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1.
Phys Rev Lett ; 130(5): 051802, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36800478

RESUMO

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

2.
Front Plant Sci ; 13: 984912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204050

RESUMO

Crop yield varies considerably within agroecology depending on the genetic potential of crop cultivars and various edaphic and climatic variables. Understanding site-specific changes in crop yield and genotype × environment interaction are crucial and needs exceptional consideration in strategic breeding programs. Further, genotypic response to diverse agro-ecologies offers identification of strategic locations for evaluating traits of interest to strengthen and accelerate the national variety release program. In this study, multi-location field trial data have been used to investigate the impact of environmental conditions on crop phenological dynamics and their influence on the yield of mungbean in different agroecological regions of the Indian subcontinent. The present attempt is also intended to identify the strategic location(s) favoring higher yield and distinctiveness within mungbean genotypes. In the field trial, a total of 34 different mungbean genotypes were grown in 39 locations covering the north hill zone (n = 4), northeastern plain zone (n = 6), northwestern plain zone (n = 7), central zone (n = 11) and south zone (n = 11). The results revealed that the effect of the environment was prominent on both the phenological dynamics and productivity of the mungbean. Noticeable variations (expressed as coefficient of variation) were observed for the parameters of days to 50% flowering (13%), days to maturity (12%), reproductive period (21%), grain yield (33%), and 1000-grain weight (14%) across the environments. The genotype, environment, and genotype × environment accounted for 3.0, 54.2, and 29.7% of the total variation in mungbean yield, respectively (p < 0.001), suggesting an oversized significance of site-specific responses of the genotypes. Results demonstrated that a lower ambient temperature extended both flowering time and the crop period. Linear mixed model results revealed that the changes in phenological events (days to 50 % flowering, days to maturity, and reproductive period) with response to contrasting environments had no direct influence on crop yields (p > 0.05) for all the genotypes except PM 14-11. Results revealed that the south zone environment initiated early flowering and an extended reproductive period, thus sustaining yield with good seed size. While in low rainfall areas viz., Sriganganagar, New Delhi, Durgapura, and Sagar, the yield was comparatively low irrespective of genotypes. Correlation results and PCA indicated that rainfall during the crop season and relative humidity significantly and positively influenced grain yield. Hence, the present study suggests that the yield potential of mungbean is independent of crop phenological dynamics; rather, climatic variables like rainfall and relative humidity have considerable influence on yield. Further, HA-GGE biplot analysis identified Sagar, New Delhi, Sriganganagar, Durgapura, Warangal, Srinagar, Kanpur, and Mohanpur as the ideal testing environments, which demonstrated high efficiency in the selection of new genotypes with wider adaptability.

3.
J Mol Graph Model ; 111: 108109, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34952481

RESUMO

The aim of this article is to investigate the sensing performance of NO gas molecule on the graphene nanoribbon domain for the determination of structural and electronic properties. Effect of an alkali metal (lithium) and a transition metal (iron) on the armchair oriented graphene nanoribbon (ArGNR) surface for the sensing purpose of NO gas has been performed through the quantum mechanics based Density Functional Theory (DFT) calculations. Various configurations of ArGNR doped with Li and Fe atoms such as one-edge doped, center doped, both-edge doped Li-ArGNR and Fe-ArGNR have been simulated, and a detailed comparative study of lithium and iron doping on different configurations of ArGNRs for the adsorption energy, stability analysis, band gap analysis and density of states analysis has been quantitatively evaluated. By comparing the adsorption energy of NO, it is found that Li doping enhances the strength of NO adsorption on the different variants of ArGNR. Computational results predict that the undoped ArGNR is insensitive to the NO gas adsorption with adsorption energy of about -0.41 eV. Our results determine that substitutional doping of Li doping at one edge doped and both-edge doped position increases the adsorption abilities of ArGNRs in these configurations with adsorption energies of approximately -6.92 eV and -9.64 eV that is 16 and 23 times greater than the pristine ArGNR (Pr-ArGNR). Band nature for both type of doping estimates the changing behavior of ArGNRs from semiconductor to metallic transition after the adsorption of NO molecule. It is concluded that the Li doping at one edge and both edge position of ArGNR makes it an excellent potential sensing material for the sensing purpose of NO gas as compared to the Fe doped configurations.


Assuntos
Grafite , Nanotubos de Carbono , Adsorção , Íons , Lítio
4.
Phys Rev Lett ; 127(20): 201801, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860065

RESUMO

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

5.
J Mol Model ; 27(9): 270, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459994

RESUMO

Density functional theory-based first-principles investigation is performed on pristine and mono vacancy induced GaAs nanoribbons to detect the presence of three volatile organic compounds (VOCs), aniline, isoprene and o-toluidine, which will aid in sensing lung cancer. The study has shown that pristine nanoribbon senses all three analytes. For the pristine structure, we observe decent adsorbing parameters and the bandgap widens after the adsorption of analytes. However, the introduction of the carrier traps induced by defect causes deep energy wells that vary the electrical properties as indicated in the bandgap analysis of GaAs, wherein adsorption of aniline and o-toluidine reduces the bandgap to 0 eV, making the structure highly conductive in nature. The adsorption energies of defect-induced nanoribbon are more as compared with the pristine counterpart. Nonetheless, the introduction of defects has improved the sensitivity further.


Assuntos
Biomarcadores Tumorais/análise , Técnicas Biossensoriais , Química Computacional , Teoria da Densidade Funcional , Neoplasias Pulmonares/diagnóstico , Arsenicais , Gálio , Humanos , Nanotubos de Carbono
6.
J Mol Model ; 26(3): 63, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32108912

RESUMO

Density functional theory based first-principles investigation study is done on armchair silicene nanoribbons (ASiNRs) for adsorption of uric acid molecule. Pristine and defect-induced variants of ASiNR are considered, and the electronic and transport properties are calculated with the adsorption. The pristine ASiNR with zero band gap is engineered with defect to create a band gap, and a significant change in the band structure of defective ASiNR after the adsorption is observed. The adsorption energy of the defective complex is calculated as - 9.21 eV which is more compared to that of the pristine counterpart, whose adsorption energy comes out to be 7.76 eV. The study shows that introduction of defect reduced the sensitivity of ASiNR toward uric acid molecule.

7.
J Mol Model ; 26(1): 4, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834483

RESUMO

A study is done to check the sensing functionality of armchair zinc oxide (ZnO) nanoribbon towards uric acid. The main focus of the research is to observe the change in the electronic properties (adsorption energy, bandstructure and density of states) and transport properties (current-voltage characteristics) of nanoribbon on adsorption of uric acid. In this work, two armchair ZnO nanoribbons of width, N = 4 and 6 atoms are used, and additional variations are created in the nanoribbon by introducing defect and doping agent. Manganese is used as a dopant. The work reveals that chemisorption occurs only in the case of doping for both widths of nanoribbons, and there is an enormous increase in the conductivity of defective armchair ZnO nanoribbon with width, N = 6 as compared to others on adsorption of uric acid. All calculations are carried out using density functional theory (DFT) and non-equilibrium Green's function (NEGF). Graphical abstract.

8.
Phys Rev Lett ; 123(15): 151803, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31702305

RESUMO

The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{µ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{µ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{µ}→ν[over ¯]_{µ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3} eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ.

9.
J Appl Microbiol ; 127(6): 1635-1645, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31517421

RESUMO

AIM: To study the association of opportunistic infection due to Myroides odoratimimus in piglets immunocompromised by porcine circovirus type 2 (PCV2) infection. METHODS AND RESULTS: The clinical samples (n = 101) were analysed bacteriologically. The isolates were identified by their phenotypes and MALDI TOF-MS analysis as Myroides species. The phylogram constructed based on nucleotide sequences of the 16S rRNA gene showed identity (~99%) with the M. odoratimimus isolates. The minimum inhibitory concentration values for antibiotics revealed M. odoratimimus to be resistant against carbapenem, cephalosporins, aminoglycosides and fluoroquinolones. The presence of PCV2 in affected tissue samples was confirmed by amplification of the 565 bp region of ORF2 of the PCV2 genome. The topology of the phylogenetic tree grouped the PCV2 with cluster-2d. CONCLUSIONS: PCV2 being immunosuppressive in nature might have impaired the immunity thereby increasing the susceptibility of immunocompromised piglets to opportunistic pathogens such as M. odoratimimus leading to disease severity and high mortality. The M. odoratimimus isolates were found to be multidrug resistant and evidenced for uncertain clinical relevance and hence could act as hidden source of public health hazard. SIGNIFICANCE AND IMPACT OF THE STUDY: Myroides odoratimimus is a rarely reported human pathogen. We reported the incidence of infection due to seemingly rare isolates of M. odoratimimus causing an outbreak of pneumonia in piglets. This appears, to the best of authors' knowledge, to be the first outbreak due to Myroides recorded in animal clinical cases described in the literature.


Assuntos
Infecções por Flavobacteriaceae/imunologia , Infecções por Flavobacteriaceae/microbiologia , Flavobacteriaceae/isolamento & purificação , Síndrome Definhante Multissistêmico de Suínos Desmamados/imunologia , Síndrome Definhante Multissistêmico de Suínos Desmamados/microbiologia , Animais , Antibacterianos/farmacologia , Circovirus/classificação , Circovirus/genética , Circovirus/isolamento & purificação , Flavobacteriaceae/classificação , Flavobacteriaceae/efeitos dos fármacos , Flavobacteriaceae/genética , Hospedeiro Imunocomprometido , Testes de Sensibilidade Microbiana , Filogenia , RNA Ribossômico 16S/genética , Suínos , Desmame
10.
3 Biotech ; 8(1): 17, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29270333

RESUMO

Out of 103 microsatellite markers used for studying the genetic diversity among local landraces of Luffa species, 56 were found polymorphic, including 38 gSSR and 18 eSSR, respectively. A total of 197 amplification products were obtained. The mean number of alleles per locus was 3.52. The PIC ranged from 0.037 to 0.986, while size of amplified product ranged from 105 to 500 bp. Cucumber-derived SSRs were amplified within L. acutangula (68%), L. aegyptiaca (61.16%), and L. hermaphrodita (60.2%), with an average of 63.12% cross-transferability. The Jaccard's coefficient ranged from 0.66 to 0.97, with an average of 0.81. High genetic variability was observed for node of 1st hermaphrodite flower (6.4-17), days to 1st hermaphrodite flower (38-52.1), days to 1st fruit harvest (43-65), number of fruit per cluster (1-5.9), fruit length (3.9-25 cm), fruit weight (18.4-175 g), number of fruit per plant (20-147.5), and yield per plant (2.2-4.7 kg). Two sub-populations were identified including 21 genotypes (sub-population I) and 06 genotypes (sub-population II), these two sub-populations showed 0.608-0.395% of the ancestral relationship to each other. This study provides information for future exploration, collection, and utilization of Luffa genotypes, as well as the polymorphic markers identified could be available for the study of landmarks in linkages, genomic structures, evolutionary ecology, and marker-assisted selection (MAS) in Luffa species.

11.
Lett Appl Microbiol ; 66(1): 44-48, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29063630

RESUMO

Leclercia adecarboxylata, a Gram-negative bacillus of family Enterobacteriaceae, is an uncommonly identified pathogen isolated from environmental and clinical specimens. Most of the human infections are polymicrobial and commonly occur in immunocompromised hosts, although nosocomial infections in immunocompetent hosts have been documented. Here, we describe the case of isolation of Leclercia species as polymicrobial infection from bovine suffering from respiratory distress in Chhattisgarh state of India. The isolates were identified by their phenotypes, 16S rDNA sequencing and MALDI-TOF-MS. The isolate was found to be resistant to aminoglycosides and fluoroquinolone antibiotics and intermediate resistant to cephalosporins and evidenced for uncertain clinical relevance and could act as hidden source of public health hazard. SIGNIFICANCE AND IMPACT OF THE STUDY: Leclercia adecarboxylata is a rarely reported human pathogen. We report here the case from bovine suffering from respiratory distress; the sample yielded Leclercia species as polymicrobial culture. The isolate was found to be multidrug resistant and evidenced for uncertain clinical relevance and could act as hidden source of public health hazard. The limited literature available on this organism is reviewed, and the potential implications of findings are discussed. To the best of our knowledge, this is the first report of isolation and characterization of multidrug-resistant Leclercia species from animal clinical case from India.


Assuntos
Antibacterianos/farmacologia , Doenças dos Bovinos/microbiologia , Coinfecção/veterinária , Infecções por Enterobacteriaceae/veterinária , Enterobacteriaceae/isolamento & purificação , Animais , Bovinos , Cefalosporinas/farmacologia , Coinfecção/microbiologia , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Hospitais Veterinários , Hospedeiro Imunocomprometido , Índia
12.
Phys Rev Lett ; 118(23): 231801, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28644674

RESUMO

Results are reported from an improved measurement of ν_{µ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{µ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.

13.
Phys Rev Lett ; 118(15): 151802, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28452513

RESUMO

This Letter reports new results on muon neutrino disappearance from NOvA, using a 14 kton detector equivalent exposure of 6.05×10^{20} protons on target from the NuMI beam at the Fermi National Accelerator Laboratory. The measurement probes the muon-tau symmetry hypothesis that requires maximal θ_{23} mixing (θ_{23}=π/4). Assuming the normal mass hierarchy, we find Δm_{32}^{2}=(2.67±0.11)×10^{-3} eV^{2} and sin^{2}θ_{23} at the two statistically degenerate values 0.404_{-0.022}^{+0.030} and 0.624_{-0.030}^{+0.022}, both at the 68% confidence level. Our data disfavor the maximal mixing scenario with 2.6σ significance.

14.
Biochimie ; 135: 154-163, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28196676

RESUMO

Dihydroorotate dehydrogenase (DHODH) is the key enzyme in de novo biosynthesis of pyrimidine in both prokaryotes and eukaryotes. The de novo pathway of pyrimidine biosynthesis is essential in cancer cells proliferation. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Despite the potential role of DHODH inhibitors in cancer therapy, their mechanisms of action remain obscure and await further elucidation. Here, we evaluated the effect of DHODH inhibitors on the production of ATP and ROS in sensitive and non-sensitive breast cancer cells. Subsequently, the effects of DHODH inhibitors on cell cycle as well as on signalling molecules such as p53, p65 and STAT6 were evaluated in sensitive T-47D and non-sensitive MDAMB-436 cells. The correlations between DHODH protein expression, proliferation speed and sensitivity to DHODH inhibitors were also investigated in a panel of cancer cell lines. DHODH inhibitors-sensitive T-47D and MDAMB-231 cells appeared to preserve ROS production closely to endogenous ROS level whereas the opposite was observed in non-sensitive MDAMB-436 and W3.006 cells. In addition, we observed approximately 90% of intracellular ATP depletion in highly sensitive T-47D and MDAMB-231 cells compared to non-sensitive MDAMB-436 cells. There was significant over-expression of p53, p65 and STAT6 signalling molecules in sensitive cells which may be involved in mediating the S-phase arrest in cell cycle progression. The current study suggests that DHODH inhibitors are most effective in cells that express high levels of DHODH enzyme. The inhibition of cell proliferation by these inhibitors appears to be accompanied by ROS production as well as ATP depletion. The increase in expression of signalling molecules observed may be due to pyrimidine depletion which subsequently leads to cell cycle arrest at S-phase.


Assuntos
Trifosfato de Adenosina/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Inibidores Enzimáticos/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Di-Hidro-Orotato Desidrogenase , Feminino , Humanos , Espécies Reativas de Oxigênio/metabolismo
15.
Indian J Cancer ; 53(1): 181-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27146774

RESUMO

INTRODUCTION: Endometrial cancer (EC) is one of the most common gynecological cancers and the fourth most common cancer in the female. Although clinical evaluation with diagnostic imaging has not yet proved to be accurate enough in the evaluation of tumor extent to replace surgical staging, it may enable optimization of the surgical procedure and a better tailored therapeutic strategy. This study will review the characteristic magnetic resonance imaging (MRI) findings in endometrial carcinomas in the pre-operative staging of endometrial carcinomas and compare it with the newly revised Federation of Gynecology and Obstetrics (FIGO) staging scheme of 2009 based on post-operative surgical histopathology. MATERIALS AND METHODS: It is a retrospective analysis of 36 patients diagnosed and treated for endometrial carcinoma in our institute from January 2009 to December 2012. RESULTS: Majority of the patients (61%) were between the age group of 41-60 years. Most of the patients (72%) were postmenopausal at the time of presentation. Most common histopathology of endometrial carcinoma was endometroid adenocarcinoma (27 patients, 75%). FIGO staging of 12 patients (85.7%) showed concordance with MRI Staging for Stage Ia, with up-gradation of two patients to Stage Ib. CONCLUSION: The information provided by MRI can define prognosis, help planning the surgical approach and identify those patients requiring neoadjuvant chemotherapy or radiation therapy.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Adulto , Animais , Embrião de Galinha , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
16.
J Orthop Surg (Hong Kong) ; 24(1): 67-71, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27122516

RESUMO

PURPOSE: To compare blade cultures in surgery for closed fracture using a single or double blade technique to determine whether the current practice of double blade technique is justified. METHODS: 155 men and 29 women aged 20 to 60 (mean, 35) years who underwent surgery for closed fracture with healthy skin at the incision site were included. Patients were block randomised to the single (n=92) or double (n=92) blade technique. Blades were sent for bacteriological analysis. Outcome measures were early surgical site infection (SSI) within 30 days and cultures from the blades. RESULTS: The 2 groups were comparable in baseline characteristics. In the single blade group, 6 surgical blades and 2 control blades showed positive cultures; 4 patients developed SSI, but only one had a positive culture from the surgical blade (with different organism isolated from the wound culture). In the double blade group, 6 skin blades, 7 deep blades, and 0 control blade showed positive culture; only 2 patients had the same bacteria grown from both skin and deep blade. Five patients developed SSI, but only one patient had a positive culture from the deep blade (with different organism isolated from the wound culture). The difference in incidence of culture-positive blade or SSI between the 2 groups was not significant. The relative risk of SSI in the single blade group was 0.8. Positive blade culture was not associated with SSI in the single or double blade group. CONCLUSION: The practice of changing blade following skin incision has no effect on reducing early SSI in surgery for closed fracture in healthy patients with healthy skin.


Assuntos
Dissecação/instrumentação , Fraturas Fechadas/cirurgia , Procedimentos Ortopédicos/instrumentação , Instrumentos Cirúrgicos/microbiologia , Infecção da Ferida Cirúrgica/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Estudos Prospectivos , Ferida Cirúrgica , Infecção da Ferida Cirúrgica/microbiologia , Adulto Jovem
17.
Phys Rev Lett ; 116(15): 151806, 2016 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27127961

RESUMO

We report results from the first search for ν_{µ}→ν_{e} transitions by the NOvA experiment. In an exposure equivalent to 2.74×10^{20} protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.99±0.11(syst) events based on the Near Detector measurement. A secondary analysis observes 11 events with a background of 1.07±0.14(syst). The 3.3σ excess of events observed in the primary analysis disfavors 0.1π<δ_{CP}<0.5π in the inverted mass hierarchy at the 90% C.L.

18.
Cancer Lett ; 320(1): 56-64, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22266192

RESUMO

The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Reparo de Erro de Pareamento de DNA/fisiologia , Fluoruracila/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/fisiologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Células HCT116 , Humanos , L-Lactato Desidrogenase/metabolismo , Proteína 1 Homóloga a MutL , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Transfecção
19.
Int J Cancer ; 130(12): 2771-82, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21805474

RESUMO

Ursodeoxycholic acid (UDCA) attenuates colon carcinogenesis in humans and in animal models by an unknown mechanism. We investigated UDCA effects on normal intestinal epithelium in vivo and in vitro to identify the potential chemopreventive mechanism. Feeding of mice with 0.4% UDCA reduced cell proliferation to 50% and suppressed several potential proproliferatory genes including insulin receptor substrate 1 (Irs-1). A similar transcriptional response was observed in the rat intestinal cell line IEC-6 which was then used as an in vitro model. UDCA slowed down the proliferation of IEC-6 cells and induced sustained hyperphosphorylation of ERK1/ERK2 kinases which completely inhibited the proproliferatory effects of EGF and IGF-1. The hyperphosphorylation of ERK1 led to a transcriptional suppression of the Irs-1 gene. Both, the hyperphosphorylation of ERK as well as the suppression of Irs-1 were sufficient to inhibit proliferation of IEC-6 cells. ERK1/ERK2 inhibition in vitro or ERK1 elimination in vitro or in vivo abrogated the antiproliferatory effects of UDCA. We show that UDCA inhibits proliferation of nontransformed intestinal epithelial cells by inducing a sustained hyperphosphorylation of ERK1 kinase which slows down the cell cycle and reduces expression of Irs-1 protein. These data extend our understanding of the physiological and potentially chemopreventive effects of UDCA and identify new targets for chemoprevention.


Assuntos
Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Fator de Crescimento Epidérmico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Proteínas Substratos do Receptor de Insulina/biossíntese , Proteínas Substratos do Receptor de Insulina/genética , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Ácido Ursodesoxicólico/metabolismo
20.
Phys Rev Lett ; 107(2): 021801, 2011 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21797594

RESUMO

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(µ) production, accumulating an exposure of 1.71 × 10²° protons on target. In the Far Detector, 97 charged current ν(µ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(µ) and ν(µ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.

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