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1.
RSC Adv ; 13(3): 2155, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36712620

RESUMO

[This corrects the article DOI: 10.1039/D2RA06050G.].

2.
RSC Adv ; 12(52): 33955-33963, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36505693

RESUMO

The article presents the method of producing gold nanoparticles using a high voltage arc discharge of alternating current with a frequency of 50 Hz in distilled water. The equipment necessary to carry out the process is described, including the construction of the reactor and the power source of a very simple design necessary to generate a high-voltage arc discharge between the electrodes. Arc discharge processes were carried out two times for 2 and 5 minutes, respectively, in ambient conditions without thermostating the reactor, at medium temperature varying in the range of 25-70 °C. The obtained gold nanoparticles were examined by means of various analytical techniques such as UV-vis spectroscopy, zeta potential measurement, energy dispersive X-ray analysis (EDS), X-ray diffraction (XRD). The morphology, surface, and size of the obtained nanoparticles were carried out using transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). The concentration of the obtained colloids were determined using the mass spectrometry ICP-MS technique. The results show that high-voltage AC arc discharge is a simple and effective way to obtain stable gold nanoparticles under environmentally friendly conditions at relatively low production costs, and can be considered as an alternative to arc discharge nanoparticles synthesis by means of direct current (DC) methods.

3.
Sci Rep ; 10(1): 3966, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103144

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

4.
Sci Rep ; 9(1): 17619, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772340

RESUMO

The regulation of aquatic carbon cycles by temperature is a significant uncertainty in our understanding of how watersheds will respond to climate change. Aquatic ecosystems transport substantial quantities of carbon to the atmosphere and ocean, yet we have limited understanding of how temperature modifies aquatic ecosystem metabolic processes and contributions to carbon cycles at watershed to global scales. We propose that geomorphology controls the distribution and quality of organic material that forms the metabolic base of aquatic ecosystems, thereby controlling the response of aquatic ecosystem metabolism to temperature across landscapes. Across 23 streams and four years during summer baseflow, we estimated variation in the temperature sensitivity of ecosystem respiration (R) among streams draining watersheds with different geomorphic characteristics across a boreal river basin. We found that geomorphic features imposed strong controls on temperature sensitivity; R in streams draining flat watersheds was up to six times more temperature sensitive than streams draining steeper watersheds. Further, our results show that this association between watershed geomorphology and temperature sensitivity of R was linked to the carbon quality of substrates that changed systematically across the geomorphic gradient. This suggests that geomorphology will control how carbon is transported, stored, and incorporated into river food webs as the climate warms.

5.
J Intensive Care Soc ; 20(3): 231-236, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31447916

RESUMO

Older people admitted to intensive care are considered to have lower physiological reserves, an increased susceptibility to infection and longer recovery times, resulting in generally poorer outcomes after intensive care treatment. However, biological heterogeneity makes identification of those with the best chances of survival within their group difficult and risks subjecting those at the end of their lives to unsuccessful treatments. There is no fit-for-purpose outcome prediction tool capable of identifying patients most at risk of these poor outcomes at the point of admission to intensive care. This retrospective study sought to identify factors associated with mortality in older patients (≥70 years) admitted to a teaching hospital critical care unit using objective variables readily available at the point of admission. A total of 15 variables were tested for a significant association with mortality. Of these, eight were identified as significant variables (myocardial infarction within 6 months, an abnormal ECG, congestive cardiac failure (NYHA ≥2), chronic pulmonary disease, chronic liver disease, metastatic cancer, a stay in hospital ≥5 days preceding ICU admission, and frailty (Clinical Frailty Score ≥4)). These variables were used from the basis of a novel outcome prediction model. The aim of such a model would be that it could be used at the point of referral to intensive care to inform considerations regarding admission, and to facilitate conversations with the patient and family regarding realistic treatment expectations.

6.
J Chem Phys ; 145(10): 104308, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27634261

RESUMO

Accurate Møller-Plesset (MP2) correlation energies calculated by means of the variational-perturbation and the finite-element methods are presented for several members of the Cu(+) isoelectronic series (N = 28), which represent closed-shell systems containing for the first time the 3d(10)-electron configuration and, consequently, closed M-shell. Total MP2 energies as well as their inner- and inter-shell components are reported for Cu(+), Zn(2+), Ge(4+), Kr(8+), Sr(10+), and Cd(20+). We found that for these ions the Z-dependence of the total MP2 energies is significantly weaker than for the members of the Ar-like series. The origin of this fact is rationalized by a detailed analysis performed at the levels of the shell- and inter-shell contributions to the MP2 energies. To get, for the first time, more general information about the (N, Z) characteristics of the MP2 energies for closed-shell atomic systems, we compare the Z-dependence of the Cu(+)-like systems with the MP2 energies calculated for other isoelectronic series. The weak Z-dependence is found for the He-, Ne-, and Cu(+)-like series, which consist of atoms having perfectly closed-shell K-, KL-, and KLM-electronic structures, respectively. In turn, for the Be-, Mg-, and Ar-series, the Z-dependence is considerably stronger.

7.
Bioresour Technol ; 190: 201-10, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25958143

RESUMO

This study presents the results of long-term semi-continuous experiments on anaerobic digestion at an HRT of 45d with ten silages: 2 annual and 4 perennial crops, and 4 mixtures of annual with perennial crops. The composition of substrates and digestates was determined with Van Soest's fractionation method. Removal of non-fiber materials ranged from 49.4% (Miscanthus sacchariflorus) to 89.3% (Zea mays alone and mixed with M. sacchariflorus), that of fiber materials like lignin ranged from 0.005% (Z. mays alone and mixed with grasses at VS ratio of 90:10%) to 46.5% (Sida hermaphrodita). The lowest stability of anaerobic digestion, as confirmed by normalized data concentrations of volatile fatty acids, was reported for both miscanthuses and sugar sorghum. The methane yield coefficients for non-fiber and fiber materials were 0.3666 and 0.2556L/g, respectively. All digestate residues had high fertilizing value, especially those from mixtures of crops.


Assuntos
Fibras na Dieta , Ácidos Graxos Voláteis/biossíntese , Esterco/microbiologia , Metano/metabolismo , Componentes Aéreos da Planta/microbiologia , Silagem/microbiologia , Anaerobiose/fisiologia , Animais , Bovinos , Ácidos Graxos Voláteis/isolamento & purificação , Metano/isolamento & purificação
8.
Environ Sci Pollut Res Int ; 22(2): 978-87, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25292297

RESUMO

The effect of traffic on the content of lead and cadmium in grass morphological parts-leaves, shoots, and inflorescences-was studied. The samples were taken on a part of the European route E30 (Siedlce by road). The following plants were tested: Dactylis glomerata, Arrhenatherum elatius, and Alopecurus pratensis. During the flowering of grasses, the plant material was collected at distances of 1, 5, 10, and 15 m from the edge of the road, on the strip of road with a length of 9 km. In the collected plant parts, the content of lead and cadmium using the atomic absorption spectroscopy (AAS) method was determined. The effect of distance from the road on the content of lead and cadmium was evaluated using regression equations. Average lead content in the above parts of tested grass species was 3.56, while cadmium 0.307 mg kg(-1) dry matter (DM). Lead content in plants of Alopecurus pratensis (average 4.11 mg kg(-1) DM) was significantly higher than in other grasses. The lowest cadmium content, significantly different from the other species, was found in plants of Arrhenatherum elatius (0.251 mg kg(-1) DM). Distance of sampling sites from the roadway significantly affects the differences in the content of cadmium and lead in plants. Analyzed aboveground plant organs of studied grasses were significantly different in contents of lead and cadmium. There were species differences in the proportions of cadmium concentration in various organs of plants. The obtained results indicate the possibility of species composition selection of grassland sward in areas with a higher risk of heavy metals associated with dust sedimentation.


Assuntos
Cádmio/análise , Chumbo/análise , Plantas/química , Poluentes do Solo/análise , Emissões de Veículos , Inflorescência
9.
Eur Psychiatry ; 30(1): 166-71, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24630377

RESUMO

The present study aimed at testing psychometric properties of the Composite Scale of Morningness (CSM) and validating it with mid sleep on free days (MSF) derived from the Munich ChronoType Questionnaire (MCTQ) in Poland, along with analyzing age and sex differences in the CSM and MSF. A sample of 952 Polish residents (62.6% females) aged between 13 and 46 was tested. Additionally, a sample of 33 university students were given MCTQ and filled in a sleep diary for 8 days. MSF derived from MCTQ was related to the one from sleep diary (r=.44). The study revealed good reliability of the CSM (α=.84) and its validity: greater morningness preference was associated with earlier MSF from MCTQ (r=-.52). CSM scores were distributed over its full range, with a mean of 34, and did not differ between sexes, although females were earlier than males by 23minutes in MSF. Regarding age, eveningness estimated with both CSM and MSF was greatest in subjects aged 16-18years, and a shift toward eveningness during puberty and a shift back toward morningness in older age was observed. The Polish version of the CSM consisted of two components of morningness. Cutoff scores were: for evening types (lower 10%) 24 or less, for morning types (upper 10%) 43 or more. The Polish CSM presents good psychometric properties, which are similar to those reported in other language versions, and also presents sex/age patterns similar to those found previously.


Assuntos
Ritmo Circadiano , Psicometria , Sono , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Análise de Componente Principal , Reprodutibilidade dos Testes , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
10.
Transl Psychiatry ; 4: e393, 2014 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-24893064

RESUMO

Empathy cultivates deeper interpersonal relationships and is important for socialization. However, frequent exposure to emotionally-demanding situations may put people at risk for burnout. Burnout has become a pervasive problem among medical professionals because occupational burnout may be highly sensitive to empathy levels. To better understand empathy-induced burnout among medical professionals, exploring the relationship between burnout severity and strength of empathy-related brain activity may be key. However, to our knowledge, this relationship has not yet been explored. We studied the relationship between self-reported burnout severity scores and psychological measures of empathic disposition, emotional dissonance and alexithymia in medical professionals to test two contradictory hypotheses: Burnout is explained by (1) 'compassion fatigue'; that is, individuals become emotionally over involved; and (2) 'emotional dissonance'; that is, a gap between felt and expressed emotion, together with reduced emotional regulation. Then, we tested whether increased or decreased empathy-related brain activity measured by fMRI was associated with burnout severity scores and psychological measures. The results showed that burnout severity of medical professionals is explained by 'reduced' empathy-related brain activity. Moreover, this reduced brain activity is correlated with stronger emotional dissonance and alexithymia scores and also greater empathic disposition. We speculate that reduced emotion recognition (that is, alexithymia) might potentially link with stronger emotional dissonance and greater burnout severity alongside empathy-related brain activity. In this view, greater empathic disposition in individuals with higher burnout levels might be due to greater difficulty identifying their own emotional reactions. Our study sheds new light on the ability to predict empathy-induced burnout.


Assuntos
Sintomas Afetivos/fisiopatologia , Esgotamento Profissional/fisiopatologia , Córtex Cerebral/fisiopatologia , Empatia/fisiologia , Enfermeiras e Enfermeiros/psicologia , Adulto , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Adulto Jovem
11.
Transplant Proc ; 45(4): 1347-50, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23726569

RESUMO

INTRODUCTION: Kidney transplantation is efficacious as a renal replacement, particularly pre-emptive living donation. In Poland, the rate of transplantation of living donor kidneys is only 3%. The aim of the study was to identify the most common reasons to disqualify a potential living kidney donor. METHODS: We evaluated 124 kidney donor candidates for 111 potential recipients at 1 medical center for genders and ages of donor and recipient; thus relation, donor disqualification reasons, number of potential donors for a particular recipient, prior transplantations, and kidney vasculature. RESULTS: The 111 recipients of ages 2-62 years had, 1, 2, or 3 potential donors were tested in 101, 1, and 7, cases respectively. We had 18.9% recipients referred for pre-emptive transplantation; 59.5% were on haemodialysis and 21.6% on peritoneal dialysis. In all, 89% recipients sought first kidney transplantations. Kidneys were procured from 49/124 (39.5%) of the initially evaluated donors. The full examination was completed by 92 potential donors with 68/124 donors disqualified early. Single and multiple renal arteries were detected in 56 and 36 potential donors, respectively. Donor disqualification was due to medical contraindications (39.7%), earlier transplantation from a deceased donor (25%), immunologic constraints (23.5%), donor consent withdrawn (6%) or psychological and social reasons (4.4%). CONCLUSIONS: A considerable number of donor candidates are disqualified for medical reasons.


Assuntos
Transplante de Rim , Doadores Vivos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Polônia , Obtenção de Tecidos e Órgãos , Adulto Jovem
12.
J Chem Phys ; 138(16): 164306, 2013 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-23635137

RESUMO

Benchmark results for electron densities in the ground states of Li(-), Be, C(2+), Ne(6+), and Ar(14+) have been generated from very accurate variational wave functions represented in terms of extensive basis sets of exponentially correlated Gaussian functions. For Ne(6+), and Ar(14+), the upper bounds to the energies improve over previous results known from the literature. For the remaining systems our bounds are from 0.1 to 1.1 µhartree higher than the most accurate ones. We present in graphical and, partially, numerical form results both for the radial electron densities and for the difference radial density distributions (DRD) (defined with respect to the Hartree-Fock radial density) that highlight the impact of correlation effects on electron densities. Next, we have employed these DRD distributions in studies of the performance of several broadly used orbital-based quantum-chemical methods in accounting for correlation effects on the density. Our computed benchmark densities for Be have been also applied for testing the possibility of using the mathematically strict result concerning exact atomic electron densities, obtained by Ahlrichs et al. [Phys. Rev. A 23, 2106 (1981)], for the determination of the reliability range of computed densities in the long-range asymptotic region. The results obtained for Be are encouraging.


Assuntos
Berílio/química , Elétrons , Teoria Quântica
13.
Cell Death Dis ; 4: e519, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23449455

RESUMO

The identification of recurrent somatic mutations in genes encoding epigenetic enzymes has provided a strong rationale for the development of compounds that target the epigenome for the treatment of cancer. This notion is supported by biochemical studies demonstrating aberrant recruitment of epigenetic enzymes such as histone deacetylases (HDACs) and histone methyltransferases to promoter regions through association with oncogenic fusion proteins such as PML-RARα and AML1-ETO. HDAC inhibitors (HDACi) are potent inducers of tumor cell apoptosis; however, it remains unclear why tumor cells are more sensitive to HDACi-induced cell death than normal cells. Herein, we assessed the biological and molecular responses of isogenic normal and transformed cells to the FDA-approved HDACi vorinostat and romidepsin. Both HDACi selectively killed cells of diverse tissue origin that had been transformed through the serial introduction of different oncogenes. Time-course microarray expression profiling revealed that normal and transformed cells transcriptionally responded to vorinostat treatment. Over 4200 genes responded differently to vorinostat in normal and transformed cells and gene ontology and pathway analyses identified a tumor-cell-selective pro-apoptotic gene-expression signature that consisted of BCL2 family genes. In particular, HDACi induced tumor-cell-selective upregulation of the pro-apoptotic gene BMF and downregulation of the pro-survival gene BCL2A1 encoding BFL-1. Maintenance of BFL-1 levels in transformed cells through forced expression conferred vorinostat resistance, indicating that specific and selective engagement of the intrinsic apoptotic pathway underlies the tumor-cell-selective apoptotic activities of these agents. The ability of HDACi to affect the growth and survival of tumor cells whilst leaving normal cells relatively unharmed is fundamental to their successful clinical application. This study provides new insight into the transcriptional effects of HDACi in human donor-matched normal and transformed cells, and implicates specific molecules and pathways in the tumor-selective cytotoxic activity of these compounds.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Histona Desacetilases/toxicidade , Histona Desacetilases/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular , Depsipeptídeos/toxicidade , Epigenômica , Regulação da Expressão Gênica , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/toxicidade , Antígenos de Histocompatibilidade Menor , Neoplasias/metabolismo , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Vorinostat
14.
Eur J Pain ; 17(7): 1068-73, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23322641

RESUMO

BACKGROUND: Diurnal variations in pain have been observed in experimental protocols, post-surgery states and pathological conditions. Chronotype is considered to have the most profound effect on diurnal variations, and in addition, previous studies suggest that evening types may be more vulnerable to pain than morning types. This study aimed to examine whether or not morning and evening chronotypes differ in terms of their daily levels and diurnal fluctuations of pain sensitivity. METHODS: A total of 16 morning-healthy and 15 evening-healthy men were selected using the Morningness-Eveningness Questionnaire and underwent nine measurements during 1 day (between 08:15 and 20:15 h), each consisting of five heat stimuli situated at the ventral side of the wrist. RESULTS: A marked difference between chronotypes was found, with morning types showing less sensitivity to pain than evening types all day long [M = 50.1; standard error (SE) = 1 and M = 47.2; SE = 1, respectively; pain thresholds in centigrade]. Diurnal variations in pain were not statistically significant. CONCLUSIONS: The results showed that chronotype could be an important factor determining sensitivity to pain, regardless of time of day.


Assuntos
Ritmo Circadiano/fisiologia , Dor/fisiopatologia , Sono/fisiologia , Adolescente , Adulto , Temperatura Alta/efeitos adversos , Humanos , Masculino , Limiar da Dor , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
15.
Oncogene ; 32(31): 3616-26, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22907436

RESUMO

Embryonal cancer can arise from postnatally persistent embryonal remnant or rest cells, which are uniquely characterized by the absence of p53 mutations. Perinatal overexpression of the MycN oncoprotein in embryonal cancer precursor cells causes postnatal rests, and later tumor formation through unknown mechanisms. However, overexpression of Myc in adult tissues normally activates apoptosis and/or senescence signals as an organismal defense mechanism against cancer. Here, we show that perinatal neuroblastoma precursor cells exhibited a transiently diminished p53 response to MycN oncoprotein stress and resistance to trophic factor withdrawal, compared with their adult counterpart cells from the TH-MYCN(+/+) transgenic mouse model of neuroblastoma. The adult stem cell maintenance factor and Polycomb group protein, Bmi1 (B-cell-specific Moloney murine leukemia virus integration site), had a critical role at neuroblastoma initiation in the model, by repressing p53 responses in precursor cells. We further show in neuroblastoma tumor cells that Bmi1 could directly bind p53 in a complex with other Polycomb complex proteins, Ring1A or Ring1B, leading to increased p53 ubiquitination and degradation. Repressed p53 signal responses were also seen in precursor cells for other embryonal cancer types, medulloblastoma and acute lymphoblastic leukemia. Collectively, these date indicate a general mechanism for p53 inactivation in some embryonal cell types and consequent susceptibility to MycN oncogenesis at the point of embryonal tumor initiation.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Estresse Fisiológico , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Humanos , Leucemia/metabolismo , Leucemia/patologia , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Camundongos , Proteína Proto-Oncogênica N-Myc , Neoplasias Embrionárias de Células Germinativas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Poliubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Estabilidade Proteica , Proteólise , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais , Ubiquitinação
16.
Oncogene ; 31(46): 4815-27, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22310292

RESUMO

The immortalization process is a fundamental step in the development of most (if not all) human cancers, including the aggressive endothelial cell (EC)-derived malignancy angiosarcoma. Inactivation of the tumor suppressor p16(INK4a) and the development of multiple chromosomal abnormalities are features of angiosarcoma that are recapitulated during telomerase-mediated immortalization of human ECs in vitro. The present study used a panel of telomerase-immortalized bone marrow EC (BMEC) lines to define the consequences of inactivation of p16(INK4a) on EC function and to identify molecular changes associated with repression of p16(INK4a). In a comparison of two immortalized BMEC mass cultures and six clones, the cell lines that repressed p16(INK4a) showed a higher rate of proliferation and an impaired ability to undergo morphogenic differentiation and form vessel-like structures in vitro. Proteomic comparison of a p16(INK4a)-negative and a p16(INK4a)-positive BMEC mass culture at early- and late-passage time points following transduction with telomerase reverse transcriptase (hTERT) revealed altered expression of cytoskeletal proteins, including vimentin and α-tropomyosin (αTm), in the immortal cells. Immunoblot analyses of a panel of 11 immortal clones showed that cells that lacked p16(INK4a) expression tended to accumulate more dramatic changes in these cytoskeletal proteins than cells that retained p16(INK4a) expression. This corresponded with aberrant cytoskeletal architectures among p16(INK4a)-negative clones, which featured thicker actin stress fibers and less fluid membrane ruffles than p16(INK4a)-positive cells. A direct link between p16(INK4a) repression and defective EC function was confirmed by analysis of normal cells transfected with small interfering RNA (siRNA) targeting p16(INK4a). siRNA-mediated repression of p16(INK4a) significantly impaired random motility and vessel formation in vitro. This report is the first to demonstrate that ECs that repress the expression of p16(INK4a) are prone to defects in motility, morphogenesis and cytoskeletal organization. These defects are likely to reflect alterations that occur during the development of EC-derived malignancies.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Citoesqueleto/fisiologia , Células Endoteliais/fisiologia , Actinas/genética , Actinas/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Movimento Celular/genética , Proliferação de Células , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Proteômica/métodos , Telomerase/genética , Telomerase/metabolismo , Tropomiosina/genética , Tropomiosina/metabolismo , Vimentina/genética , Vimentina/metabolismo
17.
Oncogene ; 29(44): 5957-68, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-20697349

RESUMO

Myc oncoproteins and histone deacetylases (HDACs) modulate gene transcription and enhance cancer cell proliferation, and HDAC inhibitors are among the most promising new classes of anticancer drugs. Here, we show that N-Myc and c-Myc upregulated HDAC2 gene expression in neuroblastoma and pancreatic cancer cells, respectively, which contributed to N-Myc- and c-Myc-induced cell proliferation. Cyclin G2 (CCNG2) was commonly repressed by N-Myc and HDAC2 in neuroblastoma cells and by c-Myc and HDAC2 in pancreatic cancer cells, and could be reactivated by HDAC inhibitors. 5-bromo-2'-deoxyuridine incorporation assays showed that transcriptional repression of CCNG2 was, in part, responsible for N-Myc-, c-Myc- and HDAC2-induced cell proliferation. Dual crosslinking chromatin immunoprecipitation assay demonstrated that N-Myc acted as a transrepressor by recruiting the HDAC2 protein to Sp1-binding sites at the CCNG2 gene core promoter. Moreover, HDAC2 was upregulated, and CCNG2 downregulated, in pre-cancerous and neuroblastoma tissues from N-Myc transgenic mice, and c-Myc overexpression correlated with upregulation of HDAC2 and repression of CCNG2 in tumour tissues from pancreatic cancer patients. Taken together, our data indicate the critical roles of upregulation of HDAC2 and suppression of CCNG2 in Myc-induced oncogenesis, and have significant implications for the application of HDAC inhibitors in the prevention and treatment of Myc-driven cancers.


Assuntos
Histona Desacetilase 2/genética , Proteínas Proto-Oncogênicas c-myc/fisiologia , Transcrição Gênica , Regulação para Cima , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Imunoprecipitação da Cromatina , Ciclina G2/genética , Primers do DNA , Humanos , Camundongos , Camundongos Transgênicos , Neuroblastoma/patologia , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
J Thromb Haemost ; 8(4): 651-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20088923

RESUMO

OBJECTIVE: Current risk stratification in acute pulmonary embolism (APE) includes assessment of clinical status, right ventricular overload and plasma troponin concentrations. As impaired renal function is one of the important predictors of mortality in cardiovascular diseases, we hypothesized that it is an independent early mortality marker in APE. MATERIAL AND METHODS: In prospective cohort study, we observed 220 consecutive patients (86M/134F, 64 +/- 18 years) with APE proven by spiral computed tomography (CT). On admission, echocardiography was performed and blood samples were collected for troponin and creatinine assays. RESULTS: The calculated glomerular filtration rate (GFR) differed significantly between 81 pts with low-, 131 pts with moderate- and 8 pts with high-risk APE [71 (19-181) vs. 55 (9-153) vs. 41 (14-68) mL min(-1); respectively P < 0.0001]. Twenty-three patients died during the 30-day observation. Importantly, GFR was lower in non-survivors than in survivors [35 (9-92) vs. 63 (14-181) mL min(-1), P < 0.0001]. The area under the curve (AUC) of the GFR receiver-operating characteristic (ROC) curve for predicting mortality was 0.760 (95% CI: 0.698-0.815). In multivariable analysis, independent mortality predictors were GFR, troponin, heart rate and history of chronic heart failure. In normotensive patients, the GFR and cardiac troponins (cTn) ROC curves for prediction of mortality showed no difference (AUC 0.789 and 0.781, respectively). However, Kaplan-Meier analysis showed an additive prognostic value of renal dysfunction. Thus, troponin-positive patients with a GFR < or = 35 mL mn(-1) showed 48% 30-day mortality, whereas troponin-positive patients with a GFR > 35 mL mn(-1) had 11% mortality, and troponin-negative patients with a GFR > 35 mL mn(-1) had good prognosis, P < 0.0001. CONCLUSION: Impaired kidney function, present in 47% of APE patients, is related to all-cause mortality. In initially normotensive patients, a GFR < 35 mL min(-1) predicts 30-day mortality. Moreover, GFR assessment can improve troponin-based risk stratification of APE.


Assuntos
Taxa de Filtração Glomerular , Cardiopatias/mortalidade , Nefropatias/mortalidade , Rim/fisiopatologia , Embolia Pulmonar/mortalidade , Troponina/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Creatinina/sangue , Feminino , Cardiopatias/sangue , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Hemodinâmica , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Nefropatias/sangue , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Curva ROC , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada Espiral , Ultrassonografia
19.
J Chem Phys ; 130(16): 164102, 2009 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-19405556

RESUMO

The problem of linking the dynamic electron correlation effects defined in traditional ab initio methods [or wave function theories (WFTs)] with the structure of the individual density functional theory (DFT) exchange and correlation functionals has been analyzed for the Ne atom, for which nondynamic correlation effects play a negligible role. A density-based approach directly hinged on difference radial-density (DRD) distributions defined with respect the Hartree-Fock radial density has been employed for analyzing the impact of dynamic correlation effects on the density. Attention has been paid to the elimination of basis-set incompleteness errors. The DRD distributions calculated by several ab initio methods have been compared to their DFT counterparts generated for representatives of several generations of broadly used exchange-correlation functionals and for the recently developed orbital-dependent OEP2 exchange-correlation functional [Bartlett et al., J. Chem. Phys. 122, 034104 (2005)]. For the local, generalized-gradient, and hybrid functionals it has been found that the dynamic correlation effects are to a large extend accounted for by densities resulting from exchange-only calculations. Additional calculations with self-interaction corrected exchange potentials indicate that this finding cannot be explained as an artifact caused by the self-interaction error. It has been demonstrated that the VWN5 and LYP correlation functionals do not represent any substantial dynamical correlation effects on the electron density, whereas these effects are well represented by the orbital-dependent OEP2 correlation functional. Critical comparison of the present results with their counterparts reported in literature has been made. Some attention has been paid to demonstrating the differences between the energy- and density-based perspectives. They indicate the usefulness of density-based criteria for developing new exchange-correlation functionals.

20.
Leukemia ; 21(5): 983-91, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17344914

RESUMO

Excessive telomere shortening has been demonstrated in inherited and acquired blood disorders, including aplastic anemia and myelodysplastic syndromes. It is possible that replicative exhaustion, owing to critical telomere shortening in hematopoietic progenitor cells (HPCs), contributes to the development of cytopenias in these disorders. However to date, a direct link between the telomere length (TL) of human HPCs and their proliferative potential has not been demonstrated. In the present investigation, the TL and level of telomerase enzyme activity (TA) detected in cord blood (CB)-derived HPCs was found to predict erythroid expansion (P<0.01 and P=0.01 respectively). These results were corroborated by a correlation between proliferation of erythroid cells and telomere loss (P=0.01). In contrast, no correlations were found between initial TL, telomere loss or TA and the expansion of other myeloid lineage-committed cells. There was also no correlation between TL or TA and the number of clonogenic progenitors, including primitive progenitors derived from long-term culture. Our investigations revealed upregulation of telomerase to tumor cell levels in CD34- cells undergoing erythroid differentiation. Together, these results provide new insight into the regulation of TL and TA during myeloid cell expansion and demonstrate that TL is an important determinant of CB-derived erythroid cell proliferation.


Assuntos
Antígenos CD34/análise , Células Precursoras Eritroides/citologia , Sangue Fetal/citologia , Telômero , Linhagem da Célula , Proliferação de Células , Humanos , Interleucina-6/farmacologia , Telomerase/metabolismo
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