Serotonin mediated changes in corticotropin releasing factor mRNA expression and feeding behavior isolated to the hypothalamic paraventricular nuclei

Fenfluramine reduces hunger and promotes body weight loss by increasing central serotonin (5-HT) signaling. More recently, neuropeptides have been linked to the regulation of feeding behavior, metabolism and body weight. To examine possible interactions between 5-HT and neuropeptides in appetite control, fenfluramine (200 nmol/0.5 μl/side) was administered directly into the hypothalamic paraventricular nuclei (PVN) of male rats. Bilateral fenfluramine produced significant hypophagia and increased expression of PVN corticotropin releasing factor (CRF) mRNA and neuropeptide Y (NPY) mRNA in the arcuate nucleus within the first hour after drug administration. Fenfluramine\u27s effects on feeding behavior and mRNA expression were blocked by PVN injections of a 5-HT1–2 receptor antagonist, metergoline (15 nmol/0.5 μl/side). These data suggest that 5-HT neurons targeting hypothalamic paraventricular CRF neurons may participate in an appetite control circuit for reducing food intake

Surface diffusion coefficients by thermodynamic integration: Cu on Cu(100)

The rate of diffusion of a Cu adatom on the Cu(100) surface is calculated using thermodynamic integration within the transition state theory. The results are found to be in excellent agreement with the essentially exact values from molecular-dynamics simulations. The activation energy and related entropy are shown to be effectively independent of temperature, thus establishing the validity of the Arrhenius law over a wide range of temperatures. Our study demonstrates the equivalence of diffusion rates calculated using thermodynamic integration within the transition state theory and direct molecular-dynamics simulations.Comment: 4 pages (revtex), two figures (postscript

Comparative pelvic development of the axolotl (Ambystoma mexicanum) and the Australian lungfish (Neoceratodus forsteri): Conservation and innovation across the fish-tetrapod transition

Background: The fish-tetrapod transition was one of the major events in vertebrate evolution and was enabled by many morphological changes. Although the transformation of paired fish fins into tetrapod limbs has been a major topic of study in recent years, both from paleontological and comparative developmental perspectives, the interest has focused almost exclusively on the distal part of the appendage and in particular the origin of digits. Relatively little attention has been paid to the transformation of the pelvic girdle from a small unipartite structure to a large tripartite weight-bearing structure, allowing tetrapods to rely mostly on their hindlimbs for locomotion. In order to understand how the ischium and the ilium evolved and how the acetabulum was reoriented during this transition, growth series of the Australian lungfish Neoceratodus forsteri and the Mexican axolotl Ambystoma mexicanum were cleared and stained for cartilage and bone and immunostained for skeletal muscles. In order to understand the myological developmental data, hypotheses about the homologies of pelvic muscles in adults of Latimeria, Neoceratodus and Necturus were formulated based on descriptions from the literature of the coelacanth (Latimeria), the Australian Lungfish (Neoceratodus) and a salamander (Necturus).Results: In the axolotl and the lungfish, the chondrification of the pelvic girdle starts at the acetabula and progresses anteriorly in the lungfish and anteriorly and posteriorly in the salamander. The ilium develops by extending dorsally to meet and connect to the sacral rib in the axolotl. Homologous muscles develop in the same order with the hypaxial musculature developing first, followed by the deep, then the superficial pelvic musculature.Conclusions: Development of the pelvic endoskeleton and musculature is very similar in Neoceratodus and Ambystoma. If the acetabulum is seen as being a fixed landmark, the evolution of the ischium only required pubic pre-chondrogenic cells to migrate posteriorly. It is hypothesized that the iliac process or ridge present in most tetrapodomorph fish is the precursor to the tetrapod ilium and that its evolution mimicked its development in modern salamanders

Diffusion of Pt dimers on Pt(111)

We report the results of a density-functional study of the diffusion of Pt dimers on the (111) surface of Pt. The calculated activation energy of 0.37 eV is in {\em exact} agreement with the recent experiment of Kyuno {\em et al.} \protect{[}Surf. Sci. {\bf 397}, 191 (1998)\protect{]}. Our calculations establish that the dimers are mobile at temperatures of interest for adatom diffusion, and thus contribute to mass transport. They also indicate that the diffusion path for dimers consists of a sequence of one-atom and (concerted) two-atom jumps.Comment: Pour pages postscript formatted, including one figure; submitted to Physical Review B; other papers of interest can be found at url http://www.centrcn.umontreal.ca/~lewi

The Knowledge Object Reference Ontology (KORO): A formalism to support management and sharing of computable biomedical knowledge for learning health systems

IntroductionHealth systems are challenged by care underutilization, overutilization, disparities, and related harms. One problem is a multiyear latency between discovery of new best practice knowledge and its widespread adoption. Decreasing this latency requires new capabilities to better manage and more rapidly share biomedical knowledge in computable forms. Knowledge objects package machineâ executable knowledge resources in a way that easily enables knowledge as a service. To help improve knowledge management and accelerate knowledge sharing, the Knowledge Object Reference Ontology (KORO) defines what knowledge objects are in a formal way.MethodsDevelopment of KORO began with identification of terms for classes of entities and for properties. Next, we established a taxonomical hierarchy of classes for knowledge objects and their parts. Development continued by relating these parts via formally defined properties. We evaluated the logical consistency of KORO and used it to answer several competency questions about parthood. We also applied it to guide knowledge object implementation.ResultsAs a realist ontology, KORO defines what knowledge objects are and provides details about the parts they have and the roles they play. KORO provides sufficient logic to answer several basic but important questions about knowledge objects competently. KORO directly supports creators of knowledge objects by providing a formal model for these objects.ConclusionKORO provides a formal, logically consistent ontology about knowledge objects and their parts. It exists to help make computable biomedical knowledge findable, accessible, interoperable, and reusable. KORO is currently being used to further develop and improve computable knowledge infrastructure for learning health systems.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143591/1/lrh210054_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143591/2/lrh210054.pd

Stable and Metastable Structures of Cobalt on Cu(001): An ab initio Study

We report results of density-functional theory calculations on the structural, magnetic, and electronic properties of (1x1)-structures of Co on Cu(001) for coverages up to two monolayers. In particular we discuss the tendency towards phase separation in Co islands and the possibility of segregation of Cu on top of the Co-film. A sandwich structure consisting of a bilayer Co-film covered by 1ML of Cu is found to be the lowest-energy configuration. We also discuss a bilayer c(2x2)-alloy which may form due to kinetic reasons, or be stabilized at strained surface regions. Furthermore, we study the influence of magnetism on the various structures and, e.g., find that Co adlayers induce a weak spin-density wave in the copper substrate.Comment: 11 pages including 4 figures. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Self-diffusion of adatoms, dimers, and vacancies on Cu(100)

We use ab initio static relaxation methods and semi-empirical molecular-dynamics simulations to investigate the energetics and dynamics of the diffusion of adatoms, dimers, and vacancies on Cu(100). It is found that the dynamical energy barriers for diffusion are well approximated by the static, 0 K barriers and that prefactors do not depend sensitively on the species undergoing diffusion. The ab initio barriers are observed to be significantly lower when calculated within the generalized-gradient approximation (GGA) rather than in the local-density approximation (LDA). Our calculations predict that surface diffusion should proceed primarily via the diffusion of vacancies. Adatoms are found to migrate most easily via a jump mechanism. This is the case, also, of dimers, even though the corresponding barrier is slightly larger than it is for adatoms. We observe, further, that dimers diffuse more readily than they can dissociate. Our results are discussed in the context of recent submonolayer growth experiments of Cu(100).Comment: Submitted to the Physical Review B; 15 pages including postscript figures; see also http://www.centrcn.umontreal.ca/~lewi

Anisotropy of Growth of the Close-Packed Surfaces of Silver

The growth morphology of clean silver exhibits a profound anisotropy: The growing surface of Ag(111) is typically very rough while that of Ag(100) is smooth and flat. This serious and important difference is unexpected, not understood, and hitherto not observed for any other metal. Using density functional theory calculations of self-diffusion on flat and stepped Ag(100) we find, for example, that at flat regions a hopping mechanism is favored, while across step edges diffusion proceeds by an exchange process. The calculated microscopic parameters explain the experimentally reported growth properties.Comment: RevTeX, 4 pages, 3 figures in uufiles form, to appear in Phys. Rev. Let