A hitchhikers guide to the Galápagos: co-phylogeography of Galápagos mockingbirds and their parasites

Background: Parasites are evolutionary hitchhikers whose phylogenies often track the evolutionary history of their hosts. Incongruence in the evolutionary history of closely associated lineages can be explained through a variety of possible events including host switching and host independent speciation. However, in recently diverged lineages stochastic population processes, such as retention of ancestral polymorphism or secondary contact, can also explain discordant genealogies, even in fully co-speciating taxa. The relatively simple biogeographic arrangement of the Galapagos archipelago, compared with mainland biomes, provides a framework to identify stochastic and evolutionary informative components of genealogic data in these recently diverged organisms. Results: Mitochondrial DNA sequences were obtained for four species of Galapagos mockingbirds and three sympatric species of ectoparasites - two louse and one mite species. These data were complemented with nuclear EF1 alpha sequences in selected samples of parasites and with information from microsatellite loci in the mockingbirds. Mitochondrial sequence data revealed differences in population genetic diversity between all taxa and varying degrees of topological congruence between host and parasite lineages. A very low level of genetic variability and lack of congruence was found in one of the louse parasites, which was excluded from subsequent joint analysis of mitochondrial data. The reconciled multi-species tree obtained from the analysis is congruent with both the nuclear data and the geological history of the islands. Conclusions: The gene genealogies of Galapagos mockingbirds and two of their ectoparasites show strong phylogeographic correlations, with instances of incongruence mostly explained by ancestral genetic polymorphism. A third parasite genealogy shows low levels of genetic diversity and little evidence of co-phylogeny with their hosts. These differences can mostly be explained by variation in life-history characteristics, primarily host specificity and dispersal capabilities. We show that pooling genetic data from organisms living in close ecological association reveals a more accurate phylogeographic history for these taxa. Our results have implications for the conservation and taxonomy of Galapagos mockingbirds and their parasites

Flemish population-based cancer screening programs: impact of COVID-19 related shutdown on short-term key performance indicators

Background Many breast, colorectal, and cervical cancer screening programs were disrupted due to the COVID-19 pandemic. This study aimed to estimate the short-term impact of the temporary shutdown (from March until May- June) of the cancer screening programs invitations in Flanders (Belgium) by looking at invitation coverage, percentage of people screened after invitation and the screening interval. Methods Yearly invitation coverage was calculated as the number of people who received an invitation, as a proportion of the people who should have received an invitation that year. Weekly response to the invitation was calculated as the number of people who were screened within 40 days of their date of invitation, as a percentage of the people who received an invitation that week (as a proxy for willingness to screen). Weekly screening interval was calculated as the mean number of months between the current screening and the previous screening of all the people who screened that week. The two last indicators were calculated for each week in 2019 and 2020, after which the difference between that week's value in 2020 and 2019 with 95% confidence intervals. Results of these two indicators were also analysed after stratification for gender, age and participation history. Results Invitation coverage was not impacted in the colorectal and cervical cancer screening program. In the breast cancer screening program invitation coverage went down from 97.5% (2019) to 88.7% (2020), and the backlog of invitations was largely resolved in the first six months of 2021. The willingness to screen was minimally influenced by COVID-19. The breast cancer screening program had a temporary increase in screening interval in the first months following the restart after COVID-19 related shutdown, when it was on average 2.1 months longer than in 2019. Conclusions Willingness to screen was minimally influenced by COVID-19, but there may be an influence on screening coverage because of lower invitation coverage, mainly for the for breast Cancer Screening Program. The increases in screening intervals for the three Cancer Screening Program seem reasonable and would probably not significantly increase the risk of delayed screening cancer diagnoses. When restarting a Cancer Screening Program after a COVID-19 related shutdown, monitoring is crucial.Clinical epidemiolog

Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation

Background Skin-based immunotherapy of type 1 allergies has recently been re-investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)-induced lung inflammation to explore the potential of laser-facilitated epicutaneous allergen-specific treatment. Methods Mice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented D pteronyssinus extract via laser-generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole-body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM-specific IgG subclass antibodies were determined by ELISA. Serum as well as cell-bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry. Results Immunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred. Conclusion Allergen-specific immunotherapy with depigmented HDM extract via laser-generated skin micropores offers a safe and effective treatment option for HDM-induced allergy and lung inflammation

Laser‐facilitated epicutaneous immunotherapy with hypoallergenic beta‐glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma

Background Allergen-specific immunotherapy via the skin targets a tissue rich in antigen-presenting cells, but can be associated with local and systemic side effects. Allergen-polysaccharide neoglycogonjugates increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects. Objective We investigated the immunogenicity, allergenicity, and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA). Methods The biological activity of LamOVA was characterized in vitro using bone marrow-derived dendritic cells. Immunogenicity and therapeutic efficacy were analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin, and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T-cell polarization were assessed. Results Conjugation of laminarin to ovalbumin reduced its IgE binding capacity fivefold and increased its immunogenicity threefold in terms of IgG generation. EPIT with LamOVA induced significantly higher IgG levels than OVA, matching the levels induced by s.c. injection of OVA/alum (SCIT). EPIT was equally effective as SCIT in terms of blocking IgG induction and suppression of lung inflammation and airway hyperresponsiveness, but SCIT was associated with higher levels of therapy-induced IgE and TH2 cytokines. EPIT with LamOVA induced significantly lower local skin reactions during therapy compared to unconjugated OVA. Conclusion Conjugation of ovalbumin to laminarin increased its immunogenicity while at the same time reducing local side effects. LamOVA EPIT via laser-generated micropores is safe and equally effective compared to SCIT with alum, without the need for adjuvant

In silico design of Phl p 6 variants with altered Fold-Stability significantly impacts antigen processing, immunogenicity and immune polarization

Introduction: Understanding, which factors determine the immunogenicity and immune polarizing properties of proteins, is an important prerequisite for designing better vaccines and immunotherapeutics. While extrinsic immune modulatory factors such as pathogen associated molecular patterns are well-understood, far less is known about the contribution of protein inherent features. Protein fold-stability represents such an intrinsic feature contributing to immunogenicity and immune polarization by influencing the amount of peptide-MHC II complexes (pMHCII). Here, we investigated how modulation of the fold-stability of the grass pollen allergen Phl p 6 affects its ability to stimulate immune responses and T cell polarization. Methods: MAESTRO software was used for in silico prediction of stabilizing or destabilizing point mutations. Mutated proteins were expressed in E. coli, and their thermal stability and resistance to endolysosomal proteases was determined. Resulting peptides were analyzed by mass spectrometry. The structure of the most stable mutant protein was assessed by X-ray crystallography. We evaluated the capacity of the mutants to stimulate T cell proliferation in vitro, as well as antibody responses and T cell polarization in vivo in an adjuvant-free BALB/c mouse model. Results: In comparison to wild-type protein, stabilized or destabilized mutants displayed changes in thermal stability ranging from −5 to +14°. While highly stabilized mutants were degraded very slowly, destabilization led to faster proteolytic processing in vitro. This was confirmed in BMDCs, which processed and presented the immunodominant epitope from a destabilized mutant more efficiently compared to a highly stable mutant. In vivo, stabilization resulted in a shift in immune polarization from TH2 to TH1/TH17 as indicated by higher levels of IgG2a and increased secretion of TNF-α, IFN-γ, IL-17, and IL-21. Conclusion: MAESTRO software was very efficient in detecting single point mutations that increase or reduce fold-stability. Thermal stability correlated well with the speed of proteolytic degradation and presentation of peptides on the surface of dendritic cells in vitro. This change in processing kinetics significantly influenced the polarization of T cell responses in vivo. Modulating the fold-stability of proteins thus has the potential to optimize and polarize immune responses, which opens the door to more efficient design of molecular vaccines

Effects of the integrated galactic IMF on the chemical evolution of the solar neighbourhood

The initial mass function determines the fraction of stars of different intial mass born per stellar generation. In this paper, we test the effects of the integrated galactic initial mass function (IGIMF) on the chemical evolution of the solar neighbourhood. The IGIMF (Weidner & Kroupa 2005) is computed from the combination of the stellar intial mass function (IMF), i.e. the mass function of single star clusters, and the embedded cluster mass function, i.e. a power law with index beta. By taking into account also the fact that the maximum achievable stellar mass is a function of the total mass of the cluster, the IGIMF becomes a time-varying IMF which depends on the star formation rate. We applied this formalism to a chemical evolution model for the solar neighbourhood and compared the results obtained by assuming three possible values for beta with the results obtained by means of a standard, well-tested, constant IMF. In general, a lower absolute value of beta implies a flatter IGIMF, hence a larger number of massive stars and larger metal ejection rates. This translates into higher type Ia and II supernova rates, higher mass ejection rates from massive stars and a larger amount of gas available for star formation, coupled with lower present-day stellar mass densities. (abridged) We also discuss the importance of the present day stellar mass function (PDMF) in providing a way to disentangle among various assumptions for beta. Our results indicate that the model adopting the IGIMF computed with beta ~2 should be considered the best since it allows us to reproduce the observed PDMF and to account for most of the chemical evolution constraints considered in this work.Comment: 22 pages, 19 figure

A new comprehensive set of elemental abundances in DLAs III. Star formation histories

We obtained comprehensive sets of elemental abundances for eleven damped Ly-alpha systems (DLAs) at z_DLA=1.7-2.5. In Paper I of this series, we showed for three DLA galaxies that we can derive their star formation histories and ages from a detailed comparison of their intrinsic abundance patterns with chemical evolution models. We determine in this paper the star formation properties of six additional DLA galaxies. The derived results confirm that no single star formation history explains the diverse sets of abundance patterns in DLAs. We demonstrate that the various star formation histories reproducing the DLA abundance patterns are typical of local irregular, dwarf starburst and quiescent spiral galaxies. Independent of the star formation history, the DLAs have a common characteristic of being weak star forming galaxies; models with high star formation efficiencies are ruled out. All the derived DLA star formation rates per unit area are moderate or low, with values between -3.2 < log SFR < -1.1 M_sol yr^{-1} kpc^{-2}. The DLA abundance patterns require a large spread in ages ranging from 20 Myr up to 3 Gyr. The oldest DLA in our sample is observed at z_DLA=1.864 with an age estimated to more than 3 Gyr; it nicely indicates that galaxies were already forming at z_f>10. But, most of the DLAs show ages much younger than that of the Universe at the epoch of observation. Young galaxies thus seem to populate the high redshift Universe at z>2, suggesting relatively low redshifts of formation (z~3) for most high-redshift galaxies. The DLA star formation properties are compared with those of other high-redshift galaxies identified in deep imaging surveys with the aim of obtaining a global picture of high-redshift objects.Comment: 19 pages, 11 figures, Accepted for publication in A&

Workplace experience of radiographers: impact of structural and interpersonal interventions

PURPOSE: Within the framework of organisational development, an assessment of the workplace experience of radiographers (RGs) was conducted. The aims of this study were to develop structural and interpersonal interventions and to prove their effectiveness and feasibility. METHODS: A questionnaire consisting of work-related factors, e.g. time management and communication, and two validated instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented and a follow-up survey (T2) was performed 18 months after the initial assessment. RESULTS: At T1, areas with highest dissatisfaction were communication and time management for ambulant patients (bad/very bad, 57% each). The interventions addressed adaptation of work plans, coaching in developing interpersonal and team leadership skills, and regular team meetings. The follow-up survey (T2) showed significantly improved communication and cooperation within the team and improved qualification opportunities, whereas no significant changes could be identified in time management and in the workplace-related scales 'effort' expended at work and 'reward' received in return for the effort. CONCLUSION: Motivating workplace experience is important for high-level service quality and for attracting well-qualified radiographers to work at a place and to stay in the team for a longer period

Variance in Centrality within Rock Hyrax Social Networks Predicts Adult Longevity

BACKGROUND: In communal mammals the levels of social interaction among group members vary considerably. In recent years, biologists have realized that within-group interactions may affect survival of the group members. Several recent studies have demonstrated that the social integration of adult females is positively associated with infant survival, and female longevity is affected by the strength and stability of the individual social bonds. Our aim was to determine the social factors that influence adult longevity in social mammals. METHODOLOGY/PRINCIPAL FINDINGS: As a model system, we studied the social rock hyrax (Procavia capensis), a plural breeder with low reproductive skew, whose groups are mainly composed of females. We applied network theory using 11 years of behavioral data to quantify the centrality of individuals within groups, and found adult longevity to be inversely correlated to the variance in centrality. In other words, animals in groups with more equal associations lived longer. Individual centrality was not correlated with longevity, implying that social tension may affect all group members and not only the weakest or less connected ones. CONCLUSIONS/SIGNIFICANCE: Our novel findings support previous studies emphasizing the adaptive value of social associations and the consequences of inequality among adults within social groups. However, contrary to previous studies, we suggest that it is not the number or strength of associations that an adult individual has (i.e. centrality) that is important, but the overall configuration of social relationships within the group (i.e. centrality SD) that is a key factor in influencing longevity

Exercise training in pediatric patients with end-stage renal disease

The objective of this study was to determine the feasibility and efficacy of an exercise training program to improve exercise capacity and fatigue level in pediatric patients with end-stage renal disease (ESRD). Twenty children on dialysis intended to perform a 12-week graded community-based exercise program. Exercise capacity and fatigue level were studied; muscle force and health-related quality of life were secondary outcomes. All outcomes were measured at baseline (T = 0) and after intervention (T = 1). Fourteen of the 20 patients (70%) either did not start the program or did not complete the program. Of these patients, seven did not complete or even start the exercise program because of a combination of lack of time and motivational problems. Six patients were not able to continue the program or were unable to do the follow-up measurements because of medical problems. Exercise capacity and muscle strength was higher after the exercise program in the children who completed the training. In conclusion, exercise training is difficult to perform in children with ESRD and is not always feasible in real-life situations for many children with ESRD