Self‐employment among French‐Canadians: The role of the regional milieu

This article examines the relationship between self‐employment among French‐Canadians and the regional milieu. Our main argument is that self‐employment among French‐Canadians depends on the specific regional milieu. The empirical analysis is based on the public use file on individuals of the 1986 Census of Canada. Self‐employment is related to mother tongue, region, industry, occupation, income and language spoken at home. Then, the association of socio‐economic and socio‐demographic attributes with self‐employment and mother tongue in different French‐Canadian communities is examined. The relation between self‐employment, regional milieus and French‐Canadian communities is further explored using the correspondence analysis method. Results show that in addition to variations in class resources and local opportunities, a majority or minority setting influences the economic niches utilized by French entrepreneurs. Among francophone minorities, small and relatively assimilated communities are usually more entrepreneurial than major francophone concentrations. However, this relationship is not causal, and does not indicate an economic benefit associated with assimilation. Still, French‐Canadians are not a typical entrepreneurial minority that utilizes extensive informal entrepreneurial networks for economic mobility, and the political and economic struggle of French‐Canadians for advancement has not been markedly focused on entrepreneur‐ship. In fact, our results suggest that self‐employment is not a major facet of group mobilization among francophones. Entrepreneurship is perceived by the francophone establishment as an important means for long‐term economic advancement. In attempting to promote entrepreneurship, the need to utilize ethnic networks and community cohesion is greatly acknowledged. We conclude that the preservation of autonomous ethno‐linguistic identity is viewed not only as a means for economic advancement but as a major goal by itself. Hence, French‐Canadians resemble, perhaps, certain sub‐national minorities in Europe, rather than other ethnic minorities in North America. The desired relationship between self‐employment and retention of group identity does not yet prevail, among French‐Canadians, and their political and economic struggle for advancement, so far, has not been focused on entrepreneurship.     

An estimate of fetal autonomic state by time-frequency analysis of fetal heart rate variability.

In this study we present a noninvasive method that enables the investigation of the fetal heart rate (FHR) fluctuations. The objective was to design a quantitative measurement to assess the fetal autonomic nervous system and to investigate its development as a function of the gestational age. Our Medical Physics group has developed a complex algorithm for online beat-to-beat detection of the fetal ECG (FECG), extracted from the maternal abdominal ECG signal. We used our previously acquired FECG data, which includes noninvasive recordings of 200 maternal abdominal ECG signals. From these, we chose 35 cases of healthy pregnancies that we divided into three groups according to gestational age: Group 1, 23 +/- 2 wk; Group 2, 32 +/- 1 wk; and Group 3, 39 +/- 1 wk. The FHR variability was analyzed by a time-frequency decomposition based on a continuous wavelet transform. We showed that, independent of the gestational age, most of the FHR power is concentrated in the very-low-frequency range (0.02-0.08 Hz) and in the low-frequency range (0.08-0.2 Hz). In addition, there is power in the high-frequency range that correlates with the frequency range of fetal respiratory motion (0.4-1.7 Hz). In the intermediate-frequency range (0.2-0.4 Hz), the power is significantly smaller. The changes in the average power spectrum in relation to gestation time were carefully and quantitatively examined. The results imply that there is a neural organization during the last trimester of the pregnancy, and the sympathovagal balance is reduced with the gestational age.     

Dissociation of the dimeric SecA ATPase during protein translocation across the bacterial membrane

The ATPase SecA mediates post-translational translocation of precursor proteins through the SecYEG channel of the bacterial inner membrane. We show that SecA, up to now considered to be a stable dimer, is actually in equilibrium with a small fraction of monomers. In the presence of membranes containing acidic phospholipids or in certain detergents, SecA completely dissociates into monomers. A synthetic signal peptide also affects dissociation into monomers. In addition, conversion into the monomeric state can be achieved by mutating a small number of residues in a dimeric and fully functional SecA fragment. This monomeric SecA fragment still maintains strong binding to SecYEG in the membrane as well as significant in vitro translocation activity. Together, the data suggest that the SecA dimer dissociates during protein translocation. Since SecA contains all characteristic motifs of a certain class of monomeric helicases, and since mutations in residues shared with the helicases abolish its translocation activity, SecA may function in a similar manner.     

Rare Variant Association Testing Under Low-Coverage Sequencing

Deep sequencing technologies enable the study of the effects of rare variants in disease risk. While methods have been developed to increase statistical power for detection of such effects, detecting subtle associations requires studies with hundreds or thousands of individuals, which is prohibitively costly. Recently, low-coverage sequencing has been shown to effectively reduce the cost of genome-wide association studies, using current sequencing technologies. However, current methods for disease association testing on rare variants cannot be applied directly to low-coverage sequencing data, as they require individual genotype data, which may not be called correctly due to low-coverage and inherent sequencing errors. In this article, we propose two novel methods for detecting association of rare variants with disease risk, using low coverage, error-prone sequencing. We show by simulation that our methods outperform previous methods under both low- and high-coverage sequencing and under different disease architectures. We use real data and simulation studies to demonstrate that to maximize the power to detect associations for a fixed budget, it is desirable to include more samples while lowering coverage and to perform an analysis using our suggested methods.     

Development and characterization of high affinity leptins and leptin antagonists

Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin.     

Neuroplasticity subserving motor skill learning

Recent years have seen significant progress in our understanding of the neural substrates of motor skill learning. Advances in neuroimaging provide new insight into functional reorganization associated with the acquisition, consolidation, and retention of motor skills. Plastic changes involving structural reorganization in gray and white matter architecture that occur over shorter time periods than previously thought have been documented as well. Data from experimental animals provided crucial information on plausible cellular and molecular substrates contributing to brain reorganization underlying skill acquisition in humans. Here, we review findings demonstrating functional and structural plasticity across different spatial and temporal scales that mediate motor skill learning while identifying converging areas of interest and possible avenues for future research.