Nerve growth factor rapidly suppresses basal, NMDA-evoked, and AMPA-evoked nitric oxide synthase activity in rat hippocampus in vivo

In adult forebrain, nerve growth factor (NGF) influences neuronal maintenance and axon sprouting and is neuroprotective in several injury models through mechanisms that are incompletely understood. Most NGF signaling is thought to occur after internalization and retrograde transport of trkA receptor and be mediated through the nucleus. However, NGF expression in hippocampus is rapidly and sensitively regulated by synaptic activity, suggesting that NGF exerts local effects more dynamically than possible through signaling requiring retrograde transport to distant afferent neurons. Interactions have been reported between NGF and nitric oxide (NO). Because NO affects both neural plasticity and degeneration, and trk receptors can mediate signaling within minutes, we hypothesized that NGF might rapidly modulate NO production. Using in vivo microdialysis we measured conversion of l-[14C]arginine to l-[14C]citrulline as an accurate reflection of NO synthase (NOS) activity in adult rat hippocampus. NGF significantly reduced NOS activity to 61% of basal levels within 20 min of onset of delivery and maintained NOS activity at less than 50% of baseline throughout 3 hr of delivery. This effect did not occur with control protein (cytochrome c) and was not mediated by an effect of NGF on glutamate levels. In addition, simultaneous delivery of NGF prevented significant increases in NOS activity triggered by the glutamate receptor agonists N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Rapid suppression by NGF of basal and glutamate-stimulated NOS activity may regulate neuromodulatory functions of NO or protect neurons from NO toxicity and suggests a novel mechanism for rapidly mediating functions of NGF and other neurotrophins.

Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

The tendency of a polypeptide chain to form alpha-helical or beta-strand secondary structure depends upon local and nonlocal effects. Local effects reflect the intrinsic propensities of the amino acid residues for particular secondary structures, while nonlocal effects reflect the positioning of the individual residues in the context of the entire amino acid sequence. In particular, the periodicity of polar and nonpolar residues specifies whether a given sequence is consistent with amphiphilic alpha-helices or beta-strands. The importance of intrinsic propensities was compared to that of polar/nonpolar periodicity by a direct competition. Synthetic peptides were designed using residues with intrinsic propensities that favored one or the other type of secondary structure. The polar/nonpolar periodicities of the peptides were designed either to be consistent with the secondary structure favored by the intrinsic propensities of the component residues or in other cases to oppose these intrinsic propensities. Characterization of the synthetic peptides demonstrated that in all cases the observed secondary structure correlates with the periodicity of the peptide sequence--even when this secondary structure differs from that predicted from the intrinsic propensities of the component amino acids. The observed secondary structures are concentration dependent, indicating that oligomerization of the amphiphilic peptides is responsible for the observed secondary structures. Thus, for self-assembling oligomeric peptides, the polar/nonpolar periodicity can overwhelm the intrinsic propensities of the amino acid residues and serves as the major determinant of peptide secondary structure.

Stable oxygen and carbon isotope of foraminifera from DSDP Leg 90 sites

High-resolution oxygen and carbon isotope stratigraphy is presented for Miocene to early Pliocene sequences at three DSDP sites from the Lord Howe Rise, southwest Pacific, at water depths ranging from 1,300 to 2,000 m. Site 588 is located in the warm subtropics (~26°S), whereas Sites 590 and 591 are positioned in transitional (northern temperate) water masses (~31°S). Benthic foraminiferal oxygen and carbon isotope analyses were conducted on all sites; planktonic foraminiferal isotope data were generated for Site 590 only. Sample resolution in these sequences is on the order of 50,000 yr. or better. The chronological framework employed in this study is based largely upon ages assigned to Neogene calcareous nannoplankton boundaries. The benthic oxygen isotope record exhibits several major features during the Neogene. During most of the early Miocene, delta18O values were relatively low, reaching minimum values in the late early Miocene (19.5 to 16.5 Ma), and recording the climax of Neogene warmth. This was followed by a major increase in benthic delta18O values between ~16.5 and 13.5 Ma, which is interpreted as representing major, permanent accumulation of the East Antarctic ice sheet and cooling of bottom waters. During the 3 m.y. 18O enrichment, surface waters at these middle latitudes warmed between 16 and 14.5 Ma. During the remainder of the middle and late Miocene, benthic delta18O values exhibit distinct fluctuations, but the average value remained unchanged. The isotopic data show two distinct episodes of climatic cooling close to the middle/late Miocene boundary. The earliest of these events occurred between 12.5 and 11.5 Ma in the latest middle Miocene. The second cooling event occurred from 11 to 9 Ma, and is marked by some of the highest delta18O values of the entire Miocene. This was followed by relative warmth during the middle part of the late Miocene. The latest Miocene and earliest Pliocene (6.2 to 4.5 Ma) were marked by relatively high delta18O values, indicating increased cooling and glaciation. During the middle Pliocene, at about 3.4 Ma, a 0.4 per mil increase in benthic delta18O documents a net increase in average global ice volume and cooling of bottom waters. During this interval of increased glaciation, surface waters warmed by 2-3°C in southern middle-latitude regions. During the late Pliocene, between 2.6 and 2.4 Ma, a further increase in delta18O occurred; this has been interpreted by previous workers as heralding the onset of Northern Hemisphere glaciation. Surface-water warming in the middle latitudes occurred in association with major high-latitude glacial increases in the early middle Miocene (16-14 Ma), middle Pliocene (-3.5 Ma), and late Pliocene (~2.4 Ma). These intervals were also marked by increases in the vertical temperature gradient in the open ocean. Intersite correlation is enhanced by using carbon isotope stratigraphy. The great similarity of the delta13C time-series records within and between ocean basins and with water depth clearly indicates that changes in oceanwide average delta13C of [HCO3]- in seawater dominated the records, rather than local effects. Broad changes in the Neogene delta13C record were caused largely by transfer of organic carbon between continental and oceanic reservoirs. These transfers were caused by marine transgressions and regressions on the continental margins. The dominant feature of Neogene delta13C stratigraphy is a broad late early to early middle Miocene increase of about lâ between ~19 and 14.5 Ma. This trend occurred contemporaneously with a period of maximum coastal onlap (transgression) and maximum Neogene climatic warmth. The delta13C trend terminated during the expansion of the Antarctic ice sheet and associated marine regression. The latest Miocene carbon isotope shift (of up to - 0.75 per mil) at 6.2 Ma is clearly recorded in all sites examined and was followed by relatively low values during the remainder of the Neogene. This shift was caused by a glacioeustatic sealevel lowering that exposed continental margins via regression and ultimately increased the flux of organic carbon to the deep sea. An increase in delta13C values during the early Pliocene (~5 to 4 Ma) resulted from marine transgression during a time of global warmth.

Modelling of wastewater treatment plants:how far shall we go with sophisticated modelling tools?

Several levels of complexity are available for modelling of wastewater treatment plants. Modelling local effects rely on computational fluid dynamics (CFD) approaches whereas activated sludge models (ASM) represent the global methodology. By applying both modelling approaches to pilot plant and full scale systems, this paper evaluates the value of each method and especially their potential combination. Model structure identification for ASM is discussed based on a full-scale closed loop oxidation ditch modelling. It is illustrated how and for what circumstances information obtained via CFD (computational fluid dynamics) analysis, residence time distribution (RTD) and other experimental means can be used. Furthermore, CFD analysis of the multiphase flow mechanisms is employed to obtain a correct description of the oxygenation capacity of the system studied, including an easy implementation of this information in the classical ASM modelling (e.g. oxygen transfer). The combination of CFD and activated sludge modelling of wastewater treatment processes is applied to three reactor configurations, a perfectly mixed reactor, a pilot scale activated sludge basin (ASB) and a real scale ASB. The application of the biological models to the CFD model is validated against experimentation for the pilot scale ASB and against a classical global ASM model response. A first step in the evaluation of the potential of the combined CFD-ASM model is performed using a full scale oxidation ditch system as testing scenario.

Atividade antiofídica do decocto das folhas de jatropha gossypiifolia l. frente o veneno de bothrops jararaca

Antiophidic activity from decoct of Jatropha gossypiifolia L. leaves against Bothrops jararaca venom. Snakebites are a serious worldwide public health problem. In Latin America, about 90 % of accidents are attributed to snakes from Bothrops genus. Currently, the main available treatment is the antivenom serum therapy, which has some disadvantages such as inability to neutralize local effects, risk of immunological reactions, high cost and difficult access in some regions. In this context, the search for alternative therapies to treat snakebites is relevant. Jatropha gossypiifolia L., a medicinal plant popularly known in Brazil as “pinhão-roxo”, is very used in folk medicine as antiophidic. So, the aim of this study is to evaluate the antiophidic properties of this species against enzymatic and biological activities from Bothrops jararaca snake venom. The aqueous leaf extract of J. gossypiifolia was prepared by decoction. The inhibition studies were performed in vitro, by pre-incubation of a fixed amount of venom with different amounts of extract from J. gossypiifolia for 60 min at 37 °C, and in vivo, through oral or intraperitoneal treatment of animals, in different doses, 60 min before venom injection. The proteolytic activity upon azocasein was efficiently inhibited, indicating inhibitory action upon metalloproteinases (SVMPs) and/or serine proteases (SVSPs). The extract inhibited the fibrinogenolytic activity, which was also confirmed by zymography, where it was possible to observe that the extract preferentially inhibits fibrinogenolytic enzymes of 26 and 28 kDa. The coagulant activity upon fibrinogen and plasma were significantly inhibited, suggesting an inhibitory action upon thrombin-like enzymes (SVTLEs), as well as upon clotting factor activators toxins. The extract prolonged the activated partial thromboplastin time (aPTT), suggesting an inhibitory action toward not only to SVTLEs, but also against endogenous thrombin. The defibrinogenating activity in vivo was efficiently inhibited by the extract on oral route, confirming the previous results. The local hemorrhagic activity was also significantly inhibited by oral route, indicating an inhibitory action upon SVMPs. The phospholipase activity in vitro was not inhibited. Nevertheless, the edematogenic and myotoxic activities were efficiently inhibited, by oral and intraperitoneal route, which may indicate an inhibitory effect of the extract upon Lys49 phospholipase (PLA2) and/ or SVMPs, or also an anti-inflammatory action against endogenous chemical mediators. Regarding the possible action mechanism, was observed that the extract did not presented proteolytic activity, however, presented protein precipitating action. In addition, the extract showed significant antioxidant activity in different models, which could justify, at least partially, the antiophidic activity presented. The metal chelating action presented by extract could be correlated with SVMPs inhibition, once these enzymes are metal-dependent. The phytochemical analysis revealed the presence of sugars, alkaloids, flavonoids, tannins, terpenes and/or steroids and proteins, from which the flavonoids could be pointed as major compounds, based on chromatographic profile obtained by thin layer chromatography (TLC). In conclusion, the results demonstrate that the J. gossypiifolia leaves decoct present potential antiophidic activity, including action upon snakebite local effects, suggesting that this species may be used as a new source of bioactive molecules against bothropic venom.

Inibição dos efeitos locais induzidos pelas peçonhas das serpentes Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de Jatropha mollissima (Pohl) Bail

Snakebites are a serious public health problem in tropical and subtropical countries and Bothrops genus is responsible for the accidents in Brazil and throughout Latin America (90% of cases). The local effects (pain, edema, hemorrhage and myonecrosis) and systemic (cardiovascular alterations, shock and blood clotting disorders) caused by the venom of Bothrops are due to the numerous protein and non-protein components, which are part of the constitution of the poison. The only form of therapy is scientifically validated antivenom serum therapy which, however, is not effective with respect to local effects produced, risk of immunological reactions, high cost and difficult access in some regions. Thus, the search for new alternatives to serum therapy becomes important, and in this context, many medicinal plants have been highlighted by the popular use as antiophidic. Among these plants, we can mention the species Jatropha mollissima (Euphorbiaceae) which has popular use in traditional medicine as antiophidic, anti-inflammatory, antimicrobial and antipyretic. Therefore, this study aims to evaluate the neutralizing potential of local effects induced by the venom of Bothrops erythromelas and Bothrops jararaca with the aqueous extract of the leaves of J. mollissima. The leaf extracts were prepared by decoction, fractionated (by liquid-liquid partition) and characterized by thin layer chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Antiophidic activity of the extract was evaluated in model of paw edema, peritonitis, bleeding and myotoxicity induced by venoms of B. jararaca and B. erythromelas. In all models, the extract was evaluated by intraperitoneal route at the doses of 50, 100 and 200 mg/kg, administered 30 minutes prior to injection of the venom (pretreatment protocol). Stains suggestive of the presence of flavonoids: apigenin, luteolin, orientin, isoorientin, vitexin and vitexin-2-O-rhamnoside were detected in the extract by co-CCD. By means of HPLC were identified isoorientin, orientin, vitexin and isovitexin. All tested doses of J. mollissima extract reduced the paw edema induced by the venom with intensity similar to dexamethasone. The aqueous extract of J. mollissima leaves on all evaluated doses, inhibited cell migration induced by B. jararaca and B. erythromelas promoting inhibition of recruitment of mononuclear cells and the polymorphonuclear cells. Local bleeding induced by B. jararaca venom was significantly inhibited by the extract. Both venoms were inhibited by the extract in myotoxic activity. These results indicate that the aqueous extract of J. mollissima leaves have snakebite potential, particularly with respect to local effects, which may justify the use of this plant in traditional medicine and complementary therapy as anti-venom serum.

Inibição dos efeitos locais induzidos pelas peçonhas das serpentes Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de Jatropha mollissima (Pohl) Bail

Snakebites are a serious public health problem in tropical and subtropical countries and Bothrops genus is responsible for the accidents in Brazil and throughout Latin America (90% of cases). The local effects (pain, edema, hemorrhage and myonecrosis) and systemic (cardiovascular alterations, shock and blood clotting disorders) caused by the venom of Bothrops are due to the numerous protein and non-protein components, which are part of the constitution of the poison. The only form of therapy is scientifically validated antivenom serum therapy which, however, is not effective with respect to local effects produced, risk of immunological reactions, high cost and difficult access in some regions. Thus, the search for new alternatives to serum therapy becomes important, and in this context, many medicinal plants have been highlighted by the popular use as antiophidic. Among these plants, we can mention the species Jatropha mollissima (Euphorbiaceae) which has popular use in traditional medicine as antiophidic, anti-inflammatory, antimicrobial and antipyretic. Therefore, this study aims to evaluate the neutralizing potential of local effects induced by the venom of Bothrops erythromelas and Bothrops jararaca with the aqueous extract of the leaves of J. mollissima. The leaf extracts were prepared by decoction, fractionated (by liquid-liquid partition) and characterized by thin layer chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Antiophidic activity of the extract was evaluated in model of paw edema, peritonitis, bleeding and myotoxicity induced by venoms of B. jararaca and B. erythromelas. In all models, the extract was evaluated by intraperitoneal route at the doses of 50, 100 and 200 mg/kg, administered 30 minutes prior to injection of the venom (pretreatment protocol). Stains suggestive of the presence of flavonoids: apigenin, luteolin, orientin, isoorientin, vitexin and vitexin-2-O-rhamnoside were detected in the extract by co-CCD. By means of HPLC were identified isoorientin, orientin, vitexin and isovitexin. All tested doses of J. mollissima extract reduced the paw edema induced by the venom with intensity similar to dexamethasone. The aqueous extract of J. mollissima leaves on all evaluated doses, inhibited cell migration induced by B. jararaca and B. erythromelas promoting inhibition of recruitment of mononuclear cells and the polymorphonuclear cells. Local bleeding induced by B. jararaca venom was significantly inhibited by the extract. Both venoms were inhibited by the extract in myotoxic activity. These results indicate that the aqueous extract of J. mollissima leaves have snakebite potential, particularly with respect to local effects, which may justify the use of this plant in traditional medicine and complementary therapy as anti-venom serum.

Unstructured grid modelling of offshore wind farm impacts on seasonally stratified shelf seas

Shelf seas comprise approximately 7% of the world’s oceans and host enormous economic activity. Development of energy installations (e.g. Offshore Wind Farms (OWFs), tidal turbines) in response to increased demand for renewable energy requires a careful analysis of potential impacts. Recent remote sensing observations have identified kilometrescale impacts from OWFs. Existing modelling evaluating monopile impacts has fallen into two camps: small-scale models with individually resolved turbines looking at local effects; and large-scale analyses but with sub-grid scale turbine parameterisations. This work straddles both scales through a 3D unstructured grid model (FVCOM): wind turbine monopiles in the eastern Irish Sea are explicitly described in the grid whilst the overall grid domain covers the south-western UK shelf. Localised regions of decreased velocity extend up to 250 times the monopile diameter away from the monopile. Shelf-wide, the amplitude of the M2 tidal constituent increases by up to 7%. The turbines enhance localised vertical mixing which decreases seasonal stratification. The spatial extent of this extends well beyond the turbines into the surrounding seas. With significant expansion of OWFs on continental shelves, this work highlights the importance of how OWFs may impact coastal (e.g. increased flooding risk) and offshore (e.g. stratification and nutrient cycling) areas.

Unstructured grid modelling of offshore wind farm impacts on seasonally stratified shelf seas

Shelf seas comprise approximately 7% of the world’s oceans and host enormous economic activity. Development of energy installations (e.g. Offshore Wind Farms (OWFs), tidal turbines) in response to increased demand for renewable energy requires a careful analysis of potential impacts. Recent remote sensing observations have identified kilometrescale impacts from OWFs. Existing modelling evaluating monopile impacts has fallen into two camps: small-scale models with individually resolved turbines looking at local effects; and large-scale analyses but with sub-grid scale turbine parameterisations. This work straddles both scales through a 3D unstructured grid model (FVCOM): wind turbine monopiles in the eastern Irish Sea are explicitly described in the grid whilst the overall grid domain covers the south-western UK shelf. Localised regions of decreased velocity extend up to 250 times the monopile diameter away from the monopile. Shelf-wide, the amplitude of the M2 tidal constituent increases by up to 7%. The turbines enhance localised vertical mixing which decreases seasonal stratification. The spatial extent of this extends well beyond the turbines into the surrounding seas. With significant expansion of OWFs on continental shelves, this work highlights the importance of how OWFs may impact coastal (e.g. increased flooding risk) and offshore (e.g. stratification and nutrient cycling) areas.

Occupational exposure to fungi and particles in animal feed industry

Background: Very few studies regarding fungal and particulate matter (PM) exposure in feed industry have been reported, although such contaminants are likely to be a significant contributing factor to several symptoms reported among workers. The purpose of this study has been to characterize fungal and dust exposure in one Portuguese feed industry. Material and Methods: Air and surface samples were collected and subject to further macro- and microscopic observations. In addition we collected other air samples in order to perform real-time quantitative polymerase chain reaction (PCR) amplification of genes from Aspergillus fumigatus and Aspergillus flavus complexes as well as Stachybotrys chartarum. Additionally, two exposure metrics were considered – particle mass concentration (PMC), measured in 5 different sizes (PM0.5, PM1, PM2.5, PM5, PM10), and particle number concentration (PNC) based on results given in 6 different sizes in terms of diameter (0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm). Results: Species from the Aspergillus fumigatus complex were the most abundant in air (46.6%) and in surfaces, Penicillium genus was the most frequently found (32%). The only DNA was detected from A. fumigatus complex. The most prevalent in dust samples were smaller particles which may reach deep into the respiratory system and trigger not only local effects but also the systemic ones. Conclusions: Future research work must be developed aiming at assessing the real health effects of these co-exposures.

Importance of size-selective particle sampling for assessing occupational exposures: results from three different occupational settings

Sampling the total air concentration of particulate matter (PM) only provides a basic estimate of exposure that normally not allows correlating with the observed health effects. Therefore is of extreme importance to know the particles size distribution and, in more detail, the exposure to fine particles (≤ 2.5 µm). This particles dimension corresponds to the respirable fraction. This particle fraction can result, besides local effects, in systemic effects due to particle deposition and clearance from the lungs and transport within the organism. This study intended to describe occupational exposure to PM2.5 in three different units located near Lisbon and related with occupational exposure to organic dust, namely: swine and poultry feed production and waste management.

Study of different atmospheric environments associated to storms development in the Madeira Island

The study aims to improve the understanding about different atmospheric environments leading to the development of storms associated with heavy precipitation in Madeira Island. For this purpose, four main goals have been considered: 1) To document the synoptic and mesoscale environments associated with heavy precipitation. 2) To characterize surface precipitation patterns that affected the island during some periods of significant accumulated precipitation using numerical modelling. 3) To study the relationship between surface precipitation patterns and mesoscale environments. 4) To highlight how the PhD findings obtained in the first three goals can be translated into an operational forecast context. Concerning the large scale environment, precipitation over the island was favoured by weather systems (e.g, mesoscale convective systems and low pressure systems), as well as by the meridional transport of high amount of moisture from a structure denominated as “Atmospheric River”. The tropical origin of this moisture is underscored, however, their impact on the precipitation in Madeira was not so high during the 10 winter seasons [2002 – 2012] studied. The main factor triggering heavy precipitation events over the island is related to the local orography. The steep terrain favours orographically-induced stationary precipitation over the highlands, although maximum of precipitation at coastal region may be produced by localized blocking effect. These orographic precipitating systems presented different structures, associated with shallow and deep convection. Essentially, the study shows that the combination of airflow dynamics, moist content, and orography is the major mechanism that produces precipitation over the island. These factors together with the event duration act to define the regions of excessive precipitation. Finally, the study highlights two useful points for the operational sector, regarding the meridional water vapour transport and local effects causing significant precipitation over the Island; RESUMO: O estudo procura melhorar o entendimento sobre os diferentes ambientes atmosféricos que favorecem o desenvolvimento de tempestades associadas com precipitação intensa na ilha da Madeira. Nesse sentido foram definidos quatro objetivos: 1) Documentar os ambientes sinópticos e de mesoescala associados com precipitação intensa; 2) Caracterizar padrões de precipitação na superfície, em eventos de elevada precipitação acumulada, utilizando modelação numérica; 3) Estudar as relações entre os padrões de precipitação e ambientes de mesoescala; 4) Mostrar como tais resultados podem ser utilizados num contexto operacional de previsão do tempo. Em relação a ambientes de larga escala, verificou-se que a ocorrência de eventos de precipitação intensa sobre a ilha foi favorecida por sistemas meteorológicos, assim como pelo transporte meridional de humidade por meio de estruturas atualmente denominadas Rios atmosféricos. Neste último caso é de destacar a origem tropical de humidade, no entanto, o seu impacto na precipitação sobre a Madeira durante os 10 invernos estudados [2002-2012] não foi tão elevada. O principal fator que favorece os eventos de precipitação intensa está relacionado com a orografia local. O terreno complexo da ilha favorece a ocorrência de precipitação estacionária induzida orograficamente sobre as terras mais altas, embora a precipitação nas zonas costeiras possa ser produzida por um efeito localizado de bloqueio. Estes sistemas orográficos precipitantes apresentaram diferentes estruturas, associados a convecção pouco profunda e profunda. O estudo mostra que a combinação entre as características do escoamento, a quantidade de humidade, e a orografia são os condimentos essenciais para o desenvolvimento da precipitação sobre a ilha, atuando de maneira a definir as regiões de precipitação excessiva. Por fim, o estudo destaca dois pontos que podem ser úteis na previsão do tempo operacional, ligados a larga escala e aos efeitos locais, os quais podem levar ao desenvolvimento de tempestades e precipitação intensa sobre a ilha.