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1.
J Invertebr Pathol ; 162: 26-42, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30735763

RESUMO

The red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) is threatening the palm family worldwide, causing important economic losses. Current tactics to manage the weevil are largely based on chemical control, although the use of pesticides is hampered by several environmental constraints. Since the first introduction of RPW in Spain in 1996 and during its progressive spread around the Mediterranean basin, the number of reports of natural infection of RPW populations by entomopathogenic fungi (EPF) has been rising for 15 years, and this rise could support a pest-mediated EPF spread. To challenge this hypothesis, we assessed the usefulness of the region of elongation factor 1-alpha (EF1-α), Bloc nuclear intergenic region (Bloc) and inter simple sequence repeat (ISSR) markers, alone or in combination, to infer the relationships among Mediterranean Beauveria and Metarhizium strains isolated from the RPW. Second, the effect of abiotic factors, such as temperature, humidity and UV-B radiation, on the germination and growth of these EPFs strains as a function of their genealogy and geographic origin were determined. Finally, the pathogenicity of strains from different genetic clades was evaluated against larvae and adults of R. ferrugineus. The phylogenetic analysis based on the EF-1α gene identified eight different sequences among 24 fungal isolates of four fungal species. Similar clades were clustered when Bloc and ISSR analyses were performed. The results showed that strains of different origins were clustered in the same clade, and this outcome could be explained by an RPW-mediated EPF spread that was also influenced by time, geographical and other RPW related factors. Neither the response to abiotic factors nor virulence to RPW larvae and adults were related to the sequence type, with all B. bassiana strains well adapted to Mediterraneam climatic conditions. Taken together, these findings may help to select the best strain for RPW management.


Assuntos
Beauveria , Mariposas/microbiologia , Micoses/diagnóstico , Controle Biológico de Vetores/métodos , Gorgulhos/microbiologia , Animais , Arecaceae , Beauveria/genética , Beauveria/patogenicidade , Marcadores Genéticos , Hypocreales/genética , Hypocreales/patogenicidade , Incidência , Espécies Introduzidas , Metarhizium/genética , Metarhizium/patogenicidade , Micoses/transmissão , Patologia Molecular , Filogenia , Espanha , Virulência
2.
Exp Appl Acarol ; 68(1): 1-20, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26471983

RESUMO

Dispersal can be an essential factor affecting the biological control of pests. Tetranychus urticae Koch (Acari: Tetranychidae) is a cosmopolitan and polyphagous species that may reach the pest status in many cropping systems including clementine orchards, where it may be found both in the trees and the associated flora. In a previous study, we demonstrated that the use of a ground cover of Festuca arundinacea Schreber (Poaceae) offered a better regulation of T. urticae populations than traditional alternatives (bare soil, multifloral wild cover). Therefore, we decided to study the ambulatory dispersal of mites crawling up and down tree trunks in a clementine mandarin orchard grown in association with a F. arundinacea cover for one season. The highest ambulatory migration rate was upward from the cover to the canopy. Multivariate regressions showed that the dynamics of T. urticae populations in the trees was strongly related to that of Phytoseiidae mites, their main natural predators. Surprisingly, canopy populations were not related to those on the ground cover or to those dispersing from it. When T. urticae individuals collected from the ground cover, the tree trunk, and the canopy were subjected to molecular analyses, the optimal number of genetic clusters (demes) was two. One clustergrouped individuals dispersed from the ground cover (e.g. collected on tree trunks) and 27.5% of individuals collected in the ground cover. The second cluster grouped all the individuals collected from trees and 72.5% of those collected in the cover. Interestingly, none of the individuals collected from the tree canopies was grouped with the first deme. This result may be taken as indicative that grass-adapted T. urticae individuals are unable to satisfactorily colonize and establish on the trees and provides evidence that host adaptation can hamper dispersal and establishment of the ground cover deme on trees, contributing to a better natural regulation of this pest species in citrus.


Assuntos
Distribuição Animal , Citrus/parasitologia , Festuca/crescimento & desenvolvimento , Cadeia Alimentar , Tetranychidae/fisiologia , Agricultura , Animais , Citrus/crescimento & desenvolvimento , Controle Biológico de Vetores
3.
Opt Express ; 22(11): 13600-15, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24921554

RESUMO

We demonstrate logic functionalities in a high-speed all-optical logic circuit based on differential Mach-Zehnder interferometers with semiconductor optical amplifiers as the nonlinear optical elements. The circuit, implemented by hybrid integration of the semiconductor optical amplifiers on a planar lightwave circuit platform fabricated in silica glass, can be flexibly configured to realize a variety of Boolean logic gates. We present both simulations and experimental demonstrations of cascaded all-optical operations for 80-Gb/s on-off keyed data.

4.
Gen Comp Endocrinol ; 194: 248-56, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24095808

RESUMO

The role of thyrotropin (thyroid-stimulating hormone, TSH) in driving peripheral thyroid function in non-mammalian species is still poorly understood. Thyroxine (T4), the principal hormone released from the thyroid gland in response to TSH stimulation, circulates with a robust daily rhythm in the teleost fish the red drum. Previous research suggests that the red drum T4 cycle is circadian in nature, driven by TSH secretion in the early photophase and inhibited by T4 feedback in the early scotophase. To determine whether TSH is produced in a pattern consistent with feedback inhibition by this T4 cycle, we used quantitative real time PCR (qPCR) to quantify the daily cycle of expression of the pituitary TSH subunits GSUα, and TSHß. We found that TSH expression cycled inversely to, and 6-12 h out of phase with, the T4 cycle, consistent with the hypothesis that TSH secretion drives the T4 cycle. To examine the potential role of deiodinases in negative feedback regulation of this TSH cycle, we also utilized qPCR to assess the pituitary expression patterns of the TH activating enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner-ring deiodinase (Dio3). Dio2 was not expressed with an obvious daily cycle, whereas Dio3 expression mirrored the expression of TSH. These results are consistent with circulating T4 providing the negative feedback signal controlling both TSH production and Dio3 expression in the pituitary, and suggest that TH inactivation by inner ring deiodination is an important component of TSH negative feedback control.


Assuntos
Iodeto Peroxidase/genética , RNA Mensageiro/genética , Tireotropina/genética , Animais , Perciformes/metabolismo , Filogenia , Hipófise/metabolismo , Tiroxina/genética , Iodotironina Desiodinase Tipo II
5.
Opt Express ; 20(2): 896-904, 2012 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-22274436

RESUMO

We propose a novel energy-efficient coherent-optical OFDM transmission scheme based on hybrid optical-electronic signal processing. We demonstrate transmission of a 0.26-Tb/s OFDM superchannel, consisting of 13 x 20-Gb/s polarization-multiplexed QPSK subcarrier channels, over 400-km standard single-mode fiber (SSMF) with BER less than 6.3x10(-4) using all-optical Fourier transform processing and electronic 7-tap blind digital equalization per subchannel. We further explore long-haul transmission over up to 960 km SSMF and show that the electronic signal processing is capable of compensating chromatic dispersion up to 16,000 ps/nm using only 15 taps per subchannel, even in the presence of strong inter-carrier interference.


Assuntos
Eletrônica/instrumentação , Eletrônica/métodos , Tecnologia de Fibra Óptica/instrumentação , Tecnologia de Fibra Óptica/métodos , Análise de Fourier , Desenho de Equipamento , Modelos Teóricos
6.
Gen Comp Endocrinol ; 177(1): 70-5, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22387984

RESUMO

Thyrotropin (TSH) is a pituitary glycoprotein hormone heterodimer that binds to its G-protein coupled receptor (TSH-R) at the thyroid to promote the synthesis and secretion of thyroid hormone. Very little is known about TSH-TSH-R interactions in teleost fish. Mammalian gonadotropins have been reported to have an intrinsic ability to activate teleost fish TSH-Rs, suggesting the TSH-R in teleost fish is more promiscuous than in other vertebrates. In this study we utilized the goldfish T(4)-release response and recombinant human TSH analogs as in vivo tools to evaluate the structural constraints on hormone-receptor interactions. We found that four positively charged lysines substituted for neutral or negatively charged amino acids within positions 11-20 of the glycoprotein hormone subunit α (GSUα) significantly increased biological activity of hTSH in fish, as it does in mammals. We further found that bovine follicle stimulating hormone but not luteinizing hormone, whose GSUα subunits also contain four lysine or arginine amino acid residues in the N-terminal portion of GSUα, was thyrotropic in goldfish, suggesting gonadotropin ß subunit contributes to the heterothyrotropic activity. Though recombinant human FSH did not produce a dose-dependent increase in T(4), thyrotropic activity could be acquired with the addition of positively charged amino acids at the N-terminal portion of its GSUα, confirming the importance of the charge on those amino acids for activation of the goldfish TSH-R. These studies demonstrate that mammalian glycoprotein hormone analogs can be utilized to evaluate the conservation of receptor binding and activation mechanisms between fish and mammals.


Assuntos
Carpa Dourada/metabolismo , Receptores da Tireotropina/metabolismo , Animais , Evolução Molecular , Carpa Dourada/sangue , Gonadotropinas/sangue , Gonadotropinas/metabolismo , Humanos , Imunoensaio , Tireotropina/farmacologia , Tiroxina/sangue
7.
Opt Express ; 19(10): 9111-7, 2011 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-21643165

RESUMO

We implement dispersion-tolerant and time-gating-free all-optical OFDM transmission using a photonic-integrated discrete Fourier transform (DFT) device. We show that 35-Gb/s OFDM data having near-unity spectral efficiency can be transmitted all-optically with 1-dB dispersion margin of ~1000 ps/nm. The passive-optical DFT circuit is implemented using multi-mode interference (MMI) couplers on a high index-contrast silica integrated-optic platform. We also propose a photonic DFT circuit based on an NxN MMI device capable of simultaneous channelization of OFDM signals into N subcarriers.

8.
Opt Express ; 19(26): B811-6, 2011 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-22274108

RESUMO

We propose that the optical OFDM technique using all optical discrete Fourier transform (DFT) has potential as a viable alternative for upgrading long-haul optical transmission systems towards 100-Gb/s. We demonstrate transmission of 35-Gb/s (7 x 5 Gb/s NRZ-OOK) all-optical OFDM signal over ~2000-km dispersion-managed span without using tunable dispersion compensation and time gating. We achieve bit error ratio of 1.2x10(-3) (7x10(-3)) for transmission over 1980-km (2310-km) all-EDFA amplified span consisting of standard single mode fiber (SSMF) and dispersion compensating fiber (DCF). We also study the nonlinear penalty impacting the all-optical OFDM transmission and discuss potential method for its mitigation.

9.
Gastrointest Endosc ; 73(4): 682-90, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21292262

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) and BE-associated early neoplasia. Most RFA studies have limited the baseline length of BE (<10 cm), and therefore little is known about RFA for longer BE. OBJECTIVE: To assess the safety and efficacy of RFA with or without prior endoscopic resection (ER) for BE ≥ 10 cm containing neoplasia. DESIGN: Prospective trial. SETTING: Two tertiary-care centers. PATIENTS: This study involved consecutive patients with BE ≥ 10 cm with early neoplasia. INTERVENTION: Focal ER for visible abnormalities, followed by a maximum of 2 circumferential and 3 focal RFA procedures every 2 to 3 months until complete remission. MAIN OUTCOME MEASUREMENTS: Complete remission, defined as endoscopic resolution of BE and no intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia) in biopsy specimens. RESULTS: Of the 26 patients included, 18 underwent ER for visible abnormalities before RFA. The ER specimens showed early cancer in 11, high-grade intraepithelial neoplasia (HGIN) in 6, and low-grade intraepithelial neoplasia (LGIN) in 1. The worst residual histology, before RFA and after any ER, was HGIN in 16 patients and LGIN in 10 patients. CR-neoplasia and CR-IM were achieved in 83% (95% confidence interval [CI], 63%-95%) and 79% (95% CI, 58%-93%), respectively. None of the patients had fatal or severe complications and 15% (95% CI, 4%-35%) had moderate complications. During a mean (± standard deviation) follow-up of 29 (± 9.1) months, no neoplasia recurred. LIMITATIONS: Tertiary-care center, short follow-up. CONCLUSION: ER for visible abnormalities, followed by RFA of residual BE is a safe and effective treatment for BE ≥ 10 cm containing neoplasia, with a low chance of recurrence of neoplasia or BE during follow-up.


Assuntos
Esôfago de Barrett/cirurgia , Ablação por Cateter/métodos , Diagnóstico Precoce , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagoscopia/métodos , Idoso , Esôfago de Barrett/patologia , Biópsia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
10.
Ann Trop Med Parasitol ; 105(5): 385-91, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21929880

RESUMO

This study aimed to evaluate the activity of cholinesterases and adenosine deaminase (ADA) in blood and serum of rats infected with Trypanosoma cruzi. Twelve adult rats were used in the experiment divided into two uniform groups. Rodents from group A (control group) were non-infected and animals from group B served as infected, receiving intraperitoneally 3·3×10(7) trypomastigotes/each. Blood collection was performed at days 60 and 120 post-infection (PI) in order to evaluate the hemogram, blood activity of acetylcholinesterase, and serum butyrylcholinesterase and ADA activities. Hematological parameters did not differ between groups. A significant increase (P<0·05) of acetylcholinesterase activity was observed in blood while butyrylcholinesterase had a significant reduction (P<0·01) in serum of infected rats at days 60 and 120 PI. ADA activity in serum showed an inhibition in infected animals when compared to non-infected at day 120 PI. Based on these results, it is possible to conclude that the activity of cholinesterases and ADA were changed in animals infected with T. cruzi. The possible causes of these alterations will be discussed in this paper.


Assuntos
Adenosina Desaminase/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Colinesterases/sangue , Coração/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Doença de Chagas/enzimologia , Masculino , Atividade Motora , Ratos
11.
Braz J Med Biol Res ; 54(8): e10850, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037096

RESUMO

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2'-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Assuntos
Adenosina Desaminase , Dipeptidil Peptidase 4 , Adenina , Humanos , Leucócitos Mononucleares , Linfócitos
12.
Opt Express ; 17(21): 19062-6, 2009 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-20372642

RESUMO

We propose a method for increased-speed all-optical XOR operation using semiconductor optical amplifiers. We demonstrate XOR and XNOR operations at 86.4 Gb/s using a pair of photonic-integrated semiconductor optical amplifier Mach-Zehnder interferometers.

13.
J Immunol Methods ; 475: 112618, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31181212

RESUMO

Fluorochrome selection is a key step in designing multi-color antibody panels. The list of available fluorochromes is continuously growing, fitting current needs in clinical flow cytometry to simultaneously use more markers to better define multiple leukocyte subpopulations in a single tube. Several criteria guide fluorochrome selection: i) the fluorescence profiles (excitation and emission), ii) relative brightness, iii) fluorescence overlap, iv) fluorochrome stability, and v) reproducible conjugation to antibodies. Here we used 75 samples (45 bone marrow and 30 blood) to illustrate EuroFlow strategies for evaluation of compatible fluorochromes, and how the results obtained guide fluorochrome selection as a critical step in the antibody-panel building process. Our results allowed identification of optimal fluorescence profiles (e.g. higher fluorescence intensity and/or resolution with limited fluorescence overlap into neighbor channels) for brilliant violet (BV)421 and BV510 in the violet laser and allophycocyanin (APC) hilite 7 (H7) or APC C750 in the red laser vs. other candidate fluorochromes generally applied for the same detectors and here evaluated. Moreover, evaluation of the same characteristics for another group of fluorochromes (e.g. BV605, BV650, PE CF594, AF700 or APC AF700) guided selection of the most appropriate fluorochrome conjugates to be combined in a multi-color antibody panel. Albeit this is a demanding approach, it could be successfully applied for selection of fluorochrome combinations for the EuroFlow antibody panels for diagnosis, classification and monitoring of hematological malignancies and primary immunodeficiencies. Consequently, sets of 8-, 10- and 12-color fluorochrome combinations are proposed as frame of reference for initial antibody panel design.


Assuntos
Citometria de Fluxo/métodos , Corantes Fluorescentes , Imunofenotipagem/métodos , Humanos
14.
Braz. j. med. biol. res ; 54(8): e10850, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1249328

RESUMO

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Assuntos
Humanos , Adenosina Desaminase , Dipeptidil Peptidase 4 , Leucócitos Mononucleares , Adenina , Linfócitos
15.
Leukemia ; 30(10): 2064-2073, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27125308

RESUMO

Although NOD-SCID IL2Rγ-/- (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, the expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis chronic myeloid leukemia patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in the expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL+ and MLL-AF9+ leukemias can be studied in detail.


Assuntos
Medula Óssea/patologia , Modelos Animais de Doenças , Proteínas de Fusão bcr-abl , Leucemia Mieloide Aguda/patologia , Proteína de Leucina Linfoide-Mieloide , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Animais , Humanos , Camundongos , Transplante Heterólogo
16.
Genetics ; 135(3): 855-68, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8293984

RESUMO

beta-Mannosidosis is a lethal lysosomal storage disease inherited as an autosomal recessive in man, cattle and goats. Laboratory assay data of plasma beta-mannosidase activity represent a mixture of homozygous normal and carrier genotype distributions in a proportion determined by genotype frequency. A maximum likelihood approach employing data transformations for each genotype distribution and assuming a diallelic model of inheritance is described. Estimates of the transformation and genotype distribution parameters, gene frequency, genotype fitness and carrier probability were obtained simultaneously from a sample of 2,812 observations on U.S. purebred Salers cattle with enzyme activity, age, gender, month of pregnancy, month of testing, and parents identified. Transformations to normality were not required, estimated gene and carrier genotype frequencies of 0.074 and 0.148 were high, and the estimated relative fitness of heterozygotes was 1.36. The apparent overdominance in fitness may be due to a nonrandom sampling of progeny genotypes within families. The mean of plasma enzyme activity was higher for males than females, higher in winter months, lower in summer months and decreased with increased age. Estimates of carrier probabilities indicate that the test is most effective when animals are sampled as calves, although effectiveness of the plasma assay was less for males than females. Test effectiveness was enhanced through averaging repeated assays of enzyme activity on each animal. Our approach contributes to medical diagnostics in several ways. Rather than assume underlying normality for the distributions comprising the mixture, we estimate transformations to normality for each genotype distribution simultaneously with all other model parameters. This process also excludes potential biases due to data preadjustment for systematic effects. We also provide a method for partitioning phenotypic variation within each genotypic distribution which allows an assessment of the value of repeat measurements of the predictive variable for genotype assignment.


Assuntos
Doenças dos Bovinos/genética , alfa-Manosidose/veterinária , Animais , Bovinos , Doenças dos Bovinos/enzimologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Manosidases/sangue , Manosidases/deficiência , Manosidases/genética , Modelos Genéticos , Modelos Estatísticos , Probabilidade , Estações do Ano , Estados Unidos , alfa-Manosidose/enzimologia , alfa-Manosidose/genética , beta-Manosidase
17.
Leukemia ; 29(3): 625-35, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25184385

RESUMO

As the transcriptional coactivator CITED2 (CBP/p300-interacting-transactivator-with-an ED-rich-tail 2) can be overexpressed in acute myeloid leukemia (AML) cells, we analyzed the consequences of high CITED2 expression in normal and AML cells. CITED2 overexpression in normal CD34(+) cells resulted in enhanced hematopoietic stem and progenitor cell (HSPC) output in vitro, as well as in better hematopoietic stem cell (HSC) engraftability in NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice. This was because of an enhanced quiescence and maintenance of CD34(+)CD38(-) HSCs, due in part to an increased expression of the cyclin-dependent kinase inhibitor CDKN1A. We demonstrated that PU.1 is a critical regulator of CITED2, as PU.1 repressed CITED2 expression in a DNA methyltransferase 3A/B (DNMT3A/B)-dependent manner in normal CD34(+) cells. CD34(+) cells from a subset of AML patients displayed higher expression levels of CITED2 as compared with normal CD34(+) HSPCs, and knockdown of CITED2 in AML CD34(+) cells led to a loss of long-term expansion, both in vitro and in vivo. The higher CITED2 expression resulted from reduced PU.1 activity and/or dysfunction of mutated DNMT3A/B. Collectively, our data demonstrate that increased CITED2 expression results in better HSC maintenance. In concert with low PU.1 levels, this could result in a perturbed myeloid differentiation program that contributes to leukemia maintenance.


Assuntos
Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Transativadores/genética , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/patologia , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Endogâmicos NOD , Mutação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Transativadores/metabolismo , Transplante Heterólogo , DNA Metiltransferase 3B
18.
J Vet Diagn Invest ; 9(4): 401-6, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9376430

RESUMO

Fenoxycarb (ethyl [2-(4-phenoxyphenoxy)-ethyl] carbamate) is an insect growth regulator used for long-term fire ant control. Because of its effects on insect reproduction and its potential use on pasturage consumed by food animals, a reproductive study was conducted using Rambouillet sheep. The sheep were dosed daily with a placebo or with fenoxycarb at 0.69 or 1.38 mg/kg/day, representing ten (10x) and 20 times (20x) the maximum amounts of fenoxycarb in forage or hay treated at recommended levels for fire ant control. Parameters that were measured included rates of weight gain of adults, serum clinical chemistry profiles of adults, spermatozoal morphology and motility, estrus cycling, pregnancy rates, maintenance of pregnancies to term, numbers of live births, and rates of weight gain of lambs to 28 days. There were no statistically significant (P < or = 0.05) differences between the exposed and control groups of sheep in any of these facets of the study. No clinical signs associated with exposure to fenoxycarb were observed in any animal at any time, and no exposure-related pattern of pathologic lesions or reproductive organ histology was observed. Means of hepatic fenoxycarb residues in the rams followed a statistically significant (P < or = 0.05) dose-related pattern. No fenoxycarb was detected (detection limit of 5 ppb) in any neonatal liver, despite the presence of hepatic fenoxycarb residues in the treated ewes, indicating that transplacental transport of fenoxycarb was minimal. No fenoxycarb was detected in any lamb liver at 28 days, although both the colostrum and the milk of exposed ewes were found to contain fenoxycarb at levels proportional to the treatments. Based on the lack of significant findings in this study, it is unlikely that use of fenoxycarb, according to label instructions (currently applicable to homeowner and registered agricultural usage) for fire ant control in pasturage or hay fields, will affect ruminant reproduction.


Assuntos
Carbamatos/toxicidade , Inseticidas/toxicidade , Fenilcarbamatos , Prenhez/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Ovinos/fisiologia , Espermatozoides/efeitos dos fármacos , Animais , Análise Química do Sangue/veterinária , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estro/efeitos dos fármacos , Feminino , Morte Fetal/induzido quimicamente , Morte Fetal/veterinária , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermátides/efeitos dos fármacos , Espermatozoides/citologia , Aumento de Peso/efeitos dos fármacos
19.
Theriogenology ; 42(7): 1095-102, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-16727613

RESUMO

The objective of this study was to determine the effectiveness of transrectal ultrasonography and serum progesterone (P(4)), estrone sulfate (E(1)S) and pregnancy-specific protein B (PSPB), without prior knowledge of reproductive status, in detecting pregnancy in elk cows. In addition, body weight and body condition score (BCS) were determined to assess whether body condition affects pregnancy status in elk cows. Twenty-five elk cows were sampled during the early rut (Period 1) and after the rut (Period 2), an interval of 120 d. Age, weight, BCS and blood samples, for P(4), E(1)S and PSPB determinations, were taken at Periods 1 and 2. Ultrasonography was performed at Period 2. The younger elk cows weighed less (P<0.05) than older cows. However, pregnancy status was not affected (P> 0.10) by age or weight of the cow. Elk cows that calved had higher (P<0.02) BCS at Periods 1 and 2 than cows that remained open. Serum P(4) and E(1)S were higher (P<0.0001) in pregnant cows at Period 2 than in open cows. Progesterone was 85.8% accurate in detecting pregnant versus open cows at Period 1, while E(1)S and PSPB were not effective. Elk cows at Period 1 were <20 d pregnant with the exception of 1 cow at 46 d. Ultrasonography was 92% accurate, P(4) was 95% accurate, and E(1)S and PSPB were both 100% accurate in determining pregnant versus open cows at Period 2. Pregnant cows at Period 2 were all > 100 d pregnant. Ultrasonography, serum E(1)S and PSPB all may provide a reliable means for pregnancy diagnosis in elk cows at > 100 d of gestation, while serum P(4) may be effective when multiple samples are compared during or after the rut, or when used in combination with the other diagnostic methods described. Further research is needed to determine the optimum time period after breeding in elk cows for accurate pregnancy detection through hormonal analysis.

20.
Theriogenology ; 49(4): 861-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10732094

RESUMO

The objectives of this investigation were to 1) determine serum concentrations of progesterone (P4), estrone sulfate (E1S) and pregnancy-specific protein B (PSPB) from estrus synchronization through mid-gestation in the fallow doe (Dama dama) and 2) characterize the hormonal profiles of does whose embryos or fetuses died in utero. Ten fallow does were synchronized for 14 d with an intravaginal P4-releasing device (CIDR) and were naturally mated after CIDR removal. Blood samples were collected at CIDR insertion, CIDR removal and at intervals through Day 203 post-CIDR removal for analysis of P4, E1S and PSPB by radioimmunoassay (RIA). Ultrasonography was performed on Days 49 and 69 post-CIDR removal. Serum P4 at the time of CIDR insertion was 4.8 +/- 0.6 ng/ml, and at CIDR withdrawal it was 6.2 +/- 0.3 ng/ml. Concentrations of E1S and PSPB were nondetectable at CIDR insertion. Serum E1S was highest at Day 93, and PSPB was first detectable in pregnant does at Days 27 to 30 post-CIDR withdrawal. Ultrasonography on Day 49 revealed that 6 does were pregnant, 2 were not pregnant and 2 others were diagnosed originally as early pregnant. At Day 69, ultrasonography revealed that 6 does (60%) were pregnant and 4 (40%) were not. A comparison of the ultrasonographic and hormonal data indicated that the 2 does diagnosed as early pregnant on Day 49 had conceived but had lost the pregnancy. A third doe which was pregnant on Day 69 lost the fetus later in gestation. Hormonal profiles of does whose embryo or fetus had died were characterized by erratic P4 and E1S profiles, with PSPB becoming undetectable in the 3 does by Days 49, 65 and 80 post-CIDR removal. These data 1) demonstrate the timing for the collection of serum samples for determining early pregnancy in fallow does using 3 hormonal methods and 2) characterize the hormonal profiles of 3 fallow does with embryonic-fetal loss.


Assuntos
Ácido Aspártico Endopeptidases/sangue , Cervos , Estrona/análogos & derivados , Morte Fetal/veterinária , Proteínas da Gravidez/sangue , Testes de Gravidez/veterinária , Progesterona/sangue , Ultrassonografia Pré-Natal/veterinária , Animais , Implantes de Medicamento , Estrona/sangue , Estro , Feminino , Morte Fetal/diagnóstico por imagem , Glicoproteínas/sangue , Gravidez , Testes de Gravidez/métodos , Progesterona/administração & dosagem
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