Eco-Evolutionary Spatial Dynamics. Rapid Evolution and Isolation Explain Food Web Persistence

One of the current challenges in evolutionary ecology is understanding the long-term persistence of contemporary-evolving predator–prey interactions across space and time. To address this, we developed an extension of a multi-locus, multi-trait eco-evolutionary individual-based model that incorporates several interacting species in explicit landscapes. We simulated eco-evolutionary dynamics of multiple species food webs with different degrees of connectance across soil-moisture islands. A broad set of parameter combinations led to the local extinction of species, but some species persisted, and this was associated with (1) high connectance and omnivory and (2) ongoing evolution, due to multi-trait genetic variability of the embedded species. Furthermore, persistence was highest at intermediate island distances, likely because of a balance between predation-induced extinction (strongest at short island distances) and the coupling of island diversity by top predators, which by travelling among islands exert global top-down control of biodiversity. In the simulations with high genetic variation, we also found widespread trait evolutionary changes indicative of eco-evolutionary dynamics. We discuss how the ever-increasing computing power and high-resolution data availability will soon allow researchers to start bridging the in vivo–in silico gap.

Theoretical and experimental studies of linkage disequilibrium in human populations

Linkage disequilibrium (LD) is defined as the nonrandom association of alleles at two or more loci in a population and may be a useful tool in a diverse array of applications including disease gene mapping, elucidating the demographic history of populations, and testing hypotheses of human evolution. However, the successful application of LD-based approaches to pertinent genetic questions is hampered by a lack of understanding about the forces that mediate the genome-wide distribution of LD within and between human populations. Delineating the genomic patterns of LD is a complex task that will require interdisciplinary research that transcends traditional scientific boundaries. The research presented in this dissertation is predicated upon the need for interdisciplinary studies and both theoretical and experimental projects were pursued. In the theoretical studies, I have investigated the effect of genotyping errors and SNP identification strategies on estimates of LD. The primary importance of these two chapters is that they provide important insights and guidance for the design of future empirical LD studies. Furthermore, I analyzed the allele frequency distribution of 26,530 single nucleotide polymorphisms (SNPs) in three populations and generated the first-generation natural selection map of the human genome, which will be an important resource for explaining and understanding genomic patterns of LD. Finally, in the experimental study, I describe a novel and simple, low-cost, and high-throughput SNP genotyping method. The theoretical analyses and experimental tools developed in this dissertation will facilitate a more complete understanding of patterns of LD in human populations. ^

STAT3 activation by the ErbB2 receptor and development of peptide-based STAT3 inhibitors

Stats (s&barbelow;ignal t&barbelow;ransducer and a&barbelow;ctivator of t&barbelow;ranscription) are latent transcription factors that translocate from the cytoplasm to nucleus. Constitutive activation of Stat3α by upstream oncoproteins and receptor tyrosine kinases has been found in many human tumors and tumor-derived cell lines and it is often correlated with the activation of ErbB-2. In order to explore the involvement of ErbB-2 in the activation of Stat3 and the mechanisms underlying this event, an erbB-2 point mutant was used as a model of a constitutively activated receptor. Phenylalanine mutations (Y-F) were made in the receptor's autophosphorylation sites and their ability to activate Stat3α was evaluated. Our results suggest that Stat3α and Janus tyrosine kinase 2 associates with ErbB-2 prior to tyrosine phosphorylation of the receptor and that full activation of Stat3α by ErbB-2 requires the participation of other non-receptor tyrosine kinases. Both Src and Jak2 kinases contribute to the activation of Stat3α while only Src binds to ErbB-2 only when the receptor is tyrosine phosphorylated. Our results also suggest that tyrosine 1139 may be important for Src SH2 domain association since a mutant lacking this tyrosine reduces the ability of the Src SH2 domain to bind to ErbB-2 and significantly decreases its ability to activate Stat3α. ^ In order to disrupt aberrant STAT3α activation which contributes to tumorigenesis, we sought small molecules which can specifically bind to the STAT3 SH2 domain, thereby abolishing its ability of being recruited into receptors, and also blocking the dimer formation required for STAT3α activation. A phosphopeptide derived from gp130 was found to have a high affinity to STAT3 SH2 domain, and we decided to use this peptide as the base for further modifications. A series of peptide based compounds were designed and tested using electrophoretic mobility shift assay and fluorescence polarization assay to evaluate their affinity to the STAT3 SH2 domain. Two promising compounds, DRIV-73C and BisPOM, were used for blocking STAT3α activity in cell culture. Either can successfully impair STAT3α activation induced by IL-6 stimulation in HepG2 cells. BisPOM proved to be the more effective in blocking STAT3α tyrosine phosphorylation in induced cells and tumor cell lines, and was the more potent in inhibiting STAT3 dependent cell growth. ^

EGFR and Notch signaling pathways are regulated by distinct isoforms of Drosophila cbl

Activation of cell surface receptors transduces extracellular signals into cellular responses such as proliferation, differentiation and survival. However, the appropriate spatial and temporal down-regulation of signaling receptors is essential for normal development and homeostasis. The Cbl family of E3-ubiquitin ligases plays a major role for the ligand-dependent inactivation of growth factor receptors through ubiquitin-mediated endocytosis and lysosomal degradation. Here, we report the D-cbl mutant phenotypes in the Drosophila eye. D-cbl mutants display overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing. Many of these phenotypes are caused by lack of down-regulation of the Drosophila EGFR signaling. However, not all D-cbl phenotypes can be explained by inappropriate EGFR activity. We found that D-Cbl also negatively regulates Notch activity during eye and wing development. D-cbl produces two isoforms by alternative splicing. Strikingly, the long isoform, D-CblL, preferentially regulates the EGFR, whereas the short isoform, D-CblS, preferentially regulates Notch. Taken together, these data suggest that D-Cbl controls at least two signaling pathways, EGFR and Notch, through production of two alternatively spliced isoforms during development in Drosophila.^

Essential elements of postabortion care: origins, evolution and future directions

In this comment, we chronicle the development and expansion of a postabortion care model designed to promote interventions that address abortion-related public health concerns even when abortion laws and policies are restrictive. We review years of program experience with the original model, which led to the development of an expanded and updated model, Essential Elements of Postabortion Care (PAC). Implementing the model challenges global public health leaders, donors, technical assistance agencies and ministries of health to work with communities to ensure that all women who want to prevent or space pregnancies can obtain contraceptive services; that all women have access to services to manage complications from abortion, whether induced or spontaneous; and that all women receiving treatment also receive counseling and the reproductive and other health services they need at the treatment visit, as well as follow-up care and contraceptive resupply

(Supplemental Table 2) Plant characteristics, GHG fluxes, and soil chemical and microbial properties in experimental treatments in Alexandra Fiord

We evaluated above- and belowground ecosystem changes in a 16 year, combined fertilization and warming experiment in a High Arctic tundra deciduous shrub heath (Alexandra Fiord, Ellesmere Island, NU, Canada). Soil emissions of the three key greenhouse gases (GHGs) (carbon dioxide, methane, and nitrous oxide) were measured in mid-July 2009 using soil respiration chambers attached to a FTIR system. Soil chemical and biochemical properties including Q10 values for CO2, CH4, and N2O, Bacteria and Archaea assemblage composition, and the diversity and prevalence of key nitrogen cycling genes including bacterial amoA, crenarchaeal amoA, and nosZ were measured. Warming and fertilization caused strong increases in plant community cover and height but had limited effects on GHG fluxes and no substantial effect on soil chemistry or biochemistry. Similarly, there was a surprising lack of directional shifts in the soil microbial community as a whole or any change at all in microbial functional groups associated with CH4 consumption or N2O cycling in any treatment. Thus, it appears that while warming and increased nutrient availability have strongly affected the plant community over the last 16 years, the belowground ecosystem has not yet responded. This resistance of the soil ecosystem has resulted in limited changes in GHG fluxes in response to the experimental treatments.

Development of mathematical models to elaborate strategies, select alternatives and development of plans for adaptation of communities to climate change in different geographical areas including costs to implement it.

There is evidence that the climate changes and that now, the change is influenced and accelerated by the CO2 augmentation in atmosphere due to combustion by humans. Such ?Climate change? is on the policy agenda at the global level, with the aim of understanding and reducing its causes and to mitigate its consequences. In most countries and international organisms UNO (e.g. Rio de Janeiro 1992), OECD, EC, etc . . . the efforts and debates have been directed to know the possible causes, to predict the future evolution of some variable conditioners, and trying to make studies to fight against the effects or to delay the negative evolution of such. The Protocol of Kyoto 1997 set international efforts about CO2 emissions, but it was partial and not followed e.g. by USA and China . . . , and in Durban 2011 the ineffectiveness of humanity on such global real challenges was set as evident. Among all that, the elaboration of a global model was not boarded that can help to choose the best alternative between the feasible ones, to elaborate the strategies and to evaluate the costs, and the authors propose to enter in that frame for study. As in all natural, technological and social changes, the best-prepared countries will have the best bear and the more rapid recover. In all the geographic areas the alternative will not be the same one, but the model must help us to make the appropriated decision. It is essential to know those areas that are more sensitive to the negative effects of climate change, the parameters to take into account for its evaluation, and comprehensive plans to deal with it. The objective of this paper is to elaborate a mathematical model support of decisions, which will allow to develop and to evaluate alternatives of adaptation to the climatic change of different communities in Europe and Latin-America, mainly in especially vulnerable areas to the climatic change, considering in them all the intervening factors. The models will consider criteria of physical type (meteorological, edaphic, water resources), of use of the ground (agriculturist, forest, mining, industrial, urban, tourist, cattle dealer), economic (income, costs, benefits, infrastructures), social (population), politician (implementation, legislation), educative (Educational programs, diffusion) and environmental, at the present moment and the future. The intention is to obtain tools for aiding to get a realistic position for these challenges, which are an important part of the future problems of humanity in next decades.

Desing and development of a robotic platform for the evaluation of search algorithms

Plant diseases represent a major economic and environmental problem in agriculture and forestry. Upon infection, a plant develops symptoms that affect different parts of the plant causing a significant agronomic impact. As many such diseases spread in time over the whole crop, a system for early disease detection can aid to mitigate the losses produced by the plant diseases and can further prevent their spread [1]. In recent years, several mathematical algorithms of search have been proposed [2,3] that could be used as a non-invasive, fast, reliable and cost-effective methods to localize in space infectious focus by detecting changes in the profile of volatile organic compounds. Tracking scents and locating odor sources is a major challenge in robotics, on one hand because odour plumes consists of non-uniform intermittent odour patches dispersed by the wind and on the other hand because of the lack of precise and reliable odour sensors. Notwithstanding, we have develop a simple robotic platform to study the robustness and effectiveness of different search algorithms [4], with respect to specific problems to be found in their further application in agriculture, namely errors committed in the motion and sensing and to the existence of spatial constraints due to land topology or the presence of obstacles.

Evolution and implementation of CDIO initiatives at ETSII-UPM

The School of Industrial Engineering at Universidad Politécnica de Madrid (ETSII-UPM) has been promoting student-centred teaching-learning activities, according to the aims of the Bologna Declaration, well before the official establishment of the European Area of Higher Education. Such student-centred teaching-learning experiences led us to the conviction that project based learning is rewarding, both for students and academics, and should be additionally promoted in our new engineering programmes, adapted to the Grade-Master structure. The level of commitment of our teachers with these activities is noteworthy, as the teaching innovation experiences carried out in the last ten years have led to the foundation of 17 Teaching Innovation Groups at ETSII-UPM, hence leading the ranking of teaching innovation among all UPM centres. Among interesting CDIO activities our students have taken part in especially complex projects, including the Formula Student, linked to the complete development of a competition car, and the Cybertech competition, aimed at the design, construction and operation of robots for different purposes. Additional project-based learning teamwork activities have been linked to toy design, to the development of medical devices, to the implementation of virtual laboratories, to the design of complete industrial installations and factories, among other activities detailed in present study. The implementation of Bologna process will culminate at ETSII-UPM with the beginning of the Master’s Degree in Industrial Engineering, in academic year 2014-15. The program has been successfully approved by the Spanish Agency for Accreditation (ANECA), with the inclusion of a set of subjects based upon the CDIO methodology denominated generally “INGENIA”, linked to the Spanish “ingeniar” (to provide ingenious solutions), also related etymologically in Spanish with “ingeniero”, engineer. INGENIA students will live through the complete development process of a complex product or system and there will be different kind of projects covering most of the engineering majors at ETSII-UPM.

First 20 years of DNDC: Model evolution and GRAMP.

The DNDC (DeNitrification and DeComposition) model was first developed by Li et al. (1992) as a rain event-driven process-orientated simulation model for nitrous oxide, carbon dioxide and nitrogen gas emissions from the agricultural soils in the U.S. Over the last 20 years, the model has been modified and adapted by various research groups around the world to suit specific purposes and circumstances. The Global Research Alliance Modelling Platform (GRAMP) is a UK-led initiative for the establishment of a purposeful and credible web-based platform initially aimed at users of the DNDC model. With the aim of improving the predictions of soil C and N cycling in the context of climate change the objectives of GRAMP are to: 1) to document the existing versions of the DNDC model; 2) to create a family tree of the individual DNDC versions; 3) to provide information on model use and development; and 4) to identify strengths, weaknesses and potential improvements for the model.

Phylogeny of genes for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification

Macromolecular transport systems in bacteria currently are classified by function and sequence comparisons into five basic types. In this classification system, type II and type IV secretion systems both possess members of a superfamily of genes for putative NTP hydrolase (NTPase) proteins that are strikingly similar in structure, function, and sequence. These include VirB11, TrbB, TraG, GspE, PilB, PilT, and ComG1. The predicted protein product of tadA, a recently discovered gene required for tenacious adherence of Actinobacillus actinomycetemcomitans, also has significant sequence similarity to members of this superfamily and to several unclassified and uncharacterized gene products of both Archaea and Bacteria. To understand the relationship of tadA and tadA-like genes to those encoding the putative NTPases of type II/IV secretion, we used a phylogenetic approach to obtain a genealogy of 148 NTPase genes and reconstruct a scenario of gene superfamily evolution. In this phylogeny, clear distinctions can be made between type II and type IV families and their constituent subfamilies. In addition, the subgroup containing tadA constitutes a novel and extremely widespread subfamily of the family encompassing all putative NTPases of type IV secretion systems. We report diagnostic amino acid residue positions for each major monophyletic family and subfamily in the phylogenetic tree, and we propose an easy method for precisely classifying and naming putative NTPase genes based on phylogeny. This molecular key-based method can be applied to other gene superfamilies and represents a valuable tool for genome analysis.

Galactosides in the rhizosphere: Utilization by Sinorhizobium meliloti and development of a biosensor

Identifying the types and distributions of organic substrates that support microbial activities around plant roots is essential for a full understanding of plant–microbe interactions and rhizosphere ecology. We have constructed a strain of the soil bacterium Sinorhizobium meliloti containing a gfp gene fused to the melA promoter which is induced on exposure to galactose and galactosides. We used the fusion strain as a biosensor to determine that galactosides are released from the seeds of several different legume species during germination and are also released from roots of alfalfa seedlings growing on artificial medium. Galactoside presence in seed wash and sterile root washes was confirmed by HPLC. Experiments examining microbial growth on α-galactosides in seed wash suggested that α-galactoside utilization could play an important role in supporting growth of S. meliloti near germinating seeds of alfalfa. When inoculated into microcosms containing legumes or grasses, the biosensor allowed us to visualize the localized presence of galactosides on and around roots in unsterilized soil, as well as the grazing of fluorescent bacteria by protozoa. Galactosides were present in patches around zones of lateral root initiation and around roots hairs, but not around root tips. Such biosensors can reveal intriguing aspects of the environment and the physiology of the free-living soil S. meliloti before and during the establishment of nodulation, and they provide a nondestructive, spatially explicit method for examining rhizosphere soil chemical composition.

Mitochondrial Single-stranded DNA-binding Protein Is Required for Mitochondrial DNA Replication and Development in Drosophila melanogaster

The discovery that several inherited human diseases are caused by mtDNA depletion has led to an increased interest in the replication and maintenance of mtDNA. We have isolated a new mutant in the lopo (low power) gene from Drosophila melanogaster affecting the mitochondrial single-stranded DNA-binding protein (mtSSB), which is one of the key components in mtDNA replication and maintenance. lopo1 mutants die late in the third instar before completion of metamorphosis because of a failure in cell proliferation. Molecular, histochemical, and physiological experiments show a drastic decrease in mtDNA content that is coupled with the loss of respiration in these mutants. However, the number and morphology of mitochondria are not greatly affected. Immunocytochemical analysis shows that mtSSB is expressed in all tissues but is highly enriched in proliferating tissues and in the developing oocyte. lopo1 is the first mtSSB mutant in higher eukaryotes, and its analysis demonstrates the essential function of this gene in development, providing an excellent model to study mitochondrial biogenesis in animals.