathway and into the clinical trial domain. Because these trials are new to the hearing community, they come with challenges in terms of trial design, regulation and delivery. In this paper, we address the key scientific and operational issues and outline the opportunities for interdisciplinary and international collaboration these trials offer. Vital to the future successful implementation of these therapeutics is to evaluate their potential for adoption into healthcare systems, including consideration of their health economic value. This requires early engagement with all stakeholder groups along the hearing innovation pathway

Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

Hitting the right note at the right time: Circadian control of audibility in Anopheles mosquito mating swarms is mediated by flight tones

Mating swarms of malaria mosquitoes form every day at sunset throughout the tropical world. They typically last less than 30 minutes. Activity must thus be highly synchronized between the sexes. Moreover, males must identify the few sporadically entering females by detecting the females’ faint flight tones. We show that the Anopheles circadian clock not only ensures a tight synchrony of male and female activity but also helps sharpen the males’ acoustic detection system: By raising their flight tones to 1.5 times the female flight tone, males enhance the audibility of females, specifically at swarm time. Previously reported “harmonic convergence” events are only a random by-product of the mosquitoes’ flight tone variance and not a signature of acoustic interaction between males and females. The flight tones of individual mosquitoes occupy narrow, partly non-overlapping frequency ranges, suggesting that the audibility of individual females varies across males

Monotone iterative procedure and systems of a finite number of nonlinear fractional differential equations

The aim of the paper is to present a nontrivial and natural extension of the comparison result and the monotone iterative procedure based on upper and lower solutions, which were recently established in (Wang et al. in Appl. Math. Lett. 25:1019-1024, 2012), to the case of any finite number of nonlinear fractional differential equations.The author is very grateful to the reviewers for the remarks, which improved the final version of the manuscript. This article was financially supported by University of Łódź as a part of donation for the research activities aimed at the development of young scientists, grant no. 545/1117

Sex and species specific hearing mechanisms in mosquito flagellar ears

Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes (Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity

Do real interest rates converge across Latin american countries?

In this study, we apply the Sequential Panel Selection Method (SPSM), pro- posed by Chortareas and Kapetanios (Journal of Banking and Finance 33:390–404, 2009), to investigate and assess the non-stationary properties of the real interest rate parity (RIRP) for fourteen Latin American countries. Utilizing the SPSM, we can classify the entire panel into a group of stationary series and a group of non-stationary series. We clearly identify how many and which series in the panel are stationary processes and provide robust evidence that clearly indicate RIRP holds true for ten countries. Our findings note that these countries’ real interest rate convergence is a mean reversion toward RIRP equilib- rium values in a non-linear way. Our results have important policy implications for these Latin American countries under study.info:eu-repo/semantics/publishedVersio

Molecular genotyping of bacillus anthracis strains from Georgia and northeastern part of Turkey

Bacillus anthracis is the causal agent of anthrax and has a history of use as a biological weapon. Anthrax cases occur worldwide and the disease is endemic in certain regions. Here we describe a study of the genetic diversity of B. anthracis strains in two endemic areas: The country of Georgia and the Kars region of Turkey. Thirty Turkish isolates and thirty Georgian isolates were subjected to Single Nucleotide Polymorphism (SNP) sub typing, followed by higher-resolution genotyping using 25-loci variable-number tandem repeat analysis (MLVA-25). Canonical SNP typing indicated that Turkish strains belonged to both the A.Br.003 linage and the Australian 94 lineage. In light of a recent analysis that placed the majority of Georgian B. anthracis isolates in one phylogenetic group, we screened the Turkish strains using a previously developed Georgian SNP panel. Minimal diversity was observed among the Kars strains within the Georgian SNP lineage: all 30 of these strains grouped with A.Br.026, ten strains were derived from A.Br.028, and only two isolates belonged to A.Br.029. According to the results of MLVA-25 genotyping, all 30 Turkish strains belong to two clusters. Cluster A is more diverse than cluster B. Our results suggest that B. anthracis strains originating from Georgia and the northeastern part of Turkey are genetically interrelated, which could be explained by the geographic proximity of the countries