bluuebunny/crossref_metadata_2025 huggingface dataset:
The Moderating Effect of Gender on Leadership Intervention Impact
Authors: Avolio Bruce J. , Mhatre Ketan , Norman Steven M. , Lester Paul
Published: April 2009

A total of 57 intervention-based leadership studies that included sufficient data on leader and follower gender were included in this meta-analysis. By intervention, the authors mean any study where the researcher overtly manipulated leadership as the independent variable through training, assignment, scenarios, or other means. Results showed a significant difference in the effect sizes for leadership interventions conducted with all-male and majority-male participants versus all-female and majority-female participant studies; however, these differences varied based on the setting of the intervention, the theoretical basis of the intervention, and the type of outcome. Implications for further research on gender differences with respect to examining cause—effect impact of leadership interventions are discussed.
Perceptions of Acceptability and Enforcement
Authors: Lauver Kristy J. , Lester Scott W. , Lentz Paula J.
Published: April 2009

In this article, two studies using both quantitative and qualitative techniques were used to examine how organizations can use policies and practices to help reduce the likelihood of employees coming to work under the influence of alcohol. Findings indicated that perceptions of currently employed students on the acceptability of being at work under the influence and the likelihood of enforcement of alcohol policies are related to employees' beliefs in how important it is to be coherent while at work and their likelihood of working with alcohol in their systems. Implications of these findings for employers are discussed.
Pride and Gratitude
Authors: Michie Susan
Published: April 2009

This study investigated whether two positive morally relevant emotions, pride and gratitude, were associated with the prosocial behaviors exhibited by organizational leaders. Pride and gratitude were measured as dispositional tendencies in leaders across various types of organizations. The results revealed that a leader's propensity to experience authentic pride was positively related to two types of prosocial behavior—social justice and altruism. Furthermore, the results indicated that leader gratitude mediated the effects of pridefulness on social justice behaviors.
Cognitive Risks of Dyslipidemia
Authors: Terre Lisa
Published: April 2009

This review discusses evidence-based perspectives on the relationship between dyslipidemia and cognitive decline, including strategic implications for risk reduction in primary care and empirically driven public policy initiatives to prevent cognitive dysfunction.
The witness in the archive: Holocaust Studies/ Memory Studies
Authors: Hirsch Marianne , Spitzer Leo
Published: April 2009

What has Holocaust Studies brought to the study of memory, and, conversely, how has theoretical work on the Holocaust been inflected by Memory Studies? Focusing on witness testimony, we argue that the theoretical and philosophical efforts to grasp and define its contours have provoked a radical rethinking of the workings of memory and transmission: in particular, a foregrounding of embodiment, affect and silence. Yet we caution against a hyperbolic emphasis on trauma and the breakdown of speech. We find that the very aporias that have made the Holocaust a touchstone for the study of twentieth-century memory have engendered two distinctive interpretive uses of witness testimony — one linked to a troubling idiom of uniqueness and exceptionalism, potentially supporting nationalist and identity politics, the other, to cosmopolitan or transnational memory cultures able to sustain efforts towards the global attainment of human rights.
When history isn't made but happens: Memories of victimhood in Halberstadt (Germany)
Authors: Neumann Klaus
Published: April 2009

Taking as its point of departure two civic ceremonies on 8 April 2006 in the East German town of Halberstadt, one to commemorate people who had been murdered in a local concentration camp, the other to commemorate the German civilian victims of an Allied air raid, this article discusses memories of victimhood. It is argued that Halberstadt's citizens remember history as something that happened to them. It is demonstrated that, for them, the town itself, rather than human casualties (be they those who perished in a concentration camp or those who were killed in a bombing raid), provides the main focus for their grief. Drawing on the work of Alexander Kluge, it is suggested that memories of the air raid of 8 April 1945 are shaped by the inertia of emotions and of the capacity to remember and mourn.
Forgetting and remembering in the margins: Constructing past and future in the Romanian Danube Delta
Authors: Van Assche Kristof , Devlieger Patrick , Teampau Petruta , Verschraegen Gert
Published: April 2009

This article investigates the process of social forgetting by relating it to the disintegration of social and spatial networks. Looking at the case of Sulina, a small town on the eastern edge of the Romanian Danube Delta, we analyze how the unraveling of networks caused a process of social forgetting with margin-specific features, a fundamental restructuring of social memory and social identities. An important focus of our investigation is the connection between social memory and spatial planning, as a coordinated effort to look forwards. While forgetting as such is seen as a positive process, constitutive of memory, its local characteristics can create problems, for example, for cooperation and planning. Theoretically, this article adopts a systems theoretical framework, incorporating notions derived from anthropology and geography. Social memory is defined as a continuous process of selection, carried out in various specialized subsystems. Concepts of social identity and network are found to be essential in a localized analysis of social memory. Concluding, we argue that local characteristics of social memory can impede the articulation of viable spatial planning strategies.
`We were all there': Remembering America in the anniversary coverage of Hurricane Katrina
Authors: Robinson Sue
Published: April 2009

The study of Hurricane Katrina's anniversary coverage in a dozen national and local mainstream outlets and six books explored whether the journalism followed the `typical' commemoration patterns that press historians have described. Nationally, the press demonized New Orleans as an example of what the country needed to avoid — politically, economically, structurally, morally. Locally, the press did not set agendas, but rather focused on the importance of ritual in recreating a lost community. Instead of creating a mnemonic quagmire, these seemingly disparate narratives sought to restore faith in American redemption, collectively, at a time of national unrest. Such research exemplifies the tension between dominant institutions of the press, government and the Church, how authority is asserted, and the process by which all of this plays out in the news media, forming collective memory according to national ideals and local interests.
Fixing the floating gap: The online encyclopaedia Wikipedia as a global memory place
Authors: Pentzold Christian
Published: April 2009

The article proposes to interpret the web-based encyclopaedia Wikipedia as a global memory place. After presenting the core elements and basic characteristics of wikis and Wikipedia respectively, the article discusses four related issues of social memory studies: collective memory, communicative and cultural memory, `memory places' and the `floating gap'. In a third step, these theoretical premises are connected to the understanding of discourse as social cognition. Fourth, comparison is made between the potential of the World Wide Web as cyberspace for collective remembrance and the obstacles that stand in its way. On this basis, the article argues that Wikipedia presents a global memory place where memorable elements are negotiated. Its complex processes of discussion and article creation are a model of the discursive fabrication of memory. Thus, they can be viewed and analysed as the transition, the `floating gap' between communicative and collective frames of memory.
Outcome Prediction in Microsurgery by Quantitative Evaluation of Perfusion Using ICG Fluorescence Angiography
Authors: MOTHES H. , DINKELAKER T. , DÖNICKE T. , FRIEDEL R. , HOFMANN G. O. , BACH O.
Published: April 2009

The purpose of this prospective study was to evaluate the clinical efficacy of laser-induced fluorescence angiography with indocyanine green (ICG-FA) for perioperative monitoring of tissue perfusion in hand surgery. Different quantitative parameters of the uptake, distribution and clearance of dye-marked blood were evaluated for their sensitivity and prognostic value in comparison to each other and to clinical parameters. One hundred and fifty-five measurements were performed prior to, or following, surgery for severe hand injuries. All quantitative parameters of ICG-FA detected intraoperatively were found to be of significant predictive value for outcome, but clinical parameters were not. For the dye uptake, a minimum slope value of 0.01 was significantly related to sufficient perfusion and good prognosis. There was no correlation between the quantitative ICG-FA results or any of the clinical parameters. Since clinical evaluation of perfusion in this surgery remains difficult, the additional use of ICG-FA may improve surgical decision making and, thereby, lead to better clinical results.
Transfer of the First Intercostal Nerve to Supra- and Infraspinatus Muscles: An Anatomical Study and Report of the First Case
Authors: DURAND S. , OBERLIN C. , FOX M. , DIVERREZ J. P. , DAUGE M. C.
Published: April 2009

We have assessed the anatomical feasibility of a transfer of the first intercostal nerve to the supra- and infraspinatus muscles and report on the first clinical application. Ten fresh cadavers were dissected for this study. Histomorphometric analysis showed the fascicular surface area of the first intercostal nerve at its origin (0.38 mm2) to be comparable to the suprascapular nerve (0.81 mm2). The first intercostal nerve is usually a pure motor nerve. Preservation of the spinal accessory nerve, lack of donor site morbidity and direct suture without nerve graft are the other advantages of this transfer. Its principal indication is in lesions of the upper brachial plexus, used in association with neurotisation of two other intercostal nerves to the anterior branch of the axillary nerve. At 21 months follow-up there was useful motor reinnervation in the first clinical case.
Proximal Row Carpectomy vs Four Corner Fusion for Scapholunate (Slac) or Scaphoid Nonunion Advanced Collapse (Snac) Wrists: A Systematic Review of Outcomes
Authors: MULFORD J. S. , CEULEMANS L. J. , NAM D. , AXELROD T. S.
Published: April 2009

Proximal row carpectomy (PRC) and scaphoid excision with four-corner fusion (4CF) are common motion-preserving, salvage procedures for the treatment of wrists with scaphoid nonunion (SNAC) or scapholunate advanced collapse (SLAC). A systematic review was undertaken to clarify controversies regarding which of these procedures has the better outcome. We collated 52 articles that examine outcomes for SNAC or SLAC patients undergoing PRC or 4CF. Although the lack of unbiased trials must be acknowledged, this systematic review confirms that both procedures give improvements in pain and subjective outcome measures for patients with symptomatic and appropriately staged SLAC or SNAC wrists. PRC may provide better postoperative range of movement and lacks the potential complications specific to 4CF (nonunion, hardware issues and dorsal impingement). However, the risk of subsequent osteoarthritis is significantly higher in PRC patients despite the majority being asymptomatic at the time of review. Grip strength, pain relief and subjective outcomes are similar in both treatment groups.
Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-α expression
Authors: Nascimbeni Michelina , Perié Leïla , Chorro Laurent , Diocou Seckou , Kreitmann Louis , Louis Stéphanie , Garderet Laurent , Fabiani Bettina , Berger Anne , Schmitz Jürgen , Marie Jean-Pierre , Molina Thierry Jo , Pacanowski Jérôme , Viard Jean-Paul , Oksenhendler Eric , Beq Stéphanie , Abehsira-Amar Orly , Cheynier Rémi , Hosmalin Anne
Published: April 2009

We characterized the localization, phenotype, and some functions of plasmacytoid dendritic cells (pDCs) in the human spleen. pDCs were localized in the marginal zone and the periarteriolar region. Some were also found in the red pulp. pDCs were immature by phenotypic labeling, consistently with their capacity to internalize Dextran in a functional assay. In spleens from HIV-infected patients with thrombocytopenic purpura, these characteristics were unaffected. However, an accumulation of pDCs, but not myeloid dendritic cells (mDCs), was observed in some HIV+ patients, correlating with high proviral loads. Moreover, although undetectable in most HIV− patients, interferon-α (IFN-α) production was evidenced in situ and by flow cytometry in most HIV+ patients. IFN-α was located in the marginal zone. Surprisingly, IFN-α colocalized only with few pDCs, but rather with other cells, including T and B lymphocytes, mDCs, and macrophages. Therefore, pDCs accumulated in spleens from HIV+ patients with high proviral loads, but they did not seem to be the main IFN-α producers.
Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes
Authors: Sharma Madhav D. , Hou De-Yan , Liu Yanjun , Koni Pandelakis A. , Metz Richard , Chandler Phillip , Mellor Andrew L. , He Yukai , Munn David H.
Published: April 2009

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining lymph nodes (TDLNs), where it can potently activate Foxp3+ regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in TDLNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induced conversion of Tregs to a polyfunctional T-helper phenotype similar to proinflammatory T-helper-17 (TH17) cells when IDO was blocked. In vitro, conversion of Tregs to the TH17-like phenotype was driven by antigen-activated effector T cells and required interleukin-6 (IL-6) produced by activated pDCs. IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion. In vivo, using a model of established B16 melanoma, the combination of an IDO-inhibitor drug plus antitumor vaccine caused up-regulation of IL-6 in pDCs and in situ conversion of a majority of Tregs to the TH17 phenotype, with marked enhancement of CD8+ T-cell activation and antitumor efficacy. Thus, Tregs in TDLNs can be actively reprogrammed in situ into T-helper cells, without the need for physical depletion, and IDO serves as a key regulator of this critical conversion.
Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures
Authors: Prokopi Marianna , Pula Giordano , Mayr Ursula , Devue Cécile , Gallagher Joy , Xiao Qingzhong , Boulanger Chantal M. , Westwood Nigel , Urbich Carmen , Willeit Johann , Steiner Marianne , Breuss Johannes , Xu Qingbo , Kiechl Stefan , Mayr Manuel
Published: April 2009

The concept of endothelial progenitor cells (EPCs) has attracted considerable interest in cardiovascular research, but despite a decade of research there are still no specific markers for EPCs and results from clinical trials remain controversial. Using liquid chromatography–tandem mass spectrometry, we analyzed the protein composition of microparticles (MPs) originating from the cell surface of EPC cultures. Our data revealed that the conventional methods for isolating mononuclear cells lead to a contamination with platelet proteins. Notably, platelets readily disintegrate into platelet MPs. These platelet MPs are taken up by the mononuclear cell population, which acquires “endothelial” characteristics (CD31, von Willebrand factor [VWF], lectin-binding), and angiogenic properties. In a large population-based study (n = 526), platelets emerged as a positive predictor for the number of colony-forming units and early outgrowth EPCs. Our study provides the first evidence that the cell type consistent with current definitions of an EPC phenotype may arise from an uptake of platelet MPs by mononuclear cells resulting in a gross misinterpretation of their cellular progeny. These findings demonstrate the advantage of using an unbiased proteomic approach to assess cellular phenotypes and advise caution in attributing the benefits in clinical trials using unselected bone marrow mononuclear cells (BMCs) to stem cell-mediated repair.
Evolutionary history of the iroquois/Irx genes in metazoans
Authors: Kerner Pierre , Ikmi Aissam , Coen Dario , Vervoort Michel
Published: April 2009

Background

The iroquois (iro/Irx) genes encode transcriptional regulators that belong to the TALE superclass of homeodomain proteins and have key functions during development in both vertebrates and insects. The Irx genes occur in one or two genomic clusters containing three genes each within the Drosophila and several vertebrate genomes, respectively. The similar genomic organization in Drosophila and vertebrates is widely considered as a result of convergent evolution, due to independent tandem gene duplications. In this study, we investigate the evolutionary history of the Irx genes at the scale of the whole metazoan kingdom.

Results

We identified in silico the putative full complement of Irx genes in the sequenced genomes of 36 different species representative of the main metazoan lineages, including non bilaterian species, several arthropods, non vertebrate chordates, and a basal vertebrate, the sea lamprey. We performed extensive phylogenetic analyses of the identified Irx genes and defined their genomic organizations. We found that, in most species, there are several Irx genes, these genes form two to four gene clusters, and the Irx genes are physically linked to a structurally and functionally unrelated gene known as CG10632 in Drosophila.

Conclusion

Three main conclusions can be drawn from our study. First, an Irx cluster composed of two genes, araucan/caupolican and mirror, is ancestral to the crustaceans+insects clade and has been strongly conserved in this clade. Second, three Irx genes were probably present in the last common ancestor of vertebrates and the duplication that has given rise to the six genes organized into two clusters found in most vertebrates, likely occurred in the gnathostome lineage after its separation from sea lampreys. Third, the clustered organization of the Irx genes in various evolutionary lineages may represent an exceptional case of convergent evolution or may point to the existence of an Irx gene cluster ancestral to bilaterians.
Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins
Authors: Alves Eliana , Costa Liliana , Carvalho Carla MB , Tomé João PC , Faustino Maria A , Neves Maria GPMS , Tomé Augusto C , Cavaleiro José AS , Cunha Ângela , Almeida Adelaide
Published: April 2009

Background

In recent times photodynamic antimicrobial therapy has been used to efficiently destroy Gram (+) and Gram (-) bacteria using cationic porphyrins as photosensitizers. There is an increasing interest in this approach, namely in the search of photosensitizers with adequate structural features for an efficient photoinactivation process. In this study we propose to compare the efficiency of seven cationic porphyrins differing in meso-substituent groups, charge number and charge distribution, on the photodynamic inactivation of a Gram (+) bacterium (Enterococcus faecalis) and of a Gram (-) bacterium (Escherichia coli). The present study complements our previous work on the search for photosensitizers that might be considered good candidates for the photoinactivation of a large spectrum of environmental microorganisms.

Results

Bacterial suspension (107 CFU mL-1) treated with different photosensitizers concentrations (0.5, 1.0 and 5.0 μM) were exposed to white light (40 W m-2) for a total light dose of 64.8 J cm-2. The most effective photosensitizers against both bacterial strains were the Tri-Py+-Me-PF and Tri-Py+-Me-CO2Me at 5.0 μM with a light fluence of 64.8 J cm-2, leading to > 7.0 log (> 99,999%) of photoinactivation. The tetracationic porphyrin also proved to be a good photosensitizer against both bacterial strains. Both di-cationic and the monocationic porphyrins were the least effective ones.

Conclusion

The number of positive charges, the charge distribution in the porphyrins' structure and the meso-substituent groups seem to have different effects on the photoinactivation of both bacteria. As the Tri-Py+-Me-PF porphyrin provides the highest log reduction using lower light doses, this photosensitizer can efficiently photoinactivate a large spectrum of environmental bacteria. The complete inactivation of both bacterial strains with low light fluence (40 W m-2) means that the photodynamic approach can be applied to wastewater treatment under natural light conditions which makes this technology cheap and feasible in terms of the light source.
Bacillus anthracis in China and its relationship to worldwide lineages
Authors: Simonson Tatum S , Okinaka Richard T , Wang Bingxiang , Easterday W Ryan , Huynh Lynn , U'Ren Jana M , Dukerich Meghan , Zanecki Shaylan R , Kenefic Leo J , Beaudry Jodi , Schupp James M , Pearson Talima , Wagner David M , Hoffmaster Alex , Ravel Jacques , Keim Paul
Published: April 2009

Background

The global pattern of distribution of 1033 B. anthracis isolates has previously been defined by a set of 12 conserved canonical single nucleotide polymorphisms (canSNP). These studies reinforced the presence of three major lineages and 12 sub-lineages and sub-groups of this anthrax-causing pathogen. Isolates that form the A lineage (unlike the B and C lineages) have become widely dispersed throughout the world and form the basis for the geographical disposition of "modern" anthrax. An archival collection of 191 different B. anthracis isolates from China provides a glimpse into the possible role of Chinese trade and commerce in the spread of certain sub-lineages of this pathogen. Canonical single nucleotide polymorphism (canSNP) and multiple locus VNTR analysis (MLVA) typing has been used to examine this archival collection of isolates.

Results

The canSNP study indicates that there are 5 different sub-lineages/sub-groups in China out of 12 previously described world-wide canSNP genotypes. Three of these canSNP genotypes were only found in the western-most province of China, Xinjiang. These genotypes were A.Br.008/009, a sub-group that is spread across most of Europe and Asia; A.Br.Aust 94, a sub-lineage that is present in Europe and India, and A.Br.Vollum, a lineage that is also present in Europe. The remaining two canSNP genotypes are spread across the whole of China and belong to sub-group A.Br.001/002 and the A.Br.Ames sub-lineage, two closely related genotypes. MLVA typing adds resolution to the isolates in each canSNP genotype and diversity indices for the A.Br.008/009 and A.Br.001/002 sub-groups suggest that these represent older and established clades in China.

Conclusion

B. anthracis isolates were recovered from three canSNP sub-groups (A.Br.008/009, A.Br.Aust94, and A.Br.Vollum) in the western most portion of the large Chinese province of Xinjiang. The city of Kashi in this province appears to have served as a crossroads for not only trade but the movement of diseases such as anthrax along the ancient "silk road". Phylogenetic inference also suggests that the A.Br.Ames sub-lineage, first identified in the original Ames strain isolated from Jim Hogg County, TX, is descended from the A.Br.001/002 sub-group that has a major presence in most of China. These results suggest a genetic discontinuity between the younger Ames sub-lineage in Texas and the large Western North American sub-lineage spread across central Canada and the Dakotas.
Studying bacteria in respiratory specimens by using conventional and molecular microbiological approaches
Authors: Rogers Geraint B , Daniels Thomas WV , Tuck Andrew , Carroll Mary P , Connett Gary J , David Gondi JP , Bruce Kenneth D
Published: April 2009

Background

Drawing from previous studies, the traditional routine diagnostic microbiology evaluation of samples from chronic respiratory conditions may provide an incomplete picture of the bacteria present in airways disease. Here, the aim was to determine the extent to which routine diagnostic microbiology gave a different assessment of the species present in sputa when analysed by using culture-independent assessment.

Methods

Six different media used in routine diagnostic microbiology were inoculated with sputum from twelve patients. Bacterial growth on these plates was harvested and both RNA and DNA extracted. DNA and RNA were also extracted directly from the same sample of sputum. All nucleic acids served as templates for PCR and reverse transcriptase-PCR amplification of "broad range" bacterial 16S rRNA gene regions. The regions amplified were separated by Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling and compared to assess the degree of overlap between approaches.

Results

A mean of 16.3 (SD 10.0) separate T-RF band lengths in the profiles from each sputum sample by Direct Molecular Analysis, with a mean of 8.8 (SD 5.8) resolved by DNA profiling and 13.3 (SD 8.0) resolved by RNA profiling. In comparison, 8.8 (SD 4.4) T-RF bands were resolved in profiles generated by Culture-derived Molecular Analysis. There were a total of 184 instances of T-RF bands detected in the direct sputum profiles but not in the corresponding culture-derived profiles, representing 83 different T-RF band lengths. Amongst these were fifteen instances where the T-RF band represented more than 10% of the total band volume (with a mean value of 23.6%). Eight different T-RF band lengths were resolved as the dominant band in profiles generated directly from sputum. Of these, only three were detected in profiles generated from the corresponding set of cultures.

Conclusion

Due to their focus on isolation of a small group of recognised pathogens, the use of culture-dependent methods to analyse samples from chronic respiratory infections can provide a restricted understanding of the bacterial species present. The use of a culture-independent molecular approach here identifies that there are many bacterial species in samples from CF and COPD patients that may be clinically relevant.
Analysis of the impact of solvent on contacts prediction in proteins
Authors: Samsonov Sergey A , Teyra Joan , Anders Gerd , Pisabarro M Teresa
Published: April 2009

Background

The correlated mutations concept is based on the assumption that interacting protein residues coevolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. Approaches based on this concept have been widely used for protein contacts prediction since the 90s. Previously, we have shown that water-mediated interactions play an important role in protein interfaces. We have observed that current "dry" correlated mutations approaches might not properly predict certain interactions in protein interfaces due to the fact that they are water-mediated.

Results

The goal of this study has been to analyze the impact of including solvent into the concept of correlated mutations. For this purpose we use linear combinations of the predictions obtained by the application of two different similarity matrices: a standard "dry" similarity matrix (DRY) and a "wet" similarity matrix (WET) derived from all water-mediated protein interfacial interactions in the PDB. We analyze two datasets containing 50 domains and 10 domain pairs from PFAM and compare the results obtained by using a combination of both matrices. We find that for both intra- and interdomain contacts predictions the introduction of a combination of a "wet" and a "dry" similarity matrix improves the predictions in comparison to the "dry" one alone.

Conclusion

Our analysis, despite the complexity of its possible general applicability, opens up that the consideration of water may have an impact on the improvement of the contact predictions obtained by correlated mutations approaches.
Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment
Authors: Stöckmann Christoph , Scheidle Marco , Dittrich Barbara , Merckelbach Armin , Hehmann Grit , Melmer Georg , Klee Doris , Büchs Jochen , Kang Hyun Ah , Gellissen Gerd
Published: April 2009

A range of industrialH. polymorpha-based processes exist, most of them for the production of pharmaceuticals. The established industrial processes lean on the use of promoters derived fromMOXandFMD, genes of the methanol metabolism pathway. InHansenula polymorphathese promoters are de-repressed upon depletion of a range of carbon sources like glucose and glycerol instead of being induced by methanol as reported for other methylotrophs. Due to these characteristics screening and fermentation modes have been defined for strains harbouring such expression control elements that lean on a limited supplementation of glycerol or glucose to a culture medium. For fermentation ofH. polymorphaa synthetic minimal medium (SYN6) has been developed. No industrial processes have been developed so far based onArxula adeninivoransand only a limited range of strong promoter elements exists, suitable for heterologous gene expression. SYN6 originally designed forH. polymorphaprovided a suitable basis for the initial definition of fermentation conditions for this dimorphic yeast. Characteristics like osmo- and thermotolerance can be addressed for the definition of culture conditions.
Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury
Authors: Vesconi Sergio , Cruz Dinna N , Fumagalli Roberto , Kindgen-Milles Detlef , Monti Gianpaola , Marinho Anibal , Mariano Filippo , Formica Marco , Marchesi Mariano , Robert René , Livigni Sergio , Ronco Claudio ,   the DOse REsponse Multicentre International collaborative Initiative (DO-RE-MI Study Group)
Published: April 2009

Introduction

The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT) dose and outcome.

Methods

We performed a prospective multicentre observational study in 30 intensive care units (ICUs) in eight countries from June 2005 to December 2007. Delivered RRT dose was calculated in patients treated exclusively with either continuous RRT (CRRT) or intermittent RRT (IRRT) during their ICU stay. Dose was categorised into more-intensive (CRRT ≥ 35 ml/kg/hour, IRRT ≥ 6 sessions/week) or less-intensive (CRRT < 35 ml/kg/hour, IRRT < 6 sessions/week). The main outcome measures were ICU mortality, ICU length of stay and duration of mechanical ventilation.

Results

Of 15,200 critically ill patients admitted during the study period, 553 AKI patients were treated with RRT, including 338 who received CRRT only and 87 who received IRRT only. For CRRT, the median delivered dose was 27.1 ml/kg/hour (interquartile range (IQR) = 22.1 to 33.9). For IRRT, the median dose was 7 sessions/week (IQR = 5 to 7). Only 22% of CRRT patients and 64% of IRRT patients received a more-intensive dose. Crude ICU mortality among CRRT patients were 60.8% vs. 52.5% (more-intensive vs. less-intensive groups, respectively). In IRRT, this was 23.6 vs. 19.4%, respectively. On multivariable analysis, there was no significant association between RRT dose and ICU mortality (Odds ratio (OR) more-intensive vs. less-intensive: CRRT OR = 1.21, 95% confidence interval (CI) = 0.66 to 2.21; IRRT OR = 1.50, 95% CI = 0.48 to 4.67). Among survivors, shorter ICU stay and duration of mechanical ventilation were observed in the more-intensive RRT groups (more-intensive vs. less-intensive for all: CRRT (median): 15 (IQR = 8 to 26) vs. 19.5 (IQR = 12 to 33.5) ICU days, P = 0.063; 7 (IQR = 4 to 17) vs. 14 (IQR = 5 to 24) ventilation days, P = 0.031; IRRT: 8 (IQR = 5.5 to 14) vs. 18 (IQR = 13 to 35) ICU days, P = 0.008; 2.5 (IQR = 0 to 10) vs. 12 (IQR = 3 to 24) ventilation days, P = 0.026).

Conclusions

After adjustment for multiple variables, these data provide no evidence for a survival benefit afforded by higher dose RRT. However, more-intensive RRT was associated with a favourable effect on ICU stay and duration of mechanical ventilation among survivors. This result warrants further exploration.

Trial Registration

Cochrane Renal Group (CRG110600093).
The Tyrosine Kinase Receptor RET Interacts in Vivo with Aryl Hydrocarbon Receptor-Interacting Protein to Alter Survivin Availability
Authors: Vargiolu Manuela , Fusco Daniela , Kurelac Ivana , Dirnberger Dietmar , Baumeister Ralf , Morra Isabella , Melcarne Antonio , Rimondini Roberto , Romeo Giovanni , Bonora Elena
Published: April 2009

Context: RET is a tyrosine kinase transmembrane receptor expressed in two main alternative isoforms: RET9 and RET51. RET transduces a positive signal leading to survival, differentiation, or migration in the presence of its ligand glial cell line-derived neurotrophic factor, whereas in its absence a proapoptotic fragment that initiates a negative signaling for apoptosis is generated. The signal transduction mechanisms leading to apoptosis are still unclear.

Objective: To shed light on the mechanisms of RET-induced apoptosis, we searched for novel interactors of RET51.

Design: The “split ubiquitin yeast two-hybrid system” was used with RET51 as bait against a human brain expression library.

Results: We identified aryl hydrocarbon receptor-interacting protein (AIP), a cochaperone recently found mutated in pituitary adenoma patients, as a novel interactor of RET. We showed that RET interacts specifically with AIP both in mammalian cell lines and in vivo in the pituitary gland, regardless of the presence of pituitary adenoma-specific mutations. AIP and RET genes were sequenced in 28 pituitary adenoma, but no relevant mutations were found. In addition, we identified the proapoptotic domain of RET as responsible for the interaction with AIP. Finally, we demonstrated that the AIP-RET interaction does not require RET kinase activity or kinase-dependent signal transduction and that it prevents the formation of the AIP-survivin complex.

Conclusions: The identification of the AIP-RET complex represents a starting point to study key cellular processes involved in RET-induced apoptosis.
“Sonic Samizdat”: Situating Unofficial Recording in the Post-Stalinist Soviet Union
Authors: Daughtry J. Martin
Published: April 2009

Magnitizdat was the slyly humorous nickname for the unofficial practice of dubbing and distributing reel-to-reel audio tapes in the post-Stalinist Soviet Union. In this article I reflect on magnitizdat's cultural significance through an examination of several amateur reel-to-reel recordings of avtorskaia pesnia, the musical genre most closely associated with the first generation of magnitizdat dubbers in the 1960s. After drawing parallels between the rhizomic, uncensored distribution of reel-to-reel tapes and samizdat's dissemination of uncensored texts, I move on to consider the differences—in scale, ideological charge, and ontological status—between the two practices. After outlining the similarities that link magnitizdat (and, by implication, samizdat) to contemporary practices of Internet file-sharing, I conclude by suggesting that we might profitably reimagine the relationship between the Soviet underground and the post-Soviet grassroots as one where continuities overwhelm disjunctures.
Reading Games/Games of Reading: Iurii Trifonov'sHouse on the Embankmentand Forms of Play beyond Samizdat
Authors: Milkova Stiliana
Published: April 2009

Iurii Trifonov (1925–1981) was a successful Soviet writer and sports journalist. He did not belong to samizdat print culture. But like other officially published Soviet literature, his works enacted an Aesopian game of hide-and-seek with the censor and the reader, whereby meaning was concealed throughout the text and marked by subtle hints. In this essay, I explore the implications of game playing as elaborated in Trifonov's most subversive, though officially published and uncensored, text, the novella House on the Embankment (Dom na Naberezhnoi, 1976). In analyzing Trifonov's novella, I examine different forms of “actual” play among author, censor, and reader, on the one hand, and rhetorical game playing in the narrative, on the other. More specifically, the essay analyzes children's games in the text to suggest that games become an Aesopian mechanism for addressing the Stalinist past and a metaphor for Aesopian language itself. The essay also suggests that game playing as an extratextual practice and rhetorical mode can be seen as bridging the gap between samizdat (underground publishing enterprises) and Gosizdat (the state publishing house).
Demystifying the Logic of Tamizdat: Philip Roth's Anti-Spectacular Literary Politics
Authors: Benatov Joseph
Published: April 2009

Shortly after Nikita Khrushchev delivered his 1956 “secret speech” at the Twentieth Congress of the Soviet Communist Party, the text of the report reached the United States by way of Poland and was published in the New York Times. The first secretary's denunciation of Stalinism thus ironically becomes one of the earliest and best-known specimens of the phenomenon of tamizdat—defined as writing from Eastern Europe illicitly smuggled out and published abroad. This essay critically examines the West's and specifically the United States' fascination with tamizdat as symptomatic of the broader politics of representing life behind the iron curtain. It argues that Philip Roth's sustained professional engagement with the Czech socialist experience can be read as his critical refusal to take part in the dominant U.S. narrative of Eastern European suffering and oppression. The essay analyzes Roth's 1985 novella The Prague Orgy and the theoretical implications of the book's central plot device—the narrative of a failed tamizdat mission. The article argues that Roth's work exposes the patterns in which tamizdat, together with the fate of the Eastern European political émigré, becomes a homogeneous, metonymic image for the totality of life under Communism. In The Prague Orgy, Roth situates himself in stark opposition to the representational practices of Milan Kundera by resisting the easy sensationalism of such “writing for the West.” Roth prefers to give voice to an array of internal Czech positions, central among which is that of the dissident author Ivan Klíma. Ultimately, Roth's resistance to stereotypical discourse on the socialist Other comes at an important sociocultural moment in the 1980s, when other American intellectuals prefer the security granted by the narrative of tamizdat.
Spoken Revolutions: Discursive Resistance in Bulgarian Late Communist Culture
Authors: Lutzkanova-Vassileva Albena
Published: April 2009

The article focuses on the brief history of Bulgarian samizdat and its attempts to challenge the regime through written discourse as well as on two forms of oral discursive resistance: the Seminar, a mode of discourse rather than any organized and rigid structure, and the group Synthesis, a more coherent formation that had a longer and more turbulent history. I explore the uniqueness of Bulgarian late Communist culture that, unlike its Soviet bloc counterparts, was never truly dissident in character. I seek to reveal why Bulgarian intelligentsia proved incapable of creating the kind of alternative samizdat literature that appeared in other former Communist countries.

While it appears questionable that such semiofficial formations as samizdat, the Seminar, or Synthesis brought down the totalitarian system in Bulgaria, the resistance that they offered played a role in Communism's breakdown. The article's main goal is thus to elucidate the peculiar nature of this resistance—to explicate the role of discourse in undermining the political order. Why did the end of totalitarian terror in Bulgaria take a theoretical turn? Is it fair to say that the breakdown of the regime was discursive? If so, how can we explain the enigma of a large political machine demolished by discourse? The article discusses the premise that what made possible the termination of a regime by theory (if this is what happened) was the very structure of the regime as total discursive control. It explores the hypothesis that, since totalitarianism was a purely linguistic phenomenon, a linguistic act would be the most efficient means to subvert and finally destroy it.
LC3-mediated fibronectin mRNA translation induces fibrosarcoma growth by increasing connective tissue growth factor
Authors: Ying Lihua , Lau Agatha , Alvira Cristina M. , West Robert , Cann Gordon M. , Zhou Bin , Kinnear Caroline , Jan Eric , Sarnow Peter , Van de Rijn Matt , Rabinovitch Marlene
Published: April 2009

Previously, we related fibronectin (Fn1) mRNA translation to an interaction between an AU-rich element in the Fn1 3′ UTR and light chain 3 (LC3) of microtubule-associated proteins 1A and 1B. Since human fibrosarcoma (HT1080) cells produce little fibronectin and LC3, we used these cells to investigate how LC3-mediated Fn1 mRNA translation might alter tumor growth. Transfection of HT1080 cells with LC3 enhanced fibronectin mRNA translation. Using polysome analysis and RNA-binding assays, we show that elevated levels of translation depend on an interaction between a triple arginine motif in LC3 and the AU-rich element in Fn1 mRNA. Wild-type but not mutant LC3 accelerated HT1080 cell growth in culture and when implanted in SCID mice. Comparison of WT LC3 with vector-transfected HT1080 cells revealed increased fibronectin-dependent proliferation, adhesion and invasion. Microarray analysis of genes differentially expressed in WT and vector-transfected control cells indicated enhanced expression of connective tissue growth factor (CTGF). Using siRNA, we show that enhanced expression of CTGF is fibronectin dependent and that LC3-mediated adhesion, invasion and proliferation are CTGF dependent. Expression profiling of soft tissue tumors revealed increased expression of both LC3 and CTGF in some locally invasive tumor types.
Microtubule plus-end binding protein EB1 is necessary for muscle cell differentiation, elongation and fusion
Authors: Zhang Tan , Zaal Kristien J. M. , Sheridan John , Mehta Amisha , Gundersen Gregg G. , Ralston Evelyn
Published: April 2009

During muscle differentiation, microtubule stability, nucleation and orientation all undergo profound changes, which are simultaneous with and possibly necessary for the elongation and fusion of muscle cells. We do not yet understand these events, but they present similarities with the polarized migration of fibroblasts, in which EB1 is necessary for microtubule stabilization. However, it was recently reported that EB3, not EB1, is involved in muscle cell elongation and fusion, and that neither of these two proteins influences microtubule stabilization. To re-examine the role of EB1, we have generated C2 cell lines permanently expressing EB1-targeted shRNAs. In these lines, EB1 is specifically knocked down by more than 90% before any differentiation-related changes can take place. We find that differentiation (assessed by myogenin expression), elongation and fusion are prevented. In addition, two early events that normally precede differentiation - microtubule stabilization and the accumulation of cadherin and β-catenin on the plasma membrane - are inhibited. Re-expression of EB1 as EB1-GFP restores all aspects of normal differentiation, whereas overexpression of EB3-GFP restores elongation but not fusion. We conclude that EB1 is necessary for the early stages of muscle differentiation.
Impairment of ubiquitylation by mutation in Drosophila E1 promotes both cell-autonomous and non-cell-autonomous Ras-ERK activation in vivo
Authors: Yan Hua , Chin Mei-Ling , Horvath Elizabeth A. , Kane Elizabeth A. , Pfleger Cathie M.
Published: April 2009

Ras signaling can promote proliferation, cell survival and differentiation. Mutations in components of the Ras pathway are found in many solid tumors and are associated with developmental disorders. We demonstrate here that Drosophila tissues containing hypomorphic mutations in E1, the most upstream enzyme in the ubiquitin pathway, display cell-autonomous upregulation of Ras-ERK activity and Ras-dependent ectopic proliferation. Ubiquitylation is widely accepted to regulate receptor tyrosine kinase (RTK) endocytosis upstream of Ras. However, although the ectopic proliferation of E1 hypomorphs is dramatically suppressed by removing one copy of Ras, removal of the more upstream components Egfr, Grb2 or sos shows no suppression. Thus, decreased ubiquitylation may lead to growth-relevant Ras-ERK activation by failing to regulate a step downstream of RTK endocytosis. We further demonstrate that Drosophila Ras is ubiquitylated. Our findings suggest that Ras ubiquitylation restricts growth and proliferation in vivo. We also report our intriguing observation that complete inactivation of E1 causes non-autonomous activation of Ras-ERK in adjacent tissue, mimicking oncogenic Ras overexpression. We demonstrate that maintaining sufficient E1 function is required both cell autonomously and non-cell autonomously to prevent inappropriate Ras-ERK-dependent growth and proliferation in vivo and may implicate loss of Ras ubiquitylation in developmental disorders and cancer.
Recruitment of vimentin to the cell surface by β3 integrin and plectin mediates adhesion strength
Authors: Bhattacharya Ramona , Gonzalez Annette M. , DeBiase Phillip J. , Trejo Humberto E. , Goldman Robert D. , Flitney Frederick W. , Jones Jonathan C. R.
Published: April 2009

Much effort has been expended on analyzing how microfilament and microtubule cytoskeletons dictate the interaction of cells with matrix at adhesive sites called focal adhesions (FAs). However, vimentin intermediate filaments (IFs) also associate with the cell surface at FAs in endothelial cells. Here, we show that IF recruitment to FAs in endothelial cells requires β3 integrin, plectin and the microtubule cytoskeleton, and is dependent on microtubule motors. In CHO cells, which lack β3 integrin but contain vimentin, IFs appear to be collapsed around the nucleus, whereas in CHO cells expressing β3 integrin (CHOwtβ3), vimentin IFs extend to FAs at the cell periphery. This recruitment is regulated by tyrosine residues in the β3 integrin cytoplasmic tail. Moreover, CHOwtβ3 cells exhibit significantly greater adhesive strength than CHO or CHO cells expressing mutated β3 integrin proteins. These differences require an intact vimentin network. Therefore, vimentin IF recruitment to the cell surface is tightly regulated and modulates the strength of adhesion of cells to their substrate.
A Ubc7p-binding domain in Cue1p activates ER-associated protein degradation
Authors: Kostova Zlatka , Mariano Jennifer , Scholz Simone , Koenig Carolin , Weissman Allan M.
Published: April 2009

Cue1p is an N-terminally anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). Cue1p contains a CUE domain, which for several proteins is known to bind ubiquitin. We now establish that the CUE domain is dispensable for ERAD of substrates of both Hrd1p and Doa10p and that the Cue1p transmembrane domain is similarly not required for degradation of the Hrd1p substrate CPY*. Cue1p interacts with the ERAD E2 Ubc7p in vivo. We show that a discrete C-terminal Ubc7p binding region (U7BR) of Cue1p is required for ERAD and for Ubc7p-dependent ubiquitylation by Hrd1p in vitro. Strikingly, when Ubc7p is stabilized by direct anchoring to the ER membrane, the U7BR is sufficient to restore ERAD in cells lacking Cue1p. Thus, discrete E2 binding sites independent of ubiquitin ligase domains have the potential to activate ubiquitylation.