Circular RNA (circRNA) has been proposed to be involved in carcinogenesis. Here, we explored the functional significance and regulatory role of circ-FARSA in colorectal cancer (CRC).
Gene expression ...was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. We determined the effect of circFARSA on CRC progression using cell count kit-8, colony formation assay, wound-healing assay, transwell invasion assay, luciferase reporter assay and in vivo assay.
circ-FARSA was upregulated in CRC tissues and cell lines, and its expression had a significant association with the overall survival of CRC patients. Knockdown of circ-FARSA inhibited the proliferation, migration, and invasion of CRC cells in vitro. Moreover, circ-FARSA functioned as a sponge of miR-330-5p, and its upregulation mitigated the inhibitory effects of miR-330-5p on CRC cell proliferation and metastasis. In addition, circ-FARSA regulated the expression of LIM and SH3 protein 1 (LASP1) by sponging miR-330-5p. Besides, inhibition of circ-FARSA repressed the growth of CRC in vivo.
Silencing of circ-FARSA restricted the growth of CRC through regulating the miR-330-5p/LASP1 axis, providing a novel regulatory mechanism for CRC tumorigenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Communication systems represent an evolutionary advantage for a group of robots solving coordinated tasks. In the field of evolutionary robotics, the emergence and establishment of communication are ...regulated by different variables. These systems are a tool produced by artificial evolution for the exchange of personal and environmental information. Since evolutionary processes involve multi-objective evolutionary methods, it is important to study all the mechanisms that affect the emergence and establishment of communication systems. One of these variables is the evolutionary advantage of emerging signals. In this article it is assumed that the signals appear because they are evolutionarily useful in solving a task. Emitter and receiver generate a process of conceptualization, which makes the signals associated with a meaning for the community. In this way an experiment is adapted to the FARSA simulator and the MARXBOT robot. This experiment consists of a group of robots that spend as much time as possible in a food zone and avoid a poisoned zone. Under normal conditions, robots tend to point to the food zone to attract the rest of the population. When the evolutionary importance of pointing out the food zone is reduced, the signals arise in different situations such as the presence of nearby objects and the poisoned zone. Communication is configured with the LED rings and linear cameras of the robots. In addition, an ethological method is adapted to quantify the behavioral effects of experimental manipulation.
El articulo presenta un análisis de la pervivencia del genero farsesco en el Teatro Invisible, y en las acciones performáticas del Yes Men y de Gianni Motti. Para tal se vale de conceptos extraídos ...de las reflexiones sociológicas de Erwing Goffman, demostrando como la relación entre cuadro primario, clave y fabricación ayuda a comprender tanto la farsa medieval como sus reutilizaciones contemporáneas. Además, se reflexiona sobre las posibilidades políticas del uso del farsesco, tiendo en vista tanto las contradicciones de la manipulación por una causa social como la noción de cinismo, presentada por el filósofo Peter Sloterdjik.
Se destacan tres aspectos valisos del trabajo de investigación reseñado.1. El libro se ocupa de la farsa, un género desdeñado por la teoría y la crítica hispanoamericanas, pero que, sin embargo, es ...vigente y vital en nuestra tradición hispanoamericana.2. El estudio tiene un gran alcance de mirada para estudair la farsa. No se limita en el tiempo o la región, sino que busca trazos mucho más extensos para ubicar las tradiciones de las que la farsa es heredera.3. El trabajo es riguroso y especializado, pero está escrito con una prosa precisa y clara que permite, tanto a especialistas como a lectores en general, leer muy bien la obra y seguir las principales vetas de la farsa hispanoamericana.
Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits ...(FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction. Exome sequencing was used to detect the candidate variants. The in silico prediction and expressional level analysis were performed to evaluate the pathogenicity of the variations. Additionally, we presented the patient's detailed clinical information and compared the clinical feature with other previously reported patients with FARSA-deficiency. We identified compound heterozygous rare missense variants (c.1172 T > C/ p.Leu391Pro and c.1211G > A/ p.Arg404His) in FARSA gene in a Chinese male patient. The protein structure prediction and the analysis of levels of FARSA and FARSB subunits indicated both variants pathogenic. Clinical feature review indicated inflammatory symptoms in young infants may be an additional key feature. Thyroid dysfunction should be considered as a phenotype with variable penetrance. Our results expanded the current phenotypic and genetic spectrum of FARSA-deficiency.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Music in Iberian early modern theater presents the complex challenge of recovery and coherent contextualization, especially in PreLopean theater. Diego Sánchez de Bajadoz deserves more attention not ...merely because some of his works operate as proto-zarzuelas but also because his drama pertains to a declining cycle in the trajectory of Spanish sacred theater. This essay will focus on how Diego Sánchez utilized music to intensify and inspirit sacred scripture to reclaim its luster, particularly in Farsa del juego de las cañas, alternating villancicos, coplas, hymns, singing, and dancing that bridged Iberian primitive and early modern musical thought, dramatic structure, and performance practice.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Variants in aminoacyl‐tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB, display brain ...abnormalities, interstitial lung disease and facial dysmorphism. We investigated four children from two unrelated consanguineous families carrying two missense homozygous variants in FARSA with significantly reduced PheRS‐mediated aminoacylation activity. In addition to the core ARS‐phenotype, all patients showed an inflammatory profile associated with autoimmunity and interferon score, a clinical feature not ascribed to PheRS‐deficient patients to date. JAK inhibition improved lung disease in one patient. Our findings expand the genetic and clinical spectrum of FARSA‐related disease.
Undifferentiated systemic autoinflammatory syndrome in children with FARSA loss of function variants.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pathogenic variants in genes encoding aminoacyl‐tRNA synthetases cause numerous disorders characterized by involvement of neurons, muscles, lungs and liver. Recently, biallelic FARSB defects have ...been shown to cause severe growth restriction with combined brain, liver and lung involvement (Rajab interstitial lung disease ILD with brain calcifications). Herein, for the first time, we present a patient with similar condition associated with biallelic mutations in FARSA (NM_004461.3: c.766T>C:p.Phe256Leu and c.1230C>A:p.Asn410Lys). Both detected FARSA variants are ultrarare and predicted to be damaging by in silico programs. Furthermore, they are both located in the active site of phenylalanyl‐tRNA synthetase (PheRS) with Asn410Lys directly affecting a residue forming the wall of the phenylalanine‐binding pocket. Clinical features shared between our patient and the FARSB syndrome include ILD with cholesterol pneumonitis, growth delay, hypotonia, brain calcifications with cysts and liver dysfunction. Our findings indicate that a disease similar to a syndrome associated with FARSB defects can also be caused by biallelic FARSA mutations. These findings are consistent with molecular structure of PheRS which is a tetramer including both FARSA and FARSB proteins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aminoacyl‐tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non‐canonical) functions outside of translation. Bi‐allelic pathogenic ...variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi‐allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl‐tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient‐derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non‐canonical function in FARS1‐associated recessive disease.
Bi‐allelic variants in the two genes (FARSA, FARSB) encoding distinct subunits of tetrameric cytosolic phenylalanyl‐tRNA synthetase (FARS1) cause a similar clinical phenotype that affects multiple organ systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aminoacyl tRNA transferases play an essential role in protein biosynthesis, and variants of these enzymes result in various human diseases. FARSA, which encodes the alpha subunit of cytosolic ...phenylalanyl-tRNA synthetase, was recently reported as a suspected causal gene for multiorgan disorder. This study aimed to validate the pathogenicity of variants in the FARSA gene. Exome sequencing revealed novel compound heterozygous variants in FARSA, P347L and R475Q, from a patient who initially presented neonatal-onset failure to thrive, liver dysfunction, and frequent respiratory infections. His developmental milestones were nearly arrested, and the patient died at 28 months of age as a result of progressive hepatic and respiratory failure. The P347L variant was predicted to disrupt heterodimer interaction and failed to form a functional heterotetramer by structural and biochemical analyses. R475 is located at a highly conserved site and is reported to be involved in phenylalanine activation and transfer to tRNA. The R475Q mutant FARSA were co-purified with FARSB, but the mutant enzyme showed an approximately 36% reduction in activity in our assay relative to the wild-type protein. Additional functional analyses on variants from previous reports (N410K, F256L, R404C, E418D, and F277V) were conducted. The R404C variant from a patient waiting for organ transplantation also failed to form tetramers but the E418D, N410K, F256L, and F277V variants did not affect tetramer formation. In the functional assay, the N410K located at the phenylalanine-binding site exhibited no catalytic activity, whereas other variants (E418D, F256L and F277V) exhibited lower ATPase activity than wild-type FARSA at low phenylalanine concentrations. Our data demonstrated the pathogenicity of biallelic variants in FARSA and suggested the implication of hypomorphic variants in severe phenotypes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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