Lightning activity in Brazilian thunderstorms during TROCCINOX: implications for NOx production

During the TROCCINOX field experiment in January and February 2005, the contribution of lightning-induced nitrogen oxides (LNOx) from tropical and subtropical thunderstorms in Southern Brazil was investigated. Airborne trace gas measurements (NO, NOy, CO and O-3) were performed up to 12.5 km with the German research aircraft Falcon. During anvil penetrations in selected tropical and subtropical thunderstorms of 4 and 18 February, NOx mixing ratios were on average enhanced by 0.7-1.2 and 0.2-0.8 nmol mol(-1) totally, respectively. The relative contributions of boundary layer NOx (BL-NOx) and LNOx to anvil-NOx were derived from the NOx-CO correlations. on average similar to 80-90% of the anvil-NOx was attributed to LNOx. A Lightning Location Network (LINET) was set up to monitor the local distribution of cloud-to-ground (CG) and intra-cloud (IC) radiation sources (here called 'strokes') and compared with lightning data from the operational Brazilian network RINDAT (Rede Integrada Nacional de Deteccao de Descargas Atmosfericas). The horizontal LNOx mass flux out of the anvil was determined from the mean LNOx mixing ratio, the horizontal outflow velocity and the size of the vertical cross-section of the anvil, and related to the number of strokes contributing to LNOx. The values of these parameters were derived from the airborne measurements, from lightning and radar observations, and from a trajectory analysis. The amount of LNOx produced per LINET stroke depending on measured peak current was determined. The results were scaled up with the Lightning Imaging Sensor (LIS) flash rate (44 flashes s(-1)) to obtain an estimate of the global LNOx production rate. The final results gave similar to 1 and similar to 2-3 kg(N) per LIS flash based on measurements in three tropical and one subtropical Brazilian thunderstorms, respectively, suggesting that tropical flashes may be less productive than subtropical ones. The equivalent mean annual global LNOx nitrogen mass production rate was estimated to be 1.6 and 3.1 Tg a(-1), respectively. By use of LINET observations in Germany in July 2005, a comparison with the lightning activity in mid-latitude thunderstorms was also performed. In general, the same frequency distribution of stroke peak currents as for tropical thunderstorms over Brazil was found. The different LNOx production rates per stroke in tropical thunderstorms compared with subtropical and mid-latitude thunderstorms seem to be related to the different stroke lengths (inferred from comparison with laboratory data and observed lengths). In comparison, the impact of other lightning parameters as stroke peak current and stroke release height was assessed to be minor. The results from TROCCINOX suggest that the different vertical wind shear may be responsible for the different stroke lengths.

Stay out (almost) all night: contrasting responses in flight activity among tropical moth assemblages

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

The long-term administration of calcineurin inhibitors decreases antioxidant enzyme activity in the rat parotid and submandibular salivary glands

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Acetaminophen as an Oral Toxicant for Nile Monitor Lizards (Varanus niloticus) and Burmese Pythons (Python molurus bivittatus)

Context. Invasive species are a growing global problem. Biological invasions can result in numerous harmful impacts on local ecologies, and non-native herpetofauna are frequently ignored. Nile monitor lizards (Varanus niloticus) and Burmese pythons (Python molurus bivittatus, recently reassessed as Python bivittatus bivittatus), have become established in southern Florida. Both are large, semi-aquatic predators that pose serious threats to a variety of threatened and endangered species, as well as to the unique ecology of the area. Aims. Acetaminophen (CAS#103-90-2), a lethal oral toxicant for the invasive brown treesnake (Boiga irregularis) on Guam, was investigated as a possible toxicant in juvenile Burmese pythons and Nile monitors. Methods. Dead neonatal mouse (DNM) baits containing 0, 10, 20, or 40 mg acetaminophen were force-fed to Nile monitors, whereas DNM containing doses of 0, 20, 40, or 80 mg were freely consumed by Burmese pythons. Subjects were frequently observed post-treatment for general condition and position, with special attention paid to activity (if any), behaviour, respiration, bleeding, emesis, ataxia, and mortality. Key results. In Nile monitors, acetaminophen doses of 10, 20, or 40 mg resulted in 0, 50 and 100% mortality, respectively. In Burmese pythons, doses of 20, 40, or 80 mg resulted in 14.3, 85.7 and 100% mortality, respectively. No mortality was observed in control individuals of either species. A negative correlation between dosage (mg kg–1) and time-to-death was observed in both species. Dosages ranging from 522 to 2438 mg kg–1 and 263 to 703 mg kg–1 were uniformly lethal to monitors and pythons, respectively. Neither species exhibited signs of pain or discomfort following acetaminophen treatment. Conclusions. Acetaminophen is an effective toxicant in juvenile Nile monitors and Burmese pythons. Further investigation into acetaminophen toxicity in adults of these species is merited. Implications. Although further investigation into adult lethal dosages and strategies to optimize bait deployment while minimizing secondary hazards is required, acetaminophen may have a role to play in the control of these invasive species in Florida.

Evaluation of Microbicidal Activity of Oxygen-Containing Plasmas using Biological Monitors with Different Lumen Calibers

New technologies and sterilization agents for heat-sensitive materials are under intense investigation. Plasma sterilization, an atoxic low-temperature substitute for conventional sterilization, uses various gases that are activated by an electrical discharge, generating reactive species that promote lethality in microorganisms. Here, assays were performed using pure O-2 and O-2 + H2O2 mixture gas plasmas against a standard load of Bacillus atrophaeus spores inoculated on glass carriers inside PVC catheters. The sterilization efficiency was studied as a function of plasma system (reactive ion etching or inductively coupled plasma), biological monitor lumen diameter, gas, radio frequency power, and sub-lethal exposition time. After sterilization, the biological monitors were disassembled and the surviving bacteria were grown in trypticase soy broth using the most probable number technique. Plasma antimicrobial activity depended on the catheter's internal diameter and radio frequency powers. The N-2 + H2O2 mixture exhibited higher microbial efficacy than pure N-2 in both plasma systems.

Synthesis, maturation, and trafficking of human Na+-dicarboxylate cotransporter NaDC1 requires the chaperone activity of cyclophilin B

Renal excretion of citrate, an inhibitor of calcium stone formation, is controlled mainly by reabsorption via the apical Na(+)-dicarboxylate cotransporter NaDC1 (SLC13A2) in the proximal tubule. Recently, it has been shown that the protein phosphatase calcineurin inhibitors cyclosporin A (CsA) and FK-506 induce hypocitraturia, a risk factor for nephrolithiasis in kidney transplant patients, but apparently through urine acidification. This suggests that these agents up-regulate NaDC1 activity. Using the Xenopus lævis oocyte and HEK293 cell expression systems, we examined first the effect of both anti-calcineurins on NaDC1 activity and expression. While FK-506 had no effect, CsA reduced NaDC1-mediated citrate transport by lowering heterologous carrier expression (as well as endogenous carrier expression in HEK293 cells), indicating that calcineurin is not involved. Given that CsA also binds specifically to cyclophilins, we determined next whether such proteins could account for the observed changes by examining the effect of selected cyclophilin wild types and mutants on NaDC1 activity and cyclophilin-specific siRNA. Interestingly, our data show that the cyclophilin isoform B is likely responsible for down-regulation of carrier expression by CsA and that it does so via its chaperone activity on NaDC1 (by direct interaction) rather than its rotamase activity. We have thus identified for the first time a regulatory partner for NaDC1, and have gained novel mechanistic insight into the effect of CsA on renal citrate transport and kidney stone disease, as well as into the regulation of membrane transporters in general.

Experimental heart transplantation: effect of cyclosporine on expression and activity of metzincins

Metzincins, such as matrix metalloproteases (MMP), and extracellular matrix (ECM) proteins are differentially regulated in inflammation. We hypothesised that metzincins are also dysregulated in experimental acute cardiac allograft rejection. We investigated the Dark Agouti-to-Lewis (DA-to-Lew) rat model of acute cardiac allograft rejection. Cyclosporine (CsA) (7.5 mg/kg/d) was given from transplantation to sacrifice (day +5). At that time, mRNA levels were analysed by Affymetrix genechip and quantitative reverse transcription polymerase chain reaction (qRTPCR). MMP protein and activities were analysed by immunohistology, fluorometry, zymography and Western blots. In untreated rejected DA allografts, mRNA levels of MMP-2/-7/-9/-/12-/14, a disintegrin and metalloprotease (ADAM)-17, tissue inhibitor of metalloprotease (TIMP)-1/-3 were increased, whereas MMP-11/-16/-24 and TIMP-2/-4 were lowered compared to native DA hearts. With respect to these untreated allografts, CsA lowered mRNA levels of MMP-7, TIMP-1/-3 (TIMP-2/-4 remained relatively low) and ADAM17, but augmented mRNA levels of MMP-11/-16/-23 and of many ECM genes. Immunohistology showed increased staining of MMP-2 in acute rejection (AR). Overall MMP activity was augmented in both transplanted groups, but CsA reduced MMP-9 activity and MMP-14 production. Taken together, MMP and TIMP were upregulated during acute AR. CsA ameliorated histology of rejection but showed potential pro-fibrotic effects. Thus, MMP and TIMP may play a role in acute cardiac allograft rejection, and beneficial modification of the MMP-ECM balance requires interventions beyond CsA.

Identification of 2-Piperidone as a Biomarker of CYP2E1 Activity Through Metabolomic Phenotyping

Cytochrome P450 2E1 (CYP2E1) is a key enzyme in the metabolic activation of many low molecular weight toxicants and also an important contributor to oxidative stress. A noninvasive method to monitor CYP2E1 activity in vivo would be of great value for studying the role of CYP2E1 in chemical-induced toxicities and stress-related diseases. In this study, a mass spectrometry-based metabolomic approach was used to identify a metabolite biomarker of CYP2E1 through comparing the urine metabolomes of wild-type (WT), Cyp2e1-null, and CYP2E1-humanized mice. Metabolomic analysis with multivariate models of urine metabolites revealed a clear separation of Cyp2e1-null mice from WT and CYP2E1-humanized mice in the multivariate models of urine metabolomes. Subsequently, 2-piperidone was identified as a urinary metabolite that inversely correlated to the CYP2E1 activity in the three mouse lines. Backcrossing of WT and Cyp2e1-null mice, together with targeted analysis of 2-piperidone in mouse serum, confirmed the genotype dependency of 2-piperidone. The accumulation of 2-piperidone in the Cyp2e1-null mice was mainly caused by the changes in the biosynthesis and degradation of 2-piperidone because compared with the WT mice, the conversion of cadaverine to 2-piperidone was higher, whereas the metabolism of 2-piperidone to 6-hydroxy-2-piperidone was lower in the Cyp2e1-null mice. Overall, untargeted metabolomic analysis identified a correlation between 2-piperidone concentrations in urine and the expression and activity of CYP2E1, thus providing a noninvasive metabolite biomarker that can be potentially used in to monitor CYP2E1 activity.

Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue.

Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in ∼50 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.

The longitudinal course of gross motor activity in schizophrenia - within and between episodes

Schizophrenia is associated with heterogeneous course of positive and negative symptoms. In addition, reduced motor activity as measured by wrist actigraphy has been reported. However, longitudinal studies of spontaneous motor activity are missing. We aimed to explore whether activity levels were stable within and between psychotic episodes. Furthermore, we investigated the association with the course of negative symptoms. In 45 medicated patients, we investigated motor behavior within a psychotic episode. In addition, we followed 18 medicated patients across 2 episodes. Wrist actigraphy and psychopathological ratings were applied. Within an episode symptoms changed but activity levels did not vary systematically. Activity at baseline predicted the course of negative symptoms. Between two episodes activity recordings were much more stable. Again, activity at the index episode predicted the outcome of negative symptoms. In sum, spontaneous motor activity shares trait and state characteristics, the latter are associated with negative symptom course. Actigraphy may therefore become an important ambulatory instrument to monitor negative symptoms and treatment outcome in schizophrenia.

Association between temperament and physical activity in a population of minority women

Physical activity has been, and remains, a significant public health issue. Thus, increasing physical activity has been identified as a top priority according to Healthy People 2010. Various behavioral variables have been associated with participation in physical activity, including the Type A behavior pattern (TABP). This study was a secondary data analysis of the Women On The Move pilot study data and examined the relationship between Type A behavior with physical activity. The study population consisted of fifty-six (56) adult minority women 40 years of age and above. The Thurstone Activity Scale was adapted for use in this study to measure TABP. Physical activity behavior was measured using an accelerometer (Computer Science Application, [CSA]) and a physical activity diary. All study questions were examined using multiple linear regression analysis. In all analyses age, household income, and level of education were entered as covariates. The results found no association with TABP and exercise or physical activity. More research involving a larger, more active study population is recommended in order to more precisely determine the relationship of TABP and physical activity. ^

Influencia del ejercicio físico desarrollado durante el embarazo en la respuesta cardiaca fetal = Influence of a physical activity program performed during pregnancy on fetal heart response

INTRODUCCIÓN: El riesgo de padecer enfermedades cardiovasculares y los índices de obesidad infantil han ido en aumento durante los últimos años empobreciendo la salud de la población. La Teoría de Barker relaciona el estado de salud de la madre con el desarrollo fetal, asociando a un deficiente estado físico y hábitos de vida negativos de la mujer embarazada con el aumento del riesgo de padecer cardiopatías en la infancia y adolescencia, así como predisponer al recién nacido a padecer sobrepeso y/u obesidad en su vida posterior. Por otro lado los estudios efectuados sobre ejercicio físico durante el embarazo reportan beneficios para salud materna y fetal. Uno de los parámetros más utilizados para comprobar la salud fetal es su frecuencia cardiaca, mediante la que se comprueba el buen desarrollo del sistema nervioso autónomo. Si se observa este parámetro en presencia de ejercicio materno podría encontrarse una respuesta crónica del corazón fetal al ejercicio materno como consecuencia de una adaptación y mejora en el funcionamiento del sistema nervioso autónomo del feto. De esta forma podría mejorar su salud cardiovascular intrauterina, lo que podría mantenerse en su vida posterior descendiendo el riesgo de padecer enfermedades cardiovasculares en la edad adulta. OBJETIVOS: Conocer la influencia de un programa de ejercicio físico supervisado en la frecuencia cardiaca fetal (FCF) en reposo y después del ejercicio materno en relación con gestantes sedentarias mediante la realización de un protocolo específico. Conocer la influencia de un programa de ejercicio físico en el desarrollo del sistema nervioso autónomo fetal, relacionado con el tiempo de recuperación de la FCF. MATERIAL Y MÉTODO: Se diseñó un ensayo clínico aleatorizado multicéntrico en el que participaron 81 gestantes (GC=38, GE=43). El estudio fue aprobado por el comité ético de los hospitales que participaron en el estudio. Todas las gestantes fueron informadas y firmaron un consentimiento para su participación en el estudio. Las participantes del GE recibieron una intervención basada en un programa de ejercicio físico desarrollado durante la gestación (12-36 semanas de gestación) con una frecuencia de tres veces por semana. Todas las gestantes realizaron un protocolo de medida de la FCF entre las semanas 34-36 de gestación. Dicho protocolo consistía en dos test llevados a cabo caminando a diferentes intensidades (40% y 60% de la frecuencia cardiaca de reserva). De este protocolo se obtuvieron las principales variables de estudio: FCF en reposo, FCF posejercicio al 40 y al 60% de intensidad, tiempo de recuperación de la frecuencia cardiaca fetal en ambos esfuerzos. El material utilizado para la realización del protocolo fue un monitor de frecuencia cardiaca para controlar la frecuencia cardiaca de la gestante y un monitor fetal inalámbrico (telemetría fetal) para registrar el latido fetal durante todo el protocolo. RESULTADOS: No se encontraron diferencias estadísticamente significativas en la FCF en reposo entre grupos (GE=140,88 lat/min vs GC= 141,95 lat/min; p>,05). Se encontraron diferencias estadísticamente significativas en el tiempo de recuperación de la FCF entre los fetos de ambos grupos (GE=135,65 s vs GC=426,11 s esfuerzo al 40%; p<,001); (GE=180,26 s vs GC=565,61 s esfuerzo al 60%; p<,001). Se encontraron diferencias estadísticamente significativas en la FCF posejercicio al 40% (GE=139,93 lat/min vs GC=147,87 lat/min; p<,01). No se encontraron diferencias estadísticamente significativas en la FCF posejercicio al 60% (GE=143,74 lat/min vs GC=148,08 lat/min; p>,05). CONLUSIÓN: El programa de ejercicio físico desarrollado durante la gestación influyó sobre el corazón fetal de los fetos de las gestantes del GE en relación con el tiempo de recuperación de la FCF. Los resultados muestran un posible mejor funcionamiento del sistema nervioso autónomo en fetos de gestantes activas durante el embarazo. ABSTRACT INTRODUCTION: The risk to suffer cardiovascular diseases and childhood obesity index has grown in the last years worsening the health around the population. Barker´s Theory related maternal health with fetal development establishing an association between a poorly physical state and an unhealthy lifestyle in the pregnant woman with the risk to suffer heart disease during childhood and adolescence, childhood overweight and/or obese is related to maternal lifestyle. By the other way researches carried out about physical exercise and pregnancy show benefits in maternal and fetal health. One of the most studied parameters to check fetal health is its heart rate, correct fetal autonomic nervous system development and work is also corroborated by fetal heart rate. Looking at this parameter during maternal exercise a chronic response of fetal heart could be found due to an adaptation and improvement in the working of the autonomic nervous system. Therefore its cardiovascular health could be enhanced during its intrauterine life and maybe it could be maintained in its posterior life descending the risk to suffer cardiovascular diseases in adult life. OBJECTIVES: To know the influence of a supervised physical activity program in the fetal heart rate (FHR) at rest, FHR after maternal exercise related to sedentary pregnant women by a FHR assessment protocol. To know the influence of a physical activity program in the development of the autonomic nervous system related to FHR recovery time. MATERIAL AND METHOD: A multicentric randomized clinical trial was design in which 81 pregnant women participated (CG=38, EG=43). The study was approved by the ethics committee of all of the hospitals participating in the study. All of the participants signed an informed consent for their participation in the study. EG participants received an intervention based on a physical activity program carried out during gestation (12-36 gestation weeks) with a three days a week frequency. All of the participants were tested between 34-36 weeks of gestation by a specific FHR assessment protocol. The mentioned protocol consisted in two test performed walking and at a two different intensities (40% and 60% of the reserve heart rate). From this protocol we obtained the main research variables: FHR at rest, FHR post-exercise at 40% and 60% intensity, and FHR recovery time at both walking test. The material used to perform the protocol were a FH monitor to check maternal HR and a wireless fetal monitor (Telemetry) to register fetal beats during the whole protocol. RESULTS: There were no statistical differences in FHR at rest between groups (EG=140,88 beats/min vs CG= 141,95 beats/min; p>,05). There were statistical differences in FHR recovery time in both walking tests between groups (EG=135,65 s vs CG=426,11 s test at 40% intensity; p<,001); (EG=180,26 s vs CG=565,61 s test at 60% intensity; p<,001). Statistical differences were found in FHR post-exercise at 40% intensity between groups (EG=139,93 beats/min vs CG=147,87 beats/min; p<,01). No statistical differences were found in FHR at rest post-exercise at 60% intensity between groups (EG=143,74 beats/min vs CG=148,08 beats/min; p>,05). CONCLUSIONS: The physical activity program performed during gestation had an influence in fetal heart of the fetus from mother in the EG related to FHR recovery time. These results show a possible enhancement on autonomic nervous system working in fetus from active mothers during gestation.

Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression

The functional expression of homo-oligomeric α7 neuronal nicotinic and type 3 serotonin receptors is dependent on the activity of a cyclophilin. In this paper we demonstrate that the mechanism of cyclophilin action during functional homo-oligomeric receptor expression in Xenopus oocytes is distinct from the calcineurin-dependent immunosuppressive mechanism by showing that a nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211–811, reduces functional receptor expression to the same extent as CsA. The cytoplasmic subtype of cyclophilin, cyclophilin A (CyPA), appears to be required for functional receptor expression. This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression. The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect. Our data also suggest that CyPA does not form a stable complex with receptor subunits.

Activity-based protein profiling: The serine hydrolases

With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. To date, proteomics efforts have primarily been confined to recording variations in protein level rather than activity. The ability to profile classes of proteins on the basis of changes in their activity would greatly accelerate both the assignment of protein function and the identification of potential pharmaceutical targets. Here, we describe the chemical synthesis and utility of an active-site directed probe for visualizing dynamics in the expression and function of an entire enzyme family, the serine hydrolases. By reacting this probe, a biotinylated fluorophosphonate referred to as FP-biotin, with crude tissue extracts, we quickly and with high sensitivity detect numerous serine hydrolases, many of which display tissue-restricted patterns of expression. Additionally, we show that FP-biotin labels these proteins in an activity-dependent manner that can be followed kinetically, offering a powerful means to monitor dynamics simultaneously in both protein function and expression.