Immune responses in Bathymodiolus azoricus upon Vibrio challenges : approaches to characterize mussel survival strategies and physiological adaptations in deep sea extreme environments

Tese de Doutoramento, Ciências do Mar, especialidade de Biologia Marinha, 18 de Dezembro de 2015, Universidade dos Açores.

A model to screen and improve business potential of micro and small enterprises in developing countries: Evidence from the Island of Mozambique

Programmes supporting micro and small enterprises in developing countries have been showing that capital is not enough to allow business success: survival and growth. Literature does not provide comprehensive and practical tool to support business development in this context, but allowed the collection of forty-nine success variables that were studied in a sample of successful and unsuccessful businesses in the Island of Mozambique to discover what were the key factors affecting those businesses’ performance. Empirical data gave the insights for the development of a model to screen and improve business potential of micro and small enterprises in this context.

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Gastric supply manipulation to modulate ghrelin production and enhance vascularization to the cardia: proof of the concept in a porcine model.

Introduction. Selective embolization of the left-gastric artery (LGA) reduces levels of ghrelin and achieves significant short-term weight loss. However, embolization of the LGA would prevent the performance of bariatric procedures because the high-risk leakage area (gastroesophageal junction [GEJ]) would be devascularized. Aim. To assess an alternative vascular approach to the modulation of ghrelin levels and generate a blood flow manipulation, consequently increasing the vascular supply to the GEJ. Materials and methods. A total of 6 pigs underwent a laparoscopic clipping of the left gastroepiploic artery. Preoperative and postoperative CT angiographies were performed. Ghrelin levels were assessed perioperatively and then once per week for 3 weeks. Reactive oxygen species (ROS; expressed as ROS/mg of dry weight [DW]), mitochondria respiratory rate, and capillary lactates were assessed before and 1 hour after clipping (T0 and T1) and after 3 weeks of survival (T2), on seromuscular biopsies. A celiac trunk angiography was performed at 3 weeks. Results. Mean (±standard deviation) ghrelin levels were significantly reduced 1 hour after clipping (1902 ± 307.8 pg/mL vs 1084 ± 680.0; P = .04) and at 3 weeks (954.5 ± 473.2 pg/mL; P = .01). Mean ROS levels were statistically significantly decreased at the cardia at T2 when compared with T0 (0.018 ± 0.006 mg/DW vs 0.02957 ± 0.0096 mg/DW; P = .01) and T1 (0.0376 ± 0.008mg/DW; P = .007). Capillary lactates were significantly decreased after 3 weeks, and the mitochondria respiratory rate remained constant over time at the cardia and pylorus, showing significant regional differences. Conclusions. Manipulation of the gastric flow targeting the gastroepiploic arcade induces ghrelin reduction. An endovascular approach is currently under evaluation.

Regulation of the memory T cell development and islet beta-cell survival by DAPK-related apoptosis-inducing protein kinase 2 (Drak2)

Drak2 est un membre de la famille des protéines associées à la mort et c’est une sérine/thréonine kinase. Chez les souris mutantes nulles Drak2, les cellules T ne présentent aucune défectuosité apparente en apoptose induite par activation, après stimulation avec anti-CD3 et anti-CD28, mais ont un seuil de stimulation réduit, comparées aux cellules T de type sauvage (TS). Dans notre étude, l’analyse d’hybridation in situ a révélé que l’expression de Drak2 est ubiquiste au stade de la mi-gestation chez les embryons, suivie d’une expression plus focale dans les divers organes pendant la période périnatale et l’âge adulte, notamment dans le thymus, la rate, les ganglions lymphatiques, le cervelet, les noyaux suprachiasmatiques, la glande pituitaire, les lobes olfactifs, la médullaire surrénale, l’estomac, la peau et les testicules. Nous avons créé des souris transgéniques (Tg) Drak2 en utilisant le promoteur humain beta-actine. Ces souris Tg montraient des ratios normaux entre cellules T versus B et entre cellules CD4 versus CD8, mais leur cellularité et leur poids spléniques étaient inférieurs comparé aux souris de type sauvage. Après activation TCR, la réponse proliférative des cellules T Tg Drak2 était normale, même si leur production d’interleukine (IL)-2 et IL-4 mais non d’interféron-r était augmentée. Les cellules T Tg Drak2 activées ont démontré une apoptose significativement accrue en présence d’IL-2 exogène. Au niveau moléculaire, les cellules T Tg Drak2 ont manifesté une augmentation moins élevée des facteurs anti-apoptotiques durant l’activation; un tel changement a probablement rendu les cellules vulnérables aux attaques subséquentes d’IL-2. L’apoptose compromise dans les cellulesT Tg Drak2 a été associée à un nombre réduit de cellules T ayant le phénotype des cellules mémoires (CD62Llo) et avec des réactions secondaires réprimées des cellules T dans l’hypersensibilité de type différé. Ces résultats démontrent que Drak2 s’exprime dans le compartiment des cellules T mais n’est pas spécifique aux cellules T; et aussi qu’il joue des rôles déterminants dans l’apoptose des cellules T et dans le développement des cellules mémoires T. En outre, nous avons recherché le rôle de Drak2 dans la survie des cellules beta et le diabète. L’ARNm et la protéine Drak2 ont été rapidement induits dans les cellules beta de l’îlot après stimulation exogène par les cytokines inflammatoires ou les acides gras libres et qui est présente de façon endogène dans le diabète, qu’il soit de type 1 ou de type 2. La régulation positive de Drak2 a été accompagnée d’une apoptose accrue des cellules beta. L’apoptose des cellules beta provoquée par les stimuli en question a été inhibée par la chute de Drak2 en utilisant petit ARNi. Inversement, la surexpression de Drak2 Tg a mené à l’apoptose aggravée des cellules beta déclenchée par les stimuli. La surexpression de Drak2 dans les îlots a compromis l’augmentation des facteurs anti-apoptotiques, tels que Bcl-2, Bcl-xL et Flip, sur stimulation par la cytokine et les acides gras libres. De plus, les expériences in vivo ont démontré que les souris Tg Drak2 étaient sujettes au diabète de type 1 dans un modèle de diabète provoqué par de petites doses multiples de streptozotocine et qu’elles étaient aussi sujettes au diabète de type 2 dans un modèle d’obésité induite par la diète. Nos données montrent que Drak2 est défavorable à la survie des cellules beta. Nous avons aussi étudié la voie de transmission de Drak2. Nous avons trouvé que Drak2 purifiée pouvait phosphoryler p70S6 kinase dans une analyse kinase in vitro. Lasurexpression de Drak2 dans les cellules NIT-1 a entraîné l’augmentation de la phosphorylasation p70S6 kinase tandis que l’abaissement de Drak2 dans ces cellules a réduit la phosphorylation. Ces recherches mécanistes ont prouvé que p70S6 kinase était véritablement un substrat de Drak2 in vitro et in vivo. Cette étude a découvert les fonctions importantes de Drak2 dans l’homéostasie des cellules T et le diabète. Nous avons prouvé que p70S6 kinase était un substrat de Drak2. Nos résultats ont approfondi nos connaissances de Drak2 à l’intérieur des systèmes immunitaire et endocrinien. Certaines de nos conclusions, comme les rôles de Drak2 dans le développement des cellules mémoires T et la survie des cellules beta pourraient être explorées pour des applications cliniques dans les domaines de la transplantation et du diabète.

The in vivo characterization of the DNA repair gene apn-1 in the model organism Caenorhabditis elegans

Les sites apuriniques/apyrimidinique (AP) représentent une forme de dommage à l’ADN hautement mutagène et ce type de dommage peut survenir spontanément ou être induit par une variété d’agents. Afin de préserver la stabilité génomique, deux familles d’endonucléases de type AP, endo-IV et exo-III, sont nécessaires pour contrecarrer les effets mutagènes des sites AP. Malgré l’identification de membres des deux familles dans plusieurs organismes unicellulaire tels que E.coli et S. cerevisiae, aucun membre de la famille endo-IV n’a été identifié chez les organismes multicellulaires à l’exception de C. elegans et de C. briggsae. Nous avons donc décidé d’investiguer l’importance biologique de APN-1 chez C. elegans par l’utilisation d’une approche de knockdown du gène. Dans notre étude, nous avons montré que le knockdown du gène apn-1 chez C. elegans, en utilisant des ARN d’interférence (ARNi), cause une accumulation de mutations spontanées et induites par des drogues résultant en un délai de l’éclosion des œufs ainsi que par une diminution de la survie et de la longévité des vers adultes. De plus, nous avons montré que cette accumulation de mutations mène à un délai dans la progression du cycle cellulaire durant l’embryogénèse, représentant possiblement une explication du délai dans l’éclosion des œufs. Nous avons montré qu’il y avait une augmentation du niveau de mutations dans la gorge des vers, sans toutefois pouvoir confirmer la distribution de APN-1 qui possède une étiquette GFP. Les animaux transgéniques APN-1-GFP n’exprimaient pas suffisamment de la protéine de fusion pour permettre une visualisation à l’aide d’un microscope à fluorescence, mais la protéine a été détectée par immunobuvardage de type western. Les animaux transgéniques APN-1-GFP étaient instables et avaient des phénotypes concordants avec les défauts génétiques. En conclusion, il semble que C. elegans aie évolué afin de retenir un niveau de base de APN-1 jouant ainsi un rôle versatile afin de maintenir l’intégrité génétique d’autant plus que cet organisme semble manquer plusieurs enzymes de la voie de réparation par excision de base.

The BTB/POZ Transcription Factor Miz-1 Is Required To Regulate The Commitment, Survival And Differentiation Of Early B And T Cell Lineages

Les lymphocytes B et T sont issus de cellules progénitrices lymphoïdes de la moelle osseuse qui se différencient grâce à l’action de facteurs de transcription, cytokines et voies de signalisation, dont l’interleukine-7 (IL-7)/IL-7 récepteur (IL-7R). Le facteur de transcription c-Myc est exprimé par les cellules lymphoïdes et contrôle leur croissance et leur différenciation. Cette régulation transcriptionnelle peut être coordonnée par le complexe c-Myc/Myc-Interacting Zinc finger protein-1 (Miz-1). Le but de ce projet était de comprendre les mécanismes qui impliquent Miz-1 et le complexe c-Myc/Miz-1 dans le développement des lymphocytes B et T. Pour réaliser ce projet, des souris déficientes pour le domaine de transactivation de Miz-1 (Miz-1POZ) et des souris à allèles mutantes pour c-MycV394D, mutation qui empêche l’interaction avec Miz-1, ont été générées. La caractérisation des souris Miz 1POZ a démontré que l’inactivation de Miz-1 perturbe le développement des lymphocytes B et T aux stades précoces de leur différenciation qui dépend de l’IL-7. L’analyse de la cascade de signalisation IL-7/IL-7R a montré que ces cellules surexpriment la protéine inhibitrice SOCS1 qui empêche la phosphorylation de STAT5 et perturbe la régulation à la hausse de la protéine de survie Bcl-2. De plus, Miz-1 se lie directement au promoteur de SOCS1 et contrôle son activité. En plus de contrôler l’axe IL-7/IL-7R/STAT5/Bcl-2 spécifiquement aux stades précoces du développement afin d’assurer la survie des progéniteurs B et T, Miz-1 régule l’axe EBF/Pax-5/Rag-1/2 dans les cellules B afin de coordonner les signaux nécessaires pour la différenciation des cellules immatures. La caractérisation des souris c-MycV394D a montré, quant à elle, que les fonctions de Miz-1 dans les cellules B et T semblent indépendantes de c-Myc. Les cellules T des souris Miz-1POZ ont un défaut de différenciation additionnel au niveau de la -sélection, étape où les signaux initiés par le TCR remplacent ceux induits par IL-7 pour assurer la prolifération et la différenciation des thymocytes en stades plus matures. À cette étape du développement, une forme fonctionnelle de Miz-1 semble être requise pour contrôler le niveau d’activation de la voie p53, induite lors du processus de réarrangement V(D)J du TCR. L’expression de gènes pro-apoptotiques PUMA, NOXA, Bax et du régulateur de cycle cellulaire p21CIP1 est régulée à la hausse dans les cellules des souris Miz-1POZ. Ceci provoque un débalancement pro-apoptotique qui empêche la progression du cycle cellulaire des cellules TCR-positives. La survie des cellules peut être rétablie à ce stade de différenciation en assurant une coordination adéquate entre les signaux initiés par l’introduction d’un TCR transgénique et d’un transgène codant pour la protéine Bcl-2. En conclusion, ces études ont montré que Miz-1 intervient à deux niveaux du développement lymphoïde: l’un précoce en contrôlant la signalisation induite par l’IL-7 dans les cellules B et T, en plus de l’axe EBF/Pax-5/Rag-1/2 dans les cellules B; et l’autre tardif, en coordonnant les signaux de survie issus par le TCR et p53 dans les cellules T. Étant donné que les thymocytes et lymphocytes B immatures sont sujets à plusieurs rondes de prolifération, ces études serviront à mieux comprendre l’implication des régulateurs du cycle cellulaire comme c-Myc et Miz-1 dans la génération des signaux nécessaires à la différenciation non aberrante et à la survie des ces cellules. Enfin, les modèles expérimentaux, souris déficientes ou à allèles mutantes, utilisés pour ce travail permettront de mieux définir les bases moléculaires de la transformation maligne des lymphocytes B et T et de révéler les mécanismes conduisant au lymphome.

Regression models for bivariate survival data

Multivariate lifetime data arise in various forms including recurrent event data when individuals are followed to observe the sequence of occurrences of a certain type of event; correlated lifetime when an individual is followed for the occurrence of two or more types of events, or when distinct individuals have dependent event times. In most studies there are covariates such as treatments, group indicators, individual characteristics, or environmental conditions, whose relationship to lifetime is of interest. This leads to a consideration of regression models.The well known Cox proportional hazards model and its variations, using the marginal hazard functions employed for the analysis of multivariate survival data in literature are not sufficient to explain the complete dependence structure of pair of lifetimes on the covariate vector. Motivated by this, in Chapter 2, we introduced a bivariate proportional hazards model using vector hazard function of Johnson and Kotz (1975), in which the covariates under study have different effect on two components of the vector hazard function. The proposed model is useful in real life situations to study the dependence structure of pair of lifetimes on the covariate vector . The well known partial likelihood approach is used for the estimation of parameter vectors. We then introduced a bivariate proportional hazards model for gap times of recurrent events in Chapter 3. The model incorporates both marginal and joint dependence of the distribution of gap times on the covariate vector . In many fields of application, mean residual life function is considered superior concept than the hazard function. Motivated by this, in Chapter 4, we considered a new semi-parametric model, bivariate proportional mean residual life time model, to assess the relationship between mean residual life and covariates for gap time of recurrent events. The counting process approach is used for the inference procedures of the gap time of recurrent events. In many survival studies, the distribution of lifetime may depend on the distribution of censoring time. In Chapter 5, we introduced a proportional hazards model for duration times and developed inference procedures under dependent (informative) censoring. In Chapter 6, we introduced a bivariate proportional hazards model for competing risks data under right censoring. The asymptotic properties of the estimators of the parameters of different models developed in previous chapters, were studied. The proposed models were applied to various real life situations.

Biologically Plausible Neural Model for the Recognition of Biological Motion and Actions

The visual recognition of complex movements and actions is crucial for communication and survival in many species. Remarkable sensitivity and robustness of biological motion perception have been demonstrated in psychophysical experiments. In recent years, neurons and cortical areas involved in action recognition have been identified in neurophysiological and imaging studies. However, the detailed neural mechanisms that underlie the recognition of such complex movement patterns remain largely unknown. This paper reviews the experimental results and summarizes them in terms of a biologically plausible neural model. The model is based on the key assumption that action recognition is based on learned prototypical patterns and exploits information from the ventral and the dorsal pathway. The model makes specific predictions that motivate new experiments.

SB.TV's successful yet unconventional establishment of a Brand based solely on Social Network Success may present a problem in long-term survival

Research Proposal in SB.TV case study. New dimension to brand model for Web 2.0 success

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia

A Demographic Model to Evaluate Population Declines in the Endangered Streaked Horned Lark

The Streaked Horned Lark (Eremophila alpestris strigata) is listed as endangered by the State of Washington, USA and by Canada under the Species at Risk Act and is also classified as a federal candidate for listing under the Endangered Species Act in the USA. A substantial portion of Streaked Horned Lark habitat has been lost or degraded, and range contraction has occurred in Oregon, Washington, and British Columbia. We estimate the vital rates (fecundity, adult and juvenile survival) and population growth rate (λ) for Streaked Horned Larks breeding in Washington, USA and conduct a Life-Stage Simulation Analysis (LSA) to evaluate which vital rate has the greatest influence on λ. We simulated changes in the three vital rates to examine how much they would need to be adjusted either independently or in concert to achieve a stable Streaked Horned Lark population (λ = 1). We also evaluated which fecundity component (the number of fledglings per egg laid or renesting interval) had the greatest impact on λ. The estimate of population growth suggests that Streaked Horned Larks in Washington are declining rapidly (λ = 0.62 ± 0.10) and that local breeding sites are not sustainable without immigration. The LSA results indicate that adult survival had the greatest influence on λ, followed by juvenile survival and fecundity. However, increases in vital rates led to λ = 1 only when adult survival was raised from 0.47 to 0.85, juvenile survival from 0.17 to 0.58, and fecundity from 0.91 to 3.09. Increases in breeding success and decreases in the renesting interval influenced λ similarly; however, λ did not reach 1 even when breeding success was raised to 100% or renesting intervals were reduced to 1 day. Only when all three vital rates were increased simultaneously did λ approach 1 without requiring highly unrealistic increases in each vital rate. We conclude that conservation activities need to target all or multiple vital rates to be successful. The baseline data presented here and subsequent efforts to manage Streaked Horned Larks will provide valuable information for management of other declining Horned Lark subspecies and other grassland songbirds across North America.

Age-specific survival of male Golden-cheeked Warblers on the Fort Hood Military Reservation, Texas

Population models are essential components of large-scale conservation and management plans for the federally endangered Golden-cheeked Warbler (Setophaga chrysoparia; hereafter GCWA). However, existing models are based on vital rate estimates calculated using relatively small data sets that are now more than a decade old. We estimated more current, precise adult and juvenile apparent survival (Φ) probabilities and their associated variances for male GCWAs. In addition to providing estimates for use in population modeling, we tested hypotheses about spatial and temporal variation in Φ. We assessed whether a linear trend in Φ or a change in the overall mean Φ corresponded to an observed increase in GCWA abundance during 1992-2000 and if Φ varied among study plots. To accomplish these objectives, we analyzed long-term GCWA capture-resight data from 1992 through 2011, collected across seven study plots on the Fort Hood Military Reservation using a Cormack-Jolly-Seber model structure within program MARK. We also estimated Φ process and sampling variances using a variance-components approach. Our results did not provide evidence of site-specific variation in adult Φ on the installation. Because of a lack of data, we could not assess whether juvenile Φ varied spatially. We did not detect a strong temporal association between GCWA abundance and Φ. Mean estimates of Φ for adult and juvenile male GCWAs for all years analyzed were 0.47 with a process variance of 0.0120 and a sampling variance of 0.0113 and 0.28 with a process variance of 0.0076 and a sampling variance of 0.0149, respectively. Although juvenile Φ did not differ greatly from previous estimates, our adult Φ estimate suggests previous GCWA population models were overly optimistic with respect to adult survival. These updated Φ probabilities and their associated variances will be incorporated into new population models to assist with GCWA conservation decision making.

Variables associated with nest survival of Golden-winged Warblers (Vermivora chrysoptera) among vegetation communities commonly used for nesting

Among shrubland- and young forest-nesting bird species in North America, Golden-winged Warblers (Vermivora chrysoptera) are one of the most rapidly declining partly because of limited nesting habitat. Creation and management of high quality vegetation communities used for nesting are needed to reduce declines. Thus, we examined whether common characteristics could be managed across much of the Golden-winged Warbler’s breeding range to increase daily survival rate (DSR) of nests. We monitored 388 nests on 62 sites throughout Minnesota, Wisconsin, New York, North Carolina, Pennsylvania, Tennessee, and West Virginia. We evaluated competing DSR models in spatial-temporal (dominant vegetation type, population segment, state, and year), intraseasonal (nest stage and time-within-season), and vegetation model suites. The best-supported DSR models among the three model suites suggested potential associations between daily survival rate of nests and state, time-within-season, percent grass and Rubus cover within 1 m of the nest, and distance to later successional forest edge. Overall, grass cover (negative association with DSR above 50%) and Rubus cover (DSR lowest at about 30%) within 1 m of the nest and distance to later successional forest edge (negative association with DSR) may represent common management targets across our states for increasing Golden-winged Warbler DSR, particularly in the Appalachian Mountains population segment. Context-specific adjustments to management strategies, such as in wetlands or areas of overlap with Blue-winged Warblers (Vermivora cyanoptera), may be necessary to increase DSR for Golden-winged Warblers.

Modelling the movement and survival of the root-feeding clover weevil, Sitona lepidus, in the root-zone of white clover

White clover (Trifolium repens) is an important pasture legume but is often difficult to sustain in a mixed sward because, among other things, of the damage to roots caused by the soil-dwelling larval stages of S. lepidus. Locating the root nodules on the white clover roots is crucial for the survival of the newly hatched larvae. This paper presents a numerical model to simulate the movement of newly hatched S. lepidus larvae towards the root nodules, guided by a chemical signal released by the nodules. The model is based on the diffusion-chemotaxis equation. Experimental observations showed that the average speed of the larvae remained approximately constant, so the diffusion-chernotaxis model was modified so that the larvae respond only to the gradient direction of the chemical signal but not its magnitude. An individual-based lattice Boltzmann method was used to simulate the movement of individual larvae, and the parameters required for the model were estimated from the measurement of larval movement towards nodules in soil scanned using X-ray microtomography. The model was used to investigate the effects of nodule density, the rate of release of chemical signal, the sensitivity of the larvae to the signal, and the random foraging of the larvae on the movement and subsequent survival of the larvae. The simulations showed that the most significant factors for larval survival were nodule density and the sensitivity of the larvae to the signal. The dependence of larval survival rate on nodule density was well fitted by the Michealis-Menten kinetics. (c) 2005 Elsevier B.V All rights reserved.