Occupational choice, number of entrepreneurs and output: theory and empirical evidence with Spanish data

This paper extends the (Lucas, Bell J Econ 9:508–523,1978) model of occupational choices by individuals with different skills, beyond the simple options of self-employment or wage-employment, by including a second choice for the self-employed. That is, an option to hire employees and so become self-employed with employees (SEWEs), or to be self-employed without employees (SEWNEs). We solve for the market equilibrium and examine the sensitivity of relative sizes of occupational groups, and of the level of productivity, to changes in the exogenous parameters. The results show that the positive (negative) association between number of SEWEs (SEWNEs) and productivity, observed in the Spanish data, can be explained, under certain conditions, as the result of cross-region and time differences in average skills. These findings point to the importance of distinguishing between SEWEs and SEWNEs in drawing valid conclusions concerning any link between entrepreneurship and economic development

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Early detection of left ventricular diastolic dysfunction in Chagas' disease

BACKGROUND: Chagas' disease may cause left ventricular diastolic dysfunction and its early detection in asymptomatic patients would allow to stratify the risk and to optimize medical treatment. The aim of this study is to investigate if transmitral Doppler flow can detect early abnormalities of the diastolic left ventricular function in patients during the indeterminate phase of Chagas' disease, in which the electrocardiogram (ECG), chest x-ray and 2-D echocardiogram (2D-echo) are normal. METHODS: a group of 54 patients with Chagas' disease was studied and compared to a control group of 27 subjects of similar age. All were assessed with an ECG, chest X-ray, 2-D echo, and transmitral Doppler flow. RESULTS: both groups had similar values in the 2D-echo. In patients with Chagas' disease, the transmitral Doppler showed a higher peak A velocity (control group: 0.44 m/sec, Chagas group: 0.55 m/sec, p = 0.001), a lower E/A ratio (control group: 1.45, Chagas group: 1.22, p < 0.05), and a lengthening of the deceleration time of early diastolic filling (control: 138.7 ± 26.8 msec, Chagas group: 167.9 ± 34.6 msec, p = 001), thus revealing an early disorder of the diastolic left ventricular function in patients with Chagas' disease. CONCLUSION: in patients with Chagas' disease who are in the indeterminate phase, transmitral Doppler flow allowed to identify early abnormalities of the left ventricular diastolic function, which provide useful clinical information for prognostic stratification and treatment

Hydrodynamic modelling of protein conformation in solution: ELLIPS and HYDRO

The last three decades has seen some important advances in our ability to represent the conformation of proteins in solution on the basis of hydrodynamic measurements. Advances in theoretical modeling capabilities have been matched by commensurate advances in the precision of hydrodynamic measurements. We consider the advances in whole-body (simple ellipsoid-based) modeling—still useful for providing an overall idea of molecular shape, particularly for those systems where only a limited amount of data is available—and outline the ELLIPS suite of algorithms which facilitates the use of this approach. We then focus on bead modeling strategies, particularly the surface or shell–bead approaches and the HYDRO suite of algorithms. We demonstrate how these are providing great insights into complex issues such as the conformation of immunoglobulins and other multi-domain complexes

Novel Indirect Calorimetry Technology to Analyze Metabolism in Individual Neonatal Rodent Pups

BACKGROUND: The ability to characterize the development of metabolic function in neonatal rodents has been limited due to technological constraints. Low respiratory volumes and flows at rest pose unique problems, making it difficult to reliably measure O(2) consumption, CO(2) production, respiratory quotient (RQ), and energy expenditure (EE). Our aim was to develop and validate a commercial-grade indirect calorimetry system capable of characterizing the metabolic phenotype of individual neonatal rodents. METHODOLOGY/PRINCIPAL FINDINGS: To address this research need, we developed a novel, highly sensitive open-circuit indirect calorimetry system capable of analyzing respiratory gas exchange in a single neonatal rodent pup. Additionally, we derived an equation from known metabolic relationships to estimate inlet flow rates, improving the efficiency of data collection. To validate the neonatal rodent indirect calorimetry system and evaluate the applicability of the derived equation for predicting appropriate flow rates, we conducted a series of experiments evaluating the impact of sex, litter size, time of day (during the light phase), and ambient temperature on neonatal rat metabolic parameters. Data revealed that the only metabolic parameter influenced by litter size is a neonatal rat's RQ, with rat pups reared in a small litter (5 pups) having lower RQ's than rat pups reared in either medium (8 pups) or large (11 pups) litters. Furthermore, data showed that ambient temperature affected all metabolic parameters measured, with colder temperatures being associated with higher CO(2) production, higher O(2) consumption, and higher energy expenditure. CONCLUSION/SIGNIFICANCE: The results of this study demonstrate that the modified Panlab Oxylet system reliably assesses early postnatal metabolism in individual neonatal rodents. This system will be of paramount importance to further our understanding of processes associated with the developmental origins of adult metabolic disease

Tipping points in the dynamics of speciation.

Speciation can be gradual or sudden and involve few or many genetic changes. Inferring the processes generating such patterns is difficult, and may require consideration of emergent and non-linear properties of speciation, such as when small changes at tipping points have large effects on differentiation. Tipping points involve positive feedback and indirect selection stemming from associations between genomic regions, bi-stability due to effects of initial conditions and evolutionary history, and dependence on modularity of system components. These features are associated with sudden 'regime shifts' in other cellular, ecological, and societal systems. Thus, tools used to understand other complex systems could be fruitfully applied in speciation research

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule-induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses

Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies