A critical examination of evidence and its relation to occupation in scientific occupational therapy articles

The introduction of scientific research evidence through evidence-based practice (EBP) into occupational therapy can potentially be used to reform and transform the profession, both as a limiting and defining process as well as a broadening and developing process. Two different approaches to the topic of EBP were found in this review. They are comprised of a position favoring a traditional evidence-hierarchy centered on RCT-studies and a multidimensional perspective incorporating qualitative data to the evidence-base of occupational therapy practice. Articles linking the evidence-perspectives to the key concept of occupation are few and pre-dominantly found in the group that conveys a multidimensional perspective on evidence. How occupational therapists in their studies relates their comprehension of the concepts of evidence and evidence-based practice to the key concept of occupation is an important factor in creating an research environment of possibilities, in which occupational therapy fully can position itself, within the future world of health and health care

MHC polymorphism in a songbird : Fitness, mate choice, and sexual conflict

Sex differences in immune responses have been observed across a wide range of animal species, with the generaltendency that males have weaker immune responses than females. These differences are at least partly caused by immune-regulating effects of sex hormones, and have been associated with an increased prevalence of autoimmune disorders in females and with a general tendency for males to be parasitized more often than females. Because of these differences, male and female phenotypes may be regarded as different immunological environments, however it has not previously been investigated whether sex differences in immune responses may lead to sexually antagonistic selection on immune system genes.The first chapter of this thesis presents a literature study of the effects of sex hormones on the strength of immune responses in vertebrates, based on which we propose the hypothesis that sexual selection may drive sexually antagonistic selection on genes associated with the immune system. In the following chapters, we investigated this hypothesis using major histocompatibility complex class I (MHC-I) genes in a species subject to strong sexual selection, a socially polygynous songbird, the great reed warbler Acrocephalus arundinaceus.MHC genes play an important role in vertebrate adaptive immunity where they enable recognition and elimination of pathogens. Due to an ongoing co-evolution between hosts and their pathogens, the MHC genes are among the most variable genes known in vertebrates. It has been hypothesized that hosts benefit from having high MHC diversity, because this confers protection against a wider range of pathogens. Interestingly, we found evidence for a sexual conflict and for sexually differential selection on MHC-I diversity in our great reed warbler study population.It has been predicted that genes associated with disease resistance should be advantageous in terms of sexual selection, and this prediction is central to our hypothesis that sexual selection may drive sexually antagonistic selection on genes associated with the immune system. We therefore investigated whether MHC-I genes were associated with sexual selection in great reed warblers. Our results indicated that MHC-I diversity (i) conveys a ‘good genes’ benefit to females that select older males and males with large song repertoires, and (ii) affects the ability of males to acquire attractive territories. These results confirmed that MHC-I genes are associated with sexual selection, and thereby corroborated our hypothesis that sexual selection may be driving the observed sexual conflict over MHC-I diversity via immune regulating effects of sex hormones.Finally, we investigated the source of MHC-I genotypic variation in great reed warblers by analyzing segregation of MHC-I haplotypes and performing phylogenetic reconstruction on MHC-I alleles. We identified five distinct clades in a phylogenetic tree that indicate the presence of several divergent MHC-I loci in the great reed warbler genome. Analyses of positive selection implied that each putative MHC-I locus may have evolved slightly different functions. Importantly, variation in MHC-I diversity between haplotypes was largely explained by variation within two specific clades, suggesting that the sexual conflict over MHC-I diversity may be caused by sexually antagonistic effects associated with alleles from these clades in particular.Our results suggest that sexually antagonistic selection is an important force in the evolution of vertebrate adaptive immunity, which may be important for a comprehensive, evolutionary understanding of autoimmune diseases and other costs associated with immune responses in vertebrates. The results presented in this thesis invite further studies that investigate the generality of sexually antagonistic selection over immune system genes in other species, as well as more detailed studies of the mechanisms underlying such sexual conflicts

Divergent Immune Responses in Behaviorally-Inhibited vs. Non-Inhibited Male Rats

Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific health outcomes, however, we have limited information on whether immune function varies by personality. In the present study, we examined the relationship between a basic behavioral trait (behavioral-inhibition vs. non-inhibition) and two immune responses (innate inflammation and delayed-type hypersensitivity, DTH) in a rodent model. In humans, behavioral inhibition (fearful temperament) is associated with altered stress physiology and allergies. In laboratory rats, the trait is associated with elevated glucocorticoid production. We hypothesized that behavioral inhibition is associated with glucocorticoid resistance and dampened T-helper 1 cell responses often associated with chronic stress and allergies. Further, this immune profile would predict poorly-regulated innate inflammation and dampened DTH. In male Sprague-Dawley rats, we quantified consistent behavioral phenotypes by measuring latency to contact two kinds of novelty (object vs. social), then measured lipopolysaccharide(LPS)-induced innate inflammation or keyhole limpet hemocyanin(KLH)-induced DTH. Behaviorally-inhibited rats had heightened glucocorticoid and interleukin-6 responses to a low/moderate dose of LPS and reduced DTH swelling to KLH re-exposure compared to non-inhibited rats. These results suggest that behavioral inhibition is associated with a glucocorticoid resistant state with poorly regulated innate inflammation and dampened cell-mediated immune responses. This immune profile may be associated with exaggerated T-helper 2 responses, which could set the stage for an allergic/asthmatic/atopic predisposition in inhibited individuals. Human and animal models of temperament-specific immune responses represent an area for further exploration of mechanisms involved in individual differences in health

Sex differences in immune responses : Hormonal effects, antagonistic selection, and evolutionary consequences

Males and females differ in both parasite load and the strength of immune responses and these effects have been verified in humans and other vertebrates. Sex hormones act as important modulators of immune responses; the male sex hormone testosterone is generally immunosuppressive while the female sex hormone estrogen tends to be immunoenhancing. Different sets of T-helper cells (Th) have important roles in adaptive immunity, e.g. Th1 cells trigger type 1 responses which are primarily cell-mediated, and Th2 cells trigger type 2 responses which are primarily humoral responses. In our review of the literature, we find that estrogen and progesterone enhance type 2 and suppress type 1 responses in females, whereas testosterone suppresses type 2 responses and shows an inconsistent pattern for type 1 responses in males. When we combine these patterns of generally immunosuppressive and immunoenhancing effects of the sex hormones, our results imply that the sex differences in immune responses should be particularly strong in immune functions associated with type 2 responses, and less pronounced with type 1 responses. In general the hormone-mediated sex differences in immune responses may lead to genetic sexual conflicts on immunity. Thus, we propose the novel hypothesis that sexually antagonistic selection may act on immune genes shared by the sexes, and that the strength of this sexually antagonistic selection should be stronger for type 2- as compared with type 1-associated immune genes. Finally, we put the consequences of sex hormone-induced effects on immune responses into behavioral and ecological contexts, considering social mating system, sexual selection, geographical distribution of hosts, and parasite abundance

Evidence for sexual conflict over major histocompatibility complex diversity in a wild songbird

Sex differences in parasite load and immune responses are found across a wide range of animals, with females generally having lower parasite loads and stronger immune responses than males. Intrigued by these general patterns, we investigated if there was any sign of sex-specific selection on an essential component of adaptive immunity that is known to affect fitness, the major histocompatibility complex class I (MHC-I) genes, in a 20-year study of great reed warblers. Our analyses on fitness related to MHC-I diversity showed a highly significant interaction between MHC-I diversity and sex, where males with higher, and females with lower, MHC-I diversity were more successful in recruiting offspring. Importantly, mean MHC-I diversity did not differ between males and females, and consequently neither sex reached its MHC-I fitness optimum. Thus, there is an unresolved genetic sexual conflict over MHC-I diversity in great reed warblers. Selection from pathogens is known to maintain MHC diversity, but previous theory ignores that the immune environments are considerably different in males and females. Our results suggest that sexually antagonistic selection is an important, previously neglected, force in the evolution of vertebrate adaptive immunity, and have implications for evolutionary understanding of costs of immune responses and autoimmune diseases

MHCtools - an R package for MHC high-throughput sequencing data : Genotyping, haplotype and supertype inference, and downstream genetic analyses in non-model organisms

The major histocompatibility complex (MHC) plays a central role in the vertebrate adaptive immune system and has been of long-term interest in evolutionary biology. While several protocols have been developed for MHC genotyping, there is a lack of transparent and standardized tools for downstream analysis of MHC data. Here, we present the r package mhctools and demonstrate the use of its functions to (i) assist accurate MHC genotyping from high-throughput amplicon-sequencing data, (ii) infer functional MHC supertypes using bootstrapped clustering analysis, (iii) identify segregating MHC haplotypes from family data, and (iv) analyse functional and genetic distances between MHC sequences. We employed mhctools to analyse MHC class I (MHC-I) amplicon data of 559 great reed warblers (Acrocephalus arundinaceus). We identified 390 MHC-I alleles which clustered into 14 functional supertypes. A phylogenetic analysis and analyses of positive selection suggested that the MHC-I alleles belong to several distinct functional groups. We furthermore identified 107 segregating haplotypes among 116 families, and found substantial variation in diversity with 4-21 MHC-I alleles and 3-13 MHC-I supertypes per haplotype. Finally, we show that the great reed warbler haplotypes harboured combinations of MHC-I supertypes with greater functional divergence than observed in simulated populations of possible haplotypes, a result that is in accordance with the divergent allele advantage hypothesis. Our study demonstrates the power of mhctools to support genotyping and analysis of MHC in non-model species, which we hope will encourage broad implementation among researchers in MHC genetics and evolution

Data from: Evidence for sexual conflict over MHC diversity in a wild songbird

Sex differences in parasite load and immune responses are found across a wide range of animals, with females generally having lower parasite loads and stronger immune responses than males. Intrigued by these general patterns, we investigated if there was any sign of sex-specific selection on an essential component of adaptive immunity that is known to affect fitness, the major histocompatibility complex class I (MHC-I) genes, in a 20-year study of great reed warblers. Our analyses on fitness related to MHC-I diversity showed a highly significant interaction between MHC-I diversity and sex, where males with higher, and females with lower, MHC-I diversity were more successful in recruiting offspring. Importantly, mean MHC-I diversity did not differ between males and females, and consequently neither sex reached its MHC-I fitness optimum. Thus, there is an unresolved genetic sexual conflict over MHC-I diversity in great reed warblers. Selection from pathogens is known to maintain MHC diversity, but previous theory ignores that the immune environments are considerably different in males and females. Our results suggest that sexually antagonistic selection is an important, previously neglected, force in the evolution of vertebrate adaptive immunity, and have implications for evolutionary understanding of costs of immune responses and autoimmune diseases

MHCtools – an R package for MHC high-throughput sequencing data : Genotyping, haplotype and supertype inference, and downstream genetic analyses in non-model organisms

The major histocompatibility complex (MHC) plays a central role in the vertebrate adaptive immune system and has been of long-term interest in evolutionary biology. While several protocols have been developed for MHC genotyping, there is a lack of transparent and standardized tools for downstream analysis of MHC data. Here, we present the r package mhctools and demonstrate the use of its functions to (i) assist accurate MHC genotyping from high-throughput amplicon-sequencing data, (ii) infer functional MHC supertypes using bootstrapped clustering analysis, (iii) identify segregating MHC haplotypes from family data, and (iv) analyse functional and genetic distances between MHC sequences. We employed mhctools to analyse MHC class I (MHC-I) amplicon data of 559 great reed warblers (Acrocephalus arundinaceus). We identified 390 MHC-I alleles which clustered into 14 functional supertypes. A phylogenetic analysis and analyses of positive selection suggested that the MHC-I alleles belong to several distinct functional groups. We furthermore identified 107 segregating haplotypes among 116 families, and found substantial variation in diversity with 4–21 MHC-I alleles and 3–13 MHC-I supertypes per haplotype. Finally, we show that the great reed warbler haplotypes harboured combinations of MHC-I supertypes with greater functional divergence than observed in simulated populations of possible haplotypes, a result that is in accordance with the divergent allele advantage hypothesis. Our study demonstrates the power of mhctools to support genotyping and analysis of MHC in non-model species, which we hope will encourage broad implementation among researchers in MHC genetics and evolution

MHC_I_sequences_JR_20180413

Fasta file with MHC class I exon 3 sequences from the great reed warbler population in Lake Kvismaren, South Central Sweden. The authors kindly request to be contacted if any of this data is used for scientific publication

Host instar influence on offspring sex ratio and female preference of Neodryinus typhlocybae (Ashmead) (Hymenoptera, Dryinidae) parasitoid of Metcalfa pruinosa (Say) (Homoptera, Flatidae)

The parasitoid wasp Neodryinus typhlocybae (Ashmead) was introduced to Europe for the biological control of nearctic planthopper Metcalfa pruinosa (Say), which causes severe damage to both crops and ornamental species in the absence of specialized natural enemies. We performed a series of experiments to evaluate the host instar preference and the effects on parasitoid offspring sex. Results showed that parasitism occurs mostly on 3rd, 4th and 5th host instars. Male parasitoid offspring were reared exclusively from 3rd instars. Both male and female offspring originated from the 4th instar, but the sex ratio remained male-biased. A greater proportion of female offspring originated from the 5th instar. Virgin mothers produced exclusively male progeny. When female wasps were exposed to an equal proportion of 3rd, 4th and 5th host instars, parasitism occurred predominantly on the 5th instar, while the least parasitized was the 3rd instar. The age of female wasps did not influence the preference for host instars or the offspring sex ratio. However, females previous experienced with small host instars resulted in a greater production of female offspring on the 5th instar, compared to females which had never encountered small instars. We discuss the relevance of these findings, which could provide new insights for the optimization of the mass rearing of this parasitoid wasp