Nerve cell differentiation in hydra requires two signals

Endogenous signals controlling nerve cell commitment in hydra were investigated using an assay for committed nerve precursors. Extracts of hydra tissue were prepared and tested for their ability to induce nerve cell commitment. The active component in such extracts was identified as a neuropeptide, the head activator [H. C. Schaller and H. Bodenmüller (1981) Proc. Natl. Acad. Sci. USA 78, 7000–7004], based on its chromatographic properties and reaction with anti-head activator antibody. In addition, synthetic head activator (10−13–10−11 M) was shown to cause nerve cell commitment. Additional experiments demonstrated that committed nerve precursors require a second signal to differentiate nerve cells. Committed precursors induced by treatment of hydra with head activator do not differentiate in whole hydra; but do differentiate when pieces of treated tissue are explanted or when whole animals are simply injured with transverse cuts. The injury stimulus is long-lived. It cannot be replaced with head activator (10−12–10−10 M) but is contained in a methanol extract of hydra tissue

Nerve commitment in Hydra. II. Localization of commitment in S phase

The kinetics of nerve differentiation were investigated during head regeneration in Hydra. In particular the cell cycle parameters of stem cells undergoing nerve commitment were determined. Head regeneration induces extensive nerve commitment localized at the regenerating tip (G. Venugopal and C. David, 1981, Develop. Biol.83, 353–360). The appearance of committed nerve precursors is followed 12 hr later by the appearance of newly differentiated nerves. Under these conditions the time from the end of S phase to nerve differentiation is about 9 hr and the time from the beginning of S phase to nerve differentiation is about 18 hr. Thus nerve commitment occurs in mid- to late S phase of the stem cell precursor

Ligand-guided homology modeling drives identification of novel histamine H3 receptor ligands

In this study, we report a ligand-guided homology modeling approach allowing the analysis of relevant binding site residue conformations and the identification of two novel histamine H3 receptor ligands with binding affinity in the nanomolar range. The newly developed method is based on exploiting an essential charge interaction characteristic for aminergic G-protein coupled receptors for ranking 3D receptor models appropriate for the discovery of novel compounds through virtual screening

Gene Family Histories: Theory and Algorithms

Detailed gene family histories and reconciliations with species trees are a prerequisite for studying associations between genetic and phenotypic innovations. Even though the true evolutionary scenarios are usually unknown, they impose certain constraints on the mathematical structure of data obtained from simple yes/no questions in pairwise comparisons of gene sequences. Recent advances in this field have led to the development of methods for reconstructing (aspects of) the scenarios on the basis of such relation data, which can most naturally be represented by graphs on the set of considered genes. We provide here novel characterizations of best match graphs (BMGs) which capture the notion of (reciprocal) best hits based on sequence similarities. BMGs provide the basis for the detection of orthologous genes (genes that diverged after a speciation event). There are two main sources of error in pipelines for orthology inference based on BMGs. Firstly, measurement errors in the estimation of best matches from sequence similarity in general lead to violations of the characteristic properties of BMGs. The second issue concerns the reconstruction of the orthology relation from a BMG. We show how to correct estimated BMG to mathematically valid ones and how much information about orthologs is contained in BMGs. We then discuss implicit methods for horizontal gene transfer (HGT) inference that focus on pairs of genes that have diverged only after the divergence of the two species in which the genes reside. This situation defines the edge set of an undirected graph, the later-divergence-time (LDT) graph. We explore the mathematical structure of LDT graphs and show how much information about all HGT events is contained in such LDT graphs

A technique for shape optimization of ducted fans

Ducted fans have found renewed interest particularly in the field of micro aerial vehicles. The complex flow interactions between the rotor, shroud and nacelle hinder the design of optimal lifting duct shapes. Further, the optimum duct shape changes with freestream velocity and rotor configuration. Analytic equations are insufficient to model and predict the performance of ducted fans, yet general CFD solvers are too slow to be used for optimization. For this research, a genetic algorithm is coupled with a simplified CFD solver based on a momentum source rotor model, creating an efficient shape optimization technique for ducted fan systems. The performance gains of the genetic algorithm are documented and the optimum duct shape for several configurations are presented as proof of concept

Gravity's Relentless Pull: An interactive, multimedia website about black holes for Education and Public Outreach

We have created a website, called "Black Holes: Gravity's Relentless Pull", which explains the physics and astronomy of black holes for a general audience. The site emphasizes user participation and is rich in animations and astronomical imagery. It won the top prize of the 2005 Pirelli INTERNETional Awards competition for the best communication of science and technology using the internet. This article provides a brief overview of the site. The site starts with an opening animation that introduces the basic concept of a black hole. The user is then invited to embark on a journey from a backyard view of the night sky to a personal encounter with a singularity. This journey proceeds through three modules, which allow the user to: find black holes in the night sky; travel to a black hole in an animated starship; and explore a black hole from up close. There are also five "experiments" that allow the user to: create a black hole; orbit around a black hole; weigh a black hole; drop a clock into a black hole; or fall into a black hole. The modules and experiments offer goal-based scenarios tailored for novices and children. The site also contains an encyclopedia of frequently asked questions and a detailed glossary that are targeted more at experts and adults. The overall result is a website where scientific knowledge, learning theory, and fun converge. Despite its focus on black holes, the site also teaches many other concepts of physics, astronomy and scientific thought. The site aims to instill an appreciation for learning and an interest in science, especially in the younger users. It can be used as an aid in teaching introductory astronomy at the undergraduate level.Comment: STScI Newsletter, 2006, vol. 23, number 2, in press; 5 pages and 2 figures. The black hole website described in this article is located at http://hubblesite.org/go/blackholes/ . We welcome all feedback and suggestions, which can be submitted through the "Contact Us" button of the sit

Putative intermediates in the nerve cell differentiation pathway in hydra have properties of multipotent stem cells

We have investigated the properties of nerve cell precursors in hydra by analyzing the differentiation and proliferation capacity of interstitial cells in the peduncle of Hydra oligactis, which is a region of active nerve cell differentiation. Our results indicate that about 50% of the interstitial cells in the peduncle can grow rapidly and also give rise to nematocyte precursors when transplanted into a gastric environment. If these cells were committed nerve cell precursors, one would not expect them to differentiate into nematocytes nor to proliferate apparently without limit. Therefore we conclude that cycling interstitial cells in peduncles are not intermediates in the nerve cell differentiation pathway but are stem cells. The remaining interstitial cells in the peduncle are in G1 and have the properties of committed nerve cell precursors (Holstein and David, 1986). Thus, the interstitial cell population in the peduncle contains both stem cells and noncycling nerve precursors. The presence of stem cells in this region makes it likely that these cells are the immediate targets of signals which give rise to nerve cells

PyRod Enables Rational Homology Model‐based Virtual Screening Against MCHR1

Several encouraging pre‐clinical results highlight the melanin‐concentrating hormone receptor 1 (MCHR1) as promising target for anti‐obesity drug development. Currently however, experimentally resolved structures of MCHR1 are not available, which complicates rational drug design campaigns. In this study, we aimed at developing accurate, homologymodel‐based 3D pharmacophores against MCHR1. We show that traditional approaches involving docking of known active small molecules are hindered by the flexibility of binding pocket residues. Instead, we derived three‐dimensional pharmacophores from molecular dynamics simulations by employing our novel open‐source software PyRod. In a retrospective evaluation, the generated 3D pharmacophores were highly predictive returning up to 35 % of active molecules and showing an early enrichment (EF1) of up to 27.6. Furthermore, PyRod pharmacophores demonstrate higher sensitivity than ligand‐based pharmacophores and deliver structural insights, which are key to rational lead optimization

Nerve commitment in Hydra. I. Role of morphogenetic signals

The kinetics of nerve commitment during head regeneration in Hydra were investigated using a newly developed assay for committed cells. Committed nerve precursors were assayed by their ability to continue nerve differentiation following explanation of small pieces of tissue. Committed nerve precursors appear at the site of regeneration within 6 hr after cutting and increase rapidly. The increase is localized to the site of regeneration and does not occur at proximal sites in the body column of the regenerate. The increase is delayed about 8–12 hr when regeneration occurs at sites lower in the body column. The results show, furthermore, that redistribution of committed precursors does not play a major role in the pattern of nerve differentiation during regeneration. Since the increase in committed nerves coincides with the increase in morphogenetic potential of the regenerating tissue, the results strengthen the idea that morphogenetic signals are involved directly in the control of nerve commitment in Hydra