A common ancestor DNA motif for invertebrate and vertebrate hormone response elements.

The ecdysone-responsive DNA sequence of the Drosophila hsp27 gene promoter contains four direct and inverted repeats reminiscent of those that compose the vertebrate palindromic estrogen response element (ERE) and the thyroid hormone/retinoic acid response element (TRE/RRE). Interestingly, a 3 bp substitution in the wild-type Hsp27 ecdysone response element (EcdRE) increases both its similarity with the vertebrate ERE and TRE/RRE and its capacity to confer ecdysone responsiveness to a heterologous promoter. Remarkably, increasing the spacing between the inverted repeats of this strong EcdRE by two nucleotides converts it into an ERE. Inversely, decreasing the spacing between the two inverted repeats of the vertebrate consensus palindromic ERE, from three to one nucleotide, converts it into a functional EcdRE. Thus, the only difference between an invertebrate EcdRE and a vertebrate palindromic ERE or TRE/RRE is in the spacing between the conserved inverted repeated motifs forming these palindromic HREs. The finding that the sequence motif 5'-GGTCA-3' present in the vertebrate ERE and TRE/RRE is also a functionally important characteristic of an invertebrate HRE, suggests that a common ancestor regulatory DNA sequence gave rise to all HREs known so far. We discuss the possibility that this progenitor motif is the GGTCA sequence.

Influência do tipo de amostragem na constante dielétrica do solo e na calibração de sondas de TDR

A técnica da TDR é uma importante ferramenta para o estudo do teor de água no solo. Para o correto emprego dessa técnica, é necessário calibrar modelos que relacionam o conteúdo volumétrico de água no solo com a constante dielétrica deste, considerando as características de cada solo. Assim, objetivou-se avaliar a influência do tipo de solo e da forma de amostragem (amostra deformada e não deformada) na constante dielétrica (Ka) do solo e no desempenho de modelos para a estimativa do conteúdo volumétrico de água no solo (), usando a técnica TDR. Os solos utilizados foram um Cambissolo Háplico Tb distrófico (CX), um Latossolo Vermelho ácrico típico (LV) e um Neossolo Quartzarênico (RQ), que apresentam diferenças quanto à textura. As amostras de solo referentes a CX e LV foram coletadas com estruturas deformadas e não deformadas, e as de RQ, apenas deformadas, devido à baixa agregação deste. A calibração foi realizada com sondas compostas de três hastes com 0,10 m de comprimento efetivo e 0,05 m de resina, com espaçamento entre hastes de 0,017 m e sem resistor na haste central, conectadas a um equipamento TDR 100 da Campbell Cientific. Os valores de Ka, para um mesmo valor de , foram alterados somente pela variação do tipo de solo, não sendo influenciados pelo tipo de amostragem do solo (deformada e não deformada). Em relação aos modelos testados para estimativa de em função de Ka, o polinomial cúbico foi o que apresentou melhor ajuste aos dados de determinados por gravimetria para o Neossolo Quartzarênico e para o Cambissolo Háplico, enquanto para o Latossolo Vermelho um modelo linear apresentou melhor ajuste.

Relação da velocidade de escoamento da solução e do comprimento da coluna de solo com os parâmetros de transporte de potássio em um latossolo e um neossolo

Devido à importância dos estudos de deslocamento de solutos em colunas de solo, para avaliar os riscos de poluição do solo e das águas subterrâneas, e à falta de padronização no comprimento da coluna de solo utilizada (L) e na velocidade de escoamento da solução aplicada (), realizou-se este trabalho com o objetivo de avaliar a relação de L e de com o coeficiente de dispersão-difusão (D), a dispersividade (λ) e o fator de retardamento (R) do K+ em um Latossolo Vermelho distrófico (LVd) e num Neossolo Quartzarênico órtico (RQo). Foram testados cinco comprimentos de colunas (0,10, 0,20, 0,30, 0,40 e 0,50 m) e quatro velocidades, sendo 0,62, 0,69, 0,75 e 0,81 m h-1 para o LVd e 0,37, 0,40, 0,44 e 0,48 m h-1 para o RQo. Aplicou-se uma solução deslocadora de 130 mg L-1 de K+ nas colunas montadas com o solo desestruturado e saturadas com uma solução de CaCl2 5 mmol L-1. Os parâmetros de transporte R e D foram obtidos utilizando-se o programa computacional Disp; a λ foi obtida pela equação D = Do + λ, sendo Do igual a 7,13 10-6 m² h-1 para o KCl. Houve relação do comprimento da coluna e da velocidade de escoamento da solução com os parâmetros de transporte do K+ tanto no LVd quanto no RQo. No LVd, o fator de retardamento aumentou com o aumento na velocidade de escoamento da solução. Em ambos os solos, o fator de retardamento diminuiu com o aumento no comprimento da coluna; o coeficiente de dispersão-difusão aumentou com o aumento na velocidade de escoamento da solução e com o aumento no comprimento da coluna de solo; e a dispersividade também aumentou com o aumento no comprimento da coluna.

Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

Efeito da aplicação sucessiva de precipitações pluviais com diferentes perfis na taxa de infiltração de água no solo

O processo de infiltração é influenciado pelas condições da superfície do solo e pela precipitação pluvial. O objetivo deste trabalho foi avaliar a influência de aplicações sucessivas de precipitações pluviais com diferentes perfis na formação do encrostamento superficial e, consequentemente, na taxa de infiltração de água em solo sem cobertura e com cobertura. Foram aplicadas três precipitações pluviais sucessivas para cada perfil de precipitação pluvial, em intervalos de 24 h, sendo usados os perfis de precipitação pluvial constante, exponencial decrescente, duplo exponencial adiantado e atrasado, com uma lâmina média de 55 mm por aplicação. Buscou-se ajustar um fator de decaimento da taxa de infiltração (Ti) em função da energia cinética acumulada da chuva, denominado de fator f, dado pela razão entre a taxa de infiltração estável (Tie) com efeito da chuva e a Tie sem o efeito da chuva. Foram avaliadas duas condições de cobertura do solo, solo sem cobertura e solo coberto com palhada, sendo os ensaios de infiltração realizados com um simulador de chuvas, em parcelas experimentais de dimensões de 1,0 x 0,7 m. Os resultados foram avaliados por meio de análises gráficas, análise de variância e teste de média. Verificou-se que os diferentes perfis de precipitação pluvial não influenciaram a infiltração de água no solo, tanto para o solo sem cobertura como para o solo com cobertura, sendo esta influenciada somente pelas aplicações sucessivas, com menores valores da taxa de infiltração obtidos na segunda e terceira aplicações. O decréscimo na Ti em solo sem cobertura foi devido à formação de encrostamento superficial, o que ocorreu logo na primeira aplicação. A Tie em solo sem cobertura teve decréscimo de 75 % se comparada à Tie em solo com cobertura. A lâmina infiltrada não foi influenciado pelos quatro perfis de precipitação pluvial. O fator f foi descrito com uso de uma equação do tipo exponencial.

Modelo para estimativa da infiltração de água e perfil de umidade do solo

A adequada modelagem da infiltração de água no solo é fundamental para estimação do movimento de água, erosão hídrica, recarga e contaminação de aquíferos. Este trabalho apresenta um modelo para estimativa da infiltração de água no solo (GAML-c), com base no modelo de Green-Ampt-Mein-Larson, que provê descrição da geometria e do deslocamento da frente de umedecimento no solo. Testes experimentais foram conduzidos em Latossolo Vermelho-Amarelo para avaliar o GAML-c, usando-se quatro diferentes cenários: considerando a condutividade hidráulica do solo igual à taxa de infiltração estável (Tie) e a umidade máxima do solo igual ao teor de água na zona de transmissão (θw) (TW); condutividade hidráulica do solo igual à do solo saturado (K0) e a umidade máxima do solo igual θw (KW); condutividade hidráulica do solo igual à Tie e a umidade máxima do solo igual ao teor de água na saturação (θs) (TS); e condutividade hidráulica do solo igual a K0 e a umidade máxima do solo igual θs (KS). Verificou-se que o GAML-c no cenário TW foi o melhor estimador do perfil de umidade do solo, resultando em aceitáveis estimativas da infiltração de água.

Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Yield gains of coffee plants from phosphorus fertilization may not be generalized for high density planting

Inconclusive responses of the adult coffee plant to phosphorus fertilization have been reported in the literature, especially when dealing with application of this nutrient in high density planting systems. Thus, this study was carried out for the purpose of assessing the response of adult coffee plants at high planting density in full production (in regard to yield and their biennial cycle/stability) to the addition of different sources and application rates of P in the Zona da Mata region of Minas Gerais, Brazil. The experiment with coffee plants of the Catucaí Amarelo 6/30 variety was carried out over four growing seasons. Treatments were arranged in a full factorial design [(4 × 3) + 1] consisting of four P sources (monoammonium phosphate, simple superphosphate, natural reactive rock phosphate from Algeria (Djebel-Onk), and FH 550®), three P rates (100, 200, and 400 kg ha-1 year-1 of P2O5), and an additional treatment without application of the nutrient (0 kg ha-¹ year-¹). A randomized block experimental design was used with three replicates. The four seasons were evaluated as subplots in a split plot experiment. The P contents in soil and leaves increased with increased rates of P application. However, there was no effect from P application on the yield and its biennial cycle/stability regardless of the source used over the four seasons assessed.

Performance of the 47-Kilodalton Membrane Protein versus DNA Polymerase I Genes for Detection of Treponema pallidum by PCR in Ulcers.

Treponema pallidum PCR (Tp-PCR) is a direct diagnostic method for primary and secondary syphilis, but there is no recommendation regarding the best choice of target gene. In this study, we sequentially tested 272 specimens from patients with sexually transmitted ulcers using Tp-PCR targeting the tpp47 and then polA genes. The two methods showed similar accuracies and an almost-perfect agreement.

Impacts of deforestation on water balance components of a watershed on the Brazilian East Coast

The Brazilian East coast was intensely affected by deforestation, which drastically cut back the original biome. The possible impacts of this process on water resources are still unknown. The purpose of this study was an evaluation of the impacts of deforestation on the main water balance components of the Galo creek watershed, in the State of Espírito Santo, on the East coast of Brazil. Considering the real conditions of the watershed, the SWAT model was calibrated with data from 1997 to 2000 and validated for the period between 2001 and 2003. The calibration and validation processes were evaluated by the Nash-Sutcliffe efficiency coefficient and by the statistical parameters (determination coefficient, slope coefficient and F test) of the regression model adjusted for estimated and measured flow data. After calibration and validation of the model, new simulations were carried out for three different land use scenarios: a scenario in compliance with the law (C1), assuming the preservation of PPAs (permanent preservation areas); an optimistic scenario (C2), which considers the watershed to be almost entirely covered by native vegetation; and a pessimistic scenario (C3), in which the watershed would be almost entirely covered by pasture. The scenarios C1, C2 and C3 represent a soil cover of native forest of 76, 97 and 0 %, respectively. The results were compared with the simulation, considering the real scenario (C0) with 54 % forest cover. The Nash-Sutcliffe coefficients were 0.65 and 0.70 for calibration and validation, respectively, indicating satisfactory results in the flow simulation. A mean reduction of 10 % of the native forest cover would cause a mean annual increase of approximately 11.5 mm in total runoff at the watershed outlet. Reforestation would ensure minimum flows in the dry period and regulate the maximum flow of the main watercourse of the watershed.

Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.

Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating the inflammatory response by mediating leukocyte tethering and rolling on adherent leukocytes. In this study, we have examined the effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding. The functional importance of these modifications was determined by analyzing soluble L-selectin binding and leukocyte rolling on CHO cells expressing various glycoforms of PSGL-1 or mutant PSGL-1 targeted at N-terminal Thr or Tyr residues. Simultaneous expression of core-2 beta1,6-N-acetylglucosaminyltransferase and fucosyltransferase VII was required for optimal L-selectin binding to PSGL-1. Substitution of Thr-57 by Ala but not of Thr-44, strongly decreased L-selectin binding and leukocyte rolling on PSGL-1. Substitution of Tyr by Phe revealed that PSGL-1 Tyr-51 plays a predominant role in mediating L-selectin binding and leukocyte rolling whereas Tyr-48 has a minor role, an observation that contrasts with the pattern seen for the interactions between PSGL-1 and P-selectin where Tyr-48 plays a key role. Molecular modeling analysis of L-selectin and P-selectin interactions with PSGL-1 further supported these observations. Additional experiments showed that core-2 O-glycans attached to Thr-57 were also of critical importance in regulating the velocity and stability of leukocyte rolling. These observations pinpoint the structural characteristics of PSGL-1 that are required for optimal interactions with L-selectin and may be responsible for the specific kinetic and mechanical bond properties of the L-selectin-PSGL-1 adhesion receptor-counterreceptor pair.

Effect of Nitrogen and Potassium Rates on Early Development of Macaw Palm

ABSTRACT The economic exploitation of macaw palm [Acrocomia aculeate(Jacq.) Lodd. ex Mart.] is currently in transition, from extractivism to agricultural cultivation, thus requiring studies on the fertilization of the crop. This study evaluated the response of three genotypes of macaw palm to increasing rates of nitrogen and potassium, grown in the field until the 2nd year and to establish reference contents of mineral nutrients in the leaf. The experiment was a split-plot randomized block design with five main treatments (N and K rates) and three secondary treatments (genotypes), with three replications, each plot containing three plants. Plant height, leaf number, vigor, and nutrient contents in leaf tissues were evaluated at the end of 2nd year of cultivation. Differential responses were observed among genotypes, indicating that some genotypes are more efficient in the use of mineral inputs. There was a differentiated and positive response to increasing side-dressed N and K rates in the vegetative development of macaw genotypes until the 2nd year of field cultivation, indicating variability in the species in terms of nutrient use efficiency. The N and K fertilization rate corresponding to 360 g N + 480 g K2O per plant, in four split applications over the two years of cultivation, was insufficient to induce maximum vegetative development in the three macaw genotypes. There was no variation in macro- and micronutrient contents in leaf dry matter of the three macaw genotypes.

Effects of endotoxin on lactate metabolism in humans.

ABSTRACT: INTRODUCTION: Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. METHODS: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. RESULTS: In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. CONCLUSIONS: LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. TRIAL REGISTRATION: ClinicalTrials.gov NCT01647997.