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1.
Bioinspir Biomim ; 17(4)2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35533656

RESUMO

Serially connected robots are promising candidates for performing tasks in confined spaces such as search and rescue in large-scale disasters. Such robots are typically limbless, and we hypothesize that the addition of limbs could improve mobility. However, a challenge in designing and controlling such devices lies in the coordination of high-dimensional redundant modules in a way that improves mobility. Here we develop a general framework to discover templates to control serially connected multi-legged robots. Specifically, we combine two approaches to build a general shape control scheme which can provide baseline patterns of self-deformation ('gaits') for effective locomotion in diverse robot morphologies. First, we take inspiration from a dimensionality reduction and a biological gait classification scheme to generate cyclic patterns of body deformation and foot lifting/lowering, which facilitate the generation of arbitrary substrate contact patterns. Second, we extend geometric mechanics, which was originally introduced to study swimming at low Reynolds numbers, to frictional environments, allowing the identification of optimal body-leg coordination in this common terradynamic regime. Our scheme allows the development of effective gaits on flat terrain with diverse numbers of limbs (4, 6, 16, and even 0 limbs) and backbone actuation. By properly coordinating the body undulation and leg placement, our framework combines the advantages of both limbless robots (modularity and narrow profile) and legged robots (mobility). Our framework can provide general control schemes for the rapid deployment of general multi-legged robots, paving the way toward machines that can traverse complex environments. In addition, we show that our framework can also offer insights into body-leg coordination in living systems, such as salamanders and centipedes, from a biomechanical perspective.


Assuntos
Robótica , Animais , Extremidades , Marcha , Locomoção , Urodelos
2.
Commun Biol ; 4(1): 1179, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635782

RESUMO

AKT-phosphorylated IWS1 promotes Histone H3K36 trimethylation and alternative RNA splicing of target genes, including the U2AF65 splicing factor-encoding U2AF2. The predominant U2AF2 transcript, upon IWS1 phosphorylation block, lacks the RS-domain-encoding exon 2, and encodes a protein which fails to bind Prp19. Here we show that although both U2AF65 isoforms bind intronless mRNAs containing cytoplasmic accumulation region elements (CAR-E), only the RS domain-containing U2AF65 recruits Prp19 and promotes their nuclear export. The loading of U2AF65 to CAR-Elements was RS domain-independent, but RNA PolII-dependent. Virus- or poly(I:C)-induced type I IFNs are encoded by genes targeted by the pathway. IWS1 phosphorylation-deficient cells therefore, express reduced levels of IFNα1/IFNß1 proteins, and exhibit enhanced sensitivity to infection by multiple cytolytic viruses. Enhanced sensitivity of IWS1-deficient cells to Vesicular Stomatitis Virus and Reovirus resulted in enhanced apoptotic cell death via caspase activation. Inhibition of this pathway may therefore sensitize cancer cells to oncolytic viruses.

3.
Nat Commun ; 12(1): 4624, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330897

RESUMO

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficient U2AF2 splice variant. Here, we show that exon 2 inclusion in the U2AF2 mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes. The exon 2-deficient U2AF2 mRNA encodes a Serine-Arginine-Rich (RS) domain-deficient U2AF65, which is defective in CDCA5 pre-mRNA processing. This results in downregulation of the CDCA5-encoded protein Sororin, a phosphorylation target and regulator of ERK, G2/M arrest and impaired cell proliferation and tumor growth. Analysis of human lung adenocarcinomas, confirmed activation of the pathway in EGFR-mutant tumors and showed that pathway activity correlates with tumor stage, histologic grade, metastasis, relapse after treatment, and poor prognosis.


Assuntos
Adenocarcinoma de Pulmão/genética , Ciclo Celular/genética , Proliferação de Células/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas de Ligação a RNA/genética , Fator de Processamento U2AF/genética , Fatores de Transcrição/genética , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Animais , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Mutação , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/metabolismo , Fator de Processamento U2AF/metabolismo , Fatores de Transcrição/metabolismo
4.
Bioinspir Biomim ; 15(6): 065005, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33111708

RESUMO

Snakes excel at moving through cluttered environments, and heterogeneities can be used as propulsive contacts for snakes performing lateral undulation. However, sidewinding, which is often associated with sandy deserts, cuts a broad path through its environment that may increase its vulnerability to obstacles. Our prior work demonstrated that sidewinding can be represented as a pair of orthogonal body waves (vertical and horizontal) that can be independently modulated to achieve high maneuverability and incline ascent, suggesting that sidewinders may also use template modulations to negotiate obstacles. To test this hypothesis, we recorded overhead video of four sidewinder rattlesnakes (Crotalus cerastes) crossing a line of vertical pegs placed in the substrate. Snakes used three methods to traverse the obstacles: a Propagate Through behavior in which the lifted moving portion of the snake was deformed around the peg and dragged through as the snake continued sidewinding (115/160 runs), Reversal turns that reorient the snake entirely (35/160), or switching to Concertina locomotion (10/160). The Propagate Through response was only used if the anterior-most region of static contact would propagate along a path anterior to the peg, or if a new region of static contact could be formed near the head to satisfy this condition; otherwise, snakes could only use Reversal turns or switch to Concertina locomotion. Reversal turns allowed the snake to re-orient and either escape without further peg contact or re-orient into a posture amenable to using the Propagate Through response. We developed an algorithm to reproduce the Propagate Through behavior in a robophysical model using a modulation of the two-wave template. This range of behavioral strategies provides sidewinders with a versatile range of options for effectively negotiating obstacles in their natural habitat, as well as provide insights into the design and control of robotic systems dealing with heterogeneous habitats.


Assuntos
Comportamento Animal/fisiologia , Locomoção/fisiologia , Serpentes/fisiologia , Algoritmos , Animais , Fenômenos Biomecânicos , Crotalus/anatomia & histologia , Crotalus/fisiologia , Ecossistema , Orientação , Serpentes/anatomia & histologia
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