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Sanchez, N.

Publications and source records attributed to Sanchez, N..

23 records · Page 2Linked to original sources

Using asymmetry to your advantage: learning to acquire and accept external assistance during prolonged split-belt walking

People often adapt their coordination patterns during walking to reduce energy cost by using sources of external assistance in the environment. Adaptation to walking on a split-belt treadmill, where one belt moves faster than the other, provides an opportunity for people to acquire positive work from the treadmill to reduce metabolic cost by modifying where they step on the faster belt. Though we know what people should do to acquire this assistance, this strategy is not observed during typical adaptation studies. Here, by extending the duration of adaptation, we show that people continuously optimize energetic cost by adjusting foot placement to acquire positive work from the treadmill and reduce the work performed by the legs. These results demonstrate that learning to acquire and take advantage of assistance to reduce energetic cost is central in shaping adaptive locomotion, but this process occurs over timescales longer than those used in typical studies.

neuroscience↗

Local adaptation fuels cryptic speciation in terrestrial annelids

Uncovering the genetic and evolutionary basis of cryptic speciation is a major focus of evolutionary biology. Next Generation Sequencing (NGS) allows the identification of genome-wide local adaptation signatures, but has rarely been applied to cryptic complexes - particularly in the soil milieu - as is the case with integrative taxonomy. The earthworm genus Carpetania, comprising six previously suggested putative cryptic lineages, is a promising model to study the evolutionary phenomena shaping cryptic speciation in soil-dwelling lineages. Genotyping-By-Sequencing (GBS) was used to provide genome-wide information about genetic variability between seventeen populations, and geometric morphometrics analyses of genital chaetae were performed to investigate unexplored cryptic morphological evolution. Genomic analyses revealed the existence of three cryptic species, with half of the previously-identified potential cryptic lineages clustering within them. Local adaptation was detected in more than 800 genes putatively involved in a plethora of biological functions (most notably reproduction, metabolism, immunological response and morphogenesis). Several genes with selection signatures showed shared mutations for each of the cryptic species, and genes under selection were enriched in functions related to regulation of transcription, including SNPs located in UTR regions. Finally, geometric morphometrics approaches partially confirmed the phylogenetic signal of relevant morphological characters such as genital chaetae. Our study therefore unveils that local adaptation and regulatory divergence are key evolutionary forces orchestrating genome evolution in soil fauna.

evolutionary biology↗

Presence of a D2 receptor truncated protein in the brain of the D2 receptor functional knockout mouse, revisiting its molecular and neurochemical features

Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein in the central nervous system. Several lines of D2R knockout mice have been generated, which share some characteristics but differ in others. The D2R functional knockout mouse, first described in 1997, is functionally null for D2R-mediated signaling but the Drd2 gene was interrupted at the most extreme distal end leaving open the question about whether transcript and protein are produced. We decided to determine if there are D2R transcripts, the characteristics of these transcripts and whether they are translated in the brain of D2R functional knockout mice. Sequence analysis of 3 Rapid Amplification of cDNA Ends showed that D2R functional knockout mice express transcripts that lack only the exon eight. Immunofluorescence showed D2R-like protein in the brain of the knockout mice. As previously reported, D2R functional knockout mice are hypoactive and insensitive to the D2R agonist quinpirole (QNP). However, the heterozygous showed locomotor activity and response to QNP similar to the wild-type mice. Intriguingly, microdialysis experiments showed that heterozygous mice, such as knockouts, have half the normal levels of synaptic dopamine in the striatum. However, heterozygous mice responded similarly to wild-type mice to an acute injection of QNP, showing a 50% decrease in synaptic dopamine. In conclusion, D2R functional knockout mice express transcripts that lead to a truncated D2R protein that lacks from the sixth transmembrane domain to the C-terminal end but retains the third intracellular loop. We discuss the implications of this truncated D2R coexisting with the native D2R that may explain the unexpected outcomes observed in the heterozygous. Finally, we suggest that the D2R functional knockout mouse can be a useful model for studying protein-protein interaction and trafficking of D2R.

neuroscience↗

Taking advantage of external mechanical work to reduce metabolic cost: the mechanics and energetics of split-belt treadmill walking

In everyday tasks such as walking and running, we exploit the work performed by external sources such as gravity to reduce the work performed by muscles. There has been considerable recent effort to design devices capable of performing mechanical work to improve walking function or reduce effort. The success of these devices relies on the user adapting their natural control strategies to take advantage of assistance provided by the device. Although locomotor adaptation is central to this process, the study of adaptation is often done using approaches that on the surface, seem to have little in common with the use of external assistance. Here, we show that one of the most common approaches for studying this process, which is adaptation to walking on a split-belt treadmill, can be understood from a perspective in which people learn to take advantage of mechanical work performed by the treadmill. During adaptation, people systematically adjust their step lengths, defined as the distance between the feet at heel strike, from one step to the next. Initially, the step length on the slow belt is longer than the step length on the fast belt, measured as a negative step length asymmetry, but people naturally reduce this asymmetry with practice. Here, we demonstrate that these modifications of step length asymmetry allow people to extract positive work from the treadmill belts to reduce the positive work performed by the legs and simultaneously reduce metabolic cost. Moreover, we show that walking with a positive step length asymmetry minimizes metabolic cost, and people prefer to walk in this manner when allowed to select their walking pattern. Together, our results suggest that split-belt adaptation can be interpreted as a process by which people learn to take advantage of mechanical work performed by an external device to improve walking economy.

neuroscience↗

Individual differences in locomotor function predict the capacity to reduce asymmetry and modify the energetic cost of walking post-stroke

Changes in the control of the lower extremities post-stroke lead to persistent biomechanical asymmetries during walking. These asymmetries are associated with an increase in energetic cost, leading to the possibility that reduction of asymmetry can improve economy. However, the influence of asymmetry on economy may depend on the direction and cause of asymmetry. For example, impairments with paretic limb advancement may result in shorter paretic steps while deficits in paretic support or propulsion result in shorter non-paretic steps. Given differences in the underlying impairments responsible for each type of step length asymmetry, the capacity to reduce asymmetry, and the associated changes in energetic cost may not be consistent across this population. Here, we identified factors explaining individual differences in the capacity to voluntarily reduce step length asymmetry and modify energetic cost during walking. Twenty-four individuals post-stroke walked on a treadmill with visual feedback of their step lengths to aid explicit modification of asymmetry. We found that individuals who naturally took longer paretic steps had a greater capacity to reduce asymmetry, and were better able to transfer the effects of training to over-ground walking. In addition, baseline energetic cost was negatively correlated with reductions in cost, such that participants with a more economical gait were more likely to reduce energetic cost by improving symmetry. These results demonstrate that many stroke survivors retain the capacity to voluntarily walk more symmetrically on a treadmill and over-ground. However, whether reductions in asymmetry reduce metabolic cost depends on individual differences in impairments affecting locomotor function.

physiology↗