bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression Patterns in Ovarian Carcinomas
Authors: Schaner Marci E. , Ross Douglas T. , Ciaravino Giuseppe , Sørlie Therese , Troyanskaya Olga , Diehn Maximilian , Wang Yan C. , Duran George E. , Sikic Thomas L. , Caldeira Sandra , Skomedal Hanne , Tu I-Ping , Hernandez-Boussard Tina , Johnson Steven W. , O'Dwyer Peter J. , Fero Michael J. , Kristensen Gunnar B. , Børresen-Dale Anne-Lise , Hastie Trevor , Tibshirani Robert , van de Rijn Matt , Teng Nelson N. , Longacre Teri A. , Botstein David , Brown Patrick O. , Sikic Branimir I.
Published: September 2003

We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.
Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells
Authors: Caporali Simona , Imai Manami , Altucci Lucia , Cancemi Massimo , Caristi Silvana , Cicatiello Luigi , Matarese Filomena , Penta Roberta , Sarkar Dipak K. , Bresciani Francesco , Weisz Alessandro
Published: September 2003

Estrogens control cell growth and viability in target cells via an interplay of genomic and extragenomic pathways not yet elucidated. Here, we show evidence that cell proliferation and survival are differentially regulated by estrogen in rat pituitary tumor PR1 cells. Pico- to femtomolar concentrations of 17β-estradiol (E2) are sufficient to foster PR1 cell proliferation, whereas nanomolar concentrations of the same are needed to prevent cell death that occurs at a high rate in these cells in the absence of hormone. Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations. Similarly, the pure antiestrogen ICI 182,780 inhibits estrogen response element-dependent trans-activation and cell death more effectively than cyclin-cdk activity, G1-S transition, or DNA synthesis rate. In antiestrogen-treated and/or estrogen-deprived cells, death is due predominantly to apoptosis. Estrogen-induced cell survival, but not E2-dependent cell cycle progression, can be prevented by an inhibitor of c-Src kinase or by blockade of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway. These data indicate the coexistence of two distinguishable estrogen signaling pathways in PR1 cells, characterized by different functions and sensitivity to hormones and antihormones.
Interaction between a Ras and a Rho GTPase Couples Selection of a Growth Site to the Development of Cell Polarity in Yeast
Authors: Kozminski Keith G. , Beven Laure , Angerman Elizabeth , Tong Amy Hin Yan , Boone Charles , Park Hay-Oak
Published: September 2003

Polarized cell growth requires the coupling of a defined spatial site on the cell cortex to the apparatus that directs the establishment of cell polarity. In the budding yeast Saccharomyces cerevisiae, the Ras-family GTPase Rsr1p/Bud1p and its regulators select the proper site for bud emergence on the cell cortex. The Rho-family GTPase Cdc42p and its associated proteins then establish an axis of polarized growth by triggering an asymmetric organization of the actin cytoskeleton and secretory apparatus at the selected bud site. We explored whether a direct linkage exists between the Rsr1p/Bud1p and Cdc42p GTPases. Here we show specific genetic interactions between RSR1/BUD1 and particular cdc42 mutants defective in polarity establishment. We also show that Cdc42p coimmunoprecipitated with Rsr1p/Bud1p from yeast extracts. In vitro studies indicated a direct interaction between Rsr1p/Bud1p and Cdc42p, which was enhanced by Cdc24p, a guanine nucleotide exchange factor for Cdc42p. Our findings suggest that Cdc42p interacts directly with Rsr1p/Bud1p in vivo, providing a novel mechanism by which direct contact between a Ras-family GTPase and a Rho-family GTPase links the selection of a growth site to polarity establishment.
Requirement for Neo1p in Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum
Authors: Hua Zhaolin , Graham Todd R.
Published: September 2003

Neo1p from Saccharomyces cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family. We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin. Here, we present evidence that epitope-tagged Neo1p localizes to the endoplasmic reticulum (ER) and Golgi complex and is required for a retrograde transport pathway between these organelles. Using conditional alleles of NEO1, we find that loss of Neo1p function causes cargo-specific defects in anterograde protein transport early in the secretory pathway and perturbs glycosylation in the Golgi complex. Rer1-GFP, a protein that cycles between the ER and Golgi complex in COPI and COPII vesicles, is mislocalized to the vacuole in neo1-ts at the nonpermissive temperature. These phenotypes suggest that the anterograde protein transport defect is a secondary consequence of a defect in a COPI-dependent retrograde pathway. We propose that loss of lipid asymmetry in the cis Golgi perturbs retrograde protein transport to the ER.
Developing the Brand: The Case of Alcohol, 1800–1880
Authors: Duguid Paul
Published: September 2003

Historians generally agree that modern brands arose from the vertically integrated corporations of the late nineteenth and early twentieth centuries and were used as competitive weapons between like firms. Looking at the alcoholic beverage trade and drawing on trade press, court reports, newspaper advertising, business records, and accounts of consumer behavior, I suggest that, on the contrary, supply chains made up of small firms played both an earlier and a significant part in the genesis of modern brands. In these chains, firms used branding not only to fight direct competitors but also to discipline and subordinate other links in the chain over whom they had no direct control and with whom they had to cooperate.
High-Tech Corporatism: Management–Employee Relations in U.S. Electronics Firms, 1920s–1960s
Authors: Lécuyer Christophe
Published: September 2003

In this article I examine corporative management practices in electronics firms in Boston and in Silicon Valley from the 1920s to the 1960s. Managers in several key firms developed these practices in response to political and professional ideologies and as a way to address the problems of hiring, using, and retaining a highly skilled work force. They did this independently of the welfare capitalism plans of corporations such as Eastman Kodak and before the guru theorists and work empowerment programs of the 1960s. The corporatist methods first developed in Boston and further refined in Silicon Valley later diffused to most U.S. firms in the software, computer, Internet, and biotechnology industries.
How long will long-term potentiation last?
Authors: Abraham Wickliffe C.
Published: September 2003

The paramount feature of long-term potentiation (LTP) as a memory mechanism is its characteristic persistence over time. Although the basic phenomenology of LTP persistence was established 30 years ago, new insights have emerged recently about the extent of LTP persistence and its regulation by activity and experience. Thus, it is now evident that LTP, at least in the dentate gyrus, can either be decremental, lasting from hours to weeks, or stable, lasting months or longer. Although mechanisms engaged during the induction of LTP regulate its subsequent persistence, the maintenance of LTP is also governed by activity patterns post-induction, whether induced experimentally or generated by experience. These new findings establish dentate gyrus LTP as a useful model system for studying the mechanisms governing the induction, maintenance and interference with long-term memory, including very long-term memory lasting months or longer. The challenge is to study LTP persistence in other brain areas, and to relate, if possible, the properties and regulation of LTP maintenance to these same properties of the information that is actually stored in those regions.
A journey from neocortex to hippocampus
Authors: Bliss T. V. P.
Published: September 2003

In the mid-1960s, it was generally agreed that the engram, the neural trace of previously experienced events, must be encoded by Hebb-like neurons in which synaptic efficacy could be modified by activity. Here, I describe my attempts as a PhD student at McGill University, Montreal, to find rules governing cortical plasticity in the neocortex, and having failed, why the hippocampus seemed to offer a far better prospect.
Long-term potentiation and memory
Authors: Morris Richard G. M.
Published: September 2003

The discovery of long-term potentiation (LTP) transformed research on the neurobiology of learning and memory. This did not happen overnight, but the discovery of an experimentally demonstrable phenomenon reflecting activity-driven neuronal and synaptic plasticity changed discussions about what might underlie learning from speculation into something much more concrete. Equally, however, the relationship between the discovery of LTP and research on the neurobiology of learning and memory has been reciprocal; for it is also true that studies of the psychological, anatomical and neurochemical basis of memory provided a developing and critical intellectual context for the physiological discovery. The emerging concept of multiple memory systems, from 1970 onwards, paved the way for the development of new behavioural and cognitive tasks, including the watermaze described in this paper. The use of this task in turn provided key evidence that pharmacological interference with an LTP induction mechanism would also interfere with learning, a finding that was by no means a foregone conclusion. This reciprocal relationship between studies of LTP and the neurobiology of memory helped the physiological phenomenon to be recognized as a major discovery.
Synaptic plasticity in animal models of early Alzheimer's disease
Authors: Rowan Michael J. , Klyubin Igor , Cullen William K. , Anwyl Roger
Published: September 2003

Amyloid β-protein (Aβ) is believed to be a primary cause of Alzheimer's disease (AD). Recent research has examined the potential importance of soluble species of Aβ in synaptic dysfunction, long before fibrillary Aβ is deposited and neurodegenerative changes occur. Hippocampal excitatory synaptic transmission and plasticity are disrupted in transgenic mice overexpressing human amyloid precursor protein with early onset familial AD mutations, and in rats after exogenous application of synthetic Aβ both
in vitro
and
in vivo
. Recently, naturally produced soluble Aβ was shown to block the persistence of long-term potentiation (LTP) in the intact hippocampus. Sub-nanomolar concentrations of oligomeric Aβ were sufficient to inhibit late LTP, pointing to a possible reason for the sensitivity of hippocampus-dependent memory to impairment in the early preclinical stages of AD. Having identified the active species of Aβ that can play havoc with synaptic plasticity, it is hoped that new ways of targeting early AD can be developed.
Long-term potentiation: outstanding questions and attempted synthesis
Authors: Lisman John
Published: September 2003

This article attempts an overview of the mechanism of NMDAR-dependent long-term potentiation (LTP) and its role in hippocampal networks. Efforts are made to integrate information, often in speculative ways, and to identify unresolved issues about the induction, expression and molecular storage processes. The pre/post debate about LTP expression has been particularly difficult to resolve. The following hypothesis attempts to reconcile the available physiological evidence as well as anatomical evidence that LTP increases synapse size. It is proposed that synapses are composed of a variable number of trans-synaptic modules, each having presynaptic release sites and a postsynaptic structure that can be AMPAfied by the addition of a hyperslot assembly that anchors 10-20 AMPA channels. According to a newly developed view of transmission, the quantal response is generated by AMPA channels near the site of vesicle release and so will depend on whether the module where release occurs has been AMPAfied. LTP expression may involve two structurally mediated processes: (i) the AMPAfication of existing modules by addition of hyperslot assemblies: this is a purely postsynaptic process and produces an increase in the probability of an AMPA response, with no change in the NMDA component; and (ii) the addition of new modules: this is a structurally coordinated pre/post process that leads to LTP-induced synapse enlargement and potentiation of the NMDA component owing to an increase in the number of release sites (the number of NMDA channels is assumed to be fixed). The protocol used for LTP induction appears to affect the proportion of these two processes; pairing protocols that involve low-frequency presynaptic stimulation induce only AMPAfication, making LTP purely postsynaptic, whereas high-frequency stimulation evokes both processes, giving rise to a presynaptic component. This model is capable of reconciling much of the seemingly contradictory evidence in the pre/post debate. The structural nature of the postulated changes is relevant to a second debate: whether a CaMKII switch or protein-dependent structural change is the molecular memory mechanism. A possible reconciliation is that a reversible CaMKII switch controls the construction of modules and hyperslot assemblies from newly synthesized proteins.
Long-term potentiation and the ageing brain
Authors: Barnes C. A.
Published: September 2003

Ageing is associated with learning and memory impairments. Data are reviewed that suggest that age-related impairments of hippocampal-dependent forms of memory, may be caused, in part, by altered synaptic plasticity mechanisms in the hippocampus, including long-term potentiation (LTP). To the extent that the mechanisms responsible for LTP can be understood, it may be possible to develop therapeutic approaches to alleviate memory decline in normal ageing.
Long-term potentiation in the Eocene
Authors: Lynch G.
Published: September 2003

The first ten years of long-term potentiation (LTP) research are reviewed. Surprisingly, given the intensity of current interest, the discovery paper did not trigger a wave of follow-on experiments. Despite this, the initial work laid out what ultimately became standard questions and paradigms. The application of the then still novel hippocampal slice technique oriented LTP towards basic neuroscience, perhaps somewhat at the cost of lesser attention to its functional significance. The use of slices led to the discovery of the events that trigger the formation of LTP and provided some first clues about its extraordinary persistence. Signs of the intense controversy over the nature of LTP expression (release vs receptors) emerged towards the end of the first decade of work. What appears to be lacking in the literature of that time is a widespread concern about LTP and memory. This may reflect a somewhat different attitude that neurobiologists then had towards memory research and a perceived need to integrate the new potentiation phenomenon into the web of established science before advancing extended arguments about its contributions to behaviour.
Structural changes at dendritic spine synapses during long-term potentiation
Authors: Harris Kristen M. , Fiala John C. , Ostroff Linnaea
Published: September 2003

Two key hypotheses about the structural basis of long-term potentiation (LTP) are evaluated in light of new findings from immature rat hippocampal slices. First, it is shown why dendritic spines do not split during LTP. Instead a small number of spine-like dendritic protrusions may emerge to enhance connectivity with potentiated axons. These ‘same dendrite multiple synapse boutons’ provide less than a 3% increase in connectivity and do not account for all of LTP or memory, as they do not accumulate during maturation. Second, polyribosomes in dendritic spines served to identify which of the existing synapses enlarged to sustain more than a 30% increase in synaptic strength. Thus, both enhanced connectivity and enlarged synapses result during LTP, with synapse enlargement being the greater effect.
Cadherins and synaptic plasticity: activity-dependent cyclin-dependent kinase 5 regulation of synaptic β-catenin-cadherin interactions
Authors: Schuman Erin M. , Murase Sachiko
Published: September 2003

Cyclin-dependent kinase 5 (Cdk5)/p35 kinase activity is known to decrease the affinity of β-catenin for cadherin in developing cortical neurons. Our recent work demonstrated that depolarization causes an increased affinity between β-catenin and cadherin. Here, we examine whether Cdk5/p35 regulates β-catenin-cadherin affinity in response to neural activity. In hippocampal neurons depolarization caused a significant decrease in Cdk5 kinase activity, without changing the protein levels of either Cdk5 or p35, suggesting that the proteasome pathway is not involved. Decreasing Cdk5 kinase activity with the inhibitor roscovitine increased the amount of β-catenin that was co-immunoprecipitated with cadherin. Inhibiting Cdk5 activity also resulted in a redistribution of EGFP-β-catenin from the dendritic shaft to the spines, where cadherins are highly concentrated. The redistribution of β-catenin induced by roscovitine is similar to that induced by depolarization. Interestingly, the redistribution induced by the Cdk5 inhibitor was completely blocked by either a tyrosine phosphatase inhibitor, orthovanadate or by point mutations of β-catenin Tyr-654 to Glu or Phe. Immunoprecipitation studies further revealed that roscovitine increases the affinity of the wild-type, but not mutated, EGFP-β-catenin for cadherin. These results suggest that Cdk5 activity regulates the affinity of β-catenin for cadherin by changing the phosphorylation level of β-catenin Tyr-654.
Biosynthesis and degradation of mammalian glycosphingolipids
Authors: Sandhoff Konrad , Kolter Thomas
Published: September 2003

Glycolipids are a large and heterogeneous family of sphingolipids that form complex patterns on eukaryotic cell surfaces. This molecular diversity is generated by only a few enzymes and is a paradigm of naturally occurring combinatorial synthesis. We report on the biosynthetic principles leading to this large molecular diversity and focus on sialic acid–containing glycolipids of the ganglio–series. These glycolipids are particularly concentrated in the plasma membrane of neuronal cells. Theirde novosynthesis starts with the formation of the membrane anchor, ceramide, at the endoplasmic reticulum (ER) and is continued by glycosyltransferases of the Golgi complex. Recent findings from genetically engineered mice are discussed. The constitutive degradation of glycosphingolipids (GSLs) occurs in the acidic compartments, the endosomes and the lysosomes. Here, water–soluble glycosidases sequentially cleave off the terminal carbohydrate residues from glycolipids. For glycolipid substrates with short oligosaccharide chains, the additional presence of membrane–active sphingolipid activator proteins (SAPs) is required. A considerable part of our current knowledge about glycolipid degradation is derived from a class of human diseases, the sphingolipidoses, which are caused by inherited defects within this pathway. A new post–translational modification is the attachment of glycolipids to proteins of the human skin.
The different mechanisms of gametophytic self–incompatibility
Authors: Franklin-Tong Vernonica E. , Franklin F. C. H.
Published: September 2003

Self–incompatibility (SI) involves the recognition and rejection of self or genetically identical pollen. Gametophytic SI is probably the most widespread of the SI systems and, so far, two completely different SI mechanisms, which appear to have evolved separately, have been identified. One mechanism is the RNase system, which is found in the Solanaceae, Rosaceae and Scrophulariaceae. The other is a complex system, so far found only in the Papaveraceae, which involves the triggering of signal transduction cascade(s) that result in rapid pollen tube inhibition and cell death. Here, we present an overview of what is currently known about the mechanisms involved in controlling pollen tube inhibition in these two systems.
Ecological and evolutionary opportunities of apomixis: insights from
Taraxacum
and
Chondrilla
Authors: van Dijk Peter J.
Published: September 2003

The ecological and evolutionary opportunities of apomixis in the short and the long term are considered, based on two closely related apomictic genera:
Taraxacum
(dandelion) and
Chondrilla
(skeleton weed). In both genera apomicts have a wider geographical distribution than sexuals, illustrating the short–term ecological success of apomixis. Allozymes and DNA markers indicate that apomictic populations are highly polyclonal. In
Taraxacum
, clonal diversity can be generated by rare hybridization between sexuals and apomicts, the latter acting as pollen donors. Less extensive clonal diversity is generated by mutations within clonal lineages. Clonal diversity may be maintained by frequency–dependent selection, caused by biological interactions (e.g. competitors and pathogens). Some clones are geographically widespread and probably represent phenotypically plastic ‘general–purpose genotypes’.

The long–term evolutionary success of apomictic clones may be limited by lack of adaptive potential and the accumulation of deleterious mutations. Although apomictic clones may be considered as ‘evolutionary dead ends’, the genes controlling apomixis can escape from degeneration and extinction via pollen in crosses between sexuals and apomicts. In this way, apomixis genes are transferred to a new genetic background, potentially adaptive and cleansed from linked deleterious mutations. Consequently, apomixis genes can be much older than the clones they are currently contained in. The close phylogenetic relationship between
Taraxacum
and
Chondrilla
and the similarity of their apomixis mechanisms suggest that apomixis in these two genera could be of common ancestry.
Integral role of Noxa in p53-mediated apoptotic response
Authors: Shibue Tsukasa , Takeda Kiyoshi , Oda Eri , Tanaka Hiroshi , Murasawa Hideki , Takaoka Akinori , Morishita Yasuyuki , Akira Shizuo , Taniguchi Tadatsugu , Tanaka Nobuyuki
Published: September 2003

The tumor suppressor p53 exerts its versatile function to maintain the genomic integrity of a cell, and the life of cancerous cells with DNA damage is often terminated by induction of apoptosis. We studied the role of Noxa, one of the transcriptional targets of p53 that encodes a proapoptotic protein of the Bcl-2 family, by the gene-targeting approach. Mouse embryonic fibroblasts deficient in Noxa [Noxa-/- mouse embryonic fibroblasts (MEFs)] showed notable resistance to oncogene-dependent apoptosis in response to DNA damage, which was further increased by introducing an additional null zygosity for Bax. These MEFs also showed increased sensitivity to oncogene-induced cell transformation in vitro. Furthermore, Noxa is also involved in the oncogene-independent gradual apoptosis induced by severe genotoxic stresses, under which p53 activates both survival and apoptotic pathways through induction of p21WAF1/Cip1 and Noxa, respectively. Noxa-/- mice showed resistance to X-ray irradiation-induced gastrointestinal death, accompanied with impaired apoptosis of the epithelial cells of small intestinal crypts, indicating the contribution of Noxa to the p53 response in vivo.
Exploration of the Cell-Cycle Genes Found Within the RIKEN FANTOM2 Data Set
Authors: Forrest Alistair R.R. , Taylor Darrin ,   RIKEN GER Group,   GSL Members, Grimmond Sean
Published: September 2003

The cell cycle is one of the most fundamental processes within a cell. Phase-dependent expression and cell-cycle checkpoints require a high level of control. A large number of genes with varying functions and modes of action are responsible for this biology. In a targeted exploration of the FANTOM2–Variable Protein Set, a number of mouse homologs to known cell-cycle regulators as well as novel members of cell-cycle families were identified. Focusing on two prototype cell-cycle families, the cyclins and the NIMA-related kinases (NEKs), we believe we have identified all of the mouse members of these families, 24 cyclins and 10 NEKs, and mapped them to ENSEMBL transcripts. To attempt to globally identify all potential cell cycle-related genes within mouse, the MGI (Mouse Genome Database) assignments for the RIKEN Representative Set (RPS) and the results from two homology-based queries were merged. We identified 1415 genes with possible cell-cycle roles, and 1758 potential paralogs. We comment on the genes identified in this screen and evaluate the merits of each approach.
Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans
Authors: Reed John C. , Doctor Kutbuddin , Rojas Ana , Zapata Juan M. , Stehlik Christian , Fiorentino Loredana , Damiano Jason , Roth Wilfried , Matsuzawa Shu-ichi , Newman Ruchi , Takayama Shinichi , Marusawa Hiroyuki , Xu Famming , Salvesen Guy ,   RIKEN GER Group,   GSL Members, Godzik Adam
Published: September 2003

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.
Targeting a Complex Transcriptome: The Construction of the Mouse Full-Length cDNA Encyclopedia
Authors: Carninci Piero , Waki Kazunori , Shiraki Toshiyuki , Konno Hideaki , Shibata Kazuhiro , Itoh Masayoshi , Aizawa Katsunori , Arakawa Takahiro , Ishii Yoshiyuki , Sasaki Daisuke , Bono Hidemasa , Kondo Shinji , Sugahara Yuichi , Saito Rintaro , Osato Naoki , Fukuda Shiro , Sato Kenjiro , Watahiki Akira , Hirozane-Kishikawa Tomoko , Nakamura Mari , Shibata Yuko , Yasunishi Ayako , Kikuchi Noriko , Yoshiki Atsushi , Kusakabe Moriaki , Gustincich Stefano , Beisel Kirk , Pavan William , Aidinis Vassilis , Nakagawara Akira , Held William A. , Iwata Hiroo , Kono Tomohiro , Nakauchi Hiromitsu , Lyons Paul , Wells Christine , Hume David A. , Fagiolini Michela , Hensch Takao K. , Brinkmeier Michelle , Camper Sally , Hirota Junji , Mombaerts Peter , Muramatsu Masami , Okazaki Yasushi , Kawai Jun , Hayashizaki Yoshihide
Published: September 2003

We report the construction of the mouse full-length cDNA encyclopedia,the most extensive view of a complex transcriptome,on the basis of preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in full-length by Cap-Trapper,and in most cases,aggressively subtracted/normalized. We have produced 1,442,236 successful 3′-end sequences clustered into 171,144 groups, from which 60,770 clones were fully sequenced cDNAs annotated in the FANTOM-2 annotation. We have also produced 547,149 5′ end reads,which clustered into 124,258 groups. Altogether, these cDNAs were further grouped in 70,000 transcriptional units (TU),which represent the best coverage of a transcriptome so far. By monitoring the extent of normalization/subtraction, we define the tentative equivalent coverage (TEC),which was estimated to be equivalent to >12,000,000 ESTs derived from standard libraries. High coverage explains discrepancies between the very large numbers of clusters (and TUs) of this project,which also include non-protein-coding RNAs,and the lower gene number estimation of genome annotations. Altogether,5′-end clusters identify regions that are potential promoters for 8637 known genes and 5′-end clusters suggest the presence of almost 63,000 transcriptional starting points. An estimate of the frequency of polyadenylation signals suggests that at least half of the singletons in the EST set represent real mRNAs. Clones accounting for about half of the predicted TUs await further sequencing. The continued high-discovery rate suggests that the task of transcriptome discovery is not yet complete.
Analysis of the Mouse Transcriptome for Genes Involved in the Function of the Nervous System
Authors: Gustincich Stefano , Batalov Serge , Beisel Kirk W. , Bono Hidemasa , Carninci Piero , Fletcher Colin F. , Grimmond Sean , Hirokawa Nobutaka , Jarvis Erich D. , Jegla Tim , Kawasawa Yuka , LeMieux Julianna , Miki Harukata , Raviola Elio , Teasdale Rohan D. , Tominaga Naoko , Yagi Ken , Zimmer Andreas ,   RIKEN GER Group,   GSL Members, Hayashizaki Yoshihide , Okazaki Yasushi
Published: September 2003

We analyzed the mouse Representative Transcript and Protein Set for molecules involved in brain function.We found full-length cDNAs of many known brain genes and discovered new members of known brain gene families, including Family 3 G-protein coupled receptors, voltage-gated channels, and connexins.We also identified previously unknown candidates for secreted neuroactive molecules.The existence of a large number of unique brain ESTs suggests an additional molecular complexity that remains to be explored.A list of genes containing CAG stretches in the coding region represents a first step in the potential identification of candidates for hereditary neurological disorders.
Phosphoregulators: Protein Kinases and Protein Phosphatases of Mouse
Authors: Forrest Alistair R.R. , Ravasi Timothy , Taylor Darrin , Huber Thomas , Hume David A. ,   RIKEN GER Group,   GSL Members, Grimmond Sean
Published: September 2003

With the completion of the human and mouse genome sequences, the task now turns to identifying their encoded transcripts and assigning gene function. In this study, we have undertaken a computational approach to identify and classify all of the protein kinases and phosphatases present in the mouse gene complement. A nonredundant set of these sequences was produced by mining Ensembl gene predictions and publicly available cDNA sequences with a panel of InterPro domains. This approach identified 561 candidate protein kinases and 162 candidate protein phosphatases. This cohort was then analyzed using TribeMCL protein sequence similarity clustering followed by CLUSTALV alignment and hierarchical tree generation. This approach allowed us to (1) distinguish between true members of the protein kinase and phosphatase families and enzymes of related biochemistry, (2) determine the structure of the families, and (3) suggest functions for previously uncharacterized members. The classifications obtained by this approach were in good agreement with previous schemes and allowed us to demonstrate domain associations with a number of clusters. Finally, we comment on the complementary nature of cDNA and genome-based gene detection and the impact of the FANTOM2 transcriptome project.
Mouse Proteome Analysis
Authors: Kanapin Alexander , Batalov Serge , Davis Melissa J. , Gough Julian , Grimmond Sean , Kawaji Hideya , Magrane Michele , Matsuda Hideo , Schönbach Christian , Teasdale Rohan D. ,   RIKEN GER Group,   GSL Members, Yuan Zheng
Published: September 2003

A general overview of the protein sequence set for the mouse transcriptome produced during the FANTOM2 sequencing project is presented here. We applied different algorithms to characterize protein sequences derived from a nonredundant representative protein set (RPS) and a variant protein set (VPS) of the mouse transcriptome. The functional characterization and assignment of Gene Ontology terms was done by analysis of the proteome using InterPro. The Superfamily database analyses gave a detailed structural classification according to SCOP and provide additional evidence for the functional characterization of the proteome data. The MDS database analysis revealed new domains which are not presented in existing protein domain databases. Thus the transcriptome gives us a unique source of data for the detection of new functional groups. The data obtained for the RPS and VPS sets facilitated the comparison of different patterns of protein expression. A comparison of other existing mouse and human protein sequence sets (e.g., the International Protein Index) demonstrates the common patterns in mammalian proteomes. The analysis of the membrane organization within the transcriptome of multiple eukaryotes provides valuable statistics about the distribution of secretory and transmembrane proteins
Kinesin Superfamily Proteins (KIFs) in the Mouse Transcriptome
Authors: Miki Harukata , Setou Mitsutoshi ,   RIKEN GER Group,   GSL Members, Hirokawa Nobutaka
Published: September 2003

In the post genomic era where virtually all the genes and the proteins are known, an important task is to provide a comprehensive analysis of the expression of important classes of genes, such as those that are required for intracellular transport. We report the comprehensive analysis of the Kinesin Superfamily, which is the first and only large protein family whose constituents have been completely identified and confirmed in silico and at the cDNA, mRNA level. In FANTOM2, we have found 90 clones from 33 Kinesin Superfamily Protein (KIF) gene loci. The clones were analyzed in reference to sequence state, library of origin, detection methods, and alternative splicing. More than half of the representative transcriptional units (TU) were full length. The FANTOM2 library also contains novel splice variants previously unreported. We have compared and evaluated various protein classification tools and protein search methods using this data set. This report provides a foundation for future research of the intracellular transport along microtubules and proves the significance of intracellular transport protein transcripts as part of the transcriptome.
Learning and trust in supply chain management
Authors: Kidd John , Richter Frank‐Jürgen , Li Xue
Published: September 2003

Firms in developed nations have practised supply chain management (SCM) for decades, but we ask here if they will be able to progress well under the modern regime of harder and faster e‐just‐in‐time systems. We assume these to be concentrated mainly in Europe and the USA, but with origins having global outreach – their management must concern themselves with explicit and tacit factors embracing the culture and ethics of people having diverse national origins. Essentially, we will discuss the challenges of knowledge management and organisational learning in the SCM systems that embrace firms located in many countries, Western as well as Asian, which have more (or less) permeable organisational boundaries and who must learn to trust each other regardless of their ethic differences.
Volume flexibility: the agile manufacturing conundrum
Authors: Yusuf Y.Y. , Adeleye E.O. , Sivayoganathan K.
Published: September 2003

Agile manufacturing is a response to competition in environments characterised by unpredictable change, so having the ability to vary capacity, respond to sporadic changes in demand, mass customise at the cost of mass production, and compete in both mass and custom markets is crucial. Empirical justification of the benefits of implementing agile manufacturing is rare in the literature and an in‐depth empirical study of the benefits of implementing agile manufacturing practices is lacking. This article aims to address this gap by conducting a preliminary analysis of a much wider empirical research. The adoption and impact of a set of tools – enablers of agile manufacturing – were studied through a survey by questionnaire. The results show lower volume flexibility at higher levels of adoption of the five enablers, thus the resource competencies for enhancing it were not in place. Also, volume flexibility ranked very low in hierarchy of future improvement plans. Suggests virtual cells, and its extension into supply chain networks, as a solution to volume flexibility.
Virtual agent modeling of an agile supply chain infrastructure
Authors: Lau Henry C.W. , Wong Christina W.Y. , Pun K.F. , Chin K.S.
Published: September 2003

In today’s volatile business environment, whether a company is able to compete in the local and global arena depends heavily on how effective the company can build up the partnership synergy with their business counterparts. Indeed, it is important that companies are able to monitor effectively on the manufacturing activities outside its boundary, such as business partners with dissimilar business nature and probably geographically isolated from each other. With the emergence of a dispersed manufacturing network, the important issue is the communication with the partners, collection of data, and making use of data. This paper calls for an effort to suggest practical and agile approaches and models to avoid a poorly managed supply chain in order to improve productivity and cost‐effectiveness to support the business. The agility of the supply chain models would also be concerned to ensure that there is enough adaptability in the system to respond and tackle problems that may occur in the turbulent market.
A conceptual model of performance measurement for supply chains
Authors: Chan Felix T.S. , Qi H.J. , Chan H.K. , Lau Henry C.W. , Ip Ralph W.L.
Published: September 2003

Supply chain management (SCM) has gained a tremendous amount of attention from both industries and researchers since the last decade. Until now, there are numerous papers, articles, and reports that address SCM, but there is still a lack of integration between the existing performance measurement methods and practical requirements for the SCM. An innovative performance measurement method is proposed to provide necessary assistance for performance improvement in SCM. The proposed method will address this purpose in these four aspects: a simplified supply chain model; tangible and intangible performance measures in multiple dimensions; a cross‐organizational performance measurement; and fuzzy set theory and weighted average method.
Management succession: a case for Chinese family‐owned business
Authors: Chung Walter W.C. , Yuen Karina P.K.
Published: September 2003

Research on the issues of management succession in Chinese family business should have a significant impact to the survival of small‐ to medium‐sized manufacturing enterprise (SME) in Hong Kong. One overlooked area in the study of SME is the continuity issue of management succession from one generation to the next generation in family‐owned businesses. The major emphasis is to delineate the difficulties, which the second‐generation owners encounter, in managing family businesses and propose a tripartite model for the second‐generation owners of SME to adopt in enhancing their abilities and re‐invent their family businesses to compete in the information age.
The migration of electronic commerce (EC): from planning to assessing the impact of EC on supply chain
Authors: Yen Benjamin P.‐C. , Ng Elsie O.S.
Published: September 2003

It has been an increasing trend for companies to migrate their businesses onto or publicize themselves on the Internet. Business process reengineering (BPR) is applied to migrate the business processes of the supply chain onto the Web. Such migration may cause some of the processes merged together, minimized or transformed into other processes within a supply chain. Therefore, careful planning for such migration with technical requirements is necessary. This paper starts with the review of related research on BPR, migration of supply chain onto the Internet, and the impact analysis of the migration. A thorough overview of how BPR can change each process of the supply chain onto the Internet is discussed. The main contribution of this paper is a framework of the electronic commerce (EC) impact on the supply chain and the measurement of impact. An industrial example is used to illustrate the evaluation as a result of EC deployment.
Customer satisfaction @ virtual organizations
Authors: Alomaim Nasser , Zihni Tunca Mustafa , Zairi Mohamed
Published: September 2003

Current organizational practice worldwide has responded to the demands of an increasingly competitive global market. Market or customer priorities derive from a focus on value, combining quality and cost integration according to the perception of the customer. The organizational improvement strategies described by Deming (1986) and Juran (1993), based on the post‐war Japanese reconstruction, have advanced the philosophy and strategy of total quality management (TQM) as a management strategy. The recent steep decline in the values of shares in Internet‐linked companies, which has led to a number of high‐profile failures, shows the importance of applying the concept of TQM to virtual environments. As the ultimate goal of TQM is customer satisfaction, it is important for the Internet companies to focus on unconditional customer satisfaction. This paper discusses the importance of customer satisfaction for virtual organizations.
Paediatric home care for acute illness: III. Parental views
Authors: Davies Carol , Dale Jeremy
Published: September 2003

Parental satisfaction with paediatric home care has previously been found to be high and the results presented here confirm this finding. This study is unique in that a well defined population from one geographical area was studied before and after the introduction of the new home care service. Referrers included general practitioners, doctors in emergency care and out‐patient clinics, referring children for a wide range of acute conditions. Compared with hospital admission only half the number of adverse effects on children and families were reported by parents. Interest has been increasing in alternative service provision to prevent or reduce paediatric hospital admissions to avoid adverse effects on children and families. This study examined the views of parents experiencing hospital at home compared with hospital referral between 1999 and 2001 across the whole spectrum of acute clinical conditions. Hospital at home was the preferred service for a wide range of illnesses. Parents and carers identified extension of hospital at home to 24‐hour cover as a future preference. Parental preference for paediatric hospital at home for acute illness was confirmed.
New performance and quality requirements in the field of operating room garments (non‐active medical devices)
Authors: Abreu M.J. , Silva M.E. , Schacher L. , Adolphe D.
Published: September 2003

In the area of technical textiles, the products depend mainly on advanced materials and these, on the other hand, depend on textile know‐how. Textile materials in the health‐care sector gradually have taken on more important roles. As more research has been completed, textiles have found their way into a variety of medical applications. Examines the medical and related health‐care sector, and more precisely the products used in the operating theatre and hospital ward for the hygiene, care and safety of staff and patients. These textiles are not very well‐known, but have great potential for development in the fields of application. Owing to recent advancements in medical procedures and textile engineering, the use of textile materials in the health‐care industry is growing. Subsequently, aims to contribute to the knowledge and clarification of single use materials used in the operating theatre according to the new technical standards.
Health education: part or all of the PSHE and citizenship framework?
Authors: Adams Paul
Published: September 2003

Recent alterations to the Key Stage 1 and 2 National Curriculum in England have located health education as a strand within a non‐statutory framework of Personal, Social, Health education and Citizenship. Starting from the premise that health education should adopt a health‐oriented approach, this paper finds the aforementioned health component lacking as a basis on which to operationalise primary school health education. Using medicines education as an example, a disease/risk factor‐oriented programme is critiqued and an alternative, health‐oriented perspective proposed. This alternative demonstrates how basing health education around every component of the personal, social and health education and citizenship framework can engender a health‐oriented approach to health education at Key Stages 1 and 2. Finally, two cautionary notes are made concerning the adoption of this approach.
Net profits? Web site development and health improvement
Authors: Duffy Mary , Wimbush Erica , Reece Jane , Eadie Douglas
Published: September 2003

The Internet has revolutionised information exchange. Its rapid connection of users and materials locally and globally make it an ideal health promotion medium, for both the public and professionals. However, the mechanisms through which it might contribute to health improvement are unclear. This paper provides an overview of Internet developments and presents findings from research carried out on behalf of the Health Education Board for Scotland, illustrating some of the assumptions implicit in using the Internet for health promotion. In the absence good evidence on the effects of delivering health promotion online, this paper argues that good practice requires greater responsiveness to user needs and circumstances at the planning stage, better quality assurance, more clearly defined indicators of “success” and the pathways to it, and more comprehensive evaluation of short‐ and long‐term impacts and outcomes.