Social capital and the equilibrium number of entrepreneurs

Social capital is viewed either as a proprietary asset that serves private interests, including those of entrepreneurs, or as a collective asset that supports trust-based transactions saving on transaction costs both in markets and within the boundaries of firms, and benefiting society as a whole. This paper explains the relative specialization between entrepreneurs and market-governed exchanges as a result of the interaction between social capital that lowers transaction costs, and the scale economies of ability in managerial jobs (Lucas 1978). The main hypothesis formulated in the paper is that higher social capital will benefit the hierarchy relatively more than the market as a governance mechanism, and therefore in economies with higher social capital, the equilibrium number of entrepreneurs will be lower and their average span of control larger than in economies with lower social capital. The empirical evidence, with data from the Spanish Autonomous Communities, is consistent with this prediction.

Validation study of the French version of the observer-rater scales measuring coping and cognitive errors (CE-CAP) on a non-clinical population

This study examined the validity and reliability of the French version of two observer-rated measures developed to assess cognitive errors (cognitive errors rating system [CERS]) [6] and coping action patterns (coping action patterns rating system [CAPRS]) [22,24]. The CE measures 14 cognitive errors, broken down according to their valence positive or negative (see the definitions by A.T. Beck), and the CAP measures 12 coping categories, based on an comprehensive review literature, each broken down into three levels of action (affective, behavioural, cognitive). Thirty (N = 30) subjects recruited in a community sample participated in the study. They were interviewed according to a standardized clinical protocol: these interviews were transcribed and analysed with both observer-rated systems. Results showed that the inter-rater reliability of the two measures is good and that their internal validity is satisfactory, due to a non-significant canonical correlation between CAP and CE. With regard to discriminant validity, we found a non-significant canonical correlation between CAPRS and CISS, one of most widely used self-report questionnaire measuring coping. The same can be said for the correlation with a self-report questionnaire measuring symptoms (SCL-90-R). These results confirm the absence of confounds in the assessment of cognitive errors and of coping as assessed by these observer-rated scales and add an argument in favour of the French validation of the CE-CAP rating scales. (C) 2010 Elsevier Masson SAS. All rights reserved.

Handling macromolecule signals in the quantification of the neurochemical profile.

In vivo localized proton magnetic resonance spectroscopy (1H MRS) became a powerful and unique technique to non-invasively investigate brain metabolism of rodents and humans. The main goal of 1H MRS is the reliable quantification of concentrations of metabolites (neurochemical profile) in a well-defined region of the brain. The availability of very high magnetic field strengths combined with the possibility of acquiring spectra at very short echo time have dramatically increased the number of constituents of the neurochemical profile. The quantification of spectra measured at short echo times is complicated by the presence of macromolecule signals of particular importance at high magnetic fields. An error in the macromolecule estimation can lead to substantial errors in the obtained neurochemical profile. The purpose of the present review is to overview methods of high field 1H MRS with a focus on the metabolite quantification, in particular in handling signals of macromolecules. Three main approaches of handling signals of macromolecules are described, namely mathematical estimation of macromolecules, measurement of macromolecules in vivo, and direct acquisition of the in vivo spectrum without the contribution of macromolecules.

"In vitro" reconstitution of the fragmentation of vacuoles

Résumé La fragmentation des membranes est un processus commun à beaucoup d'organelles dans une cellule. Les mitochondries, le noyau, le réticulum endoplasmique, les phagosomes, les peroxisomes, l'appareil de Golgi et les lysosomes (vacuoles chez la levure) se fragmentent en plusieurs copies en réponse à des sitmulis environnementaux, tels que des stresses, ou dans une situtation normale durant le cycle cellulaire, afin d' être transférer dans les cellules filles. La fragmentation des membranes est également observée pendant le processus d'endocytose, lors de la formation de vésicules endocytiques, mais également dans tout le traffic intracellulaire, lors de la genèse d'une vésicule de transport. Le processus de fragmentation est donc généralement important. La découverte en 1991 d'une dynamin-like GTPase comme protéine impliquée dans la fragmentation de la membrane plasmique durant l'endocytose a ouvert ce domaine de recherche. Dès lors des dynamines ont été découvertes sur la pluspart des organelles, ce qui suggère un processus de fragmentation des membranes commun à l'ensemble de la cellule. Cependant, l'ensemble des protéines impliquées ainsi que le mécanisme de la fragmentation reste encore à élucider. Mon projet de thèse était d'établir un test in vitro de fragmentation des vacuoles utile à la compréhension du mécanisme de ce processus. Le choix de ce système est judicieux pour plusieurs raisons; premièrement les vacuoles fragmentent naturellement durant le cycle cellulaire, deuxièment leur taille permet de visualiser facilement leur morphologie par simple microscopie optique, finalement elles peuvent être isolées en quantité intéressante avec un haut degré de pureté. In vivo, les vacuoles peuvent être facilement fragmentées par un stress osmotique. Un tel test permet d'identifier des protéines impliquées dans le mécanisme comme dans le criblage que j'ai effectué sur l'ensemble de la collection de délétions des gènes non-essentiels chez la levure. Cependant un test in vitro est ensuite indispensable pour jouer avec les protéines découvertes afin d'en élucider le mécanisme. Avec mon test in vitro, j'ai confirmé l'implication des protéines SNAREs dans la fragmentation et j'ai permis de comprendre la régulation de la quantité de vacuoles et de leur taille par le complexe TORC1 dans une situation de stress. 7 Résumé large public Les cellules de chaque organisme sont composées de différents compartiments appelés organelles. Chacun possède une fonction bien définie afin de permettre la vie et la croissance de la cellule. Ils sont entourés de membrane, qui joue le role de barrière spécifiquement perméable, afin de garder l'intégrité de chacun. Dans des conditions de croissance normale, les cellules prolifèrent. Durant la division cellulaire amenant à la formation d'une nouvelle cellule, chaque organelle doit se diviser afin de fournir l'ensemble des organelles à la cellule fille. La division de chaque organelle nécessite la fragmentation de la membrane les entourant. Des protéines dynamine-like GTPase ont été découvertes sur presque l'ensemble des organelles d'une cellule. Elles sont impliquées dans les processus de fragmentation des membranes. Dès lors l'idée d'un mécanisme commun est apparu. Cependant cette réaction, par sa complexité, ne peut pas impliquer une protéine unique. La découverte d'autres facteurs et la compréhension du mécanisme reste à faire. La première étape peut se faire par étude in vivo, c'est-à-dire avec des cellules entières, la deuxième étape, quant à elle, nécessite d'isoler les protéines impliquées et de jouer avec les différents paramètres, ce qui signifie donc un travail in vitro, séparé des cellules. Mon travail a constisté à établir un procédé expérimental in vitro pour étudier la fragmentation des membranes. Je travaille avec des vacuoles de levures pour étudier les réactions membranaires. Les vacuoles sont les plus grandes organelles présentes dans les levures. Elles sont impliquées principalement dans la digestion. Comme toute organelle, elles se fragmentent durant la division cellulaire. Le procédé expérimental comporte une première étape, l'isolation des vacuoles et, deuxièmement, l'incubation de celles-ci avec des composés essentiels à la réaction. En parallèle, j'ai mis en évidence, par un travail in vivo, de nouvelles protéines impliquées dans le processus de fragmentation des membranes. Ceci a été fait en réalisant un criblage par microscopie d'une collection de mutants. Parmi ces mutants, j'ai cherché ceux qui présentaient un défaut dans la fragmentation des vacuoles. Ces deux procédés expérimentaux, in vitro et in vivo, m'ont permis de découvrir de nouvelles protéines impliquées dans cette réaction, ainsi que de mettre en évidence un mécanisme utlilisé par la cellule pour réguler la fragmentation des vacuoles. 8 Summary Fragmentation of membranes is common for many organelles in a cell. Mitochondria, nucleus, endoplasmic reticulum, phagosomes, peroxisomes, Golgi and lysosomes (vacuoles in yeast) fragment into multiple copies in response to environmental stimuli, such as stresses, or in a normal situation during the cell cycle in order to be transferred into the daughter cell. Fragmentation of membrane occurs during endocytosis, at the latest step in endocytic vesicle formation, and also in intracellular trafficking, when traffic vesicles bud. This field of research was opened in 1991 when a dynamin-like GTPase was found to be involved in fragmentation of the plasma membrane during endocytosis. Since dynamin-like GTPases have been found on most organelles, similarities in their mechanisms of fragmentation might exist. However, many proteins involved in the mechanism of fragmentation remain unknown. My thesis project was to establish an in vitro assay for membrane fragmentation in order to create a tool to study the mechanism of this process. I chose vacuoles as a model organelle for several reasons: first of all, vacuoles fragment under physiological conditions during cell cycle, secondly their size makes their morphology easily visible under the light microscope, and finally vacuoles can be isolated in good amounts with relatively high degrees of purity. In vivo, vacuole fragmentation can be induced with an osmotic shock. Such a simple assay facilitates the identification of new proteins involved in the process. I used this tool to screen of the entire knockout collection of non-essential genes in Saccharomyces cerevisiae for mutants defective in vacuole fragmentation. The in vitro system will be useful to characterize the mutants and to study the mechanism of fragmentation in detail. I used my in vitro assay to confirm the involvement of vacuolar SNARE proteins in fragmentation of the organelle and to uncover that number and size of vacuoles in the cell is regulated by the TORC1 complex via selective stimulation of fragmentation activity.

Nematode selenoproteome: the use of the selenocysteine insertion system to decode one codon in an animal genome?

Selenocysteine (Sec) is co-translationally inserted into selenoproteins in response to codon UGA with the help of the selenocysteine insertion sequence (SECIS) element. The number of selenoproteins in animals varies, with humans having 25 and mice having 24 selenoproteins. To date, however, only one selenoprotein, thioredoxin reductase, has been detected in Caenorhabditis elegans, and this enzyme contains only one Sec. Here, we characterize the selenoproteomes of C.elegans and Caenorhabditis briggsae with three independent algorithms, one searching for pairs of homologous nematode SECIS elements, another searching for Cys- or Sec-containing homologs of potential nematode selenoprotein genes and the third identifying Sec-containing homologs of annotated nematode proteins. These methods suggest that thioredoxin reductase is the only Sec-containing protein in the C.elegans and C.briggsae genomes. In contrast, we identified additional selenoproteins in other nematodes. Assuming that Sec insertion mechanisms are conserved between nematodes and other eukaryotes, the data suggest that nematode selenoproteomes were reduced during evolution, and that in an extreme reduction case Sec insertion systems probably decode only a single UGA codon in C.elegans and C.briggsae genomes. In addition, all detected genes had a rare form of SECIS element containing a guanosine in place of a conserved adenosine present in most other SECIS structures, suggesting that in organisms with small selenoproteomes SECIS elements may change rapidly.

Genetic studies of the Roma (Gypsies): a review

Background: Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.Conclusion: Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Analysis of the multi-copy gene family FAM90A as a copy number variant in different ethnic backgrounds

Copy number variants contribute extensively to inter-individual genomic differences, but little is known about their inter-population variability and diversity. In a previous study (Bosch et al., 2007; 16:2572-2582), we reported that the primate-specific gene family FAM90A, which accounts for as many as 25 members in the human reference assembly, has expanded the number of FAM90A clusters across the hominoid lineage. Here we examined the copy number variability of FAM90A genes in 260 HapMap samples of European, African, and Asian ancestry, and showed significant inter-population differences (p<0.0001). Based on the recent study of Stranger et al. (2007; 315:848-853), we also explored the correlation between copy number variability and expression levels of the FAM90A gene family. Despite the high genomic variability, we found a low correlation between FAM90A copy number and expression levels, which could be due to the action of independent trans-acting factors. Our results show that FAM90A is highly variable in copy number between individuals and between populations. However, this variability has little impact on gene expression levels, thus highlighting the importance of genomic variability for genes located in regions containing segmental duplications.

Early Cretaceous radiolarians of the Northeast Indian Ocean (leg 123 - site 765, site 766 and dsdp site 261) - The Antarctic-Tethys connection

During ODP Leg 123, abundant and well-preserved Neocomian radiolarians were recovered at Site 765 (Argo Abyssal Plain) and Site 766 (lower Exmouth Plateau). Assemblages are characterized by the numerical dominance of a small number of non-tethyan forms and by the scarcity of tethyan taxa. Remarkable contrasts exist between radiolarian assemblages extracted from claystones of Site 765 and reexamined DSDP Site 26 1, and faunas recovered from radiolarian sand layers, only found at Site 765. Clay faunas are unusual in their low diversity of apparently ecologically tolerant (or solution resistant?), ubiquist species, whereas sand faunas are dominated by non-tethyan taxa. Comparisons with Sites 766 and 26 1, as well as sedimentological observations, lead to the conclusion that this faunal contrast resulted from a difference in provenance, rather than from hydraulic sorting or selective dissolution. The ranges of 27 tethyan taxa from Site 765 were compared to the tethyan radiolarian zonation by Jud (1992) by means of the Unitary Associations Method. This calculation allows to directly date the Site 765 assemblages and to estimate the amount of truncation of ranges for tethyan taxa. Over 70% of the already few tethyan species of Site 765, have truncated ranges during the Valanginian-Hauterivian. Radiolarian assemblages recovered from claystones at Sites 765 and 261 in the Argo Basin apparently reflect restricted oceanic conditions during the latest Jurassic-Barremian. Neither sedimentary facies nor faunal associations bear any resemblance to what we know from typical tethyan sequences. We conclude that the Argo Basin was paleoceanographically separated from the Tethys during the Late Jurassic and part of the Early Cretaceous by its position at higher paleolatitudes and/or by enclosing land masses. Assemblages recovered from radiolarian sand layers are dominated by non-tethyan species that are interpreted as circumantarctic. Their first appearance in the late Berriasian-early Valanginian predates the oceanization of the Indo-Australian breakup (M11, late Valanginian), but coincides with a sharp increase in margin-derived pelagic turbidites. The Indo-Australian rift zone and the adjacent margins must have been submerged deeply enough to allow an intermittent influx of circumantarctic cold water into the Argo Basin, creating increased bottom current activity. Cold-water radiolarians carried into the Argo Basin upwelled along the margin, died, and accumulated in radiolarite layers due to winnowing by bottom currents. High rates of faunal change and the sharp increase of bottom current activity are thought to be synchronous with possible pronounced late Berriasian-early Valanginian lowstands in sea level. Hypothetically, both phenomena might have been.caused by a tendency to glaciation on the Antarctic-Australian continent, which was for the first time isolated from the rest of Gondwana by oceanic seaways as a result of Jurassic-Early Cretaceous sea-floor spreading. The absence of most typical tethyan radiolarian species during the Valanginian-Hauterivian is interpreted as reflecting a time of strong influx of circumantarctic cold water following oceanization (M11) and rapid spreading between Southeast India and West Australia. The reappearance and gradual abundance/diversity increase of tethyan taxa, along with the still dominant circumantarctic species are thought to result from overall more equitable climatic conditions during the Barremian-early Aptian and from the establishment of an oceanic connection with the Tethys Ocean during the early Aptian.

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: effects of an antibody treatment neutralizing Nogo-A.

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

Content validation of the dimensions constituting non-adherence to treatment of arterial hypertension

The objective of the study was to validate the content of the dimensions that constituted nonadherence to treatment of arterial systemic hypertension. It was a methodological study of content validation. Initially an integrative review was conducted that demonstrated four dimensions of nonadherence: person, disease/treatment, health service, and environment. Definitions of these dimensions were evaluated by 17 professionals, who were specialists in the area, including: nurses, pharmacists and physicians. The Content Validity Index was calculated for each dimension (IVCi) and the set of the dimensions (IVCt), and the binomial test was conducted. The results permitted the validation of the dimensions with an IVCt of 0.88, demonstrating reasonable systematic comprehension of the phenomena of nonadherence.

On the number of independent cultural traits carried by individuals and populations.

In species subject to individual and social learning, each individual is likely to express a certain number of different cultural traits acquired during its lifetime. If the process of trait innovation and transmission reaches a steady state in the population, the number of different cultural traits carried by an individual converges to some stationary distribution. We call this the trait-number distribution. In this paper, we derive the trait-number distributions for both individuals and populations when cultural traits are independent of each other. Our results suggest that as the number of cultural traits becomes large, the trait-number distributions approach Poisson distributions so that their means characterize cultural diversity in the population. We then analyse how the mean trait number varies at both the individual and population levels as a function of various demographic features, such as population size and subdivision, and social learning rules, such as conformism and anti-conformism. Diversity at the individual and population levels, as well as at the level of cultural homogeneity within groups, depends critically on the details of population demography and the individual and social learning rules.

Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study.

BACKGROUND: Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. METHODS: Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. RESULTS: Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. CONCLUSION: Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.