Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2 when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

Sensitivity of mycobacteria to different species of eucalyptus l'herit

Sensitivity profile of 10 mycobacteria of clinical interest to eight different species of Eucalyptus L'Herit was studied. A Proportion Method Indirect Test was performed to detect resistant bacilli utilizing 5 and 10 mg/ml of essential oils incorporated to Lowestein-Jensen medium. Mycobaterium tuberculosis and other slow growing mycobacteria were more sensitive to essential oils than faster growing ones. The most effective essential oils, in decreasing order, were Eucalyptus citriodora, Eucalyptus maculata and Eucalyptus tereticornis.

The δ expansion and the principle of minimal sensitivity

The δ-expansion is a nonperturbative approach for field theoretic models which combines the techniques of perturbation theory and the variational principle. Different ways of implementing the principle of minimal sensitivity to the δ-expansion produce in general different results for observables. For illustration we use the Nambu-Jona-Lasinio model for chiral symmetry restoration at finite density and compare results with those obtained with the Hartree-Fock approximation.

Sensitivity of AMPA receptor channel to calcium oscillations: A computational study

We used a computational model of biochemical pathways that are involved in the phosphorylation/dephosphorylation of AMPA receptor to study the receptor responses to calcium oscillations. In the model, the biochemical pathways are assumed to be located immediately under the postsynaptic membrane and we included three states of AMPA receptor: dephosphorylated, and phosphorylated in one or in two sites. To characterize the effects of calcium oscillations on the AMPA receptor, we exposed the model to stimuli with three varying parameters, namely frequency, number of pulses and calcium spike duration. Our model showed sensitivity to all of these three parameters. © 2002 Elsevier Science B.V. All rights reserved.

Benomyl sensitivity of isolates of Colletotrichum acutatum and C. gloeosporioides from citrus

Postbloom fruit drop (PFD) of citrus, caused by Colletotrichum acutatum, produces orange-brown lesions on petals and results in premature fruit drop and the retention of calyces. C. gloeosporioides is common in groves and causes postharvest anthracnose on fruit. Both diseases are controlled effectively by the fungicide benomyl in research fields and commercial orchards. Highly sensitive and resistant isolates of C. gloeosporioides were found, whereas all isolates of C. acutatum tested were moderately resistant. In preliminary studies conducted in vitro with three isolates of each, mycelial growth of sensitive isolates of C. gloeosporioides was inhibited completely by benomyl (Benlate 50 WP) at 1.0 μg/ml, whereas resistant isolates grew well at 10 μg/ml. Growth of all isolates of C. acutatum was inhibited by about 55% at 0.1 μg/ml and by 80% at 1.0 μg/ml. Spore germination of C. acutatum was inhibited more at 0.1 μg/ml than at 1.0 μg/ml or higher concentrations. In all, 20 isolates of C. acutatum from 17 groves and 20 isolates of C. gloeosporioides from 7 groves were collected from locations with different histories of benomyl usage in São Paulo, Brazil, and Florida, United States. Benomyl at 1.0 μ.g/ml completely inhibited growth of 133 isolates of C. gloeosporioides, with the exception of 7 isolates that were highly resistant to the fungicide, whereas all isolates of C. acutatum were only partially inhibited at 0.1 and 1.0 μg/ml. Analysis of variance indicated that the sensitivity of the isolates of C. acutatum was not affected by benomyl usage or grove of origin, and country of origin had only minor effects. No highly resistant or sensitive isolate of C. acutatum was recovered. Partial sequencing of the β-tubulin gene did not reveal nucleotide substitutions in codons 198 or 200 in C. acutatum that usually are associated with benomyl resistance in other fungi.

On designing linearly tunable high-Q OTA-C filters with low sensitivity

This paper discusses a design approach for a high-Q low-sensitivity OTA-C biquad bandpass section. An optimal relationship is established between transconductances defining the differenceβ - γ in the Q-factor denominator, setting the Q-sensitivity to tuning voltages around unity. A 30-MHz filter was designed based on a 0.35μn CMOS process and VDD=3.3V. A range of circuit simulation supports the theoretical analysis. Q-factor spans from 20.5 to 60, while ensuring filter stability along the tuning range. Although a Mode-operating OTA is used, the procedure can be extended to other types of transconductor.

A low-voltage low-sensitivity sinusoidal VCO for DPLL realizations

A quasi-sinusoidal linearly tunable OTA-C VCO built with triode-region transconductors is presented. Oscillation upon power-on is ensured by RHP poles associated with gate-drain capacitances of OTA input devices. Since the OTA nonlinearity stabilizes the amplitude, the oscillation frequency f0 is first-order independent of VDD, making the VCO adequate to mixed-mode designs. A range of simulations attests the theoretical analysis. As part of a DPLL, the VCO was prototyped on a 0.8μm CMOS process, occupying an area of 0.15mm2. Nominal f0 is 1MHz, with K VCo=8.4KHz/mV. Measured sensitivity to VDD is below 2.17, while phase noise is -86dBc at 100-KHz offset. The feasibility of the VCO for higher frequencies is verified by a redesign based on a 0.35μm CMOS process and VDD=3.3V, with a linear frequency-span of l3.2MHz - 61.5MHz.

High sensitivity low cost capacitive strain gage

This paper describes a high senstivity low cost capacitive strain gage sensor. The theory, design, and sensor construction details are presented. It consists of eight capacitive sensors connected in two full bridges. The capacitive strain gage sensor structure was designed in order to produce high sensitivity and low dependence with temperature. By using a simple signal conditioning circuit constituted by a differential amplifier, a band-pass filter, and a precision rectifier the device can measure forces with resolution of 0.009 N and precision of 98.7%. It is rugged, presents linear response, and good repeatability. It presents sensitivity of 8.7 V/N and fall time of 12 ms.

The effect of adhesive and flowable composite on postoperative sensitivity: 2-Week results

Objective: To measure 2-week postoperative sensitivity in Class II composite restorations placed with a self-etching adhesive (Clearfil SE Bond) or a total-etch adhesive (Prime&Bond NT) with or without a flowable composite as cervical increment. Method and materials: Upon approval by the University of Guarulhos Committee on Human Subjects, 100 restorations were inserted in 46 patients who required Class II restorations in their molars and premolars. Enamel and dentin walls were conditioned with a self-etching primer (for Clearfil SE Bond) or etched with 34% phosphoric acid (for Prime&Bond NT). A 1- to 2-mm-thick increment of a flowable composite (Filtek Flow) was used in the proximal box in 50% of the restorations of each adhesive. Preparations were restored with a packable composite (Surefil). The restorations were evaluated preoperatively and 2 weeks postoperatively for sensitivity to cold, air, and masticatory forces using a visual analog scale. Marginal integrity of the accessible margins was also evaluated. Statistical analysis used a mixed linear model with subject as a random effect. Results: Ninety-eight teeth from 44 subjects were observed at 2 weeks. The type of adhesive and use of flowable composite had no significant effects or interaction for any of the four outcomes of interest, ie, change from baseline to 2 weeks in sensitivity and response time for the cold or air stimulus. For the air stimulus, the overall average change from baseline was not significant for either sensitivity or response time. For the cold stimulus, the overall average change from baseline was significant for both sensitivity and response time. No case of sensitivity to masticatory forces was observed. Conclusion: No differences in postoperative sensitivity were observed between a self-etch adhesive and a total-etch adhesive at 2 weeks. The use of flowable composite did not decrease postoperative sensitivity.

A new firefly luciferase with bimodal spectrum: Identification of structural determinants of spectral pH-sensitivity in firefly luciferases

Fireflies emit flashes in the green-yellow region of the spectrum for the purpose of sexual attraction. The bioluminescence color is determined by the luciferases. It is well known that the in vitro bioluminescence color of firefly luciferases can be shifted toward the red by lower pH and higher temperature; for this reason they are classified as pH-sensitive luciferases. However, the mechanism and structural origin of pH sensitivity in fireflies remains unknown. Here we report the cloning of a new luciferase from the Brazilian twilight active firefly Macrolampis sp2, which displays an unusual bimodal spectrum. The recombinant luciferase displays a sensitive spectrum with the peak at 569 nm and a shoulder in the red region. Comparison of the bioluminescence spectra of Macrolampis, Photinus and Cratomorphus firefly luciferases shows that the distinct colors are determined by the ratio between green and red emitters under luciferase influence. Comparison of Macrolampis luciferase with the highly similar North American Photinus pyralis luciferase (91%) showed few substitutions potentially involved with the higher spectral sensitivity in Macrolampis luciferase. Site-directed mutagenesis showed that the natural substitution E354N determines the appearance of the shoulder in the red region of Macrolampis luciferase bioluminescence spectrum, helping to identify important interactions and residues involved in the pH-sensing mechanism in firefly luciferases. © 2005 American Society for Photobiology.

Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats

Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times, P < 0.05), which can be involved in the 2-fold increased (P < 0.05) hepatic glycogen content. The GLUT2 protein content was unchanged. Our findings point out that liver plays a role in enhanced insulin sensitivity induced by low ethanol consumption. © 2005 Elsevier Inc. All rights reserved.

Sensitivity analysis for overload-relief in transmission lines using an implicitly coupled method (CRIC)

The restructuring of energy markets to provide free access to the networks and the consequent increase of the number of power transactions has been causing congestions in transmission systems. As consequence, the networks suffer overloads in a more frequent way. One parameter that has strong influence on transfer capability is the reactive power flow. A sensitivity analysis can be used to find the best solution to minimize the reactive power flows and relief, the overload in one transmission line. The proposed methodology consists on the computation of two sensitivities based on the use of the Lc matrix from CRIC (Constant Reactive Implicitly Coupled) power flow method, that provide a set of actions to reduce the reactive power flow and alleviate overloads in the lines: (a) sensitivity between reactive power flow in lines and reactive power injections in the buses, (b) sensitivity between reactive power flow in lines and transformer's taps. © 2006 IEEE.

Different stress biomarkers sensitivity during acute treadmill running exercise in rats

The level of stress during acute or chronic exercise is important since higher levels of stress may impair homeostasis. The adrenal gland is an essential stress-responsive organ involved in the hypothalamic-pituitary-adrenal axis. The aim of the study was to analyze the sensitivity of different stress biomarkers of the adrenal gland during acute treadmill running at different intensities. Adult rats performed three 25 min running tests at velocities of 15, 20 and 25 m/min, for determination of maximum lactate steady state (MLSS). After obtaining individual MLSS animals were assigned to two groups: M, sacrificed after 25 minutes of exercise at MLSS, and AM, sacrificed after exercise at 25% above MLSS. For comparison, a control group C was sacrificed at rest. Blood corticosterone concentrations, as well, adrenal gland cholesterol and ascorbic acid concentrations were used as biomarkers. Serum corticosterone concentrations were higher after exercise in both M (1802,74±700,42) and AM (2027,96±724,94) groups when compared C group (467,11±262,12), but were not different as a function of exercise intensity. No difference in adrenal ascorbic acid (M=2,37±0,66; AM=2,11±0,50 and C=2,54±0,53) and cholesterol (M=1,04±0,12; AM=0,91±0,31 and C=1,15±0,40) levels were observed when the three groups were compared. Serum corticosterone concentrations showed to be sensitive to acute treadmill exercise intensity. On the other hand, ascorbic acid and cholesterol concentrations in adrenal were biomarkers not adequate to evaluate exercise stress in rats.

The structural origin and biological function of pH-sensitivity in firefly luciferases

Firefly luciferases are called pH-sensitive because their bioluminescence spectra display a typical red-shift at acidic pH, higher temperatures, and in the presence of heavy metal cations, whereas other beetle luciferases (click beetles and railroadworms) do not, and for this reason they are called pH-insensitive. Despite many studies on firefly luciferases, the origin of pH-sensitivity is far from being understood. This subject is revised in view of recent results. Some substitutions of amino-acid residues influencing pH-sensitivity in firefly luciferases have been identified. Sequence comparison, site-directed mutagenesis and modeling studies have shown a set of residues differing between pH-sensitive and pH-insensitive luciferases which affect bioluminescence colors. Some substitutions dramatically affecting bioluminescence colors in both groups of luciferases are clustered in the loop between residues 223-235 (Photinus pyralis sequence). A network of hydrogen bonds and salt bridges involving the residues N229-S284-E311-R337 was found to be important for affecting bioluminescence colors. It is suggested that these structural elements may affect the benzothiazolyl side of the luciferin-binding site affecting bioluminescence colors. Experimental evidence suggest that the residual red light emission in pH-sensitive luciferases could be a vestige that may have biological importance in some firefly species. Furthermore, the potential utility of pH-sensitivity for intracellular biosensing applications is considered. © The Royal Society of Chemistry and Owner Societies.

Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets

Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca2 2+ signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca2 2+signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally,weexplored the status of Ca2 2+-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase Cα as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the β-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity. Copyright © 2010 by The Endocrine Society.