The search for migraine genes: an overview of current knowledge

Migraine is a complex familial condition that imparts a significant burden on society. There is evidence for a role of genetic factors in migraine, and elucidating the genetic basis of this disabling condition remains the focus of much research. In this review we discuss results of genetic studies to date, from the discovery of the role of neural ion channel gene mutations in familial hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the more common forms of migraine. The success of FHM regarding discovery of genetic defects associated with the disorder remains elusive in common migraine, and causative genes have not yet been identified. Thus we suggest additional approaches for analysing the genetic basis of this disorder. The continuing search for migraine genes may aid in a greater understanding of the mechanisms that underlie the disorder and potentially lead to significant diagnostic and therapeutic applications. Received 16 December 2005; received after revision 9 October 2006; accepted 13 November 2006     

The karyotype and genome structure of the pirate perchAphredoderus sayanus (Aphredoderidae: Teleostei)

Summary The standard karyotype, genome size (DNA content), and genomic DNA base composition and distribution of the relict paracanthopterygian fish,Aphredoderus sayanus, were investigated. Several features of theA. sayanus genome appear to be derived rather than primitive conditions. These include a large number (at least 10 pairs) of bi-armed chromosomes, a low genome size, and high DNA asymmetry. This may indicate thatA. sayanus is not a typical paracanthopterygian fish in terms of its genome structure.     

基因组学:生命科学的系统化研究和生物世纪的科学革命

DNA(脱氧核糖核酸)是基因的“文字”，基因是生命的“语言”，生命的“剧本”用基因来编写。基因组学则是生命剧本的“导演”。DNA序列因此就成了舞台剧本。基因组学是一门大规模地、系统地研究物种全部基因和它们生物学意义和运动的学问。如今，我们正站在一个革命性的转折点上，也就是基因组学正处于生命科学的领导前沿。我们不该为此恐慌、怀疑甚或因而改变方向。获得一个物种的基本的基因组信息，比如基因的图谱及其在细胞中的产物，是我们了解该物种生物学意义的第一步。我们应该根据基础研究、经济效益和社会的需要来考虑测序日程上物种的先后次序。     

Embodied Odysseys: Relics of stories about journeys through past,present, and future

This paper argues that the heritage represented by a museum should be seen not just in its individual objects but also in the relationships between them. The Conservatoire Nationale des Arts et Métiers and the Science Museum in London, the earliest great European science museums, were deeply concerned with the relationship between science and practice. The foundation speeches of the Deutsches Museum emphasised the concern with both past and future. Such ancestry provided hard-to-escape templates within which collections were built up over the subsequent century and more. Thus the Science Museum’s biotechnology collection developed at the very end of the twentieth century and albeit based on detailed historical research reflects the same concerns with science–technology relations as could be seen in the 1876 Loan Exhibition which started off the Science Museum. The physical presence of such carefully-structured accumulations of objects could embody and reinforce the reality of such categories as pure and applied science.     

The history of science as the progress of the human spirit: The historiography of astronomy in the eighteenth century

In the eighteenth century, the historiography of astronomy was part of a wider discussion concerning the history of the human spirit. The concept of the human spirit was very popular among Enlightenment authors because it gave the history of human knowledge continuity, unity and meaning. Using this concept, scientists and historians of science such as Montucla, Lalande, Bailly and Laplace could present the history of astronomy in terms of a progress towards contemporary science that was slow and could be interrupted at times, but was still constant, regular, and necessary. In my paper I intend to explain how the originally philosophical concept of the human spirit was transferred to the history of astronomy. I also introduce the basic principles to which the development of the spirit is subject in astronomy, according to historians of astronomy. The third part of the paper describes how historians of astronomy took into account the effect of social and natural factors on the history of astronomy.     

The molecular role of the Rothmund-Thomson-, RAPADILINO- and Baller-Gerold-gene product, RECQL4: recent progress

The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome integrity in humans. Received 31 October 2006; received after revision 4 January 2007; accepted 5 February 2007     

The mode of antifungal action of plant, insect and human defensins

Defensins are small (~5 kDa), basic, cysteine-rich antimicrobial peptides that fulfill an important role in the innate immunity of their host by combating pathogenic invading micro-organisms. Defensins can inhibit the growth or virulence of microorganisms directly or can do so indirectly by enhancing the host's immune system. Because of their wide distribution in nature, defensins are believed to be ancient molecules with a common ancestor that arose more than a billion years ago. This review summarizes current knowledge concerning the mode of antifungal action of plant, insect and human defensins.     

The effect of isoforms of the cell polarity protein, human ASIP, on the cell cycle and Fas/FasL-mediated apoptosis in human hepatoma cells

Human ASIP (hASIP) is expressed as numerous alternative splicing isoforms and there is an atypical protein kinease C (aPKC) phosphorylation site in exon 17b of the encoded sequence. We have identified an important role for exon 17b in cancer cells. Our results showed that hASIP-sa and sb had different effects on cell growth and Fas/FasL-mediated apoptosis in BEL-7404 human hepatoma cells. Human ASIP-sa modified the S phase of the cell cycle and might stimulate cell proliferation. Growth inhibition by hASIP-a antisense oligonucleotide-confirmed the positive action of hASIP-sa. Compared with hASIP-sa, hASIP-sb accelerated Fas/FasL-induced apoptosis, examined by sub-G1 accumulation, chromatin condensation, nuclear fragmentation, PARP cleavage, caspase-8 degradation and mitochondria- regulated cell death. Treatment with aPKC inhibitor could enhance Fas/FasL-mediated apoptosis in hASIP-sa-overexpressing cells, suggesting that hASIP-sa and its interaction with aPKC might contribute to the malignant growth and the blocking of Fas/FasL-mediated apoptosis, while hASIP-sb might function as an antagonist of hASIP-sa.Received 24 March 2005; received after revision 31 May 2005; accepted 21 June 2005     

Forecasting price delay and future stock returns: The role of corporate social responsibility

This paper investigates the role of corporate social responsibility (CSR) performance in forecasting companys' stock prices and future returns. The forecasting analysis identifies a negative association between CSR performance and proxies of price delay. The negative CSR–delay association is weak for state‐owned enterprises (SOEs) because of their politically oriented motivation of CSR activities, but significantly strong for non‐SOEs. Furthermore, we find that forecasting delayed firms is expected to have higher future returns. In particular, the returns premium is most attributable to the CSR component of delay, compared with the non‐CSR component. Taken together, these results suggest that CSR performance plays a positive role in enhancing stock price efficiency, and a potential explanation is that CSR performance can be considered as additional information for equity predictions.     

The comparative biology of neuromelanin and lipofuscin in the human brain

Neuromelanin and lipofuscin are two pigments produced within the human brain that, until recently, were considered inert cellular waste products of little interest to neuroscience. Recent research has increased our understanding of the nature and interactions of these pigments with their cellular environment and suggests that these pigments may, indeed, influence cellular function. The physical appearance and distribution of the pigments within the human brain differ, but both accumulate in the aging brain and the pigments share some structural features. Lipofuscin accumulation has been implicated in postmitotic cell aging, while neuromelanin is suggested to function as an iron-regulatory molecule with possible protective functions within the cells which produce this pigment. This review presents comparative aspects of the biology of neuromelanin and lipofuscin, as well as a discussion of their hypothesized functions in brain and their possible roles in aging and neurodegenerative disease.     

The pharmacology of Parkinson's disease: Basic aspects and recent advances

Summary Basic aspects and recent advances in the understanding of the pharmacological mechanism of action of the clinically most used antiparkinson drugs are reviewed. Recent human and animal biochemical investigations clearly confirm and extend previous findings indicating that benserazide is much more potent than carbidopa as peripheral decarboxylase inhibitor. L-DOPA in combination with benserazide or carbidopa constitutes the best available therapy for Parkinson's disease (PD). To reduce peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) a slow-release formulation of L-DOPA in combination with benserazide or with benserazide plus catechol-O-methyltransferase inhibitors should be developed. In parkinsonian patients under long-term L-DOPA therapy monoamine oxidase inhibitors type B (MAO-B) e.g. (–)-deprenyl and firect dopamine receptor agonists (bromocriptine, lisuride, pergolide etc.), due to their L-DOPA-sparing effects, alleviate in some cases L-DOPA-induced side-effects e.g. dyskinesias and on-off phenomena. However, since (–)-deprenylm, due to its metabolism to (–)methamphetamine and (–)amphetamine, seem to have indirect sympathomimetic activity, new selective MAO-B inhibitors devoid of indirect sympathomimetic effects should be tested clinically to assess the functional role of pure MAO-B inhibition in the therapy of PD. The auxiliary therapy with direct dopmaine receptor agonists of the D-2 subtype represents another valid approach which should be further investigated in order to find novel dopamine agonists, less expensive than bromocriptine and strictly selective for D-2 receptor sites.     

How human and nature shake hands: The role of no-conspiracy in physical theories

No-conspiracy is the requirement that measurement settings should be probabilistically independent of the elements of reality responsible for the measurement outcomes. In this paper we investigate what role no-conspiracy generally plays in a physical theory; how it influences the semantical role of the event types of the theory; and how it relates to such other concepts as separability, compatibility, causality, locality and contextuality.     

The scorpine family of defensins: gene structure,alternative polyadenylation and fold recognition

Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens. This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource. Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins. From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1–4). Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3 untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals. The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification. Two large introns were found to be located within the 5 UTR and at the boundary of the mature peptide-coding region. Such a gene structure is distinct, when compared with other scorpion venom peptide genes. However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization. Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains. The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids. Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs.Received 5 April 2004; accepted 17 May 2004