Suspending loads decreases load stability but may slightly improve body stability

Here, we seek to determine how compliantly suspended loads could affect the dynamic stability of legged locomotion. We theoretically model the dynamic stability of a human carrying a load using a coupled spring-mass-damper model and an actuated spring-loaded inverted pendulum model, as these models have demonstrated the ability to correctly predict other aspects of locomotion with a load in prior work, such as body forces and energetic cost. We report that minimizing the load suspension natural frequency and damping ratio significantly reduces the stability of the load mass but may slightly improve the body stability of locomotion when compared to a rigidly attached load. These results imply that a highly-compliant load suspension could help stabilize body motion during human, animal, or robot load carriage, but at the cost of a more awkward (less stable) load.     

Ankle and knee moment and power adaptations are elicited through load carriage conditioning in males

Soldiers routinely conduct load carriage and physical training to meet occupational requirements. These tasks are physically arduous and are believed to be the primary cause of musculoskeletal injury. Physical training can help mitigate injury risk when specifically designed to address injury mechanisms and meet task demands. This study aimed to assess lower-limb biomechanics and neuromuscular adaptations during load carriage walking in response to a 10-week evidence-based physical training program. Thirteen male civilian participants donned 23 kg and completed 5 km of load carriage treadmill walking, at 5.5 km h⁻¹ before and after a 10-week physical training program. Three-dimensional motion capture and force plate data were acquired in over-ground walking trials before and after treadmill walking. These data were inputs to a musculoskeletal model which estimated lower-limb joint kinematics and kinetics (i.e., moments and powers) using inverse kinematics and dynamics, respectively. A two-way analysis of variance revealed significant main effect of training for kinematic and kinetics parameters at the knee and ankle joints (p < 0.05). Post-Hoc comparisons demonstrated a significant decrease (4.2%) in total negative knee power between pre- and post-March 5 km measures after training (p < 0.05). Positive power contribution shifted distally after training, increasing at the post-march measure from 39.9% to 43.6% at the ankle joint (p < 0.05). These findings demonstrate that a periodised training program may reduce injury risk through favourable ankle and knee joint adaptations.     

Influence of muscle activity on the forces in the femur: An in vivo study

Experiments were performed on two patients with custom-made instrumented massive proximal femoral prostheses implanted after tumour resection. In vivo axial forces transmitted along the prostheses were telemetered during level walking, single- and double-leg stance, and isometric exercises of the hip muscles. These activities varied the lever arms available to the external loads: minimum for double-leg stance and maximum for hip isometric exercises. Kinematic, force plate, EMG and telemetered force data were recorded simultaneously. The force magnification ration (FMR; the ratio of the telemetered axial force to the external force) was calculated. The FMRs ranged from 1.3 (during double-leg stance) to 29.8 (during abductors test), indicating that a major part of the axial force in the long bones is a response to muscle activity, the strength of which depends on the lever arms available to the external loads. From these results, it was shown that the bulk of the bending moment along limbs is transmitted by a combination of tensile forces in muscles and compressive forces in bones, so moments transmitted by the bones are smaller than the limb moments. It was concluded that appropriate simulation of muscle forces is important in experimental or theoretical studies of load transmission along bones.     

Evolutionary processes and evolutionary noise at the molecular level

Summary On account, notably, of a competition between different component functions for individual sites in polypeptide chains, each protein molecule represents a functional compromise, with some functions optimized, but the overall state of the molecule –suboptimal–. The proposal is made that the selection coefficient relating to a protein molecule under given conditions can in principle be broken down into partial selection coefficients relevant to the different functions that the molecule carries out. At generalfunction sites, each fixation improves some function, while others deteriorate, at first nonsignificantly, and the overall adaptive state of the molecule fluctuates around its maximum. A selective mechanism is described whereby kaleidoscopic changes in primary structure at variable sites are indefinitely promoted, independently of any environmental changes and with the molecule remaining close to a state of maximal overall adaptation. The paradoxical aspect of this proposal is analyzed. The implication of specific functions in substitutions at general-function sites is noted. Further, it is shown that a certain category of changes in the internal environment of the organism can be integrated into the constantenvironment model for selection. Genetic sufficiency is considered a notion more adequate than genetic optimality for describing biological fitness and for providing a basis for the present model. On this basis selection occurs without genetic load. Multipolymorphism is one of the consequences. Several lines of evidence, in particular observations on polymorphism in deep sea organisms, seem to support the model. It is pointed out that it provides a theoretical foundation for a molecular evolutionary clock. The theoretical constancy of the clock depends on the constancy of functional density. The question of the evolution of functional density is examined. Comparisons of observed substitution frequencies with values expected on a random basis are rejected as a measure of the contribution to evolution of nondetermination. They are considered to reflect a hierarchy in the resistance of the molecules to different amino acid residues as substituents. A limited component of –true– randomness, again accompanied by selection, is on the other hand provided by the model. Most amino acid substitutions are considered evolutionary noise, even though noise compatible with selection. It is proposed that evolutionarily significant substitutions may be identified by monitoring changes in functional density and weighted functional density.Directeur de Recherche at Centre National de la Recherche Scientifique, Paris.     

Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent

Pathogen‐mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole‐genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.     

The Genomic Architecture of Adaptation to Larval Malnutrition Points to a Trade-off with Adult Starvation Resistance in Drosophila

Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajima’s D, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.     

Cascaded valorization of brown seaweed to produce l-lysine and value-added products using Corynebacterium glutamicum streamlined by systems metabolic engineering

Seaweeds emerge as promising third-generation renewable for sustainable bioproduction. In the present work, we valorized brown seaweed to produce l-lysine, the world's leading feed amino acid, using Corynebacterium glutamicum, which was streamlined by systems metabolic engineering. The mutant C. glutamicum SEA-1 served as a starting point for development because it produced small amounts of l-lysine from mannitol, a major seaweed sugar, because of the deletion of its arabitol repressor AtlR and its engineered l-lysine pathway. Starting from SEA-1, we systematically optimized the microbe to redirect excess NADH, formed on the sugar alcohol, towards NADPH, required for l-lysine synthesis. The mannitol dehydrogenase variant MtlD D75A, inspired by 3D protein homology modelling, partly generated NADPH during the oxidation of mannitol to fructose, leading to a 70% increased l-lysine yield in strain SEA-2C. Several rounds of strain engineering further increased NADPH supply and l-lysine production. The best strain, SEA-7, overexpressed the membrane-bound transhydrogenase pntAB together with codon-optimized gapN, encoding NADPH-dependent glyceraldehyde 3-phosphate dehydrogenase, and mak, encoding fructokinase. In a fed-batch process, SEA-7 produced 76 g L⁻¹ l-lysine from mannitol at a yield of 0.26 mol mol⁻¹ and a maximum productivity of 2.1 g L⁻¹ h⁻¹. Finally, SEA-7 was integrated into seaweed valorization cascades. Aqua-cultured Laminaria digitata, a major seaweed for commercial alginate, was extracted and hydrolyzed enzymatically, followed by recovery and clean-up of pure alginate gum. The residual sugar-based mixture was converted to l-lysine at a yield of 0.27 C-mol C-mol⁻¹ using SEA-7. Second, stems of the wild-harvested seaweed Durvillaea antarctica, obtained as waste during commercial processing of the blades for human consumption, were extracted using acid treatment. Fermentation of the hydrolysate using SEA-7 provided l-lysine at a yield of 0.40 C-mol C-mol⁻¹. Our findings enable improvement of the efficiency of seaweed biorefineries using tailor-made C. glutamicum strains.     

Implementing a spatial model of Urban Carrying Capacity Load Number (UCCLN) to monitor the environmental loads of urban ecosystems. Case study: Tehran metropolis

The non-linear, unexpected and severe responses of ecosystems to the environmental changes crossing ecological thresholds or environmental limits, necessitate the regular monitoring of the human-induced pressures to the urban ecosystems. The present study aims to introduce a spatial decision support system for sustainable environmental planning and management of urban ecosystems by establishing an Urban Carrying Capacity Load Number model (UCCLN) based on carrying capacity concepts and sustainability principles .This model, by applying 30 temporal and spatial indicators continuously monitors the environmental loads on the urban ecosystems. Environmental load was represented by load number index. It was calculated in each zone of study area (urban districts). Geographical Information System (GIS) was used to establish UCCLN model and Spatial Decision Support System (SDSS). The study area was Tehran metropolis, the capital of Iran. The results showed that none of the 115 urban districts of Tehran had optimal Total Load Number (TLN) ranging from (10 to100); 7 districts (6%) had low-to-medium range of TLN (TLN = 100–200); 11 districts (9.5%) had medium-to-high range (TLN = 200–300); 57 districts (49.5%) had high-to-very high range (TLN = 300–400); 40 districts (34.7%) had the TLN range of very high-to-critical (TLN = 400–500); and none of them had the TLN of 500. Furthermore, the results revealed that Tehran has already overshot its ecological thresholds. Not only most of the 30 indicators of environmental pressure in most of the districts (85%) had high DCC and LN scores, but also most of the 115 districts obtained high DCC, and as a result LN scores. The need for developing more efficient urban planning and management strategies to cope with the increasing environmental loads in the study area is inevitable.     

Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection

Long-term balancing selection typically leaves narrow footprints of increased genetic diversity, and therefore most detection approaches only achieve optimal performances when sufficiently small genomic regions (i.e., windows) are examined. Such methods are sensitive to window sizes and suffer substantial losses in power when windows are large. Here, we employ mixture models to construct a set of five composite likelihood ratio test statistics, which we collectively term B statistics. These statistics are agnostic to window sizes and can operate on diverse forms of input data. Through simulations, we show that they exhibit comparable power to the best-performing current methods, and retain substantially high power regardless of window sizes. They also display considerable robustness to high mutation rates and uneven recombination landscapes, as well as an array of other common confounding scenarios. Moreover, we applied a specific version of the B statistics, termed B₂, to a human population-genomic data set and recovered many top candidates from prior studies, including the then-uncharacterized STPG2 and CCDC169–SOHLH2, both of which are related to gamete functions. We further applied B₂ on a bonobo population-genomic data set. In addition to the MHC-DQ genes, we uncovered several novel candidate genes, such as KLRD1, involved in viral defense, and SCN9A, associated with pain perception. Finally, we show that our methods can be extended to account for multiallelic balancing selection and integrated the set of statistics into open-source software named BalLeRMix for future applications by the scientific community.     

Genome-Wide Association Analysis Identifies a Genetic Basis of Infectivity in a Model Bacterial Pathogen

Knowledge of the genetic architecture of pathogen infectivity and host resistance is essential for a mechanistic understanding of coevolutionary processes, yet the genetic basis of these interacting traits remains unknown for most host–pathogen systems. We used a comparative genomic approach to explore the genetic basis of infectivity in Pasteuria ramosa, a Gram-positive bacterial pathogen of planktonic crustaceans that has been established as a model for studies of Red Queen host–pathogen coevolution. We sequenced the genomes of a geographically, phenotypically, and genetically diverse collection of P. ramosa strains and performed a genome-wide association study to identify genetic correlates of infection phenotype. We found multiple polymorphisms within a single gene, Pcl7, that correlate perfectly with one common and widespread infection phenotype. We then confirmed this perfect association via Sanger sequencing in a large and diverse sample set of P. ramosa clones. Pcl7 codes for a collagen-like protein, a class of adhesion proteins known or suspected to be involved in the infection mechanisms of a number of important bacterial pathogens. Consistent with expectations under Red Queen coevolution, sequence variation of Pcl7 shows evidence of balancing selection, including extraordinarily high diversity and absence of geographic structure. Based on structural homology with a collagen-like protein of Bacillus anthracis, we propose a hypothesis for the structure of Pcl7 and the physical location of the phenotype-associated polymorphisms. Our results offer strong evidence for a gene governing infectivity and provide a molecular basis for further study of Red Queen dynamics in this model host–pathogen system.