An inherited limb deformity created by insertional mutagenesis in a transgenic mouse

We have created an insertional mutation that leads to a severe defect in the pattern of limb formation in the developing mouse. The novel recessive mutation is phenotypically identical and non-complementary to two previously encountered limb deformity mutations, and is closely linked to a dominant mutation that gives rise to a related limb dysmorphism. The inserted element thus provides a molecular genetic link with the control of pattern formation in the mammalian embryo.     

Instrumentalizing Failure: Edison's Invention of the Carbon Microphone

For Thomas Edison, experiencing a failure did not mean that he had failed. Through an examination of the process that led to his invention of the carbon microphone, I argue that his positive approach to failure contributed both to his success as an inventor and to the functional success of his inventions. Edison's laboratory notebooks and legal testimony reveal that his seemingly erratic approach and reliance on trial and error methods in fact had a consistent direction and a rational basis, well suited to the under-determined problems he faced. The outcome of this process, the carbon microphone, contributed significantly to the commercial success of the telephone and remains in use today. Thomas Hughes has observed that nineteenth century inventors made use of the unexpected behaviour of their inventions as sources of novel phenomena to exploit in new inventions. This paper identifies other ways in which Edison made use of failure and proposes that, paradoxically, the success of technological artefacts can be determined by the thoroughness with which failure is pursued in their creation. It also notes a parallel between Edison's instrumentalizing of failure and the way in which recent philosophers of science have proposed that scientists should make use of error.     

Natural polyploidization within tetraploid and hexaploid populations of the desert shrub Atriplex confertifolia

Shadscale ( Atriplex confertifolia ) is a wind-pollinated dioecious shrub of western North America with an unusual development of apparently autoploid races, showing all even ploidy levels from 2x to 12x (base x = 9). Of these, tetraploid races are the most frequently encountered, with octoploids the next most common, and hexaploids being much less common. In this study, the occurrence of neopolyploid individuals within tetraploid and hexaploid populations of shadscale was examined at natural sites in order to investigate the pathways by which octoploids may be formed and to find a possible explanation for the predominance of octoploids over hexaploids. The frequencies of apparent neopolyploid individuals among adults and the frequencies of their backcrosses were tabulated, as was the occurrence of neopolyploidy among seeds of female plants from some of the same populations. The neopolyploids encountered in these surveys were almost exclusively those expected from unions involving single unreduced gametes. 6x presumed neopolyploid plants were observed in tetraploid populations at a frequency of 0.20%, and 6x seeds were observed at a frequency of 1.91%. Within examined hexaploid populations, 9x adults were not encountered, but 9x seeds were observed at a rate of 0.52%. Evidence was obtained for the operation of some postulated autoploid pathways for generation of octoploids, but these routes did not operate at rates comparable to those for the production of hexaploids. Although the question needs to be studied by genetic methods, the most probable reason for scarcity of hexaploids in nature appears to be that some tetraploid races are diploidized, which would result in irregularities of meiosis in their neohexaploids and a failure to form new races due to infertility and inviability. El “shadscale” ( Atriplex confertifolia ) es un arbusto dioico del oeste de Norteamérica polinizado por el viento que exhibe el desarrollo inusual de razas aparentemente poliploides, con todos los niveles pares de ploidía desde 2x hasta 12x (x base = 9). De éstos, los más comunes son los tetraploides y luego los octoploides. Los hexaploides son mucho menos comunes. En este estudio, examinamos la presencia de individuos neopoliploides entre poblaciones tetraploides y hexaploides del shadscale en sitios naturales para investigar los medios por los cuales se pueden formar los octoploides y para encontrar una posible explicación para el predominio de los octoploides sobre los hexaploides. Tabulamos la frecuencia de individuos aparentemente neopoliploides entre adultos y su descendencia retrocruzada, así como la presencia de neopoliploides entre semillas de las plantas femeninas de algunas de las mismas poblaciones. Los neopoliploides encontrados en estos muestreos fueron casi exclusivamente los que se esperarían de la unión de un gameto no reducido y un gameto reducido. Observamos plantas 6x presunta mente neopoliploides en poblaciones tetraploides con una frecuencia del 0.20%, o del 1.91% en las semillas. Entre las poblaciones examinadas de hexaploides, no encontramos adultos 9x, aunque los observamos con una frecuencia del 0.52% en las semillas. Obtuvimos evidencia de la operación de algunos procesos autoploides postulados para explicar la generación de octoploides, pero estos procesos no operan a frecuencias comparables a aquellas para la producción de hexaploides. Aunque es preciso investigar el tema mediante métodos genéticos, la causa más probable para la escasez de los hexaploides en entornos naturales parece ser que algunas razas tetraploides son diploidizadas, produciendo irregularidades meióticas en sus neohexaploides, los cuales no logran formar razas nuevas debido a su infertilidad o inviabilidad.     

数学索隐

数学是从哪里来的？它是早已存在着等待我们去发现的，还是人类在进步中把它制造出来的？柏拉图认为，数学概念确实在某种离奇而完美的现实中存在，这种完美的现实紧挨着宇宙的边缘。一个圆不只是一种观念，它是一种理想。我们这些不无缺陷的生物可以追求那种理想，但永远得不到它，倒不只是因为铅笔尖太粗。但是有这么一些人．他们说．数学只存在手旁观者的头脑平．它在与人类思维无关的地方并不存在，如同语言、音乐足球规则一样。它是人类想象的虚构物。自然的型式那么上面两种意见谁对？不错，在柏拉图主义者的观点中，有那种非常的诱惑…     

Symmetry in locomotor central pattern generators and animal gaits.

Animal locomotion is controlled, in part, by a central pattern generator (CPG), which is an intraspinal network of neurons capable of generating a rhythmic output. The spatio-temporal symmetries of the quadrupedal gaits walk, trot and pace lead to plausible assumptions about the symmetries of locomotor CPGs. These assumptions imply that the CPG of a quadruped should consist of eight nominally identical subcircuits, arranged in an essentially unique matter. Here we apply analogous arguments to myriapod CPGs. Analyses based on symmetry applied to these networks lead to testable predictions, including a distinction between primary and secondary gaits, the existence of a new primary gait called 'jump', and the occurrence of half-integer wave numbers in myriapod gaits. For bipeds, our analysis also predicts two gaits with the out-of-phase symmetry of the walk and two gaits with the in-phase symmetry of the hop. We present data that support each of these predictions. This work suggests that symmetry can be used to infer a plausible class of CPG network architectures from observed patterns of animal gaits.     

Radical Constructivism in Biology and Cognitive Science

This article addresses the issue of “objectivism vs constructivism” in two areas,biology and cognitive science, which areintermediate between the natural sciences suchas physics (where objectivism is dominant) andthe human and social sciences (whereconstructivism is widespread). The issues inbiology and in cognitive science are intimatelyrelated; in each of these twin areas, the “objectivism vs constructivism” issue isinterestingly and rather evenly balanced; as aresult, this issue engenders two contrastingparadigms, each of which has substantialspecific scientific content. The neo-Darwinianparadigm in biology is closely resonant withthe classical cognitivist paradigm in cognitivescience, and both of them are intrinsicallyobjectivist. The organismic paradigm inbiology, based on the concept of autopoiesis,is consonant with the paradigm of “enaction” incognitive science; the latter paradigms are bothprofoundly constructivist.In cognitive science, the objectivism vsconstructivism issue is internal to thescientific field itself and reflexivity isinescapable. At this level, strong ontologicalobjectivism is self-contradictory and thereforeuntenable. Radical constructivism isself-coherent; but it also rehabilitatesa weak form of objectivism as a pragmaticallyviable alternative. In conclusion, there is aneven-handed reciprocity between “objectivist”and “constructivist” perspectives. Finally, thearticle examines the consequences of thisconclusion for fields other than cognitivescience: biology; physics and the naturalsciences; and the human and social sciences.     

GPR39: a Zn<Superscript>2+</Superscript>-activated G protein-coupled receptor that regulates pancreatic,gastrointestinal and neuronal functions

GPR39 is a vertebrate G protein-coupled receptor related to the ghrelin/neurotensin receptor subfamily. The receptor is expressed in a range of tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in some regions of the brain. GPR39 was initially thought to be the cognitive receptor for the peptide hormone, obestatin. However, subsequent in vitro studies have failed to demonstrate binding of this peptide to the receptor. Zn²⁺ has been shown to be a potent stimulator of GPR39 activity via the Gα_q, Gα_12/13 and Gα_s pathways. The potency and specificity of Zn²⁺ in activating GPR39 suggest it to be a physiologically important agonist. GPR39 is now emerging as an important transducer of autocrine and paracrine Zn²⁺ signals, impacting upon cellular processes such as insulin secretion, gastric emptying, neurotransmission and epithelial repair. This review focuses on the molecular, structural and biological properties of GPR39 and its various physiological functions.