bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing the participation of gastroenterologists and hepatologists in clinical research
Authors: Dev Anouk T , Kauf Teresa L , Zekry Amany , Patel Keyur , Heller Karen , Schulman Kevin A , McHutchison John G
Published: October 2008

Background

Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.

Methods

We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.

Results

A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; P < .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.

Conclusion

This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.
Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans
Authors: Sela Noa , Stern Adi , Makalowski Wojciech , Pupko Tal , Ast Gil
Published: October 2008

Transposable elements may acquire unrelated gene fragments into their sequences in a process called transduplication. Transduplication of protein-coding genes is common in plants, but is unknown of in animals. Here, we report that the Turmoil-1 transposable element in C. elegans has incorporated two protein-coding sequences into its inverted terminal repeat (ITR) sequences. The ITRs of Turmoil-1 contain a conserved RNA recognition motif (RRM) that originated from the rsp-2 gene and a fragment from the protein-coding region of the cpg-3 gene. We further report that an open reading frame specific to C. elegans may have been created as a result of a Turmoil-1 insertion. Mutations at the 5' splice site of this open reading frame may have reactivated the transduplicated RRM motif.

Reviewers

This article was reviewed by Dan Graur and William Martin. For the full reviews, please go to the Reviewers' Reports section.
Analysis of N-terminal pro-B-type natriuretic peptide and cardiac index in multiple injured patients: a prospective cohort study
Authors: Kirchhoff Chlodwig , Leidel Bernd A , Kirchhoff Sonja , Braunstein Volker , Bogner Viktoria , Kreimeier Uwe , Mutschler Wolf , Biberthaler Peter
Published: October 2008

Introduction

Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS.

Methods

Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP® assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution.

Results

Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 ± 21 pg/mL in group A versus 209 ± 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001).

Conclusions

Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.
Power and sample size estimation in high dimensional biology
Authors: Gadbury Gary L , Page Grier P , Edwards Jode , Kayo Tsuyoshi , Prolla Tomas A , Weindruch Richard , Permana Paska A , Mountz John D , Allison David B
Published: October 2008

Genomic scientists often test thousands of hypotheses in a single experiment. One example is a microarray experiment that seeks to determine differential gene expression among experimental groups. Planning such experiments involves a determination of sample size that will allow meaningful interpretations. Traditional power analysis methods may not be well suited to this task when thousands of hypotheses are tested in a discovery oriented basic research. We introduce the concept of expected discovery rate (EDR) and an approach that combines parametric mixture modelling with parametric bootstrapping to estimate the sample size needed for a desired accuracy of results. While the examples included are derived from microarray studies, the methods, herein, are ‘extraparadigmatic’ in the approach to study design and are applicable to most high dimensional biological situations. Pilot data from three different microarray experiments are used to extrapolate EDR as well as the related false discovery rate at different sample sizes and thresholds.
Update in Endocrine Autoimmunity
Authors: Anderson Mark S.
Published: October 2008

Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

Synthesis: Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process.

Conclusion: Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.
MicroRNAs Differentially Expressed in ACTH-Secreting Pituitary Tumors
Authors: Amaral Fernando Colbari , Torres Natalia , Saggioro Fabiano , Neder Luciano , Machado Hélio Rubens , Silva Wilson Araújo , Moreira Ayrton Custódio , Castro Margaret
Published: October 2008

Context: MicroRNAs (miRNAs) are small noncoding RNAs, functioning as antisense regulators of gene expression by targeting mRNA and contributing to cancer development and progression. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome.

Objective: The aim of the study was to analyze the differential expression of let-7a, miR-15a, miR-16, miR-21, miR-141, miR-143, miR-145, and miR-150 in corticotropinomas and normal pituitary tissue and verify whether their profile of expression correlates with tumor size or remission after treatment.

Material and Methods: ACTH-secreting pituitary tumor samples were obtained during transphenoidal surgery from patients with Cushing disease and normal pituitary tissues from autopsies. The relative expression of miRNAs was measured by real-time PCR using RNU44 and RNU49 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2−ΔΔCt method.

Results: We found underexpression of miR-145 (2.0-fold; P = 0.04), miR-21 (2.4-fold; P = 0.004), miR-141 (2.6-fold; P = 0.02), let-7a (3.3-fold; P = 0.003), miR-150 (3.8-fold; P = 0.04), miR-15a (4.5-fold; P = 0.03), miR-16 (5.0-fold; P = 0.004), and miR-143 (6.4-fold; P = 0.004) in ACTH-secreting pituitary tumors when compared to normal pituitary tissues. There were no differences between miRNA expression and tumor size as well as miRNA expression and ratio of remission after surgery, except in patients presenting lower miR-141 expression who showed a better chance of remission.

Conclusion: Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.
Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Human Fetal Lung and Regulation of Its Expression by Interleukin-1β and Cortisol
Authors: Yang Zhen , Zhu Ping , Guo Chunming , Zhu Xiaoou , Sun Kang
Published: October 2008

Context: Glucocorticoids are crucial in fetal lung function. The amount of cortisol available to its receptors is increased by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Glucocorticoids and IL-1β are known to induce 11β-HSD1 expression in a number of tissues, but controversial results were obtained with regard to 11β-HSD1 expression in human fetal lung.

Objective: We examined the expression of 11β-HSD1 and its regulation by cortisol and IL-1β in human fetal lung.

Results: Immunohistochemistry revealed 11β-HSD1 expression in the epithelium and mesenchymal layer of the small bronchus and bronchiole of human fetal lung at 8 months but not at 4 months gestation, which was confirmed by PCR revealing 11β-HSD1 mRNA expression in the fetal lung tissue. By using a cell line derived from human fetal lung fibroblasts, we demonstrated that cortisol (10−5 to 10−3 mmol/liter) or IL-1β (0.1 to 10 ng/ml) induced 11β-HSD1 mRNA expression in a concentration-dependent manner. The induction of 11β-HSD1 by IL-1β was further increased by cortisol, whereas the induction of cyclooxygenase 2 by IL-1β was inhibited by cortisol. Nuclear factor κB activation inhibitor could only block the induction of cyclooxygenase 2 but not 11β-HSD1 by IL-1β, suggesting that different mechanisms were utilized by IL-1β in the regulation of 11β-HSD1 versus proinflammatory mediators. Global inhibition of CCAAT-enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression plasmid could attenuate the induction of 11β-HSD1 by IL-1β, suggesting that C/EBPs may mediate the induction of 11β-HSD1 by IL-1β.

Conclusions: 11β-HSD1 is expressed in human fetal lung; cortisol and IL-1β could synergistically induce its expression.
El Pueblo Mestizo: Modernity, Tradition, and Statecraft in Yucatán, 1870-1907
Authors: Eiss Paul K.
Published: October 2008

This article concerns the concept and rhetoric of “el pueblo” in Yucatán during the regime of Mexican president Porfirio Díaz, from the 1870s forward. In Yucatán, this era was one of radical change, bringing the transformation and expansion of the region's henequen hacienda economy, the rise of the institution of debt servitude, affecting both indigenous Yucatec Mayan and working-class mestizo populations, and the rise of encompassing political rhetorics of order, progress, and nation building among Porfirian government officials and pueblo-level landowning gentry.

El pueblo both mediated these transformations and was reshaped by them. Local gentry worked as cultural and political brokers, joining forces with state officials in remaking Yucatán as a “modern” and “civilized” state through infrastructural improvements and education aimed at transforming largely indigenous, rural pueblos into staging areas of a modern Mexico. At the same time, the gentry, many of them also of mestizo background, avidly boosted mestizo pueblo “traditions” as forms of statecraft, appropriating pueblo cultural styles as a repertoire through which state and nation might be constructed and the social hierarchies of henequen society might be legitimated. More than just a place, el pueblo became a strategy through which modernity and tradition were collaboratively produced by state officials and local elites. Such performative renderings of el pueblo became paradigmatic signifiers of both mestizo culture and regional Yucatecan identity, occupying pride of place in the cultural repertoire of rule embraced by Yucatán's regional elites from the Porfiriato forward.
“Hard Working, Orderly Little Women”: Mayan Vendors and Marketplace Struggles in Early-Twentieth-Century Guatemala
Authors: Carey David
Published: October 2008

During the first half of the twentieth century, Guatemala was dominated by two of Latin America's most repressive regimes: first that of Manuel Estrada Cabrera (1898-1920) and then that of General Jorge Ubico (1931-44). Though the marketplace was one venue through which these dictators sought to impose their modernization programs of progress and order, criminal records abound with Mayan women disobeying market regulations and more generally disrupting the peace. Beyond putting the women's livelihoods at stake, these conflicts were also struggles over ethnic, gender, and state power. As such, marketplaces were critical both to elite efforts to mold the economy, society, and politics to their ideals and to Mayan efforts to carve out spaces of autonomy. At the same time, some Mayan women used the very institutions and laws that criminalized vendors' behavior to press for their own rights. Even though the state's structures were based on patriarchal and racist notions of authority, they offered Mayan women considerable space to contest male, ladino, and elite power.
Mexico's National Indigenist Institute and the Negotiation of Applied Anthropology in Highland Chiapas, 1951-1954
Authors: Lewis Stephen E.
Published: October 2008

Based on documents housed in Mexico City and Chiapas, this essay describes how Mexico's National Indigenist Institute (INI) managed to establish its pilot Coordinating Center in highland Chiapas in 1951. Facing opposition from the state government, the state alcohol monopoly, and many Tzeltal and Tzotzil indigenous communities, the INI employed bilingual indigenous “cultural promoters” to negotiate its programs in education, road construction, and public health. As it turns out, the INI's most innovative negotiating tool was a bilingual hand-puppet troupe, the Teatro Petul, which promoted the INI's unpopular public health campaigns. By 1954, the INI and its cultural promoters had built dozens of bilingual schools and a road network in the highlands and were challenging the abuses of local non-Indians, especially those associated with the alcohol monopoly.

Paradoxically, the INI's initial success in Chiapas also contained the seeds for its eventual failure. In its bids to overcome opposition to its programs, the INI relied heavily on its indigenous brokers. Many of these men later used their relatively privileged positions to control access to government resources and secure political positions within their communities. The INI's negotiations with the state government and the alcohol monopoly taught indigenistas that it was easier to induce change on Indians than it was to challenge the overarching political and economic systems that exploited them. Mexican indigenistas crafted a development model that focused inward, on the indigenous themselves, and avoided clashes with powerful interests. This strategy allowed the INI to perpetuate itself and survive politically for five decades in Chiapas and the rest of Mexico, but it greatly limited the extent to which Mexican indigenismo could effect real change.
A Visual Political Economy of Maya Representations in Guatemala, 1931-1944
Authors: Little Walter E.
Published: October 2008

This essay discusses how Mayas, and visual images of them as discursively constructed subjects/objects, are located in dictator Jorge Ubico's economic development and modernization policies in the 1930s and 1940s. Ubico's contradictory policies of promoting Maya essentialness in contrast to the cultural and economic assimilation of Mayas informs both Guatemalan and scholarly attitudes about Mayas today. The essay recontextualizes this position by discussing a specific cultural event—the annual fairs that Ubico organized to highlight Guatemala's economic and technological potential—in relation to the photographic representation of Mayas. In the fair, backward, inefficient “Indian” Guatemala was contrasted with a modern, efficient nation. Maya “pueblos,” showcasing crafts and indigenous life, were reconstructed alongside midway rides and technology exhibits. Using a political economic analysis, particular attention is given to the visual representation of Mayas during this time, in order to discuss their role in tourism within the government's modernization agenda and how this ultimately contributed to Maya and national identity constructions.
Mechanotransduction – a field pulling together?
Authors: Chen Christopher S.
Published: October 2008

Mechanical stresses are ever present in the cellular environment, whether through external forces that are applied to tissues or endogenous forces that are generated within the active cytoskeleton. Despite the wide array of studies demonstrating that such forces affect cellular signaling and function, it remains unclear whether mechanotransduction in different contexts shares common mechanisms. Here, I discuss possible mechanisms by which applied forces, cell-generated forces and changes in substrate mechanics could exert changes in cell function through common mechanotransduction machinery. I draw from examples that are primarily focused on the role of adhesions in transducing mechanical forces. Based on this discussion, emerging themes arise that connect these different areas of inquiry and suggest multiple avenues for future studies.
Kazrin regulates keratinocyte cytoskeletal networks, intercellular junctions and differentiation
Authors: Sevilla Lisa M. , Nachat Rachida , Groot Karen R. , Watt Fiona M.
Published: October 2008

Kazrin is an evolutionarily conserved protein that is upregulated during keratinocyte terminal differentiation. Kazrin localizes to desmosomes and binds the epidermal cornified envelope protein periplakin. Kazrin overexpression in human epidermal keratinocytes caused profound changes in cell shape, reduced filamentous actin, reorganized keratin filaments, and impaired assembly of intercellular junctions. These effects were attributable to decreased Rho activity in kazrin-overexpressing cells. Kazrin overexpression also stimulated terminal differentiation and reduced clonal growth in culture. Knockdown of kazrin decreased expression of differentiation markers and stimulated proliferation without changing total Rho activity. We conclude that kazrin is a dual regulator of intercellular adhesion and differentiation in keratinocytes and regulates these processes by Rho-dependent and -independent mechanisms.
An intracellular wave of cytochrome c propagates and precedes Bax redistribution during apoptosis
Authors: Lartigue Lydia , Medina Chantal , Schembri Laura , Chabert Paul , Zanese Marion , Tomasello Flora , Dalibart Renée , Thoraval Didier , Crouzet Marc , Ichas François , De Giorgi Francesca
Published: October 2008

Bax is considered to be pivotal in inducing cytochrome c release (CCR) from mitochondria during apoptosis. Indeed, Bax redistributes to the mitochondrial outer membrane (MOM) upon activation and forms homo-multimers that are capable of permeabilizing the MOM. Our attempts to image this sequence of events in single live cells resulted in unexpected observations. Bax redistribution exhibited two distinct components: an early minor redistribution that was silent in terms of homo-multimerization and a major late redistribution that was synchronous with the formation of Bax multimers, but that proceeded belatedly, i.e. only after caspase 3/7 (C3/7) had already been activated. Intriguingly, neither of these two components of redistribution correlated with CCR, which turned out to be spatially organized, propagating as a traveling wave at constant velocity. Strikingly, propagation of the CCR wave (1) preceded signs of in situ Bax conformational activation; (2) appeared to be independent of autocatalytic loops involving a positive feedback of either C3/7, Ca2+ mobilization or mitochondrial permeability transition; and (3) was triggered by diffuse stimulation with the synthetic Bak activator BH3I-1 but then proceeded independently of Bak activation. Thus, the CCR wave not only questions the exact role of Bax redistribution in cell death, but also indicates the existence of yet unidentified positive-feedback loops that ensure a spatiotemporal control of apoptosis at the subcellular scale.
PI3-kinase signaling contributes to orientation in shallow gradients and enhances speed in steep chemoattractant gradients
Authors: Bosgraaf Leonard , Keizer-Gunnink Ineke , Van Haastert Peter J. M.
Published: October 2008

Dictyostelium cells that chemotax towards cAMP produce phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] at the leading edge, which has been implicated in actin reorganization and pseudopod extension. However, in the absence of PtdIns(3,4,5)P3 signaling, cells will chemotax via alternative pathways. Here we examined the potential contribution of PtdIns(3,4,5)P3 to chemotaxis of wild-type cells. The results show that steep cAMP gradients (larger than 10% concentration difference across the cell) induce strong PtdIns(3,4,5)P3 patches at the leading edge, which has little effect on the orientation but strongly enhances the speed of the cell. Using a new sensitive method for PtdIns(3,4,5)P3 detection that corrects for the volume of cytosol in pixels at the boundary of the cell, we show that, in shallow cAMP gradient (less than 5% concentration difference across the cell), PtdIns(3,4,5)P3 is still somewhat enriched at the leading edge. Cells lacking PI3-kinase (PI3K) activity exhibit poor chemotaxis in these shallow gradients. Owing to the reduced speed and diminished orientation of the cells in steep and shallow gradients, respectively, cells lacking PtdIns(3,4,5)P3 signaling require two- to six-fold longer times to reach a point source of chemoattractant compared with wild-type cells. These results show that, although PI3K signaling is dispensable for chemotaxis, it gives the wild type an advantage over mutant cells.
Lkb1 is required for TGFβ-mediated myofibroblast differentiation
Authors: Vaahtomeri Kari , Ventelä Eeva , Laajanen Kaisa , Katajisto Pekka , Wipff Pierre-Jean , Hinz Boris , Vallenius Tea , Tiainen Marianne , Mäkelä Tomi P.
Published: October 2008

Inactivating mutations of the tumor-suppressor kinase gene LKB1 underlie Peutz-Jeghers syndrome (PJS), which is characterized by gastrointestinal hamartomatous polyps with a prominent smooth-muscle and stromal component. Recently, it was noted that PJS-type polyps develop in mice in which Lkb1 deletion is restricted to SM22-expressing mesenchymal cells. Here, we investigated the stromal functions of Lkb1, which possibly underlie tumor suppression. Ablation of Lkb1 in primary mouse embryo fibroblasts (MEFs) leads to attenuated Smad activation and TGFβ-dependent transcription. Also, myofibroblast differentiation of Lkb1–/– MEFs is defective, resulting in a markedly decreased formation of α-smooth muscle actin (SMA)-positive stress fibers and reduced contractility. The myofibroblast differentiation defect was not associated with altered serum response factor (SRF) activity and was rescued by exogenous TGFβ, indicating that inactivation of Lkb1 leads to defects in myofibroblast differentiation through attenuated TGFβ signaling. These results suggest that tumorigenesis by Lkb1-deficient SM22-positive cells involves defective myogenic differentiation.
The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration
Authors: Undyala Vishnu V. , Dembo Micah , Cembrola Katherine , Perrin Benjamin J. , Huttenlocher Anna , Elce John S. , Greer Peter A. , Wang Yu-li , Beningo Karen A.
Published: October 2008

Cell migration involves the dynamic formation and release of cell-substrate adhesions, where the exertion and detection of mechanical forces take place. Members of the calpain family of calcium-dependent proteases are believed to have a central role in these processes, possibly through the regulation of focal adhesion dynamics. The ubiquitous calpains, calpain 1 (μ-calpain) and calpain 2 (m-calpain), are heterodimers consisting of large catalytic subunits encoded by the Capn1 and Capn2 genes, respectively, and the small regulatory subunit encoded by Capn4. We have examined the role of the calpain regulatory small subunit in traction force production and mechanosensing during cell migration. Capn4-deficient or rescued cells were plated on flexible polyacrylamide substrates, for both the detection of traction forces and the application of mechanical stimuli. The total force output of Capn4-deficient cells was ∼75% lower than that of rescued cells and the forces were more randomly distributed and less dynamic in Capn4-deficient cells than in rescued cells. Furthermore, Capn4-deficient cells were less adhesive than wild-type cells and they also failed to respond to mechanical stimulations by pushing or pulling the flexible substrate, or by engaging dorsal receptors to the extracellular matrix. Surprisingly, fibroblasts deficient in calpain 1 or calpain 2 upon siRNA-mediated knockdown of Capn1 or Capn2, respectively, did not show the same defects in force production or adhesion, although they also failed to respond to mechanical stimulation. Interestingly, stress fibers were aberrant and also contained fewer colocalised vinculin-containing adhesions in Capn4-deficient cells than Capn1- and Capn2-knockdown cells. Together, these results suggest that the calpain small subunit plays an important role in the production of mechanical forces and in mediating mechanosensing during fibroblast migration. Furthermore, the Capn4 gene product might perform functions secondary to, or independent of, its role as a regulatory subunit for calpain 1 and calpain 2.
ADictyosteliumhomologue of the metazoan Cbl proteins regulates STAT signalling
Authors: Langenick Judith , Araki Tsuyoshi , Yamada Yoko , Williams Jeffrey G.
Published: October 2008

Cbl proteins downregulate metazoan signalling pathways by ubiquitylating receptor tyrosine kinases, thereby targeting them for degradation. They contain a phosphotyrosine-binding region, comprising an EF-hand and an SH2 domain, linked to an E3 ubiquitin-ligase domain. CblA, a Dictyostelium homologue of the Cbl proteins, contains all three conserved domains. In a cblA– strain early development occurs normally but migrating cblA– slugs frequently fragment and the basal disc of the culminants that are formed are absent or much reduced. These are characteristic features of mutants in signalling by DIF-1, the low-molecular-mass prestalk and stalk cell inducer. Tyrosine phosphorylation of STATc is induced by DIF-1 but in the cblA– strain this response is attenuated relative to parental cells. We present evidence that CblA fulfils this function, as a positive regulator of STATc tyrosine phosphorylation, by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. Thus Cbl proteins have an ancient origin but, whereas metazoan Cbl proteins regulate tyrosine kinases, the Dictyostelium Cbl regulates via a tyrosine phosphatase.
Benchmarking Performance in Retail Chains: An Integrated Approach
Authors: Gauri Dinesh Kumar , Pauler Janos Gabor , Trivedi Minakshi
Published: October 2008

Standardizing performance expectations across different outlets within a chain, differing in their individual features, their consumers, and the nature of competition they face, can be an onerous task. We develop an integrated, nonlinear, block group-level market share model of store expectations that draws upon the existing trade area as well as store performance literatures. By incorporating and normalizing a large number of external and internal factors impacting performance, we are able to offer a means for the retailer to determine equitable standards. The model is estimated using a variation of the maximum-likelihood estimation, on a data set fashioned from several sources and aggregated at the block group and store levels. Finally, we propose a set of indices that allows us to evaluate relative performances of stores and regions given the competitive environments they face. We find that a block group-level model offers a better fit, as well as significantly richer implications, than a traditional store-level model. Results show that a significant number of stores operate well below their expected levels, an insight not obvious from the raw numbers used to report store statistics to upper management.
Research Note—How Much Should You Invest in Each Customer Relationship? A Competitive Strategic Approach
Authors: Musalem Andrés , Joshi Yogesh V.
Published: October 2008

We analyze firms' decisions to invest in customer relationship management (CRM) initiatives such as acquisition and retention in a competitive context, a topic largely ignored in past CRM research. We characterize each customer by her intrinsic preference towards each firm, the contribution margin she generates for each firm, and her responsiveness to each firm's retention and acquisition efforts. We show that a firm should invest most heavily in retaining those customers that exhibit moderate responsiveness to its CRM efforts. Further, a firm should most aggressively seek to attract those customers that exhibit moderate responsiveness to their provider's CRM efforts and those that are moderately profitable for their current provider. Investing more in customers that are more responsive does not always lead to higher firm profits, because stronger competition for such customers tends to erode the effects of higher CRM efforts of an individual firm. When firms develop a customer relationship over time to generate higher contribution margin or customer responsiveness, we show that such developments may not always be desirable, because sometimes these future benefits may lead to more intense competition and hence lower profits for both firms.
Exploring the Relationship Between Scientist Human Capital and Firm Performance: The Case of Biomedical Academic Entrepreneurs in the SBIR Program
Authors: Toole Andrew A. , Czarnitzki Dirk
Published: October 2008

There is an emerging debate in the scholarly literature regarding the extent to which academic human capital contributes to firm performance. This debate centers on the nature of an academic scientist's human capital and its institutional specificity. Using data on the human capital of biomedical scientists developed during their careers in academe, this paper analyzes how the depth of their scientifically and commercially oriented academic human capital contributes to firm performance when these scientists subsequently start or join for-profit firms. We find that the scientific and commercial components of an academic scientist's human capital have differential effects on the performance of research and invention tasks at the firm. We also find that the contribution of an academic scientist to a firm's patent productivity is decreasing with the depth of their scientifically oriented human capital, all else constant. These results support the view that academic human capital is heterogeneous and has an institutional specificity that mediates its value when applied in a commercialization environment.
Team Familiarity, Role Experience, and Performance: Evidence from Indian Software Services
Authors: Huckman Robert S. , Staats Bradley R. , Upton David M.
Published: October 2008

Much of the literature on team learning views experience as a unidimensional concept captured by the cumulative production volume of, or the number of projects completed by, a team. Implicit in this approach is the assumption that teams are stable in their membership and internal organization. In practice, however, such stability is rare, because the composition and structure of teams often change over time (e.g., between projects). In this paper, we use detailed data from an Indian software services firm to examine how such changes may affect the accumulation of experience within, and the performance of, teams. We find that the level of team familiarity (i.e., the average number of times that each member has worked with every other member of the team) has a significant positive effect on performance, but we observe that conventional measures of the experience of individual team members (e.g., years at the firm) are not consistently related to performance. We do find, however, that the role experience of individuals in a team (i.e., years in a given role within a team) is associated with better team performance. Our results offer an approach for capturing the experience held by fluid teams and highlight the need to study context-specific measures of experience, including role experience. In addition, our findings provide insight into how the interactions of team members may contribute to the development of broader firm capabilities.
Product-Line Competition: Customization vs. Proliferation
Authors: Mendelson Haim , Parlaktürk Ali K.
Published: October 2008

We study a market with customers who have heterogeneous preferences for product attributes. We consider two types of firms that compete on price and product variety: A traditional firm, which chooses a limited set of product configurations, and a customizing firm, which can produce any configuration to order. The traditional firm carries product inventories and experiences a lead-time delay. The customizing firm does not carry inventory, and its customers incur waiting costs until they receive their orders. We assume that the customizing firm has limited capacity in the short run (e.g., when it does not outsource production to high-volume manufacturers). We derive the equilibrium for a duopoly competition between the customizing firm and the traditional firm, study its characteristics, and compare it to a monopoly. We characterize conditions that favor customization under competition. We find that the customizing firm's profit is not monotone in the market size and its ease of customization. Similarly, a decline in the traditional firm's holding cost may increase or decrease its profit. We show that the unit cost differential between the firms crucially affects the customizing firm's ideal market size, its returns from expanding capacity, its product variety, and the way operational improvements affect its performance.
The Influence of Psychological Safety and Confidence in Knowledge on Employee Knowledge Sharing
Authors: Siemsen Enno , Roth Aleda V. , Balasubramanian Sridhar , Anand Gopesh
Published: October 2008

This research empirically examines the influence of psychological safety on knowledge sharing among coworkers in manufacturing and service operations contexts. Reconciling conflicting findings in the literature, we demonstrate that whereas psychological safety is an important antecedent of knowledge sharing, the relationship between psychological safety and knowledge sharing is moderated by the level of confidence that employees have in what they know. The greater this confidence, the lesser is the importance of psychological safety in facilitating knowledge sharing. Linking this result to social network theory, we find that psychological safety increases with the frequency of communication among coworkers and that the confidence of employees in their knowledge is related to the codifiability of the knowledge involved. We further investigate direct and indirect antecedents of psychological safety. This research offers insights into actions that managers can take to enhance psychological safety and, consequently, motivate their employees to share knowledge.
Certification in the Indian Offshore IT Services Industry
Authors: Gopal Anandasivam , Gao Guodong (Gordon)
Published: October 2008

Third-party process certification programs such as the ISO 9001 and capability maturity model (CMM) have been widely adopted in recent years. In this study we employ three competing theoretical frameworks—signaling, efficiency gains, and institutional theory—to analyze the motivations for a firm to acquire quality certification and the performance implications thereafter. We test these hypotheses in the context of CMM certification based on data from the Indian offshore IT services industry between 1997 and 2002. Our results indicate that more cost-effective firms and export-oriented firms are more likely to seek out and acquire certification. In addition, CMM-certified firms show significant improvements in exports, but not on the firm's cost structure. Furthermore, our findings suggest that CMM certification helps indicate firm capabilities to potential customers and thus appear to be most consistent with signaling explanations of certification rather than the efficiency gains or institutional theories.
Note—Pricing and Inventory Control for a Perishable Product
Authors: Li Yanzhi , Lim Andrew , Rodrigues Brian
Published: October 2008

In this note, we study the concurrent determination of pricing and inventory replenishment decisions for a perishable product in an infinite horizon. Demands in consecutive periods are independent and influenced by prices charged in each period. In particular, we treat price as a decision variable to maximize the total discounted profit. We analyze the optimal solution-structure of a two-period lifetime problem and from insights gained in numerical experiments, develop a base-stock/list-price heuristic policy for products with arbitrary fixed lifetimes. Experiments show this policy to be effective.
Phenotypic response of the diatomPhaeodactylum tricornutumBohlin to experimental changes in the inorganic carbon system
Authors: Bartual Ana , Gálvez J. Angel , Ojeda Fernando
Published: October 2008

The physiology and biochemistry ofPhaeodactylum tricornutumhave been extensively studied, and some aspects of its biology are well known. Phenotypic plasticity is probably one of its most remarkable features. Two basic morphotypes, fusiform and triradiate, can be found in natural liquid environments. Although the transformation from one morphotype to the other has been previously reported, ecological causes and consequences of such transformation remain unknown. Here, we report changes in the relative abundance of the two morphotypes ofPhaeodactylumassociated with changes in the inorganic carbon system. The relative abundance of the triradiate morphotype increased in cultures grown at either high pH or high dissolved inorganic carbon, and markedly so under subsaturating illumination for growth. At high pH, this increase was strongly correlated with a decrease in the overall culture growth rate. At the individual (cell) level, there was a larger increase in the surface area of the triradiate morphotype (resulting in a higher surface-to-volume ratio) than in the fusiform morph under subsaturating illumination for growth. These results provide new insights into the biology of this diatom, mainly related to the performance (fitness) of the two basic morphotypes under contrasting illumination for growth and different inorganic carbon conditions.
Deep-water gelatinous rhodophytes from southern Espírito Santo State, Brazil
Authors: Guimarães Silvia Maria P.B. , Amado-Filho Gilberto Menezes
Published: October 2008

Espírito Santo State lies in a region of transition between tropical and subtropical benthic-algal floras; the region is considered to have the richest algal assemblage in the whole of Brazil. Extensive rhodolith beds cover much of the subtidal substratum in this area and host a diverse assemblage of frondose macrophytes. A detailed exploration at several localities has revealed many little-known and previously unreported taxa that are new to the southwestern Atlantic Ocean. In November 2004, the gelatinous rhodophytesAcrosymphyton caribaeum,Dudresnaya crassa,Naccaria corymbosa,Platomasp. andPredaea feldmanniiwere discovered on rhodoliths at a depth of 18 m. Morphological and reproductive features of the species are provided here, with emphasis on post-fertilization events. The holotype ofPlatoma tenuis, originally described from Brazil, was examined and shown to be a species ofPredaea.Acrosymphyton caribaeumhosted the epiphyte/endophyteColaconema ophioglossum, and this also represents a new report from Brazil. This diverse community probably represents an ephemeral spring-summer element of the wider macroalgal flora.
Champia harveyana sp. nov. (Champiaceae, Rhodophyta) from Puerto Rico, Caribbean Sea
Authors: Ballantine David L. , Lozada-Troche Chad
Published: October 2008

Examination of specimens referable to Champia
salicornioides from offshore algal plains in southwest Puerto Rico (Caribbean Sea) resulted in recognition of algae with different branching origins. Plants with branching from the septal regions are referred to a new species, Champia harveyana. Segregation of the new species is supported by 18S and rbcL sequence analyses as well as differences in internal morphologies. In the new species, walls of older portions are reinforced by a proliferation of longitudinal medullary filaments that line the interior of the cortical layer and nodal septa. Additionally, nodal regions in older parts become thickened by a proliferation of cells outside the original cortical layer. A lectotype of Champia salicornioides is designated.
RuBisCO cistron sequence variation and phylogeography of Ceramium kondoi (Ceramiaceae, Rhodophyta)
Authors: Yang Eun Chan , Cho Ga Youn , Kogame Kazuhiro , Carlile Amy Lynn , Min Boo Sung
Published: October 2008

Ceramium kondoi is a morphologically variable ceramiaceous red alga that occurs commonly in the northwest Pacific Ocean region and has recently been reported in the United States. Forty-five specimens of C. kondoi from 29 locations in Korea, Japan, Russia, and the USA were examined for DNA sequence variation along the whole plastid-encoded RuBisCO cistron: 1406 bp for rbcL, 103 bp for the spacer, and 387 bp for rbcS. C. kondoi specimens were variable, having up to nine haplotypes, with six found in Korea, southern Japan, far-eastern Russia, and the USA, and three found in northern Japan and far-eastern Russia. The occurrence of the same haplotype on both sides of the North Pacific Ocean provides evidence of recent introduction of the species from the west to the east. Phylogenetic reconstructions revealed the monophyly of C. kondoi and two well-supported lineages: a ‘southern lineage’ that contained specimens from Korea, southern Japan, far-eastern Russia and the USA, and a ‘northern lineage’ that included specimens from northern Japan and far-eastern Russia. The two genetic lineages are morphologically indistinguishable and referred to as cryptic species. The boundary between the two cryptic species is at the Tsugaru Strait, Japan.
Distribution, abundance and diversity of modern dinoflagellate cyst assemblages from southern Chile (43–54° S)
Authors: Alves-de-Souza Catharina , Varela Daniel , Navarrete Florencia , Fernández Pamela , Leal Pablo
Published: October 2008

The distribution, abundance and diversity of modern dinoflagellate cyst assemblages were investigated in sediments from the inshore seas of southern Chile (43°08′–54°55′ S) at eight sites from April 2004 to January 2005. A total of 24 cyst types were recorded, of which 12 and five were identified at the species and genus levels, respectively. Dinoflagellate cysts were recorded from all sampling sites, but they differed in total abundance (15–270 cysts ml-1) and diversity index (H′ 0.88–2.40). Heterotrophic dinoflagellate cysts assigned to heterotrophic species were the most abundant trophic form, with 418 cysts ml-1, representing 55% of the total cyst abundance. Cluster analysis based on the abundance of dinoflagellate cyst species indicated that sampling sites were segregated into three groups likely to be related to the proportion of autotrophic vs. heterotrophic species cysts and the total abundance of cysts at each site. Distinctive cyst species composition differences among sampling sites may allow inferences about local nutrient and feeding dynamics within the water column.
The Influence of ΔFosB in the Nucleus Accumbens on Natural Reward-Related Behavior
Authors: Wallace Deanna L , Vialou Vincent , Rios Loretta , Carle-Florence Tiffany L. , Chakravarty Sumana , Kumar Arvind , Graham Danielle L. , Green Thomas A. , Kirk Anne , Iñiguez Sergio D. , Perrotti Linda I. , Barrot Michel , DiLeone Ralph J. , Nestler Eric J. , Bolaños-Guzmán Carlos A.
Published: October 2008

The transcription factor deltaFosB (ΔFosB), induced in nucleus accumbens (NAc) by chronic exposure to drugs of abuse, has been shown to mediate sensitized responses to these drugs. However, less is known about a role for ΔFosB in regulating responses to natural rewards. Here, we demonstrate that two powerful natural reward behaviors, sucrose drinking and sexual behavior, increase levels of ΔFosB in the NAc. We then use viral-mediated gene transfer to study how such ΔFosB induction influences behavioral responses to these natural rewards. We demonstrate that overexpression of ΔFosB in the NAc increases sucrose intake and promotes aspects of sexual behavior. In addition, we show that animals with previous sexual experience, which exhibit increased ΔFosB levels, also show an increase in sucrose consumption. This work suggests that ΔFosB is not only induced in the NAc by drugs of abuse, but also by natural rewarding stimuli. Additionally, our findings show that chronic exposure to stimuli that induce ΔFosB in the NAc can increase consumption of other natural rewards.