Competitive asymmetry, foraging area size and coexistence of annuals

Individuals allocate resources to the expansion of their foraging area and those resources are no longer available for the traits that determine how well those individuals are able to protect their foraging area against competitors. The resulting trade‐off between foraging area size and the traits associated with the ability to compete for the resources within the foraging area applies to ecological scenarios as different as territorial defence by individuals and colonies, and light competition in plants. Whether the trade‐off affects species performance in competition for resources at the area of overlap between foraging areas depends on the symmetry of resource division. In symmetric competition resources are divided equally between the competitors, while in asymmetric competition the individual with the smallest foraging area, and consequently the greatest competitive ability, gains all the resources. Competition may also be a combination of the symmetric and asymmetric processes. I studied the effects of competitive asymmetry on population dynamics and coexistence of two annual species with different sized foraging areas using an individual‐based spatially explicit simulation model. Symmetric competition favoured the species with the larger foraging area and did not allow coexistence. Competitive asymmetry favoured the species with smaller foraging area and allowed coexistence, which was due to the consequences of losing an asymmetric competition being more severe than losing a symmetric competition. The mechanism of coexistence is the larger foraging area's superiority in low population densities (little competition) and the smaller foraging area's ability to win a large foraging area when competition was intense. Competitive asymmetry and small size of both foraging areas led to population dynamics dominated by long‐term fluctuations of small intensity. Symmetric competition and large size of the foraging areas led to large short‐term fluctuations, which often resulted in the extinction of one or both of the species due to demographic stochasticity.     

Optimal growth strategies under divergent predation pressure

The conditions leading to gigantism in nine‐spined sticklebacks Pungitius pungitius were analysed by modelling fish growth with the von Bertalanffy model searching for the optimal strategy when the model's growth constant and asymptotic fish size parameters are negatively related to each other. Predator‐related mortality was modelled through the increased risk of death during active foraging. The model was parameterized with empirical growth data of fish from four different populations and analysed for optimal growth strategy at different mortality levels. The growth constant and asymptotic fish size were negatively related in most populations. Optimal fish size, fitness and life span decreased with predator‐induced mortality. At low mortality, the fitness of pond populations was higher than that of sea populations. The differences disappeared at intermediate mortalities, and sea populations had slightly higher fitness at extremely high mortalities. In the scenario where all populations mature at the same age, the pond populations perform better at low mortalities and the sea populations at high mortalities. It is concluded that a trade‐off between growth constant and asymptotic fish size, together with different mortality rates, can explain a significant proportion of body size differentiation between populations. In the present case, it is a sufficient explanation of gigantism in pond P. pungitius.     

New separation-free assay technique for SNPs using two-photon excitation fluorometry

A new separation-free method for detection of single nucleotide polymorphisms (SNPs) is described. The method is based on the single base extension principle, fluorescently labeled dideoxy nucleotides and two-photon fluorescence excitation technology, known as ArcDia™ TPX technology. In this assay technique, template-directed single base extension is carried out for primers which have been immobilized on polymer microparticles. Depending on the sequence of the template DNA, the primers are extended either with a labeled or with a non-labeled nucleotide. The genotype of the sample is determined on the basis of two-photon excited fluorescence of individual microparticles. The effect of various assay condition parameters on the performance of the assay method is studied. The performance of the new assay method is demonstrated by genotyping the SNPs of human individuals using double-stranded PCR amplicons as samples. The results show that the new SNP assay method provides sensitivity and reliability comparable to the state-of-the-art SNaPshot™ assay method. Applicability of the new method in routine laboratory use is discussed with respect to alternative assay techniques.     

A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70–0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FINRISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.     

Anti-EGFR biparatopic-SEED antibody has enhanced combination-activity in a single molecule

Certain combinations of non-competitive anti-EGFR antibodies have been reported to produce new effects on cells compared to either antibody used separately. New and enhanced combination-activity includes increased inhibition of signaling, increased receptor internalization and degradation, reduced proliferation of tumor cell lines and induction of complement-dependent cytotoxicity (CDC) effector function. To test requirements and mechanisms to elicit enhanced combination-activity with different EGFR binding domains, we created an anti-EGFR biparatopic antibody. A biparatopic antibody interacts through two different antigen-binding sites to a single antigen. A heterodimeric antibody with one binding domain derived from the C225 antibody and one binding domain derived from the humanized 425 (hu425) antibody was built on the strand-exchange engineered domain (SEED) scaffold. This anti-EGFR biparatopic-SEED antibody was compared to parental antibodies used alone and in combination, and to the corresponding monovalent anti-EGFR-SEED antibodies used alone or in combination. We found that the anti-EGFR biparatopic-SEED had enhanced activity, similar to the combination of the two parental antibodies. Combinations of monovalent anti-EGFR-SEED antibodies did not produce enhanced effectiveness in cellular assays. Our results show that the anti-EGFR biparatopic antibody created using the SEED scaffold has enhanced combination-activity in a single molecule. Furthermore, these data suggest that the potential to cross-link the two different epitopes is an important requirement in the mechanism of enhanced combination-activity.     

Arresten,a Collagen-Derived Angiogenesis Inhibitor,Suppresses Invasion of Squamous Cell Carcinoma

The turnover of extracellular matrix liberates various cryptic molecules with novel biological activity. Among these are the collagen-derived anti-angiogenic fragments, some of which are suggested to affect carcinoma cells also directly. Arresten is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of the basement membrane collagen IV α1 chain. As the mere prevention of tumor angiogenesis leads to hypoxia that can result in selection of more aggressive cell types and reduces the efficacy of chemotherapy, we aimed here to elucidate how arresten influences the aggressive human carcinoma cells. Arresten efficiently inhibited migration and invasion of HSC-3 tongue carcinoma cells in culture and in an organotypic model. Subcutaneous Arr-HSC xenografts grew markedly more slowly in nude mice and showed reduced tumor cell proliferation, vessel density and local invasiveness. In the organotypic assay, HSC-3 cells overproducing arresten (Arr-HSC) showed induction of cell death. In monolayer culture the Arr-HSC cells grew in aggregated cobblestone-like clusters and, relative to the control cells, showed increased expression and localization of epithelial marker E-cadherin in cell-cell contacts. Application of electric cell-substrate impedance sensing (ECIS) further supported our observations on altered morphology and motility of the Arr-HSC cells. Administration of a function-blocking α1 integrin antibody abolished the impedance difference between the Arr-HSC and control cells suggesting that the effect of arresten on promotion of HSC-3 cell-cell contacts and cell spreading is at least partly mediated by α1β1 integrin. Collectively, our data suggest novel roles for arresten in the regulation of oral squamous carcinoma cell proliferation, survival, motility and invasion through the modulation of cell differentiation state and integrin signaling.     

Optimality and phenotypic plasticity of shoot-to-root ratio under variable light and nutrient availabilities

We studied the phenotypic plasticity of shoot-to-root ratio with a model of plant growth in different availabilities of light and nutrients. Optimal shoot-to-root ratio was defined as the equal limitation of growth by light and nutrients. An optimally growing plant had a curved relative growth rate (RGR) isoclines and a faster growth rate than a fixed-allocation plant having right-angled RGR isoclines. We assumed the plant be exposed to a unit standard deviation of bivariate normally distributed resources. Plants were more plastic in a low than in a high resource availability. Negative correlation between resources increased and positive correlation decreased plasticity. Plasticity was high in plants that saturate at low resource availabilities but independent of maximum growth rate. A trade-off between the maximum growth rate and plasticity of shoot-to-root allocation may rise indirectly from the tendency of fast-growing plants to have high resource requirements.     

Island properties dominate species traits in determining plant colonizations in an archipelago system

The extrinsic determinants hypothesis emphasizes the essential role of environmental heterogeneity in species’ colonization. Consequently, high resident species diversity can increase community susceptibility to colonizations because good habitats may support more species that are functionally similar to colonizers. On the other hand, colonization success is also likely to depend on species traits. We tested the relative importance of environmental characteristics and species traits in determining colonization success using census data of 587 vascular plant species collected about 70 yr apart from 471 islands in the archipelago of SW Finland. More specifically, we explored potential new colonization as a function of island properties (e.g. location, area, habitat diversity, number of resident species per unit area), species traits (e.g. plant height, life-form, dispersal vector, Ellenberg indicator values, association with human impact), and species’ historical distributions (number of inhabited islands, nearest occurrence). Island properties and species’ historical distributions were more effective than plant traits in explaining colonization outcomes. Contrary to the extrinsic determinants hypothesis, colonization success was neither associated with resident species diversity nor habitat diversity per se, although colonization was lowest on sparsely vegetated islands. Our findings lead us to propose that while plant traits related to dispersal and establishment may enhance colonization, predictions of plant colonizations primarily require understanding of habitat properties and species’ historical distributions.