Genetic heterogeneity in erythropoietic protoporphyria: a study of the enzymatic defect in nine affected families

Erythropoietic protoporphyria (EPP) is associated with a deficiency of protohaem ferrolyase. We have used a novel assay for this enzyme based on its ability to utilize zinc as a substrate to investigate the inheritance of EPP in nine affected families. Zinc chelatase activity was markedly reduced in peripheral blood mononuclear cells from 14 EPP patients (mean, 3.3 nmol Zn protohaem/h/mg protein; range, 0.3-8.0) when compared with 41 controls (16.8 +/- 3.6) p less than 0.01. In three families with parent-to-child transmission of disease, the asymptomatic parent had an enzymatic activity within the normal range. In three pedigrees where the parents were asymptomatic, enzymatic activities were below the 95% confidence limits in both. Zinc chelatase activity was below the mean control value in 17 of the 18 parents in nine affected pedigrees, and six of seven asymptomatic offspring of patients with protoporphyria. The findings suggest that EPP is not transmitted as a simple dominant trait and that inheritance of more than one gene may be required for disease expression.

Energy exchange in a dense urban environment Part II: impact of spatial heterogeneity of the surface

The centre of cities, characterised by spatial and temporal complexity, are challenging environments for micrometeorological research. This paper considers the impact of sensor location and heterogeneity of the urban surface on flux observations in the dense city centre of London, UK. Data gathered at two sites in close vicinity, but with different measurement heights, were analysed to investigate the influence of source area characteristics on long-term radiation and turbulent heat fluxes. Combining consideration of diffuse radiation and effects of specular reflections, the non-Lambertian urban surface is found to impact the measurements of surface albedo. Comparisons of observations from the two sites reveal that turbulent heat fluxes are similar under some flow conditions. However, they mostly observe processes at different scales due to their differing measurement heights, highlighting the critical impact of siting sensors in urban areas. A detailed source area analysis is presented to investigate the surface controls influencing the energy exchanges at the different scales

Monopolistic product line competition with ex post consumer heterogeneity

We model monopolistic competition in product lines, assuming that consumer heterogeneity is the result rather than the cause of product variety. Our results contradict some well-known policy implications yielded by the standard monopolistic competition framework.

Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

Firms in international trade: importers’ and exporters’ heterogeneity in Italian manufacturing industry

Combining data on structural characteristics and economic performance for a large sample of Italian firms with data on exporting and importing activity, we uncover evidence supporting recent theories on firm heterogeneity and international trade, together with some new facts. In particular, we find that importing is associated with substantial firm heterogeneity. First, we document that trade is more concentrated than employment and sales, and show that importing is even more concentrated than exporting both within sectors and along the sector- and country-extensive margins. Second, while supporting the fact that firms involved in both are the best performers, we also find that firms involved only in importing activities perform better than those involved only in exporting. Our evidence suggests there is a strong self-selection effect in the case of importers and the performance premia of internationalised firms correlate relatively more with the degree of geographical and sectoral diversification of imports.

Productivity and the international firm: dissecting heterogeneity

Higher productivity of multinational firms and exporters has been widely documented in the literature, but the sources of this heterogeneity are still a black box. Using an original dataset on Italian firms, we show that higher total factor productivity of international firms can be to some extent explained by higher R&D intensity and managerial capabilities. However, our results suggest that heterogeneity is more in the slope than in the constant of the production function. In particular, allowing international firms to have different return to labour and capital inputs, we are able to account for their entire productivity premium. This has implications for both labour and capital market reforms.

The compositional and configurational heterogeneity of matrix habitats shape woodland carabid communities in wooded-agricultural landscapes

Landscape heterogeneity (the composition and configuration of matrix habitats) plays a major role in shaping species communities in wooded-agricultural landscapes. However, few studies consider the influence of different types of semi-natural and linear habitats in the matrix, despite their known ecological value for biodiversity. Objective To investigate the importance of the composition and configuration of matrix habitats for woodland carabid communities and identify whether specific landscape features can help to maintain long-term populations in wooded-agricultural environments. Methods Carabids were sampled from woodlands in 36 tetrads of 4 km2 across southern Britain. Landscape heterogeneity including an innovative representation of linear habitats was quantified for each tetrad. Carabid community response was analysed using ordination methods combined with variation partitioning and additional response trait analyses. Results Woodland carabid community response was trait-specific and better explained by simultaneously considering the composition and configuration of matrix habitats. Semi-natural and linear features provided significant refuge habitat and functional connectivity. Mature hedgerows were essential for slow-dispersing carabids in fragmented landscapes. Species commonly associated with heathland were correlated with inland water and woodland patches despite widespread heathland conversion to agricultural land, suggesting that species may persist for some decades when elements representative of the original habitat are retained following landscape modification. Conclusions Semi-natural and linear habitats have high biodiversity value. Landowners should identify features that can provide additional resources or functional connectivity for species relative to other habitat types in the landscape matrix. Agri-environment options should consider landscape heterogeneity to identify the most efficacious changes for biodiversity.

Gender, race, and heterogeneous effects of epidemic malaria on human capital and income

This article investigates the impact of exposure to a serious, unusual, and unforeseen malaria epidemic in northeast Brazil in 1938–40 on subsequent human capital attainment and income. Arguing the event was exogenous, the article exploits cohort and regional heterogeneity in exposure to identify effects. Results are consistent with differential mortality rates according to gender and socioeconomic status, such that heterogeneous selection and scarring effects are observed. Analyzing by gender alone, positive (selection) effects are found for men, and mixed (positive and negative) effects for women. Allowing for heterogeneity by race, selection effects persist for men. In contrast, positive (selection) effects are observed for nonwhite women, and negative (scarring) effects for white women. Results contribute to evidence suggesting that exposure to negative environmental shocks affects human capital attainment, while also suggesting it heterogeneously affects cohort composition.

Socioeconomic correlates of global mammalian conservation status

The main causes of biodiversity decline are related to human use of resources, which is ultimately triggered by the socioeconomic decisions made by individuals and nations. Characterizing the socioeconomic attributes of areas in which biodiversity is most threatened can help us identify decisions and conditions that promote the presence or absence of threats and potentially suggest more sustainable strategies. In this study we explored how diverse indicators of social and economic development correlate with the conservation status of terrestrial mammals within countries explicitly exploring hypothesized linear and quadratic relationships. First, comparing countries with and without threatened mammals we found that those without threatened species are a disparate group formed by European countries and Small Island Developing States (SIDS) with little in common besides their slow population growth and a past of human impacts. Second, focusing on countries with threatened mammals we found that those with a more threatened mammalian biota have mainly rural populations, are predominantly exporters of goods and services, receive low to intermediate economic benefits from international tourism, and have medium to high human life expectancy. Overall, these results provide a comprehensive characterization of the socioeconomic profiles linked to mammalian conservation status of the world's nations, highlighting the importance of transborder impacts reflected by the international flux of goods, services and people. Further studies would be necessary to unravel the actual mechanisms and threats that link these socioeconomic profiles and indicators with mammalian conservation. Nevertheless, this study presents a broad and complete characterization that offers testable hypotheses regarding how socioeconomic development associates with biodiversity.

The evolution and heterogeneity of outward foreign direct investment from Latin America

The PhD dissertation investigates the rise of emerging country multinationals (EMNEs), a phenomenon that has opened up a series of research themes and debates. The main debate in this field is the extent to which the theories/frameworks on foreign direct investment (FDI), which have been developed from investigations on multinationals from developed countries, is relevant in explaining outward FDI from EMNEs. This debate is sparked by research suggesting that EMNEs supposedly do not hold the characteristics that are seen as a prerequisite to engaging in FDI. The underlying theme in this PhD is that the field should move away from a one size fit all categorisation of EMNEs, and explore the heterogeneity within EMNEs. Collecting data through various databases, archival articles and annual reports, there was an examination of the internationalisation process of 136 Latin American Multinationals (LAMNEs). The research explores the differences in internationalisation trajectories and global strategies and classifies firms into one of four categories. The four categories that LAMNEs fall into are: Natural-Resource Vertical Integrator, which are firms that are in resource seeking sectors; Accelerated Global, which depict firms that have become global over a very short period of time; Traditional Global, which are EMNEs that have internationalised at the same pace as developed country MNEs and Local Optimisers that only acquire or internationalise to developing countries. The analysis also looks at which decade LAMNEs engaged in FDI, to see if LAMNEs that internationalised during the 1970s and 1980s, during a time when Latin America had a closed economy, was different to LAMNEs that internationalised during the Washington consensus era of the 1990s or to firms that have only just internationalised within the last decade. The findings show that LAMNEs that internationalised before 1990 were more likely to adopt Local Optimiser strategies. However, more LAMNEs that started to internationalise during the 1990s started to adopt Traditional Global strategies, although Local Optimisers were the most prominent strategy. From 2002, there was more prominence of Accelerated Global strategies and a lot more heterogeneity among LAMNEs. Natural-Resource Vertical Integrator LAMNEs, tended to start to internationalisation process during the 1970s/1980s. Despite the rise of EMNEs, and by extension LAMNEs opting to use cross border merger and acquisitions (M&A), there is little research on whether this entry mode has been successful. Contrary to the argument that EMNEs are “internationalising successfully” through this strategy, the findings show that these firms are highly geared and are running less efficiently against their Western competitors. In comparison, LAMNEs internationalising through a more gradual approach, are outperforming their Western competitors on efficiency and are not highly geared- i.e. do not hold a lot of debt. The conclusion of the thesis is the emphasis of moving away from evaluating firms from their country or region of origin, but rather through the global strategy they are using. This will give a more a robust firm level of analysis, and help develop the understanding of EMNEs and international business theory.

Latitudinal gradients in butterfly population variability are influenced by landscape heterogeneity

The variability of populations over time is positively associated with their risk of local extinction. Previous work has shown that populations at the high-latitude boundary of species’ ranges show higher inter-annual variability, consistent with increased sensitivity and exposure to adverse climatic conditions. However, patterns of population variability at both high- and low-latitude species range boundaries have not yet been concurrently examined. Here, we assess the inter-annual population variability of 28 butterfly species between 1994 and 2009 at 351 and 18 sites in the United Kingdom and Catalonia, Spain, respectively. Local population variability is examined with respect to the position of the species’ bioclimatic envelopes (i.e. whether the population falls within areas of the ‘core’ climatic suitability or is a climatically ‘marginal’ population), and in relation to local landscape heterogeneity, which may influence these range location – population dynamic relationships. We found that butterfly species consistently show latitudinal gradients in population variability, with increased variability in the more northerly UK. This pattern is even more marked for southerly distributed species with ‘marginal’ climatic suitability in the UK but ‘core’ climatic suitability in Catalonia. In addition, local landscape heterogeneity did influence these range location – population dynamic relationships. Habitat heterogeneity was associated with dampened population dynamics, especially for populations in the UK. Our results suggest that promoting habitat heterogeneity may promote the persistence of populations at high-latitude range boundaries, which may potentially aid northwards expansion under climate warming. We did not find evidence that population variability increases towards southern range boundaries. Sample sizes for this region were low, but there was tentative evidence, in line with previous ecological theory, that local landscape heterogeneity may promote persistence in these retracting low-latitude range boundary populations.

The heterogeneity of wooded-agricultural landscape mosaics influences woodland bird community assemblages

Context Landscape heterogeneity (the composition and configuration of different landcover types) plays a key role in shaping woodland bird assemblages in wooded-agricultural mosaics. Understanding how species respond to landscape factors could contribute to preventing further decline of woodland bird populations. Objective To investigate how woodland birds with different species traits respond to landscape heterogeneity, and to identify whether specific landcover types are important for maintaining diverse populations in wooded-agricultural environments. Methods Birds were sampled from woodlands in 58 2 x 2 km tetrads across southern Britain. Landscape heterogeneity was quantified for each tetrad. Bird assemblage response was determined using redundancy analysis combined with variation partitioning and response trait analyses. Results For woodland bird assemblages, the independent explanatory importance of landscape composition and landscape configuration variables were closely interrelated. When considered simultaneously during variation partitioning, the community response was better represented by compositional variables. Different species responded to different landscape features and this could be explained by traits relating to woodland association, foraging strata and nest location. Ubiquitous, generalist species, many of which were hole-nesters or ground foragers, correlated positively with urban landcover while specialists of broadleaved woodland avoided landscapes containing urban areas. Species typical of coniferous woodland correlated with large conifer plantations. Conclusions At the 2 x 2 km scale, there was evidence that the availability of resources provided by proximate landcover types was highly important for shaping woodland bird assemblages. Further research to disentangle the effects of composition and configuration at different spatial scales is advocated.