Modelling habitat-suitability using museum collections: an example with three sympatric Apodemus species from the Alps

Aim, Location Although the alpine mouse Apodemus alpicola has been given species status since 1989, no distribution map has ever been constructed for this endemic alpine rodent in Switzerland. Based on redetermined museum material and using the Ecological-Niche Factor Analysis (ENFA), habitat-suitability maps were computed for A. alpicola, and also for the co-occurring A. flavicollis and A. sylvaticus. Methods In the particular case of habitat suitability models, classical approaches (GLMs, GAMs, discriminant analysis, etc.) generally require presence and absence data. The presence records provided by museums can clearly give useful information about species distribution and ecology and have already been used for knowledge-based mapping. In this paper, we apply the ENFA which requires only presence data, to build a habitat-suitability map of three species of Apodemus on the basis of museum skull collections. Results Interspecific niche comparisons showed that A. alpicola is very specialized concerning habitat selection, meaning that its habitat differs unequivocally from the average conditions in Switzerland, while both A. flavicollis and A. sylvaticus could be considered as 'generalists' in the study area. Main conclusions Although an adequate sampling design is the best way to collect ecological data for predictive modelling, this is a time and money consuming process and there are cases where time is simply not available, as for instance with endangered species conservation. On the other hand, museums, herbariums and other similar institutions are treasuring huge presence data sets. By applying the ENFA to such data it is possible to rapidly construct a habitat suitability model. The ENFA method not only provides two key measurements regarding the niche of a species (i.e. marginality and specialization), but also has ecological meaning, and allows the scientist to compare directly the niches of different species.

Unpacking the cognitive map: the parallel map theory of hippocampal function

In the parallel map theory, the hippocampus encodes space with 2 mapping systems. The bearing map is constructed primarily in the dentate gyrus from directional cues such as stimulus gradients. The sketch map is constructed within the hippocampus proper from positional cues. The integrated map emerges when data from the bearing and sketch maps are combined. Because the component maps work in parallel, the impairment of one can reveal residual learning by the other. Such parallel function may explain paradoxes of spatial learning, such as learning after partial hippocampal lesions, taxonomic and sex differences in spatial learning, and the function of hippocampal neurogenesis. By integrating evidence from physiology to phylogeny, the parallel map theory offers a unified explanation for hippocampal function.

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.

Population structure and diversity of the pathogenic fungus Aspergillus fumigatus isolated from different sources and geographic origins

Fifty-five clinical and environmental Aspergillus fumigatus isolates from Mexico, Argentina, France and Peru were analyzed to determine their genetic variability, reproductive system and level of differentiation using amplified fragment length polymorphism markers. The level of genetic variability was assessed by measuring the percentage of polymorphic loci, number of effective alleles, expected heterozygocity and by performing an association index test (I A). The degree of genetic differentiation and variation was determined using analysis of molecular variance at three levels. Using the paired genetic distances, a dendrogram was built to detect the genetic relationship among alleles. Finally, a network of haplotypes was constructed to determine the geographic relationship among them. The results indicate that the clinical isolates have greater genetic variability than the environmental isolates. The I A of the clinical and environmental isolates suggests a recombining population structure. The genetic differentiation among isolates and the dendrogram suggest that the groups of isolates are different. The network of haplotypes demonstrates that the majority of the isolates are grouped according to geographic origin.

New genetic models and mesenchymal cells as tools to ameliorate anti-tumor immunity

Résumé Le but final de ce projet est d'utiliser des cellules T ou des cellules souches mésenchymateuses modifiées génétiquement afin de surexprimer localement les deux chémokines CXCL13 et CCL2 ensemble ou chacune séparément à l'intérieur d'une tumeur solide. CXCL13 est supposé induire des structures lymphoïdes ectopiques. Un niveau élevé de CCL2 est présumé initier une inflammation aiguë. La combinaison des deux effets amène à un nouveau modèle d'étude des mécanismes régulateur de la tolérance périphérique et de l'immunité tumorale. Les connaissances acquises grâce à ce modèle pourraient permettre le développement ou l'amélioration des thérapies immunes du cancer. Le but premier de ce travail a été l'établissement d'un modèle génétique de la souris permettant d'exprimer spécifiquement dans la tumeur les deux chémokines d'intérêt à des niveaux élevés. Pour accomplir cette tâche, qui est en fait une thérapie génétique de tumeurs solides, deux types de cellules porteuses potentielles ont été évaluées. Des cellules CD8+ T et des cellules mésenchymateuses de la moelle osseuse transférées dans des receveurs portant une tumeur. Si on pouvait répondre aux besoins de la thérapie génétique, indépendamment de la thérapie immune envisagée, on posséderait là un outil précieux pour bien d'autres approches thérapeutiques. Plusieurs lignées de souris transgéniques ont été générées comme source de cellules CD8+ T modifiées afin d'exprimer les chémokines d'intérêt. Dans une approche doublement transgénique les propriétés de deux promoteurs spécifiques de cellules T ont été combinées en utilisant la technologie Cre-loxP. Le promoteur de granzyme B confère une dépendance d'activation et le promoteur distal de lck assure une forte expression constitutive dès que les cellules CD8+ T ont été activées. Les transgènes construits ont montré une bonne performance in vivo et des souris qui expriment CCL2 dans des cellules CD8+ T activées ont été obtenues. Ces cellules peuvent maintenant être utilisées avec différents protocoles pour transférer des cellules T cytotoxiques (CTL) dans des receveurs porteur d'une tumeur, permettant ainsi d'évaluer leur capacité en tant que porteuse de chémokine d'infiltrer la tumeur. L'établissement de souris transgéniques, qui expriment pareillement CXCL13 est prévu dans un avenir proche. L'évaluation de cellules mésenchymateuses de la moelle osseuse a démontré que ces cellules se greffent efficacement dans le stroma tumoral suite à la co-injection avec des cellules tumorales. Cela représente un outil précieux pour la recherche, vu qu'il permet d'introduire des cellules manipulées dans un modèle tumoral. Les résultats confirment partiellement d'autres résultats rapportés dans un modèle amélioré. Cependant, l'efficacité et la spécificité suggérées de la migration systémique de cellules mésenchymateuses de la moelle osseuse dans une tumeur n'ont pas été observées dans notre modèle, ce qui indique, que ces cellules ne se prêtent pas à une utilisation thérapeutique. Un autre résultat majeur de ce travail est l'établissement de cultures de cellules mésenchymateuses de la moelle osseuse in vitro conditionnées par des tumeurs, ce qui a permis à ces cellules de s'étendre plus rapidement en gardant leur capacité de migration et de greffe. Cela offre un autre outil précieux, vu que la culture in vitro est un pas nécessaire pour une manipulation thérapeutique. Abstract The ultimate aim of the presented project is to use genetically modified T cells or mesenchymal stem cells to locally overexpress the two chemokines CXCL13 and CCL2 together or each one alone inside a solid tumor. CXCL13 is supposed to induce ectopic lymphoid structures and a high level of CCL2 is intended to trigger acute inflamation. The combination of these two effects represents a new model for studying mechanisms that regulate peripheral tolerance and tumor immunity. Gained insights may help developing or improving immunotherapy of cancer. The primary goal of the executed work was the establishment of a genetic mouse model that allows tumor-specific expression of high levels of the two chemokines of interest. For accomplishing this task, which represents gene therapy of solid tumors, two types of potentially useful carrier cells were evaluated. CD8+ T cells and mesenchymal bone marrow cells to be used in adoptive cell transfers into tumor-bearing mice. Irrespectively of the envisaged immunotherapy, satisfaction of so far unmet needs of gene therapy would be a highly valuable tool that may be employed by many other therapeutic approaches, too. Several transgenic mouse lines were generated as a source of CD8+ T cells modified to express the chemokines of interest. In a double transgenic approach the properties of two T cell-specific promoters were combined using Cre-loxP technology. The granzyme B promoter confers activation-dependency and the lck distal promoter assures strong constitutive expression once the CD8+ T cell has been activated. The constructed transgenes showed a good performance in vivo and mice expressing CCL2 in activated CD8+ T cells were obtained. These cells can now be used with different protocols for adoptively transferring cytotoxic T cells (CTL) into tumor-bearing recipients, thus allowing to study their capacity as tumor-infiltrating chemokine carrier. The establishment of transgenic mice likewisely expressing CXCL13 is expected in the near future. In addition, T cells from generated single transgenic mice that have high expression of an EGFP reporter in both CD4+ and CD8+ cells can be easily traced in vivo when setting up adoptive transfer conditions. The evaluation of mesenchymal bone marrow cells demonstrated that these cells can efficiently engraft into tumor stroma upon local coinjection with tumor cells. This represents a valuable tool for research purposes as it allows to introduce manipulated stromal cells into a tumor model. Therefore, the established engraftment model is suited for studying the envisaged immunotherapy. These results confirm to some extend previously reported results in an improved model, however, the suggested systemic tumor homing efficiency and specificity of mesenchymal bone marrow cells was not observed in our model indicating that these cells may not be suited for therapeutic use. Another major result of the presented work is the establishment oftumor-conditioned in vitro culture of mesenchymal bone marrow cells, which allowed to more rapidly expand these cells while maintaining their tumor homing and engrafting capacities. This offers another valuable tool as in vitro culture is a necessary step for therapeutic manipulations.

On the use of principal components in contemporany population genetics: a case study

In human Population Genetics, routine applications of principal component techniques are oftenrequired. Population biologists make widespread use of certain discrete classifications of humansamples into haplotypes, the monophyletic units of phylogenetic trees constructed from severalsingle nucleotide bimorphisms hierarchically ordered. Compositional frequencies of the haplotypesare recorded within the different samples. Principal component techniques are then required as adimension-reducing strategy to bring the dimension of the problem to a manageable level, say two,to allow for graphical analysis.Population biologists at large are not aware of the special features of compositional data and normally make use of the crude covariance of compositional relative frequencies to construct principalcomponents. In this short note we present our experience with using traditional linear principalcomponents or compositional principal components based on logratios, with reference to a specificdataset

An approach to vision-based station keeping for an unmanned underwater vehicle

This paper presents an automatic vision-based system for UUV station keeping. The vehicle is equipped with a down-looking camera, which provides images of the sea-floor. The station keeping system is based on a feature-based motion detection algorithm, which exploits standard correlation and explicit textural analysis to solve the correspondence problem. A visual map of the area surveyed by the vehicle is constructed to increase the flexibility of the system, allowing the vehicle to position itself when it has lost the reference image. The testing platform is the URIS underwater vehicle. Experimental results demonstrating the behavior of the system on a real environment are presented

A system to evaluate the accuracy of a visual mosaicking methodology

When underwater vehicles navigate close to the ocean floor, computer vision techniques can be applied to obtain motion estimates. A complete system to create visual mosaics of the seabed is described in this paper. Unfortunately, the accuracy of the constructed mosaic is difficult to evaluate. The use of a laboratory setup to obtain an accurate error measurement is proposed. The system consists on a robot arm carrying a downward looking camera. A pattern formed by a white background and a matrix of black dots uniformly distributed along the surveyed scene is used to find the exact image registration parameters. When the robot executes a trajectory (simulating the motion of a submersible), an image sequence is acquired by the camera. The estimated motion computed from the encoders of the robot is refined by detecting, to subpixel accuracy, the black dots of the image sequence, and computing the 2D projective transform which relates two consecutive images. The pattern is then substituted by a poster of the sea floor and the trajectory is executed again, acquiring the image sequence used to test the accuracy of the mosaicking system

Moderating effects of management control systems and innovation on performance. Simple methods for correcting the effects of measurement error for interaction effects in small samples

In the accounting literature, interaction or moderating effects are usually assessed by means of OLS regression and summated rating scales are constructed to reduce measurement error bias. Structural equation models and two-stage least squares regression could be used to completely eliminate this bias, but large samples are needed. Partial Least Squares are appropriate for small samples but do not correct measurement error bias. In this article, disattenuated regression is discussed as a small sample alternative and is illustrated on data of Bisbe and Otley (in press) that examine the interaction effect of innovation and style of use of budgets on performance. Sizeable differences emerge between OLS and disattenuated regression

Changes in health related quality of life 3 months after an acute coronary syndrome

BACKGROUND The aim of the study was to identify the changes in Health Related Quality of Life (HRQL) 3 months after discharge from hospital, in patients who have had an acute coronary episode, and to determine the clinical and sociodemographic variables that explain those changes. METHODS HRQL was assessed in 132 patients while they were admitted to the hospital and at 3 months after discharge, using the SF-36 health questionnaire. To identify the variables associated with the change, multiple linear regression models were constructed for two summary dimensions of the SF-36 (PCS and MCS) taking the change in the score of the dimension as dependent variable. RESULTS There were no significant differences between the patients who completed the monitoring (n = 76) and those who were dropped out. After three months, a significant decrease was observed in the dimensions of physical functioning, general health, vitality, and Physical Summary Component (PCS). The variables revascularisation, age, and the interaction between previous history of coronary heart disease (CHD) and the presence of one or more risk factors explained 16.6% of the decrease in the PCS. The decrease in the PCS was 6.4 points less in the patients who had undergone revascularisation, 0.2 points less for each year of age, and 4.7 points less in the patients who had antecedents of the illness as well as one or more risk factors. CONCLUSION The dimensions most affected at three months after an acute coronary episode were those related to the physical component. Undergoing revascularisation improved the PCS in patients, but in the younger patients and those without personal antecedents or risk factors, the PCS was affected more, perhaps due to greater expectations for recovery in these patients.

Patterns of Subject Mix in Higher Education Institutions : A First Empirical Analysis Using the AQUAMETH Database

Teaching and research are organised differently between subject domains: attempts to construct typologies of higher education institutions, however, often do not include quantitative indicators concerning subject mix which would allow systematic comparisons of large numbers of higher education institutions among different countries, as the availability of data for such indicators is limited. In this paper, we present an exploratory approach for the construction of such indicators. The database constructed in the AQUAMETH project, which includes also data disaggregated at the disciplinary level, is explored with the aim of understanding patterns of subject mix. For six European countries, an exploratory and descriptive analysis of staff composition divided in four large domains (medical sciences, engineering and technology, natural sciences and social sciences and humanities) is performed, which leads to a classification distinguishing between specialist and generalist institutions. Among the latter, a further distinction is made based on the presence or absence of a medical department. Preliminary exploration of this classification and its comparison with other indicators show the influence of long term dynamics on the subject mix of individual higher education institutions, but also underline disciplinary differences, for example regarding student to staff ratios, as well as national patterns, for example regarding the number of PhD degrees per 100 undergraduate students. Despite its many limitations, this exploratory approach allows defining a classification of higher education institutions that accounts for a large share of differences between the analysed higher education institutions.

Improved efficiency of a Salmonella-based vaccine against human papillomavirus type 16 virus-like particles achieved by using a codon-optimized version of L1.

Cervical cancer results from cervical infection by human papillomaviruses (HPVs), especially HPV16. An effective vaccine against these HPVs is expected to have a dramatic impact on the incidence of this cancer and its precursor lesions. The leading candidate, a subunit prophylactic HPV virus-like particle (VLP) vaccine, can protect women from HPV infection. An alternative improved vaccine that avoids parenteral injection, that is efficient with a single dose, and that induces mucosal immunity might greatly facilitate vaccine implementation in different settings. In this study, we have constructed a new generation of recombinant Salmonella organisms that assemble HPV16 VLPs and induce high titers of neutralizing antibodies in mice after a single nasal or oral immunization with live bacteria. This was achieved through the expression of a HPV16 L1 capsid gene whose codon usage was optimized to fit with the most frequently used codons in Salmonella. Interestingly, the high immunogenicity of the new recombinant bacteria did not correlate with an increased expression of L1 VLPs but with a greater stability of the L1-expressing plasmid in vitro and in vivo in absence of antibiotic selection. Anti-HPV16 humoral and neutralizing responses were also observed with different Salmonella enterica serovar Typhimurium strains whose attenuating deletions have already been shown to be safe after oral vaccination of humans. Thus, our findings are a promising improvement toward a vaccine strain that could be tested in human volunteers.

Influence of anti-filarial chemotherapy strategies on the genetic structure of Wuchereria bancrofti populations

Lymphatic filarial (LF) parasites have been under anti-filarial drug pressure for more than half a century. Currently, annual mass drug administration (MDA) of diethylcarbamazine (DEC) or ivermectin in combination with albendazole (ALB) have been used globally to eliminate LF. Long-term chemotherapies exert significant pressure on the genetic structure of parasitic populations. We investigated the genetic variation among 210 Wuchereria bancrofti populations that were under three different chemotherapy strategies, namely MDA with DEC alone (group I, n = 74), MDA with DEC and ALB (group II, n = 60) and selective therapy (ST) with DEC (group III, n = 34) to understand the impact of these three drug regimens on the parasite genetic structure. Randomly amplified polymorphic DNA profiles were generated for the three groups of parasite populations; the gene diversity, gene flow and genetic distance values were determined and phylogenetic trees were constructed. Analysis of these parameters indicated that parasite populations under ST with a standard dose of DEC (group III) were genetically more diverse (0.2660) than parasite populations under MDA with DEC alone (group I, H = 0.2197) or with DEC + ALB (group II, H = 0.2317). These results indicate that the MDA may reduce the genetic diversity of W. bancrofti populations when compared to the genetic diversity of parasite populations under ST.

Construction and Quantitative Evaluation of a Dual Specific Promoter System for Monitoring the Expression Status of Stra8 and c-kit Genes.

Applications of genetic constructs with multiple promoters, which are fused with reporter genes and simultaneous monitoring of various events in cells, have gained special attention in recent years. Lentiviral vectors, with their distinctive characteristics, have been considered to monitor the developmental changes of cells in vitro. In this study, we constructed a novel lentiviral vector (FUM-M), containing two germ cell-specific promoters (Stra8 and c-kit), fused with ZsGreen and DsRed2 reporter genes, and evaluated its efficiency in different cells following treatments with retinoic acid and DMSO. Several cell lines (P19, GC-1 spg and HEK293T) were transduced with this vector, and functional capabilities of the promoters were verified by flow cytometry and quantitative RT-PCR. Our results indicate that FUM-M shows dynamic behavior in the presence and absence of extrinsic factors. A correlation was also observed between the function of promoters, present in the lentiviral construct and the endogenous level of the Stra8 and c-kit mRNAs in the cells. In conclusion, we recommend this strategy, which needs further optimization of the constructs, as a beneficial and practical way to screen chemical inducers involved in cellular differentiation toward germ-like cells.

Insights into the transcriptome of oenocytes from Aedes aegypti pupae

Oenocytes are ectodermic cells present in the fat body of several insect species and these cells are considered to be analogous to the mammalian liver, based on their role in lipid storage, metabolism and secretion. Although oenocytes were identified over a century ago, little is known about their messenger RNA expression profiles. In this study, we investigated the transcriptome of Aedes aegypti oenocytes. We constructed a cDNA library from Ae. aegypti MOYO-R strain oenocytes collected from pupae and randomly sequenced 687 clones. After sequences editing and assembly, 326 high-quality contigs were generated. The most abundant transcripts identified corresponded to the cytochrome P450 superfamily, whose members have roles primarily related to detoxification and lipid metabolism. In addition, we identified 18 other transcripts with putative functions associated with lipid metabolism. One such transcript, a fatty acid synthase, is highly represented in the cDNA library of oenocytes. Moreover, oenocytes expressed several immunity-related genes and the majority of these genes were lysozymes. The transcriptional profile suggests that oenocytes play diverse roles, such as detoxification and lipid metabolism, and increase our understanding of the importance of oenocytes in Ae. aegypti homeostasis and immune competence.