Ubiquitin proteasome system and the atypical kinase PfPK7 are involved in melatonin signaling in Plasmodium falciparum

We previously reported that melatonin modulates the Plasmodium falciparum erythrocytic cycle by increasing schizont stage population as well as diminishing ring stage population. In addition, the importance of calcium and cAMP in melatonin signaling pathway in P. falciparum was also demonstrated. Nevertheless, the molecular effectors of the indoleamine signaling pathway remain elusive. We now demonstrate by real-time PCR that melatonin treatment up-regulates genes related to ubiquitin/proteasome system (UPS) components and that luzindole, a melatonin receptor antagonist, inhibits UPS transcription modulation. We also show that protein kinase PfPK7, a P. falciparum orphan kinase, plays a crucial role in the melatonin transduction pathway, since following melatonin treatment of P. falciparum parasites where pfpk7 gene is disrupted (pfpk7- parasites) (i) the ratio of asexual stages remain unchanged, (ii) the increase in cytoplasmatic calcium in response to melatonin was strongly diminished and (iii) up-regulation of UPS genes did not occur. The wild-type melatonin-induced alterations in cell cycle features, calcium rise and UPS gene transcription were restored by re-introduction of a functional copy of the pfpk7 gene in the pfpk7- parasites.

The Oligocene-Neogene deep-sea Columbia Channel system in the South Brazilian Basin: Seismic stratigraphy and environmental changes

The Columbia Channel (CCS) system is a depositional system located in the South Brazilian Basin, south of the Vitoria-Trindade volcanic chain. It lies in a WNW-ESE direction on the continental rise and abyssal plain, at a depth of between 4200 and 5200 m. It is formed by two depocenters elongated respectively south and north of the channel that show different sediment patterns. The area is swept by a deep western boundary current formed by AABW. The system has been previously interpreted has a mixed turbidite-contourite system. More detailed study of seismic data permits a more precise definition of the modern channel morphology, the system stratigraphy as well as the sedimentary processes and control. The modern CCS presents active erosion and/or transport along the channel. The ancient Oligo-Neogene system overlies a ""upper Cretaceous-Paleogene"" sedimentary substratum (Unit U1) bounded at the top by a major erosive ""late Eocene-early Oligocene"" discordance (D2). This ancient system is subdivided into 2 seismic units (U2 and U3). The thick basal U2 unit constitutes the larger part of the system. It consists of three subunits bounded by unconformities: D3 (""Oligocene-Miocene boundary""), D4 (""late Miocene"") and D5 (""late Pliocene""). The subunits have a fairly tabular geometry in the shallow NW depocenter associated with predominant turbidite deposits. They present a mounded shape in the deep NE depocenter, and are interpreted as forming a contourite drift. South of the channel, the deposits are interpreted as a contourite sheet drift. The surficial U3 unit forms a thin carpet of deposits. The beginning of the channel occurs at the end of U1 and during the formation of D2. Its location seems to have been determined by active faults. The channel has been active throughout the late Oligocene and Neogene and its depth increased continuously as a consequence of erosion of the channel floor and deposit aggradation along its margins. Such a mixed turbidite-contourite system (or fan drift) is characterized by frequent, rapid lateral facies variations and by unconformities that cross the whole system and are associated with increased AABW circulation. (C) 2009 Elsevier B.V. All rights reserved.

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

NURSES AND THE ASSESSMENT IN HEALTH SYSTEM MANAGEMENT

The objective of this study was to undertake a critical reflection regarding assessment as a managerial tool that promotes the inclusion of nurses in the health system management process. Nurses, because of their education and training, which encompasses knowledge in both the clinical and managerial fields and is centered on care, have the potential to assume a differentiated attitude in management, making decisions and proposing health policies. Nevertheless, it is necessary to first create and consolidate an expressive inclusion in decisive levels of management. Assessment is a component of management, the results of which may contribute to making decisions that are more objective and allow for improving healthcare interventions and reorganizing health practice within a political, economic, social and professional context; it is also an area for the application of knowledge that has the potential to change the current panorama of including nurses in management.

Leptin as a link between the immune system and kidney-related diseases: leading actor or just a coadjuvant?

Food intake and nutritional status modify the physiological responses of the immune system to illness and infection and regulate the development of chronic inflammatory processes, such as kidney disease. Adipose tissue secretes immune-related proteins called adipokines that have pleiotropic effects on both the immune and neuroendocrine systems, linking metabolism and immune physiology. Leptin, an adipose tissue-derived adipokine, displays a variety of immune and physiological functions, and participates in several immune responses. Here, we review the current literature on the role of leptin in kidney diseases, linking adipose tissue and the immune system with kidney-related disorders. The modulation of this adipose hormone may have a major impact on the treatment of several immune- and metabolic-related kidney diseases.

Comparative electrical behavior at low and high current of SnO(2)- and ZnO-based varistors

The complete I-V characteristics of SnO(2)-based varistors, particularly of the Pianaro system SCNCr consisting in 98.9%SnO(2)+1%CoO+0.05%Nb(2)O(5)+0.05%Cr(2)O(3), all in mol%, have been seldom reported in the literature. A comparative study at low and high currents of the nonohmic behavior of SCNCr- and ZnO-based varistors (modified Matsuoka system) is proposed in this work. The SCNCr system showed higher nonlinearity coefficients in the whole range of measured current. The electrical breakdown field (E(b)) was twice as high for the SCNCr system (5400 V/cm) than for the ZnO varistor (2600 V/cm) due to a smaller average grain size of the former (4.5 mu m) with respect to the latter (8.5 mu m). Nevertheless, we consider that another important factor responsible for the high E(b) in the SCNCr system is the great number of electrically active interfaces (85%) as determined with electrostatic force microscopy (EFM). It was also established that the SCNCr system might be produced in disks of smaller dimensions than that of commercial ZnO-based product, with a 5.0 cm(-1) minimal area-volume (A/V) ratio. The SCNCr reached the saturation current in a short time because of the high resistivity of the grains, which is five times higher than that of the grains in ZnO-based varistors.

The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats

The aim of the present study was to investigate the participation of the sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating pathways in white adipose tissue (WAT) of rats in three situations in which the plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was surgical denervated and the G3P generation pathways were evaluated. Food deprivation, diabetes and the HP diet provoke a marked decrease in the rate of glucose uptake and glycerokinase (GyK) activity, but a significant increase in the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK) activity and the incorporation of 1-[C-14]-pyruvate into glycerol-TAG. The denervation provokes a reduction (similar to 70%) in the NE content of WAT in fasted, diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%, respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The denervation caused a similar to 35% decrease in GyK activity of control rats and a further similar to 35% reduction in the already low enzyme activity of fasted, diabetic and HP diet-fed rats. These data suggest that the SNS plays an important role in modulating G3P generating pathways in WAT, in situations where insulin levels are low. (C) 2012 Elsevier Inc. All rights reserved.

The Brazilian National Health Agency and the Mental Health Policy in the Context of the Private Health System: developments and challenges

This work analyses the mental health policy-making activity of the Brazilian National Health Agency (ANS), responsible for controlling health insurance companies. Three points are discussed: a) the framework of an economic and private health assistance regulatory activity, b) the ANS and its regulation activity and c) the rules produced by ANS in the mental health care field. It was concluded that, despite advances like the legal obligation to ensure medical treatment to all the diseases listed in ICD-10, the inclusion of suicidal patient damage and self-inflicted damage care, care provided by a multiprofessional team, the increase in the number of sessions with a psychologist, with an occupational therapist and of psychotherapy sessions, and mental health day hospitals included as part of the services offered, the authors identified specific regulatory gaps in this area. Some issues that ANS has to solve so that it can really play its institutional role of defending the public interest in the private health system are: the regulation of co-participation and franchise mechanisms, the increasing co-participation as a limitation of psychiatric hospitalization, and the limited number of crisis intervention psychotherapy sessions.

Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 mu g/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram-negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real-time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T-maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism-like effects and also a hypoactivation of the dopaminergic system. (c) 2012 Wiley Periodicals, Inc.

Optical transition radiation used in the diagnostic of low energy and low current electron beams in particle accelerators

Optical transition radiation (OTR) plays an important role in beam diagnostics for high energy particle accelerators. Its linear intensity with beam current is a great advantage as compared to fluorescent screens, which are subject to saturation. Moreover, the measurement of the angular distribution of the emitted radiation enables the determination of many beam parameters in a single observation point. However, few works deals with the application of OTR to monitor low energy beams. In this work we describe the design of an OTR based beam monitor used to measure the transverse beam charge distribution of the 1.9-MeV electron beam of the linac injector of the IFUSP microtron using a standard vision machine camera. The average beam current in pulsed operation mode is of the order of tens of nano-Amps. Low energy and low beam current make OTR observation difficult. To improve sensitivity, the beam incidence angle on the target was chosen to maximize the photon flux in the camera field-of-view. Measurements that assess OTR observation (linearity with beam current, polarization, and spectrum shape) are presented, as well as a typical 1.9-MeV electron beam charge distribution obtained from OTR. Some aspects of emittance measurement using this device are also discussed. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4748519]

QUANTIFICATION OF LEFT VENTRICULAR MYOCARDIAL COLLAGEN SYSTEM IN CHILDREN, YOUNG ADULTS, AND THE ELDERLY

Studies on the collagen system of the human myocardium are still limited compared to those on small laboratory animals. The aim of this work was to observe the collagen tissue of the myocardium of the human heart as a function of age. The types of collagen, as well as the density of collagen tissue and the diameter of collagen fibrils, were examined. Fragments of the left ventricular wall from 15 hearts, 5 from children, 5 from young adults, and 5 from elderly individuals, were analyzed by using the Picrosirius-polarization method and by transmission electron microscopy (TEM). The results showed the presence of collagen type III and collagen type I, both in the endomysium and perimysium of the 3 groups studied. Measurements of collagen content in myocardial tissue displayed that both endomysial and perimysial collagen increase in number and thickness in the adult and elderly. These histochemical results coincided with the observations obtained with the electron microscope in showing an increase in the number of collagen fibrils with a large diameter in the adult and elderly hearts. The present results on cardiac collagen may be important for assessing the pathogenesis of several cardiopathies in the hearts of children, young adults, and the elderly.

Electroluminescence and electric current response spectroscopy applied to the characterization of polymer light-emitting electrochemical cells

Frequency-dependent electroluminescence and electric current response spectroscopy were applied to polymeric light-emitting electrochemical cells in order to obtain information about the operation mechanism regimes of such devices. Three clearly distinct frequency regimes could be identified: a dielectric regime at high frequencies; an ionic transport regime, characterized by ionic drift and electronic diffusion; and an electrolytic regime, characterized by electronic injection from the electrodes and electrochemical doping of the conjugated polymer. From the analysis of the results, it was possible to evaluate parameters like the diffusion speed of electronic charge carriers in the active layer and the voltage drop necessary for operation. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4752438]

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or "rapid") monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction.

Effect of the interaction between food state and the action of estrogen on oxytocinergic system activity

Increased plasma osmolality by food intake evokes augmentation of plasma oxytocin (OT). Ovarian steroids may also influence the balance of body fluids by acting on OT neurones. Our aim was to determine if estrogen influences the activity of OT neurones in paraventricular nucleus (PVN) and supraoptic nucleus (SON) under different osmotic situations. Ovariectomized rats (OVX) were treated with either estradiol (E-2) or vehicle and were divided into three groups: group I was fed ad libitum, group II underwent 48 h of fasting, and group III was refed after 48 h of fasting. On the day of the experiment, blood samples were collected to determine the plasma osmolality and OT. The animals were subsequently perfused, and OT/FOS immunofluorescence analysis was conducted on neurones in the PVN and the SON. When compared to animals which were fasted or fed ad libitum, the plasma osmolality of refed animals was higher, regardless of whether they were treated with vehicle or E-2. We observed neural activation of OT cells in vehicle-or E-2-treated OVX rats refed after 48 h of fasting, but not in animals fed ad libitum or in animals that only underwent 48 h of fasting. Finally, the percentage of neurones that co-expressed OT and FOS was lower in both the PVN and the SON of animals treated with E-2 and refed, when compared to vehicle-treated animals. These results suggest that E-2 may have an inhibitory effect on OT neurones and may modulate the secretion of OT in response to the increase of osmolality induced by refeeding. Journal of Endocrinology (2012) 212, 129-138