Potassium channel modulation by a toxin domain in matrix metalloprotease

Peptide toxins found in a wide array of venoms block K+ channels, causing profound physiological and pathological effects. Here we describe the first functional K+ channel-blocking toxin domain in a mammalian protein. MMP23 (matrix metalloprotease 23) contains a domain (MMP23TxD) that is evolutionarily related to peptide toxins from sea anemones. MMP23TxD shows close structural similarity to the sea anemone toxins BgK and ShK. Moreover, this domain blocks K+ channels in the nanomolar to low micromolar range (Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4, in decreasing order of potency) while sparing other K+ channels (Kv1.2, Kv1.5, Kv1.7, and KCa3.1). Full-length MMP23 suppresses K+ channels by co-localizing with and trapping MMP23TxD-sensitive channels in the ER. Our results provide clues to the structure and function of the vast family of proteins that contain domains related to sea anemone toxins. Evolutionary pressure to maintain a channel-modulatory function may contribute to the conservation of this domain throughout the plant and animal kingdoms.

Space vector modulation based fast speed response field-orientation control of induction motor drive with adaptive neural integrator

This paper presents a novel fast speed response control strategy for the poly-phase induction motor drive system based on flux angle. The control scheme is derived in rotor field coordinates and employs the estimation of the rotor flux and its position. An adaptive notch filter is proposed to eliminate the dc component of the integration of signals used for the rotor flux estimation. To improve the performance of the rotor flux estimator, derivative term of the back emf is incorporated in the system. The voltage components in the synchronous reference frame are generated in the controllers which are transformed to stationary reference frame for driving the motor. Space vector modulation technique is used here. Simulation of the drive system was carried out and the results were compared with those obtained for a system that produces the above mentioned voltage components using the conventional PI controller. It is observed that the proposed control methodology provides faster response than the conventional PI controller incorporated system.

Lack of seasonal and moult-related stress modulation in an opportunistically breeding bird: the white-plumed honeyeater (Lichenostomus penicillatus).

In most vertebrate species, glucocorticoid levels and stress sensitivity vary in relation to season and life-history stage. In birds, baseline corticosterone (CORT) and stress sensitivity are typically highest while breeding and decrease substantially during moult. Because elevated CORT adversely affects protein synthesis, moult-related CORT suppression is thought to be necessary for forming high-quality feathers. Surprisingly, some passerine species lack moult-related CORT suppression, but these are distinguished by having slow rates of moult and being opportunistic breeders. We examined baseline and stress-induced CORT levels in an opportunistically breeding Australian passerine, the white-plumed honeyeater (Lichenostomus penicillatus). Although this species has a slower moult rate than high-latitiude breeders, it differs little from north-temperate passerines. Neither baseline nor stress-induced CORT levels varied with season (winter, spring or summer), sex or moult status in adult birds. While breeding tended to be highest in early spring through late summer, laparotomies revealed only limited reduction in testicular size in males the year round. In all but one sampling period, at least some females displayed follicular hierarchy. Breeding usually coincides with outbreaks of phytophagous insects, which can happen at any time of the year. This results in moult/breeding overlap when infestations occur in late spring or summer. The ability of this species to moult and breed at the same time while having breeding-levels of CORT demonstrates that CORT suppression is not a prerequisite for synthesis of high-quality feathers. An experimental design incorporating moulting and non-moulting phenotypes is suggested to test the functional significance of CORT suppression in other species.

miRNA modulation of SOCS1 using an influenza A virus delivery system

Difficulties associated with efficient delivery and targeting of miRNAs to cells is hampering the real world application of miRNA technology. This study utilized an influenza A-based delivery system to express miR-155 in order to knockdown SOCS1 mRNA. Using qPCR and dual luciferase technology we show that miR-155 delivery resulted in a significant increase in cellular miR-155 which facilitated a downregulation of SOCS1 gene expression and a functional increase in IL-6 and IFN-β cytokines.

Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

The performance of a repetitive index finger flexion–extension task at maximal voluntary rate (MVR) begins to decline just a few seconds into the task and we have previously postulated that this breakdown has a central origin. To test this hypothesis, we have combined two objectives; to determine whether motor practice can lessen the performance deterioration in an MVR task, and whether further gains can be achieved with a transcranial magnetic stimulation (TMS) protocol that increases corticomotor excitability (CME). Eleven right-handed subjects participated in a randomized crossover study design that consisted of a 15-min interventional TMS at I-wave periodicity (ITMS) and single-pulsed Sham intervention prior to six 10-s practice sets of a repetitive finger flexion–extension task at MVR. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. The starting movement rate, and the percentage decline in rate by the end of the MVR were quantitated. Training of the MVR task improved the sustainability of the task by reducing the decline in movement rate. CME increased steadily after each training bout, and this increase was maintained up to 20 min after the last bout. ITMS further increased CME, and was associated with an increase in both the starting rate of the MVR task and its sustainability, when compared to Sham. The results implicate central motor processes in the performance and sustainability of the MVR task, and indicate that MVR kinematics can improve with short-term training and with non-invasive neuro-modulation.

Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson’s disease and is reversed by levodopa

Objectives: In healthy subjects, fatiguing exercises induce a period of post-exercise corticomotor depression (PECD) that is absent in Parkinson’s disease (PD). Our objective is to determine the time-course of corticomotor excitability changes following a 10-s repetitive index finger flexion–extension task performed at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD patients OFF and ON levodopa.
Methods: In 11 PD patients and 10 healthy age-matched controls, motor evoked potentials (MEPs) were recorded from the extensor indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the dominant arm immediately after the two tasks and at 2-min intervals for 10 min.
Results: In the OFF condition the PECD was absent in the two test muscles after both the MVR and MSR tasks. In the ON condition finger movement kinematics improved and a period of PECD comparable to that in controls was present after both tasks.
Conclusion: The absence of PECD in PD subjects off medication indicates a persisting increase in corticomotor excitability after non-fatiguing repetitive finger movement that is reversed by levodopa.

Allosteric modulation of pyrophosphatase activity of rat osseous plate alkaline phosphatase by magnesium ions

Pyrophosphatase activity of rat osseous plate alkaline phosphatase was studied at different concentrations of calcium and magnesium ions. with the aim of characterizing the modulation of enzyme activity by these metals. In the absence of metal ions, the enzyme hydrolysed pyrophosphate following Michaelian kinetics with a specific activity of 36.7 U/mg and K-0.5 = 88 mu M. In the presence of low concentrations (0.1 mM) of magnesium (or calcium) ions, the enzyme also exhibited Michaclian kinetics for the hydrolysis of pyrophosphate, but a significant increase in specific activity (123 U/mg) was observed. K-m values remained almost unchanged. Quite different behavior occurred in the presence of 2 mM magnesium (or calcium) ions. In addition to low-affinity sites (K-0.5 = 40 and 90 mu M, for magnesium and calcium, respectively), high-affinity sites were also observed with K-0.5 values 100-fold lower. The high-affinity sites observed in the presence of calcium ions represented about 10% of those observed for magnesium ions. This was correlated with the fact that only magnesium ions triggered conformational changes yielding a fully active enzyme. These results suggested that the enzyme could hydrolyse pyrophosphate, even at physiological concentrations (4 mu M), since magnesium concentrations are high enough to trigger conformational changes increasing the enzyme activity. A model, suggesting the involvement of magnesium ions in the hydrolysis of pyrophosphate by rat osseous plate alkaline phosphatase is proposed. (C) 1998 Published by Elsevier B.V. Ltd. All rights reserved.

Analysis of cardiac autonomic modulation in obese and eutrophic children

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

Context-specific modulation of cocaine-induced locomotor sensitization and ERK and CREB phosphorylation in the rat nucleus accumbens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

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

Enhancement of optical absorption by modulation of the oxygen flow of TiO2 films deposited by reactive sputtering

Oxygen-deficient TiO2 films with enhanced visible and near-infrared optical absorption have been deposited by reactive sputtering using a planar diode radio frequency magnetron configuration. It is observed that the increase in the absorption coefficient is more effective when the O-2 gas supply is periodically interrupted rather than by a decrease of the partial O-2 gas pressure in the deposition plasma. The optical absorption coefficient at 1.5 eV increases from about 1 x 10(2) cm(-1) to more than 4 x 10(3) cm(-1) as a result of the gas flow discontinuity. A red-shift of similar to 0.24 eV in the optical absorption edge is also observed. High resolution transmission electron microscopy with composition analysis shows that the films present a dense columnar morphology, with estimated mean column width of 40nm. Moreover, the interruptions of the O-2 gas flow do not produce detectable variations in the film composition along its growing direction. X-ray diffraction and micro-Raman experiments indicate the presence of the TiO2 anatase, rutile, and brookite phases. The anatase phase is dominant, with a slight increment of the rutile and brookite phases in films deposited under discontinued O-2 gas flow. The increase of optical absorption in the visible and near-infrared regions has been attributed to a high density of defects in the TiO2 films, which is consistent with density functional theory calculations that place oxygen-related vacancy states in the upper third of the optical bandgap. The electronic structure calculation results, along with the adopted deposition method and experimental data, have been used to propose a mechanism to explain the formation of the observed oxygen-related defects in TiO2 thin films. The observed increase in sub-bandgap absorption and the modeling of the corresponding changes in the electronic structure are potentially useful concerning the optimization of efficiency of the photocatalytic activity and the magnetic doping of TiO2 films. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4724334]

Glia-Pinealocyte Network: The Paracrine Modulation of Melatonin Synthesis by Tumor Necrosis Factor (TNF)

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

NF-kappa B signaling modulation by EBV and KSHV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Use of corticosteroid therapy on the modulation of uterine inflammatory response in mares after artificial insemination with frozen semen

In order to modulate uterine inflammatory response and evaluate the effect of corticosteroid therapy on fertility, 90 cycles of 45 mares were used for artificial insemination with frozen semen, using three different protocols: G1 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma; G2 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + corticosteroid therapy; G3 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma + corticosteroid therapy. Corticosteroid therapy consisted on one administration of prednisolone acetate (0.1 mg/Kg - Predef (R)) when mares presented 35mm follicles and uterine edema, concomitantly with the unique dose of hCG (human chorionic gonadotropin), then repeated each 12 hours until ovulation. on first fertility trial, with normal mares, there was no difference between control and treated groups (p>0.05), using seminal plasma associated with corticosteroid therapy (40 vs. 38%, respectively) or corticosteroid therapy alone (40 vs. 45% respectively). The second fertility trial, performed with mares with previous history of post-insemination endometritis, demonstrated a significant increase of pregnancy rate when mares were submitted to corticosteroid therapy (0.0 vs. 64.5%, respectively; p<0.05). Corticosteroid therapy was shown to be safe, with no physical or reproductive alterations on treated mares, demonstrating to be an adequate option to those animals with history of post-breeding or post-insemination endometritis. Further clinical research is necessary to confirm these results and contribute to the establishment of preventive therapy for cases of post-insemination endometritis.