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Werling, K.

Publications and source records attributed to Werling, K..

6 recordsLinked to original sources

AddBiomechanics: Automating model scaling, inverse kinematics, and inverse dynamics from human motion data through sequential optimization

Creating large-scale public datasets of human motion biomechanics could unlock data-driven breakthroughs in our understanding of human motion, neuromuscular diseases, and assistive devices. However, the manual effort currently required to process motion capture data and quantify the kinematics and dynamics of movement is costly and limits the collection and sharing of large-scale biomechanical datasets. We present a method, called AddBiomechanics, to automate and standardize the quantification of human movement dynamics from motion capture data. We use linear methods followed by a non-convex bilevel optimization to scale the body segments of a musculoskeletal model, register the locations of optical markers placed on an experimental subject to the markers on a musculoskeletal model, and compute body segment kinematics given trajectories of experimental markers during a motion. We then apply a linear method followed by another non-convex optimization to find body segment masses and fine tune kinematics to minimize residual forces given corresponding trajectories of ground reaction forces. The optimization approach requires approximately 3-5 minutes to determine a subjects skeleton dimensions and motion kinematics, and less than 30 minutes of computation to also determine dynamically consistent skeleton inertia properties and fine-tuned kinematics and kinetics, compared with about one day of manual work for a human expert. We used AddBiomechanics to automatically reconstruct joint angle and torque trajectories from previously published multi-activity datasets, achieving close correspondence to expert-calculated values, marker root-mean-square errors less than 2 cm, and residual force magnitudes smaller than 2% of peak external force. Finally, we confirmed that AddBiomechanics accurately reproduced joint kinematics and kinetics from synthetic walking data with low marker error and residual loads. We have published the algorithm as an open source cloud service at AddBiomechanics.org, which is available at no cost and asks that users agree to share processed and de-identified data with the community. As of this writing, hundreds of researchers have used the prototype tool to process and share about ten thousand motion files from about one thousand experimental subjects. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to use state-of-the-art biomechanical analysis, do so at lower cost, and share larger and more accurate datasets.

bioengineering↗

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses

Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. Here, we examine single and co-infection of Mayaro virus (-D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27{degrees}C) and hot (32{degrees}C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes, with a tendency for higher titers in co-infected mosquitoes at both temperatures and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs single infections and was more evident at earlier timepoints (7 vs 14 days post infection). The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses, but further studies are necessary to clarify the role of co-infection at different and variable temperature regimes. Author summaryGlobal warming is having devastating consequences for the environment, and a cause of concern is the increase in local abundance and geographic range of mosquitoes and the associated viruses they transmit. This study explores how temperature affects the mosquitos ability to survive and potentially spread two viruses, Mayaro and dengue, in single or co-infections. We found that Mayaro virus was not clearly affected by temperature or the presence of dengue infection. In contrast, dengue virus showed higher infection and potential for higher transmission in mosquitoes kept at high temperatures, and this trend was stronger in co-infections compared to single infections. Mosquito survival consistently decreased at high temperatures. We hypothesize the differences observed for dengue virus are due to the faster growth and viral activity in the mosquito at hotter temperatures, a pattern not observed for Mayaro virus. More studies under different temperature regimes are needed to clarify the role of co-infection.

microbiology↗

Rapid bilevel optimization to concurrently solve musculoskeletal scaling, marker registration, and inverse kinematic problems for human motion reconstruction

Creating large-scale public datasets of human motion biomechanics could unlock data-driven breakthroughs in our understanding of human motion, neuromuscular diseases, and assistive devices. However, the manual effort currently required to process motion capture data is costly and limits the collection and sharing of large-scale biomechanical datasets. We present a method to automate and standardize motion capture data processing: bilevel optimization that is able to scale the body segments of a musculoskeletal model, register the locations of optical markers placed on an experimental subject to the markers on a musculoskeletal model, and compute body segment kinematics given trajectories of experimental markers during a motion. The optimization requires less than five minutes of computation to process a subjects motion capture data, compared with about one day of manual work for a human expert. On a sample of 34 trials of experimental data, the root-mean-square marker reconstruction error (RMSE) was 1.38 cm, approximately 40% lower than the 2.58 cm achieved manually by 3 experts. Optimization solutions reconstructed known joint angle trajectories from four diverse motion trials of synthetic data to an average of 0.79 degrees RMSE. We have published an open source cloud service at AddBiomechanics.org to process experimental motion capture data, which is available at no cost and asks that users agree to share processed and de-identified data with the community. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to engage in state-of-the-art biomechanical analysis in their work, do so at lower cost, and share larger and more accurate datasets. Author summaryCreating large-scale public datasets of human motion could unlock data-driven breakthroughs in our understanding of neuromuscular diseases, assistive devices, and human motion more broadly. The manual effort currently required to process these motion datasets is costly and limits the collection and sharing of large-scale datasets. Our cloud-based software tool, called AddBiomechanics, uses state-of-the-art optimization techniques to automatically scale the body segments of a musculoskeletal model to match the subject of interest, and then compute body segment kinematics during a motion. The optimization requires less than five minutes of computation to process a subjects motion capture data, compared with about one day of manual work for a human expert. The accuracy of the approach in quantifying the body segment kinematics is as good or better than the results achieved manually by experts. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to engage in state-of-the-art biomechanical analysis, do so at lower cost, and share larger and more accurate datasets.

physiology↗

Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors

Anopheles coluzzii females, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where the traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be a determinant of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results reveal overlapping roles played by CHCs in mate choice and insecticide resistance, and point to sexual selection for insecticide resistance traits that limit the efficacy of our best malaria control tools.

ecology↗

A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection

Anopheles mosquitoes have transmitted Plasmodium parasites for millions of years, yet it remains unclear whether they suffer fitness costs to infection. Here we report that the fecundity of virgin and mated females of two important vectors--Anopheles gambiae and Anopheles stephensi--is not affected by infection with Plasmodium falciparum, demonstrating that these human malaria parasites do not inflict reproductive costs to their natural mosquito hosts. Additionally, parasite development is not impacted by mating status. However, in field studies using different P. falciparum isolates in Anopheles coluzzii, we find that Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive gene strongly induced after mating by the sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), protects females from incurring fecundity costs to infection. MISO-silenced females produce fewer eggs as they become increasingly infected with P. falciparum, while parasite development is not impacted by this gene silencing. Interestingly, previous work had shown that sexual transfer of 20E has specifically evolved in Cellia species of the Anopheles genus, driving the co-adaptation of MISO. Our data therefore suggest that evolution of male-female sexual interactions may have promoted Anopheles tolerance to P. falciparum infection in the Cellia subgenus, which comprises the most important malaria vectors. Author summaryPlasmodium falciparum, the deadliest form of human malaria, is transmitted when female Anopheles mosquitoes bite people and take a blood meal in order to develop eggs. To date, it is still poorly understood whether Anopheles mosquitoes that get infected with P. falciparum suffer fitness costs. Here, we find that the number of eggs produced by Anopheles gambiae and Anopheles stephensi females is not affected by P. falciparum infection, and that the mating status of the mosquitoes does not impact the parasite. However, in field experiments infecting a related species, Anopheles coluzzii, with P. falciparum using blood from donors in Burkina Faso, we find that interfering with the expression of a gene normally triggered by the sexual transfer of the steroid hormone 20-hydroxyecdysone induces increasing costs to egg development as females become more infected with P. falciparum, with no impacts on the parasite. The results of our study suggest that pathways triggered by mating may help Anopheles prevent reproductive costs associated with P. falciparum infection, providing new insights into evolutionary strategies adopted by anophelines in the face of a longstanding association with Plasmodium parasites.

microbiology↗

Current estimates of malaria basic reproduction number underestimate parasite transmission efficiency due to multiple blood feeding

Many mosquito species, including the major malaria vector Anopheles gambiae, naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time. We measured P. falciparum oocyst size and performed sporozoite time course analyses to determine the parasite’s extrinsic incubation period (EIP), i.e. the time required by parasites to reach infectious sporozoite stages, in An. gambiae females blood fed either once or twice. An additional blood feed at 3 days post infection drastically accelerates oocyst growth rates, causing earlier sporozoite accumulation in the salivary glands, thereby shortening the EIP (reduction of 2.25 ± 0.39 days). Moreover, parasite growth is further accelerated in transgenic mosquitoes with reduced reproductive capacity, which mimic genetic modifications currently proposed in population suppression gene drives. We incorporate our shortened EIP values into a measure of transmission potential, the basic reproduction number R0, and find the average R0 is remarkably higher (range: 10.1%–12.1% increase) across sub-Saharan Africa than when using traditional EIP measurements. These data suggest that malaria elimination may be substantially more challenging and that younger mosquitoes or those with reduced reproductive ability may provide a larger contribution to infection than currently believed. Our findings have profound implications for current and future mosquito control interventions.Significance Statement In natural settings the female Anopheles gambiae mosquito, the major malaria vector, blood feeds multiple times in her lifespan. Here we demonstrate that an additional blood feed accelerates the growth of Plasmodium falciparum malaria parasites in this mosquito. Incorporating these data into a mathematical model across sub-Saharan Africa reveals that malaria transmission potential is likely to be substantially higher than previously thought, making disease elimination more difficult. Additionally, we show that control strategies that manipulate mosquito reproduction with the aim of suppressing Anopheles populations may inadvertently favor malaria transmission. Our data also suggest that parasites can be transmitted by younger mosquitoes, which are less susceptible to insecticide killing, with negative implications for the success of insecticide-based strategies.Competing Interest StatementThe authors have declared no competing interest.View Full Text

microbiology↗