The neuroligin and neurexin families: from structure to function at the synapse

Proper brain connectivity and neuronal transmission rely on the accurate assembly of neurotransmitter receptors, cell adhesion molecules and several other scaffolding and signaling proteins at synapses. Several new exciting findings point to an important role for the neuroligin family of adhesion molecules in synapse development and function. In this review, we summarize current knowledge of the structure of neuroligins and neurexins, their potential binding partners at the synapse. We also discuss their potential involvement in several aspects of synapse development, including induction, specificity and stabilization. The implication of neuroligins in cognitive disorders such as autism and mental retardation is also discussed. Received 6 February 2006; received after revision 17 March 2006; accepted 26 April 2006     

Science,politics and regulation: The trust-based approach to the demarcation problem

Drawing on literature on values in science and a case-study of UK cancer policy, this paper argues for a novel account of the demarcation project in terms of trustworthiness. The first part of the paper addresses the relationship between science, politics and demarcation. In 2010, the UK government decided to pay more for cancer drugs than for drugs for other diseases; in 2016, this Cancer Drugs Fund was reformed so as to lower the evidential standards for approving cancer drugs, rather than paying more for them. Are these two ways of treating cancer as “special” importantly different? This paper argues that, if we the argument from inductive risk seriously, they seem equivalent. This result provides further reason to doubt the notion of demarcating science from non-science. However, the second part of the paper complicates this story, arguing that considerations of epistemic trust might give us reasons to prefer epistemic communities centred around “broadly acceptable” standards, and which are “sociologically well-ordered”, regardless of inductive risk concerns. After developing these claims through the cancer case-study, the final section suggests how these concerns might motivate novel versions of the demarcation project.     

Disciplines,models, and computers: The path to computational quantum chemistry

Many disciplines and scientific fields have undergone a computational turn in the past several decades. This paper analyzes this sort of turn by investigating the case of computational quantum chemistry. The main claim is that the transformation from quantum to computational quantum chemistry involved changes in three dimensions. First, on the side of instrumentation, small computers and a networked infrastructure took over the lead from centralized mainframe architecture. Second, a new conception of computational modeling became feasible and assumed a crucial role. And third, the field of computational quantum chemistry became organized in a market-like fashion and this market is much bigger than the number of quantum theory experts. These claims will be substantiated by an investigation of the so-called density functional theory (DFT), the arguably pivotal theory in the turn to computational quantum chemistry around 1990.     

Number and measure: Hermann von Helmholtz at the crossroads of mathematics, physics, and psychology

In 1887 Helmholtz discussed the foundations of measurement in science as a last contribution to his philosophy of knowledge. This essay borrowed from earlier debates on the foundations of mathematics (Grassmann / Du Bois), on the possibility of quantitative psychology (Fechner / Kries, Wundt / Zeller), and on the meaning of temperature measurement (Maxwell, Mach). Late nineteenth-century scrutinisers of the foundations of mathematics (Dedekind, Cantor, Frege, Russell) made little of Helmholtz’s essay. Yet it inspired two mathematicians with an eye on physics (Poincaré and Hölder), and a few philosopher-physicists (Mach, Duhem, Campbell). The aim of the present paper is to situate Helmholtz’s contribution in this complex array of nineteenth-century philosophies of number, quantity, and measurement.     

The right neuron at the wrong place: biology of heterotopic neurons in cortical neuronal migration disorders, with special reference to associated pathologies

During the development of the neocortex, neurogenesis and neuronal differentiation occur in two separate locations. Thus neurons have to migrate through the future white matter. Arrested or excessive migration leads neurons to differentiate in a heterotopic position. Such neuronal migration disorders (NMDs) occur sporadically in normal development but are markedly increased as a consequence of genetic defects or after exposure to toxic drugs during the period of migration. Anatomofunctional studies in rodents with NMDs have revealed that heterotopic neurons form essentially normal afferent and efferentconnections, which has been interpreted as evidence that the connectionpattern of cortical neurons is specified prior to migration. In addition, recent data show that heterotopic neurons can be contacted by environmental, that is local, fibres that normally never innervate the neocortex. This dual connectivity leads heterotopias to form bridges between their environmental and original network. Such an abnormal pattern of connectivity could contribute to the pathophysiology of disorders associated with NMDs such as epilepsy. Received 16 December 1998; received after revision 5 February 1999; accepted 9 February 1999     

Science,sensitivity and the sociozoological scale: Constituting and complicating the human-animal boundary at the 1875 Royal Commission on Vivisection and beyond

Arnold Arluke and Clinton Sanders (1996) have argued that human societies index both humans and animals as belonging to particular rungs of the social hierarchy. They term this multispecies ranking the “sociozoological scale”. This paper will investigate how claims at the 1875 Royal Commission on Vivisection about the sensitivity of particular species and breeds not only reflected assumptions about human social hierarchy but also blurred the boundaries between the human and the animal in the process. It will further be shown how these claims were informed by 18th and 19th century humanitarianism, classism, scientific racism and evolutionary theory, and how these influences combined in claims-making about the relative capacity of particular animals to sense pain and ethical duties towards them that followed from this sensitivity. Particular attention will be given to the opposing efforts of commissioners Thomas Henry Huxley and Richard Holt Hutton to demarcate human and animal sensitivity and exempt companion animals from vivisection respectively. The paper concludes by considering the sociozoological orders constituted by the 1876 Cruelty to Animals Act, particularly through its focus on calculating pain, and the legacy and limitations of this constitution.     

Structure-activity relationship of the cardenolide,with special reference to the substituents and configurations at C-14 and C-15

Zusammenfassung Es wurden die kardiotonischen Wirkungen sechs neuer Derivate von 14-Deoxy-14H-digitoxigenin und 14-Deoxy-14-chloro-digitoxigenin auf das isolierte Froschherz untersucht, sowie die Beziehungen zwischen deren chemischen Strukturen und Wirkungen diskutiert.

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This study was supported by a research grant (No. 78 7012) from the Ministry of Education, Japan, and by a Grant-in-Aid from Tokyo Biochemical Research Foundation.