Optimal Initial Public O¤ering design with aftermarket trading.

We characterize the optimal pricing and allocation of shares in the presence of distinct adverse selection problems. Some investors have private information at the time of the IPO and sell their shares in the after-market upon facing liquidity needs. Others learn their private interest in the after-market, and sell their shares strategically. The optimal mechanism trades-o¤ informational rents and rents to strategic traders. Flipping facilitates truthful information revelation. When liquidity needs are likely, it is optimal to allocate all shares to investors informed at the IPO stage. Otherwise, some shares are allocated to those who trade strategically in the after-market.

Optimal Initial Public Offering design with aftermarket trading

We characterize the optimal pricing and allocation of shares in the presence of distinct adverse selection problems. Some investors have private information at the time of the IPO and sell their shares in the after-market upon facing liquidity needs. Others learn their private interest in the after-market, and sell their shares strategically. The optimal mechanism trades-off informational rents and rents to strategic traders. Flipping facilitates truthful information revelation. When liquidity needs are likely, it is optimal to allocate all shares to investors informed at the IPO stage. Otherwise, some shares are allocated to those who trade strategically in the after-market

Clonage positionnel de gènes prédisposant aux anomalies congénitales majeures dans l'espèce porcine

Les anomalies congénitales sont définies comme des défauts de structure ou de fonction présents à la naissance. Chez le porc, les anomalies les plus fréquentes sont de type urogénital (hernie inguino-scrotale congénitale, cryptorchidie et intersexualité) et représentent un problème majeur pour l'industrie porcine (pertes économiques, atteinte au bien être des animaux). Les études ayant montré qu'une part de leur déterminisme était génétique, l'identification des gènes sous-jacents est devenue une priorité pour la filière porcine. Les outils récents de génomique offrent la possibilité de rechercher, à l'échelle du génome, des régions chromosomiques associées à un caractère. Des analyses TDT (Transmission Disequilibrium Test) ont été réalisées à partir d'un dispositif de 200 familles nucléaires de descendants atteints, et ont permis d'identifier deux régions significativement associées aux maladies : une région localisée en extrémité du chromosome X, significative pour les trois maladies étudiées, et une région sur le chromosome 12 associée à l'intersexualité. D'autres régions suggestives ont également été mises en évidence pour la hernie et la cryptorchidie. Des travaux de cartographie physique et génétique sur le chromosome X ont montré que le signal significatif était localisé sur la région pseudo-autosomale porcine et qu'il correspondait à un biais de l'analyse, dû au mode de ségrégation très particulier de la région. L'absence de recombinaison a également été observée pour un tiers du chromosome X, riche en motifs répétés. La région du chromosome 12 associée à l'intersexualité est une excellente région candidate car un seul gène y est annoté et correspond à un des acteurs majeurs de la différenciation sexuelle chez le mâle. La cartographie fine de la région n'a pas permis la détection de mutation causale ou de CNV (Copie Number Variation) mais son implication dans le déterminisme de l'intersexualité a été confirmée. Les loci identifiés pour les trois principales anomalies congénitales permettront de prévenir leur apparition dans les élevages porcins par sélection assistée par marqueurs. De plus, ces résultats apportent des données nouvelles en génétique humaine.Congenital anomalies are defined as physical or functional defects which are present at birth. The most defects occurring in piglets are urogenital (congenital inguino-scrotal hernia, cryptorchidism, intersexuality) and have a serious impact on the pig industry (severe economic loss and poor animal welfare). Studies have shown that a part of determinism is genetic, thus the identification of underlying genes is a priority for the pig industry. Recently the developed genomics tools offer possibilities to underlie pan-genomics chromosomal regions associated with traits. TDT analyses (Transmission Disequilibrium Test) performed on 200 nuclear families with affected offspring allowed to identify two significant regions associated with diseases: one on chromosome X for the three diseases and the other on chromosome 12 involved in intersexuality. Other suggestive regions are highlighted for hernia and cryptorchidism. Genetic and physical mapping of chromosome X subsequently showed that the significant signal was located on the porcine pseudo-autosomal region. Further analyses showed it was an analysis bias, due to the specific segregation of the region. Absence of recombination was observed for one third of chromosome X, enriched in repeated motifs. The region on chromosome 12 involved in intersexuality is an excellent candidate region because the only annotated gene in is one of the key genes for sexual differentiation in males. Fine mapping did not allow detection of a causative mutation or CNV (Copies Number Variation) but its implication was confirmed. For the three major defects, the loci identified can be used in pig breeding for effective marker assisted selection against diseases. Moreover, these results provide new data for human genetics

Impact of exposure to diesel exhaust during pregnancy on mammary gland development and milk composition in the rabbit

Exposure to fine-particulate air pollution is a major global health concern because it is associated with reduced birth weight and an increased risk of cardiovascular disease. Here we have investigated the potential for exposure to diesel exhaust during pregnancy to influence mammary gland development and milk composition. Female rabbits were therefore exposed by nose-only inhalation to either diluted diesel exhaust fumes (1 mg/m3) or clean air for 2h/day, 5 days/week, from the 3rd to the 27th days of pregnancy. On Day 28 of pregnancy, mammary glands were collected from twelve females (six controls and six diesel-exposed) and assessed for morphological and functional alterations. Milk samples were collected from eighteen dams (nine controls and nine diesel-exposed) during early (days 2 to 4) and established (days 13 to 16) lactation to verify the composition of fatty acids and major proteins and leptin levels. The mammary alveolar lumina contained numerous fat globules, and stearoyl CoA reductase expression was higher in mammary epithelia from diesel exhaust-exposed rabbits, which together suggested increased mammary lipid biosynthesis. Gas chromatography analysis of the composition of milk fatty acids revealed a sharp rise in the total fatty acid content, mainly due to monounsaturated fatty acids. Liquid chromatography-mass spectrometry analysis of milk samples enabled identification and quantification of the main rabbit milk proteins and their main phosphorylated isoforms, and revealed important changes to individual casein and whey protein contents and to their most phosphorylated isoforms during early lactation. Taken together, these findings suggest that repeated daily exposure to diesel exhaust fumes during pregnancy at urban pollution levels can influence lipid metabolism in the mammary gland and the lipid and protein composition of milk. As milk may contribute to metabolic programming, such alterations affecting milk composition should be taken into account from a public health perspective

Innovative models for collaboration and student mobility in Europe

This report is based on new developments in higher education and international collaboration as collected by EADTU's Task Force and Peer Learning Activity on Virtual Mobility. The result is a report on three types of collaboration mobility: physical, blended and online. Main parameters for innovative education and mobility formats are defined as well as basic principles of international course and curriculum design. Examples illustrate the complete opportunity space between fully face to face and fully online collaboration. They relate to mobility within single courses, exchange mobility (classical Erasmus), networked programmes and mobility windows and joint programmes with embedded mobility. Mobility offers opportunities to institutions to strengthen their programmes and to students to enrich their study. They benefit from an international learning experience or following courses not provided by their own institution. The report shows concrete mobility schemes used in the membership (and beyond). It underpins policies for international networking and delivers tools to organise innovative education and mobility formats

Secondary Structure and Glycosylation of Mucus Glycoproteins by Raman Spectroscopies

The major structural components of protective mucus hydrogels on mucosal surfaces are the secreted polymeric gel-forming mucins. The very high molecular weight and extensive O-glycosylation of gel-forming mucins, which are key to their viscoelastic properties, create problems when studying mucins using conventional biochemical/structural techniques. Thus, key structural information, such as the secondary structure of the various mucin subdomains, and glycosylation patterns along individual molecules, remains to be elucidated. Here, we utilized Raman spectroscopy, Raman optical activity (ROA), circular dichroism (CD), and tip-enhanced Raman spectroscopy (TERS) to study the structure of the secreted polymeric gel-forming mucin MUC5B. ROA indicated that the protein backbone of MUC5B is dominated by unordered conformation, which was found to originate from the heavily glycosylated central mucin domain by isolation of MUC5B O-glycan-rich regions. In sharp contrast, recombinant proteins of the N-terminal region of MUC5B (D1-D2-D′-D3 domains, NT5B), C-terminal region of MUC5B (D4-B-C-CK domains, CT5B) and the Cys-domain (within the central mucin domain of MUC5B) were found to be dominated by the β-sheet. Using these findings, we employed TERS, which combines the chemical specificity of Raman spectroscopy with the spatial resolution of atomic force microscopy to study the secondary structure along 90 nm of an individual MUC5B molecule. Interestingly, the molecule was found to contain a large amount of α-helix/unordered structures and many signatures of glycosylation, pointing to a highly O-glycosylated region on the mucin

Secondary Structure and Glycosylation of Mucus Glycoproteins by Raman Spectroscopies

The major structural components of protective mucus hydrogels on mucosal surfaces are the secreted polymeric gel-forming mucins. The very high molecular weight and extensive O-glycosylation of gel-forming mucins, which are key to their viscoelastic properties, create problems when studying mucins using conventional biochemical/structural techniques. Thus, key structural information, such as the secondary structure of the various mucin subdomains, and glycosylation patterns along individual molecules, remains to be elucidated. Here, we utilized Raman spectroscopy, Raman optical activity (ROA), circular dichroism (CD), and tip-enhanced Raman spectroscopy (TERS) to study the structure of the secreted polymeric gel-forming mucin MUC5B. ROA indicated that the protein backbone of MUC5B is dominated by unordered conformation, which was found to originate from the heavily glycosylated central mucin domain by isolation of MUC5B O-glycan-rich regions. In sharp contrast, recombinant proteins of the N-terminal region of MUC5B (D1-D2-D′-D3 domains, NT5B), C-terminal region of MUC5B (D4-B-C-CK domains, CT5B) and the Cys-domain (within the central mucin domain of MUC5B) were found to be dominated by the β-sheet. Using these findings, we employed TERS, which combines the chemical specificity of Raman spectroscopy with the spatial resolution of atomic force microscopy to study the secondary structure along 90 nm of an individual MUC5B molecule. Interestingly, the molecule was found to contain a large amount of α-helix/unordered structures and many signatures of glycosylation, pointing to a highly O-glycosylated region on the mucin

Protuberant Electrode Structures for New Retinal Implants

Focal stimulation of neural tissue is a challenge in retinal prosthetic devices in which the aim is to improve the spatial resolution of the stimulation and therefore increase the electrode density of the prosthetic devices. Our work intends to create a new implant able to enhance the focalisation of the stimulation signal through protuberant electrodes. These electrodes are micro fabricated on a soft polyimide substrate using classical metal electrodeposition techniques. Before proceeding with fabrication a FEM model of the electrode’s current density was done to select the best-performing structures and geometries in terms of local stimulation. Based on these models, several prototypes were fabricated and implanted in vivo into a rat’s eye to verify the adaptation to the retina tissue

Effect of maternal obesity and preconceptional weight loss on male and female offspring metabolism and olfactory performance in mice

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours

Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis.

Glutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer.This work was supported by funds from the following institutions: Agencia Estatal de Investigación/European Regional Development Fund, European Union (PGC2018-096244- B-I00, SAF2016-75442-R), Ministry of Science, Innovation and Universities of Spain, Spanish National Research Council—CSIC, Institut National de la Santé et de la Recherche Médicale —INSERM, Université de Bordeaux, Fondation pour la Recherche Médicale, the Conseil Régional d’Aquitaine, SIRIC-BRIO, Fondation ARC, and Institut Européen de Chimie et Biologie. C.B. was recipient of fellowships from the Minister of Higher Education, Research and Innovation (France) and the Fondation ARC (France). We thank Prof. Patricia Boya (Centro de Investigaciones Biologicas, Madrid, Spain) for kindly providing with the ATG5+/+ and ATG5−/− MEFs. We thank Prof. Benoit Viollet (Institute Cochin, Paris, France) for kindly providing with the AMPK+/+ and AMPK−/− MEFs, and the CA-AMPK plasmid