Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects.

All-trans-retinoic acid causes striking digit pattern changes when it is continuously released from a bead implanted in the anterior margin of an early chick wing bud. In addition to the normal set of digits (234), extra digits form in a mirror-symmetrical arrangement, creating digit patterns such as a 432234. These retinoic acid-induced pattern duplications closely mimic those found after grafts of polarizing region cells to the same positions with regard to dose-response, timing, and positional effects. To elucidate the mechanism by which retinoic acid induces these pattern duplications, we have studied the temporal and spatial distribution of all-trans-retinoic acid and its potent analogue TTNPB in these limb buds. We find that the induction process is biphasic: there is an 8-h lag phase followed by a 6-h duplication phase, during which additional digits are irreversibly specified in the sequence digit 2, digit 3, digit 4. On average, formation of each digit seems to require between 1 and 2 h. The tissue concentrations, metabolic pattern, and spatial distribution of all-trans-retinoic acid and TTNPB in the limb rapidly reach a steady state, in which the continuous release of the retinoid is balanced by loss from metabolism and blood circulation. Pulse-chase experiments reveal that the half-time of clearance from the bud is 20 min for all-trans-retinoic acid and 80 min for TTNPB. Manipulations that change the experimentally induced steep concentration gradient of TTNPB suggest that a graded distribution of retinoid concentrations across the limb is required during the duplication phase to induce changes in the digit pattern. The extensive similarities between results obtained with retinoids and with polarizing region grafts raise the possibility that retinoic acid serves as a natural "morphogen" in the limb

Bubble statistics and positioning in superhelically stressed DNA

We present a general framework to study the thermodynamic denaturation of double-stranded DNA under superhelical stress. We report calculations of position- and size-dependent opening probabilities for bubbles along the sequence. Our results are obtained from transfer-matrix solutions of the Zimm-Bragg model for unconstrained DNA and of a self-consistent linearization of the Benham model for superhelical DNA. The numerical efficiency of our method allows for the analysis of entire genomes and of random sequences of corresponding length ($10^6-10^9$ base pairs). We show that, at physiological conditions, opening in superhelical DNA is strongly cooperative with average bubble sizes of $10^2-10^3$ base pairs (bp), and orders of magnitude higher than in unconstrained DNA. In heterogeneous sequences, the average degree of base-pair opening is self-averaging, while bubble localization and statistics are dominated by sequence disorder. Compared to random sequences with identical GC-content, genomic DNA has a significantly increased probability to open large bubbles under superhelical stress. These bubbles are frequently located directly upstream of transcription start sites.Comment: to be appeared in Physical Review

A knowledge-based approach to VLSI-design in an open CAD-environment

A knowledge-based approach is suggested to assist a designer in the increasingly complex task of generating VLSI-chips from abstract, high-level specifications of the system. The complexity of designing VLSI-circuits has reached a level where computer-based assistance has become indispensable. Not all of the design tasks allow for algorithmic solutions. AI technique can be used, in order to support the designer with computer-aided tools for tasks not suited for algorithmic approaches. The approach described in this paper is based upon the underlying characteristics of VLSI design processes in general, comprising all stages of the design. A universal model is presented, accompanied with a recording method for the acquisition of design knowledge - strategic and task-specific - in terms of the design actions involved and their effects on the design itself. This method is illustrated by a simple design example: the implementation of the logical EXOR-component. Finally suggestions are made for obtaining a universally usable architecture of a knowledge-based system for VLSI-design

Conservation Strategies for West Indian Rock Iguanas (Genus Cyclura): Current Efforts and Future Directions

As a result of habitat loss and the negative impact of introduced mammalian predators and competitors, West Indian Rock Iguanas (genus Cyclura) are among the most endangered lizards in the world. Because they are important seed dispersers for native plants, their loss has serious ecological consequences for dry tropical forest and scrub habitats. Six of the nine species of Rock Iguanas are considered critically endangered by the IUCN (the World Conservation Union), with C. collei and C. pinguis numbering only a few hundred individuals in the wild and C. lewisi fewer than 25 individuals. Conservation recommendations include further research to better understand population dynamics and ecological requirements, establishment of new protected areas and stronger enforcement within existing ones, control programs for introduced species, captive breeding and headstarting where appropriate, and public education at the local, national, and international levels

Ribosome recycling induces optimal translation rate at low ribosomal availability

Funding statement The authors thank BBSRC (BB/F00513/X1, BB/I020926/1 and DTG) and SULSA for funding. Acknowledgement The authors thank R. Allen, L. Ciandrini, B. Gorgoni and P. Greulich for very helpful discussions and careful reading of the manuscript.Peer reviewedPublisher PD

Conservation Strategies for West Indian Rock Iguanas (Genus Cyclura): Current Efforts and Future Directions

As a result of habitat loss and the negative impact of introduced mammalian predators and competitors, West Indian Rock Iguanas (genus Cyclura) are among the most endangered lizards in the world. Because they are important seed dispersers for native plants, their loss has serious ecological consequences for dry tropical forest and scrub habitats. Six of the nine species of Rock Iguanas are considered critically endangered by the IUCN (the World Conservation Union), with C. collei and C. pinguis numbering only a few hundred individuals in the wild and C. lewisi fewer than 25 individuals. Conservation recommendations include further research to better understand population dynamics and ecological requirements, establishment of new protected areas and stronger enforcement within existing ones, control programs for introduced species, captive breeding and headstarting where appropriate, and public education at the local, national, and international levels

Effective Medium Theory of Filamentous Triangular Lattice

We present an effective medium theory that includes bending as well as stretching forces, and we use it to calculate mechanical response of a diluted filamentous triangular lattice. In this lattice, bonds are central-force springs, and there are bending forces between neighboring bonds on the same filament. We investigate the diluted lattice in which each bond is present with a probability $p$. We find a rigidity threshold $p_b$ which has the same value for all positive bending rigidity and a crossover characterizing bending-, stretching-, and bend-stretch coupled elastic regimes controlled by the central-force rigidity percolation point at $p_{\textrm{CF}} \simeq 2/3$ of the lattice when fiber bending rigidity vanishes.Comment: 15 pages, 9 figure

Non-equilibrium mechanics and dynamics of motor activated gels

The mechanics of cells is strongly affected by molecular motors that generate forces in the cellular cytoskeleton. We develop a model for cytoskeletal networks driven out of equilibrium by molecular motors exerting transient contractile stresses. Using this model we show how motor activity can dramatically increase the network's bulk elastic moduli. We also show how motor binding kinetics naturally leads to enhanced low-frequency stress fluctuations that result in non-equilibrium diffusive motion within an elastic network, as seen in recent \emph{in vitro} and \emph{in vivo} experiments.Comment: 21 pages, 8 figure