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1.
Nano Lett ; 20(7): 4864-4871, 2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32551703

RESUMEN

An organic-inorganic hybrid superlattice with near perfect synergistic integration of organic and inorganic constituents was developed to produce properties vastly superior to those of either moiety alone. The complementary hybrid superlattice is composed of multiple quantum wells of 4-mercaptophenol organic monolayers and amorphous ZnO nanolayers. Within the superlattice, multichannel formation was demonstrated at the organic-inorganic interfaces to produce an excellent-performance field effect transistor exhibiting outstanding field-effect mobility with band-like transport and steep subthreshold swing. Furthermore, mutual stabilizations between organic monolayers and ZnO effectively reduced the performance degradation notorious in exclusively organic and ZnO transistors.

2.
Small ; 13(48)2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29105986

RESUMEN

Recently, deoxyribonucleic acid (DNA) is studied for electronics due to its intrinsic benefits such as its natural plenitude, biodegradability, biofunctionality, and low-cost. However, its applications are limited to passive components because of inherent insulating properties. In this report, a metal-insulator-metal tunnel diode with Au/DNA/NiOx junctions is presented. Through the self-aligning process of DNA molecules, a 2D DNA nanosheet is synthesized and used as a tunneling barrier, and semitransparent conducting oxide (NiOx ) is applied as a top electrode for resolving metal penetration issues. This molecular device successfully operates as a nonresonant tunneling diode, and temperature-variable current-voltage analysis proves that Fowler-Nordheim tunneling is a dominant conduction mechanism at the junctions. DNA-based tunneling devices appear to be promising prototypes for nanoelectronics using biomolecules.


Asunto(s)
ADN/química , Electricidad , Electrónica , Secuencia de Bases , Termodinámica
3.
J Nanosci Nanotechnol ; 15(8): 5543-52, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26369115

RESUMEN

Silver nanoparticles (AgNPs) have been shown to be effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). In this study, AgNPs were synthesized using Caesalpinia sappan extract as a reducing agent to convert Ag+ to AgNPs. Seven stabilizers (surfactants and polymers) were added during the reduction step to increase the colloidal stability and to enhance the antibacterial activity of the AgNPs. Spherical and amorphous particles were primarily observed, with estimated diameters ranging from 30.2 to 47.5 nm. X-ray diffraction confirmed the face centered cubic structures of the AgNPs. Among the employed stabilizers, the cationic surfactant cetyltrimethylammonium bromide (CTAB) exhibited the highest antibacterial activity against 19 strains of MRSA, followed by polyvinylpyrrolidone (PVP, average molecular weight of 10,000). In contrast, the anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (NaDDBS) did not exhibit any significant antibacterial activity, suggesting that the cationic surfactant head group contributed to the higher antibacterial activity of the AgNPs against MRSA.


Asunto(s)
Caesalpinia/química , Cristalización/métodos , Nanopartículas del Metal/administración & dosificación , Staphylococcus aureus Resistente a Meticilina/fisiología , Extractos Vegetales/administración & dosificación , Plata/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/síntesis química , Supervivencia Celular/efectos de los fármacos , Difusión , Ensayo de Materiales , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Tamaño de la Partícula , Extractos Vegetales/química , Sustancias Reductoras/química , Plata/química , Propiedades de Superficie
4.
Nanomedicine ; 11(7): 1677-88, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26003298

RESUMEN

Here we developed a novel green synthesis method for gold nanoparticles (CGA-AuNPs) using chlorogenic acid (CGA) as reductants without the use of other chemicals and validated the anti-inflammatory efficacy of CGA-AuNPs in vitro and in vivo. The resulting CGA-AuNPs appeared predominantly spherical in shape with an average diameter of 22.25±4.78nm. The crystalline nature of the CGA-AuNPs was confirmed by high-resolution X-ray diffraction and by selected-area electron diffraction analyses. High-resolution liquid chromatography/electrospray ionization mass spectrometry revealed that the caffeic acid moiety of CGA forms quinone structure through a two-electron oxidation causing the reduction of Au(3+) to Au(0). When compared to CGA, CGA-AuNPs exhibited enhanced anti-inflammatory effects on NF-κB-mediated inflammatory network, as well as cell adhesion. Collectively, green synthesis of CGA-AuNPs using bioactive reductants and mechanistic studies based on mass spectrometry may open up new directions in nanomedicine and CGA-AuNPs can be an anti-inflammatory nanomedicine for future applications. FROM THE CLINICAL EDITOR: Gold nanoparticles (Au NPs) have been shown to be very useful in many applications due to their easy functionalization capability. In this article, the authors demonstrated a novel method for the synthesis of gold nanoparticles using chlorogenic acid (CGA) as reductants. In-vitro experiments also confirmed biological activity of the resultant gold nanoparticles. Further in-vivo studies are awaited.


Asunto(s)
Ácido Clorogénico/administración & dosificación , Oro/administración & dosificación , Inflamación/tratamiento farmacológico , Nanopartículas del Metal/administración & dosificación , Animales , Ácidos Cafeicos/metabolismo , Ácido Clorogénico/química , Oro/química , Humanos , Inflamación/patología , Macrófagos/efectos de los fármacos , Nanopartículas del Metal/química , Ratones , FN-kappa B/biosíntesis , Difracción de Rayos X
5.
Antonie Van Leeuwenhoek ; 105(1): 191-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24287870

RESUMEN

A Gram-stain negative, strictly aerobic, non-motile, non-spore-forming, and rod-shaped bacterial strain designated FW-3(T) was isolated from fresh water and its taxonomic position was investigated by using a polyphasic approach. Strain FW-3(T) was found to grow at 10-37 °C and at pH 7.0 in the absence of NaCl on nutrient agar. On the basis of 16S rRNA gene sequence similarity, strain FW-3(T) was shown to belong to the family Acetobacteraceae and to be related to Roseomonas lacus TH-G33(T) (97.2 % sequence similarity) and Roseomonas terrae DS-48(T) (96.4 %). The G+C content of the genomic DNA was determined to be 68.0 %. The major menaquinone was determined to be Q-10 and the major fatty acids were identified as summed feature 7 (comprising C18:1 ω9c/ω12t/ω7c as defined by the MIDI system; 55.4 %), and C18:1 2OH (29.8 %). DNA and chemotaxonomic data supported the affiliation of strain FW-3(T) to the genus Roseomonas. Strain FW-3(T) could be differentiated genotypically and phenotypically from the recognized species of the genus Roseomonas. The novel isolate therefore represents a novel species, for which the name Roseomonas sediminicola sp. nov. is proposed, with the type strain FW-3(T) (=KACC 16616(T) = JCM 18210(T)).


Asunto(s)
Agua Dulce/microbiología , Methylobacteriaceae/clasificación , Methylobacteriaceae/aislamiento & purificación , ADN Bacteriano/genética , ADN Ribosómico/genética , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Methylobacteriaceae/genética , Methylobacteriaceae/metabolismo , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética
6.
Int J Syst Evol Microbiol ; 63(Pt 11): 4196-4201, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23771627

RESUMEN

Three strictly anaerobic, methanogenic strains JH1(T), JH4 and JH8 were isolated from rumen of the Korean native cattle (HanWoo; Bos taurus coreanae) in South Korea. The colonies were circular, opaque, and slightly yellowish. Phylogenetic analyses of 16S rRNA gene and mcrA (encoding α subunit of methyl-coenzyme M reductase) sequences confirmed the affiliation of the novel strains with the Methanobacteriales, and Methanobrevibacter wolinii SH(T) was the most closely related species. The 16S rRNA gene and mcrA sequence similarities between strains JH1(T), JH4 and JH8 and M. wolinii SH(T) were 96.2 and 89.0 % respectively, and DNA-DNA hybridization of the isolates and M. wolinii DSM 11976(T) showed a 20 % reassociation. Strain JH1(T) exhibited 92 % DNA-DNA relatedness with strains JH4 and JH8, and their 16S rRNA gene and mcrA sequences were identical. Cells stained Gram-positive and were non-motile rods, 1.5-1.8 µm long and 0.6 µm wide. The strains were able to use H2/CO2 and formate. The optimum temperature and pH ranges for growth were 37-40 °C and pH 6.5-7.0. The DNA G+C content of strain JH1(T) was 28 mol%. Based on data from this study using a polyphasic approach, the three strains represent a novel species of genus Methanobrevibacter, for which the name Methanobrevibacter boviskoreani sp. nov. is proposed. The type strain is JH1(T) ( = KCTC 4102(T) = JCM 18376(T)).


Asunto(s)
Bovinos/microbiología , Methanobrevibacter/clasificación , Filogenia , Rumen/microbiología , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , Methanobrevibacter/genética , Methanobrevibacter/aislamiento & purificación , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Oxidorreductasas/genética , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN
7.
Antonie Van Leeuwenhoek ; 103(6): 1385-93, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23553363

RESUMEN

A Gram-positive, coccoid to rod-shaped, non-spore-forming bacterium, designated Gsoil 958(T), was isolated from soil of a ginseng field located in Pocheon province in South Korea. This bacterium was characterized in order to determine its taxonomic position by using a polyphasic approach. Strain Gsoil 958(T) was observed to grow well at 25-30 °C and at pH 7.0 on R2A and nutrient agar without NaCl supplementation. Strain Gsoil 958(T) was determined to have ß-glucosidase activity and the ability to transform ginsenoside Rb1 (one of the dominant active components of ginseng) to F2 via gypenoside XVII and Rd. On the basis of 16S rRNA gene sequence similarity, strain Gsoil 958(T) was shown to belong to the family Nocardioidaceae and related most closely to Nocardioides koreensis MSL-09(T) (97.6 % 16S rRNA gene sequence similarity), Nocardioides aquiterrae GW-9(T) (97.0 %), and Nocardioides sediminis MSL-01(T) (97.0 %). The sequence similarities with other validly named species within the genus Nocardioides were less than 96.8 %. Strain Gsoil 958(T) was characterized chemotaxonomically as having LL-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H4) as the predominant menaquinone, and iso-C16:0, iso-C16:1 H, iso-C14:0, iso-C15:0 were identified as the major fatty acids. The G + C content of genomic DNA was determined to be 70.8 mol %. The chemotaxonomic properties and phenotypic characteristics supported the affiliation of strain Gsoil 958(T) to the genus Nocardioides. The results of both physiological and biochemical tests allowed for differentiation of strain Gsoil 958(T) from the recognized Nocardioides species. Therefore, strain Gsoil 958(T) is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioides panaciterrulae sp. nov. is proposed, with the type strain Gsoil 958(T) (KACC 14271(T) = KCTC 19471(T) = DSM 21350(T)).


Asunto(s)
Ginsenósidos/metabolismo , Panax/microbiología , Propionibacteriaceae/aislamiento & purificación , Propionibacteriaceae/metabolismo , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , Secuencia de Bases , ADN Bacteriano/genética , Ácido Diaminopimélico/análisis , Ácidos Grasos/análisis , Datos de Secuencia Molecular , Filogenia , Propionibacteriaceae/clasificación , Propionibacteriaceae/genética , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análisis , beta-Glucosidasa/metabolismo
8.
Micromachines (Basel) ; 14(8)2023 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-37630132

RESUMEN

This study presents the disorderedness effects on the subthreshold characteristics of atomically deposited ZnO thin-film transistors (TFTs). Bottom-gate ZnO TFTs show n-type enhancement-mode transfer characteristics but a gate-voltage-dependent, degradable subthreshold swing. The charge-transport characteristics of the disordered semiconductor TFTs are severely affected by the localized trap states. Thus, we posit that the disorderedness factors, which are the interface trap capacitance and the diffusion coefficient of electrons, would result in the degradation. Considering the factors as gate-dependent power laws, we derive the subthreshold current-voltage relationship for disordered semiconductors. Notably, the gate-dependent disorderedness parameters are successfully deduced and consistent with those obtained by the gm/Ids method, which was for the FinFETs. In addition, temperature-dependent current-voltage analyses reveal that the gate-dependent interface traps limit the subthreshold conduction, leading to the diffusion current. Thus, we conclude that the disorderedness factors of the ZnO films lead to the indefinable subthreshold swing of the ZnO TFTs.

9.
Materials (Basel) ; 16(8)2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37109775

RESUMEN

In this paper, we present a threshold-voltage extraction method for zinc oxide (ZnO) thin-film transistors (TFTs). Bottom-gate atomic-layer-deposited ZnO TFTs exhibit typical n-type enhancement-mode transfer characteristics but a gate-voltage-dependent, unreliable threshold voltage. We posit that this obscure threshold voltage is attributed to the localized trap states of ZnO TFTs, of which the field-effect mobility can be expressed as a gate-bias-dependent power law. Hence, we derived the current-voltage relationship by dividing the drain current with the transconductance to rule out the gate-bias-dependent factors and successfully extract the reliable threshold voltage. Furthermore, we investigated the temperature-dependent characteristics of the ZnO TFTs to validate that the observed threshold voltage was genuine. Notably, the required activation energies from the low-temperature measurements displayed an abrupt decrease at the threshold voltage, which was attributed to the conduction route change from diffusion to drift. Thus, we conclude that the reliable threshold voltage of accumulation-mode ZnO TFTs can be determined using a gate-bias-dependent factor-removed current-voltage relationship with a low-temperature analysis.

10.
J Bacteriol ; 194(22): 6362, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23105088

RESUMEN

Oscillibacter ruminantium strain GH1 was isolated from the rumen of Korean native cattle (HanWoo; Bos taurus coreanae). Here, we present the 3.07-Mb draft genome of this strain, which could reveal the presence of certain fiber-specific glycoside hydrolases and butyric acid-producing genes.


Asunto(s)
Bacterias/clasificación , Bacterias/genética , Bovinos/microbiología , Genoma Bacteriano , Rumen/microbiología , Animales , Datos de Secuencia Molecular , República de Corea
11.
Materials (Basel) ; 15(24)2022 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-36556862

RESUMEN

Although artificial porous materials are useful for dissipating acoustic waves, they pose a major environmental threat as most are non-recyclable. Developing sustainable structural materials with the mechanical and energy-absorption properties required to replace artificial porous materials is currently a key challenge. Here, we report, for the first time, a novel microstructure using all-natural moss with a compressive strength of up to 2.35 GPa and a sound-absorption performance of up to 90%, depending on the additives, such as yogurt, starch, and beer. In addition, the moss-based microstructure was applied as graffiti to a three-dimensionally printed house model to demonstrate improved performance against the effects of sound. By incorporating energy-absorbing materials without harmful substances, the desired structure can be decorated with the graffiti method. This work could pave the way for attenuating sound-wave and impact noise by using graffiti work on structural composite materials.

12.
Mol Cancer Res ; 20(3): 412-424, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34728553

RESUMEN

Loss of NF2 (merlin) has been suggested as a genetic cause of neurofibromatosis type 2 and malignant peripheral nerve sheath tumor (MPNST). Previously, we demonstrated that NF2 sustained TGFß receptor 2 (TßR2) expression and reduction or loss of NF2 activated non-canonical TGFß signaling, which reduced Raf kinase inhibitor protein (RKIP) expression via TßR1 kinase activity. Here, we show that a selective RKIP inducer (novel chemical, Nf18001) inhibits tumor growth and promotes schwannoma cell differentiation into mature Schwann cells under NF2-deficient conditions. In addition, Nf18001 is not cytotoxic to cells expressing NF2 and is not disturb canonical TGFß signaling. Moreover, the novel chemical induces expression of SOX10, a marker of differentiated Schwann cells, and promotes nuclear export and degradation of SOX2, a stem cell factor. Treatment with Nf18001 inhibited tumor growth in an allograft model with mouse schwannoma cells. These results strongly suggest that selective RKIP inducers could be useful for the treatment of neurofibromatosis type 2 as well as NF2-deficient MPNST. IMPLICATIONS: This study identifies that a selective RKIP inducer inhibits tumor growth and promotes schwannoma cell differentiation under NF2-deficient conditions by reducing SOX2 and increasing SOX10 expression.


Asunto(s)
Neurilemoma , Neurofibromatosis 2 , Neurofibrosarcoma , Animales , Diferenciación Celular , Humanos , Ratones , Neurilemoma/genética , Neurilemoma/metabolismo , Neurilemoma/patología , Neurofibromatosis 2/genética , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Proteínas de Unión a Fosfatidiletanolamina/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
13.
Polymers (Basel) ; 14(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35012024

RESUMEN

Herein, we report the fabrications of high-performance polymer field-effect transistors (PFETs) with wire bar-coated semiconducting polymer film as an active layer. For an active semiconducting material of the PFETs, we employed cyclopentadithiophene-alt-benzothiadiazole (CDT-BTZ) that is a D-A-type-conjugated copolymer consisting of a repeated electron-donating unit and an electron-accepting unit, and the other two CDT-based D-A-type copolymer analogues are cyclopentadithiophene-alt-fluorinated-benzothiadiazole (CDT-FBTZ) and cyclopentadithiophene-alt-thiadiazolopyridine (CDT-PTZ). The linear field-effect mobility values obtained from the transfer curve of the PFETs fabricated with the spin-coating were 0.04 cm2/Vs, 0.16 cm2/Vs, and 0.31 cm2/Vs, for CDT-BTZ, CDT-FBTZ, and CDT-PTZ, respectively, while the mobility values measured from the PFETs with the wire bar-coated CDT-BTZ film, CDT-FBTZ film, and CDT-PTZ film were 0.16 cm2/Vs, 0.28 cm2/Vs, and 0.95 cm2/Vs, respectively, which are about 2 to 4 times higher values than those of the PFETs with spin-coated films. These results revealed that the aligned molecular chain is beneficial for the D-A-type semiconducting copolymer even though the charge transport in the D-A-type semiconducting copolymer is known to be less critical to the degree of disorder in film.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33807417

RESUMEN

In the present study we investigated the ability of the microalgal strain Parachlorella sp. AA1 to biologically uptake a radionuclide waste material. Batch experiments were conducted to investigate the biosorption of uranyl ions (U(VI)) in the 0.5-50.0 mg/L concentration range by strain AA1. The results showed that AA1 biomass could uptake U(VI). The highest removal efficiency and biosorption capacity (95.6%) occurred within 60 h at an initial U(VI) concentration of 20 mg/L. The optimum pH for biosorption was 9.0 at a temperature of 25 °C. X-ray absorption near edge structure analysis confirmed the presence of U(VI) in pellets of Parachlorella sp. AA1 cells. The biosorption methods investigated here may be useful in the treatment and disposal of nuclides and heavy metals in diverse wastewaters.


Asunto(s)
Chlorophyta , Contaminantes Químicos del Agua , Adsorción , Biomasa , Concentración de Iones de Hidrógeno , Iones , Cinética
15.
ACS Appl Mater Interfaces ; 13(45): 54227-54236, 2021 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-34734703

RESUMEN

It is essential to tune the electrical properties of inorganic semiconductors via a doping process in the fabrication of cutting-edge electronic devices; however, the doping in organic field-effect transistors (OFETs) is limited by the uncontrollable dopant diffusion and low doping efficiencies. This study proposes the use of a fluorinated functional group in a polymer dielectric layer as an effective p-type doping strategy for ambipolar diketopyrrolopyrrole (DPP)-based donor-acceptor (D-A)-type semiconducting copolymer films used in OFETs, without generating structural perturbations. To experimentally verify the surface polarization doping effect of the fluorinated group, two terpolymers─poly(pentafluorostyrene-co-3-azidopropyl-methacrylate-co-propargyl-methacrylate) (5F-SAPMA), wherein fluorinated units are included, and poly(phenyl-methacrylate-co-3-azidopropyl-methacrylate-co-propargyl-methacrylate) (PhAPMA), without fluorinated units─are designed and synthesized for use in OFETs. The synthesized 5F-SAPMA and PhAPMA films were cross-linked through the click reaction between the alkyne and azide units in the terpolymers at 150 °C to provide chemical, thermal, and mechanical stabilities and solvent resistance. The electrical characterization of the OFETs with the newly synthesized terpolymer dielectrics reveals that the surface polarization induced by the fluorinated groups of the 5F-SAPMA dielectrics leads to the generation of additional hole charges and helps minimize the broadening of the extended tail states in the vicinity of the valence band (highest occupied molecular orbital (HOMO) level). This not only enables a transition from the ambipolar to p-type dominant characteristics but also helps increase the hole mobility from 0.023 to 0.305 cm2/(V·s).

16.
Materials (Basel) ; 14(20)2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34683616

RESUMEN

In this study, the effects of heating rate and compressive strength on the spalling behavior of single-sided heated ring-restrained concrete with compressive strengths of 60 and 100 MPa were investigated. The vapor pressure and restrained stress inside the concrete were evaluated under fast- and slow-heating conditions. Regardless of the heating rate, the concrete vapor pressure and restrained stress increased as the temperature increased, and it was confirmed that spalling occurred in the 100-MPa concrete. Specifically, it was found that moisture migration and restrained stress inside the concrete varied depending on the heating rate. Under fast heating, moisture clogging and restrained stress occurred across the concrete surface, causing continuous surface spalling for the 100-MPa concrete. Under slow heating, moisture clogging occurred, and restrained stress continuously increased in the deep area of the concrete cross-section owing to the small internal temperature difference, resulting in explosive spalling for the 100-MPa concrete with a dense internal structure. Additionally, while the tensile strength of concrete is reduced by heating, stress in the heated surface direction is generated by restrained stress. The combination of stress in the heated concrete surface and the internal vapor pressure generates spalling. The experimental results confirm that heating rate has a significant influence on moisture migration and restrained stress occurrence inside concrete, which are important factors that determine the type of spalling.

17.
Sci Rep ; 11(1): 9122, 2021 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-33907225

RESUMEN

Werner syndrome (WRN) is a rare progressive genetic disorder, caused by functional defects in WRN protein and RecQ4L DNA helicase. Acceleration of the aging process is initiated at puberty and the expected life span is approximately the late 50 s. However, a Wrn-deficient mouse model does not show premature aging phenotypes or a short life span, implying that aging processes differ greatly between humans and mice. Gene expression analysis of WRN cells reveals very similar results to gene expression analysis of Hutchinson Gilford progeria syndrome (HGPS) cells, suggesting that these human progeroid syndromes share a common pathological mechanism. Here we show that WRN cells also express progerin, an abnormal variant of the lamin A protein. In addition, we reveal that duplicated sequences of human WRN (hWRN) from exon 9 to exon 10, which differ from the sequence of mouse WRN (mWRN), are a natural inhibitor of progerin. Overexpression of hWRN reduced progerin expression and aging features in HGPS cells. Furthermore, the elimination of progerin by siRNA or a progerin-inhibitor (SLC-D011 also called progerinin) can ameliorate senescence phenotypes in WRN fibroblasts and cardiomyocytes, derived from WRN-iPSCs. These results suggest that progerin, which easily accumulates under WRN-deficient conditions, can lead to premature aging in WRN and that this effect can be prevented by SLC-D011.


Asunto(s)
Lamina Tipo A/metabolismo , Progeria/patología , Helicasa del Síndrome de Werner/metabolismo , Síndrome de Werner/genética , Adulto , Envejecimiento Prematuro/genética , Animales , Línea Celular , Senescencia Celular/efectos de los fármacos , Niño , Modelos Animales de Enfermedad , Femenino , Fibroblastos/patología , Expresión Génica , Humanos , Masculino , Ratones Mutantes , Progeria/genética , Isoformas de Proteínas , Síndrome de Werner/patología , Helicasa del Síndrome de Werner/genética
18.
Microorganisms ; 9(5)2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34065548

RESUMEN

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

19.
Commun Biol ; 4(1): 1397, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34912047

RESUMEN

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu, Zn-superoxide dismutase (SOD1) causing the gain of its toxic property are the major culprit of familial ALS (fALS). The abnormal SOD1 aggregation in the motor neurons has been suggested as the major pathological hallmark of ALS patients. However, the development of pharmacological interventions against SOD1 still needs further investigation. In this study, using ELISA-based chemical screening with wild and mutant SOD1 proteins, we screened a new small molecule, PRG-A01, which could block the misfolding/aggregation of SOD1 or TDP-43. The drug rescued the cell death induced by mutant SOD1 in human neuroblastoma cell line. Administration of PRG-A01 into the ALS model mouse resulted in significant improvement of muscle strength, motor neuron viability and mobility with extended lifespan. These results suggest that SOD1 misfolding/aggregation is a potent therapeutic target for SOD1 related ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Neuronas Motoras/fisiología , Degeneración Nerviosa/fisiopatología , Pliegue de Proteína , Superóxido Dismutasa-1/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Modelos Animales de Enfermedad , Mutación , Degeneración Nerviosa/genética , Superóxido Dismutasa-1/metabolismo
20.
Commun Biol ; 4(1): 5, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33398110

RESUMEN

Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient's cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.


Asunto(s)
Progeria/tratamiento farmacológico , Adolescente , Animales , Niño , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Células HEK293 , Humanos , Lamina Tipo A/antagonistas & inhibidores , Masculino , Ratones , Cultivo Primario de Células
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