Mathematical modelling of digit specification by a sonic hedgehog gradient

Background: The three chick wing digits represent a classical example of a pattern specified by a morphogen gradient. Here we have investigated whether a mathematical model of a Shh gradient can describe the specification of the identities of the three chick wing digits and if it can be applied to limbs with more digits. Results: We have produced a mathematical model for specification of chick wing digit identities by a Shh gradient that can be extended to the four digits of the chick leg with Shh-producing cells forming a digit. This model cannot be extended to specify the five digits of the mouse limb. Conclusions: Our data suggest that the parameters of a classical-type morphogen gradient are sufficient to specify the identities of three different digits. However, to specify more digit identities, this core mechanism has to be coupled to alternative processes, one being that in the chick leg and mouse limb, Shh-producing cells give rise to digits; another that in the mouse limb, the cellular response to the Shh gradient adapts over time so that digit specification does not depend simply on Shh concentration

Amino acid residue doublet propensity in the protein–RNA interface and its application to RNA interface prediction

Protein–RNA interactions play essential roles in a number of regulatory mechanisms for gene expression such as RNA splicing, transport, translation and post-transcriptional control. As the number of available protein–RNA complex 3D structures has increased, it is now possible to statistically examine protein–RNA interactions based on 3D structures. We performed computational analyses of 86 representative protein–RNA complexes retrieved from the Protein Data Bank. Interface residue propensity, a measure of the relative importance of different amino acid residues in the RNA interface, was calculated for each amino acid residue type (residue singlet interface propensity). In addition to the residue singlet propensity, we introduce a new residue-based propensity, which gives a measure of residue pairing preferences in the RNA interface of a protein (residue doublet interface propensity). The residue doublet interface propensity contains much more information than the sum of two singlet propensities alone. The prediction of the RNA interface using the two types of propensities plus a position-specific multiple sequence profile can achieve a specificity of about 80%. The prediction method was then applied to the 3D structure of two mRNA export factors, TAP (Mex67) and UAP56 (Sub2). The prediction enables us to point out candidate RNA interfaces, part of which are consistent with previous experimental studies and may contribute to elucidation of atomic mechanisms of mRNA export

Genetic characterization of Erve virus, a European Nairovirus distantly related to Crimean-Congo hemorrhagic fever virus

Erve virus (ERVEV) is a European Nairovirus that is suspected to cause severe headache (thunderclap headache) and intracerebral hemorrhage. The mode of transmission to humans (ticks or mosquitoes) is still unknown. Currently, no standardized testing method for ERVEV exists and only a small partial sequence of the polymerase gene is available. Here, we present the first complete genome sequence of ERVEV S, M, and L segments. Phylogenetic comparison of the amino acid sequence of the L-protein (RNA-dependent RNA polymerase) revealed only 48 % homology to available L-protein sequences of other Nairoviruses like Crimean-Congo hemorrhagic fever virus, Nairobi sheep disease virus, Hazara virus, Kupe virus, and Dugbe virus. Among themselves, these Nairoviruses show 62-89 % homology in the L-protein sequences. Therefore, ERVEV seems to be only distantly related to other Nairoviruses. The new sequence data can be used for the development of diagnostic methods and the identification of the natural vector

Elevated baseline work rate slows pulmonary oxygen uptake kinetics and decreases critical power during upright cycle exercise

Critical power is a fundamental parameter defining high-intensity exercise tolerance, and is related to the phase II time constant of pulmonary oxygen uptake kinetics (O2). Whether this relationship is causative is presently unclear. The present study determined the impact of raised baseline work rate, which increases O2, on critical power during upright cycle exercise. Critical power was determined via four constant-power exercise tests to exhaustion in two conditions: 1) with exercise initiated from an unloaded cycling baseline (U→S), and 2) with exercise initiated from a baseline work rate of 90% of the gas exchange threshold (M→S). During these exercise transitions, O2 and the time constant of muscle deoxyhaemoglobin kinetics (τ[HHb + Mb]) (the latter via near-infrared spectroscopy) were determined. In M→S, critical power was lower (M→S = 203 ± 44 W vs. U→S = 213 ± 45 W, P = 0.011) and O2 was greater (M→S = 51 ± 14 s vs. U→S = 34 ± 16 s, P = 0.002) when compared to U→S. Additionally, τ[HHb + Mb] was greater in M→S compared to U→S (M→S = 28 ± 7 s vs. U→S = 14 ± 7 s, P = 0.007). The increase inO2 and concomitant reduction in critical power inM→S compared to U→S suggests a causal relationship between these two parameters. However, that τ[HHb + Mb] was greater in M→S exculpates reduced oxygen availability as being a confounding factor. These data therefore provide the first experimental evidence that O2 is an independent determinant of critical power. Keywords critical power, exercise tolerance, oxygen uptake kinetics, power-duration relationship, muscle deoxyhaemoglobin kinetics, work-to-work exercise

Exploring intersectionality issues in entrepreneurial finance: Policy responses and future research directions

Main Message Entrepreneurial finance scholars (and policy-makers) need to adopt an intersectional approach to their analysis (and policy-making) and pay more attention to the interplay between the owner-manager characteristics of ethnicity/race, gender, and social class. Shorter Title of the manuscript Exploring intersectionality issues in entrepreneurial finance Key points Since most literature on entrepreneurial finance treats ethnicity/race, gender, and class separately, an intersectional approach to analysis is complex, whether social (race, gender, social class) or situational characteristics (entrepreneur versus migrant/social or health care worker). Women, ethnic minorities, and working-class people are disadvantaged when seeking finance. We integrate the literature and proposes intersectionality as a framework for policy-makers, since the interplay between these characteristics can be addressed to develop innovative methods of finance

The role of social and human capital among nascent entrepreneurs

This study examines nascent entrepreneurship by comparing individuals engaged in nascent activities (n = 380) with a control group (n=608), after screening a sample from the general population (n=30,427). The study then follows the developmental process of nascent entrepreneurs for 18 months. Bridging and bonding social capital, consisting of both strong and weak ties, was a robust predictor regarding who became a nascent entrepreneur as well as for advancing through the start-up process. With regard to outcomes like first sale or showing a profit, only one aspect of social capital, viz. being a member of a business network, had a statistically significant positive effect. The study supports human capital in predicting entry into nascent entrepreneurship, but only weakly for carrying the start-up process towards successful completion

A closer look at business planning: early stage outcome effects of how it is prepared and used

The widespread use of business planning in combination with the mixed theoretical and empirical support for its effect suggest research is needed that takes a deeper into the quality of plans and how they are used. In this study we longitudinally examine use vs. non-use; degree of formalizations; revision of plans, and moderation of planning effects by product novelty,among nascent firms. We relate these to attainment of profitability after 12 months. We find that business planning is negatively related to profitability, but that revising plans is positively related to profitability. Both these effects are stronger under conditions of high product novelty

Compensatory Entrepreneurship: Avoiding the Pitfalls of Global Isomorphic Entrepreneurship Research and Activities

Entrepreneurship promotion is a ubiquitous activity, promoted world-wide as offering solutions ranging from economic development to poverty reduction and mobility. This paper examines the research literature suggesting learning opportunities that might be provided to Brazilian scholars and practitioners. The paper also introduces a new concept in entrepreneurship: that of compensatory entrepreneurship. It is defined as the political endorsement of entrepreneurial promotion activities, including training, incubation, and media dissemination, for the primary objective of maintaining political and/or economic control of one population over another. The paper provides examples and suggestions for developing a uniquely effective mode of Brazilian entrepreneurship development. Entrepreneurship promotion is a ubiquitous activity, promoted world-wide as offering solutions ranging from economic development to poverty reduction and mobility. This paper examines the research literature suggesting learning opportunities that might be provided to Brazilian scholars and practitioners. The paper also introduces a new concept in entrepreneurship: that of compensatory entrepreneurship. It is defined as the political endorsement of entrepreneurial promotion activities, including training, incubation, and media dissemination, for the primary objective of maintaining political and/or economic control of one population over another. The paper provides examples and suggestions for developing a uniquely effective mode of Brazilian entrepreneurship development.