The physiology of movement

Movement, from foraging to migration, is known to be under the influence of the environment. The translation of environmental cues to individual movement decision making is determined by an individual's internal state and anticipated to balance costs and benefits. General body condition, metabolic and hormonal physiology mechanistically underpin this internal state. These physiological determinants are tightly, and often genetically linked with each other and hence central to a mechanistic understanding of movement. We here synthesise the available evidence of the physiological drivers and signatures of movement and review (1) how physiological state as measured in its most coarse way by body condition correlates with movement decisions during foraging, migration and dispersal, (2) how hormonal changes underlie changes in these movement strategies and (3) how these can be linked to molecular pathways. We reveale that a high body condition facilitates the efficiency of routine foraging, dispersal and migration. Dispersal decision making is, however, in some cases stimulated by a decreased individual condition. Many of the biotic and abiotic stressors that induce movement initiate a physiological cascade in vertebrates through the production of stress hormones. Movement is therefore associated with hormone levels in vertebrates but also insects, often in interaction with factors related to body or social condition. The underlying molecular and physiological mechanisms are currently studied in few model species, and show -in congruence with our insights on the role of body condition- a central role of energy metabolism during glycolysis, and the coupling with timing processes during migration. Molecular insights into the physiological basis of movement remain, however, highly refractory. We finalise this review with a critical reflection on the importance of these physiological feedbacks for a better mechanistic understanding of movement and its effects on ecological dynamics at all levels of biological organization

Resistance risk assessment of the novel complex II inhibitor pyflubumide in the polyphagous pest Tetranychus urticae

Pyflubumide is a novel selective carboxanilide acaricide that inhibits mitochondrial complex II of spider mite species such as Tetranychus urticae. We explored the baseline toxicity and potential cross-resistance risk of pyflubumide in a reference panel of T. urticae strains resistant to various acaricides with different modes of action. A cyenopyrafen-resistant strain (JPR) was identified as the only strain with low-to-moderate level of cross-resistance to pyflubumide (LC50 = 49.07 mg/L). In a resistance risk assessment approach, JPR was subsequently selected which led to two highly resistant strains JPR-R1 (RR = 466.7) and JPR-R2 (RR = 614.8). Interestingly, compared to adult females, resistance was much less pronounced in adult males and eggs of the two JPR-R strains. In order to elucidate resistance mechanisms, we first sequenced the complex II subunits in susceptible and resistant strains, but target-site insensitivity could not be detected. In contrast, synergism/antagonism experiments strongly suggested that cytochrome P450 monooxygenases are involved in pyflubumide resistance. We therefore conducted genome-wide gene expression experiments to investigate constitutive and induced expression patterns and documented the overexpression of five cytochrome P450 and four carboxyl/choline esterase genes in the JPR-R strains after pyflubumide exposure. Together, we provide a first resistance risk assessment of a novel complex II inhibitor and provide first evidence for metabolic resistance mediated by cytochrome P450s in T. urticae

Intersexuality in a natural population of the terrestrial isopod Porcellio scaber

Intersex phenotypes are rarely observed in natural isopod populations and their expression is typically associated with infection of Wolbachia, a reproductive parasite that manipulates arthropod reproduction. During an intensive sampling effort of a natural population of the isopod Porcellio scaber, an adult individual was isolated that expressed both male and female traits. The intersex individual exhibited clearly developed external male genitalia and carried multiple eggs in its brood pouch. No Wolbachia infection could be identified in this individual, a result that needs to be approached with caution due to suboptimal DNA preservation for diagnostic PCR assays. Wolbachia were, however, detected in two adult females of the same population, and appear closely related to isolates that infect other terrestrial isopod species. This is the first demonstration that intersex phenotypes can arise under natural conditions in P. scaber

Deferiprone and gallium-protoporphyrin have the capacity to potentiate the activity of antibiotics in Staphylococcus aureus small colony variants

Small colony variants (SCVs) of bacteria like Staphylococcus aureus are characterized by a reduced colony size and are linked to increased antibiotic tolerance and resistance. Their altered expression of virulence factors, slow growing properties and their ability to form biofilms make the eradication of SCVs challenging. In the context of biofilm-related infectious diseases involving S. aureus SCVs, a therapy targeting bacterial iron metabolism was evaluated. The combination of the iron-chelator deferiprone (Def) and the heme-analog gallium-protoporphyrin (GaPP), in solution and incorporated in a surgical wound gel, was tested for activity against planktonic and sessile SCVs. To this end, the activity of Def-GaPP was assessed against planktonic S. aureus SCVs, as well as against in vitro and in vivo biofilms in the colony biofilm model, an artificial wound model and a Caenorhabditis elegans infection model. While Def alone failed to show substantial antibacterial activity, GaPP and the combination of Def-GaPP demonstrated concentration- and strain-dependent antibacterial properties. Specifically, the Def-GaPP combination significantly reduced the bacterial load in an artificial wound model and increased the survival of S. aureus SCV infected C. elegans. When Def-GaPP were combined with gentamicin or ciprofloxacin, the triple combinations exceeded the antibiofilm activity of the individual compounds in the colony biofilm model. In targeting bacterial iron metabolism, Def-GaPP showed significant activity against planktonic and sessile SCVs. Moreover, Def-GaPP could potentiate the activity of gentamicin and ciprofloxacin. Delivered in a wound healing gel, Def-GaPP showed promise as a new topical strategy against infections with S. aureus SCVs.Katharina Richter, Nicky Thomas, Guimin Zhang, Clive A. Prestidge, Tom Coenye, Peter-John Wormald and Sarah Vreugd

Transcriptomic plasticity in the arthropod generalist Tetranychus urticae upon long-term acclimation to different host plants

The two-spotted spider mite Tetranychus urticae is an important pest with an exceptionally broad host plant range. This generalist rapidly acclimatizes and adapts to a new host, hereby overcoming nutritional challenges and a novel pallet of constitutive and induced plant defenses. Although recent studies reveal that a broad transcriptomic response upon host plant transfer is associated with a generalist life style in arthropod herbivores, it remains uncertain to what extent these transcriptional changes are general stress responses or host-specific. In the present study, we analyzed and compared the transcriptomic changes that occur in a single T. urticae population upon long-term transfer from Phaseolus vulgaris to a similar, but chemically defended, host (cyanogenic Phaseolus lunatus) and to multiple economically important crops (Glycine max, Gossypium hirsutum, Solanum lycopersicum and Zea mays). These long-term host plant transfers were associated with distinct transcriptomic responses with only a limited overlap in both specificity and directionality, suggestive of a fine-tuned transcriptional plasticity. Nonetheless, analysis at the gene family level uncovered overlapping functional processes, recruiting genes from both well-known and newly discovered detoxification families. Of note, our analyses highlighted a possible detoxification role for Tetranychus-specific short-chain dehydrogenases and single PLAT domain proteins, and manual genome annotation showed that both families are expanded in T. urticae. Our results shed new light on the molecular mechanisms underlying the remarkable adaptive potential for host plant use of generalist arthropods and set the stage for functional validation of important players in T. urticae detoxification of plant secondary metabolites

Horizontal gene transfer contributes to the evolution of arthropod herbivory

Within animals, evolutionary transition toward herbivory is severely limited by the hostile characteristics of plants. Arthropods have nonetheless counteracted many nutritional and defensive barriers imposed by plants and are currently considered as the most successful animal herbivores in terrestrial ecosystems. We gather a body of evidence showing that genomes of various plant feeding insects and mites possess genes whose presence can only be explained by horizontal gene transfer (HGT). HGT is the asexual transmission of genetic information between reproductively isolated species. Although HGT is known to have great adaptive significance in prokaryotes, its impact on eukaryotic evolution remains obscure. Here, we show that laterally transferred genes into arthropods underpin many adaptations to phytophagy, including efficient assimilation and detoxification of plant produced metabolites. Horizontally acquired genes and the traits they encode often functionally diversify within arthropod recipients, enabling the colonization of more host plant species and organs. We demonstrate that HGT can drive metazoan evolution by uncovering its prominent role in the adaptations of arthropods to exploit plants

Estimation of treatment policy estimands for continuous outcomes using off treatment sequential multiple imputation

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In late-stage clinical trials, it is common to handle intercurrent events like "treatment discontinuation" using the treatment policy strategy and target the treatment effect on all outcomes regardless of treatment discontinuation. For continuous repeated measures, this type of effect is often estimated using all observed data before and after discontinuation using either a mixed model for repeated measures (MMRM) or multiple imputation (MI) to handle any missing data. In basic form, both of these estimation methods ignore treatment discontinuation in the analysis and therefore may be biased if there are differences in patient outcomes after treatment discontinuation compared to patients still assigned to treatment, and missing data being more common for patients who have discontinued treatment. We therefore propose and evaluate a set of MI models that can accommodate differences between outcomes before and after treatment discontinuation. The models are evaluated in the context of planning a phase 3 trial for a respiratory disease. We show that analyses ignoring treatment discontinuation can introduce substantial bias and can sometimes underestimate variability. We also show that some of the MI models proposed can successfully correct the bias but inevitably lead to increases in variance. We conclude that some of the proposed MI models are preferable to the traditional analysis ignoring treatment discontinuation, but the precise choice of MI model will likely depend on the trial design, disease of interest and amount of observed and missing data following treatment discontinuation

Fitness maximization by dispersal : evidence from an invasion experiment

Dispersal is essential for population persistence in transient environments. While costs of dispersal are ubiquitous, individual advantages of dispersal remain poorly understood. Not all individuals from a population disperse, and individual heterogeneity in costs and benefits of dispersal underlie phenotype-dependent dispersal strategies. Dispersing phenotypes are always expected to maximize their fitness by adaptive decision making relative to the alternative strategy of remaining philopatric. While this first principle is well acknowledged in theoretical ecology, empirical verification is extremely difficult, due to a plethora of experimental constraints. We studied fitness prospects of dispersal in a game theoretical context using the two-spotted spider mite Tetranychus urticae as a model species. We demonstrate that dispersing phenotypes represent those individuals able to maximize their fitness in a novel, less populated environment reached after dispersal. In contrast to philopatric phenotypes, successful dispersers performed better in a low density post-dispersal context, but worse in a high density philopatric context. They increased fitness about 450% relative to the strategy of remaining philopatric. The optimization of phenotype-dependent dispersal, thus, maximizes fitness

Genome wide gene-expression analysis of facultative reproductive diapause in the two-spotted spider mite Tetranychus urticae

Background: Diapause or developmental arrest, is one of the major adaptations that allows mites and insects to survive unfavorable conditions. Diapause evokes a number of physiological, morphological and molecular modifications. In general, diapause is characterized by a suppression of the metabolism, change in behavior, increased stress tolerance and often by the synthesis of cryoprotectants. At the molecular level, diapause is less studied but characterized by a complex and regulated change in gene-expression. The spider mite Tetranychus urticae is a serious polyphagous pest that exhibits a reproductive facultative diapause, which allows it to survive winter conditions. Diapausing mites turn deeply orange in color, stop feeding and do not lay eggs. Results: We investigated essential physiological processes in diapausing mites by studying genome-wide expression changes, using a custom built microarray. Analysis of this dataset showed that a remarkable number, 11% of the total number of predicted T. urticae genes, were differentially expressed. Gene Ontology analysis revealed that many metabolic pathways were affected in diapausing females. Genes related to digestion and detoxification, cryoprotection, carotenoid synthesis and the organization of the cytoskeleton were profoundly influenced by the state of diapause. Furthermore, we identified and analyzed an unique class of putative antifreeze proteins that were highly upregulated in diapausing females. We also further confirmed the involvement of horizontally transferred carotenoid synthesis genes in diapause and different color morphs of T. urticae. Conclusions: This study offers the first in-depth analysis of genome-wide gene-expression patterns related to diapause in a member of the Chelicerata, and further adds to our understanding of the overall strategies of diapause in arthropods

Transcriptomic responses of the olive fruit fly Bactrocera oleae and its symbiont Candidatus Erwinia dacicola to olive feeding

The olive fruit fly, Bactrocera oleae, is the most destructive pest of olive orchards worldwide. The monophagous larva has the unique capability of feeding on olive mesocarp, coping with high levels of phenolic compounds and utilizing non-hydrolyzed proteins present, particularly in the unripe, green olives. On the molecular level, the interaction between B. oleae and olives has not been investigated as yet. Nevertheless, it has been associated with the gut obligate symbiotic bacterium Candidatus Erwinia dacicola. Here, we used a B. oleae microarray to analyze the gene expression of larvae during their development in artificial diet, unripe (green) and ripe (black) olives. The expression profiles of Ca. E. dacicola were analyzed in parallel, using the Illumina platform. Several genes were found overexpressed in the olive fly larvae when feeding in green olives. Among these, a number of genes encoding detoxification and digestive enzymes, indicating a potential association with the ability of B. oleae to cope with green olives. In addition, a number of biological processes seem to be activated in Ca. E. dacicola during the development of larvae in olives, with the most notable being the activation of amino-acid metabolism