Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

MASP-1 is a versatile serine protease that cleaves a number of substrates in human blood. In recent years it became evident that besides playing a crucial role in complement activation MASP-1 also triggers other cascade systems and even cells to mount a more powerful innate immune response. In this review we summarize the latest discoveries about the diverse functions of this multi-faceted protease. Recent studies revealed that among MBL-associated serine proteases, MASP-1 is the one responsible for triggering the lectin pathway via its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. The crystal structure of MASP-1 explains its more relaxed substrate specificity compared to the related complement enzymes. Due to the relaxed specificity, MASP-1 interacts with the coagulation cascade and the kinin generating system, and it can also activate endothelial cells eliciting pro-inflammatory signaling.

Comparison of two fiber-optical temperature measurement systems in magnetic fields up to 9.4 Tesla.

PURPOSE Precise temperature measurements in the magnetic field are indispensable for MR safety studies and for temperature calibration during MR-guided thermotherapy. In this work, the interference of two commonly used fiber-optical temperature measurement systems with the static magnetic field B0 was determined. METHODS Two fiber-optical temperature measurement systems, a GaAs-semiconductor and a phosphorescent phosphor ceramic, were compared for temperature measurements in B0 . The probes and a glass thermometer for reference were placed in an MR-compatible tube phantom within a water bath. Temperature measurements were carried out at three different MR systems covering static magnetic fields up to B0  = 9.4T, and water temperatures were changed between 25°C and 65°C. RESULTS The GaAs-probe significantly underestimated absolute temperatures by an amount related to the square of B0 . A maximum difference of ΔT = -4.6°C was seen at 9.4T. No systematic temperature difference was found with the phosphor ceramic probe. For both systems, the measurements were not dependent on the orientation of the sensor to B0 . CONCLUSION Temperature measurements with the phosphor ceramic probe are immune to magnetic fields up to 9.4T, whereas the GaAs-probes either require a recalibration inside the MR system or a correction based on the square of B0 . Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms.

Salmonella typhimurium can colonize the gut, invade intestinal tissues, and cause enterocolitis. In vitro studies suggest different mechanisms leading to mucosal inflammation, including 1) direct modulation of proinflammatory signaling by bacterial type III effector proteins and 2) disruption or penetration of the intestinal epithelium so that penetrating bacteria or bacterial products can trigger innate immunity (i.e., TLR signaling). We studied these mechanisms in vivo using streptomycin-pretreated wild-type and knockout mice including MyD88(-/-) animals lacking an adaptor molecule required for signaling via most TLRs. The Salmonella SPI-1 and the SPI-2 type III secretion systems (TTSS) contributed to inflammation. Mutants that retain only a functional SPI-1 (M556; sseD::aphT) or a SPI-2 TTSS (SB161; DeltainvG) caused attenuated colitis, which reflected distinct aspects of the colitis caused by wild-type S. typhimurium: M556 caused diffuse cecal inflammation that did not require MyD88 signaling. In contrast, SB161 induced focal mucosal inflammation requiring MyD88. M556 but not SB161 was found in intestinal epithelial cells. In the lamina propria, M556 and SB161 appeared to reside in different leukocyte cell populations as indicated by differential CD11c staining. Only the SPI-2-dependent inflammatory pathway required aroA-dependent intracellular growth. Thus, S. typhimurium can use two independent mechanisms to elicit colitis in vivo: SPI-1-dependent and MyD88-independent signaling to epithelial cells and SPI-2-dependent intracellular proliferation in the lamina propria triggering MyD88-dependent innate immune responses.

Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

We explored the host-pathogen interactions of the human opportunistic fungus Candida albicans using Drosophila melanogaster. We established that a Drosophila strain devoid of functional Toll receptor is highly susceptible to the human pathogen C. albicans. Using this sensitive strain, we have been able to show that a set of specific C. albicans mutants of different virulence in mammalian infection models are also impaired in virulence in Drosophila and remarkably display the same rank order of virulence. This immunodeficient insect model also revealed virulence properties undetected in an immunocompetent murine model of infection. The genetic systems available in both host and pathogen will enable the identification of host-specific components and C. albicans genes involved in the host-fungal interplay.

Fish Immune Responses to Myxozoa

Myxozoans evoke important economic losses in aquaculture production, but there is almost a total lack of disease control methods as no vaccines or commercial treatments are currently available. Knowledge of the immune responses that lead to myxozoan elimination and subsequent disease resistance is vital for shaping the future development of disease control measures. Different fish immune factors triggered by myxozoan parasites are reviewed in this chapter. Detailed information on the phenotypic and underlying molecular aspects of innate and adaptive responses, at both cellular and humoral levels, is provided for some well-studied fishmyxozoan systems. The importance of the local immune response, mainly at mucosal sites, is also highlighted. Myxozoan tactics to disable or avoid immune responses, such as modulation of immune gene transcription and immune evasion, are also reviewed. The existence of innate and acquired resistance to some myxozoan species suggest promising possibilities for controlling myxozooses through immune-based strategies, such as genetic selection for host resistance, vaccination, immune therapies and administration of immunostimulants.

Biomechanical evaluation of different angle-stable locking plate systems for mandibular surgery

PURPOSE To compare the initial stability and stability after fatigue of three different locking systems (Synthes(®), Stryker(®) and Medartis(®)) for mandibular fixation and reconstruction. METHOD Standard mandible locking plates with identical profile height (1,5 mm), comparable length and screws with identical diameter (2,0 mm) were used. Plates were fixed with six screws according a preparation protocol. Four point bending tests were then performed using artificial bone material to compare their initial stability and failure limit under realistic loading conditions. Loading of the plates was performed using of a servo hydraulic driven testing machine. The stiffness of the implant/bone construct was calculated using a linear regression on the experimental data included in a range of applied moment between 2 Nm and 6 Nm. RESULTS No statistical difference in the elastic stiffness was visible between the three types of plate. However, differences were observed between the systems concerning the maximal load supported. The Stryker and Synthes systems were able to support a significantly higher moment. CONCLUSION For clinical application all systems show good and reliable results. Practical aspects such as handling, possible angulation of screw fixation, possibility of screw/plate removal, etc. may favour one or the other plating system.

New algorithms for automated phylogenetic reconstruction using artificial intelligence and data mining techniques

Academic and industrial research in the late 90s have brought about an exponential explosion of DNA sequence data. Automated expert systems are being created to help biologists to extract patterns, trends and links from this ever-deepening ocean of information. Two such systems aimed on retrieving and subsequently utilizing phylogenetically relevant information have been developed in this dissertation, the major objective of which was to automate the often difficult and confusing phylogenetic reconstruction process. ^ Popular phylogenetic reconstruction methods, such as distance-based methods, attempt to find an optimal tree topology (that reflects the relationships among related sequences and their evolutionary history) by searching through the topology space. Various compromises between the fast (but incomplete) and exhaustive (but computationally prohibitive) search heuristics have been suggested. An intelligent compromise algorithm that relies on a flexible “beam” search principle from the Artificial Intelligence domain and uses the pre-computed local topology reliability information to adjust the beam search space continuously is described in the second chapter of this dissertation. ^ However, sometimes even a (virtually) complete distance-based method is inferior to the significantly more elaborate (and computationally expensive) maximum likelihood (ML) method. In fact, depending on the nature of the sequence data in question either method might prove to be superior. Therefore, it is difficult (even for an expert) to tell a priori which phylogenetic reconstruction method—distance-based, ML or maybe maximum parsimony (MP)—should be chosen for any particular data set. ^ A number of factors, often hidden, influence the performance of a method. For example, it is generally understood that for a phylogenetically “difficult” data set more sophisticated methods (e.g., ML) tend to be more effective and thus should be chosen. However, it is the interplay of many factors that one needs to consider in order to avoid choosing an inferior method (potentially a costly mistake, both in terms of computational expenses and in terms of reconstruction accuracy.) ^ Chapter III of this dissertation details a phylogenetic reconstruction expert system that selects a superior proper method automatically. It uses a classifier (a Decision Tree-inducing algorithm) to map a new data set to the proper phylogenetic reconstruction method. ^

Endemic tuberculosis, the homeless, and public transportation: A merging of geographical information systems surveillance and the Houston Tuberculosis Initiative Surveillance project

To reach the goals established by the Institute of Medicine (IOM) and the Centers for Disease Control's (CDC) STOP TB USA, measures must be taken to curtail a future peak in Tuberculosis (TB) incidence and speed the currently stagnant rate of TB elimination. Both efforts will require, at minimum, the consideration and understanding of the third dimension of TB transmission: the location-based spread of an airborne pathogen among persons known and unknown to each other. This consideration will require an elucidation of the areas within the U.S. that have endemic TB. The Houston Tuberculosis Initiative (HTI) was a population-based active surveillance of confirmed Houston/Harris County TB cases from 1995–2004. Strengths in this dataset include the molecular characterization of laboratory confirmed cases, the collection of geographic locations (including home addresses) frequented by cases, and the HTI time period that parallels a decline in TB incidence in the United States (U.S.). The HTI dataset was used in this secondary data analysis to implement a GIS analysis of TB cases, the locations frequented by cases, and their association with risk factors associated with TB transmission. ^ This study reports, for the first time, the incidence of TB among the homeless in Houston, Texas. The homeless are an at-risk population for TB disease, yet they are also a population whose TB incidence has been unknown and unreported due to their non-enumeration. The first section of this dissertation identifies local areas in Houston with endemic TB disease. Many Houston TB cases who reported living in these endemic areas also share the TB risk factor of current or recent homelessness. Merging the 2004–2005 Houston enumeration of the homeless with historical HTI surveillance data of TB cases in Houston enabled this first-time report of TB risk among the homeless in Houston. The homeless were more likely to be US-born, belong to a genotypic cluster, and belong to a cluster of a larger size. The calculated average incidence among homeless persons was 411/100,000, compared to 9.5/100,000 among housed. These alarming rates are not driven by a co-infection but by social determinants. The unsheltered persons were hospitalized more days and required more follow-up time by staff than those who reported a steady housing situation. The homeless are a specific example of the increased targeting of prevention dollars that could occur if TB rates were reported for specific areas with known health disparities rather than as a generalized rate normalized over a diverse population. ^ It has been estimated that 27% of Houstonians use public transportation. The city layout allows bus routes to run like veins connecting even the most diverse of populations within the metropolitan area. Secondary data analysis of frequent bus use (defined as riding a route weekly) among TB cases was assessed for its relationship with known TB risk factors. The spatial distribution of genotypic clusters associated with bus use was assessed, along with the reported routes and epidemiologic-links among cases belonging to the identified clusters. ^ TB cases who reported frequent bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis, yet 75% of bus riders were genotypically clustered, indicating recent transmission, compared to 56% of non-bus riders (OR=2.4, 95%CI(2.0, 2.8), p<0.001). Bus riders had a mean cluster size of 50.14 vs. 28.9 (p<0.001). Second order spatial analysis of clustered fingerprint 2 (n=122), a Beijing family cluster, revealed geographic clustering among cases based on their report of bus use. Univariate and multivariate analysis of routes reported by cases belonging to these clusters found that 10 of the 14 clusters were associated with use. Individual Metro routes, including one route servicing the local hospitals, were found to be risk factors for belonging to a cluster shown to be endemic in Houston. The routes themselves geographically connect the census tracts previously identified as having endemic TB. 78% (15/23) of Houston Metro routes investigated had one or more print groups reporting frequent use for every HTI study year. We present data on three specific but clonally related print groups and show that bus-use is clustered in time by route and is the only known link between cases in one of the three prints: print 22. (Abstract shortened by UMI.)^

Grandparental immune priming in S.typhle - Gene expression and Size of F2

Data table shows life history (size-length) and gene expression measurements of 44 target genes and 4 housekepping genes for 192 samples (F2 juveniles) of the experiment "Grandparental immune priming in Syngnathus typhle". Gene expression was measured using Fluidigm chip systems in May 2014. Shown are the mean Ct values (Cycle time) of two technical replicates.

Artificial Neural Nets with Interaction of Afferents

The aim is to obtain computationally more powerful, neuro physiologically founded, artificial neurons and neural nets. Artificial Neural Nets (ANN) of the Perceptron type evolved from the original proposal by McCulloch an Pitts classical paper [1]. Essentially, they keep the computing structure of a linear machine followed by a non linear operation. The McCulloch-Pitts formal neuron (which was never considered by the author’s to be models of real neurons) consists of the simplest case of a linear computation of the inputs followed by a threshold. Networks of one layer cannot compute anylogical function of the inputs, but only those which are linearly separable. Thus, the simple exclusive OR (contrast detector) function of two inputs requires two layers of formal neurons

Dendritic-Like Reliable Computation in Artificial Neurons

Dendritic computation is a term that has been in neuro physiological research for a long time [1]. It is still controversial and far for been clarified within the concepts of both computation and neurophysiology [2], [3]. In any case, it hasnot been integrated neither in a formal computational scheme or structure, nor into formulations of artificial neural nets. Our objective here is to formulate a type of distributed computation that resembles dendritic trees, in such a way that it shows the advantages of neural network distributed computation, mostly the reliability that is shown under the existence of holes (scotomas) in the computing net, without ?blind spots?.

Autonomous vehicle control systems for safe crossroads

This article presents a cooperative manoeuvre among three dual mode cars – vehicles equipped with sensors and actuators, and that can be driven either manually or autonomously. One vehicle is driven autonomously and the other two are driven manually. The main objective is to test two decision algorithms for priority conflict resolution at intersections so that a vehicle autonomously driven can take their own decision about crossing an intersection mingling with manually driven cars without the need for infrastructure modifications. To do this, the system needs the position, speeds, and turning intentions of the rest of the cars involved in the manoeuvre. This information is acquired via communications, but other methods are also viable, such as artificial vision. The idea of the experiments was to adjust the speed of the manually driven vehicles to force a situation where all three vehicles arrive at an intersection at the same time.

Towards architectural foundations for cognitive self-aware systems

In this talk we address a proposal concerning a methodology for extracting universal, domain neutral, architectural design patterns from the analysis of biological cognition. This will render a set of design principles and design patterns oriented towards the construction of better machines. Bio- inspiration cannot be a one step process if we we are going to to build robust, dependable autonomous agents; we must build solid theories first, departing from natural systems, and supporting our designs of artificial ones.

Simulating accepting networks of evolutionary processors with filtered connections by accepting evolutionary P systems

In this work, we propose a variant of P system based on the rewriting of string-objects by means of evolutionary rules. The membrane structure of such a P system seems to be a very natural tool for simulating the filters in accepting networks of evolutionary processors with filtered connections. We discuss an informal construction supporting this simulation. A detailed proof is to be considered in an extended version of this work.

Análisis de la técnica de recarga artificial en la Cubeta de Sant Andreu de la Barca (Barcelona)

El presente proyecto pretende mostrar las posibilidades de la recarga artificial como elemento de gestión de los recursos de agua subterránea del acuífero aluvial del río Llobregat, en su sector de la Cubeta de Sant Andreu de la Barca (Barcelona), el cual es fuente de abastecimiento urbano, agrícola e industrial del entorno de Sant Andreu de la Barca. Igualmente, se revisa la efectividad de la aplicación de dicha técnica que se practica actualmente. Hace años, las condiciones naturales del río hacían posible la recarga natural de la Cubeta, pero la implantación de industrias en la zona y la regulación mediante la presa de La Baells desde el año 1976, han originado cambios en el comportamiento natural del acuífero, que se han manifestado básicamente en una disminución de la recarga natural como consecuencia de la impermeabilización de los suelos originada por la urbanización de los mismos. Se ha producido también un fenómeno de colmatación del lecho del río, al dificultarse la removilización de los materiales finos depositados en el fondo del cauce, produciendo también una disminución de la recarga al acuífero a través del lecho. Por último, la mayor demanda de suministro por parte del sector industrial ha influido negativamente en el almacenamiento del acuífero. Desde hace décadas, se lleva efectuando una recarga artificial en el lecho del río para tratar de paliar en lo posible estos efectos perjudiciales. La misma se efectúa mediante dos sistemas distintos: escarificando el lecho del río para aumentar su capacidad de infiltración, y mediante la utilización de balsas de recarga, a través de las cuales se infiltra el agua en el acuífero. El objetivo de este proyecto es analizar el efecto actual que la recarga mediante balsas está teniendo sobre el acuífero. Para ello, se utilizarán, entre otras técnicas, la elaboración de un modelo matemático con el que poder simular el efecto de la recarga. VIII ABSTRACT This project aims to show the possibilities of artificial recharge as groundwater resources management element in the alluvial aquifer of the Llobregat River, in the sector of the Basin of Sant Andreu de la Barca (Barcelona), which is a source of urban, agricultural and industrial supply of the Sant Andreu de la Barca area. Too, the effectiveness of the current implementation of this technique is reviewed. Years ago, natural river conditions made possible the natural recharge of the aquifer, but the establishment of industries in the area and the river regulation by the la Baells dam since 1976, have led to changes in the natural behavior of the aquifer, which basically are a decrease in natural recharge, because the soil has become impervious, due to land urbanization. There has been also a phenomenon of clogging of the river bed, caused by the difficult in the remobilization of fine materials deposited on the river bed, which has produced a decrease in the groundwater recharge through the river. Finally, the increase in water demand by the industrial sector, has diminished aquifer storage. For decades, artificial recharge in the river bed has been practiced to alleviate negative effects. It is done by two different systems: scratching the river bed to increase its infiltration capacity, and using recharge ponds, through which water infiltrates into the aquifer. The objective of this project is to analyze the current effect that recharge by ponds is having in the aquifer. Among other techniques, mathematical modeling has been used for simulating the effect of artificial recharge in the aquifer.