bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic modeling of cellulosic biomass to ethanol via simultaneous saccharification and fermentation: Part II. Experimental validation using waste paper sludge and anticipation of CFD analysis
Authors: Shao Xiongjun , Lynd Lee , Wyman Charles
Published: July 2008

A kinetic model of cellulosic biomass conversion to ethanol via simultaneous saccharification and fermentation (SSF) developed previously was validated experimentally using paper sludge as the substrate. Adsorption parameters were evaluated based on the data obtained at various values for fractional cellulose conversion. The adsorption model was then combined with batch SSF data to evaluate the cellulose hydrolysis parameters. With the parameters evaluated for the specific substrate, the discrete model was able to predict SSF successfully both with discrete addition of cellulase only and with discrete feeding of substrate, cellulase, and media. The model tested in this study extends the capability of previous SSF models to semi‐continuous feeding configurations, and invites a mechanistic interpretation of the recently observed trend of increasing conversion with decreasing feeding frequency [Fan et al. (2007a) Bioprocess Biosyst Eng 30(1):27–34]. Our results also support the feasibility and utility of determining adsorption parameters based on data obtained at several conversions, particularly when the model is to be applied to extended reaction times rather than only initial hydrolysis rates. The revised model is considerably more computationally efficient than earlier models, and appears for many conditions to be within the capability of simulation using computational fluid dynamics. Biotechnol. Bioeng. 2009;102: 66–72. © 2008 Wiley Periodicals, Inc.
Kinetic modeling of cellulosic biomass to ethanol via simultaneous saccharification and fermentation: Part I. Accommodation of intermittent feeding and analysis of staged reactors
Authors: Shao Xiongjun , Lynd Lee , Wyman Charles , Bakker André
Published: July 2008

The model of South et al. [South et al. (1995) Enzyme Microb Technol 17(9): 797–803] for simultaneous saccharification of fermentation of cellulosic biomass is extended and modified to accommodate intermittent feeding of substrate and enzyme, cascade reactor configurations, and to be more computationally efficient. A dynamic enzyme adsorption model is found to be much more computationally efficient than the equilibrium model used previously, thus increasing the feasibility of incorporating the kinetic model in a computational fluid dynamic framework in the future. For continuous or discretely fed reactors, it is necessary to use particle conversion in conversion‐dependent hydrolysis rate laws rather than reactor conversion. Whereas reactor conversion decreases due to both reaction and exit of particles from the reactor, particle conversion decreases due to reaction only. Using the modified models, it is predicted that cellulose conversion increases with decreasing feeding frequency (feedings per residence time, f). A computationally efficient strategy for modeling cascade reactors involving a modified rate constant is shown to give equivalent results relative to an exhaustive approach considering the distribution of particles in each successive fermenter. Biotechnol. Bioeng. 2009;102: 59–65. © 2008 Wiley Periodicals, Inc.
Dependence of computed tomography volume measurements upon section thickness: An application to human dry skulls
Authors: Sahin Bunyamin , Mazonakis Michael , Akan Huseyin , Kaplan Suleyman , Bek Yuksel
Published: July 2008

Estimation of intracranial volume (ICV) using computed tomography (CT) scans has previously been described. However, we were not able to identify a gold standard study that analyzed the effect of section thickness on the estimation of ICV. Therefore, we conducted the present study, scanning five dry skulls in the coronal and axial planes using a multislice CT machine (Toshiba TSX‐101A, Aquilion 16 Slice, Tochigi, Japan). Consecutive sections of variable thicknesses of 2, 3, 5, 7, and 10 mm, respectively, were used to estimate ICV by means of the planimetry method of the Cavalieri principle. All estimations were done by the same observer. However, the estimated volumes did not concur with the actual volumes of the skulls as determined by the fluid displacement technique (P < 0.05). In fact, results revealed that the section thicknesses created over‐ or under‐projection effects for the estimated volumes. The results were analyzed to reveal the deviation principles of the estimates based on section thickness. Prediction formulas were calculated to estimate the deviation percentage of the ICV depending on section thickness and section plane. Ultimately, the results showed that the effect of section thickness on ICV estimates could not be overlooked, but that the values obtained could be corrected using the proposed prediction formulas presented in this study. Clin. Anat. 21:479–485, 2008. © 2008 Wiley‐Liss, Inc.
Staying or returning: Pre‐migration influences on the migration process of German migrants to New Zealand
Authors: Bürgelt Petra T. , Morgan Mandy , Pernice Regina
Published: July 2008

Changes in migrants' backgrounds and societies sending and receiving migrants might increase adaptation issues and reduce retention. To enhance migrants' well‐being/health and their likelihood of staying it is necessary to gain an understanding of psychological and social factors that contribute to resilience and adaptation. This paper presents findings from a qualitative study that investigated the experiences, interpretations and actions of German migrant couples to New Zealand throughout the whole migration process to identify these factors. In depth, episodic interviews were conducted with four couples who decided to stay in New Zealand and four couples who decided to return to Germany. Interview data were complemented with participant observation. This paper provides insights into how the pre‐migration experiences, interpretations and actions of German migrants to New Zealand influenced their establishment, their interpretations and actions and consequently adaptation, well‐being/health and the decision whether to stay in New Zealand or to return to Germany. The findings illuminate the influence of psychological and social factors on migration experiences, interpretations and actions throughout the migration process. The paper offers some solutions for addressing the identified barriers to successful migration and integration into host societies. Copyright © 2008 John Wiley & Sons, Ltd.
Territorial sense of community, ethnic prejudice and political orientation
Authors: Prezza Miretta , Zampatti Emanuela , Pacilli Maria G. , Paoliello Annalisa
Published: July 2008

This research focused on territorial sense of community and ethnic prejudice. In particular, we related these two constructs and investigated their relationship to individual characteristics (personal political orientation, contact with immigrants, etc.) and community‐level ones (such as ethnic composition and the political orientation of the local government). Two studies were conducted in four small towns in central and southern Italy. For each study, 160 people were contacted. The instruments used were a questionnaire, the Italian Sense of Community Scale and the Blatant Prejudice Scale. The results showed that territorial sense of community is not related to ethnic prejudice or to the ethnic heterogeneity of the territory. It was also found that people with right‐wing political sympathies revealed higher levels of prejudice than people with left‐wing sympathies. Finally, in a town with a stable and consolidated left‐wing orientation of the local government we found, when the influence of personal political orientation was controlled for, lower levels of prejudice than in a town with a right‐wing orientation. Copyright © 2008 John Wiley & Sons, Ltd.
Political exile and the construction of identity: A life stories approach
Authors: Cornejo Marcela
Published: July 2008

This paper centres its attention on the impact political exile—a result of the 1973 military coup in Chile—had on the life of exiles, particularly on their identity, based on life stories. It examines the life experiences of four groups of exiles living in Belgium following two criteria: (1) whether they remained in the host country or returned to Chile once the political conditions permitted them to do so, and (2) whether they belonged to the first generation (the exiles themselves) or the second generation (the children of exiles). The results are organized into three main categories of analysis: the places of exile, that is the symbolic sites, the different meanings exile has acquired in the personal histories of the interviewees, showing that the main place is where the individual had to test him/herself, the place they seem to have been sent forever; the return, that is the role the prohibition to come back played and still plays today, which has been characterized as a myth, a possibility and an option; and, finally, the narration of exile, which examines special features of the narration of the exile experience viewed retrospectively and in relation to whether the events are still in vigour, thus giving birth to stories about exile after the exile. Copyright © 2008 John Wiley & Sons, Ltd.
Protection, manipulation or interference with relationships? Discourse analysis of New Zealand lawyers' talk about supervised access and partner violence
Authors: Pond Rachael , Morgan Mandy
Published: July 2008

Violence against women within the context of intimate relationships is a complex social problem in Aotearoa/New Zealand and internationally. Such abuse by men is particularly problematic because of its prevalence, and because of the extent and magnitude of deleterious effects on the health and psychological well‐being of women and children. In New Zealand, the legal system is assumed to play an important role in protecting women and children from domestic violence. Through the Domestic Violence Act 1995 and the amended Guardianship Act 1968, persons who are physically, sexually or psychologically abusive to their children, or to their partner whilst children are present, may only be entitled to supervised access to these children. Although supervised access has been found to increase the safety of women and children, it remains a contentious issue. Because of the role that legal professionals have in the implementation of relevant legislation, the present research explored how lawyers make sense of supervised access in the context of domestic violence. Eighteen male and female lawyers were interviewed. Their interview transcripts were then subject to discourse analysis. This paper illustrates and discusses discourses used in relation to supervised access, including those that support protecting children from the harm of domestic violence through supervised access, and those that challenge the need for children's protection. Within the cluster of latter discourses, supervised access was not considered a means of balancing children's relationships with both parents with children's need for protection, or a way of enabling men to have a safe relationship with their children. Rather, it was constructed as violating men's rights to a relationship with their children, and children's right to a relationship with both parents. The prevalence of discourses opposing supervised access could affect the likelihood of women obtaining protection orders and supervised access conditions, and hence, women and children's safety. However, perpetuation of ‘supportive’ discourses could enhance women and children's well‐being, and facilitate safe ongoing relationships between children and non‐custodial parents. Copyright © 2008 John Wiley & Sons, Ltd.
Conditions for dialogue and illuminating inequality in multicultural societies
Authors: Chryssides Alison
Published: July 2008

In a recent article, Nesbitt‐Larking (2007) postulated the notion of ‘deep multiculturalism’, dependent, at least in part, on dialogue and on ‘host’ societies questioning their core values. In this commentary I suggest that whilst such a proposal is indeed a worthy ideal, the social psychological processes underpinning how this can be achieved need to be adequately addressed if such a vision is to become a reality. Using Social Representation Theory, I hope to explicate the operation of power, ideologies and collective memory on the process of representation, and suggest that understanding this process may better enable one to manage the obstacles involved in a project of deep multiculturalism. Drawing on Whiteness studies, I suggest that for a host society to question their core values, certain unconsciously held values need first to be illuminated; however, in so doing, I postulate that caution is exercised in order that such exposure does not perpetuate racialising representations. Using the concepts of anchoring and objectification, I propose that highlighting the similarities and shared experiences of a society's members may be a more successful strategy for achieving deep multiculturalism, than focusing on diversity and difference. Copyright © 2008 John Wiley & Sons, Ltd.
Dissolving the Diaspora
Authors: Garner Steve
Published: July 2008

[Dissolving the Diaspora] provides a Canadian perspective on the problem of intergration viewed through the prism of a particular understanding of multiculturalism. In this article the three key themes; the conceptualisation of diversities, diaspora and dialogue, are identified, and these conceptes are engaged with critically. I argue that despite the many advantages of the multicultural paradigm, there are still a number of fault lines that require critical attention, among which are the relationship of culture to class, and the failure to fully incorporate racism in its vocabulary. I suggest, using the phrase ‘the grammar of social location’, that the language of multiculturalism still ties us to a relatively static model of culture and away from an analysis of the complexity of inequalities. Copyright © 2008 John Wiley & Sons, Ltd.
Cobalt‐Mediated Radical Polymerization of Acrylonitrile: Kinetics Investigations and DFT Calculations
Authors: Debuigne Antoine , Michaux Catherine , Jérôme Christine , Jérôme Robert , Poli Rinaldo , Detrembleur Christophe
Published: July 2008

The successful controlled homopolymerization of acrylonitrile (AN) by cobalt‐mediated radical polymerization (CMRP) is reported for the first time. As a rule, initiation of the polymerization was carried out starting from a conventional azo‐initiator (V‐70) in the presence of bis(acetylacetonato)cobalt(II) ([Co(acac)2]) but also by using organocobalt(III) adducts. Molar concentration ratios of the reactants, the temperature, and the solvent were tuned, and the effect of these parameters on the course of the polymerization is discussed in detail. The best level of control was observed when the AN polymerization was initiated by an organocobalt(III) adduct at 0 °C in dimethyl sulfoxide. Under these conditions, poly(acrylonitrile) with a predictable molar mass and molar mass distribution as low as 1.1 was prepared. A combination of kinetic data, X‐ray analyses, and DFT calculations were used to rationalize the results and to draw conclusions on the key role played by the solvent molecules in the process. These important mechanistic insights also permit an explanation of the unexpected “solvent effect” that allows the preparation of well‐defined poly(vinyl acetate)‐b‐poly(acrylonitrile) by CMRP.
Modular Chiral Bidentate Phosphonites: Design, Synthesis, and Application in Catalytic Asymmetric Hydroformylation Reactions
Authors: Zhao Baoguo , Peng Xingao , Wang Zheng , Xia Chungu , Ding Kuiling
Published: July 2008

A new class of C2‐symmetric chiral bidentate phosphonite ligands has been synthesized in moderate to good yields from readily available starting materials. Application of these air‐stable chiral phosphonites in the RhI‐catalyzed asymmetric hydroformylation of styrene derivatives, vinyl acetate, and allyl cyanide afforded the corresponding chiral aldehydes with high regio‐ and enantioselectivities under mild reaction conditions. The modular nature of the ligands allows fine‐tuning of the selectivities through judicious modifications of the substituents on the ligand backbone. X‐ray structural analysis of the catalyst precursor suggested that the steric hindrance caused by the protruding remote substituents of the ligands into the vicinity of the metal center might be an important factor for the enantio‐control of the reaction, whereas the sense of asymmetric induction can be rationalized on the basis of a trigonal‐bipyramidal transition state diagram.
HP‐Ca2Si5N8—A New High‐Pressure Nitridosilicate: Synthesis, Structure, Luminescence, and DFT Calculations
Authors: Römer S. Rebecca , Braun Cordula , Oeckler Oliver , Schmidt Peter J. , Kroll Peter , Schnick Wolfgang
Published: July 2008

HP‐Ca2Si5N8was obtained by means of high‐pressure high‐temperature synthesis utilizing the multianvil technique (6 to 12 GPa, 900 to 1200 °C) starting from the ambient‐pressure phase Ca2Si5N8. HP‐Ca2Si5N8crystallizes in the orthorhombic crystal system (Pbca(no. 61),a=1058.4(2),b=965.2(2),c=1366.3(3) pm,V=1395.7(7)×106 pm3,Z=8,R1=0.1191). The HP‐Ca2Si5N8structure is built up by a three‐dimensional, highly condensed nitridosilicate framework with N[2]as well as N[3]bridging. Corrugated layers of corner‐sharing SiN4tetrahedra are interconnected by further SiN4units. The Ca2+ions are situated between these layers with coordination numbers 6+1 and 7+1, respectively. HP‐Ca2Si5N8as well as hypothetical orthorhombic o‐Ca2Si5N8(isostructural to the ambient‐pressure modifications of Sr2Si5N8and Ba2Si5N8) were studied as high‐pressure phases of Ca2Si5N8up to 100 GPa by using density functional calculations. The transition pressure into HP‐Ca2Si5N8was calculated to 1.7 GPa, whereas o‐Ca2Si5N8will not be adopted as a high‐pressure phase. Two different decomposition pathways of Ca2Si5N8(into Ca3N2and Si3N4or into CaSiN2and Si3N4) and their pressure dependence were examined. It was found that a pressure‐induced decomposition of Ca2Si5N8into CaSiN2and Si3N4is preferred and that Ca2Si5N8is no longer thermodynamically stable under pressures exceeding 15 GPa. Luminescence investigations (excitation at 365 nm) of HP‐Ca2Si5N8:Eu2+reveal a broadband emission peaking at 627 nm (FWHM=97 nm), similar to the ambient‐pressure phase Ca2Si5N8:Eu2+.
pKa‐Directed Host–Guest Assemblies: Rational Analysis of Molecular Adducts of 2,4‐Diamino‐6‐methyl‐1,3,5‐triazine with Various Aliphatic Dicarboxylic Acids
Authors: Delori Amit , Suresh Eringathodi , Pedireddi V. R.
Published: July 2008

Molecular adducts of 2,4‐diamino‐6‐methyl‐1,3,5‐triazine (1) have been prepared with various aliphatic dicarboxylic acids. The molecular complexes (1 a–1 i) thus formed by co‐crystallizing 1 with oxalic, malonic, succinic, fumaric, acetylene dicarboxylic, glutaric, thiodiglycolic, diglycolic, and adipic acids have been found to give two types of host–guest assemblies that have voids or channels in a three‐dimensional arrangement. The different types of host–guest arrangement appear to result from differences in the acidity of the dicarboxylic acids, that is, acids with pKa<3.0 give host networks that consist of 1 and the corresponding acid with water or solvent molecules of crystallization present as guests, whereas acids with pKa>3.0 exist as guests in voids in a host network formed by 1. The former arrangement is observed in adducts 1 a, 1 b, 1 e, and 1 h and the latter arrangement is found in adducts 1 c, 1 d, 1 f, 1 g, and 1 i.
Na8[Cr4B12P8O44(OH)4][P2O7]⋅nH2O: A 3D Borophosphate Framework with Spherical Cages
Authors: Yang Tao , Sun Junliang , Li Guobao , Eriksson Lars , Zou Xiaodong , Liao Fuhui , Lin Jianhua
Published: July 2008

A chromium borophosphate–phosphate (Na8[Cr4B12P8O44(OH)4][P2O7]⋅nH2O, 1), which has an unusual 3D framework structure, was synthesized under hydrothermal conditions. The framework consists of spherical cages composed of CrO6, PO4, BO4, and BO3 polyhedra. The cages are located at the vertices and the body center of the cubic cell and are interconnected through 12‐membered‐ring windows along the {111} direction. The actual framework structure is very complex, but the description can be simplified by using the 5‐connected fundamental building cluster [CrP5B3O24]11−. In addition, 1 represents the first borate‐rich borophosphate that contains a 3D borophosphate partial framework (${{{\hfill 3\atop \hfill \infty }}}$[B3P2O11(OH)]) in which the fundamental building unit is an oB dreier single ring (Δ4□:□<Δ2□>□). The cavities of the framework are filled with disengaged water molecules and Na+ counterions. The former can be reversibly desorbed and reabsorbed and the latter can be exchanged by Li+ ions, which results in significant shrinkages of the cell volume.
Screening Electronic Communication through ortho‐, meta‐ and para‐Substituted Linkers Separating Subphthalocyanines and C60
Authors: González‐Rodríguez David , Torres Tomás , Herranz María Ángeles , Echegoyen Luis , Carbonell Esther , Guldi Dirk M.
Published: July 2008

We have prepared two complementary series of SubPc–C60 (SubPc=subphthalocyanine) electron/energy donor–acceptor systems, in which the two constituents are linked through ortho‐, meta‐, or para‐substituted phenoxy spacers. In one of the series (1 a) the SubPc units bear iodine atoms, while in the other series (1 b) diphenylamino groups are linked to the SubPc macrocycles. The iodine atoms and diphenylamino groups both influence the resulting oxidation potentials of the electron‐donating SubPc. They also modulate the outcome of excited state interactions, namely, energy and/or charge transfer. In addition, we have studied the impact that the substitution pattern in the phenoxy spacer exerts onto intramolecular processes in the ground and excited states. Although some of these processes are governed by the spatial separation between both components, the different electronic coupling through ortho‐, meta‐, or para‐ connections also plays decisive roles in some cases.
The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia
Authors: Aribi Ahmed , Kantarjian Hagop , Koller Charles , Thomas Deborah , Faderl Stefan , Garcia‐Manero Guillermo , Cortes Jorge
Published: July 2008

BACKGROUND.

During therapy with tyrosine kinase inhibitors (TKIs), approximately 20% to 50% of patients with chronic myeloid leukemia (CML) develop grade ≥3 thrombocytopenia leading to treatment interruptions and dose reductions. Interleukin 11 (IL‐11) reduces the incidence and the severity of thrombocytopenia in solid tumors.

METHODS.

The authors investigated the efficacy and safety of low‐dose IL‐11 for improving thrombocytopenia associated with TKI therapy in 14 patients with CML. The starting dose of IL‐11 was 10 μg/kg 3 times weekly, and the dose was escalated by 1 dose level every 2 weeks if the patients had no sustained platelet increase.

RESULTS.

The median patient age was 52 years. The median platelet count at the time IL‐11 was started was 37 × 109/L. All patients had prior TKI dose reductions. After the initiation of IL‐11, 8 of 14 patients (57%) had an increase in platelet count with a median peak platelet count of 110 × 109/L. One additional patient had no platelet increase but was able to tolerate an imatinib dose increase. Eleven patients had a decrease in the number of days of TKI therapy interruption secondary to thrombocytopenia after the initiation of IL‐11 (6% of total treatment time vs 34% of total treatment time before IL‐11). Therapy was well tolerated.

CONCLUSIONS.

The current results indicated that IL‐11 may correct thrombocytopenia associated with TKI therapy for patients with CML and that it has a favorable toxicity profile. Cancer 2008. © 2008 American Cancer Society.
Hydrogen Generation at Ambient Conditions: Application in Fuel Cells
Authors: Boddien Albert , Loges Björn , Junge Henrik , Beller Matthias
Published: July 2008

The efficient generation of hydrogen from formic acid/amine adducts at ambient temperature is demonstrated. The highest catalytic activity (TOF up to 3630 h−1 after 20 min) was observed in the presence of in situ generated ruthenium phosphine catalysts. Compared to the previously known methods to generate hydrogen from liquid feedstocks, the systems presented here can be operated at room temperature without the need for any high‐temperature reforming processes, and the hydrogen produced can then be directly used in fuel cells. A variety of Ru precursors and phosphine ligands were investigated for the decomposition of formic acid/amine adducts. These catalytic systems are particularly interesting for the generation of H2 for new applications in portable electric devices.
Generation of flow cytometry data files with a potentially infinite number of dimensions
Authors: Pedreira Carlos E. , Costa Elaine S. , Barrena Susana , Lecrevisse Quentin , Almeida Julia , van Dongen Jacques J. M. , Orfao Alberto
Published: July 2008

Immunophenotypic characterization of B‐cell chronic lymphoproliferative disorders (B‐CLPD) is associated with the use of increasingly larger panels of multiple combinations of 3 to ≥6 monoclonal antibodies (Mab), data analysis being separately performed for each of the different stained sample aliquots. Here, we describe and validate an automated method for calculation of flow cytometric data from several multicolor stainings of the same cell sample—i.e., the merging of data from different aliquots stained with partially overlapping combinations of Mab reagents (focusing on ≥1 cell populations)—into one data file as if it concerned a single “super” multicolor staining. Evaluation of the performance of the method described was done in a group of 60 B‐CLPD studied at diagnosis with 18 different reagents in a panel containing six different 3‐ and 4‐color stainings, which systematically contained CD19 for the identification of B‐cells. Our results show a high degree of correlation and agreement between originally measured and calculated data about cell surface stainings, providing a basis for the use of this approach for the generation of flow cytometric data files containing information about a virtually infinite number of stainings for each individual cellular event measured in a sample, using a limited number of fluorochrome stainings. © 2008 International Society for Advancement of Cytometry
Polychromatic plots: Graphical display of multidimensional data
Authors: Roederer Mario , Moody M. Anthony
Published: July 2008

Limitations of graphical displays as well as human perception make the presentation and analysis of multidimensional data challenging. Graphical display of information on paper or by current projectors is perforce limited to two dimensions; the encoding of information from other dimensions must be overloaded into the two physical dimensions. A number of alternative means of encoding this information have been implemented, such as offsetting data points at an angle (e.g., three‐dimensional projections onto a two‐dimensional surface) or generating derived parameters that are combinations of other variables (e.g., principal components). Here, we explore the use of color to encode additional dimensions of data. PolyChromatic Plots are standard dot plots, where the color of each event is defined by the values of one, two, or three of the measurements for that event. The measurements for these parameters are mapped onto an intensity value for each primary color (red, green, or blue) based on different functions. In addition, differential weighting of the priority with which overlapping events are displayed can be defined by these same measurements. PolyChromatic Plots can encode up to five independent dimensions of data in a single display. By altering the color mapping function and the priority function, very different displays that highlight or de‐emphasize populations of events can be generated. As for standard black‐and‐white dot plots, frequency information can be significantly biased by this display; care must be taken to ensure appropriate interpretation of the displays. PolyChromatic Plots are a powerful display type that enables rapid data exploration. By virtue of encoding as many as five dimensions of data independently, an enormous amount of information can be gleaned from the displays. In many ways, the display performs somewhat like an unsupervised cluster algorithm, by highlighting events of similar distributions in multivariate space. Published 2008 Wiley‐Liss, Inc.
Morphogenesis of the node and notochord: The cellular basis for the establishment and maintenance of left–right asymmetry in the mouse
Authors: Lee Jeffrey D. , Anderson Kathryn V.
Published: July 2008

Establishment of left–right asymmetry in the mouse embryo depends on leftward laminar fluid flow in the node, which initiates a signaling cascade that is confined to the left side of the embryo. Leftward fluid flow depends on two cellular processes: motility of the cilia that generate the flow and morphogenesis of the node, the structure where the cilia reside. Here, we provide an overview of the current understanding and unresolved questions about the regulation of ciliary motility and node structure. Analysis of mouse mutants has shown that the motile cilia must have a specific structure and length, and that they must point posteriorly to generate the necessary leftward fluid flow. However, the precise structure of the motile cilia is not clear and the mechanisms that position cilia on node cells have not been defined. The mouse node is a teardrop‐shaped pit at the distal tip of the early embryo, but the morphogenetic events that create the mature node from cells derived from the primitive streak are only beginning to be characterized. Recent live imaging experiments support earlier scanning electron microscopy (SEM) studies and show that node assembly is a multi‐step process in which clusters of node precursors appear on the embryo surface as overlying endoderm cells are removed. We present additional SEM and confocal microscopy studies that help define the transition stages during node morphogenesis. After the initiation of left‐sided signaling, the notochordal plate, which is contiguous with the node, generates a barrier at the embryonic midline that restricts the cascade of gene expression to the left side of the embryo. The field is now poised to dissect the genetic and cellular mechanisms that create and organize the specialized cells of the node and midline that are essential for left–right asymmetry. Developmental Dynamics 237:3464–3476, 2008. © 2008 Wiley‐Liss, Inc.
Live imaging of cell protrusive activity, and extracellular matrix assembly and remodeling during morphogenesis in the frog, Xenopus laevis
Authors: Davidson Lance A. , Dzamba Bette D. , Keller Ray , Desimone Douglas W.
Published: July 2008

Cell motility and matrix assembly have traditionally been studied in isolation because of a lack of suitable model systems in which both can be observed simultaneously. With embryonic tissues from the gastrulating frog Xenopus laevis we observe stages of fibronectin fibrillogenesis coincident with protrusive activity in the overlying cells. Using live confocal time‐lapse images collected from Cy3‐tagged fibronectin and plasma membrane tethered green fluorescent protein, we describe the movement and the elaboration of a complex fibrillar network undergoing topological rearrangements of fibrils on the surface of an embryonic tissue. Discrete processes of annealing, polymerization, stretching, breaking, and recoiling are recorded. Elaboration and maintenance of the complex topology of the extracellular matrix appears to require filamentous actin. These findings support a mechanical‐model in which cell tractive forces elaborate the complex topological fibrillar network and are part of a homeostatic mechanism for the regulation of the extracellular matrix. Developmental Dynamics 237:2684–2692, 2008. © 2008 Wiley‐Liss, Inc.
Formation of the asymmetric pineal complex in zebrafish requires two independently acting transcription factors
Authors: Snelson Corey D. , Burkart Jarred T. , Gamse Joshua T.
Published: July 2008

The pineal complex of zebrafish consists of a pineal organ and a left‐sided parapineal organ. Mutation of the floating head (flh) gene, which encodes a homeodomain protein, causes premature termination of pineal cell division without affecting specification or asymmetric placement of the parapineal. The from beyond (fby) mutation, a premature stop codon in the T‐domain‐containing protein Tbx2b, disrupts formation of the parapineal while leaving the pineal largely intact. However, flh is reported as being required for tbx2b transcription. To resolve the paradox that flhand tbx2b mutants have opposite phenotypes but have been placed in the same genetic pathway, we have examined transcriptional cross‐regulation in single flh or fby mutants and genetic epistasis in double mutants. Careful analysis shows that flh is not required for tbx2b transcription and double mutants exhibit an additive phenotype. We conclude that Flh and Tbx2b regulate separate programs of pineal and parapineal development. Developmental Dynamics 237:3538–3544, 2008. © 2008 Wiley‐Liss, Inc.
Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines
Authors: Nielsen Sonja K. , Møllgård Kjeld , Clement Christian A. , Veland Iben R. , Awan Aashir , Yoder Bradley K. , Novak Ivana , Christensen Søren Tvorup
Published: July 2008

Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell lines, PANC‐1 and CFPAC‐1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC‐1 and CFPAC‐1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis. Developmental Dynamics 237:2039–2052, 2008. © 2008 Wiley‐Liss, Inc.
Role for primary cilia in the regulation of mouse ovarian function
Authors: Johnson Ellen T. , Nicola Teodora , Roarty Kevin , Yoder Bradley K. , Haycraft Courtney J. , Serra Rosa
Published: July 2008

Ift88 is a component of the intraflagellar transport complex required for formation and maintenance of cilia. Disruption of Ift88 results in depletion of cilia. The goal of the current study was to determine the role of primary cilia in ovarian function. Deletion of Ift88 in ovary using Cre‐Lox recombination in mice resulted in a severe delay in mammary gland development including lack of terminal end bud structures, alterations in the estrous cycle, and impaired ovulation. Because estrogen drives the formation of end buds and Cre was expressed in the granulosa cells of the ovary, we tested the hypothesis that addition of estradiol to the mutant mice would compensate for defects in ovarian function and rescue the mammary gland phenotype. Mammary gland development including the formation of end bud structures resumed in mutant mice that were injected with estradiol. Together the results suggest that cilia are required for ovarian function. Developmental Dynamics 237:2053–2060, 2008. © 2008 Wiley‐Liss, Inc.
Msx1 and Msx2 are expressed in sub‐populations of vascular smooth muscle cells
Authors: Goupille Olivier , Saint Cloment Cécile , Lopes Miguel , Montarras Didier , Robert Benoît
Published: July 2008

Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze the expression of these homeogenes in the adult mouse. We observed that Msx genes are prominently expressed in a subset of blood vessels. The Msx2nlacZ allele is mainly expressed in a restricted population of mural cells in peripheral arteries and veins. Msx1nlacZ is expressed to a lesser extent by vascular smooth muscle cells of peripheral arteries, but is highly expressed in arterioles and capillaries, making Msx1 a novel marker for a subpopulation of pericytes. Expression is set up early in developing vessels and maintained throughout life. In addition, expression of both genes is observed in a few endothelial cells of the aorta at fetal stages, and only Msx2 continues to be expressed in this layer at the adult stage. These results suggest major functions for Msx genes in vascular mural cell formation and remodeling. Developmental Dynamics 237:2187–2194, 2008. © 2008 Wiley‐Liss, Inc.
Xenopus zinc finger transcription factor IA1 (Insm1) expression marks anteroventral noradrenergic neuron progenitors in Xenopus embryos
Authors: Parlier Damien , Ariza Ana , Christulia Fotini , Genco Flavio , Vanhomwegen Jessica , Kricha Sadia , Souopgui Jacob , Bellefroid Eric J.
Published: July 2008

The evolutionarily conserved IA1 (Insm1) gene is strongly expressed in the developing nervous system. Here, we show that IA1 is expressed during Xenopus laevis embryogenesis in neural plate primary neurons as well as in a population of uncharacterized anteroventral cells that form in front of the cement gland and that we identified as noradrenergic neurons. We also show that the formation of those anteroventral cells is dependent on BMPs and inhibited by Notch and that it is regulated by the transcription factors Xash1, Phox2, and Hand2. Finally, we provide functional evidence suggesting that IA1 may also play a role in their formation. Together, our results reveal that IA1 constitutes a novel player downstream of Xash1 in the formation of a previously unidentified population of Xenopus noradrenergic primary neurons. Developmental Dynamics 237:2147–2157, 2008. © 2008 Wiley‐Liss, Inc.
Gene nomenclature guidelines for the planarian Schmidtea mediterranea
Authors: Reddien Peter W. , Newmark Phillip A. , Alvarado Alejandro Sánchez
Published: July 2008

We describe a gene nomenclature system for the freshwater planarian Schmidtea mediterranea. Guidelines are specified for designating names for genes and proteins, as well as for describing RNA‐mediated genetic interference (RNAi) experiments. The proposed conventions aim to avoid multiple names being ascribed to single genes and to establish a uniform, simple method for naming genes in S. mediterranea that is readily understood by researchers working on planarians and other organisms. Developmental Dynamics 237:3099–3101, 2008. © 2008 Wiley‐Liss, Inc.
Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2
Authors: Iklé Jennifer , Elwell Jennifer A. , Bryantsev Anton L. , Cripps Richard M.
Published: July 2008

The myocyte enhancer factor‐2 (MEF2) family of transcription factors plays key roles in the activation of muscle structural genes. In Drosophila, MEF2 accumulates at high levels in the embryonic muscles, where it activates target genes throughout the mesoderm. Here, we identify the Transglutaminase gene (Tg; CG7356) as a direct transcriptional target of MEF2 in the cardiac musculature. Tg is expressed in cells forming the inflow tracts of the dorsal vessel, and we identify the enhancer responsible for this expression. The enhancer contains three binding sites for MEF2, and can be activated by MEF2 in tissue culture and in vivo. Moreover, loss of MEF2 function, or removal of the MEF2 binding sites from the enhancer, results in loss of Tg expression. These studies identify a new MEF2 target in the cardiac musculature. These studies provide a possible mechanism for the activation of transglutaminase genes. Furthermore, given the relevance of transglutaminase genes to human disease, these studies provide a possible mechanism for their activation. Developmental Dynamics 237:2090–2099, 2008. © 2008 Wiley‐Liss, Inc.
Functional characterization of lmo2‐Cre transgenic zebrafish
Authors: Wang Lei , Zhang Yong , Zhou Ting , Fu Yan‐Fang , Du Ting‐Ting , Jin Yi , Chen Yi , Ren Chun‐Guang , Peng Xiao‐Lan , Deng Min , Liu Ting Xi
Published: July 2008

Cre/loxP system is a powerful tool to manipulate the genome. Transgenic animals expressing Cre recombinase in specific tissues or cells have been widely used for conditional gene targeting, lineage tracing, and other genetic analyses. In zebrafish, the transgenic line with stable expression of Cre in specific tissues and cell subtypes has not been generated and its functional activity remains to be defined. Here we report the establishment of a stable transgenic fish Tg(zlmo2:Cre), which specifically expresses Cre in the primitive hematopoietic progenitors and vascular endothelial cells, under the control of lmo2 promoter. Our result shows that the Cre expression pattern recapitulates the endogenous lmo2 expression pattern during embryogenesis. Crossing of the Tg(zlmo2:Cre) line with another established transgenic reporter line Tg(zlmo2:loxP‐DsRed‐loxP‐EGFP), induces a robust recombination activity in hematopoietic progenitors and vascular endothelial cells. Thus, the Tg(zlmo2:Cre) transgenic line provides an invaluable tool to dissect genetic pathways in hematopoietic development and diseases. Developmental Dynamics 237:2139–2146, 2008. © 2008 Wiley‐Liss, Inc.
Engagement of Toll‐like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non‐oxidative and TNF‐independent anti‐mycobacterial activity
Authors: Gomes M. Salomé , Sousa Fernandes Sofia , Cordeiro João V. , Silva Gomes Sandro , Vieira André , Appelberg Rui
Published: July 2008

Toll‐like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra‐macrophagic growth of M. avium, using macrophages from TLR2‐deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow‐derived macrophages in a MyD88‐dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20–25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2‐mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47‐kDa guanosine triphosphatase (LRG‐47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as‐yet‐unknown mechanism that may involve increased phagosome maturation.
Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA‐electroporated B cells
Authors: Park Mi‐Young , Kim Hye‐Sung , Woo Sun‐Je , Kim Chang‐Hyun , Park Jung‐Sun , Sohn Hyun‐Jung , Kim Hyung‐Jin , Oh Seong‐Taek , Kim Tai‐Gyu
Published: July 2008

RNA electroporation as a gene delivery method is more feasible and safer as compared with viral vectors. RNA‐loaded dendritic cells (DC) have been used to induce T cell responses against tumor rejection antigens and B cells can also act as antigen‐presenting cells for cellular vaccines. In this study, we compared B cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for their capacity to generate cytotoxic T lymphocytes and antitumor immunity. Vaccination using these B cells induced levels of IFN‐γ‐secreting T cells and cytotoxic T cells comparable to those induced by DC. Intravenous administration was the optimum route for the B cell vaccine, while subcutaneous administration was the optimum route for the DC vaccine. The B cell vaccine predominantly generated CEA‐specific CD4+ T cells, whereas the DC vaccine generated CD8+ T cells. Moreover, the B cell vaccine induced higher levels of anti‐CEA antibodies than the DC vaccine. A heterogeneous prime‐boost using B cells and DC failed to show any synergistic effects; however, the B cell vaccine did inhibit tumor growth and prolonged survival to a similar extent as the DC vaccine. Such RNA‐electroporated B cells may prove useful as cellular tumor vaccines with potential clinical application.
Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules
Authors: Kaser Arthur , Hava David L. , Dougan Stephanie K. , Chen Zhangguo , Zeissig Sebastian , Brenner Michael B. , Blumberg Richard S.
Published: July 2008

Lipid antigens are presented to T cells by the non‐polymorphic MHC class I‐related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)‐resident chaperone that has been shown to lipidate the group 2 CD1 molecule CD1d and thus to regulate its function. We now report that MTP also regulates the function of group 1 CD1 molecules CD1a, CD1b, and CD1c. Pharmacological inhibition of MTP in monocyte‐derived dendritic cells and lymphoblastoid B cell lines transfected with group 1 CD1 resulted in a substantial decrease in endogenous self lipid antigen presentation to several CD1‐restricted T cell lines. Silencing MTP expression in CD1c‐transfected HeLa cells similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER‐resident MTP, which was confirmed by confocal microscopy, also markedly decreased presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation.
Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome
Authors: Qian Youcun , Giltiay Natalia , Xiao Jianhua , Wang Yue , Tian Jun , Han Shuhua , Scott Martin , Carter Robert , Jorgensen Trine N. , Li Xiaoxia
Published: July 2008

CD40L and B lymphocyte‐activating factor (BAFF), members of the TNF superfamily, play critical roles in B cell survival and activation, and in the regulation of humoral immunity. We previously reported that the adaptor molecule Act1 functions as a negative regulator of CD40‐ and BAFF‐mediated B cell survival. Here we demonstrated that mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjögren's syndrome (SS), in association with systemic lupus erythematosus‐like nephritis. Analyses of Act1−/−CD40−/− and Act1−/−BAFF−/− double‐deficient mice revealed that Act1 regulates different stages of the disease development through its impact on both CD40‐ and BAFF‐mediated pathways. We found that Act1 modulates the survival of autoreactive B cells mainly through its negative regulatory role in BAFF‐mediated cell survival, while the effect of Act1 on autoantibody production is likely through modulation of CD40‐mediated T cell‐dependent antibody response. The impact of Act1 on both BAFF and CD40 pathways establishes Act1‐deficient mice as a unique model to study distinct steps of autoimmunity and regulation of self tolerance.