The Poultry Red Mite, Dermanyssus gallinae, travels far but not frequently, and takes up permanent residence on farms.

Management of Dermanyssus gallinae, a cosmopolitan hematophagous mite responsible for damage in layer poultry farming, is hampered by a lack of knowledge of its spatio-temporal population dynamics. Previous studies have shown that the circulation of this pest between farms is of strictly anthropogenic origin, that a mitochondrial haplogroup has been expanding on European farms since the beginning of the 21st century and that its local population growth may be particularly rapid. To refine our understanding of how D. gallinae spreads within and among farms, we characterized the genetic structure of mite populations at different spatial scales and sought to identify the main factors interrupting gene flow between poultry houses and between mitochondrial haplogroups. To this end, we selected and validated the first set of nuclear microsatellite markers for D. gallinae and sequenced a region of the CO1-encoding mitochondrial gene in a subsample of microsatellite-genotyped mites. We also tested certain conditions required for effective contamination of a poultry house through field experimentation, and conducted a survey of practices during poultry transfers. Our results confirm the role of poultry transport in the dissemination of mite populations, but the frequency of effective contamination after the introduction of contaminated material into poultry houses seems lower than expected. The high persistence of mites on farms, even during periods when poultry houses are empty and cleaned, and the very large number of nodes in the logistic network (large number of companies supplying pullets or transporting animals) undoubtedly explain the very high prevalence on farms. Substantial genetic diversity was measured in farm populations, probably as a result of the mite's known haplodiploid mode of sexual reproduction, coupled with the dense logistic network. The possibility of the occasional occurrence of asexual reproduction in this sexually reproducing mite was also revealed in our analyses, which could explain the extreme aggressiveness of its demographic dynamics under certain conditions.

Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study.

BACKGROUND: MRT5005, a codon-optimized CFTR mRNA, delivered by aerosol in lipid nanoparticles, was designed as a genotype-agnostic treatment for CF lung disease. METHODS: This was a randomized, double-blind, placebo-controlled Phase 1/2 study performed in the US. Adults with 2 severe class I and/or II CFTR mutations and baseline ppFEV1 values between 50 and 90% were randomized 3:1 (MRT5005: placebo). Six dose levels of MRT5005 (4, 8, 12, 16, 20, and 24 mg) or placebo (0.9% Sodium Chloride) were administered by nebulization. The single ascending dose cohort was treated over a range from 8 to 24 mg; the multiple ascending dose cohort received five weekly doses (range 8-20 mg); and the daily dosing cohort received five daily doses (4 mg). RESULTS: A total of 42 subjects were assigned to MRT5005 [31] or placebo [11]. A total of 14 febrile reactions were observed in 10 MRT5005-treated participants, which were mild [3] or moderate [11] in severity; two subjects discontinued related to these events. Additionally, two MRT5005-treated patients experienced hypersensitivity reactions, which were managed conservatively. The most common treatment emergent adverse events were cough and headache. No consistent effects on FEV1 were noted. CONCLUSIONS: MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed.

The effects of wet wipe pollution on the Asian clam, Corbicula fluminea (Mollusca: Bivalvia) in the River Thames, London.

The aim of the present study was to evaluate "flushable" and "non-flushable" wet wipes as a source of plastic pollution in the River Thames at Hammersmith, London and the impacts they have on the invasive Asian clam, Corbicula fluminea, in this watercourse. Surveys were conducted to assess whether the density of wet wipes along the foreshore upstream of Hammersmith Bridge affected the distribution of C. fluminea. High densities of wet wipes were associated with low numbers of clams and vice versa. The maximum wet wipe density recorded was 143 wipes m-2 and maximum clam density 151 individuals m-2. Clams adjacent to the wet wipe reefs were found to contain synthetic polymers including polypropylene (57%), polyethylene (9%), polyallomer (8%), nylon (8%) and polyester (3%). Some of these polymers may have originated from the wet wipe reefs.

Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.

BACKGROUND: Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF. METHODS: Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15). RESULTS: Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins. CONCLUSIONS: Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease. TRIAL REGISTRATION: United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).

Prevalence of Anaplasma phagocytophilum in small rodents in France.

Anaplasma phagocytophilum is an emerging zoonotic tick-borne pathogen affecting a wide range of mammals. Rodents are suspected to be natural reservoirs for this bacterium, but their role in the epidemiologic cycles affecting domestic animals and wild ungulates has not been demonstrated. This study aimed to improve our knowledge on A. phagocytophilum prevalence in Apodemus sylvaticus, A. flavicollis and Myodes glareolus using data collected in 2010 in one area in eastern France and in 2012-2013 in two others areas in western France. Rodents were captured in each site and infection was tested using qualitative real-time PCR assays on either blood or spleen samples. Prevalence showed high variability among sites. The highest prevalence was observed in the most eastern site (with an average infection rate of 22.8% across all species), whereas no rodent was found to be PCR positive in the south-west site and only 6.6% were positive in the north-west of France. Finally, a significant increase in prevalence was observed in autumn samples compared to spring samples in the north-west, but no change was found in the other two sites.

Relative fitness of a generalist parasite on two alternative hosts: a cross-infestation experiment to test host specialization of the hen flea Ceratophyllus gallinae (Schrank).

Host range is a key element of a parasite's ecology and evolution and can vary greatly depending on spatial scale. Generalist parasites frequently show local population structure in relation to alternative sympatric hosts (i.e. host races) and may thus be specialists at local scales. Here, we investigated local population specialization of a common avian nest-based parasite, the hen flea Ceratophyllus gallinae (Schrank), exploiting two abundant host species that share the same breeding sites, the great tit Parus major (Linnaeus) and the collared flycatcher Ficedula albicollis (Temminck). We performed a cross-infestation experiment of fleas between the two host species in two distinct study areas during a single breeding season and recorded the reproductive success of both hosts and parasites. In the following year, hosts were monitored again to assess the long-term impact of cross-infestation. Our results partly support the local specialization hypothesis: in great tit nests, tit fleas caused higher damage to their hosts than flycatcher fleas, and in collared flycatcher nests, flycatcher fleas had a faster larval development rates than tit fleas. However, these results were significant in only one of the two studied areas, suggesting that the location and history of the host population can modulate the specialization process. Caution is therefore called for when interpreting single location studies. More generally, our results emphasize the need to explicitly account for host diversity in order to understand the population ecology and evolutionary trajectory of generalist parasites.

CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.

Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.

Purification, biochemical characterization, and implications of an alkali-tolerant catalase from the spacecraft-associated and oxidation-resistant Acinetobacter gyllenbergii 2P01AA.

Herein, we report on the purification, characterization, and sequencing of catalase from Acinetobacter gyllenbergii 2P01AA, an extremely oxidation-resistant bacterium that was isolated from the Mars Phoenix spacecraft assembly facility. The Acinetobacter are dominant members of the microbial communities that inhabit spacecraft assembly facilities and consequently may serve as forward contaminants that could impact the integrity of future life-detection missions. Catalase was purified by using a 3-step chromatographic procedure, where mass spectrometry provided respective subunit and intact masses of 57.8 and 234.6 kDa, which were consistent with a small-subunit tetrameric catalase. Kinetics revealed an extreme pH stability with no loss in activity between pH 5 and 11.5 and provided respective kcat/Km and kcat values of ∼10(7) s(-1) M(-1) and 10(6) s(-1), which are among the highest reported for bacterial catalases. The amino acid sequence was deduced by in-depth peptide mapping, and structural homology suggested that the catalases from differing strains of A. gyllenbergii differ only at residues near the subunit interfaces, which may impact catalytic stability. Together, the kinetic, alkali-tolerant, and halotolerant properties of the catalase from A. gyllenbergii 2P01AA are significant, as they are consistent with molecular adaptations toward the alkaline, low-humidity, and potentially oxidizing conditions of spacecraft assembly facilities. Therefore, these results support the hypothesis that the selective pressures of the assembly facilities impact the microbial communities at the molecular level, which may have broad implications for future life-detection missions.

Standardised animal models of host microbial mutualism.

An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions.

Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Characterization of hydrogen peroxide-resistant Acinetobacter species isolated during the Mars Phoenix spacecraft assembly.

The microbiological inventory of spacecraft and the associated assembly facility surfaces represent the primary pool of forward contaminants that may impact the integrity of life-detection missions. Herein, we report on the characterization of several strains of hydrogen peroxide-resistant Acinetobacter, which were isolated during the Mars Phoenix lander assembly. All Phoenix-associated Acinetobacter strains possessed very high catalase specific activities, and the specific strain, A. gyllenbergii 2P01AA, displayed a survival against hydrogen peroxide (no loss in 100 mM H2O2 for 1 h) that is perhaps the highest known among Gram-negative and non-spore-forming bacteria. Proteomic characterizations reveal a survival mechanism inclusive of proteins coupled to peroxide degradation (catalase and alkyl hydroperoxide reductase), energy/redox management (dihydrolipoamide dehydrogenase), protein synthesis/folding (EF-G, EF-Ts, peptidyl-tRNA hydrolase, DnaK), membrane functions (OmpA-like protein and ABC transporter-related protein), and nucleotide metabolism (HIT family hydrolase). Together, these survivability and biochemical parameters support the hypothesis that oxidative tolerance and the related biochemical features are the measurable phenotypes or outcomes for microbial survival in the spacecraft assembly facilities, where the low-humidity (desiccation) and clean (low-nutrient) conditions may serve as selective pressures. Hence, the spacecraft-associated Acinetobacter, due to the conferred oxidative tolerances, may ultimately hinder efforts to reduce spacecraft bioburden when using chemical sterilants, thus suggesting that non-spore-forming bacteria may need to be included in the bioburden accounting for future life-detection missions.

Outline-based morphometrics, an overlooked method in arthropod studies?

Modern methods allow a geometric representation of forms, separating size and shape. In entomology, as well as in many other fields involving arthropod studies, shape variation has proved useful for species identification and population characterization. In medical entomology, it has been applied to very specific questions such as population structure, reinfestation of insecticide-treated areas and cryptic species recognition. For shape comparisons, great importance is given to the quality of landmarks in terms of comparability. Two conceptually and statistically separate approaches are: (i) landmark-based morphometrics, based on the relative position of a few anatomical "true" or "traditional" landmarks, and (ii) outline-based morphometrics, which captures the contour of forms through a sequence of close "pseudo-landmarks". Most of the studies on insects of medical, veterinary or economic importance make use of the landmark approach. The present survey makes a case for the outline method, here based on elliptic Fourier analysis. The collection of pseudo-landmarks may require the manual digitization of many points and, for this reason, might appear less attractive. It, however, has the ability to compare homologous organs or structures having no landmarks at all. This strength offers the possibility to study a wider range of anatomical structures and thus, a larger range of arthropods. We present a few examples highlighting its interest for separating close or cryptic species, or characterizing conspecific geographic populations, in a series of different vector organisms. In this simple application, i.e. the recognition of close or cryptic forms, the outline approach provided similar scores as those obtained by the landmark-based approach.

Constructive and Destructive Marital Conflict, Parenting, and Children's School and Social Adjustment.

This study addresses the links between destructive and constructive marital conflict and mothers' and fathers' parenting to understand associations with children's social and school adjustment. Multi-method, longitudinal assessments of 235 mothers, fathers, and children (129 girls) were collected across kindergarten, first, and second grades (ages 5-7 at Time 1; ages 7-9 at Time 3). Whereas constructive marital conflict was related to both mothers' and fathers' warm parenting, destructive marital conflict was only linked to fathers' use of inconsistent discipline. In turn, both mothers' and fathers' use of psychological control was related to children's school adjustment, and mothers' warmth was related to children's social adjustment. Reciprocal links between constructs were also explored, supporting associations between destructive marital conflict and mothers' and fathers' inconsistent discipline. The merit of examining marital conflict and parenting as multidimensional constructs is discussed in relation to understanding the processes and pathways within families that affect children's functioning.

Intestinal bacteria induce TSLP to promote mutualistic T-cell responses.

Thymic stromal lymphopoietin (TSLP) is constitutively expressed in the intestine and is known to regulate inflammation in models of colitis. We show that steady-state TSLP expression requires intestinal bacteria and has an important role in limiting the expansion of colonic T helper type 17 (Th17) cells. Inappropriate expansion of the colonic Th17 cells occurred in response to an entirely benign intestinal microbiota, as determined following the colonization of germ-free C57BL/6 or TSLPR(-/-) mice with the altered Schaedler flora (ASF). TSLP-TSLPR (TSLP receptor) interactions also promoted the expansion of colonic Helios(-)Foxp3(+) regulatory T cells, necessary for the control of inappropriate Th17 responses following ASF bacterial colonization. In summary, these data reveal an important role for TSLP-TSLPR signaling in promoting steady-state mutualistic T-cell responses following intestinal bacterial colonization.

Insights into the extremotolerance of Acinetobacter radioresistens 50v1, a gram-negative bacterium isolated from the Mars Odyssey spacecraft.

The microbiology of the spacecraft assembly process is of paramount importance to planetary exploration, as the biological contamination that can result from remote-enabled spacecraft carries the potential to impact both life-detection experiments and extraterrestrial evolution. Accordingly, insights into the mechanisms and range of extremotolerance of Acinetobacter radioresistens 50v1, a Gram-negative bacterium isolated from the surface of the preflight Mars Odyssey orbiter, were gained by using a combination of microbiological, enzymatic, and proteomic methods. In summary, A. radioresistens 50v1 displayed a remarkable range of survival against hydrogen peroxide and the sequential exposures of desiccation, vapor and plasma phase hydrogen peroxide, and ultraviolet irradiation. The survival is among the highest reported for non-spore-forming and Gram-negative bacteria and is based upon contributions from the enzyme-based degradation of H(2)O(2) (catalase and alkyl hydroperoxide reductase), energy management (ATP synthase and alcohol dehydrogenase), and modulation of the membrane composition. Together, the biochemical and survival features of A. radioresistens 50v1 support a potential persistence on Mars (given an unintended or planned surface landing of the Mars Odyssey orbiter), which in turn may compromise the scientific integrity of future life-detection missions.

Trans-oceanic host dispersal explains high seabird tick diversity on Cape Verde islands.

Parasites represent ideal models for unravelling biogeographic patterns and mechanisms of diversification on islands. Both host-mediated dispersal and within-island adaptation can shape parasite island assemblages. In this study, we examined patterns of genetic diversity and structure of Ornithodoros seabird ticks within the Cape Verde Archipelago in relation to their global phylogeography. Contrary to expectations, ticks from multiple, geographically distant clades mixed within the archipelago. Trans-oceanic colonization via host movements probably explains high local tick diversity, contrasting with previous research that suggests little large-scale dispersal in these birds. Although host specificity was not obvious at a global scale, host-associated genetic structure was found within Cape Verde colonies, indicating that post-colonization adaptation to specific hosts probably occurs. These results highlight the role of host metapopulation dynamics in the evolutionary ecology and epidemiology of avian parasites and pathogens.

The function of secretory IgA in the context of the intestinal continuum of adaptive immune responses in host-microbial mutualism.

The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into the continuum of intestinal CD4 T cell responses, to achieve a mutualistic relationship between the intestinal commensal microbiota and the host.

Cortical sulcal areas in baboons (Papio hamadryas spp.) with generalized interictal epileptic discharges on scalp EEG.

Brain MRI studies in people with idiopathic generalized epilepsies demonstrate regional morphometric differences, though variable in magnitude and location. As the baboon provides an excellent electroclinical and neuroimaging model for photosensitive generalized epilepsy in humans, this study evaluated MRI volumetric and morphometric differences between baboons with interictal epileptic discharges (IEDs) on scalp EEG and baboons with normal EEG studies. Seventy-seven baboons underwent high-resolution brain MRI and scalp EEG studies. The scans were acquired using an 8-channel primate head coil (Siemens TRIO 3T scanner, Erlangen, Germany). After spatial normalization, sulcal measurements were obtained by object-based-morphology methods. One-hour scalp EEG studies were performed in animals sedated with ketamine. Thirty-eight (22F/16M) baboons had normal EEGs (IED-), while 39 (22F/17M) had generalized IEDs (IED+). The two groups were compared for age, total brain volume, and sulcal areas (Hotelling's Trace) as well as between-subjects comparison of 11 individual sulcal areas (averaged between left and right hemispheres). There were no differences between IED- and IED+ groups with respect to age or total brain (gray or white matter) volume, and multivariate tests demonstrated a marginally significant decrease of sulcal areas in IED+ baboons (p=0.075). Tests of between-subjects effects showed statistically significant decreases in the intraparietal (p=0.002), central (p=0.03) and cingulate sulci (p=0.02), and marginal decreases involving the lunate (p=0.07) and superior temporal sulci (p=0.08). Differences in sulcal areas in IED+ baboons may reflect global developmental abnormalities, while decreases of areas of specific sulci reflect anatomical markers for potential generators or cortical nodes of the networks underlying spontaneous seizures and photosensitivity in the baboon.

The immune geography of IgA induction and function.

The production of immunoglobulin A (IgA) in mammals exceeds all other isotypes, and it is mostly exported across mucous membranes. The discovery of IgA and the realization that it dominates humoral mucosal immunity, in contrast to the IgG dominance of the systemic immune system, was early evidence for the distinct nature of mucosal immunology. It is now clear that IgA can function in high-affinity modes for neutralization of toxins and pathogenic microbes, and as a low-affinity system to contain the dense commensal microbiota within the intestinal lumen. The basic map of induction of IgA B cells in the Peyer's patches, which then circulate through the lymph and bloodstream to seed the mucosa with precursors of plasma cells that produce dimeric IgA for export through the intestinal epithelium, has been known for more than 30 years. In this review, we discuss the mechanisms underlying selective IgA induction of mucosal B cells for IgA production and the immune geography of their homing characteristics. We also review the functionality of secretory IgA directed against both commensal organisms and pathogens.

The population genetic structure of vectors and our understanding of disease epidemiology.

Understanding and predicting disease epidemiology relies on clear knowledge about the basic biology of the organisms involved. Despite the key role that arthropod vectors play in disease dynamics and detailed mechanistic work on the vector-pathogen interface, little information is often available about how these populations function under natural conditions. Population genetic studies can help fill this void by providing information about the taxonomic status of species, the spatial limits of populations, and the nature of gene flow among populations. Here, I briefly review different types of population genetic structure and some recent examples of where this information has provided key elements for understanding pathogen transmission in tick-borne systems.