A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

What form of relative performance evaluation?

We study relative performance evaluation in executive compensation whenexecutives have private information about their ability. We assume that thejoint distribution of an individual firm s profit and market movements dependson the ability of the executive that runs the firm. In the equilibrium of theexecutive labor market, compensation schemes exploit this fact to sortexecutives of di ?erent abilities. This implies that executive compensation isincreasing in own performance, but may also be increasing in industryperformance-a sharp departure from standard relative performance evaluation.This result provides an explanation for the scarcity of relative performanceconsiderations in executive compensation documented by the empirical literature.

The choice of the form of representation in multinational banking: Evidence from Spain

This paper investigates foreign direct investment in the bankingsector. The attention has been addressed to test the importanceof OLI advantages as the determinants of the bank's decisionto invest in foreign locations. Nevertheless, since banks canexpand their activities abroad through different organizationalforms that imply different levels of foreign involvement, theissue of the form of representation has been tackled. Theresults show the importance of OLI advantages in the form ofrepresentation in multinational banking.

Causal assessment in finite extensive-form games

Two finite extensive-form games are empirically equivalent when theempirical distribution on action profiles generated by every behaviorstrategy in one can also be generated by an appropriately chosen behaviorstrategy in the other. This paper provides a characterization ofempirical equivalence. The central idea is to relate a game's informationstructure to the conditional independencies in the empirical distributionsit generates. We present a new analytical device, the influence opportunitydiagram of a game, describe how such a diagram is constructed for a givenextensive-form game, and demonstrate that it provides a complete summaryof the information needed to test empirical equivalence between two games.

Stochastic evolution of rules for playing normal form games

The evolution of boundedly rational rules for playing normal form games is studied within stationary environments ofstochastically changing games. Rules are viewed as algorithms prescribing strategies for the different normal formgames that arise. It is shown that many of the folk results of evolutionary game theory typically obtained witha fixed game and fixed strategies carry over to the present case. The results are also related to recent experimentson rules and games.

Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to form beta-structures and filaments.

The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta-structure conformation. Here we show that the conformational change of the peptide from random coil to beta-structure is important in binding ss- and dsDNA. The beta-structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta-structure. A beta-structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed.

Overexpression of a mutant form of TGFBI/BIGH3 induces retinal degeneration in transgenic mice.

PURPOSE: Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation. METHODS: Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy. RESULTS: Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals. CONCLUSIONS: Cellular degeneration in the retina of transgenic animals suggest that perturbation of the transforming growth factor beta (TGFbeta) family regulation may affect photoreceptor survival and may induce possible accelerated aging in several tissues. No corneal phenotype could be observed, probably due to the lack of transgene expression in this tissue.

Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.

OBJECTIVE: To validate a revision of the Mini Nutritional Assessment short-form (MNA(R)-SF) against the full MNA, a standard tool for nutritional evaluation. METHODS: A literature search identified studies that used the MNA for nutritional screening in geriatric patients. The contacted authors submitted original datasets that were merged into a single database. Various combinations of the questions on the current MNA-SF were tested using this database through combination analysis and ROC based derivation of classification thresholds. RESULTS: Twenty-seven datasets (n=6257 participants) were initially processed from which twelve were used in the current analysis on a sample of 2032 study participants (mean age 82.3y) with complete information on all MNA items. The original MNA-SF was a combination of six questions from the full MNA. A revised MNA-SF included calf circumference (CC) substituted for BMI performed equally well. A revised three-category scoring classification for this revised MNA-SF, using BMI and/or CC, had good sensitivity compared to the full MNA. CONCLUSION: The newly revised MNA-SF is a valid nutritional screening tool applicable to geriatric health care professionals with the option of using CC when BMI cannot be calculated. This revised MNA-SF increases the applicability of this rapid screening tool in clinical practice through the inclusion of a "malnourished" category.

Slip-Form Paving as Developed and Pioneered in Iowa,1961.

Summarizes Iowa's 14 years of experience in pioneering and developing slip-form paving methods

Recueil de pièces relatives au prieuré de Dhuisy, diocèse de Meaux, formé par Charles de Chantecler, prieur et seigneur de Dhnisy, pour les besoins de son procès contre Henri de Bourbon, prince de Condé, en 1573.

L'acte de fondation de ce prieuré (fol. 17) porte la date de 1170. — Ce ms. a appartenu à « l'abbé de Sencour, chanoine de Rouen. »

Recueil de pièces, manuscrites et imprimées, formé par le président Achille III DE HARLAY, relatives principalement à l'histoire religieuse, politique, administrative, diplomatique et littéraire des XVIe et XVIIe siècles. VIII.

Contient : Lettre d'Innocent XI ; « Observations sur l'Histoire du luthérianisme du P. Maimbourg » ; Extraits des Registres capitulaires de l'Église de Paris, 1654 ; Copies de pièces du XIIIe et du XIVe siècles relatives à différentes affaires ecclésiastiques ; Copie d'une lettre à Baluze sur un manuscrit chaldéen reçu du Levant par Colbert ; Sur la « Conférence de Cartage » ; Fragment orig . d'Ismaël Boulliau sur l'échéance du jour de Pâques ; « Observations sur un Traité de l'Usure fait par M. Poncet » ; « Oraison funèbre de M. de Candale par M. l'abbé Roquette, depuis évêque d'Autun » ; « Éclaircissement par M. Bernier sur le livre de Monsr de La Ville » pour la défense d'opinions de Descartes ; Mémoire pour la liberté de la Faculté de théologie de Paris ; Extraits impr. des Registres capitulaires de l'Église de Paris ; Sur la Visitation d'Angers ; Mémoires de procédure impr. relatifs à la Sainte-Chapelle ; Recueil de pièces mss et impr., bulles pontificales, lettres royales, etc., relatives à la Régale, 1198-1681 ; Établissement d'une Chambre royale à Metz, et extraits des Registres de cette Chambre royale, impr ; Lettre orig. de D. Godefroy, 1680 ; Pièces relatives à la principauté de Charleville ; Entrée de la reine de Suède Ulrique-Éléonore à Stockholm, 1680 ; Pièces impr. relatives à l'Hôpital général de Paris ; Ordonnances impr. du magistrat d'Amsterdam portant interdiction des carrosses dans ladite ville, en hollandais

Recueil de pièces, manuscrites et imprimées, formé par le président Achille III DE HARLAY, relatives principalement à l'histoire religieuse, politique, administrative, diplomatique et littéraire des XVIe et XVIIe siècles. XXXI.

Contient : Pièces sur les Jésuites (f. 1), — sur les Frères Prêcheurs, impr. (f. 34), — sur la Sorbonne (f. 48) ; Pièces sur Descartes ; Extrait des Registres du Conseil d'État relatif à l'acquisition, pour la Bibliothèque du roi, d'une partie de la bibliothèque de Mazarin, 1668 ; « Epistola » R. Rapini, S. J., « ad... Cl. Pelterium », impr., 1684, in-8° ; Extraits de Registres du Parlement ; « Procédures faites... contre Antoine, comte de Shaftsbury », 1681 ; Sur la « Prévention » en Anjou ; Factums divers impr., affaire Bruant des Carrières ; Pièces relatives à la Compagnie des Indes orientales ; Factums impr., affaire Marcara Avachins ; Pièces relatives au commerce : « Avis sur le fait des ardoises », impr., 1683, in-4° ; Notes sur « Les édits et règlements des libraires, imprimeurs, relieurs et doreurs » ; Note sur le commerce des harengs

Recueil, formé de 1573 à 1578, d'extraits (généalogies, chartes, épitaphes, etc.) concernant l'histoire des familles de Lorraine, attribué à Nicolas Bousmard, chanoine de l'église de Verdun (d'après D. Calmet, Bibl. lorr., 165).

Contient : Épitaphes des Cordeliers de Neufchâteau ; Épitaphes de Bayon ; Épitaphes de l'abbaye de Beaupré ; Épitaphes de Magnières ; Épitaphes des Cordeliers de Mirecourt ; Épitaphes des Carmes de Besançon ; Épitaphes des Cordeliers de Besançon ; Épitaphes de Bourbonne ; Épitaphes de l'abbaye de Morimond ; Épitaphes de Beaufrémont ; Épitaphes de Remennecourt ; Copie abrégée de l'épitomé de Jean Daucy ; Extrait du Trésor de l'évêché de Verdun