Biology subjects

Garcia, O.

Publications and source records attributed to Garcia, O..

4 recordsLinked to original sources

bioRxiv2025

Adaptive Increase of Amylase Gene Copy Number in Peruvians Driven by Potato-rich Diets

Summary/AbstractThe salivary amylase gene (AMY1) exhibits remarkable copy number variation linked to dietary shifts in human evolution. While global studies highlight its structural complexity and association with starch-rich diets, localized selection patterns remain under explored. Here, we analyzed AMY1 copy number in 3,723 individuals from 85 populations, revealing that Indigenous Peruvian Andean populations possess the highest AMY1 copy number globally. A genome-wide analysis showed significantly higher amylase copy numbers in Peruvian Andean genomes compared to closely related populations. Further, we identified positive selection (selection coefficient of 0.0124, log likelihood ratio of 11.1543) at the nucleotide level on a haplotype harboring at least five haploid AMY1 copies, with a Peruvian Andean-specific expansion coinciding with potato domestication ([~]6-10 kya). Using ultra-long-read sequencing, we demonstrated that previously described recombination-based mutational mechanisms drive the formation of high-copy AMY1 haplotypes observed in Andean population. Our study provides a framework for investigating structurally complex loci and their role in human dietary adaptation.

genetics↗

bioRxiv2025

Multiple, not single, recipient muscle tendon transfers produce well-directed thumb-tip forces in lateral pinch grasp: a simulation study with application to restoration of improved grasp after tetraplegia

Thumb tendon transfer surgical procedures in patients with cervical spinal injury engage the paralyzed flexor pollicis longus (FPL) muscle to enable lateral pinch grasp. However, functional outcomes are mixed, in part because the FPL cannot produce force at the thumb tip to promote a stable grasp. We used simulation to investigate whether a multi-site tendon transfer, targeting sets of paralyzed muscles driven by a single donor muscle, could outperform a single-site tendon transfer with the FPL alone and restore lateral pinch. We formed 36 groups of 2 muscles, 84 groups of 3 muscles, and 126 groups of 4 muscles. We used nonlinear optimization and in-situ measurements of endpoint forces in 3 lateral pinch postures. We found that 116 of the 246 muscle groups outperformed the FPL for wide and narrow lateral pinch postures and a posture in between. On average, the 116 muscle groups produced endpoint forces 8{degrees} to 40{degrees} better directed than the FPL, and groups of four muscles statistically significantly outperformed the FPLs force production. Our findings highlight the possibility of using multi-insertion site tendon transfers to restore grasp following cervical spinal cord injury.

bioengineering↗

bioRxiv2023

Melt electrowritten scaffold architectures to mimic vasculature mechanics and control neo-tissue orientation

Cardiovascular disease is one of the leading causes of death worldwide, commonly associated with the development of an arteriosclerotic plaque and impairment of blood flow in arteries. Current adopted grafts to bypass the stenosed vessel fail to recapitulate the unique mechanical behaviour of native vessels, particularly in the case of small diameter vessels (<6 mm), leading to graft failure. Therefore, in this study, melt-electrowriting (MEW) was adopted to produce a range of fibrous grafts to mimic the extracellular matrix (ECM) architecture of the tunica media of vessels, in an attempt to match the mechanical and biological behaviour of the native tissue. Initially, the range of collagen architectures within the native vessel was determined, and subsequently replicated using MEW (winding angles (WA) 45{degrees}, 26.5{degrees}, 18.4{degrees}, 11.3{degrees}). These scaffolds recapitulated the anisotropic, non-linear mechanical behaviour of native carotid blood vessels. Moreover, these grafts facilitated human mesenchymal stromal/stem cell (hMSC) infiltration, differentiation, and ECM deposition that was independent of WA. The bioinspired MEW fibre architecture promoted cell alignment and preferential neo-tissue orientation in a manner similar to that seen in native tissue, particularly for WA 18.4{degrees} and 11.3{degrees}, which is a mandatory requirement for long-term survival of the regenerated tissue post-scaffold degradation. Lastly, the WA 18.4{degrees} was translated to a tubular graft and was shown to mirror the mechanical behaviour of small diameter vessels within physiological strain. Taken together, this study demonstrates the capacity to use MEW to fabricate bioinspired grafts to mimic the tunica media of vessels and recapitulate vascular mechanics which could act as a framework for small diameter graft development and functional long-term tissue regeneration.

bioengineering↗

bioRxiv2021

Integrating melt-electrowriting and inkjet bioprinting for engineering structurally organized articular cartilage

Successful cartilage engineering requires the generation of biological grafts mimicking the structure, composition and mechanical behaviour of the native tissue. Here melt-electrowriting (MEW) was used to produce arrays of polymeric structures whose function was to orient the growth of cellular aggregates spontaneously generated within these structures, and to provide tensile reinforcement to the resulting tissues. Inkjeting was used to deposit defined numbers of cells into MEW structures, which self-assembled into an organized array of spheroids within hours, ultimately generating a hybrid tissue that was hyaline-like in composition. Structurally, the engineered cartilage mimicked the histotypical organization observed in skeletally immature synovial joints. This biofabrication framework was then used to generate scaled-up (50mm x 50mm) cartilage implants containing over 3,500 cellular aggregates in under 15 minutes. After 8 weeks in culture, a 50-fold increase in the compressive properties of these MEW reinforced tissues were observed, while the tensile properties were still dominated by the polymer network, resulting in a composite construct demonstrating tension-compression nonlinearity mimetic of the native tissue. Helium ion microscopy further demonstrated the development of an arcading collagen network within the engineered tissue. This hybrid bioprinting strategy provides a versatile and scalable approach to engineer cartilage biomimetic grafts for biological joint resurfacing.

bioengineering↗