Optimization of Muscle Activity for Task-Level Goals Predicts Complex Changes in Limb Forces across Biomechanical Contexts

Optimality principles have been proposed as a general framework for understanding motor control in animals and humans largely based on their ability to predict general features movement in idealized motor tasks. However, generalizing these concepts past proof-of-principle to understand the neuromechanical transformation from task-level control to detailed execution-level muscle activity and forces during behaviorally-relevant motor tasks has proved difficult. In an unrestrained balance task in cats, we demonstrate that achieving task-level constraints center of mass forces and moments while minimizing control effort predicts detailed patterns of muscle activity and ground reaction forces in an anatomically-realistic musculoskeletal model. Whereas optimization is typically used to resolve redundancy at a single level of the motor hierarchy, we simultaneously resolved redundancy across both muscles and limbs and directly compared predictions to experimental measures across multiple perturbation directions that elicit different intra- and interlimb coordination patterns. Further, although some candidate task-level variables and cost functions generated indistinguishable predictions in a single biomechanical context, we identified a common optimization framework that could predict up to 48 experimental conditions per animal (n = 3) across both perturbation directions and different biomechanical contexts created by altering animals' postural configuration. Predictions were further improved by imposing experimentally-derived muscle synergy constraints, suggesting additional task variables or costs that may be relevant to the neural control of balance. These results suggested that reduced-dimension neural control mechanisms such as muscle synergies can achieve similar kinetics to the optimal solution, but with increased control effort (≈2×) compared to individual muscle control. Our results are consistent with the idea that hierarchical, task-level neural control mechanisms previously associated with voluntary tasks may also be used in automatic brainstem-mediated pathways for balance

Rare missense variants in Tropomyosin-4 (TPM4) are associated with platelet dysfunction, cytoskeletal defects, and excessive bleeding

Background: A significant challenge is faced for the genetic diagnosis of inherited platelet disorders in which candidate genetic variants can be found in more than 100 bleeding, thrombotic, and platelet disorder genes, especially within families in which there are both normal and low platelet counts. Genetic variants of unknown clinical significance (VUS) are found in a significant proportion of such patients in which functional studies are required to prove pathogenicity. Objective: To identify the genetic cause in patients with a suspected platelet disorder and subsequently perform a detailed functional analysis of the candidate genetic variants found. Methods: Genetic and functional studies were undertaken in three patients in two unrelated families with a suspected platelet disorder and excessive bleeding. A targeted gene panel of previously known bleeding and platelet genes was used to identify plausible genetic variants. Deep platelet phenotyping was performed using platelet spreading analysis, transmission electron microscopy, immunofluorescence, and platelet function testing using lumiaggregometry and flow cytometry. Results: We report rare conserved missense variants (p.R182C and p.A183V) in TPM4 encoding tromomyosin-4 in 3 patients. Deep platelet phenotyping studies revealed similar platelet function defects across the 3 patients including reduced platelet secretion, and aggregation and spreading defects suggesting that TPM4 missense variants impact platelet function and show a disordered pattern of tropomyosin staining. Conclusions: Genetic and functional TPM4 defects are reported making TPM4 a diagnostic grade tier 1 gene and highlights the importance of including TPM4 in diagnostic genetic screening for patients with significant bleeding and undiagnosed platelet disorders, particularly for those with a normal platelet count

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Multi-model seascape genomics identifies distinct environmental drivers of selection among sympatric marine species

Background As global change and anthropogenic pressures continue to increase, conservation and management increasingly needs to consider species’ potential to adapt to novel environmental conditions. Therefore, it is imperative to characterise the main selective forces acting on ecosystems, and how these may influence the evolutionary potential of populations and species. Using a multi-model seascape genomics approach, we compare putative environmental drivers of selection in three sympatric southern African marine invertebrates with contrasting ecology and life histories: Cape urchin (Parechinus angulosus), Common shore crab (Cyclograpsus punctatus), and Granular limpet (Scutellastra granularis). Results Using pooled (Pool-seq), restriction-site associated DNA sequencing (RAD-seq), and seven outlier detection methods, we characterise genomic variation between populations along a strong biogeographical gradient. Of the three species, only S. granularis showed significant isolation-by-distance, and isolation-by-environment driven by sea surface temperatures (SST). In contrast, sea surface salinity (SSS) and range in air temperature correlated more strongly with genomic variation in C. punctatus and P. angulosus. Differences were also found in genomic structuring between the three species, with outlier loci contributing to two clusters in the East and West Coasts for S. granularis and P. angulosus, but not for C. punctatus. Conclusion The findings illustrate distinct evolutionary potential across species, suggesting that species-specific habitat requirements and responses to environmental stresses may be better predictors of evolutionary patterns than the strong environmental gradients within the region. We also found large discrepancies between outlier detection methodologies, and thus offer a novel multi-model approach to identifying the principal environmental selection forces acting on species. Overall, this work highlights how adding a comparative approach to seascape genomics (both with multiple models and species) can elucidate the intricate evolutionary responses of ecosystems to global change

Genetics and evidence for balancing selection of a sex-linked colour polymorphism in a songbird

Colour polymorphisms play a key role in sexual selection and speciation, yet the mechanisms that generate and maintain them are not fully understood. Here, we use genomic and transcriptomic tools to identify the precise genetic architecture and evolutionary history of a sex-linked colour polymorphism in the Gouldian finch Erythrura gouldiae that is also accompanied by remarkable differences in behaviour and physiology. We find that differences in colour are associated with an ~72-kbp region of the Z chromosome in a putative regulatory region for follistatin, an antagonist of the TGF-β superfamily genes. The region is highly differentiated between morphs, unlike the rest of the genome, yet we find no evidence that an inversion is involved in maintaining the distinct haplotypes. Coalescent simulations confirm that there is elevated nucleotide diversity and an excess of intermediate frequency alleles at this locus. We conclude that this pleiotropic colour polymorphism is most probably maintained by balancing selection

The transcriptomic basis of oviposition behaviour in the parasitoid wasp Nasonia vitripennis

Linking behavioural phenotypes to their underlying genotypes is crucial for uncovering the mechanisms that underpin behaviour and for understanding the origins and maintenance of genetic variation in behaviour. Recently, interest has begun to focus on the transcriptome as a route for identifying genes and gene pathways associated with behaviour. For many behavioural traits studied at the phenotypic level, we have little or no idea of where to start searching for "candidate" genes: the transcriptome provides such a starting point. Here we consider transcriptomic changes associated with oviposition in the parasitoid wasp Nasonia vitripennis. Oviposition is a key behaviour for parasitoids, as females are faced with a variety of decisions that will impact offspring fitness. These include choosing between hosts of differing quality, as well as making decisions regarding clutch size and offspring sex ratio. We compared the whole-body transcriptomes of resting or ovipositing female Nasonia using a "DeepSAGE" gene expression approach on the Illumina sequencing platform. We identified 332 tags that were significantly differentially expressed between the two treatments, with 77% of the changes associated with greater expression in resting females. Oviposition therefore appears to focus gene expression away from a number of physiological processes, with gene ontologies suggesting that aspects of metabolism may be down-regulated during egg-laying. Nine of the most abundant differentially expressed tags showed greater expression in ovipositing females though, including the genes purity-of-essence (associated with behavioural phenotypes in Drosophila) and glucose dehydrogenase (GLD). The GLD protein has been implicated in sperm storage and release in Drosophila and so provides a possible candidate for the control of sex allocation by female Nasonia during oviposition. Oviposition in Nasonia therefore clearly modifies the transcriptome, providing a starting point for the genetic dissection of oviposition.Publisher PDFPeer reviewe