Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulurn Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PR,L) action, functional changes that are characterized by increased glucose-induced insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to nonpregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (U). The expression of the sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in P-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of PI 9 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.

Settling analysis of MOS regulated current mirrors applied to micropower D/A converters

This paper provides an insight to the trade-off between settling time and power consumption in regulated current mirrors as building parts in micropower current-switching D/A converters. The regulation-loop frequency characteristic is obtained and difficulties to impose a dominant-pole condition to the resulting 2nd-order system are evaluated. Raising pole frequencies in micropower circuits, while meeting consumption requirements, is basically limited by parasitic capacitances. For such cases, an alternative is to impose a twin-pole condition in which design constraints are somewhat relieved and settling slightly improved. Relationships between pole frequencies, transistor geometry and bias are established and design guidelines for regulated current mirrors founded. By placing loop-transistors in either weak or strong inversion, small (W/L) ratios are allowed and stray capacitances reduced. Simulated waveforms suggest a good agreement with theory. The proposed approach applied to the design of a micropower current-mode D/A converter improves both simulated and experimental settling performance.

GLUCOCORTICOID-REGULATED GENE IN TRANSFORMED TO NORMAL PHENOTYPIC REVERSION

Glucocorticoid hormones modulate the actions of peptide growth factors and constitute important therapeutic tools as anti-inflammatory and anti-tumor agents. The C6 rat glioma cell line responds to glucocorticoids with changes in morphology and growth block. The hyper-responsive ST1 cell variant displays a dramatic phenotypic reversion under the influence of these hormones. Thus, the transformed and tumorigenic cells reversibly change to a normal and non-tumorigenic phenotype. In addition, the cells also produce a C-type retrovirus. We used poly A(+) mRNA from ST1 cells that had been treated with hydrocortisone to generate a cDNA library that was then screened, by differential hybridization,for glucocorticoid-responsive cellular sequences. The retroviral genomic RNA was used to generate a viral-specific probe. Cross hybridization led to the isolation of at least 4 cDNA clones of which 3 are cellular sequences and one corresponds to a retroviral gene. These clones were characterized by DNA sequencing and Northern blot hybridization analysis.

A 12 kW three-phase low THD rectifier with high-frequency isolation and regulated DC output

A robust 12 kW rectifier with low THD in the line currents, based on an 18-pulse transformer arrangement with reduced kVA capacities followed by a high-frequency isolation stage is presented in this work. Three full-bridge (buck-based) converters are used to allow galvanic isolation and to balance the dc-link currents, without current sensing or current controller. The topology provides a regulated dc output with a very simple and well-known control strategy and natural three-phase power factor correction. The phase-shift PWM technique, with zero-voltage switching is used for the high-frequency dc-dc stage. Analytical results from Fourier analysis of winding currents and the vector diagram of winding voltages are presented. Experimental results from a 12 kW prototype are shown in the paper to verify the efficiency, robustness and simplicity of the command circuitry to the proposed concept.

Cloning of glucocorticoid-regulated genes in C6/ST1 rat glioma phenotypic reversion

The C6 rat glioma cell line is responsive to glucocorticoid hormones. C6 variants that are hyper-responsive (ST1) and resistant (P7) to hormone treatment have been derived previously. Glucocorticoid treatment of ST1 cells leads to complete reversion of the transformed phenotype and loss of tumorigenic potential. Production of C type retrovirus particles is also induced by glucocorticoids in ST1 cells. Cloning of the genes regulated by glucocorticoids in this cell system was used here as a strategy to uncover the gene products involved in the transformed-to-normal phenotypic change. Construction of a cDNA library from glucocorticoid-treated ST1 cells and screening by differential hybridization resulted in the isolation of three cellular sequences that code for rat metallothioneins (C27 and C41) and α1-acid glycoprotein (C36). Northern blot analysis revealed that expression of these genes was dramatically induced by hydrocortisone in ST1 but not in P7 cells. Viral genomic RNA was used to isolate and characterize retrovirus-related sequences that could also be responsible for the phenotypic reversion phenomenon.

On optimizing micropower MOS regulated cascode circuits on switched current techniques

Trade-off between settling time and micropower consumption in MOS regulated cascode current sources as building parts in high-accuracy, current-switching D/A converters is analyzed. The regulation-loop frequency characteristic is obtained and difficulties to impose a dominant-pole condition to the resulting 2nd-order system are discussed. Raising pole frequencies while meeting consumption requirements is basically limited by parasitic capacitances. An alternative is found by imposing a twin-pole system in which design constraints are somewhat relaxed and settling slightly faster. Relationships between pole frequencies, transistor geometry and bias are established. Simulated waveforms obtained with PSpice of designed circuits following a voltage perturbation suggest a good agreement with theory. The proposed approach applied to the design of a micropower current-mode D/A converter improves its simulated settling performance.

New 12kW three-phase 18-pulse high power factor AC-DC converter with regulated output voltage for rectifier units

This work presents a new high power factor three-phase rectifier based on a Y-connected differential autotransformer with reduced kVA and 18-pulse input current followed by three DC-DC boost converters. The topology provides a regulated output voltage and natural three-phase input power factor correction. The lowest input current harmonic components are the 17th and the 19th. Three boost converters, with constant input currents and regulated parallel connected output voltages are used to process 4kW each one. Analytical results from Fourier analyses of winding currents and the vector diagram of winding voltages are presented. Simulation results to verify the proposed concept and experimental results are shown in the paper.

A new three-phase low THD power supply with high-frequency isolation and 60V/200A regulated DC output

This work proposes a new isolated high power factor 12kW power supply based on an 18-pulse transformer arrangement. Three full-bridge converters are used for isolation and to balance the DC-link currents, without current sensing or a current controller. The topology provides a regulated DC output with a very simple control strategy. Simulation and experimental results are presented in this paper.

Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

Background: Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Methods: Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C - pregnant control, W - tumour-bearing, and P - pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L - pregnant leucine, WL - tumour-bearing, and PL - pair-fed, which received the same amount of food as ingested by the WL group. Results: The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ∼35% for eIF2α and eIF5, ∼17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. Conclusion: The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway. © 2007 Ventrucci et al; licensee BioMed Central Ltd.

Metabolismo do glicogênio em Neurospora crassa: um estudo molecular e bioquímico e análise de interação proteína-proteína

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bone marrow mesenchymal stem cells stimulated by bFGF up-regulated protein expression in comparison with periodontal fibroblasts in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)