PRPF8 increases the aggressiveness of hepatocellular carcinoma by regulating FAK/AKT pathway via fibronectin 1 splicing

López-Cánovas Juan L.,Hermán-Sánchez Natalia,del Rio-Moreno Mercedes,Fuentes-Fayos Antonio C.,Lara-López Araceli,Sánchez-Frias Marina E.,Amado Víctor,Ciria Rubén,Briceño Javier,de la Mata Manuel,Casta 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Hepatocellular carcinoma (HCC) pathogenesis is associated with alterations in splicing machinery components (spliceosome and splicing factors) and aberrant expression of oncogenic splice variants. We aimed to analyze the expression and potential role of the spliceosome component PRPF8 (pre-mRNA processing factor 8) in HCC. PRPF8 expression (mRNA/protein) was analyzed in a retrospective cohort of HCC patients (n = 172 HCC and nontumor tissues) and validated in two in silico cohorts (TCGA and CPTAC). PRPF8 expression was silenced in liver cancer cell lines and in xenograft tumors to understand the functional and mechanistic consequences. In silico RNAseq and CLIPseq data were also analyzed. Our results indicate that PRPF8 is overexpressed in HCC and associated with increased tumor aggressiveness (patient survival, etc.), expression of HCC-related splice variants, and modulation of critical genes implicated in cancer-related pathways. PRPF8 silencing ameliorated aggressiveness in vitro and decreased tumor growth in vivo. Analysis of in silico CLIPseq data in HepG2 cells demonstrated that PRPF8 binds preferentially to exons of protein-coding genes, and RNAseq analysis showed that PRPF8 silencing alters splicing events in multiple genes. Integrated and in vitro analyses revealed that PRPF8 silencing modulates fibronectin (FN1) splicing, promoting the exclusion of exon 40.2, which is paramount for binding to integrins. Consistent with this finding, PRPF8 silencing reduced FAK/AKT phosphorylation and blunted stress fiber formation. Indeed, HepG2 and Hep3B cells exhibited a lower invasive capacity in membranes treated with conditioned medium from PRPF8-silenced cells compared to medium from scramble-treated cells. This study demonstrates that PRPF8 is overexpressed and associated with aggressiveness in HCC and plays important roles in hepatocarcinogenesis by altering FN1 splicing, FAK/AKT activation and stress fiber formation.

Two-Stage H∞ Optimization Approach to Multirate Controller Design

Sergio López-López,Athanasios Sideris,Jie Yu 제어·로봇·시스템학회 2012 International Journal of Control, Automation, and Vol.10 No.4

A two-stage H∞ optimization methodology is presented for designing multirate controllers achieving comparable H∞ closed-loop performance with that of an optimal fast rate design at a reduced real-time computational load. In the first stage, a fast rate controller is designed by solving an H∞ optimal control problem formulated to address the design specifications; then the fast rate controller is decomposed into low frequency and high frequency parts. In the second stage, the high frequency part of the controller is retained and the low frequency part is redesigned at the slow rate using lifting and H∞ optimization. In the proposed approach, potential problems of aliasing due to the multirate nature of the controller are addressed by taking into consideration closed-loop performance.

A Simplified FE Simulation of Welded I Beam-to-RHS Column Joints

Miguel A. Serrano-López,Carlos López-Colina,Jorge González,Fernando López-Gayarre 한국강구조학회 2016 International Journal of Steel Structures Vol.16 No.4

This paper presents a study of the validity of different finite element models that can be used to simulate the welds at beamcolumn joints involving rectangular hollow sections (RHS). By comparing with actual test results several finite element models that include shell and solid element types and the presence or not of the welds, it is possible to extract some interesting conclusions about which is the simplest and most appropriate simulation mode to faithfully represent the behavior of these connections. Research in this field will guide and help further work to better knowledge of the behavior in terms of strength and stiffness of the semi-rigid joints involving welded rectangular hollow section as columns to be able to propose an extension of the component method to these kind of joints.

The genetically healthy terrestrial orchid Liparis krameri on southern Korean Peninsula

정미윤,정재민,손성원,Kangshan Mao,Jordi LÓPEZ-PUJOL,정명기 한국식물분류학회 2019 식물 분류학회지 Vol.49 No.4

Neutral genetic diversity found in plant species usually leaves an indelible footprint of historical events. Korea’s main mountain range (referred to as the Baekdudaegan [BDDG]), is known to have served as a glacial refugium primarily for the boreal and temperate flora of northeastern Asia. In addition, life-history traits (life forms, geographic range, and breeding systems) influence the within- and among-population genetic diversity of seed plant species. For example, selfing species harbor significantly less within-population genetic variation compared to predominantly outcrossers. A previous study of two Liparis species (L. makinoana and L. kumokiri) emphasizes the role of the abovementioned factors shaping the levels of genetic diversity. Liparis makinoana, mainly occurring on the BDDG and self-incompatible, harbors high levels of within-population genetic diversity (expected heterozygosity, HeP = 0.319), whereas there is no allozyme variation (HeP = 0.000) in L. kumokiri, which is self-compatible and mainly occurs in lowland hilly areas. To determine if this trend is also found in other congeners, we sampled five populations of L. krameri from the southern part of the Korean Peninsula and investigated the allozyme-based genetic diversity at 15 putative loci. The somewhat intermediate levels of within-population genetic variation (HeP = 0.145) found in L. krameri are most likely due to its occurrence in mountainous areas that, despite being outside of the main BDDG, still served as refugia, and a self-incompatible breeding system. Management strategies are suggested for L. krameri and L. makinoana based on the levels and distribution of genetic diversity and inbreeding.

Effect of the Combination Hot Water - Calcium Chloride on the In Vitro Growth of Colletotrichum gloeosporioides and the Postharvest Quality of Infected Papaya

Lidia Elena Ayón-Reyna,José Ángel López-Valenzuela,Francisco Delgado-Vargas,Martha Edith López-López,Francisco Javier Molina-Corral,Armando Carrillo-López,Misael Odín Vega-García 한국식물병리학회 2017 Plant Pathology Journal Vol.33 No.6

Anthracnose of papaya fruit caused by the fungus Colletotrichum gloeosporioides is one of the most economically important postharvest diseases. Hot water immersion (HW) and calcium chloride (Ca) treatments have been used to control papaya postharvest diseases; however, the effect of the combination HW-Ca on the pathogen growth and the development of the disease in infected papaya fruit has been scarcely studied. The aim of this study was to evaluate the effect of the HWCa treatment on the in vitro growth of C. gloesporioides conidia and the quality of infected papaya. In vitro, the HW-Ca treated conidia showed reduced mycelial growth and germination. In vivo, the HW-Ca treatment of infected papaya delayed for 5 days the onset of the anthracnose symptoms and improved the papaya postharvest quality. The combined treatment HW-Ca was better than any of the individual treatments to inhibit the in vitro development of C. gloeosporioides and to reduce the negative effects of papaya anthracnose.

CARMA LARGE AREA STAR FORMATION SURVEY: DENSE GAS IN THE YOUNG L1451 REGION OF PERSEUS

Storm, Shaye,Mundy, Lee G.,Lee, Katherine I.,Ferná,ndez-Ló,pez, Manuel,Looney, Leslie W.,Teuben, Peter,Arce, Hé,ctor G.,Rosolowsky, Erik W.,Meisner, Aaron M.,Isella, Andrea,Kauffmann American Astronomical Society 2016 The Astrophysical journal Vol.830 No.2

<P>We present a 3 mm spectral line and continuum survey of L1451 in the Perseus Molecular Cloud. These observations are from the CARMA Large Area Star Formation Survey (CLASSy), which also imaged Barnard. 1, NGC 1333, Serpens Main, and Serpens South. L1451 is the survey region with the lowest level of star formation activity-it contains no confirmed protostars. HCO+, HCN, and N2H+ (J = 1 -> 0). are all detected throughout the region, with HCO+ being the most spatially widespread, and molecular emission seen toward 90% of the area above N(H-2) column densities of 1.9 x 10(21) cm(-2). HCO+ has the broadest velocity dispersion, near 0.3 km s(-1) on average, compared with similar to 0.15 km s(-1) for the other molecules, thus representing a range of subsonic to supersonic gas motions. Our non-binary dendrogram analysis reveals that the dense gas traced by each molecule has a similar hierarchical structure, and that gas surrounding the candidate first hydrostatic core (FHSC), L1451-mm, and other previously detected single-dish continuum clumps has similar hierarchical structure; this suggests that different subregions of L1451 are fragmenting on the pathway to forming young stars. We determined that the three-dimensional morphology of the largest detectable dense-gas structures was relatively ellipsoidal compared with other CLASSy regions, which appeared more flattened at the largest scales. A virial analysis shows that the most centrally condensed dust structures are likely unstable against collapse. Additionally, we identify a new spherical, centrally condensed N2H+ feature that could be a new FHSC candidate. The overall results suggest that L1451 is a young region starting to form its generation of stars within turbulent, hierarchical structures.</P>

Flow Diverter Treatment for Non-Ruptured Carotid Aneurysms: Efficacy and Safety

López-Callejas Orlando,Ortiz-Giraldo Andres F,Vera Daniela D,Ramirez-Rojas Diego A,Villamizar-Barahona Ana B,Ferreira-Prada Carlos A.,Galvis Melquizidel,Vargas-Pérez Oliverio,Serrano-Gómez Sergio,Reye 대한신경중재치료의학회 2023 Neurointervention Vol.18 No.1

Purpose: Internal carotid artery (ICA) aneurysm treatment with a flow diverter (FD) has shown an adequate efficacy and safety profile, presenting high complete occlusion or near occlusion rates with low complications during follow-up. The purpose of this study was to evaluate the efficacy and safety of FD treatment in non-ruptured internal carotid aneurysms.Materials and Methods: This is a retrospective, single-center, observational study evaluating patients diagnosed with unruptured ICA aneurysms treated with an FD between January 1, 2014, and January 1, 2020. We analyzed an anonymized database. The primary effectiveness endpoint was complete occlusion (O’Kelly–Marotta D, OKM-D) of the target aneurysm through 1-year follow-up. The safety endpoint was the evaluation of modified Rankin Scale (mRS) 90 days after treatment, considering a favorable outcome an mRS 0-2.Results: A total of 106 patients were treated with an FD, 91.5% were women; the mean follow- up was 427.2±144.8 days. Technical success was achieved in 105 cases (99.1%). All patients included had 1-year follow-up digital subtraction angiography control; 78 patients (73.6%) completed the primary efficacy endpoint by achieving total occlusion (OKM-D). Giant aneurysms had a higher risk of not achieving complete occlusion (risk ratio, 3.07; 95% confidence interval, 1.70 - 5.54]). The safety endpoint of mRS 0-2 at 90 days was accomplished in 103 patients (97.2%).Conclusion: Treatment of unruptured ICA aneurysms with an FD showed high 1-year total occlusion results, with very low morbidity and mortality complications.

Probing spin and orbital Kondo effects with a mesoscopic interferometer

Ló,pez, Rosa,Sá,nchez, David,Lee, Minchul,Choi, Mahn-Soo,Simon, Pascal,Le Hur, Karyn American Physical Society 2005 Physical review. B, Condensed matter and materials Vol.71 No.11

Thermoelectrical detection of Majorana states

Ló,pez, Rosa,Lee, Minchul,Serra, Llorenç,Lim, Jong Soo American Physical Society 2014 Physical review. B, Condensed matter and materials Vol.89 No.20

We discuss the thermoelectrical properties of nanowires hosting Majorana states. For a Majorana nanowire directly coupled to two normal reservoirs the thermopower always vanishes regardless of the value of the Majorana overlap parameter epsilon(M), due to the particle-hole symmetric nature of the Majorana states. This situation changes drastically if a quantum dot (QD) is inserted to break the particle-hole symmetry. Then, the Majorana-side-coupled QD system exhibits a different behavior for the thermopower depending on the value of epsilon(M). The thermopower globally reverses its sign when the half-fermionic nature of the Majorana state is relevant, i.e., for epsilon(M) less than or similar to k(B)T(b), where T-b is the background temperature. For large overlap, epsilon(M) greater than or similar to k(B)T(b), on the other hand, the Seebeck coefficient behaves similarly to that in a resonant level system. The sign change of the thermopower and the fact that both the electrical and thermal conductances reach their half-fermionic value when Majorana physics are maximal could serve as a proof of the existence of Majorana states in nanowires.

Kinetic Scale Structure of Low-frequency Waves and Fluctuations

Ló,pez, Rodrigo A.,Viñ,as, Adolfo F.,Araneda, Jaime A.,Yoon, Peter H. American Astronomical Society 2017 The Astrophysical journal Vol.845 No.1

<P>The dissipation of solar wind turbulence at kinetic scales is believed to be important for the heating of the corona and for accelerating the wind. The linear Vlasov kinetic theory is a useful tool for identifying various wave modes, including kinetic Alfven, fast magnetosonic/whistler, and ion-acoustic (or kinetic slow), and their possible roles in the dissipation. However, the kinetic mode structure in the vicinity of ion-cyclotron modes is not clearly understood. The present paper aims to further elucidate the structure of these low-frequency waves by introducing discrete particle effects through hybrid simulations and Klimontovich formalism of spontaneous emission theory. The theory and simulation of spontaneously emitted low-frequency fluctuations are employed to identify and distinguish the detailed mode structures associated with ion-Bernstein modes versus quasi-modes. The spontaneous emission theory and simulation also confirm the findings of the Vlasov theory in that the kinetic Alfven waves can be defined over a wide range of frequencies, including the proton cyclotron frequency and its harmonics, especially for high-beta plasmas. This implies that these low-frequency modes may play predominant roles even in the fully kinetic description of kinetic scale turbulence and dissipation despite the fact that cyclotron harmonic and Bernstein modes may also play important roles in wave-particle interactions.</P>