bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular Delivery of Bioactive Peptides to RBL‐2H3 Cells Induces β‐Hexosaminidase Secretion and Phospholipase D Activation
Authors: Howl John , Jones Sarah , Farquhar Michelle
Published: December 2003

This investigation compared the secretory efficacies of a series of peptides delivered to the cytoplasm of RBL‐2H3 mast cells. Mimetic peptides, designed to target intracellular proteins that regulate cell signalling and membrane fusion, were synthesised as transportan 10 (TP10) chimeras for efficient plasma membrane translocation. Exocytosis of β‐hexosaminidase, a secretory lysosomal marker, indicated that peptides presenting sequences derived from protein kinase C (PKC; C1 H‐CRRLSVEIWDWDL‐NH2) and the CB1 cannabinoid receptor (C3 H‐RSKDLRHAFRSMFPSCE‐NH2) induced β‐hexosaminidase secretion. Other peptide cargoes, including a Rab3A‐derived sequence and a homologue of C3, were inactive in similar assays. Translocated C1 also activated phospholipase D (PLD), an enzyme intimately involved in the regulated secretory response of RBL‐2H3 cells, but C1‐induced secretion was not dependent upon phosphatidate synthesis. Neither down‐regulation of Ca2+‐sensitive isoforms of PKC nor the application of a selective PKC inhibitor attenuated the secretory efficacy of C1. These observations indicate that the molecular target of C1 is a protein involved in the regulated secretory pathway that is upstream of PLD but is not a PKC isoform. This study also confirmed that TP10 is a relatively inert cell‐penetrating vector and is, therefore, widely suitable for studies in cells that are sensitive to peptidyl secretagogues.
Prion Diseases: From Molecular Biology to Intervention Strategies
Authors: Nunziante Max , Gilch Sabine , Schätzl Hermann M.
Published: December 2003

Prion diseases are fatal neurodegenerative infectious disorders for which no therapeutic or prophylactic regimens exist. Understanding the molecular process of conformational conversion of the cellular prion protein (PrPc) into its pathological isoform (PrPSc) will be necessary to devise effective antiprion strategies. In recent years, new findings in the cell biology of PrPc, in the molecular pathogenesis of PrPSc, and in the cellular quality control mechanisms involved in these scenarios have accumulated. A function of the prion protein in signalling, the possible impact of the proteasome, and aggresomes as intracellular waste deposits have been described. Here, important pathogenetic similarities with the more frequent neurodegenerative disorders are evident. The need for therapeutic, postexposure, and prophylactic possibilities was drastically illustrated by the emergence of variant Creutzfeldt–Jakob disease (vCJD), a new human prion disease caused by bovine spongiform encephalopathy (BSE) derived prions. Although prion infectivity in humans is usually restricted to the central nervous system, in vCJD patients prions are present in the lympho‐reticular system, posing a theoretical risk of accidental human‐to‐human transmission. A variety of chemical antiprion substances have been reported in in vitro and cell culture based assays or in animal studies. Occasionally, they have also made their way into the first human trials. In addition, various promising interference strategies have been devised in transgenic models, although they are usually hard to transfer into nontransgenic in vivo situations. New findings in the fields of peripheral prion pathogenesis and immune system involvement fuelled the search for antiprion strategies formerly considered to be entirely impossible. This opened the door towards classical immunological interference techniques. Remarkably, passive and even active vaccination approaches now seem to be realistic goals.
Functionalizing Nanocrystalline Metal Oxide Electrodes With Robust Synthetic Redox Proteins
Authors: Topoglidis Emmanuel , Discher Bohdana M. , Moser Christopher C. , Dutton P. Leslie , Durrant James R.
Published: December 2003

De novo designed synthetic redox proteins (maquettes) are structurally simpler, working counterparts of natural redox proteins. The robustness and adaptability of the maquette protein scaffold are ideal for functionalizing electrodes. A positive amino acid patch has been designed into a maquette surface for strong electrostatic anchoring to the negatively charged surfaces of nanocrystalline, mesoporous TiO2 and SnO2 films. Such mesoporous metal oxide electrodes offer a major advantage over conventional planar gold electrodes by facilitating formation of high optical density, spectroelectrochemically active thin films with protein loading orders of magnitude greater (up to 8 nmol cm−2) than that achieved with gold electrodes. The films are stable for weeks, essentially all immobilized‐protein display rapid, reversible electrochemistry. Furthermore, carbon monoxide ligand binding to the reduced heme group of the protein is maintained, can be sensed optically and reversed electrochemically. Pulsed UV excitation of the metal oxide results in microsecond or faster photoreduction of an immobilized cytochrome and millisecond reoxidation. Upon substitution of the heme‐group Fe by Zn, the light‐activated maquette injects electrons from the singlet excited state of the Zn protoporphyrin IX into the metal oxide conduction band. The kinetics of cytochrome/metal oxide interfacial electron transfer obtained from the electrochemical and photochemical data obtained are discussed in terms of the free energies of the observed reactions and the electronic coupling between the protein heme group and the metal oxide surface.
Adhesion Inhibition of F1C‐Fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by Multivalent Carbohydrate Ligands
Authors: Autar Reshma , Khan A. Salam , Schad Matthias , Hacker Jörg , Liskamp Rob M. J. , Pieters Roland J.
Published: December 2003

In order to evaluate their inhibition of bacterial adhesion, the carbohydrate sequences GalNAcβ1→4Gal and GalNAcβ1→4Galβ1→4Glc were synthesized. The disaccharide was conjugated to dendrons based on the 3,5‐di‐(2‐aminoethoxy)‐benzoic acid branching unit to yield di‐ and tetravalent versions of these compounds. A divalent compound was also prepared that had significantly longer spacer arms. Relevant monovalent compounds were prepared for comparison. Their anti‐adhesion properties against F1C‐fimbriated uropathogenic Escherichia coli were evaluated in an ELISA‐type assay by using a recombinant strain and also by using Pseudomonas aeruginosa strains PAO and PAK. Adhesion inhibition was observed in all cases, and multivalency effects of up to one order of magnitude were observed. The combination of spacer and multivalency effects led to a 38‐fold increase in the potency of a divalent inhibitor with long spacer arms towards the PAO strain when compared with the free carbohydrate.
Cover Picture: DNA Mismatch‐Specific Base Flipping by a Bisacridine Macrocycle (ChemBioChem 12/2003)
Authors: David Arnaud , Bleimling Nathalie , Beuck Christine , Lehn Jean‐Marie , Weinhold Elmar , Teulade‐Fichou Marie‐Paule
Published: December 2003

The cover picture shows how the conformational equilibrium of a nucleobase in DNA can be changed from the predominant intrahelical position to the extrahelical position (center). This process of base (nucleotide) flipping is achieved naturally by DNA glycosylases and DNA methyltransferases like M.TaqI, which binds the target base in its extrahelical conformation and fills the resulting hole in the DNA (left). Base flipping can also be induced by a small synthetic bisacridine macrocycle that specifically inserts at thermodynamically weakened sites (e.g. base mismatches) in DNA and hence stabilizes the extrahelical conformation of a nucleobase (right). Further details on binding of the bisacridine macrocycle to DNA can be found in the article by E. Weinhold, M.‐P. Teulade‐Fichou et al. on p. 1326 ff.
Microwave‐Assisted Chemical Reactions
Authors: Nüchter M. , Müller U. , Ondruschka B. , Tied A. , Lautenschläger W.
Published: December 2003

This article reviews the state of the art of microwave‐assisted reactions and the influence of microwaves on mass and heat transfer. The heating behavior of representative test reactions and single substances is compared for heating with microwaves and thermal energy. Similarities and differences between convective heating and dielectric irradiation methods are discussed with regard to the yield, the selectivity, and the enantiomeric purity of the reaction products. Furthermore, prevailing problems related to the scale‐up of microwave‐assisted reactions are discussed considering the energy absorption of the substances and mixtures to be heated, and their dependence on the energy consumption and the amount of substance.
Hydrodynamics and Mass Transfer in Gas‐Liquid‐Solid Circulating Fluidized Beds
Authors: Liu Z. , Vatanakul M. , Jia L. , Zheng Y.
Published: December 2003

Although extensive work has been performed on the hydrodynamics and gas‐liquid mass transfer in conventional three‐phase fluidized beds, relevant documented reports on gas‐liquid‐solid circulating fluidized beds (GLSCFBs) are scarce. In this work, the radial distribution of gas and solid holdups were investigated at two axial positions in a GLSCFB. The results show that gas bubbles and solid particles distribute uniformly in the axial direction but non‐uniformly in the radial direction. The radial non‐uniformity demonstrates a strong factor on the gas‐liquid mass transfer coefficients. A local mass transfer model is proposed to describe the gas‐liquid mass transfer at various radial positions. The local mass transfer coefficients appear to be symmetric about the central line of the riser with a lower value in the wall region. The effects of gas flow rates, particle circulating rates and liquid velocities on gas‐liquid mass transfer have also been investigated.
Novel Liquid‐Flow Splitting Unit Specifically Made for Numbering‐Up of Liquid/Liquid Chemical Microprocessing
Authors: Schenk R. , Hessel V. , Hofmann C. , Löwe H. , Schönfeld F.
Published: December 2003

A liquid‐flow splitting unit for dividing one main liquid stream into six substreams was developed without the need for active flow regulation. The tool has six fluid connectors that allow the numbering‐up of a respective number of microprocess devices for liquid or liquid/liquid processes. One such liquid/liquid process for which the current tool design and tests in particular have been conceived, is the forced precipitation of precious inorganic powders by the segmented flow tubular reactor (SFTR) technique. Such investigations were performed with six micromixers of impinging‐jet or interdigital separation layer type attached to the liquid‐flow splitting unit. Fluid equipartition is achieved via the action of the microdevices as flow resistors, thereby increasing the pressure drop of the system. Liquid splitting was carried out in a cylindrical liquid tank with one inlet and six outlet holes that also served for pulsation dampening. By CFD simulations the impact of two important geometric parameters of this tank, namely, the height at a given diameter and the position of the inlet hole, on the fluid splitting was studied. In addition, the influence of the injection direction with respect to the normal of the tank was analyzed. It turned out that in the presence of flow resistors (typically generating a pressure drop at about 60 mbar) this impact is negligible, i.e., principally, a large flexibility on design and operation is provided. Without these resistors, the before‐mentioned parameters in turn have a large impact that is discussed in detail. Experiments with a liquid‐flow splitting unit and six coupled impinging‐jet micromixers using water as liquid proved a reasonable fluid distribution with a standard and maximum deviation of the substream flow rates of 4 and 11 %, respectively. These deviations are mainly caused by different pressure drops (Δp) of the individual impinging‐jet mixers as a result of tolerances in the microfabrication method, die sinking μEDM manufacture. Already small differences in the microstructured outlet hole diameters (d = 300 μm) of the impinging‐jet mixer have a large influence due to the d–4 ∼ Δp dependence. Additionally, attaching specially adapted interdigital separation layer micromixers to the liquid‐flow splitting unit, a minimum/maximum (standard) deviation of the water distribution below 5 (2) % could be achieved. To obtain this improved result, it was necessary to optimize the choice of material, the design of the microstructure inside the mixer, and the fabrication process.
Isomerization and Hydrocracking of n‐Decane over Magnesium‐Containing Molecular Sieves with AEL, AFI, and AFO Topology
Authors: Hartmann M. , Elangovan S.P.
Published: December 2003

The present contribution deals with model studies on n‐decane isomerization over the magnesium‐containing aluminophosphates MgAPO‐11 (AEL topology), MgAPO‐5 (AFI), and MgAPO‐41 (AFO). A particular aim of this study was to elucidate the influence of the pore diameter on the product selectivity. The pore diameter was reduced in the following order: MgAPO‐5 (dp = 0.73 nm) > MgAPO‐41 (dp = 0.43 × 0.70 nm) > MgAPO‐11 (dp = 0.39 × 0.63 nm).
Aggregation and loss of cytokeratin filament networks inhibit Golgi organization in liver‐derived epithelial cell lines
Authors: Kumemura Hiroto , Harada Masaru , Omary M. Bishr , Sakisaka Shotaro , Suganuma Tatsuo , Namba Masayoshi , Sata Michio
Published: December 2003

Intermediate filaments are one of the three major cytoskeletons. Some roles of intermediate filaments in cellular functions have emerged based on various diseases associated with mutations of cytokeratins. However, the precise functions of intermediate filament are still unclear. To resolve this, we manipulated intermediate filaments of cultured cells by expressing a mutant cytokeratin. Arginine 89 of cytokeratin18 plays an important role in intermediate filament assembly. The expression of green fluorescent protein‐tagged cytokeratin18 arg89cys induced aggregations and loss of the intermediate filament network composed of cytokeratins in liver‐derived epithelial cells, Huh7 and OUMS29, but only induced the formation of cytokeratin aggregates and did not affect the intermediate filament network of endogenous vimentin in HEK293. The expression of this mutant affected the distribution of Golgi apparatus and the reassembly of Golgi apparatus after perturbations by nocodazole or brefeldin A in both Huh7 and OUMS29, but not in HEK293. Our data show that loss of the original intermediate filament network, but not the existence of cytokeratin aggregates, induces redistribution of the Golgi apparatus. The original intact intermediate filament network is necessary for the organization of Golgi apparatus. Cell Motil. Cytoskeleton 57:37–52, 2004. © 2003 Wiley‐Liss, Inc.
Higher plant cortical microtubule array analyzed in vitro in the presence of the cell wall
Authors: Tian Guo‐Wei , Smith Damien , Glück Susanne , Baskin Tobias I.
Published: December 2003

Plant morphogenesis depends on an array of microtubules in the cell cortex, the cortical array. Although the cortical array is known to be essential for morphogenesis, it is not known how the array becomes organized or how it functions mechanistically. Here, we report the development of an in vitro model that provides good access to the cortical array while preserving the array's organization and, importantly, its association with the cell wall. Primary roots of maize (Zea mays) are sectioned, without fixation, in a drop of buffer and then incubated as desired before eventual fixation. Sectioning removes cytoplasm except for a residuum comprising cortical microtubules, vesicles, and fragments of plasma membrane underlying the microtubules. The majority of the cortical microtubules remain in the cut‐open cells for more than 1 h, fully accessible to the incubation solution. The growth zone or more mature tissue can be sectioned, providing access to cortical arrays that are oriented either transversely or obliquely to the long axis of the root. Using this assay, we report, first, that cortical microtubule stability is regulated by protein phosphorylation; second, that cortical microtubule stability is a function of orientation, with divergent microtubules within the array depolymerizing within minutes of sectioning; and third, that the polarity of microtubules in the cortical array is not uniform. These results suggest that the organization of the cortical array involves random nucleation followed by selective stabilization of microtubules formed at the appropriate orientation, and that the signal specifying alignment must treat orientations of ± 180° as equivalent. Cell Motil. Cytoskeleton 57:26–36, 2004. © 2003 Wiley‐Liss, Inc.
Developmental distribution of reelin‐positive cells and their secreted product in the rodent spinal cord
Authors: Kubasak Marc D. , Brooks Rona , Chen Songbo , Villeda Saul A. , Phelps Patricia E.
Published: December 2003

To date, only sympathetic and parasympathetic preganglionic neurons are known to migrate abnormally inreelermutant spinal cord. Reelin, the large extracellular matrix protein absent inreeler, is found in wild‐type neurons bordering both groups of preganglionic neurons. To understand better Reelin's function in the spinal cord, we studied its developmental expression in both mice and rats. A remarkable conservation was found in the spatiotemporal pattern of Reelin in both species. Numerous Reelin‐expressing cells were found in the intermediate zone, except for regions containing somatic and autonomic motor neurons. A band of Reelin‐positive cells filled the superficial dorsal horn, whereas only a few immunoreactive cells populated the deep dorsal horn and dorsal commissure. High levels of diffuse Reelin product were detected in the lateral marginal and ventral ventricular zones in both rodent species. This expression pattern was detected at all segmental spinal cord levels during embryonic development and remained detectable at lower levels throughout the first postnatal month. To discriminate between the cellular and secreted forms of Reelin, brefeldin A was used to block secretion in organotypic cultures. Such perturbations revealed that the high levels of secreted Reelin in the lateral marginal zone were derived from varicose axons of more medially located Reelin‐positive cells. Thus, the laterally located secreted Reelin product may normally prevent the preganglionic neurons from migrating too far medially. Based on the strong evolutionary conservation of Reelin expression and its postnatal detection, Reelin may have other important functions in addition to its role in neuronal migration. J. Comp. Neurol. 468:165–178, 2004. © 2003 Wiley‐Liss, Inc.
A study of prebiotic evolution
Authors: Corbet Aaron
Published: December 2003

A very simple model prebiotic system is explored, both, to elucidate the full complexity of its dynamic behavior, and from the standpoint of what a thermal analysis can tell us about evolution more generally. The system consists of a coacervate containing a four variable enzymatic oscillator that is driven by a single input concentration. The reaction scheme is “nested”; i.e., by “turning on” one reaction at a time we can go from a two‐variable system, to one of three variables, to one of four, each developing more complex behavior. The four‐variable system is shown to have at least five distinct genera of complex attractors within the range examined. Two of these coexist for the same parameter values; the other three are substantially separated in the bifurcation space. The fixed points, characteristic roots, Lyapunov exponents, stability (dissipation), Kaplan‐Yorke dimensions, and correlation dimensions are all calculated for each attractor. A six‐variable amplification of the reaction scheme is considered as a simple model of nucleation in a coacervate and is shown to totally stabilize the corresponding attractor. An Evolutionary Potential is proposed that is wholly beyond the purview of classical thermostatics, yet incorporates entropy effects via Clausius' strong version of the Second Law. It is shown that the latter is a necessary condition for the sort of structuring characteristic of living systems. © 2003 Wiley Periodicals, Inc. Complexity 8: 45–67, 2003
Variable segmentation based on intrinsic video rate characteristics to transport pre‐stored video across networks
Authors: Fu Huirong , Zhang Liren
Published: December 2003

A variable segmentation scheme based on intrinsic video rate characteristics (VSIVRC) is proposed for efficient dynamic bandwidth allocation to transport pre‐stored variable bit rate (VBR) video across networks. The proposed scheme is evaluated with a set of real‐life MPEG video traces and also compared with two fixed segmentation schemes: equal data segmentation (EDS) and equal frame segmentation (EFS). The obtained results show that the proposed VSIVRC scheme significantly outperforms both EDS and EFS in terms of range of selective bandwidth, matchness between arrival stream and playback stream, buffer occupancy and bandwidth allocation as well. Copyright © 2003 John Wiley & Sons, Ltd.
Immunocytochemical evaluation of estrogen receptor on archival Papanicolaou‐stained fine‐needle aspirate smears
Authors: Krishnamurthy Savitri , Dimashkieh Haytham , Patel Shobha , Sneige Nour
Published: December 2003

The availability of limited fine‐needle aspirate smears necessitates the selection of immunocytochemical (IC) methods that allow reuse of Pap‐stained smears to assess the estrogen receptor (ER) status of breast carcinoma. The objective of the current study was to compare IC evaluation of ER status on FNA smears by three methods: 1) ER‐ICA using H222 monoclonal antibody performed on slides fixed in formaldehyde–methanol–acetone; 2) destained Pap slides using 1D5 antibody; and 3) Pap‐stained slides without destaining using the same 1D5 antibody. Two representative Pap smears of breast carcinoma were selected from 48 cases of breast carcinoma in which ER was previously evaluated by ER‐ICA. One of these Pap smears was used as such and the other was destained prior to immunostaining by a modified ABC method using 1D5 monoclonal antibody. The number of cells with positive nuclear staining was expressed as a percentage and the intensity of staining was semiquantitatively scored on a scale of 1+ to 3+. The degree of agreement between the three methods was evaluated statistically by weighted kappa statistics. Thirty cases (63%) showed varying degrees of positive staining while 18 cases (38%) were entirely negative by all three methods. Significant discrepancies in the number of cells with positive staining and in the intensity of staining between the three methods occurred in 40% and 23% of the cases and was mainly due to a reduction in the number of cells with positive staining and the intensity of staining using Pap slides in comparison to ER‐ICA. Weighted kappa agreement of the percentage of cells with positive staining using Pap‐stained slides and destained Pap‐slides in comparison to ER‐ICA was 0.75 and 0.64, respectively, and that for the intensity of staining was 0.75 and 0.66, respectively. Therefore, IC evaluation of ER using Pap‐stained smears as such or destained Pap smears compared favorably with ER‐ICA. However, Pap‐stained smears used as such for ER immunostaining showed a slightly better agreement with ER‐ICA than destained Pap smears. Because significant differences in ER‐IC staining can occur with any of the immunocytochemical methods, a negative result is less reliable as an indicator of true ER status than a positive result. Diagn. Cytopathol. 2003;29:309–314. © 2003 Wiley‐Liss, Inc.
Comparative fine‐needle aspiration and pathologic study of malignant fibrous histiocytoma: Cytodiagnostic features of 95 tumors in 71 patients
Authors: Klijanienko Jerzy , Caillaud Jean‐Michel , Lagacé Réal , Vielh Philippe
Published: December 2003

To determine diagnostic cytomorphologic features of malignant fibrous histiocytoma (MFH) on fine‐needle aspiration (FNA) materials, we reviewed the cytologic material and corresponding histologic slides of 95 tumors in 71 patients. Forty‐four (46%) tumors were primary, 38 (40%) were recurrent, and 13 (14%) were metastatic. Histological variants of MFH were as follows: 52 (54.7%, 43 patients) were of the storiform/pleomorphic, seven (7.4%, five patients) were giant cells, four (4.2%, four patients) were inflammatory, and 31 (33.7%, 19 patients) were myxoid type. Review of original cytology reports showed that only 23 (24.2%) tumors were diagnosed as MFH and 68 (71.6%) as other types of malignancies. Four (4.2%) cases were reported as unsatisfactory/suspicious. Our findings showed that spindle‐shaped, round, giant cells, osteoclastic‐like giant, and inflammatory cells were the most consistent features that allow identification of the storiform/pleomorphic, giant cell, and inflammatory variants of MFH. The myxoid tumors had marked myxoid background matrix with spindle‐shaped cells and, less frequently, round and giant cells. Pleomorphic leiomyosarcoma and dedifferentiated liposarcoma should be considered in the differential diagnosis of stroriphorm/pleomorphic, giant cells, and inflammatory variants of MFH. However, myxoid MFH may resemble their leiomyosarcoma and liposarcoma counterparts. Diagn. Cytopathol. 2003;29:320–326. © 2003 Wiley‐Liss, Inc.
Statistical analysis of cytologic features useful in separation of metastatic urothelial carcinoma from other metastatic epithelial malignancies
Authors: Layfield Lester J. , Jones Claudia , Hirschowitz Sharon
Published: December 2003

The identification of a site of origin and direction of differentiation for metastatic neoplasms is clinically important, but is often difficult purely by cytologic analysis of aspirated material. Cytologic separation of metastatic urothelial carcinoma (UC) from other moderate or poorly differentiated epithelial malignancies is difficult, with few cytologic criteria identified in the literature as valuable for this distinction. Several investigators have suggested that “cercariform cells” (CCs) are highly correlated with the presence of metastatic UC. We statistically analyzed the utility of 37 cytomorphologic features for the recognition of urothelial differentiation in a series of 26 metastatic UCs, 10 metastatic squamous cell carcinomas (SCCs), and 15 metastatic adenocarcinomas (ADCs). All specimens had been obtained from metastatic deposits in the lung, liver, lymph nodes, or soft tissues. Stepwise discriminate function analysis with all three diagnoses showed that the strongest discrimination could be made using the findings of waxy metaplastic cytoplasm, with significant increments in prediction added by analysis for (CCs) followed by spindle cells, multiple nucleoli, and columnar‐shaped cells. The combination of these five variables accurately predicted 90% of all diagnoses, including 26 accurate diagnoses of UC, 9 accurate diagnoses of SCC, and 11 accurate diagnoses of ADC. CCs were present in highest numbers in UCs and present least frequently in cases of poorly differentiated ADC. While CCs were useful in the identification of UC, CCs occurred in a significant number of SCCs, limiting their diagnostic value as a single variable. Diagn. Cytopathol. 2003;29:334–338. © 2003 Wiley‐Liss, Inc.
Melanotic neuroectodermal tumor of infancy in the soft tissues of the arm: Fine needle aspiration biopsy and histologic correlation–a case report
Authors: Al‐Marzooq Yusef M. , Al‐Bagshi Muneer H. , Chopra Rajan , Hashish Hany
Published: December 2003

A case of melanotic neuroectodermal tumor of infancy (MNTI) presenting as a soft tissue mass in the right arm of a 6‐mo female child is discussed. The mass was diagnosed by fine‐needle aspiration biopsy (FNAB) and confirmed by histological examination. This communication emphasizes the characteristic cytology of MNTI and discusses its significance in the context of this tumor occurring in the soft tissues. The cytology smears were distinctive in showing a dual population of small, rounded, undifferentiated cells and larger melanin‐containing epithelial‐like cells. It is the identification of the latter cells in the smears which differentiates this tumor from other round cell tumors of infancy and helps in the correct diagnosis by FNAB. Diagn. Cytopathol. 2003;29:352–355. © 2003 Wiley‐Liss, Inc.
Deterministic and stochastic processes in children's isometric force variability
Authors: Deutsch Katherine M. , Newell Karl M.
Published: December 2003

This study examined the influence of deterministic and stochastic processes (including white Gaussian noise) on reductions in the amount of force output variability through childhood. The structure of the force signal produced during a constant isometric pinch grip task was examined as a function of age (6, 8, and 10 years, and young adults), availability of feedback information (with and without vision), digit (thumb and index finger), and force level (5, 15, 25, and 35% of maximal voluntary contraction). The amount of white Gaussian noise in the force signals was negligible and not age related. The availability of vision led increasingly over the older age groups to lower long‐range correlations with more than a single scaling range in a 1/f‐like decay process. The reductions in the amount of force variability from childhood to adulthood were related in large part to deterministic organization that increased the adaptive use of higher frequency components, due to the more flexible use of information feedback and feedforward processes. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 335–345, 2003.
Infant hand‐use preferences for grasping objects contributes to the development of a hand‐use preference for manipulating objects
Authors: Hinojosa Trisha , Sheu Ching‐Fan , Michel George F.
Published: December 2003

Twenty‐five infants, divided into three approximately equal groups according to their hand‐use preference for reaching for and grasping objects (right, left, or no‐preference), were videotaped at 7 and 11 months while involved in a semiplay activity in which they were presented with 26 toys (20–40 s for each presentation). Unimanual manipulation activity was coded, and the increase or decrease in preferred hand use across the two ages was analyzed. Infants with a right preference for reaching showed an increase in right‐hand use for unimanual manipulatory actions from 7 to 11 months. Infants with a left preference for reaching showed an increase in left‐hand use whereas infants with no preference for reaching showed a modest increase in the use of the right hand. These results support a modified progressive lateralization theory, which posits that a hand‐use preference for reaching for and grasping objects will concatenate during development into a hand‐use preference for manipulating objects. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 328–334, 2003.
Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty
Authors: Byrnes Elizabeth M. , Rigero Beth A. , Bridges Robert S.
Published: December 2003

The peripubertal period in the female rat is the time when the stimulatory effects of opioids on prolactin (PRL) secretion develop. In the adult rat, the administration of chronic high‐dose morphine has been shown to attenuate the ability of opiates to stimulate PRL secretion. One function of PRL in adult virgin rats is the induction of maternal behavior. The present study examined whether chronic high‐dose morphine exposure during the peripubertal period alters PRL‐mediated induction of maternal behavior in adult female rats. Two groups of juvenile female rats were administered increasing doses of morphine or vehicle (sc) from age 30 to 50 days. As adults, these females either remained intact or were ovariectomized and treated with a PRL‐dependent, steroid hormone regimen that stimulates a rapid onset of maternal behavior. All females were then exposed daily to rat foster pups to determine whether peripubertal morphine exposure affected their latencies to induce maternal behavior. Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment. Thus, chronic morphine exposure in the pubertal female did not impact the expression of pup‐induced maternal care. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 367–372, 2003.
Neurochemical correlates of sparing from motor deficits in rats depleted of striatal dopamine as weanlings
Authors: Sandstrom Michael I. , Nelson Christopher L. , Bruno John P.
Published: December 2003

The behavioral and neurochemical effects of striatal DA depletions were investigated in rats lesioned as weanlings (Day 27) or as adults (250–300 g). Administration of 6‐OHDA into the medial forebrain bundle resulted in comparably large (≥95%) depletions of tissue levels of DA in both age groups. As expected, rats depleted of DA as adults exhibited marked deficits in motoric behavior and body weight regulation that persisted for the 8 days of postsurgical observation. In contrast, rats depleted of DA as weanlings were spared from such deficits, and their behavior closely resembled that of age‐matched controls. Microdialysis studies revealed dialysate levels of striatal DA that paralleled these age‐dependent behavioral differences. At a time when age‐related behavioral differences were still quite pronounced (5–6 days postsurgery), basal DA levels were reduced by 80% of control values in rats lesioned as adults whereas basal DA levels in rats lesioned as weanlings were unchanged relative to their controls. Finally, adults depleted of striatal DA as weanlings were no more sensitive to the movement‐impairing effects of intrastriatal sulpiride (3.0 or 10.0 μg/hemisphere) infusions than were control rats. These data suggest that weanlings compensate for large, but incomplete, denervation of striatal DA with markedly enhanced release and turnover from residual terminals. This developmental plasticity may prevent the occurrence of behavioral deficits soon after the lesion and also the supersensitivity to the challenging effects of DA antagonists as animals grow into adulthood. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 373–383, 2003.
Nerve conduction velocity and evoked potential latencies in streptozotocin‐diabetic rats: effects of treatment with an angiotensin converting enzyme inhibitor
Authors: Manschot Sanne M. , Gispen Willem Hendrik , Kappelle L. Jaap , Biessels Geert Jan
Published: December 2003

Background

Diabetes mellitus is associated with deficits in cerebral function. Vascular disorders may play a role in the pathogenesis and provide a potential target for treatment. The present study examined if prevention and intervention treatment with the angiotensin converting enzyme inhibitor enalapril could improve peripheral and central neurophysiological deficits in streptozotocin‐diabetic rats.

Methods

Sciatic nerve conduction velocities were measured prior to diabetes induction and again every three weeks. In the prevention study, the final nerve conduction measurements were performed at 15 weeks and in the intervention study at 24 weeks. Brain stem auditory and visual evoked potential latencies were measured every 3 weeks from 10 weeks after diabetes induction. In the prevention study, the final evoked potential measurements were performed at 16 weeks and in the intervention study at 25 weeks. Treatment with the angiotensin converting enzyme inhibitor enalapril was started directly after diabetes induction (prevention treatment) and after 15 weeks of diabetes (intervention treatment).

Results

Nerve conduction velocity, brain stem auditory and visual evoked potential latencies were impaired in diabetic rats. Enalapril prevented deficits in nerve conduction velocity (p < 0.001), brain stem auditory evoked potential latencies (p < 0.01) and visual evoked potential latencies (p < 0.005). Enalapril intervention treatment had no effect on nerve conduction velocity and on visual evoked potential latencies, but improved brain stem auditory evoked potential latencies (p < 0.05) after 10 weeks of treatment.

Conclusion

Enalapril partially prevents the development of neurophysiological alterations in the peripheral and central nervous system and partially reverses deficits in brain stem auditory evoked potential latencies in STZ‐diabetic rats. Copyright © 2003 John Wiley & Sons, Ltd.
Enteroviruses and type 1 diabetes
Authors: Varela‐Calvino Ruben , Peakman Mark
Published: December 2003

The development of type 1 diabetes mellitus (T1DM) has been linked to exposure to environmental triggers, with Enteroviruses (EV) historically considered the prime suspects. Early serological studies suggested a link between EV infections and the development of T1DM and, though controversial, have been bolstered by more recent studies using more sensitive techniques such as direct detection of the EV genome by RT‐PCR in peripheral blood. In this review, we consider the weight of evidence that EV can be considered a candidate trigger of T1DM, using three major criteria: (1) is EV infection associated with clinical T1DM, (2) can EV trigger the development of autoimmunity and (3) what would explain the putative association? Copyright © 2003 John Wiley & Sons, Ltd.
Tetraploid development in the mouse
Authors: Eakin Guy S. , Behringer Richard R.
Published: December 2003

Spontaneous duplication of the mammalian genome occurs in approximately 1% of fertilizations. Although one or more whole genome duplications are believed to have influenced vertebrate evolution, polyploidy of contemporary mammals is generally incompatible with normal development and function of all but a few tissues. The production of tetraploid (4n) embryos has become a common experimental manipulation in the mouse. Although development of tetraploid mice has generally not been observed beyond midgestation, tetraploid:diploid (4n:2n) chimeras are widely used as a method for rescuing extraembryonic defects. The tolerance of tissues to polyploidy appears to be dependent on genetic background. Indeed, the recent discovery of a naturally tetraploid rodent species suggests that, in rare genetic backgrounds, mammalian genome duplications may be compatible with the development of viable and fertile adults. Thus, the range of developmental potentials of tetraploid embryos remains in large part unexplored. Here, we review the biological consequences and experimental utility of tetraploid mammals, in particular the mouse. Developmental Dynamics 228:751–766, 2003. © 2003 Wiley‐Liss, Inc.
Mouse muscle identity: The position‐dependent and fast fiber‐specific expression of a transgene in limb muscles is methylation‐independent and cell‐autonomous
Authors: Ngô‐Muller Valerie , Bertrand Anne , Concordet Jean‐Paul , Daegelen Dominique
Published: December 2003

We previously characterised transgenic mice in which fast‐muscle‐specific regulatory sequences from the human aldolase A pM promoter drive the chloramphenicol acetyltransferase gene expression. Mutation of a NF1/MEF2 binding site (M2 motif) in this promoter does not affect fibre‐type specificity of the transgene but modifies its expression in a subset of fast‐twitch fibres at the limb level, preferentially affecting distal limb muscles. We investigated the molecular and cellular bases of this peculiar expression pattern that provided an adequate model to characterise the mechanisms responsible for muscle positional information. By direct electrotransfer of mutated M2 construct in adult muscle, we demonstrate that positional differences in mutated M2 transgene expression are not observed when the transgene is not integrated into chromatin. Also, this transgene expression pattern does not seem to be correlated with the extent of CpG methylation in its promoter sequence. Finally, we show that positional values reflected by CAT levels are maintained in primary cultures established from different adult limb muscles, as well as in heterotopically transplanted muscles. Our results suggest that mutation of the M2 site contributes to reveal a molecular memory of fibre fate that would be set up on pM promoter during development and persist into adulthood possibly through a chromatin imprint maintained in satellite cells associated with various limb muscles. Developmental Dynamics 228:594–605, 2003. © 2003 Wiley‐Liss, Inc.
Neurotrophin‐3 signaling in mammalian Merkel cell development
Authors: Szeder Viktor , Grim Miloš , Kucera Jan , Sieber‐Blum Maya
Published: December 2003

Merkel cells are sensory cells of neural crest origin. Because little is known about the mechanisms that direct their differentiation, we have investigated the potential role of a candidate regulatory factor, neurotrophin‐3 (NT‐3). At embryonic day 16.5 (E 16.5), neither NT‐3 nor its primary receptors, TrkC and p75NTR are expressed by Merkel cells in the murine whisker. At the time of birth, however, Merkel cells are immunoreactive for NT‐3, TrkC and p75NTR. In TrkC null and NT‐3 null mice, Merkel cells differentiate initially, but undergo apoptosis perinatally. These results show that NT‐3 signaling is not required for the differentiation of Merkel cells, but that it is essential for their postnatal survival. Developmental Dynamics 228:623–629, 2003. © 2003 Wiley‐Liss, Inc.
Role of Hertwig's epithelial root sheath cells in tooth root development
Authors: Zeichner‐David Margarita , Oishi Keiji , Su Zhengyan , Zakartchenko Vassili , Chen Li‐Sha , Arzate Higinio , Bringas Pablo
Published: December 2003

During tooth development, after the completion of crown formation, the apical mesenchyme forms the developing periodontium while the inner and outer enamel epithelia fuse below the level of the crown cervical margin to produce a bilayered epithelial sheath termed Hertwig's epithelial root sheath (HERS). The role of HERS cells in root formation is widely accepted; however, the precise function of these cells remains controversial. Functions suggested have ranged from structural (subdivide the dental ectomesenchymal tissues into dental papilla and dental follicle), regulators of timing of root development, inducers of mesenchymal cell differentiation into odontoblasts and cementoblasts, to cementoblast cell precursors. The characterization of the HERS phenotype has been hindered by the small amount of tissue present at a given time during root formation. In this study, we report the establishment of an immortal HERS‐derived cell line that can be maintained in culture and then induced to differentiate in vitro. Characterization of the HERS phenotype using reverse transcriptase‐polymerase chain reaction and Western blot immunostaining suggests that HERS cells initially synthesize and secrete some enamel‐related proteins such as ameloblastin, and then these cells appear to change their morphology and produce a mineralized extracellular matrix resembling acellular cementum. These studies suggest that the acellular and cellular cementum are synthesized by two different types of cells, the first one by HERS‐derived cementoblasts and the later by neural crest‐derived cementoblasts. Developmental Dynamics 228:651–663, 2003. © 2003 Wiley‐Liss, Inc.
Skin‐specific expression of ictacalcin, a homolog of the S100 genes, during zebrafish embryogenesis
Authors: Hsiao Chung‐Der , Ekker Marc , Tsai Huai‐Jen
Published: December 2003

Full‐length cDNA coding for the ictacalcin gene, a homolog of the S100 genes, was isolated in zebrafish and mapped on linkage group 16 using the LN54 radiation hybrid panel. The homology and phylogenetic analyses, based on the deduced amino acid sequences, showed the orthologous relationship of ictacalcin genes between zebrafish and other fish species. However, ictacalcin genes constitute an out‐group with respect to other members of the S100 gene family. This result supports the findings that fish ictacalcin genes are new members of the S100 gene family and may have evolved after the divergence of teleosts and tetrapods. The zebrafish ictacalcin gene was zygotically transcribed from 12 hours postfertilization onward and was stably expressed throughout adulthood. During zebrafish embryogenesis, the ictacalcin gene was specifically expressed in striated epidermal cells covering the entire embryo. The ictacalcin staining in keratinocytes of striated epithelia was absent in the cytoplasm surrounding the nuclei, but it was highly concentrated in the peripheral margin. Tissues enriched with epithelia folds, such as olfactory epithelium, hatching gland, pectoral fin buds, urogenital opening, and pharynx, showed a robust ictacalcin expression. The strikingly heavy staining of ictacalcin in the pharyngeal region provides us with an early marker to follow the pharynx formation in zebrafish embryos. Developmental Dynamics 228:751–766, 2003. © 2003 Wiley‐Liss, Inc.
Left–right asymmetric morphogenesis in the Xenopus digestive system
Authors: Muller Jennifer K. , Prather Deva R. , Nascone‐Yoder Nanette M.
Published: December 2003

The morphogenetic mechanisms by which developing organs become left–right asymmetric entities are unknown. To investigate this issue, we compared the roles of the left and right sides of the Xenopus embryo during the development of anatomic asymmetries in the digestive system. Although both sides contribute equivalently to each of the individual digestive organs, during the initial looping of the primitive gut tube, the left side assumes concave topologies where the right side becomes convex. Of interest, the concave surfaces of the gut tube correlate with expression of the LR gene, Pitx2, and ectopic Pitx2 mRNA induces ectopic concavities in a localized manner. A morphometric comparison of the prospective concave and convex surfaces of the gut tube reveals striking disparities in their rate of elongation but no significant differences in cell proliferation. These results provide insight into the nature of symmetry‐breaking morphogenetic events during left–right asymmetric organ development. Developmental Dynamics 228:672–682, 2003. © 2003 Wiley‐Liss, Inc.
Molecular markers of cardiac endocardial cushion development
Authors: Gitler Aaron D. , Lu Min Min , Jiang Yue Qin , Epstein Jonathan A. , Gruber Peter J.
Published: December 2003

Endocardial cushions are precursors of mature heart valves. They form within the looped heart tube as discrete swellings and develop into thin, pliable leaflets that prevent regurgitation of blood. The embryonic origins of cardiac valves include endothelial, myocardial, and neural crest cells. Recently, an increasing number of animal models derived from mutational screens, gene inactivation, and transgenic studies have identified specific molecules required for normal development of the cardiac valves, and critical molecular pathways are beginning to emerge. To further this process, we have sought to assemble a diverse set of molecular markers encompassing all stages of cardiac valve development. Here, we provide a detailed comparative gene expression analysis of thirteen endocardial cushion markers. We identify endocardial cushion expression of the transcription factor Fog1, and we demonstrate active Wnt/β‐catenin signaling in developing endocardial cushions suggesting pathways that have not been previously appreciated to participate in cardiac valve formation. Developmental Dynamics 228:643–650, 2003. © 2003 Wiley‐Liss, Inc.