bluuebunny/crossref_metadata_2025 huggingface dataset:
TheDrosophilaKinesin-like Protein KLP67A Is Essential for Mitotic and Male Meiotic Spindle Assembly
Authors: Gandhi Rita , Bonaccorsi Silvia , Wentworth Diana , Doxsey Stephen , Gatti Maurizio , Pereira Andrea
Published: September 2003

We have performed a mutational analysis together with RNA interference to determine the role of the kinesin-like protein KLP67A in Drosophila cell division. During both mitosis and male meiosis, Klp67A mutations cause an increase in MT length and disrupt discrete aspects of spindle assembly, as well as cytokinesis. Mutant cells exhibit greatly enlarged metaphase spindle as a result of excessive MT polymerization. The analysis of both living and fixed cells also shows perturbations in centrosome separation, chromosome segregation, and central spindle assembly. These data demonstrate that the MT plus end-directed motor KLP67A is essential for spindle assembly during mitosis and male meiosis and suggest that the regulation of MT plus-end polymerization is a key determinant of spindle architecture throughout cell division.
Gangliosides That Associate with Lipid Rafts Mediate Transport of Cholera and Related Toxins from the Plasma Membrane to Endoplasmic Reticulm
Authors: Fujinaga Yukako , Wolf Anne A. , Rodighiero Chiara , Wheeler Heidi , Tsai Billy , Allen Larry , Jobling Michael G. , Rapoport Tom , Holmes Randall K. , Lencer Wayne I.
Published: September 2003

Cholera toxin (CT) travels from the plasma membrane of intestinal cells to the endoplasmic reticulum (ER) where a portion of the A-subunit, the A1 chain, crosses the membrane into the cytosol to cause disease. A related toxin, LTIIb, binds to intestinal cells but does not cause toxicity. Here, we show that the B-subunit of CT serves as a carrier for the A-subunit to the ER where disassembly occurs. The B-subunit binds to gangliosides in lipid rafts and travels with the ganglioside to the ER. In many cells, LTIIb follows a similar pathway, but in human intestinal cells it binds to a ganglioside that fails to associate with lipid rafts and it is sorted away from the retrograde pathway to the ER. Our results explain why LTIIb does not cause disease in humans and suggest that gangliosides with high affinity for lipid rafts may provide a general vehicle for the transport of toxins to the ER.
Microbial growth in aviation fuel
Authors: Hill Ted
Published: September 2003

Growth of microorganisms in petroleum products has been recorded since 1895, causing fouling, malfunction and corrosion in storage tanks, airfield equipment, pipelines, airframes and engines. This paper considers the problems that fuel microbes pose to the aviation industry and discusses the International Air Transport Association Aviation Working Group's “Guidance Material on Microbiological Contamination in Aircraft Fuel Tanks”.
Pills by post? German retail pharmacies and the Internet
Authors: Schmidt Ruth A. , Pioch Elke A.
Published: September 2003

The advent of Internet trading in medicines, as epitomized by the recently attempted market entry of the Dutch Internet pharmacy DocMorris into the tightly regulated German retail pharmacy sector, presents a new competitive challenge to this industry. Based on the findings of a 1999 field study of retail pharmacies in Berlin and Brandenburg and an examination of pharmacy Web sites, as well as pharmacy related professional portals and networks on the Internet, this paper applies Bickerton et al.’s framework of competitive forces to structure the analysis of attitudes and developments in the application of information technology in this sector.
Export market‐oriented behavior and export performance
Authors: Cadogan John W. , Cui Charles C. , Kwok Yeung Li Erik
Published: September 2003

This study examines the issue of how export market‐oriented behaviors influence export success. Using survey data obtained from Hong Kong based manufacturing exporters, our findings suggest that export market‐oriented behaviors are important predictors of several dimensions of export performance. In particular, it appears that this behavior is most important for exporters operating under conditions of high environmental turbulence. The export market‐oriented behavior – export performance relationship for these firms, was generally positive and strong. However, under conditions of low environmental turbulence, the costs of developing and implementing high levels of export market‐oriented behavior may outweigh the benefits accrued.
Electrodeposition of biomedical hydroxyapatite coatings on titanium alloy substrate
Authors: Hanna F. , Hamid Z.A.
Published: September 2003

This work concerns the electrodeposition of highly pure brushite (CaHPO4·2H2O) on titanium alloy substrates and the transformation of the brushite to hydroxyapatite (HAp) Ca10(PO4)6(OH)2 as a coating for orthopaedic implants. Thus, the electrodeposition of electrolyte containing calcium nitrate and ammonium hydrogen phosphate was carried out. The influences of the substrate surface treatment, the electroplating conditions (bath composition, current density, pH value and temperature) and the hydrothermal post treatment conditions on the deposition rate, the throwing power, the adhesion, the morphology and the structure of the coating were evaluated. High adhesion bond strength (around 23 mPa) was achieved on a rough clean substrate, which is slightly higher than plasma sprayed HAp coating on titanium alloy.
Accelerating change in the academy
Authors: Wilms Wellford W. , Zell Deone M.
Published: September 2003

Forces that are transforming the global economy are now sweeping through higher education. As the higher education environment becomes more turbulent, administrators and academic leaders are caught between opposing forces that both demand and resist change. Suggests five strategies to help universities adapt to the changing environment while preserving important academic values.
Shared perceptions: black officers discuss continuing barriers in policing
Authors: Bolton Kenneth
Published: September 2003

Informed by the experiential‐racism theoretical approach, which maintains that racism must be analyzed as a process that is manifested in multiple relations and situations in everyday life, interviews with 50 male and female black police officers in a southern state are drawn upon to analyze the impact race has on policing. Accounts demonstrate in considerable detail a shared perception of the continuing attitudinal and institutional dimensions of racism that impedes full participation in law enforcement agencies. Training, evaluation, discipline, assignment and promotion are discussed as processes within police agencies felt to be impacted by race. The conclusion is promoted that racism is persistent in agencies to the extent that white officers disproportionately occupy positions of authority with unfettered subjective discretion and to the extent there are few black officers relative to white officers. As an exploratory examination of the shared experiences and perceptions of black officers, findings should be further tested empirically.
Customer relationship management: strategic lessons and future directions
Authors: Kotorov Rado
Published: September 2003

Investigates customer relationship management (CRM) as a new concept. Follows the introduction of CRM in various settings, from departments to corporations, and the changes, commitment and support that are required to make the implementation of it a success. Points out that CRM is a strategy not a solution and can provide enormous competitive advantage if implemented in a co‐operative environment. Points out that the committed involvement of senior management is essential in promoting and supporting the concept of customer relationship management within the organization. Looks at what might be emerging in the future and how customer relationship management may be used in different areas of business, such as human resources.
CRM packaged software: a study of organisational experiences
Authors: Light Ben
Published: September 2003

Customer relationship management (CRM) packaged software has become a key contributor to attempts at aligning business and IT strategies in recent years. Throughout the 1990s there was, in many organisations' strategies, a shift from the need to manage transactions and toward relationship management. Where enterprise resource planning packages dominated the management of transactions era, CRM packages lead in regard to relationships. At present, balanced views of CRM packages are scantly presented, instead relying on vendor rhetoric. This paper uses case study research to analyse some of the issues associated with CRM packages. These issues include the limitations of CRM packages, the need for a relationship orientation and the problems of a dominant management perspective of CRM. It is suggested that these issues could be more readily accommodated by organisational detachment from beliefs in IT as utopia, consideration of prior IS theory and practice and a more informed approach to CRM package selection.
Understanding customer relationship management (CRM)
Authors: Chen Injazz J. , Popovich Karen
Published: September 2003

Customer relationship management (CRM) is a combination of people, processes and technology that seeks to understand a company's customers. It is an integrated approach to managing relationships by focusing on customer retention and relationship development. CRM has evolved from advances in information technology and organizational changes in customer‐centric processes. Companies that successfully implement CRM will reap the rewards in customer loyalty and long run profitability. However, successful implementation is elusive to many companies, mostly because they do not understand that CRM requires company‐wide, cross‐functional, customer‐focused business process re‐engineering. Although a large portion of CRM is technology, viewing CRM as a technology‐only solution is likely to fail. Managing a successful CRM implementation requires an integrated and balanced approach to technology, process, and people.
Long‐term incentive schemes, executive remuneration and corporate performance: an empirical study
Authors: Pass Christopher
Published: September 2003

UK plcs use option schemes and increasingly long‐term incentive plans (LTIP’s) to reward their executive directors in order to improve corporate performance and align their interests more closely with those of the shareholders of the company. This paper presents a study of the option and LTIP arrangements used by a sample of 51 large UK companies over the period 1994‐2001. The general finding is that a substantial proportion of the schemes are “undemanding” rewarding average rather than exceptional performance.
Corporate social responsibility in a total quality management context: opportunities for sustainable growth
Authors: McAdam Rodney , Leonard Denis
Published: September 2003

The aim of this paper is to explore how quality management can act as a foundation and key catalyst for developing corporate social responsibility (CSR) within organizations. CSR is an emergent discourse within organizational research and praxis. It has parallels to sustainable development, environmental protection, social equity and economic growth. Although some organizations consider CSR to be a peripheral and sector specific issue, it is becoming increasingly mainstream, supported by government legislation. Key questions arising are, is there a conflict between profit earning and CSR? How can CSR be implemented without impairing business performance? Can CSR build on existing quality management based business initiatives from a philosophical and practical manner? The critique and case study analysis within this paper shows how the ethical basis of quality management can be used to develop CSR within organizations. Quality management models and methodologies established on the broad principles of quality are seen as a foundation and catalyst for effective CSR in organizations.
Management turnarounds: diagnosing business ailments
Authors: Scherrer Phillip Scott
Published: September 2003

The process of business decline can be identified through various warning signals that are concomitant with the decline process. These warning signals are noticed in both the internal and external business environments. The successful turnaround of a failing or declining business requires that management analyze the causes of decline and then implement a strategy for reversal of the decline. This article addresses the signals of decline, internal and external business environments and the strategies for reversal of decline.
On a Two‐Point Boundary‐Value Problem with Spurious Solutions
Authors: Ou C. H. , Wong R.
Published: September 2003

The Carrier–Pearson equation with boundary conditions u(−1) =u(1) = 0 is studied from a rigorous point of view. Known solutions obtained from the method of matched asymptotics are shown to approximate true solutions within an exponentially small error estimate. The so‐called spurious solutions turn out to be approximations of true solutions, when the locations of their “spikes” are properly assigned. An estimate is also given for the maximum number of spikes that these solutions can have.
On Stratified Shear Flow in Sea Straits of Arbitrary Cross Section
Authors: Deng Jian , Pratt Larry , Howard Lou , Jones Chris
Published: September 2003

Equations and theorems governing the flow of an inviscid, incompressible, continuously‐stratified fluid in a gradually varying channel with an arbitrary cross section are developed. The stratification and longitudinal velocity are assumed to be uniform in the transverse direction, an assumption that is supported under the assumption of gradual topographic variations. Extended forms of Long's model and the Taylor–Goldstein equation are developed. Interestingly, the presence of topographic variation does not alter the necessary condition for instability (Richardson number ) nor the bounds on unstable eigenvalues (the semi‐circle theorem). The former can be proved using a new technique introduced herein. For the special case of homogeneous shear flow, generalized versions of the theorems of Rayleigh and Fjørtoft do depend on the form of the topography, though no general tendency toward stabilization or destabilization is apparent. Previous results on the bounds and enumeration of neutral modes are also extended. The results should be of use in the hydraulic interpretation of exchange flow in sea straits.
An intelligent agent with layered architecture for operating systems resource management
Authors: Feng Shan , Da Xu Li , Tang Chao , Yang Simon
Published: September 2003

Abstract: A software agent is defined as an autonomous software entity that is able to interact with its environment. Such an agent is able to respond to other agents and/or its environment to some degree, and has some sort of control over its internal state and actions. In belief–desire–intention (BDI) theory, an agent's behavior is described in terms of a processing cycle. In this paper, based on BDI theory, the processing cycle is studied with a software feedback mechanism. A software feedback or loop‐back control mechanism can perform functions without direct external intervention. A feedback mechanism can continuously monitor the output of the system under control (the target system), compare the result against preset values (goals of the feedback control) and feed the difference back to adjust the behavior of the target system in a processing cycle. We discuss the modeling and design aspects of an autonomous, adaptive monitoring agent with layered control architecture. The architecture consists of three layers: a scheduling layer, an optimizing layer and a regulating layer. Experimental results show that the monitoring agent developed for an e‐mail server is effective.
A new and efficient ant‐based heuristic method for solving the traveling salesman problem
Authors: Tsai Cheng‐Fa , Tsai Chun‐Wei , Tseng Ching‐Chang
Published: September 2003

Abstract: In this paper, we present an efficient metaheuristic approach for solving the problem of the traveling salesman. We introduce the multiple ant clans concept from parallel genetic algorithms to search solution space using different islands to avoid local minima in order to obtain a global minimum for solving the traveling salesman problem. Our simulation results indicate that the proposed novel traveling salesman problem method (called the ACOMAC algorithm) performs better than a promising approach named the ant colony system. This investigation is concerned with a real life logistics system design which optimizes the performance of a logistics system subject to a required service level in the vehicle routing problem. In this work, we also concentrate on developing a vehicle routing model by improving the ant colony system and using the multiple ant clans concept. The simulation results reveal that the proposed method is very effective and potentially useful in solving vehicle routing problems.
A Comparison of Approaches for Setting Standards for Technological Products
Authors: Rosen Barry Nathan , Schnaars Steven P. , Shani David
Published: September 2003

It is widely believed that setting industry‐wide standards of uniformity for technological products hastens their diffusion. In this article, Barry Rosen, Steven Schnaars and David Shani examine whether standards merely make markets less competitive, or whether they promote economic growth through the accelerated diffusion of certain new products. The authors also examine conditions which are most conducive to setting standards and reflect on alternative approaches to achieving technical standards. Finally, they ask who should set industry standards? The article presents opposing arguments for allowing industry to cooperate in the setting of standards and for letting the marketplace be the ultimate arbiter of standards—acting to weed out the weak and promote the strongest technological entry.
Developing and Using Forecasting Models of Consumer Durables The Case of Color Television
Authors: Bayus Barry L. , Hong Saman , Labe Russell P.
Published: September 2003

Predicting the future sales of new and established products is a critical activity for companies to be able to plan and control their operations. Forecasting consumer durable sales is an especially difficult and challenging task since the marketplace is always changing. Barry Bayus, Saman Hong and Russell Labe present the concept of a market‐driven forecasting model and discuss an application involving the forecasting of color television industry sales for RCA's Consumer Electronics Division. An important aspect of this application is that a single approach or model was inadequate to accurately forecast sales over the entire period since the introduction of color TV. Econometric and simulation models which were developed are described, along with their forecasting performance and management acceptance and use.
Learning in New Technology Development Teams
Authors: Meyers Patricia W. , Wilemon David
Published: September 2003

One factor that may distinguish effective new product development teams from ineffective ones is the ability to learn in purposeful and cumulative ways. History can sometimes teach important lessons, yet history is not always transmitted efficiently within organizations. Patricia Meyers and David Wilemon present a study of new product development teams' learning in technology‐based organizations. They note especially the learning modes employed by teams, the conditions blocking team learning which create errors and the learning transfer among teams. Using findings from previous and current research, the authors establish the importance of effective team learning whenever teams are asked to deal with complex new product development challenges. Further, they suggest ways to create a productive learning climate for new product teams and close with a discussion of both managerial implications and suggestions for further research.
New Product Management Practices of Small High Technology Firms
Authors: Boag David A. , Rinholm Brenda L.
Published: September 2003

Various methods exist for managing the planning, cost estimating, scheduling and statusing of new product development projects. David Boag and Brenda Rinholm investigate whether the use of formal management procedures and structured frameworks are the most effective methods for achieving control over new product development activities. This article describes the new product development management practices of 33 small and medium‐sized high technology companies. The authors employ a judgmental procedure to group the firms into three stages of development for their management of new products. Findings indicate that success at new product development is greater for more formalized companies than for companies which are less formalized or which use informal methods.
Technical Development and the Innovation Process
Authors: Livesay Harold C. , Rorke Marcia L. , Lux David S.
Published: September 2003

Independent and small‐business inventors face enormous difficulties as they attempt to commercialize new technologies. Harold Livesay, Marcia Rorke and David Lux share a number of their useful insights based on their experience. They find that many inventors wish to focus only on certain aspects of their emerging programs. In fact, these inventors resist the need to develop a balanced program involving not only technical development but also marketing and the creation of sustaining business structures. This article provides a systematic elaboration of these difficulties, suggests a more balanced approach and thus describes a process of education and communication that may increase overall effectiveness.
A Discussion of the Link Between One Organization's Style and Structure and Its Connection With Its Market
Authors: Bentley Kathleen
Published: September 2003

A growing body of literature has identified some important characteristics of organizations that produce product innovations. This work demonstrates the importance of staying close to the customer and using market input for new product development. In this study, Kathleen Bentley helps us understand the relevance of this research for one small high‐technology firm. She uses qualitative data to develop a detailed picture of what close customer contact means for this firm, and how the firm's ability to relate to its customers is tied to the nature of its organization. The article concludes that the organization's structure and style are tightly linked to its ability to connect with its market and maintain its competitive edge.
Purchase Intentions and the Dimensions of Innovation: An Exploratory Model
Authors: Holak Susan L. , Lehmann Donald R.
Published: September 2003

The ultimate success of new product R&D depends as much on customer acceptance as on technological breakthroughs. In this article, Susan Holak and Donald Lehmann focus on customer acceptance by exploring the manner in which the general attributes of Rogers (relative advantage, compatibility, complexity, divisibility and communicability) plus perceived risk combine to form the intention to buy an innovation. Results demonstrate a causal structure among these attributes and lead to various implications for R&D guidelines and product design.
Product/Market Innovations: A Study of Top Management Involvement Among Four Cultures
Authors: Hegarty W. Harvey , Hoffman Richard C.
Published: September 2003

Over the years, many authors have stressed that successful new product development requires the support of top management. Harvey Hegarty and Richard Hoffman explore this involvement through survey data obtained from top managers employed by a cross‐cultural sample of organizations. Reported influence on innovations varied by the respondents' functional specialties rather than their cultural backgrounds. However, both the use of strategic management activities and their association with influence on innovations were found to vary across cultures.
It's Still Caveat, Inventor
Authors: Udell Gerald G.
Published: September 2003

Independent inventors are major contributors to industrial innovation and provide an important source of new products to industry. However, they are more often abused than appreciated by the marketplace. In addition, they frequently lack the skills, knowledge and resources either to translate their inventions into innovations or to transfer them effectively to others.

In this article, Gerald G. Udell describes the invention development and commercialization services available to independent inventors. He places particular emphasis on the growing problem of ineffectual and perhaps fraudulent invention marketing and promotion in the United States.
New Products Over the Business Cycle
Authors: Devinney Timothy M.
Published: September 2003

Studies of new product innovations and new product strategy have traditionally abstracted from the impact of general economic conditions on marketing decision making. Despite the obvious importance of the role that the business cycle plays in determining product profitability, it is relegated to ancillary discussion. Timothy Devinney feels that part of this neglect is due to a lack of academic study of the influence of macroeconomic influences in the determination of marketing strategy. This article attempts to fill a portion of this gap by examining the role that the business cycle plays in new product introductions. The results show that new product introductions, in the aggregate, vary systematically over the business cycle, where the cycle is defined as having income, price, and investment components.
Evolving Toward Product and Market‐Orientation: The Early Years of Technology‐Based Firms
Authors: Roberts Edward B.
Published: September 2003

Research studies of 114 technology‐based firms within the Greater Boston area indicate evolution over the first several years after founding toward more product‐oriented businesses and away from consulting and R&D contracting, and increased orientation of the founders to sales and marketing, with lessened emphasis on engineering. In this article Edward Roberts reports that the character of many of these firms changes over time. Evolution toward market‐orientation is manifested in many ways. Firms' use of direct sales forces and sales representatives grows over time, as does their adoption of more formal mechanisms such as marketing departments, sales forecasting and analyses of potential markets. Greater orientation toward marketing in all its dimensions is especially true for multifounder firms, the single founder company being slower to evolve in the characteristics cited.
Small conductance Ca2+‐activated K+ channels and calmodulin
Authors: Maylie James , Bond Chris T. , Herson Paco S. , Lee Wei‐Sheng , Adelman John P.
Published: September 2003

Small conductance Ca2+‐activated K+ channels (SK channels) contribute to the long lasting afterhyperpolarization (AHP) that follows an action potential in many central neurones. The biophysical and pharmacological attributes of cloned SK channels strongly suggest that one or more of them underlie the medium component of the AHP that regulates interspike interval and plays an important role in setting tonic firing frequency. The cloned SK channels comprise a distinct subfamily of K+ channels. Heterologously expressed SK channels recapitulate the biophysical and pharmacological hallmarks of native SK channels, being gated solely by intracellular Ca2+ ions with no voltage dependence to their gating, small unitary conductance values and sensitivity to the bee venom peptide toxin, apamin. Molecular, biochemical and electrophysiological studies have revealed that Ca2+ gating in SK channels is due to heteromeric assembly of the SK α pore‐forming subunits with calmodulin (CaM). Ca2+ binding to the N‐terminal E–F hands of CaM is responsible for SK channel gating. Crystallographic studies suggest that SK channels gate as a dimer‐of‐dimers, and that the physical gate of SK channels resides at or near the selectivity filter of the channels. In addition, Ca2+‐independent interactions between the SK channel α subunits and CaM are necessary for proper membrane trafficking.
The sources and sequestration of Ca2+ contributing to neuroeffector Ca2+ transients in the mouse vas deferens
Authors: Brain Keith L. , Cuprian Alina M. , Williams Damian J. , Cunnane Thomas C.
Published: September 2003

The detection of focal Ca2+ transients (called neuroeffector Ca2+ transients, or NCTs) in smooth muscle of the mouse isolated vas deferens has been used to detect the packeted release of ATP from nerve terminal varicosities acting at postjunctional P2X receptors. The present study investigates the sources and sequestration of Ca2+ in NCTs. Smooth muscle cells in whole mouse deferens were loaded with the Ca2+ indicator Oregon Green 488 BAPTA‐1 AM and viewed with a confocal microscope. Ryanodine (10 µm) decreased the amplitude of NCTs by 45 ± 6 %. Cyclopiazonic acid slowed the recovery of NCTs (from a time course of 200 ± 10 ms to 800 ± 100 ms). Caffeine (3 mm) induced spontaneous focal smooth muscle Ca2+ transients (sparks). Neither of the T‐type Ca2+ channel blockers NiCl2 (50 µm) or mibefradil dihydrochloride (10 µm) affected the amplitude of excitatory junction potentials (2 ± 5 % and −3 ± 10 %) or NCTs (−20 ± 36 % and 3 ± 13 %). In about 20 % of cells, NCTs were associated with a local, subcellular twitch that remained in the presence of the α1‐adrenoceptor antagonist prazosin (100 nm), showing that NCTs can initiate local contractions. Slow (5.8 ± 0.4 µm s−1), spontaneous smooth muscle Ca2+ waves were occasionally observed. Thus, Ca2+ stores initially amplify and then sequester the Ca2+ that enters through P2X receptors and there is no amplification by local voltage‐gated Ca2+ channels.
Pacing of interstitial cells of Cajal in the murine gastric antrum: neurally mediated and direct stimulation
Authors: Beckett Elizabeth A. H. , McGeough Cathrine A. , Sanders Kenton M. , Ward Sean M.
Published: September 2003

Phase advancement of electrical slow waves and regulation of pacemaker frequency was investigated in the circular muscle layer of the gastric antra of wild‐type and W/WV mice. Slow waves in the murine antrum of wild‐type animals had an intrinsic frequency of 4.4 cycles min−1 and were phase advanced and entrained to a maximum of 6.3 cycles min−1 using 0.1 ms pulses of electrical field stimulation (EFS) (three pulses delivered at 3–30 Hz). Pacing of slow waves was blocked by tetrodotoxin (TTX) and atropine, suggesting phase advancement was mediated via intrinsic cholinergic nerves. Phase advancement and entrainment of slow waves via this mechanism was absent in W/WV mutants which lack intramuscular interstitial cells of Cajal (ICC‐IM). These data suggest that neural regulation of slow wave frequency and regulation of smooth muscle responses to slow waves are mediated via nerve‐ICC‐IM interactions. With longer stimulation parameters (1.0–2.0 ms), EFS phase advanced and entrained slow waves in wild‐type and W/WV animals. Pacing with 1–2 ms pulses was not inhibited by TTX or atropine. These data suggest that stimulation with longer pulse duration is capable of directly activating the pacemaker mechanism in ICC‐MY networks. In summary, intrinsic excitatory neurons can phase advance and increase the frequency of antral slow waves. This form of regulation is mediated via ICC‐IM. Longer pulse stimulation can directly activate ICC‐MY in the absence of ICC‐IM.
Variable amplification of synaptic input to cat spinal motoneurones by dendritic persistent inward current
Authors: Hultborn H. , Denton M. Enríquez , Wienecke J. , Nielsen J. B.
Published: September 2003

Electrophysiological and computational evidence indicate that the excitatory current from the synapses on the somato‐dendritic membrane is not large enough to drive the motoneurones to the firing frequencies actually attained under normal motor activity. It has been proposed that this paradox could be explained if the voltage‐dependent persistent inward currents (PICs) present in the dendrites of motoneurones served to amplify synaptic excitation. We report here that dendritic PICs cause a large amplification of synaptic excitation, and that this amplification is enhanced when the background firing by current injection is increased. Moreover the frequency reduction by synaptic inhibition is greatly enhanced at higher firing frequencies, when the current through the recording electrode has activated the dendritic PICs, as is the case when the current‐to‐frequency slope suddenly becomes steeper. We also demonstrate that synaptic inhibition is several times more effective in reducing the firing caused by synaptic excitation than firing evoked by current injection through the recording microelectrode. That would be explained if motoneuronal discharge by synaptic excitation – but not by current injection in the soma – is always supported by dendritic PICs. We conclude that dendritic PICs contribute dynamically to the transformation of synaptic input into a motoneuronal frequency code.
Free Magnesium Concentration in Salamander Photoreceptor Outer Segments
Authors: Chen Chunhe , Nakatani Kei , Koutalos Yiannis
Published: September 2003

Magnesium ions (Mg2+) play an important role in biochemical functions. In vertebrate photoreceptor outer segments, numerous reactions utilize MgGTP and MgATP, and Mg2+ also regulates several of the phototransduction enzymes. Although Mg2+ can pass through light‐sensitive channels under certain conditions, no clear extrusion mechanism has been identified and removing extracellular Mg2+ has no significant effect on the light sensitivity or the kinetics of the photoresponse. We have used the fluorescent Mg2+ dye Furaptra to directly measure and monitor the free Mg2+ concentration in photoreceptor outer segments and examine whether the free Mg2+ concentration changes under physiological conditions. Resting free Mg2+ concentrations in bleached salamander rod and cone photoreceptor cell outer segments were 0.86 ± 0.06 and 0.81 ± 0.09 mm, respectively. The outer segment free Mg2+ concentration was not significantly affected by changes in extracellular pH, Ca2+ and Na+, excluding a significant role for the respective exchangers in the regulation of Mg2+ homeostasis. The resting free Mg2+ concentration was also not significantly affected by exposure to 0 Mg2+, suggesting the lack of significant basal Mg2+ flux. Opening the cGMP‐gated channels led to a significant increase in the Mg2+ concentration in the absence of Na+ and Ca2+, but not in their presence, indicating that depolarization can cause a significant Mg2+ influx only in the absence of other permeant ions, but not under physiological conditions. Finally, light stimulation did not change the Mg2+ concentration in the outer segments of dark‐adapted photoreceptors. The results suggest that there are no influx and efflux pathways that can significantly affect the Mg2+ concentration in the outer segment under physiological conditions. Therefore, it is unlikely that Mg2+ plays a significant role in the dynamic modulation of phototransduction.
Estrogen, Bone, and Osteoporosis
Authors: Riggs B. Lawrence
Published: September 2003

Until 1995, scientists held five widely accepted pillars of belief about estrogen action in the skeleton. Since then, a sea change in conventional wisdom has swept away these five beliefs. This lecture reviews data that have proved them wrong--or at least incomplete--and describes the new paradigms that have emerged to replace them.

[Presentation]

References

1.
B. L. Riggs, S. Khosla, L. J. Melton III, Sex steroids and the construction and conservation of the adult skeleton.
Endocr. Rev.
23
, 279-302 (2003).
[Abstract]
[Full Text]
The Persistence of Senescence
Authors: Sharpless Norman E.
Published: September 2003

Senescence is a potent anticancer mechanism, representing a barrier that most, if not all, would-be tumor cells must traverse on their path to malignant transformation. In this Perspective, I discuss two recent publications (
1
,
2
) that deal with the durability of senescence. These findings are of interest not only to those who study aging, but to those who study cancer as well.
Small Groups, Big Trouble
Authors: Davenport R. John
Published: September 2003

It takes only a small band of miscreants to stir up trouble. Small, free-floating groups of β-amyloid molecules accumulate in brains of people with Alzheimer's disease and glom onto neurons, possibly impairing nerve signals, according to new work. The results support the idea that the intimate gatherings, rather than the crowds of β-amyloid protein in plaques, spur the beginnings of dementia.
Amyotrophic Lateral Sclerosis
Authors: Gordon Paul H. , Mitsumoto Hiroshi , Hays Arthur P.
Published: September 2003

In this case study, we describe the symptoms, neurological examination, and pathology of a woman with amyotrophic lateral sclerosis (ALS). ALS is a rare disorder leading to degeneration of the voluntary motor system and death in, on average, 3 to 4 years. The loss of motor neurons in the brain and spinal cord causes the progressive symptoms of muscular weakness, atrophy, fasciculation (muscle twitching), spasticity, and hyperreflexia. Signs of disease in both upper and lower motor neurons are required for a definitive clinical diagnosis. Pathology shows degeneration of the lateral corticospinal tracts, loss of motor neurons and astrogliosis in the brain and brain stem, and neuronal inclusions. This case was marked by the onset of weakness and muscle atrophy in the hand, which spread to involve contiguous muscle segments. Cognition, the extraocular muscles, and the urinary sphincters were spared. Respiratory muscle weakness was a late manifestation.
Ups and Downs
Authors: Seydel Caroline
Published: September 2003

Some people dread getting older, imagining that the first signs of forgetfulness presage the loss of all their hard-won skills. Others take a more hopeful stance: Although they might lose their lightning reflexes, say, they'll hold on to their way with words or their ability to piece together a jigsaw puzzle. Psychologists debate which vision comes closer to the truth, and a new paper supports the second notion, showing that older people retain their relative strengths and weaknesses rather than deteriorating across the board.
Live Fast, Die Old?
Authors: Leslie Mitch
Published: September 2003

"Live fast, die young" might be the unofficial motto of rock 'n' roll, but it's also one of the oldest hypotheses for differences in aging rates. The notion hasn't matured gracefully, however, and a new study weakens it further, showing that some flies endure without turning down their metabolism.
Flexible Retinotopy: Motion-Dependent Position Coding in the Visual Cortex
Authors: Whitney David , Goltz Herbert C. , Thomas Christopher G. , Gati Joseph S. , Menon Ravi S. , Goodale Melvyn A.
Published: September 2003

Although the visual cortex is organized retinotopically, it is not clear whether the cortical representation of position necessarily reflects perceived position. Using functional magnetic resonance imaging (fMRI), we show that the retinotopic representation of a stationary object in the cortex was systematically shifted when visual motion was present in the scene. Whereas the object could appear shifted in the direction of the visual motion, the representation of the object in the visual cortex was always shifted in the opposite direction. The results show that the representation of position in the primary visual cortex, as revealed by fMRI, can be dissociated from perceived location.
A Kelch β Propeller Featuring as a Gβ Structural Mimic: Reinventing the Wheel?
Authors: Gettemans Jan , Meerschaert Kris , Vandekerckhove Joël , De Corte Veerle
Published: September 2003

New genetic and protein interaction data suggest that G protein α subunits may have partners with primary sequences that are quite divergent. How this is achieved may be through the adoption of similar structures, the β propeller, by both proteins containing WD-40 repeats and kelch domains. Gettemans
et al
. describe results in yeast that suggest that kelch-domain proteins may serve as previously unrecognized β subunits in the heterotrimeric G protein complex.
Activation of Ras by Grb2-SOS: Demonstrating an Assembly Role of SH3 Domains
Authors: Zarrinpar Ali , Bhattacharyya Roby P. , Lim Wendell A. , Gough Nancy R.
Published: September 2003

The animation shows a schematic representation of the assembly role of SH3 domain-containing proteins using Grb2 as an example. Growth factor stimulation leads to the activation of receptor tyrosine kinases and to the phosphorylation of the receptor tail and the stimulation of phosphorylation of related adaptor proteins (not shown). The resultant phosphotyrosines form docking sites for the adaptor protein Grb2 (through its SH2 domain). The Grb2 SH3 domains bind proline-rich motifs in SOS, the guanine nucleotide exchange factor for Ras, recruiting SOS to the membrane and colocalizing it with Ras. The resultant stimulation of Ras activates a mitogen-activated protein kinase cascade, leading to cell growth and differentiation. The animation could be useful in demonstrating how different protein domains allow dynamic regulation of protein activity, protein assembly, and protein recruitment, allowing cells to respond to signals from their extracellular environment.

[
Resource Details
]
Running Interference for Hedgehog Signaling
Authors: Michelson Alan M.
Published: September 2003

The new technology of RNA interference (RNAi) is allowing high-throughput screening of cells to examine many biological processes. Michelson discusses one such system in which the
Drosophila
Hedgehog (Hh) pathway was analyzed by systematic genome-wide RNAi analysis. The results not only suggest unexpected overlap in the Hh and Wingless (Wg) pathways, but also provide proof of principle for the development of high-throughput assays using RNAi techniques.
Biolistic Transfection of Cultured Myotubes
Authors: Antolik Christian , De Deyne Patrick G. , Bloch Robert J.
Published: September 2003

Transfection of cells in culture with cDNA constructs is a powerful tool in cell biology, but postmitotic cells, including myotubes, can be hard to transfect with classic methods. Biolistics provides an alternative. We have used this biolistic technique to introduce cDNAs into cultured rat, chick, and C2C12 myotubes. This protocol results in efficient (20 to 70%, depending on cell type) transfection of myotubes, high levels of cDNA expression in individual myotubes, and little cellular damage. Using this procedure, we have expressed different muscle-specific cDNAs as green fluorescent protein (GFP) fusions. This technique is rapid, reliable, uses minimal amounts of reagent per transfection, and yields high transfection rates in a previously hard-to-transfect cell type. Its efficiency and reliability are high, regardless of plasmid size or epitope tag. Muscle cell biologists may now perform experiments in mature myotubes rather than relying on transfection of myoblast cultures or heterologous expression systems.
AIF: A Multifunctional Cog in the Life and Death Machine
Authors: Hansen Tania M. , Nagley Phillip
Published: September 2003

Mitochondria have a dual role in cellular life and death as life-promoting energy providers and as contributors to programmed cell death (apoptosis). The precise sequence of events resulting in the permeabilization of the mitochondrial membrane and the release of mitochondrial resident proteins remains an actively explored topic. Hansen and Nagley describe results from mammalian cells and from the nematode
C. elegans
that lead to a feedforward model for mitochondrial destabilization. Furthermore, they describe the mitochondrial and apoptotic functions of several proteins released from mitochondria during progression toward cell death.
Circadian Rhythms in
Drosophila
: A Connections Map
Authors: Van Gelder Russell N.
Published: September 2003

Genetic and biochemical experiments over the past decade have allowed the construction of a viable working model for the molecular mechanisms underlying circadian rhythm generation in
Drosophila
. The basic mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a Per-Arnt-Sim (PAS)-domain-containing positive transcription factor, Clock. The second loop--the "negative loop"--controls the transcription of
period
and
timeless
, two genes encoding repressor proteins. The loops are intertwined because Period and Timeless directly repress transcription mediated by the Clock:Cycle heterodimer, whereas Clock:Cycle drives transcription of
period
and
timeless
, as well as that of
vrille
, a repressor of
Clock
expression. Other proteins, including kinases encoded by
doubletime
,
shaggy
,
Andante
, and
Timekeeper
, also have essential functions in the timekeeping mechanism. Light cycles can synchronize the
Drosophila
circadian pathway by directly stimulating Cryptochrome-dependent degradation of Timeless. This Pathway Map of the
Drosophila
circadian mechanism describes the individual known components of the fly circadian clock and their mutual interactions. An accompanying animation schematizes the dynamic interactions of the different components.

Science Viewpoint

R. N. Van Gelder, E. D. Herzog, W. J. Schwartz, P. H. Taghert, Circadian rhythms: In the loop at last.
Science
300
, 1534-1535 (2003). [
Abstract
] [
Full Text
]
The FasL-Fas Signaling Network
Authors: Wajant Harald
Published: September 2003

Fas ligand (FasL; also known as APO-1L or CD95L) belongs to the tumor necrosis factor (TNF) ligand family, and its corresponding receptor, Fas (also known as APO-1 or CD95), is a typical member of the death receptor subgroup of the TNF receptor superfamily. Both molecules were originally identified through their apoptosis-inducing capabilities. In recent years, however, roles for Fas and FasL in nonapoptotic processes have become apparent. Fas and FasL have been implicated in such diverse processes as activation-induced cell death (AICD) in T cells, cytotoxic T cell (CTL) function, immune privilege, tumor surveillance, T cell proliferation, dendritic cell differentiation, cardiac hypertrophy, and neurite growth. Many fundamental aspects of the extrinsic apoptotic pathway, including the identification of the death domain, the definition of the death-inducing signaling complex (DISC), the cell type-specific dependency of death receptor induced apoptosis from a mitochondrial amplification loop, and the mechanisms of procaspase activation, were initially identified in the context of Fas-FasL-related studies; thus, this system is a paradigm for apoptotic death receptor signaling. The canonical Fas signaling pathway depicted in the Connections Map provides a comprehensive overview of the molecules and their relations that contribute to the complex signaling network triggered by Fas-FasL interaction.

Science Viewpoint

H. Wajant, The Fas signaling pathway: More than a paradigm.
Science
296
, 1635-1636 (2002). [
Abstract
] [
Full Text
]