A review on molecular topology: applying graph theory to drug discovery and design

Molecular topology is an application of graph theory and statistics in fields like chemistry, biology, and pharmacology, in which the molecular structure matters. Its scope is the topological characterization of molecules by means of numerical invariants, called topological indices, which are the main ingredients of the molecular topological models. These are statistical models that are instrumental in the discovery of new applications of naturally occurring molecules, as well as in the design of synthetic molecules with specific chemical, biological, or pharmacological properties. In this review, we focus on pharmacology, which is a novel field of application of molecular topology. Besides summarizing some recent developments, we also seek to bring closer this interesting biomedical application of mathematics to an interdisciplinary readership.

Immune activation affects chemical sexual ornaments of male Iberian wall lizards

Many animals use chemical signals in sexual selection, but it is not clear how these sexual traits might have evolved to signal honestly male condition. It is possible that there is a trade-off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide), without pathogenic effects, to explore whether the immune activation affected chemical ornaments. Immune activation resulted in decreased proportions of a major chemical in femoral secretions (cholesta-5,7-dien-3-ol = provitamin D(3)) known to be selected in scent of males by females and which active form (vitamin D) has a variety of important effects on immune system function. This result suggests the existence of a potential trade-off between physiological regulation of the immune system and the allocation of essential nutrients (vitamins) to sexual chemical ornaments in male lizards.     

Feeding the world's increasing population while limiting climate change impacts: linking N2O and CH4 emissions from agriculture to population growth

The global demand for agricultural products, including food, is rapidly increasing due to population growth and shifts in consumption patterns. The required increase in agricultural production is predominantly to be achieved in countries with relatively low agricultural production levels at present. These are mainly developing countries and countries in transition, the so-called non-Annex I countries of the UNFCCC. However, intensification of agricultural production systems is currently closely linked to high emissions of greenhouse gases notably nitrous oxide (N₂O) and methane (CH₄). In this paper the relations between population growth, agricultural development and emissions of N₂O and CH₄ were assessed for 10 non-Annex I countries, viz. China, India, Vietnam, Brazil, Argentina, Mexico, Mongolia, Nigeria, Tanzania and South Africa. We combined FAO data on agricultural production levels, CENSUS data on population statistics and EDGAR data on N₂O and CH₄ emissions. The projected trends in agricultural production indicate that emissions of N₂O and CH₄ are expected to increase rapidly in the coming years and will level off from 2040 onwards. The results confirm the positive relation between population increase and increased emissions from agricultural activities for most countries. However, for some countries (South Africa, China and Mexico) this relation was weak or absent. Although numerous factors (e.g. changes in international trade) may have scattered the relation and we were unable to explain this decoupling, it suggests that population growth can be possible without additional emissions. The variation between the different countries and farming systems is however large and mitigation measures at farm-level should be tailored to the wide diversity in environmental conditions, regional customs and farming systems.     

Expression and Immunoreactivities of Hepatitis E Virus Genotype 3 Open Reading Frame-2 (ORF-2) Recombinant Proteins Expressed in Insect Cells

Hepatitis E virus (HEV) is a fecal-orally transmitted virus that is endemic in many geographical areas with poor sanitary conditions and inadequate water supplies. In Europe, a low-endemic area, an increased number of autochthonous sporadic human cases of patients infected with HEV strains of genotype 3, have been reported lately. The relatively high prevalence of HEV genotype 3 infections in European pigs has raised concerns about a potential zoonotic transmission to humans. Determination of HEV seroprevalence in pigs would help to clarify its incidence and possible zoonotic implications. To this purpose, we have expressed and partially characterized swine genotype 3 HEV open reading frame-2 proteins upon infection of Sf21 insect cells with recombinant baculoviruses. The use of the expressed proteins as diagnostic antigens for the detection of antibodies to HEV has been further assayed with human and swine sera.     

Spatial structure effects on the detection of patches boundaries using local operators

Landscapes exhibit various degrees of spatial heterogeneity according to the differential intensity and interactions among processes and disturbances that they are subjected to. The management of these spatially dynamical landscapes requires that we can accurately map them and monitor the evolution of their spatial arrangement through time. Such a mapping requires first the delineation of various spatial features present in the landscape such as patches and their boundaries. However, there are several environmental (spatial variability) as well as technical (spatial resolution) factors that impair our ability to accurately delineate patches and their boundaries as polygons. Here, we investigate how the spatial structure and spatial resolution of the data affect the accuracy of detecting patches and their boundaries over simulated landscapes and real data. Simulated landscapes consisted of two patches with parameterized spatial properties (patches’ level of spatial autocorrelation, mean value and variance) separated by a boundary of known location. Real data allowed the investigation of a more complex landscape where there is a known transition between two forest domains with unknown spatial properties. Boundary locations are defined using the lattice-wombling edge detector at various aggregation levels and the degree of patch homogeneity is determined using Getis-Ord’s G*. Results show that boundary detection using a local edge detector is greatly affected by the spatial conditions of the data, namely variance, abruptness of the spatial gradient between two patches and patches’ level of spatial autocorrelation. They also suggest that data aggregation is not a panacea for bringing out the ecological process creating the patches and that indicators derived from local measures of spatial association can be complementary tools for analysing spatial structures affecting boundary delineation.

Environmental indicators GIS of the Catalan coast

This paper describes the environmental indicators GIS of the Catalan coast, Spain. The spatial data model is based on vector and raster layers with three main modules: the biodiversity, the general biophysical and the socioeconomic. Presently, the database has a number of pressure and impact indicators that have been used to model the components and structure of the system and are suggested to build ecological resilience. Special interest has been given to the analysis of functional groups of species that are relevant to the dynamics of the coastal system, and preliminary results are presented. This system constitutes a user-oriented analytical and monitoring tool for coastal zone managers and researchers. Although, the system is under development it is expected that resulting spatial indicators of environmental condition can be used to promote more sustainable coastal strategies and actions in the Catalan coast.     

Habitat fragmentation lowers survival of a tropical forest bird.

Population ecology research has long been focused on linking environmental features with the viability of populations. The majority of this work has largely been carried out in temperate systems and, until recently, has examined the effects of habitat fragmentation on survival. In contrast, we looked at the effect of forest fragmentation on apparent survival of individuals of the White-ruffed Manakin (Corapipo altera) in southern Costa Rica. Survival and recapture rates were estimated using mark-recapture analyses, based on capture histories from 1993 to 2006. We sampled four forest patches ranging in size from 0.9 to 25 ha, and four sites in the larger 227-ha Las Cruces Biological Station Forest Reserve (LCBSFR). We found a significant difference in annual adult apparent survival rates for individuals marked and recaptured in forest fragments vs. individuals marked and recaptured in the larger LCBSFR. Contrary to our expectation, survival and recapture probabilities did not differ between male and female manakins. Also, there was no support for the existence of annual variation in survival within each study site. Our results suggest that forest fragmentation is likely having an effect on population dynamics for the White-ruffed Manakin in this landscape. Therefore, populations that appear to be persisting in fragmented landscapes might still be at risk of local extinction, and conservation action for tropical birds should be aimed at identifying and reducing sources of adult mortality. Future studies in fragmentation effects on reproductive success and survival, across broad geographical scales, will be needed before it is possible to achieve a clear understanding of the effects of habitat fragmentation on populations for both tropical and temperate regions.     

Characterizing source-sink dynamics with genetic parentage assignments

Source-sink dynamics have been suggested to characterize the population structure of many species, but the prevalence of source-sink systems in nature is uncertain because of inherent challenges in estimating migration rates among populations. Migration rates are often difficult to estimate directly with demographic methods, and indirect genetic methods are subject to a variety of assumptions that are difficult to meet or to apply to evolutionary timescales. Furthermore, such methods cannot be rigorously applied to high-gene-flow species. Here, we employ genetic parentage assignments in conjunction with demographic simulations to infer the level of immigration into a putative sink population. We use individual-based demographic models to estimate expected distributions of parent-offspring dyads under competing sink and closed-population models. By comparing the actual number of parent-offspring dyads (identified from multilocus genetic profiles) in a random sample of individuals taken from a population to expectations under these two contrasting demographic models, it is possible to estimate the rate of immigration and test hypotheses related to the role of immigration on population processes on an ecological timescale. The difference in the expected number of parent-offspring dyads between the two population models was greatest when immigration into the sink population was high, indicating that unlike traditional population genetic inference models, the highest degree of statistical power is achieved for the approach presented here when migration rates are high. We used the proposed genetic parentage approach to demonstrate that a threatened population of Marbled Murrelets (Braclhyrarmphus marmotus) appears to be supplemented by a low level of immigration (approximately 2-6% annually) from other populations.     

Oceanic variability and coastal topography shape genetic structure in a long-dispersing sea urchin

Understanding the scale of marine population connectivity is critical for the conservation and sustainable management of marine resources. For many marine species adults are benthic and relatively immobile, so patterns of larval dispersal and recruitment provide the key to understanding marine population connectivity. Contrary to previous expectations, recent studies have often detected unexpectedly low dispersal and fine-scale population structure in the sea, leading to a paradigm shift in how marine systems are viewed. Nonetheless, the link between fine-scale marine population structure and the underlying physical and biological processes has not been made. Here we show that patterns of genetic structure and population connectivity in the broadcast-spawning and long-distance dispersing sea urchin Centrostephanus rodgersii are influenced by physical oceanographic and geographic variables. Despite weak genetic differentiation and no isolation-by-distance over thousands of kilometers among samples from eastern Australia and northern New Zealand, fine-scale genetic structure was associated with sea surface temperature (SST) variability and geography along the southeastern Australian coast. The zone of high SST variability is characterized by periodic shedding of eddies from the East Australian Current, and we suggest that ocean current circulation may, through its influence on larval transport and recruitment, interact with the genetic consequences of large variance in individual reproductive success to generate patterns of fine-scale patchy genetic structure. If proven consistent across species, our findings suggest that the optimal scale for fisheries management and reserve design should vary among localities in relation to regional oceanographic variability and coastal geography.     

Contrasting natural experiments confirm competition between House Finches and House Sparrows

After House Finches were introduced from the western to the eastern United States and rapidly increased in numbers, House Sparrows declined, leading to suggestions that the decline was caused by interspecific competition. However, other potential causes were not excluded. The rapid decline in House Finches following the emergence of a new disease (mycoplasmal conjunctivitis) caused by a novel strain of Mycoplasma gallisepticum (MG) in 1994 has provided a natural experiment and an opportunity to revisit the hypothesis that interspecific competition from House Finches drives population changes in House Sparrows. If true, the recent decline in House Finches should lead to an increase in House Sparrows. In this paper we test the hypothesis that House Sparrow and House Finch numbers in the northeastern United States vary inversely by examining data from three independent volunteer programs that monitor bird species' abundance and distribution (Christmas Bird Count, Project FeederWatch, and Breeding Bird Survey). In the first analysis we found that House Sparrow and House Finch numbers varied inversely during a time interval when House Finches were increasing and a time interval when House Finches were decreasing. In the second analysis, we found that the rates of geometric change in House Sparrow abundance (ln[HOSP(t+1)/HOSP(t)]) were negatively correlated with initial House Finch (HOFI(t)) and sparrow (HOSP(t)) abundances at individual sites, irrespective of the time period. Given that finch range expansion and subsequent declines in abundance are the result of two very different phenomena, it would be very unlikely for apparent competition or spurious correlations to cause the observed concomitant changes in House Sparrow abundance. We conclude that interspecific competition exists between these two species.