Role of estrogens in brain and behavioral development

Une même hormone peut exercer des effets différents sur le développement des caractéristiques de type femelle selon la période à laquelle elle est produite : l’œstradiol nous a ainsi dévoilé son double jeu, révélant à la fois des effets déféminisants prénataux pouvant s’exercer jusqu’5ème jour postnatal et des effets féminisants s’exerçant dès le 15ème jour postnatal. / A steroid hormone can have different effects on female characteristics development according to the period it is produced : estradiol has defeminizing effects on brain development until postnatal day 5, and feminizing effects from postnatal day 15

Pediatric eye exam for the primary care practitioner

Pediatric eye exam for the primary care practitione

Cut elimination in multifocused linear logic

We study cut elimination for a multifocused variant of full linear logic in the sequent calculus. The multifocused normal form of proofs yields problems that do not appear in a standard focused system, related to the constraints in grouping rule instances in focusing phases. We show that cut elimination can be performed in a sensible way even though the proof requires some specific lemmas to deal with multifocusing phases, and discuss the difficulties arising with cut elimination when considering normal forms of proofs in linear logic.Comment: In Proceedings LINEARITY 2014, arXiv:1502.0441

Female sexual behavior in mice is controlled by kisspeptin neurons.

Sexual behavior is essential for the survival of many species. In female rodents, mate preference and copulatory behavior depend on pheromones and are synchronized with ovulation to ensure reproductive success. The neural circuits driving this orchestration in the brain have, however, remained elusive. Here, we demonstrate that neurons controlling ovulation in the mammalian brain are at the core of a branching neural circuit governing both mate preference and copulatory behavior. We show that male odors detected in the vomeronasal organ activate kisspeptin neurons in female mice. Classical kisspeptin/Kiss1R signaling subsequently triggers olfactory-driven mate preference. In contrast, copulatory behavior is elicited by kisspeptin neurons in a parallel circuit independent of Kiss1R involving nitric oxide signaling. Consistent with this, we find that kisspeptin neurons impinge onto nitric oxide-synthesizing neurons in the ventromedial hypothalamus. Our data establish kisspeptin neurons as a central regulatory hub orchestrating sexual behavior in the female mouse brain

Normalization by Evaluation for Call-by-Push-Value and Polarized Lambda-Calculus

We observe that normalization by evaluation for simply-typed lambda-calculus with weak coproducts can be carried out in a weak bi-cartesian closed category of presheaves equipped with a monad that allows us to perform case distinction on neutral terms of sum type. The placement of the monad influences the normal forms we obtain: for instance, placing the monad on coproducts gives us eta-long beta-pi normal forms where pi refers to permutation of case distinctions out of elimination positions. We further observe that placing the monad on every coproduct is rather wasteful, and an optimal placement of the monad can be determined by considering polarized simple types inspired by focalization. Polarization classifies types into positive and negative, and it is sufficient to place the monad at the embedding of positive types into negative ones. We consider two calculi based on polarized types: pure call-by-push-value (CBPV) and polarized lambda-calculus, the natural deduction calculus corresponding to focalized sequent calculus. For these two calculi, we present algorithms for normalization by evaluation. We further discuss different implementations of the monad and their relation to existing normalization proofs for lambda-calculus with sums. Our developments have been partially formalized in the Agda proof assistant

Normalization by evaluation for call-by-push-value and polarized lambda calculus

We observe that normalization by evaluation for simply-typed lambda-calculus with weak coproducts can be carried out in a weak bi-cartesian closed category of presheaves equipped with a monad that allows us to perform case distinction on neutral terms of sum type. The placement of the monad influences the normal forms we obtain: for instance, placing the monad on coproducts gives us eta-long beta-pi normal forms where pi refers to permutation of case distinctions out of elimination positions. We further observe that placing the monad on every coproduct is rather wasteful, and an optimal placement of the monad can be determined by considering polarized simple types inspired by focalization. Polarization classifies types into positive and negative, and it is sufficient to place the monad at the embedding of positive types into negative ones. We consider two calculi based on polarized types: pure call-by-push-value (CBPV) and polarized lambda-calculus, the natural deduction calculus corresponding to focalized sequent calculus. For these two calculi, we present algorithms for normalization by evaluation. We further discuss different implementations of the monad and their relation to existing normalization proofs for lambda-calculus with sums. Our developments have been partially formalized in the Agda proof assistant

Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development

Background: CHD8 haploinsufficiency causes autism and macrocephaly with high penetrance in the human population. Chd8 heterozygous mice exhibit relatively subtle brain overgrowth and little gene expression changes in the embryonic neocortex. The purpose of this study was to generate new, sub-haploinsufficient Chd8 mouse models to allow us to identify and study the functions of CHD8 during embryonic cortical development. Methods: To examine the possibility that certain phenotypes may only appear at sub-heterozygous Chd8 levels in the mouse, we created an allelic series of Chd8-deficient mice to reduce CHD8 protein levels to approximately 35% (mild hypomorph), 10% (severe hypomorph) and 0% (neural-specific conditional knockout) of wildtype levels. We used RNA sequencing to compare transcriptional dysregulation, structural MRI and brain weight to investigate effects on brain size, and cell proliferation, differentiation and apoptosis markers in immunostaining assays to quantify changes in neural progenitor fate. Results: Mild Chd8 hypomorphs displayed significant postnatal lethality, with surviving animals exhibiting more pronounced brain hyperplasia than heterozygotes. Over 2000 genes were dysregulated in mild hypomorphs, including autism-associated neurodevelopmental and cell cycle genes. We identify increased proliferation of non-ventricular zone TBR2+ intermediate progenitors as one potential cause of brain hyperplasia in these mutants. Severe Chd8 hypomorphs displayed even greater transcriptional dysregulation, including evidence for p53 pathway upregulation. In contrast to mild hypomorphs, these mice displayed reduced brain size and increased apoptosis in the embryonic neocortex. Homozygous, conditional deletion of Chd8 in early neuronal progenitors resulted in pronounced brain hypoplasia, partly caused by p53 target gene derepression and apoptosis in the embryonic neocortex. Limitations Our findings identify an important role for the autism-associated factor CHD8 in controlling the proliferation of intermediate progenitors in the mouse neocortex. We propose that CHD8 has a similar function in human brain development, but studies on human cells are required to confirm this. Because many of our mouse mutants with reduced CHD8 function die shortly after birth, it is not possible to fully determine to what extent reduced CHD8 function results in autism-associated behaviours in mice. Conclusions: Together, these findings identify important, dosage-sensitive functions for CHD8 in p53 pathway repression, neurodevelopmental gene expression and neural progenitor fate in the embryonic neocortex. We conclude that brain development is acutely sensitive to reduced CHD8 expression and that the varying sensitivities of different progenitor populations and cellular processes to CHD8 dosage result in non-linear effects on gene transcription and brain growth. Shaun Hurley, Conor Mohan and Philipp Suetterlin have contributed equally to this work

Observed in-plume gaseous elemental mercury depletion suggests significant mercury scavenging by volcanic aerosols

Terrestrial volcanism is known to emit mercury (Hg) into the atmosphere. However, despite many years of investigation, its net impact on the atmospheric Hg budget remains insufficiently constrained, in part because the transformations of Hg in volcanic plumes as they age and mix with background air are poorly understood. Here we report the observation of complete gaseous elemental mercury (GEM) depletion events in dilute and moderately aged (& SIM;3-7 hours) volcanic plumes from Piton de la Fournaise on Reunion Island. While it has been suggested that co-emitted bromine could, once photochemically activated, deplete GEM in a volcanic plume, we measured low bromine concentrations in both the gas- and particle-phase and observed complete GEM depletion even before sunrise, ruling out a leading role of bromine chemistry here. Instead, we hypothesize that the GEM depletions were mainly caused by gas-particle interactions with sulfate-rich volcanic particles (mostly of submicron size), abundantly present in the dilute plume. We consider heterogeneous GEM oxidation and GEM uptake by particles as plausible manifestations of such a process and derive empirical rate constants. By extrapolation, we estimate that volcanic aerosols may scavenge 210 Mg y(-1) (67-480 Mg y(-1)) of Hg from the atmosphere globally, acting effectively as atmospheric mercury sink. While this estimate is subject to large uncertainties, it highlights that Hg transformations in aging volcanic plumes must be better understood to determine the net impact of volcanism on the atmospheric Hg budget and Hg deposition pathways

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Probing BFKL Dynamics in the Dijet Cross Section at Large Rapidity Intervals in ppbar Collisions at sqrt{s}=1800 and 630 GeV

Inclusive dijet production at large pseudorapidity intervals (delta_eta) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large delta_eta in ppbar collisions at sqrt{s}=1800 and 630 GeV using the DO detector. The partonic cross section increases strongly with the size of delta_eta. The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of a_{BFKL}(20GeV)=1.65+/-0.07.Comment: Published in Physical Review Letter