bluuebunny/crossref_metadata_2025 huggingface dataset:
The Establishment of the European Company: The First Cases from an Industrial Relations Perspective
Authors: Keller Berndt , Werner Frank
Published: April 2008

This article presents the first systematic empirical analysis of all European Companies established at the time of writing, and focuses on industrial relations issues and the negotiated rules of employee involvement in particular. It elaborates on the election procedures, the special negotiation body and the mechanisms of employee information and consultation and board-level representation. Some tentative conclusions consider the likely impact on the development of European industrial relations.
Varieties of Capitalism and Diversity in Labour Standards Regulation: The Case of Italy
Authors: Michelotti Marco , Nyland Chris
Published: April 2008

Many scholars and policy-makers argue that advanced market economies are converging towards a neoliberal labour market model with diluted labour standards. However, others insist that `capitalism allows variety'. The primary purpose of this article is to provide empirical evidence that supports the latter position, by comparing legally mandated labour standards in Italy through 1979—2003 and by juxtaposing the results against OECD panel data which allegedly show a decline in labour standards. This comparison suggests that a more complex regulatory transformation occurred than is allowed for by the OECD: indeed, labour standards for core workers in Italy were actually strengthened. This discrepancy reflects the limited focus of the OECD data.
A New Transducer for Rotational and Translational Impedance Measurement
Authors: Hou Xiaoyan  , Ling Shih-Fu , Kok Hui Heng
Published: April 2008

Measurement of rotational frequency response functions (FRFs) is important for a complete description of a dynamic system, as a full description requires consideration of both translational and rotational excitations. However, so far rotational FRFs have usually been neglected from analysis due to the absence of reliable and accurate measurement transducers and methods. This study presents a novel bimorph impedance transducer (BIT), which can accurately and easily measure rotational FRFs as well as translational ones. Through careful design, this transducer is only sensitive to one translational and one rotational degree of freedom (DOF) at a structural point, which are further decoupled from each other through controlling the phase of the electrical excitation supplied to the transducer. To investigate the effectiveness of the transducer, experiments using a one-dimensional beam as a test structure are carried out. The results show that the BIT is accurate in measuring both rotational and translational impedance of elastic structures. The measurement is performed simply by measuring the input electrical parameters of the BIT; consequently the direct measurement of moment/force and linear velocity/angular velocity, which are usually difficult to conduct in experiments, is avoided. As this transducer functions actuating and sensing simultaneously during measurement, the measurement system is also greatly simplified and the accurate driving-point measurement is achieved.
High Speed Model Implementation and Inversion Techniques for Ferroelectric and Ferromagnetic Transducers
Authors: Braun T.R. , Smith R.C.
Published: April 2008

Ferroelectric and ferromagnetic materials are employed as both actuators and sensors in a wide variety of applications including fluid pumps, nanopositioning stages, sonar transducers, vibration control, ultrasonic sources, and high-speed milling. They are attractive because the resulting transducers are solid-state and often very compact. However, the coupling of field to mechanical deformation, which makes these materials effective transducers, also introduces hysteresis and time-dependent behavior that must be accommodated in device designs and models before the full potential of compounds can be realized. In this article, we present highly efficient modeling techniques to characterize hysteresis and constitutive nonlinearities in ferroelectric and ferromagnetic compounds and model inversion techniques which permit subsequent linear control designs.
Studies on Area-controlled Electrostatic Actuation of Small Membrane Reflectors
Authors: Korde Umesh A.
Published: April 2008

Membrane mirrors are advantageous in several applications due to their light weight and potential for deployability. Desired optical performance often requires dynamic actuation, however, and electrostatic actuators are frequently employed for this purpose. This paper investigates a variable area/constant voltage method for electrostatic actuation of small circular membrane mirrors designed to meet specified performance requirements for a beam steering and focus/defocus application. The proposed technique involves selective application of a constant voltage to area segments that together make up an electrode pad. The paper shows that a lumped parameter model for this system also has the property of differential flatness (similar to variable voltage/constant area systems), based on which the reference trajectory for membrane deflection can be specified in phase space. The phase space trajectory is derived from the required transient response characteristics (rise time, settling time, etc.). A closed loop system comprised of a controller and an observer is devised using a Lyapunov function-based approach. A `quad cell' beam position finder is used to detect the beam angular deflection and intensity. The overall system is simulated numerically in this paper. The control system is found to provide efficient trajectory tracking for both symmetric and antisymmetric mode excitation. Although the area changes for the proposed system are discrete, the present simulations only consider continuously-variable area actuation.
Compensation of Parameter-dependent Complex Hysteretic Actuator Nonlinearities In Smart Material Systems
Authors: Kuhnen Klaus
Published: April 2008

In many mechatronic applications actuators which are based on active materials are found and thus show a strong complex hysteretic output-input characteristic. A typical example is the hysteresis in actuators based on magnetostrictive materials. Unfortunately, especially in this case the hysteretic characteristic depends on a second input parameter, the mechanical stress in the material, which affects strongly the form of the hysteretic curves. In the best case these undesired effects lead to a reduced system perfomance and in the worst case to an unpredictable behavior of the superior control unit. Therefore, it is useful and effective to linearize these nonlinearities by a compensator which is also able to consider the dependence of the output on the second input. For this purpose this study describes the design of a compensator for parameter-dependent complex hysteretic nonlinearities which are based on a new so-called threshold-discrete formulation of the Preisach hysteresis operator. Finally, some experimental results are presented, which document the capability of the method for practical applications.
Influence of Fruit Development Stage on the Physiological Response to Ethylene in Cantaloupe Charentais Melon
Authors: Flores F.B. , Martínez-Madrid M.C. , Romojaro F.
Published: April 2008

An experiment has been designed and performed using Cantaloupe Charentais melon as climacteric fruit with the aim of finding out at which point of their development they are able to sense the plant hormone ethylene. Fruit were harvested at 20, 25, and 35 days after pollination (DAP), treated for 5 days at 20 °C with 5 ppm of ethylene, and stored for a further 10 days. Nontreated wild type fruit was used as control. Ethylene-treated genetically modified 1-aminocyclopropane-1-carboxylic acid oxidase antisense fruits with inhibited autocatalytic ethylene production were also used to avoid masking effects because of endogenous ethylene produced by control fruits. Ethylene-treated wild type fruits with 25 DAP were able to produce autocatalytic ethylene. A climacteric respiration increase was observed in treated wild type fruit with 25 and 35 DAP. The degreening of the rind was induced by ethylene in the youngest fruit, showing a total dependence on the hormone for its activation. Loss of pulp firmness induced by exogenous ethylene was found only in 20 DAP-fruit. The existence of ethylene-dependent and developmental factors in the regulation of this ripening process was observed.
Quality of Ornate Emperor (Lethrinus ornatus) Packed in a Combination of Dry Ice and Wet Ice and Stored Under Refrigeration
Authors: Jeyasekaran G. , Anandaraj R. , Ganesan P. , Shakila R. Jeya , Sukumar D.
Published: April 2008

Ornate emperor (Lethrinus ornatus) stored under refrigeration (5 °C) in a combination of dry ice and wet ice at an optimum level of 1 : 0.2 : 0.5 (w/w/w) were found to be sensory acceptable up to 12 days without re-icing. Samples stored in wet ice at 1 : 1 (w/w) were acceptable for only 8 days. Total bacterial load ranged from 104 to 106 cfu/g, while total psychrotrophs increased 6 log cycles. Lactic acid bacteria count increased 3 log cycles and H 2S producers increased 4 log cycles. Micrococcus constituted 79% of the flora in fresh fish. Micrococcus (40%) was also the dominant flora in the combination pack, while Alcaligenes (26%) was dominant in wet ice pack. TVB-N content did not exceed the limit in any of the packs. Free fatty acid and hypoxanthine contents reached to 18.27% as oleic acid and 13.36mg/100g, respectively at the end of storage. Total fat was very low (0.26%), but total protein was high (25.5%) in the raw fish. During storage in the combined ice pack, there was a gradual reduction in the salt soluble proteins from 77.1 to 62.9%. Raw fish contain health beneficial ω-3 fatty acids particularly docosahexaenoic acid (DHA) at a level of 7.15% out of total fat. The loss of this essential fatty acid during storage in the combined pack was only 61%, while in the control pack, the loss was high (88%).
Use of Modified Atmosphere Packaging with Microperforated Polypropylene Films to Maintain Postharvest Loquat Fruit Quality
Authors: Amorós A. , Pretel M.T. , Zapata P.J. , Botella M.A. , Romojaro F. , Serrano M.
Published: April 2008

Loquat fruits (Eriobotrya japonica Lindl cv. `Algerie') were stored in modified atmosphere packaging (MAP), using five types of microperforated polypropylene (PP) films during 2, 4, and 6 weeks at 2 °C and for a subsequent period of 4 days at 20 °C shelf life (SL) out of the bags. Loquat fruits stored without packaging and in normal air served as control. The atmosphere composition at the steady state depended on the film permeability, ranging from 1.2 to 8.5 kPa for CO2 and from 19.5 to 13 kPa for O2 as film permeability decreased. Weight loss was drastically reduced by MAP conditions. Softening, color evolution, and decreases in sugars and organic acids were delayed, these effects also being evident after the SL period. Scores for visual aspect and facility of peeling were also higher for loquat stored in MAP than for controls. Taking into account results form all quality parameters, the most suitable atmosphere for loquat storage was found to be around 2—4 and 16—18 kPa for CO2 and O2, respectively, reached in the PA-80 and PA-60 films. In addition, the storage period for optimum loquat quality maintenance was established as 2 weeks of cold storage plus SL for control fruits, while under MAP conditions, storage periods could be extended up to 6 weeks plus SL, especially using PA-80 and PA-60 films.
Effect of Storage on Cloud Stability of Cloudy Apple Juice
Authors: Zhao Guang-Yuan , Wei Zong  , An Guang-Jie
Published: April 2008

Cloud stability of particles in cloudy apple juice during its storage for 120 days at 4, 22 and 40 °C is conducted. The juices are added with or without ascorbic acid. The cloud stability of juices during storage is studied by optical microscopy, electron microscopy and size distribution analysis of suspending particles combined with a polyphenols component analysis by high performance liquid chromatography. At the beginning of storage, the turbidity of juice added with or without ascorbic acid decreased quickly because particles of larger size in juices aggregated and deposited, and since there are less larger particles at the upper portion of the bottles, the depositing speed of particles decreases. The loss of total phenolic compounds, epicatechin, chlorogenic acid and tannin increases with the increase of temperature and storage time. The polyphenols degraded quickly during the initial period of storage and then it slowed down. The addition of ascorbic acid to the juice can inhibit the oxidation and polymerisation of phenolic compounds to avoid the formation of new small insoluble particles during the storage, and the efficacy of inhibiting between adding 0.024% or 0.006% (w/w) ascorbic acid is not remarkably different.
Gender Differences in Emotion Regulation: An fMRI Study of Cognitive Reappraisal
Authors: McRae Kateri , Ochsner Kevin N. , Mauss Iris B. , Gabrieli John J. D. , Gross James J.
Published: April 2008

Despite strong popular conceptions of gender differences in emotionality and striking gender differences in the prevalence of disorders thought to involve emotion dysregulation, the literature on the neural bases of emotion regulation is nearly silent regarding gender differences (Gross, 2007; Ochsner & Gross, in press). The purpose of the present study was to address this gap in the literature. Using functional magnetic resonance imaging, we asked male and female participants to use a cognitive emotion regulation strategy (reappraisal) to down-regulate their emotional responses to negatively valenced pictures. Behaviorally, men and women evidenced comparable decreases in negative emotion experience. Neurally, however, gender differences emerged. Compared with women, men showed (a) lesser increases in prefrontal regions that are associated with reappraisal, (b) greater decreases in the amygdala, which is associated with emotional responding, and (c) lesser engagement of ventral striatal regions, which are associated with reward processing. We consider two non-competing explanations for these differences. First, men may expend less effort when using cognitive regulation, perhaps due to greater use of automatic emotion regulation. Second, women may use positive emotions in the service of reappraising negative emotions to a greater degree. We then consider the implications of gender differences in emotion regulation for understanding gender differences in emotional processing in general, and gender differences in affective disorders.
Immigrant Status as a Potential Correlate of Organizational Commitment
Authors: Glazer Sharon , De La Rosa Gabriel M.
Published: April 2008

Propositions for the relationship between immigrant status and organizational commitment are developed. A limited test of part of the conceptual framework is tested to examine the influence of immigrant status on continuance and affective commitment. Based on a sample of 506 nurses working in Israeli hospitals who completed self-report surveys, it was found that age and immigrant status (or `years in Israel') were significant correlates of affective and continuance commitment. However, whereas the relationship between `years in Israel' and affective commitment was not significant when age was controlled, additional variance in continuance commitment could be accounted for by `years in Israel' after controlling for age. Furthermore, nurses born in Israel had significantly lower continuance commitment than those who had immigrated to the country. These results suggest that the number of years after immigration has an impact on an individual's attachment to his/her organization. Immigrant status and years living in host country are important factors to consider when assessing organizational commitment, especially in multicultural organizations composed of immigrant workers.
Outdoor Management Development as Organizational Transformation
Authors: Stokes Peter
Published: April 2008

Outdoor management development (OMD) is a controversial management development technique generating revealing perspectives on potential transformations in embedded practices in cultural contexts. OMD takes place in outdoor (mountainous) locations and embraces outdoor pursuits (hiking, climbing and canoeing) and `alternative'styled activities, for example, using theatre or story-telling. `Alternative' here makes a contrast with notional mainstream British and French management development approaches. Using field research carried out in the UK and France, the article explores why OMD and its `alternative' human resource development approaches, so readily engaged in British corporate settings, have been less applied in French organizational contexts. The article argues that, relative to the UK, the use of the outdoors in France for the development of managers or cadres is significantly less extensive and develops and explores reasons why this may be the case.
Creating the Right Reality: Communication Message Strategies and the Republican Party
Authors: Goodall H.L. , Wiener Seth
Published: April 2008

This critical essay explores the parallels between the communicative strategies and methods of totalitarian movements and those of the modern American conservative movement. The Origins of Totalitarianism by Hannah Arendt (1968) serves as the standard by which the authors investigate the properties of such strategies. The authors find that the conservative movement in general and the Republican Party specifically, though not totalitarian, exhibit numerous common characteristics in the sphere of communication such as the suspension of reality, propaganda techniques, and the use of movement opinion to subvert, transform, and replace fact. Through a commitment to an independent press and civic responsibility, the authors believe it is possible to counter these effects and preserve a society where the free exchange of ideas and the freedom of thought are not threatened by rigid doctrines parading as objective facts.
"Myth, Mask, Shield, and Sword": Dr. John H. Marburger III's Rhetoric of Neutral Science for the Nation
Authors: Keränen Lisa , Lesko Jason , Vogelaar Alison , Irvin Lisa
Published: April 2008

This article analyzes presidential science advisor John H. Marburger III's use of an idealized vision of science in his February 14, 2005, address on science policy in the context of allegations of Bush administration science politicization. The authors contend that Marburger's speech is both a performative enactment and an active construction of a linear model of science supported by an entrepreneurial vision of science policy. Although incompatible with the actual conduct of science, this view is rhetorically advantageous for Marburger and the present administration in that it both encourages the demarcation of science from politics in ways that serve elite interests and allows for the negotiation of role tensions inherent in the science advisor position.
Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia
Authors: Kujawski Lisa , Ouillette Peter , Erba Harry , Saddler Chris , Jakubowiak Andrzej , Kaminski Mark , Shedden Kerby , Malek Sami N.
Published: April 2008

Chronic lymphocytic leukemia (CLL) has a variable clinical course. Presence of specific genomic aberrations has been shown to impact survival outcomes and can help categorize CLL into clinically distinct subtypes. We studied 178 CLL patients enrolled in a prospective study at the University of Michigan, of whom 139 and 39 were previously untreated and previously treated, respectively. We obtained unbiased, high-density, genome-wide measurements of subchromosomal copy number changes in highly purified DNA from sorted CD19+ cells and buccal cells using the Affymetrix 50kXbaI SNP array platform (Santa Clara, CA). Genomic complexity scores were derived and correlated with the surrogate clinical end points time to first therapy (TTFT) and time to subsequent therapy (TTST): measures of disease aggressiveness and/or therapy efficaciousness. In univariate analysis, progressively increasing complexity scores in previously untreated CLL patients identified patients with short TTFT at high significance levels. Similarly, TTST was significantly shorter in pretreated patients with high as opposed to low genomic complexity. In multivariate analysis, genomic complexity emerged as an independent risk factor for short TTFT and TTST. Finally, algorithmic subchromosomal complexity determination was developed, facilitating automation and future routine clinical application of CLL whole-genome analysis.
CXCR4 dimerization and β-arrestin–mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome
Authors: Lagane Bernard , Chow Ken Y. C. , Balabanian Karl , Levoye Angélique , Harriague Julie , Planchenault Thierry , Baleux Françoise , Gunera-Saad Nathalie , Arenzana-Seisdedos Fernando , Bachelerie Françoise
Published: April 2008

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribute to the immunohematologic clinical manifestations of the syndrome. CXCR4 desensitization and endocytosis are dependent on β-arrestin (βarr) recruitment to the cytoplasmic tail, so that the truncated CXCR4 are refractory to these processes and so have enhanced G protein–dependent signaling. Here, we show that the augmented responsiveness of WHIM leukocytes is also accounted for by enhanced βarr2-dependent signaling downstream of the truncated CXCR4 receptor. Indeed, the WHIM-associated receptor CXCR41013 maintains association with βarr2 and triggers augmented and prolonged βarr2-dependent signaling, as revealed by ERK1/2 phosphorylation kinetics. Evidence is also provided that CXCR41013-mediated chemotaxis critically requires βarr2, and disrupting the SHSK motif in the third intracellular loop of CXCR41013 abrogates βarr2-mediated signaling, but not coupling to G proteins, and normalizes chemotaxis. We also demonstrate that CXCR41013 spontaneously forms heterodimers with wild-type CXCR4. Accordingly, we propose a model where enhanced functional interactions between βarr2 and receptor dimers account for the altered responsiveness of WHIM leukocytes to CXCL12.
MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility
Authors: Ellis Nathan A. , Huo Dezheng , Yildiz Ozlem , Worrillow Lisa J. , Banerjee Mekhala , Le Beau Michelle M. , Larson Richard A. , Allan James M. , Onel Kenan
Published: April 2008

The p53 tumor suppressor directs the cellular response to many mechanistically distinct DNA-damaging agents and is selected against during the pathogenesis of therapy-related acute myeloid leukemia (t-AML). We hypothesized that constitutional genetic variation in the p53 pathway would affect t-AML risk. Therefore, we tested associations between patients with t-AML (n = 171) and 2 common functional p53-pathway variants, the MDM2 SNP309 and the TP53 codon 72 polymorphism. Although neither polymorphism alone influenced the risk of t-AML, an interactive effect was detected such that MDM2 TT TP53 Arg/Arg double homozygotes, and individuals carrying both a MDM2 G allele and a TP53 Pro allele, were at increased risk of t-AML (P value for interaction is .009). This interactive effect was observed in patients previously treated with chemotherapy but not in patients treated with radiotherapy, and in patients with loss of chromosomes 5 and/or 7, acquired abnormalities associated with prior exposure to alkylator chemotherapy. In addition, there was a trend toward shorter latency to t-AML in MDM2 GG versus TT homozygotes in females but not in males, and in younger but not older patients. These data indicate that the MDM2 and TP53 variants interact to modulate responses to genotoxic therapy and are determinants of risk for t-AML.
Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction
Authors: Devine Steven M. , Vij Ravi , Rettig Michael , Todt Laura , McGlauchlen Kiley , Fisher Nicholas , Devine Hollie , Link Daniel C. , Calandra Gary , Bridger Gary , Westervelt Peter , DiPersio John F.
Published: April 2008

Allografts from HLA-matched sibling donors were mobilized and collected without granulocyte colony-stimulating factor (G-CSF) using AMD3100, a direct antagonist of CXCR4/stromal-derived factor 1 (SDF-1/CXCL12). Donors (N = 25) were treated with AMD3100 at a dose of 240 μg/kg by subcutaneous injection, and leukapheresis was then initiated just 4 hours later. Two-thirds of the donors collected an allograft with a CD34+ cell dose sufficient for transplantation after just one dose of AMD3100. No donor experienced more than grade 1 toxicity. After a myeloablative regimen, 20 patients with hematologic malignancies received allografts collected after AMD3100 alone. All patients engrafted neutrophils (median day 10) and platelets (median day 12) promptly. Acute graft-versus-host disease (GVHD) grades 2 through 4 occurred in 35% of patients. One patient died due to complications related to acute GVHD. No unexpected adverse events were observed in any of the recipients. All 14 patients surviving in remission have robust trilineage hematopoiesis and are transfusion-free with a median follow-up of 277 days (range, 139-964 days). Direct antagonism of CXCR4 by AMD3100 may provide a more rapid and possibly less toxic and cumbersome alternative to traditional G-CSF–based mobilization in normal donors. This trial was registered as no. NCT00241358 at www.ClinicalTrials.gov.
Endotoxin receptor CD14 in PiZ α-1-antitrypsin deficiency individuals
Authors: Sandström Caroline S , Novoradovskaya Natalia , Cilio Corrado M , Piitulainen Eeva , Sveger Tomas , Janciauskiene Sabina
Published: April 2008

Background

CD14, a receptor for lipopolysaccharides (LPS), is found in both a membrane-bound form (mCD14) and a soluble form (sCD14). It is suggested that sCD14 is mainly released from blood monocytes by serine protease-mediated shedding. Because α1-antitrypsin (AAT), an inhibitor of serine proteases, has been shown to regulate CD14 expression in human monocytesin vitro, we sought to investigate plasma levels of sCD14 and monocyte expression of mCD14 in subjects at age 30 years with normal MM and deficient PiZZ and PiSZ genotypes of AAT.

Methods

Plasma levels of AAT and sCD14 were measured in 75 PiZZ and 34 PiSZ individuals with normal lung function identified from the Swedish neonatal AAT deficiency screening, and in 95 age matched PiMM controls. The mCD14 expression in monocytes from 9 PiZZ, 6 PiSZ and 11 PiMM subjects was analysed by FACS and Quantitative Real Time Reverse Transcription PCA.

Results

As expected, plasma AAT concentrations were PiMM>PiSZ>PiZZ (p < 0.001). Plasma sCD14 levels were higher in PiZZ than in PiMM subjects (p < 0.01). The expression level of mCD14 was higher (1.89-fold) in monocytes isolated from PiZZ subjects compared to PiMM controls (p = 0.00189).

Conclusion

This study is the first to show higher levels of plasma sCD14 and monocyte mCD14 expression in young, clinically healthy PiZZ AAT subjects.
Postnatal stem/progenitor cells derived from the dental pulp of adult chimpanzee
Authors: Cheng Pei-Hsun , Snyder Brooke , Fillos Dimitri , Ibegbu Chris C , Huang Anderson Hsien-Cheng , Chan Anthony WS
Published: April 2008

Background

Background

Chimpanzee dental pulp stem/stromal cells (ChDPSCs) are very similar to human bone marrow derived mesenchymal stem/stromal cells (hBMSCs) as demonstrated by the expression pattern of cell surface markers and their multipotent differentiation capability.

Results

ChDPSCs were isolated from an incisor and a canine of a forty-seven year old female chimpanzee. A homogenous population of ChDPSCs was established in early culture at a high proliferation rate and verified by the expression pattern of thirteen cell surface markers. The ChDPSCs are multipotent and were capable of differentiating into osteogenic, adipogenic and chondrogenic lineages under appropriate in vitro culture conditions. ChDPSCs also express stem cell (Sox-2, Nanog, Rex-1, Oct-4) and osteogenic (Osteonectin, osteocalcin, osteopontin) markers, which is comparable to reported results of rhesus monkey BMSCs (rBMSCs), hBMSCs and hDPSCs. Although ChDPSCs vigorously proliferated during the initial phase and gradually decreased in subsequent passages, the telomere length indicated that telomerase activity was not significantly reduced.

Conclusion

These results demonstrate that ChDPSCs can be efficiently isolated from post-mortem teeth of adult chimpanzees and are multipotent. Due to the almost identical genome composition of humans and chimpanzees, there is an emergent need for defining the new role of chimpanzee modeling in comparative medicine. Teeth are easy to recover at necropsy and easy to preserve prior to the retrieval of dental pulp for stem/stromal cells isolation. Therefore, the establishment of ChDPSCs would preserve and maximize the applications of such a unique and invaluable animal model, and could advance the understanding of cellular functions and differentiation control of adult stem cells in higher primates.
Disruption of Four Kinesin Genes in Dictyostelium
Authors: Nag Dilip K , Tikhonenko Irina , Soga Ikko , Koonce Michael P
Published: April 2008

Background

Kinesin and dynein are the two families of microtubule-based motors that drive much of the intracellular movements in eukaryotic cells. Using a gene knockout strategy, we address here the individual function(s) of four of the 13 kinesin proteins in Dictyostelium. The goal of our ongoing project is to establish a minimal motility proteome for this basal eukaryote, enabling us to contrast motor functions here with the often far more elaborate motor families in the metazoans.

Results

We performed individual disruptions of the kinesin genes, kif4, kif8, kif10, and kif11. None of the motors encoded by these genes are essential for development or viability of Dictyostelium. Removal of Kif4 (kinesin-7; CENP-E family) significantly impairs the rate of cell growth and, when combined with a previously characterized dynein inhibition, results in dramatic defects in mitotic spindle assembly. Kif8 (kinesin-4; chromokinesin family) and Kif10 (kinesin-8; Kip3 family) appear to cooperate with dynein to organize the interphase radial microtubule array.

Conclusion

The results reported here extend the number of kinesin gene disruptions in Dictyostelium, to now total 10, among the 13 isoforms. None of these motors, individually, are required for short-term viability. In contrast, homologs of at least six of the 10 kinesins are considered essential in humans. Our work underscores the functional redundancy of motor isoforms in basal organisms while highlighting motor specificity in more complex metazoans. Since motor disruption in Dictyostelium can readily be combined with other motility insults and stresses, this organism offers an excellent system to investigate functional interactions among the kinesin motor family.
Proliferating mesodermal cells in murine embryos exhibiting macrophage and lymphendothelial characteristics
Authors: Buttler Kerstin , Ezaki Taichi , Wilting Jörg
Published: April 2008

Background

The data on the embryonic origin of lymphatic endothelial cells (LECs) from either deep embryonic veins or mesenchymal (or circulating) lymphangioblasts presently available remain inconsistent. In various vertebrates, markers for LECs are first expressed in specific segments of embryonic veins arguing for a venous origin of lymph vessels. Very recently, studies on the mouse have strongly supported this view. However, in the chick, we have observed a dual origin of LECs from veins and from mesodermal lymphangioblasts. Additionally, in murine embryos we have detected mesenchymal cells that co-express LEC markers and the pan-leukocyte marker CD45. Here, we have characterized the mesoderm of murine embryos with LEC markers Prox1, Lyve-1 and LA102 in combination with macrophage markers CD11b and F4/80.

Results

We observed cells co-expressing both types of markers (e.g. Prox1 – Lyve-1 – F4/80 triple-positive) located in the mesoderm, immediately adjacent to, and within lymph vessels. Our proliferation studies with Ki-67 antibodies showed high proliferative capacities of both the Lyve-1-positive LECs of lymph sacs/lymphatic sprouts and the Lyve-1-positive mesenchymal cells.

Conclusion

Our data argue for a dual origin of LECs in the mouse, although the primary source of embryonic LECs may reside in specific embryonic veins and mesenchymal lymphangioblasts integrated secondarily into lymph vessels. The impact of a dual source of LECs for ontogenetic, phylogenetic and pathological lymphangiogenesis is discussed.
Phylogenomics of plant genomes: a methodology for genome-wide searches for orthologs in plants
Authors: Conte Matthieu G , Gaillard Sylvain , Droc Gaetan , Perin Christophe
Published: April 2008

Background

Gene ortholog identification is now a major objective for mining the increasing amount of sequence data generated by complete or partial genome sequencing projects. Comparative and functional genomics urgently need a method for ortholog detection to reduce gene function inference and to aid in the identification of conserved or divergent genetic pathways between several species. As gene functions change during evolution, reconstructing the evolutionary history of genes should be a more accurate way to differentiate orthologs from paralogs. Phylogenomics takes into account phylogenetic information from high-throughput genome annotation and is the most straightforward way to infer orthologs. However, procedures for automatic detection of orthologs are still scarce and suffer from several limitations.

Results

We developed a procedure for ortholog prediction between Oryza sativa and Arabidopsis thaliana. Firstly, we established an efficient method to cluster A. thaliana and O. sativa full proteomes into gene families. Then, we developed an optimized phylogenomics pipeline for ortholog inference. We validated the full procedure using test sets of orthologs and paralogs to demonstrate that our method outperforms pairwise methods for ortholog predictions.

Conclusion

Our procedure achieved a high level of accuracy in predicting ortholog and paralog relationships. Phylogenomic predictions for all validated gene families in both species were easily achieved and we can conclude that our methodology outperforms similarly based methods.
Methylation alterations are not a major cause of PTTG1 missregulation
Authors: Hidalgo Manuel , Galan Jose Jorge , Sáez Carmen , Ferrero Eduardo , Castilla Carolina , Ramirez-Lorca Reposo , Pelaez Pablo , Ruiz Agustin , Japón Miguel A , Royo Jose Luis
Published: April 2008

Background

On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear.

Method

We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus.

Conclusion

Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of missregulation associated to PTTG1 over-expression.
Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions
Authors: Akhouri Reetesh Raj , Sharma Ashwani , Malhotra Pawan , Sharma Amit
Published: April 2008

Background

Thrombospondin-related anonymous protein (TRAP) is essential for sporozoite motility and for liver cell invasion. TRAP is a type 1 membrane protein that possesses multiple adhesive domains in its extracellular region.

Methods

Plasmodium falciparum TRAP (PfTRAP) and its subdomains were expressed in a mammalian expression system, and eleven different mutants generated to study interaction of PfTRAP with liver cells. Binding studies between HepG2 cell extracts and PfTRAP were performed using co-immunoprecipitation protocols.

Results

Five different amino acid residues of PfTRAP that are involved in liver cell binding have been identified. These PfTRAP mutants bound to heparin like the wild type PfTRAP thereby suggesting a non-heparin mediated binding of PfTRAP to liver cells. Three Src family proteins -Lyn, Lck and CrkL which interact with PfTRAP are also identified. Liver cell extracts and immunoprecipitated Src family kinases phosphorylated PfTRAP at multiple sites. An analysis of multiple TRAP sequences revealed Src homology 3 domain (SH3) binding motifs.

Conclusion

Binding of PfTRAP to SH3-domain containing proteins like Src-family kinases and their ability to phosphorylate PfTRAP suggests a novel role for PfTRAP in cell signaling during sporozoite invasion and homing inside the liver cells. These data shed new light on TRAP-liver cell interactions.
Enhanced detection of gametocytes by magnetic deposition microscopy predicts higher potential for Plasmodium falciparum transmission
Authors: Karl Stephan , David Makindi , Moore Lee , Grimberg Brian T , Michon Pascal , Mueller Ivo , Zborowski Maciej , Zimmerman Peter A
Published: April 2008

Background

Aggregated haemozoin crystals within malaria-infected erythrocytes confer susceptibility of parasitized cells to a magnetic field. Here the utility of this method for diagnosis of human malaria is evaluated in a malaria-endemic region of Papua New Guinea (PNG).

Methods and findings

Individuals with Plasmodium falciparum malaria symptoms (n = 55) provided samples for conventional blood smear (CBS) and magnetic deposition microscopy (MDM) diagnosis. Standard Giemsa staining and light microscopy was performed to evaluate all preparations. Plasmodium falciparum parasitaemia observed on MDM slides was consistently higher than parasitaemia observed by (CBS) for ring (CBS = 2.6 vs. MDM = 3.4%; t-test P-value = 0.13), trophozoite (CBS = 0.5 vs. MDM = 1.6%; t-test P-value = 0.01), schizont (CBS = 0.003 vs. MDM = 0.1%; t-test P-value = 0.08) and gametocyte (CBS = 0.001 vs. MDM = 0.4%; t-test P-value = 0.0002) parasitaemias. Gametocyte prevalence determined by CBS compared to MDM increased from 7.3% to 45%, respectively.

Conclusion

MDM increased detection sensitivity of P. falciparum-infected, haemozoin-containing erythrocytes from infected humans while maintaining detection of ring-stage parasites. Gametocyte prevalence five-fold higher than observed by CBS suggests higher malaria transmission potential in PNG endemic sites compared to previous estimates.
Fatal bacteremia due to immotile Vibrio cholerae serogroup O21 in Vientiane, Laos – a case report
Authors: Phetsouvanh Rattanaphone , Nakatsu Masami , Arakawa Eiji , Davong Viengmone , Vongsouvath Manivanh , Lattana Olay , Moore Catrin E , Nakamura Satoshi , Newton Paul N
Published: April 2008

Background

Human infections with non-O1, non-O139 V. cholerae have been described from Laos. Elsewhere, non cholera-toxin producing, non-O1, non-O139 V. cholerae have been described from blood cultures and ascitic fluid, although they are exceedingly rare isolates.

Case presentation

We describe a farmer who died with Vibrio cholerae O21 bacteremia and peritonitis in Vientiane, Laos, after eating partially cooked apple snails (Pomacea canaliculata) and mussels (Ligumia species). The cultured V. cholerae were non-motile. PCR detected ompW and toxR gene regions but not the ctxA, ompU, omp K and TCP gene regions. Although the organisms lacked flagellae on scanning electron microscopy, they possessed the Vibrio flagellin flaA gene.

Conclusion

Severe bacteremic non-O1, non-O139 V. cholerae is reported from Laos. The organisms were unusual in being non-motile. They possessed the Vibrio flagellin flaA gene. Further research to determine the reasons for the non-motility and virulence is required.
Molecular analysis reveals heterogeneity of mouse mammary tumors conditionally mutant for Brca1
Authors: Wright Mollie H , Robles Ana I , Herschkowitz Jason I , Hollingshead Melinda G , Anver Miriam R , Perou Charles M , Varticovski Lyuba
Published: April 2008

Background

Development of therapies for patients with BRCA1 mutations has been hampered by lack of readily available in vitro and in vivo models. We recently showed that transplantation of transgenic mammary tumors as cell suspensions into naïve recipients generates reproducible tumors with remarkable stability of gene expression profile. We examined the expression profiles of original and serially transplanted mammary tumors from Brca1 deficient mice, and tumor derived cell lines to validate their use for preclinical testing and studies of tumor biology.

Methods

Original tumors, serially transplanted and multiple cell lines derived from Brca1 mammary tumors were characterized by morphology, gene and protein expression, and cell surface markers.

Results

Gene expression among Brca1 tumors showed more heterogeneity than among previously characterized tumors from MMTV-PyMT and -Wnt1 models. Gene expression data segregated Brca1 tumors into 3 distinct types: basal, mixed luminal, and tumors with epithelial-to-mesenchymal transition (EMT). Serial transplantation of individual tumors and multiple cell lines derived from the original tumors recapitulated the molecular characteristics of each tumor of origin. One tumor had distinct features of EMT and gave rise to cell lines that contained a distinct CD44+/CD24-/low population that may correlate with human breast cancer stem cells.

Conclusion

Although individual tumors expanded by transplantation maintain the genomic profile of the original tumors, the heterogeneity among Brca1 tumors limits the extent of their use for preclinical testing. However, cell lines offer a robust material for understanding tumor biology and response to therapies driven by BRCA1 deficiency.
Percent body fat estimations in college men using field and laboratory methods: A three-compartment model approach
Authors: Moon Jordan R , Tobkin Sarah E , Smith Abbie E , Roberts Michael D , Ryan Eric D , Dalbo Vincent J , Lockwood Chris M , Walter Ashley A , Cramer Joel T , Beck Travis W , Stout Jeffrey R
Published: April 2008

Background

Methods used to estimate percent body fat can be classified as a laboratory or field technique. However, the validity of these methods compared to multiple-compartment models has not been fully established. The purpose of this study was to determine the validity of field and laboratory methods for estimating percent fat (%fat) in healthy college-age men compared to the Siri three-compartment model (3C).

Methods

Thirty-one Caucasian men (22.5 ± 2.7 yrs; 175.6 ± 6.3 cm; 76.4 ± 10.3 kg) had their %fat estimated by bioelectrical impedance analysis (BIA) using the BodyGram™ computer program (BIA-AK) and population-specific equation (BIA-Lohman), near-infrared interactance (NIR) (Futrex®6100/XL), four circumference-based military equations [Marine Corps (MC), Navy and Air Force (NAF), Army (A), and Friedl], air-displacement plethysmography (BP), and hydrostatic weighing (HW).

Results

All circumference-based military equations (MC = 4.7% fat, NAF = 5.2% fat, A = 4.7% fat, Friedl = 4.7% fat) along with NIR (NIR = 5.1% fat) produced an unacceptable total error (TE). Both laboratory methods produced acceptableTEvalues (HW = 2.5% fat; BP = 2.7% fat). The BIA-AK, and BIA-Lohman field methods produced acceptableTEvalues (2.1% fat). A significant difference was observed for the MC and NAF equations compared to both the 3C model and HW (p< 0.006).

Conclusion

Results indicate that the BP and HW are valid laboratory methods when compared to the 3C model to estimate %fat in college-age Caucasian men. When the use of a laboratory method is not feasible, BIA-AK, and BIA-Lohman are acceptable field methods to estimate %fat in this population.
HIV-1 latency in actively dividing human T cell lines
Authors: Jeeninga Rienk E , Westerhout Ellen M , van Gerven Marja L , Berkhout Ben
Published: April 2008

Background

Eradication of HIV-1 from an infected individual cannot be achieved by current drug regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy and are able to replenish systemic infection upon interruption of the treatment. Therapeutic targeting of viral latency will require a better understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 in resting memory CD4 T cells, the most prominent reservoir of transcriptional silent provirus. However, the molecular mechanisms that permit long-term transcriptional control of proviral gene expression in these cells are still not well understood. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication.

Results

We set out to develop a new in vitro HIV-1 latency model system using the doxycycline (dox)-inducible HIV-rtTA variant. Stable cell clones were generated with a silent HIV-1 provirus, which can subsequently be activated by dox-addition. Surprisingly, only a minority of the cells was able to induce viral gene expression and a spreading infection, eventhough these experiments were performed with the actively dividing SupT1 T cell line. These latent proviruses are responsive to TNFα treatment and alteration of the DNA methylation status with 5-Azacytidine or genistein, but not responsive to the regular T cell activators PMA and IL2. Follow-up experiments in several T cell lines and with wild-type HIV-1 support these findings.

Conclusion

We describe the development of a new in vitro model for HIV-1 latency and discuss the advantages of this system. The data suggest that HIV-1 proviral latency is not restricted to resting T cells, but rather an intrinsic property of the virus.