bluuebunny/crossref_metadata_2025 huggingface dataset:
STRATEGIC MANAGEMENT IN ENTREPRENEURSHIP: ANALOGIES FROM SUN TZU'S "THE ART OF WAR"
Authors: NG BEOY KUI
Published: November 2004

The paper attempts to draw some of the analogies from Sun Tzu's The art of War for the purpose of formulating and implementing strategic management by an entrepreneur. It is important for an entrepreneur to have vision and strategic intent for his company and this has the same analogy of "dau" in Sun Tzu's military treatise. Sun Tzu also set out five critical success factors for comparative assessment. Incidentally, the five factors are very relevant for the entrepreneur not only for his company's strategic control but also for strategic assessment in business competition. In addition, Sun Tzu also mentioned the importance of building up "strategic advantage" which is equivalent to competitive advantage mentioned in strategic management literature. For strategic positioning, Sun Tzu used "zheng" and "qi" and these two positionings can be varied in accordance with changing circumstances. The concepts have practical importance in formulating functional-level, business-level, global-level and corporate-level strategies. On strategic implementation, Sun Tzu emphasized appropriate organizational structure for strategic fit and the intelligent use of information to grasp opportunities to achieve final victory.
MANAGEMENT TRAINING FOR THE SMALL-MEDIUM SIZED ENTERPRISE: DEVELOPING A RESEARCH APPROACH FOR THE FIRST TIME SMALL BUSINESS RESEARCHER
Authors: WYER PETER , JOHL SATIRENJIT KAUR
Published: November 2004

A young researcher who is new to small business research needs to accept that management is a nascent discipline and that the process of advancing knowledge is fraught with difficulties. This paper focuses on the approach utilised by a young new management studies lecturer, specialising in a large company oriented Human Resource Management knowledge-base, wishing to research for the first time on small business and its management training needs. The paper demonstrates how the shortcomings and difficulties of small business management research can be utilised as "signposts" to guide any future small business researcher. Integral to this signposting is the debate on quantitative versus qualitative research methodology. An alternative philosophical foundation is then considered allowing the co-existence of both methodologies. The paper also draws attention to the difficulties and shortcomings inherent in such a research approach and considers the role of "partial frameworking" in assisting the new researcher to develop an understanding from which to achieve a structured approach to case study methodology.
THE INTERNATIONALISATION OF SMALL-AND MEDIUM SIZED ENTERPRISES: TOWARDS AN ALTERNATIVE CONCEPTUAL FRAMEWORK
Authors: WYER PETER , BOOCOCK GRAHAME , ABDUL-HAMID IBRAHIM
Published: November 2004

The business world today is characterised by a high degree of globalisation and internationalisation - a phenomena which affect all firms irrespective of size. After a summary of current learning theories, and the representation of an SME as a 'potentially unique problem type', the paper offers a critique of previous studies on internationalisation. A research methodology of 'bootstrapping' is utilised to develop a framework for explaining how SMEs in Malaysia identify, then tackle, opportunities and threats in the international arena. A broad analytical framework is developed, combining partial frameworks of insight from the literature in a range of academic disciplines (SMEs, strategic management, internationalisation and learning theory) with insights from key informants in current empirical work. The value chain is an essential component of the overall framework, underpinned by an organisational learning perspective. Our initial findings are only tentative. We do not present a 'model' of good business practice, rather a conceptual framework to examine how SMEs learn to develop in an international sense. This framework is helpful in explaining the development of firms encountered in our empirical research.
TOWARDS THE DEVELOPMENT OF AN ENTREPRENEURIAL CULTURE IN INDIAN COMMERCIAL BANKS USING A VALUE BASE MODEL
Authors: ROHMETRA NEELU
Published: November 2004

The entrepreneurial role of a manager depends on the entrepreneurial culture. Developing entrepreneurial culture assumes the importance of Human Resource Development (HRD). It is the function of the general climate, development mechanisms and the value base. The present work is based on an indepth study conducted by the author to examine the impact of prevailing entrepreneurial culture in selected Indian Commercial banks. They are: State Bank of India (SBI), Punjab National Bank (PNB), Oriental Bank of Commerce (OBC), and Dena Bank (DB). The entrepreneurial climate leading to entrepreneurial culture has been studied under three broad aspects: (i) general climate, (ii) development mechanisms, and (iii) the value base. The value base forms the main focus of the study. The effectiveness of the value based entrepreneurial culture has been judged in relation to the level of satisfaction enjoyed in all the banks covered under study. The study reveals the existence of an intimate relationship between entrepreneurial culture and employee satisfaction which is supported by the level of mean scores obtained for both the variables in these banks. While the entrepreneurial climate for SBI, PNB, OBC and OB has been estimated at mean score levels of 3.49, 3.41, 3.88 and 2.84 respectively, the corresponding satisfaction level has been calculated at mean scores of 3.84, 3.63, 4.01 and 3.06 for these banks.
THE ENTREPRENEUR'S CHOICE: GROWTH INHIBITING BUSINESS PRACTICES OF SMEs IN SCOTLAND AND IRELAND
Authors: MAYFIELD WILLIAM M. , HYNES BRIGA
Published: November 2004

It is critical to the economic development of a given society that entrepreneurs initiate and grow new ventures. Even though the maturation process is unique for every business, there are predictable patterns that occur in sequential and progressive stages of the maturation process (Eggers, Leahy and Churchill, 1994; Hynes, 1992; Dodge and Robbins, 1992; Churchill and Lewis, 1983).

Hay and Kaushad (1994) suggested that decisions made by entrepreneurs effect the growth of a business. Therefore, this paper assumes that the choices and/or decisions, as made by the entrepreneur, effects the growth of SMEs. The purpose of this study was an attempt to identify those business choices and/or decisions that inhibit the growth of Irish and Scottish SMEs. The researchers utilised an American model the SME growth patterns developed by Eggers, Leahy and Churchill.

The business practices that were ascertained to be growth inhibiting were identified as such within the contexts and environments in which they were found. As an analysis of the findings from this study indicates, the entrepreneur is the primary controlling factor of the growth for SMEs. It may be that the aspiration or desire for growth exists, however, it is not translated into action due to the inability or unwillingness of the entrepreneur. The result is the firm never reaches its maximum growth potential.
Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases
Authors: Makino Ayako , Glogauer Michael , Bokoch Gary M. , Chien Shu , Schmid-Schönbein Geert W.
Published: November 2004

Blood vessels and blood cells are under continuous fluid shear. Studies on vascular endothelium and smooth muscle cells have shown the importance of this mechanical stress in cell signal transduction, gene expression, vascular remodeling, and cell survival. However, in circulating leukocytes, shear-induced signal transduction has not been investigated. Here we examine in vivo and in vitro the control of pseudopods in leukocytes under the influence of fluid shear stress and the role of the Rho family small GTPases. We used a combination of HL-60 cells differentiated into neutrophils (1.4% dimethyl sulfoxide for 5 days) and fresh leukocytes from Rac knockout mice. The cells responded to shear stress (5 dyn/cm2) with retraction of pseudopods and reduction of their projected cell area. The Rac1 and Rac2 activities were decreased by fluid shear in a time- and magnitude-dependent manner, whereas the Cdc42 activity remained unchanged (up to 5 dyn/cm2). The Rho activity was transiently increased and recovered to static levels after 10 min of shear exposure (5 dyn/cm2). Inhibition of either Rac1 or Rac2 slightly but significantly diminished the fluid shear response. Transfection with Rac1-positive mutant enhanced the pseudopod formation during shear. Leukocytes from Rac1-null and Rac2-null mice had an ability to form pseudopods in response to platelet-activating factor but did not respond to fluid shear in vitro. Leukocytes in wild-type mice retracted pseudopods after physiological shear exposure, whereas cells in Rac1-null mice showed no retraction during equal shear. On leukocytes from Rac2-null mice, however, fluid shear exerted a biphasic effect. Leukocytes with extended pseudopods slightly decreased in length, whereas initially round cells increased in length after shear application. The disruption of Rac activity made leukocytes nonresponsive to fluid shear, induced cell adhesion and microvascular stasis, and decreased microvascular density. These results suggest that deactivation of Rac activity by fluid shear plays an important role in stable circulation of leukocytes.
Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria
Authors: Hagopian Kevork , Harper Mary-Ellen , Ram Jesmon J. , Humble Stephen J. , Weindruch Richard , Ramsey Jon J.
Published: November 2004

Calorie restriction (CR) without malnutrition increases maximal life span in diverse species. It has been proposed that reduction in energy expenditure and reactive oxygen species (ROS) production could be a mechanism for life span extension with CR. As a step toward testing this theory, mitochondrial proton leak, H2O2production, and markers of oxidative stress were measured in liver from FBNF1rats fed control or 40% CR diets for 12 or 18 mo. CR was initiated at 6 mo of age. Proton leak kinetics curves, generated from simultaneous measures of oxygen consumption and membrane potential, indicated a decrease in proton leak after 18 mo of CR, while only a trend toward a proton leak decrease was observed after 12 mo. Significant shifts in phosphorylation and substrate oxidation curves also occurred with CR; however, these changes occurred in concert with the proton leak changes. Metabolic control analysis indicated no difference in the overall pattern of control of the oxidative phosphorylation system between control and CR animals. At 12 mo, no significant differences were observed between groups for H2O2production or markers of oxidative stress. However, at 18 mo, protein carbonyl content was lower in CR animals, as was H2O2production when mitochondria were respiring on either succinate alone or pyruvate plus malate in the presence of rotenone. These results indicate that long-term CR lowers mitochondrial proton leak and H2O2production, and this is consistent with the idea that CR may act by decreasing energy expenditure and ROS production.
Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet
Authors: Segawa Hiroko , Yamanaka Setsuko , Ito Mikiko , Kuwahata Masashi , Shono Masayuki , Yamamoto Tadashi , Miyamoto Ken-ichi
Published: November 2004

Dietary phosphate levels regulate the renal brush-border type IIa Na-Pi cotransporter. Another Na-Pi cotransporter, type IIc, colocalizes with type IIa Na-Pi cotransporter in the apical membrane of renal proximal tubular cells. The goal of the present study was to determine whether dietary phosphate levels also rapidly regulate the type IIc Na-Pi cotransporter. Type IIa and type IIc transporter protein levels were increased in rats chronically fed a low-Pi diet compared with those fed a normal-Pi diet. Two hours after beginning a high-Pi diet, type IIa transporter levels were decreased, whereas type IIc protein levels remained unchanged. Western blot analysis of brush-border membrane prepared 4 h after beginning a high-Pi diet showed a significant reduction in type IIc transporter protein levels, and immunohistochemistry showed translocation of the type IIc-immunoreactive signal from the entire brush border to subapical membrane. Membrane fractionation studies revealed a decrease in apical membrane type IIc protein without changes in total cortical type IIc protein, which is compatible with redistribution of type IIc protein from the apical membrane to the dense membrane fraction. The microtubule-disrupting reagent colchicine prevented this reduction in apical type IIc transporter at the apical membrane but had no effect on type IIa transporter levels. These data suggest that the type IIc Na-Pi cotransporter level is rapidly regulated by rapid adaptation to dietary Pi in a microtubule-dependent manner. Furthermore, the mechanisms of the internalization of the type IIc transporter are distinct from those of the type IIa transporter.
Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2in bladder microvascular endothelial cells
Authors: Rickard Alice , Portell Craig , Kell Pamela J. , Vinson Suzanne M. , McHowat Jane
Published: November 2004

Increased mast cell numbers and mast cell activation represent one of the prevalent etiologic theories for interstitial cystitis, an inflammatory condition in the bladder. This study was designed primarily to determine whether increased mast cell tryptase in the bladder wall may play a role in activating bladder endothelial cell phospholipase A2(PLA2), leading to increased inflammatory phospholipid metabolite accumulation, which may propagate the inflammatory process. We stimulated human bladder microvascular endothelial cells with thrombin or tryptase and measured the activation of PLA2and the production of multiple membrane phospholipid-derived inflammatory mediators. Thrombin and tryptase stimulation resulted in activation of a Ca2+-independent PLA2, leading to increased release of arachidonic acid and prostacyclin and increased production of platelet-activating factor. These responses were blocked completely by pretreatment of human bladder microvascular endothelial cells with the Ca2+-independent PLA2-selective inhibitor bromoenol lactone. The combination of increased prostacyclin and platelet-activating factor in the bladder circulation may result in vasodilation and increased polymorphonuclear leukocyte adherence to the endothelium and may facilitate recruitment of polymorphonuclear leukocytes to the bladder wall of patients with interstitial cystitis.
Tracking Whisker and Head Movements in Unrestrained Behaving Rodents
Authors: Knutsen Per Magne , Derdikman Dori , Ahissar Ehud
Published: November 2004

Due to recent advances that enable real-time electrophysiological recordings in brains of awake behaving rodents, effective methods for analyzing the large amount of behavioral data thus generated, at millisecond resolution, are required. We describe a semiautomated, efficient method for accurate tracking of head and mystacial vibrissae (whisker) movements in freely moving rodents using high-speed video. By tracking the entire length of individual whiskers, we show how both location and shape of whiskers are relevant when describing the kinematics of whisker movements and whisker interactions with objects during a whisker-dependent task and exploratory behavior.
Isotopic Renal Function Studies in Severe Hypothyroidism and after Thyroid Hormone Replacement Therapy
Authors: Karanikas Georgios , Schütz Matthias , Szabo Monica , Becherer Alexander , Wiesner Karoline , Dudczak Robert , Kletter Kurt
Published: November 2004

Aim: To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using 99mTc-MAG3 renography. Methods: 27 consecutive thyroidectomized patients (7 males and 20 females) aged 19–79 (mean 53) years were included in the present study. 99mTc-MAG3 renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, 51Cr-EDTA clearance and serum creatinine concentrations were determined. Results: The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 ± 0.44 vs. 1.04 ± 0.32 mg/dl, p < 0.05). According to the 51Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 ± 18 vs. 75 ± 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for 99mTc-MAG3 before and after treatment (total excreted activity 20 min after administration 51 ± 12 vs. 54 ± 14%; Tmax left:right 4.2 ± 1.77 : 3.91 ± 1.06 min vs. 4.1 ± 1.66 : 4.4 ± 1.96 min). Conclusions: We did not find any influence of thyroid hormones on the outcome of 99m Tc-MAG3 renography. As 99mTc-MAG3 reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.
"borrowing Foreign Mirrors and Candles To Illuminate Chinese Civilization": Xue Shaohui's Moral Vision in The Biographies of Foreign Women
Authors: Qian Nanxiu
Published: November 2004

Waiguo lienü zhuan (Biographies of foreign women), the first systematic introduction of foreign women to the Chinese audience, was compiled by the late Qing writer Xue Shaohui (1866-1911) and her husband Chen Shoupeng (1857-?). This project represented an effort to advance the goals of the abortive 1898 reforms, a serious quest to incorporate Western experiences into the education of Chinese women. Through a close comparison with Western language sources, this article examines Xue Shaohui's reconceptualization of women's virtues through rewriting and sometimes twisting the original stories. The analysis focuses on sensitive moral issues—sex and power, the relationship between husband and wife, and the redefinition of wickedness when the conventional definition of a bad woman was no longer pertinent.
Harmonising Computer Crime Laws in Europe
Authors: Walden Ian
Published: November 2004

As the ‘Information Society’ emerges, the European economy and its citizens have become dependent on computers and communication networks. However, with the ravages of the viruses MyDoom and MS Blaster still being felt around the world, the vulnerability of computer systems and networks to criminal crime, as well as potentially terrorist activity, is still fresh in our minds. There is no agreed definition of what constitutes a ‘computer crime’. A computer may constitute the instrument of the crime, such as in murder and fraud; the object of the crime, such as the theft of processor chips; or the subject of the crime, such as ‘hacking’ or ‘cracking’. The involvement of computers may challenge traditional criminal concepts, such as fraud, as well as facilitating particular types of crime, such as child pornography. This article is concerned with the computer as the subject of the crime and with laws that have been established to specifically address activities that attack the integrity of computer and communications networks, such as the distribution of computer viruses. This article examines various initiatives to harmonise substantive criminal law to address the threat of computer integrity crimes, focusing specifically on a draft Council Framework Decision on ‘attacks against information systems’. Consideration is given to the impact the Decision may have when transposed into UK law, through an amendment of existing legislation, the Computer Misuse Act 1990.
Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma
Authors: Choi Carmen , Witzens Mathias , Bucur Marianna , Feuerer Markus , Sommerfeldt Nora , Trojan Andreas , Ho Anthony , Schirrmacher Volker , Goldschmidt Hartmut , Beckhove Philipp
Published: November 2004

Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite extensive therapeutical approaches, cures remain rare exceptions. An important issue for future immunologic treatments is the characterization of appropriate tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was detected on a majority of multiple myeloma cell lines. We analyzed bone marrow and peripheral blood of 68 patients with HLA-A2–positive myeloma for the presence and functional activity of CD8 T cells specific for the MUC1-derived peptide LLLLTVLTV. Forty-four percent of the patients with MM contained elevated frequencies of MUC1-specific CD8 T cells in freshly isolated samples from peripheral blood (PB) or bone marrow (BM) compared with corresponding samples from healthy donors. BM-residing T cells possessed a higher functional capacity upon specific reactivation than PB-derived T cells with regard to interferon γ (IFN-γ) secretion, perforin production, and cytotoxicity.
Tau interaction with microtubules in vivo
Authors: Samsonov Andrey , Yu Jiang-Zhou , Rasenick Mark , Popov Sergey V.
Published: November 2004

Tau is a major microtubule-associated protein which induces bundling and stabilization of axonal microtubules (MTs). To investigate the interaction of tau with MTs in living cells, we expressed GFP-tau fusion protein in cultured Xenopus embryo neurons and performed time-lapse imaging of tau-labeled MTs. Tau uniformly labeled individual MTs regardless of their assembly/disassembly status and location along the axon. Photobleaching experiments indicated that interaction of tau with MTs is very dynamic, with a half-time of fluorescence recovery of the order of 3 seconds. Treatment of cells with taxol, a drug that suppresses MT dynamics, rapidly induced detachment of tau from MTs. Although binding of tau to straight MTs was uniform, there was a heightened concentration of tau at the sites of high MT curvature. Our results suggest that dynamic interaction of tau with MTs may modify local mechanical properties of individual MTs and play a crucial role in the remodeling of the MT cytoskeleton during neuronal plasticity.
Distinct roles for multiple Src family kinases at fertilization
Authors: O'Neill Forest J. , Gillett Jessica , Foltz Kathy R.
Published: November 2004

Egg activation at fertilization requires the release of Ca2+ from the endoplasmic reticulum of the egg. Recent evidence indicates that Src family kinases (SFKs) function in the signaling pathway that initiates this Ca2+ release in the eggs of many deuterostomes. We have identified three SFKs expressed in starfish (Asterina miniata) eggs, designated AmSFK1, AmSFK2 and AmSFK3. Antibodies made against the unique domains of each AmSFK protein revealed that all three are expressed in eggs and localized primarily to the membrane fraction. Both AmSFK1 and AmSFK3 (but not AmSFK2) are necessary for egg activation, as determined by injection of starfish oocytes with dominant-interfering Src homology 2 (SH2) domains, which specifically delay and reduce the initial release of Ca2+ at fertilization. AmSFK3 exhibits a very rapid and transient kinase activity in response to fertilization, peaking at 30 seconds post sperm addition. AmSFK1 kinase activity also increases transiently at fertilization, but peaks later, at 2 minutes. These results indicate that there are multiple SFKs present in starfish eggs with distinct, perhaps sequential, signaling roles.
Function of Rho GTPases in embryonic blood cell migration inDrosophila
Authors: Paladi Magda , Tepass Ulrich
Published: November 2004

Hemocyte development in the Drosophila embryo is a genetic model to study blood cell differentiation, cell migration and phagocytosis. Macrophages, which make up the majority of embryonic hemocytes, migrate extensively as individual cells on basement membrane-covered surfaces. The molecular mechanisms that contribute to this migration process are currently not well understood. We report the generation, by P element replacement, of two Gal4 lines that drive expression of UAS-controlled target genes during early (gcm-Gal4) or late (Coll-Gal4) stages of macrophage migration. gcm-Gal4 is used for live imaging analysis showing that macrophages extend large, dynamic lamellipodia as their main protrusions as well as filopodia. We use both Gal4 lines to express dominantnegative and constitutively active isoforms of the Rho GTPases Rac1, Cdc42, Rho1 and RhoL in macrophages, and complement these experiments by analyzing embryos mutant for Rho GTPases. Our findings suggest that Rac1 and Rac2 act redundantly in controlling migration and lamellipodia formation in Drosophila macrophages, and that the third Drosophila Rac gene, Mtl, makes no significant contribution to macrophage migration. Cdc42 appears not to be required within macrophages but in other tissues of the embryo to guide macrophages to the ventral trunk region. No evidence was found for a requirement of Rho1 or RhoL in macrophage migration. Finally, to estimate the number of genes whose zygotic expression is required for macrophage migration we analyzed 208 chromosomal deletions that cover most of the Drosophila genome. We find eight deletions that cause defects in macrophage migration suggesting the existence of approximately ten zygotic genes essential for macrophage migration.
Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma membrane following EGF stimulation
Authors: Merino-Trigo Ana , Kerr Markus C. , Houghton Fiona , Lindberg Anna , Mitchell Christina , Teasdale Rohan D. , Gleeson Paul A.
Published: November 2004

Sorting nexins are a large family of proteins that contain the phosphoinositide-binding Phox homology (PX) domain. A number of sorting nexins are known to bind to PtdIns(3)P, which mediates their localization to membranes of the endocytic pathway. We show here that sorting nexin 5 (SNX5) can be recruited to two distinct membrane compartments. In non-stimulated cells, the PX domain was independently targeted to endosomal structures and colocalized with full-length SNX5. The membrane binding of the PX domain was inhibited by the PI 3-kinase inhibitor, wortmannin. Although SNX5 colocalized with a fluid-phase marker and was found predominantly within a PtdIns(3)P-rich endosomal domain, very little colocalization was observed between SNX5 and the PtdIns(3)P-binding protein, EEA1. Using liposome-based binding assays, we have shown that the PX domain of SNX5 interacts not only with PtdIns(3)P but also with PtdIns(3,4)P2. In response to EGF stimulation, either the SNX5-PX domain or full-length SNX5 was rapidly recruited to the plasma membrane. The localization of SNX1, which does not bind PtdIns(3,4)P2, was unaffected by EGF signalling. Therefore, SNX5 is localized to a subdomain of the early endosome distinct from EEA1 and, following EGF stimulation and elevation of PtdIns(3,4)P2, is also transiently recruited to the plasma membrane. These results indicate that SNX5 may have functions not only associated with endosomal sorting but also with the phosphoinositide-signalling pathway.
Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains
Authors: Mazzone Marco , Baldassarre Massimiliano , Beznoussenko Galina , Giacchetti Giada , Cao Jian , Zucker Stanley , Luini Alberto , Buccione Roberto
Published: November 2004

The integral membrane type 1 matrix metalloprotease (MT1-MMP) is a pivotal protease in a number of physiological and pathological processes and confers both non-tumorigenic and tumorigenic cell lines with a specific growth advantage in a three-dimensional matrix. Here we show that, in a melanoma cell line, the majority (80%) of MT1-MMP is sorted to detergent-resistant membrane fractions; however, it is only the detergent-soluble fraction (20%) of MT1-MMP that undergoes intracellular processing to the mature form. Also, this processed MT1-MMP is the sole form responsible for ECM degradation in vitro. Finally, furin-dependent processing of MT1-MMP is shown to occur intracellularly after exit from the Golgi apparatus and prior to its arrival at the plasma membrane. It is thus proposed that the association of MT1-MMP with different membrane subdomains might be crucial in the control of its different activities: for instance in cell migration and invasion and other less defined ones such as MT1-MMP-dependent signaling pathways.
Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane
Authors: Schuck Sebastian , Simons Kai
Published: November 2004

Polarized cells establish and maintain functionally distinct surface domains by an elaborate sorting process, which ensures accurate delivery of biosynthetic cargo to different parts of the plasma membrane. This is particularly evident in polarized epithelial cells, which have been used as a model system for studies of sorting mechanisms. The clustering of lipid rafts through the oligomerization of raft components could be utilized for segregating apical from basolateral cargo and for the generation of intracellular transport carriers. Besides functioning in polarized sorting in differentiated cells, raft clustering might also play an important role in the biogenesis of apical membrane domains during development.
Implications of Pharmaceutical Industry Funding on Clinical Research
Authors: Lexchin Joel R
Published: November 2004

This commentary explores the influence of industry funding and offers suggestions for overcoming some of the problems. First, it is difficult to obtain funding from some sources for research with limited commercial value. Second, lack of communication among researchers can impede scientific progress. Stopping research before meaningful results are available is another area of concern. Next, suppressed or delayed publication of data may bias the results of meta-analyses, resulting in incorrect risk—benefit profiles for drugs. Finally, commercially funded clinical research is more likely to yield positive results than when funding comes from other sources. Possible solutions are explored.
Aprepitant: A Novel Antiemetic for Chemotherapy-Induced Nausea and Vomiting
Authors: Massaro Alison M , Lenz Kristi L
Published: November 2004

OBJECTIVE:

To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV).

DATA SOURCES:

MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869.

STUDY SELECTION AND DATA EXTRACTION:

Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information.

DATA SYNTHESIS:

The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted.

CONCLUSIONS:

Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.
Peroxynitrite-Induced Neuronal Apoptosis Is Mediated by Intracellular Zinc Release and 12-Lipoxygenase Activation
Authors: Zhang Yumin , Wang Hong , Li Jianrong , Jimenez Daniel A. , Levitan Edwin S. , Aizenman Elias , Rosenberg Paul A.
Published: November 2004

Peroxynitrite toxicity is a major cause of neuronal injury in stroke and neurodegenerative disorders. The mechanisms underlying the neurotoxicity induced by peroxynitrite are still unclear. In this study, we observed that TPEN [N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylenediamine], a zinc chelator, protected against neurotoxicity induced by exogenous as well as endogenous (coadministration of NMDA and a nitric oxide donor, diethylenetriamine NONOate) peroxynitrite. Two different approaches to detecting intracellular zinc release demonstrated the liberation of zinc from intracellular stores by peroxynitrite. In addition, we found that peroxynitrite toxicity was blocked by inhibitors of 12-lipoxygenase (12-LOX), p38 mitogen-activated protein kinase (MAPK), and caspase-3 and was associated with mitochondrial membrane depolarization. Inhibition of 12-LOX blocked the activation of p38 MAPK and caspase-3. Zinc itself induced the activation of 12-LOX, generation of reactive oxygen species (ROS), and activation of p38 MAPK and caspase-3. These data suggest a cell death pathway triggered by peroxynitrite in which intracellular zinc release leads to activation of 12-LOX, ROS accumulation, p38 activation, and caspase-3 activation. Therefore, therapies aimed at maintaining intracellular zinc homeostasis or blocking activation of 12-LOX may provide a novel avenue for the treatment of inflammation, stroke, and neurodegenerative diseases in which the formation of peroxynitrite is thought to be one of the important causes of cell death.
Decreased Synaptic Activity Shifts the Calcium Dependence of Release at the Mammalian Neuromuscular JunctionIn Vivo
Authors: Wang Xueyong , Engisch Kathrin L. , Li Yingjie , Pinter Martin J. , Cope Timothy C. , Rich Mark M.
Published: November 2004

We examined the mechanism underlying increased quantal content after block of activity at the mouse neuromuscular junctionin vivo. We found that, when quantal content was measured in solution containing normal extracellular calcium, block of activity had no effect on either quantal content or the response to repetitive stimulation. However, when quantal content was measured in low extracellular calcium, there was a large increase in quantal content after block of activity. The increase in quantal content was accompanied by increased depression during repetitive stimulation. The explanation for these findings was that there was a shift in the calcium dependence of release after block of activity that manifested as an increase in probability of release in low extracellular calcium. Block of presynaptic P/Q channels eliminated the increase in probability of release. We propose that activity-dependent regulation of presynaptic calcium entry may contribute to homeostatic regulation of quantal content.
Control of Attention Shifts between Vision and Audition in Human Cortex
Authors: Shomstein Sarah , Yantis Steven
Published: November 2004

Selective attention contributes to perceptual efficiency by modulating cortical activity according to task demands. Visual attention is controlled by activity in posterior parietal and superior frontal cortices, but little is known about the neural basis of attentional control within and between other sensory modalities. We examined human brain activity during attention shifts between vision and audition. Attention shifts from vision to audition caused increased activity in auditory cortex and decreased activity in visual cortex and vice versa, reflecting the effects of attention on sensory representations. Posterior parietal and superior prefrontal cortices exhibited transient increases in activity that were time locked to the initiation of voluntary attention shifts between vision and audition. These findings reveal that the attentional control functions of posterior parietal and superior prefrontal cortices are not limited to the visual domain but also include the control of crossmodal shifts of attention.
A Role of Ventral Tegmental Area Glutamate in Contextual Cue-Induced Relapse to Heroin Seeking
Authors: Bossert Jennifer M. , Liu Shirley Y. , Lu Lin , Shaham Yavin
Published: November 2004

The environmental context previously associated with opiate use plays an important role in human relapse, but the neuronal mechanisms involved in context-induced drug relapse are not known. Using a rat relapse model, we determined the effect of a group II metabotropic glutamate receptor agonist [LY379268 ((-)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic acid)] on contextual cue-induced reinstatement of heroin seeking.LY379268, which acts centrally to reduce evoked glutamate release, was injected systemically or directly into the ventral tegmental area (VTA), a brain area involved in opiate reward and conditioned drug effects. Rats were trained to self-administer intravenous heroin for 12 d; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of lever responding,LY379268was injected systemically or into the VTA, and nonreinforced responding was determined in the extinction context or the drug context. Exposure to the heroin-associated context induced robust reinstatement of drug seeking, and this effect was attenuated by systemic or intra-VTA injections of LY379268. Results indicate that glutamate transmission in the VTA plays an important role in contextual cue-induced relapse to heroin seeking.
Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction
Authors: Santoro Bina , Wainger Brian J. , Siegelbaum Steven A.
Published: November 2004

Hyperpolarization-activated cation currents (Ih) are carried by channels encoded by a family of four genes (HCN1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. HCN1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density ofIh. Expression ofIhis also regulated by neuronal activity. To isolate proteins that may control HCN channel expression or function, we performed yeast two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as bait. We identified a brain-specific protein, which has been previously termed TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p-related protein), that specifically interacts with all four HCN channels through a conserved sequence in their C-terminal tails.In situhybridization and immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is disrupted after deletion of HCN1 through homologous recombination, demonstrating a keyin vivointeraction between HCN1 and TRIP8b. TRIP8b dramatically alters the trafficking of HCN channels heterologously expressed inXenopusoocytes and human embryonic kidney 293 cells, causing a specific decrease in surface expression of HCN protein andIhdensity, with a pronounced intracellular accumulation of HCN protein that is colocalized in discrete cytoplasmic clusters with TRIP8b. Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases nativeIhdensity. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane.
Estrogen Receptor (ER)β Isoforms Rather Than ERα Regulate Corticotropin-Releasing Hormone Promoter Activity through an Alternate Pathway
Authors: Miller William J. Schouler , Suzuki Shotaro , Miller Lydia K. , Handa Robert , Uht Rosalie M.
Published: November 2004

The hypothalamic-pituitary-adrenal axis regulates mammalian stress responses by secreting glucocorticoids. The magnitude of the response is in part determined by gender, for in response to a given stressor, circulating glucocorticoids reach higher levels in female rats than in males. This gender difference could result from estrogen regulation of the corticotropin-releasing hormone (CRH) promoter via either of its receptors: estrogen receptor (ER)α or ERβ. Immunocytochemistry revealed that a subset (12%) of medial parvocellular CRH neurons in the rat hypothalamus contain ERβ but not ERα. To determine whether ERs could regulate CRH promoter activity, we cotransfected cells with a CRH promoter construct and either ERα or individual ERβ isoforms. ERα weakly stimulated CRH promoter transcriptional activity in a ligand-independent manner. Conversely, all ERβ isoforms tested stimulated CRH promoter activity with different ligand profiles. ERβ1 and ERβ2δ3 displayed constitutive activity (ERβ1 more than ERβ2δ3). Ligand-dependent activity of β isoforms 1 and 2 was altered by anExon3splice variant (δ3) or by the additional 18 amino acids in the ligand-binding domain of ERβ2 isoforms. Lastly, we suggest that ER regulation of CRH takes place through an alternate pathway, one that requires protein-protein interactions with other transcription factors or their associated complexes. However, a pure ER-activator protein-1 alternate pathway does not appear to be involved.
Culture and ideology in the English‐speaking Caribbean: a view from Jamaica
Authors: AUSTIN DIANE J.
Published: November 2004

Anthropology in the English‐speaking Caribbean displays a tension between analyses that stress opposition and those that stress domination. I specify this antinomy as one between cultural opposition and ideological domination and illustrate how both themes can and should be incorporated within a single analytical perspective. To this end I offer a reinterpretation of the plural society debate and discuss some aspects of class culture and ideological domination in Kingston, Jamaica. [Caribbean, class, culture, ideology, domination, Jamaica]
kin selection and culture
Authors: HAWKES KRISTEN
Published: November 2004

Social kinship is not equivalent to genetic relatedness, and it is social kinship that organizes much of human action. The soundness of this generalization does not imply that the theory of kin selection developed in evolutionary biology is inapplicable to culture. This paper uses data from Binumarien, a small Highland New Guinea community, to test a prediction from kin selection and to illustrate the use of sociobiological perspectives to explain culture, not explain it away. [culture and biology, kinship, inclusive fitness, social organization, sociobiology, Highland New Guinea]
shamanism and schizophrenia: a state‐specific approach to the “schizophrenia metaphor” of shamanic states
Authors: NOLL RICHARD
Published: November 2004

Shamanism and schizophrenia are examined as altered states of consciousness. A state‐specific approach to the phenomenology of these altered states is employed to demonstrate that the existence in the anthropological literature of the “schizophrenia metaphor” of shamanism and its altered states is untenable. A current psychiatric diagnostic manual is utilized to show that significant phenomenological differences exist between the shamanic and schizophrenic states of consciousness. [shamanism, schizophrenia, altered states of consciousness, spirit possession, ethnopsychiatry, psychological anthropology].
sexism and the construction of reality: an Afro‐American example
Authors: PRICE SALLY
Published: November 2004

The literature on the art of the Suriname Maroons depicts men as active artists producing decorative woodcarvings as gifts of love for their women, who are passive connoisseurs. This paper explores the ways by which Maroon women use their own arts to affirm their social relationships and to reflect on them. It also traces misconceptions about Maroon women and their arts to notions of gender that are held by ethnographers and by the Maroons themselves. [Afro‐America, gender, art, song, women].
Icelandic foremen and skippers: the structure and evolution of a folk model
Authors: PÁLSSON GÍSLI , DURRENBERGER E. PAUL
Published: November 2004

There are two folk models to explain differential fishing success in Iceland. One applies to the short term and is based on material factors; the other refers to the long term of seasons and careers and centers on the personal qualities of skippers, or the skipper effect. We show first that the skipper effect cannot account for differential fishing success. We then develop a sociological explanation for the ideology of the skipper effect and show how the ideology developed in response to historical changes in the social relations of production in fishing from the 19th century as labor and fish both became commodities, as Iceland gained independence from Denmark, and as new fishing technology developed. Finally, we describe the earlier conceptual scheme of fishing, which entailed foremen rather than skippers, and show how the role of skipper became elaborated as fishing developed into an autonomous economic field separate from other aspects of peasant production. [fishing, folk models, Iceland, social relations of production, history]
inheritance and social organization among family farmers
Authors: ROGERS SUSAN CAROL , SALAMON SONYA
Published: November 2004

Comparative analysis of two French farming communities and two communities of Illinois grain farmers indicates that a similar range of variation in social organization is to be found at different levels of economic development. This is explained by the proposition that agriculturalists in all four communities share, as family farmers, a common set of fundamental concerns and a limited range of responses to them. Two contrasting French/American pairs may be distinguished according to preferred inheritance strategies and are shown to be distinguishable according to demographic traits as well. A second set of opposing French!American pairs, defined according to degree of conformity to ideal inheritance systems, are found to be associated with contrasting patterns of social relations.[farmers, inheritance, family relationships, agricultural development, North America, western Europe]
ritual and cultural reproduction in non‐Islamic Java
Authors: HEFNER ROBERT W.
Published: November 2004

Recent studies link the problem of cultural transmission to the larger issue of how we conceptualize cultural history and integration. I address this question here by examining reproduction and change in lava's only surviving Indic priesthood. The conflict of meanings characteristic of priestly and popular ritual culture in modern Tengger has a history shaped by the differing modes of cultural transmission around which this non‐Islamic tradition was organized. I also raise some questions as to the relation of social order to cultural form and of public symbolism to private thought, [cultural transmission, religious change, Indonesia, Islam and Hinduism, myth and ritual]
goals in reproductive decision making
Authors: NARDI BONNIE A.
Published: November 2004

This paper presents a model of fertility decision making in which goals, plans, and expectations organize the cultural knowledge used in deciding on the number and timing of children for Western Samoan village women. Coals, plans, and expectations coalesce into scenarios that depict the imagined consequences of a course of actions under consideration by the decision maker. These scenarios are loosely connected to one another in a life sketch that links the major life goals of the decision maker, [decision making, knowledge systems, goals, fertility behavior, Samoa]