TGF-b2 induction regulates invasiveness of Theileria-transformed leukocytes and disease susceptibility

Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva), or tropical theileriosis (T. annulata). Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF) cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK). We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence.

[Arginine-vasopressin in septic and vasodilatorial shock]

Current therapy of septic/vasodilatory cardiovascular failure includes volume resuscitation and infusion of inotropic and vasopressor agents. Norepinephrine is the first-line vasoconstrictor, and can stabilize hemodynamic variables in most patients. Nonetheless, irreversible cardiovascular failure which is resistant to conventional hemodynamic therapies still is the main cause of death in patients with severe sepsis and septic shock. In such advanced, catecholamine-resistant shock states, arginine-vasopressin (AVP) has repeatedly caused an increase in mean arterial blood pressure, a decrease in toxic norepinephrine-dosages, as well as further beneficial hemodynamic, endocrinologic and renal effects. Although AVP exerted negative inotropic effects in previous clinical trials and in selected animal experiments, a continuous low-dose AVP infusion during advanced septic/vasodilatory shock caused a decrease in cardiac index only in patients with a hyperdynamic circulation. Adverse effects on gastrointestinal circulation and the systemic microcirculation can not be excluded, but have not yet been confirmed in clinical prospective trials. Negative side effects of a supplementary AVP therapy are an increase in total bilirubin concentrations, and a decrease in platelet count. A transient increase in hepatic transaminases during AVP infusion is most likely related to preceding hypotensive episodes. Important points which must be considered when using AVP as a "rescue vasopressor" in septic/vasodilatory shock states are: 1) AVP infusion only in advanced shock states that can not be adequately reversed by conventional hemodynamic therapy (e.g. norepinephrine >0,5-0,6 mug/kg/min), 2) presence of normovolemia, 3) AVP infusion only in combination with norepinephrine, 4) strict avoidance of bolus injections and dosages >4 IU/h. Effects of a supplementary AVP infusion in advanced vasodilatory shock on survival are currently examined in a large, prospective multicenter trial in North America and Australia.

Insulin-like growth factors (IGFs), IGF binding proteins, and other endocrine factors in milk: role in the newborn

The role of colostrum and milk in the neonate has been chiefly recognized as a comprehensive nutrient foodstuff. In addition, the provision of colostrum-the first milk-for early immune capacity has been well documented for several species. Colostrum is additionally a rich and concentrated source of various factors that demonstrate biological activity in vitro. Three hypotheses have been proposed for the phenotypic function of these secreted bioactive components: (1) only mammary disposal, (2) mammary cell regulation, and (3) neonatal function [gastrointestinal tract (GIT) or systemic]. Traditionally, it was assumed that the development of the GIT is preprogrammed and not influenced by events occurring in the intestinal lumen. However, a large volume of research has demonstrated that colostrum (or milk-borne) bioactive components can basically contribute to the regulation of GIT growth and differentiation, while their role in postnatal development at physiological concentrations has remained elusive. Much of our current understanding is derived from cell culture and laboratory animals, but experimentation with agriculturally important species is taking place. This chapter provides an overview of work conducted primarily in neonatal calves and secondarily in other species on the effects on neonates of selected peptide endocrine factors (hormones, growth factors, in part cytokines) in colostrum. The primary focus will be on insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) and other bioactive peptides, but new interest and concern about steroids (especially estrogens) in milk are considered as well.

Effect of discharge desynchronization on the size of motor evoked potentials: an analysis

OBJECTIVE: Motor evoked potentials (MEPs) after transcranial magnetic brain stimulation (TMS) are smaller than CMAPs after peripheral nerve stimulation, because desynchronization of the TMS-induced motor neurone discharges occurs (i.e. MEP desynchronization). This desynchronization effect can be eliminated by use of the triple stimulation technique (TST; Brain 121 (1998) 437). The objective of this paper is to study the effect of discharge desynchronization on MEPs by comparing the size of MEP and TST responses. METHODS: MEP and TST responses were obtained in 10 healthy subjects during isometric contractions of the abductor digiti minimi, during voluntary background contractions between 0% and 20% of maximal force, and using 3 different stimulus intensities. Additional data from other normals and from multiple sclerosis (MS) patients were obtained from previous studies. RESULTS: MEPs were smaller than TST responses in all subjects and under all stimulating conditions, confirming the marked influence of desynchronization on MEPs. There was a linear relation between the amplitudes of MEPs vs. TST responses, independent of the degree of voluntary contraction and stimulus intensity. The slope of the regression equation was 0.66 on average, indicating that desynchronization reduced the MEP amplitude on average by one third, with marked inter-individual variations. A similar average proportion was found in MS patients. CONCLUSIONS: The MEP size reduction induced by desynchronization is not influenced by the intensity of TMS and by the level of facilitatory voluntary background contractions. It is similar in healthy subjects and in MS patients, in whom increased desynchronization of central conduction was previously suggested to occur. Thus, the MEP size reduction observed may not parallel the actual amount of desynchronization.

Neural reprogramming in retinal degeneration.

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration. METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP. RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina. CONCLUSIONS: RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.

One Health approach to use of veterinary pharmaceuticals

An estimated 6051 tons of active substances went into the production of veterinary pharmaceuticals (VPs) for the treatment of food animals in the European Union (EU) in 2004, including 5393 tons of antibiotics and 194 tons of antiparasitics (1). With global meat production projected to increase (2) and the growing market for companion animal pharmaceuticals (3), the use of VPs will continue to increase. Although VPs may benefit the health and welfare of domestic animals and the efficiency of food animal production, they can contaminate the environment through manufacturing, treatment of animals, and disposal of carcasses, offal, urine, feces, and unused products (4) (see the chart). This contamination is a threat to nontarget species, including humans. With Spain having recently authorized marketing of a VP that was banned in South Asia in the past decade in light of environmental impacts, we recommend strengthening of current procedures and addition of a more proactive, holistic, One Health approach applicable to all VPs.

Soybean Aphid Efficacy Evaluation

Soybean (Glycine max), grown in Iowa and most of the north central region of the United States, has not required regular insecticide use. The soybean aphid, Aphis glycines (Hemiptera: Aphididae), causes yield losses from direct plant feeding, and has been shown to transmit several plant viruses. In Iowa, soybean aphid can colonize soybean fields in June and has developed into outbreaks in July and August capable of reducing yields by nearly 40 percent.

Soybean Aphid Efficacy Evaluation

Soybean, Glycine max (L.), grown in Iowa and most of the north central region of the United States, has not required regular insecticide usage. The soybean aphid, Aphis glycines (Hemiptera: Aphididae), causes yield losses from direct plant feeding, and has been shown to transmit several plant viruses. In Iowa, soybean aphid can colonize soybean fields in June and has developed into outbreaks in July and August capable of reducing yields by nearly 40 percent.

Mid-Pleistocene benthic foraminiferal record in the Southwest Pacific

Benthic foraminiferal faunas from three bathyal sequences provide a proxy record of oceanographic changes through the mid-Pleistocene transition (MPT) on either side of the Subtropical Front (STF), east of New Zealand. Canonical correspondence analyses show that factors related to water depth, latitude and climate cycles were more significant than oceanographic factors in determining changes in faunal assemblage composition over the last 1 Ma. Even so, mid-Pleistocene faunal changes are recognizable and can be linked to inferred palaeoceanographic causes. North of the largely stationary STF the faunas were less variable than to the south, perhaps reflecting the less extreme glacial-interglacial fluctuations in the overlying Subtropical Surface Water. Prior to Marine Isotope Stage (MIS) 21 and after MIS 15, the northern faunas had fairly constant composition, but during most of the MPT faunal composition fluctuated in response to climate-related food-supply variations. Faunal changes through the MPT suggest increasing food supply and decreasing dissolved bottom oxygen. South of the STF, beneath Subantarctic Surface Water, mid-Pleistocene faunas exhibited strong glacial-interglacial fluctuations, inferred to be due to higher interglacial nutrient supply and lower oxygen levels. The most dramatic faunal change in the south occurred at the end of the MPT (MIS 17- 12). with an acme of Abditodentrix pseudothalmanni, possibly reflecting higher carbon flux and lower bottom oxygen. This study suggests that the mid-Pleistocene decline and extinction of a group of elongate, cylindrical deep-sea foraminifera may have been related to decreased bottom oxygen concentrations as aresult of slower deep-water currents.

Carbonate and Aluminium accumulation in the central equatorial Pacific Ocean

We examined the flux of Al to sediment accumulating beneath the zone of elevated productivity in the central equatorial Pacific Ocean, along a surface sediment transect at 135°W as well as downcore for a 650 kyr record at 1.3°N, 133.6°W. Across the surface transect, a pronounced, broadly equatorially symmetric increase in Al accumulation is observed, relative to Ti, with Al/Ti ratios reaching values 3-4 times that of potential detrital sources. The profile parallels biogenic accumulation and the modeled flux of particulate 234Th, suggesting rapid and preferential adsorptive removal of Al from seawater by settling biogenic particles. Normative calculations confirm that most Al is unsupported by the terrigenous fraction. The observed distributions are consistent with previous observations of the relative and absolute behavior of Al and Ti in seawater, and we can construct a reasonable mass balance between the amount of seawater-sourced Al retained in the sediment and the amount of seawater Al available in the overlying column. The close tie between Al/Ti and biogenic accumulation (as opposed to concentration) emphasizes that biogenic sedimentary Al/Ti responds to removal-transport phenomena and not bulk sediment composition. Thus, in these sediments dominated by the biogenic component, the bulk Al/Ti ratio reflects biogenic particle flux, and by extension, productivity of the overlying seawater. The downcore profile of Al/Ti at 1.3°N displays marked increases during glacial episodes, similar to that observed across the surface transect, from a background value near Al/Ti of average upper crust. The excursions in Al/Ti are stratigraphically coincident with maxima in both bulk and CaCO3 accumulation and the excess Al appears to not be preferentially affiliated with opaline or organic phases. Consistent with the similar behavioral removal of Al and 234Th, the latter of which responds to the total particle flux, the Al flux reflects carbonate accumulation only because carbonate comprises the dominant flux in these particular deposits. These results collectively indicate that (1) Al in biogenic sediment and settling biogenic particles is strongly affected by a component adsorbed from seawater. Therefore, the common tenet that Al is dominantly associated with terrestrial particulate matter, and the subsequent use of Al distributions to calculate the abundance and flux of terrestrial material in settling particles and sediment, needs to be reevaluated. (2) The Al/Ti ratio in biogenic sediment can be used to trace the productivity of the overlying water, providing a powerful new paleochemical tool to investigate oceanic response to climatic variation. (3) The close correlation between the Al/Ti productivity signal and carbonate maxima downcore at 1.3°N suggests that the sedimentary carbonate maxima in the central equatorial Pacific Ocean record increased productivity during glacial episodes.

Salinity estimation from Gulf of Guinea, sediment core MD03-2707

The isotopic composition of surface seawater is widely used to infer past changes in sea surface salinity using paired foraminiferal Mg/Ca and d18O from marine sediments. At low latitudes, paleosalinity reconstructions using this method have largely been used to document changes in the hydrological cycle. This method usually assumes that the modern seawater d18O (d18Osw)/salinity relationship remained constant through time. Modelling studies have shown that such assumptions may not be valid because large-scale atmospheric circulation patterns linked to global climate changes can alter the seawater d18Osw/salinity relationship locally. Such processes have not been evidenced by paleo-data so far because there is presently no way to reconstruct past changes in the seawater d18Osw/salinity relationship. We have addressed this issue by applying a multi-proxy salinity reconstruction from a marine sediment core collected in the Gulf of Guinea. We measured hydrogen isotopes in C37:2 alkenones (dDa) to estimate changes in seawater dD. We find a smooth, long-term increase of ~10 per mil in dDa between 10 and 3 kyr BP, followed by a rapid decrease of ~10 per mil in dDa between 3 kyr BP and core top to values slightly lighter than during the early Holocene. Those features are inconsistent with published salinity estimations based on d18Osw and foraminiferal Ba/Ca, as well as nearby continental rainfall history derived from pollen analysis. We combined dDa and d18Osw values to reconstruct a Holocene record of salinity and compared it to a Ba/Ca-derived salinity record from the same sedimentary sequence. This combined method provides salinity trends that are in better agreement with both the Ba/Ca-derived salinity and the regional precipitation changes as inferred from pollen records. Our results illustrate that changes in atmospheric circulation can trigger changes in precipitation isotopes in a counter-intuitive manner that ultimately impacts surface salinity estimates based on seawater isotopic values. Our data suggest that the trends in Holocene rainfall isotopic values at low latitudes may not uniquely result from changes in local precipitation associated with the amount effect.

Pb concentrations, Pb isotopic composition, and amount of metalliferous components in pelagic sediments from the Pacific Ocean

The amount of lead annually transferred from oceanic crust to metalliferous sediments was estimated in order to test the hypothesis that a non-magmatic flux of lead causes the Pb surplus in the continental crust. A Pb surplus has been inferred from global crust-mantle lead mass balances derived from lead concentration correlations with other trace elements and from lead isotope systematics in oceanic basalts. DSDP/ODP data on the amount of metalliferous sediments in the Pacific Ocean and along a South Atlantic traverse are used to calculate the mean worldwide thickness of 3 (+/-1) m for purely metalliferous sediment componens. Lead isotope ratios of 39 metalliferous sediments from the Pacific define mixing lines between continent-derived (seawater) and mantle-derived (basaltic) lead, with the most metal-rich sediments usually having the most mantle-like Pb isotope composition. We used this isotope correlation and the Pb content of the 39 metalliferous sediments to derive an estimate of 130 (+/-70) µg/g for the concentration of mantle-derived lead in the purely metalliferous end-member. Mass balance calculations show that at least 12 (+/-8)% of the lead, annually transferred from upper mantle to oceanic crust at the ocean ridges, is leached out by hydrothermal processes and re-deposited in marine sediments. If all of the metalliferous lead is ultimately transferred to the continental crust during subduction, the annual flux of this lead from mantle to continental crust is 2.6 (+/-2.0) * 10**6 kg. Assuming this transfer rate to be proportional to the rate of oceanic plate production, one can fit the lead transfer to models of plate production rate variations through time. Integrating over 4 Ga, hydrothermal lead transfer to the continental crust accounts for a significant portion of the Pb surplus in the continental crust. It therefore appears to be one of the main reasons for the anomalous behavior of lead in the global crust-mantle system.

Vision-based active safety system for automatic stopping

ntelligent systems designed to reduce highway fatalities have been widely applied in the automotive sector in the last decade. Of all users of transport systems, pedestrians are the most vulnerable in crashes as they are unprotected. This paper deals with an autonomous intelligent emergency system designed to avoid collisions with pedestrians. The system consists of a fuzzy controller based on the time-to-collision estimate – obtained via a vision-based system – and the wheel-locking probability – obtained via the vehicle’s CAN bus – that generates a safe braking action. The system has been tested in a real car – a convertible Citroën C3 Pluriel – equipped with an automated electro-hydraulic braking system capable of working in parallel with the vehicle’s original braking circuit. The system is used as a last resort in the case that an unexpected pedestrian is in the lane and all the warnings have failed to produce a response from the driver.

Sistema para cambiar la geometría de un motor

En este proyecto se desarrolla un sistema electrónico para variar la geometría de un motor de un monoplaza que participa en la competición Fórmula SAE. Fórmula SAE es una competición de diseño de monoplazas para estudiantes, organizado por “Society of Automotive Enginners” (SAE). Este concurso busca la innovación tecnológica de la automoción, así como que estudiantes participen en un trabajo real, en el cual el objetivo es obtener resultados competitivos cumpliendo con una serie de requisitos. La variación de la geometría de un motor en un vehículo permite mejorar el rendimiento del monoplaza consiguiendo elevar el par de potencia del motor. Cualquier mejora en del vehículo en un ámbito de competición puede resultar determinante en el desenlace de la misma. El objetivo del proyecto es realizar esta variación mediante el control de la longitud de los tubos de admisión de aire o “runners” del motor de combustión, empleando un motor lineal paso a paso. A partir de la información obtenida por sensores de revoluciones del motor de combustión y la posición del acelerador se debe controlar la distancia de dichos tubos. Integrando este sistema en el bus CAN del vehículo para que comparta la información medida al resto de módulos. Por todo esto se realiza un estudio aclarando los aspectos generales del objetivo del trabajo, para la comprensión del proyecto a realizar, las posibilidades de realización y adquisición de conocimientos para un mejor desarrollo. Se presenta una solución basada en el control del motor lineal paso a paso mediante el microcontrolador PIC32MX795F512-L. Dispositivo del fabricante Microchip con una arquitectura de 32 bits. Este dispone de un módulo CAN integrado y distintos periféricos que se emplean en la medición de los sensores y actuación sobre el motor paso a paso empleando el driver de Texas Instruments DRV8805. Entonces el trabajo se realiza en dos líneas, una parte software de programación del control del sistema, empleando el software de Microchip MPLABX IDE y otra parte hardware de diseño de una PCB y circuitos acondicionadores para la conexión del microcontrolador, con los sensores, driver, motor paso a paso y bus CAN. El software empleado para la realización de la PCB es Orcad9.2/Layout. Para la evaluación de las medidas obtenidas por los sensores y la comprobación del bus CAN se emplea el kit de desarrollo de Microchip, MCP2515 CAN Bus Monitor Demo Board, que permite ver la información en el bus CAN e introducir tramas al mismo. ABSTRACT. This project develops an electronic system to vary the geometry of a car engine which runs the Formula SAE competition. Formula SAE is a design car competition for students, organized by "Society of Automotive Engineers" (SAE). This competition seeks technological innovation in the automotive industry and brings in students to participate in a real job, in which the objective is to obtain competitive results in compliance with certain requirements. Varying engine’s geometry in a vehicle improves car’s performance raising engine output torque. Any improvement in the vehicle in a competition field can be decisive in the outcome of it. The goal of the project is the variation by controlling the length of the air intake pipe or "runners" in a combustion engine, using a linear motor step. For these, uses the information gathered by speed sensors from the combustion engine and by the throttle position to control the distance of these tubes. This system is integrated in the vehicle CAN bus to share the information with the other modules. For all this is made a study to clarify the general aspects of the project in order to understand the activities developed inside the project, the different options available and also, to acquire knowledge for a better development of the project. The solution is based on linear stepper motor control by the microcontroller PIC32MX795F512-L. Device from manufacturer Microchip with a 32-bit architecture. This module has an integrated CAN various peripherals that are used in measuring the performance of the sensors and drives the stepper motor using Texas Instruments DRV8805 driver. Then the work is done in two lines, first, control programming software system using software MPLABX Microchip IDE and, second, hardware design of a PCB and conditioning circuits for connecting the microcontroller, with sensors, driver stepper motor and CAN bus. The software used to carry out the PCB is Orcad9.2/Layout. For the evaluation of the measurements obtained by the sensors and CAN bus checking is used Microchip development kit, MCP2515 CAN Bus Monitor Demo Board, that allows you to see the information on the CAN bus and enter new frames in the bus.

Pantalla táctil para el piloto en un monoplaza de la fórmula SAE

En este proyecto se ha desarrollado un sistema electrónico para un vehículo de Fórmula SAE. La Fórmula SAE es una competición orientada a estudiantes que se basa en el diseño y fabricación de un vehículo de carreras. Este vehículo será posteriormente testeado en una competición a nivel mundial. El principal objetivo de este proyecto es el estudio, diseño y creación de un sistema para la visualización de información en un vehículo a través de una pantalla táctil. El núcleo del sistema será un microcontrolador de 32 bits de Microchip programado en C sobre un sistema de desarrollo integrado. El sistema mostrará información que pueda ser de utilidad para el piloto del coche. La información que se mostrará en la pantalla provendrá de los diferentes sensores del propio vehículo (velocidad, rpm, temperatura, estado de la batería). Dichos sensores se comunicarán con el sistema a través de comunicación CAN Bus. Para el testeo del sistema se utilizará una herramienta de simulación CAN. Además de mostrar información, el piloto será capaz de seleccionar entre diferentes configuraciones para la conducción desde el propio volante. El sistema contiene además los elementos necesarios para la programación y depuración del microcontrolador PIC. ABSTRACT. In this project, an electronic application for a Formula SAE vehicle has been developed. The Formula SAE is a student-oriented competition based on the design and manufacture of a race car. This car will be later tested in a worldwide competition. The principal aim of this project is the study, design and manufacture of a system for the display of a vehicle’s information through a touch screen. The system core will be a 32-bit Microchip microcontroller programmed in C code over an Integrated Development Environment. The system will display useful information to the car driver. The information shown on the screen will come from the different sensors of the vehicle itself (speed, rpm, temperature, battery status). Those sensors will communicate with the system via CAN Bus. A CAN Bus simulator device will be used during the design testing. In addition to displaying information, the pilot will be able to select different driving configurations from the steering wheel itself. The system also contains the necessary elements for programming and debugging the PIC microcontroller.