bluuebunny/crossref_metadata_2025 huggingface dataset:
Plane-grating flat-field soft x-ray spectrometer
Authors: Hague C. F. , Underwood J. H. , Avila A. , Delaunay R. , Ringuenet H. , Marsi M. , Sacchi M.
Published: January 2005

We describe a soft x-ray spectrometer covering the 120–800 eV range. It is intended for resonant inelastic x-ray scattering experiments performed at third generation synchrotron radiation (SR) facilities and has been developed with SOLEIL, the future French national SR source in mind. The Hettrick–Underwood principle is at the heart of the design using a combination of varied line-spacing plane grating and spherical-mirror to provide a flat-field image. It is slitless for optimum acceptance. This means the source size determines the resolving power. A spot size of ⩽5μm is planned at SOLEIL which, according to simulations, should ensure a resolving power ⩾1000 over the whole energy range. A 1024×1024 pixel charge-coupled device (CCD) with a 13μm×13μm pixel size is used. This is an improvement on the use of microchannel-plate detectors, both as concerns efficiency and spatial resolution. Additionally spectral line curvature is avoided by the use of a horizontal focusing mirror concentrating the beam in the nondispersing direction. It allows for readout using a binning mode to reduce the intrinsically large CCD readout noise. Preliminary results taken at beamlines at Elettra (Trieste) and at BESSY (Berlin) are presented.
Cyclodextrin driven hydrophobic∕hydrophilic transformation of semiconductor nanoparticles
Authors: Feng Jun , Ding Shi-You , Tucker Melvin P. , Himmel Michael E. , Kim Yong-Hyun , Zhang S. B. , Keyes Brian M. , Rumbles Garry
Published: January 2005

Quantum dots (QDs) have been the subject of considerable study in theoretical physics, and water soluble QDs now appear to have numerous applications in biological tagging, molecular electronic devices, and nanoscale engineering. The work reported here supports the notion that the aliphatic chains of the trioctylphosphine oxide molecules decorating these (CdSe)ZnS core-shell QDs are stabilized by the hydrophobic cyclodextrin (CD) lumen. Photoluminescence studies show a redshift of over 15nm in the emission wavelength of the QDs upon complexation with the CD, and first-principles calculations reveal an exothermic exchange of the S in the ZnS shell with the CD hydroxyl oxygen. Unlike simple water-driven surface transformations, the directed bonding of hydroxyl groups to the ZnS shell results in stable structures, verified by photoluminescence and Fourier transform infrared spectroscopy.
Two- and three-dimensional connectivity and current distribution in YBa2Cu3Ox-coated conductors
Authors: van der Laan D. C. , Dhallé M. , van Eck H. J. N. , Metz A. , ten Haken B. , ten Kate H. H. J. , Naveira L. M. , Davidson M. W. , Schwartz J.
Published: January 2005

The microstructure of YBa2Cu3Ox (YBCO)-coated conductors depends strongly on the deposition method and thickness of the YBCO layer. This letter shows how the clear qualitative difference in grain connectivity between vacuum-deposited and solution-grown layers has direct consequences for the spatial distribution of the critical current density (Jc). Pulsed-laser-deposited YBCO conductors usually have a columnar grain structure that results in a two-dimensional current network, as demonstrated with magneto-optical imaging. Consequently, their transport Jc varies considerably on length scales from 50μm up to 5mm, with current suppression occurring even at defects that run parallel to the macroscopic current. In contrast, the thicker YBCO coatings in metalorganic-deposited samples have a layered structure, leading to a three-dimensional current path. Magneto-optically, this is deduced from sample-wide shielding currents, while transport experiments reveal much smaller spatial variations in Jc. These results are encouraging for the further development of nonvacuum produced YBCO-coated conductors, since such three-dimensional systems are inherently more “forgiving” of local defects.
Nanoparticles: An approach to controlling an electro-optical behavior of nematic liquid crystals
Authors: Sikharulidze David
Published: January 2005

We report an orientational effect in suspension of nematic liquid crystal (NLC) with solid nanoparticles, controlled by the optically “hidden” electrophoretic effect: electrophoretically controlled nematic (EPCN). Adding the nanoparticles results in an additional phenomenon in conventionally designed NLC cell: polarity-controlled bistable/multistable switching. The EPCN is based on the nature of an interaction of nanoparticles with LC molecules and not on specific fabrication technology, which makes it applicable to various current LC displays technologies and gives a big opportunity to produce low power consumption high informative displays, including low cost large scale flexible displays.
The p53 regulatory geneMDM2is a direct transcriptional target of MYCN in neuroblastoma
Authors: Slack Andrew , Chen Zaowen , Tonelli Roberto , Pule Martin , Hunt Lisa , Pession Andrea , Shohet Jason M.
Published: January 2005

TheMYCNoncogene is the major negative prognostic marker in neuroblastoma with important roles in both the pathogenesis and clinical behavior of this aggressive malignancy.MYConcogenes activate both proliferative and apoptotic cellular pathways and, accordingly, inhibition of p53-mediated apoptosis is a prerequisite for MYC-driven tumorigenesis. To identify novel transcriptional targets mediating the MYCN-dependent phenotype, we screened a MYCN-amplified neuroblastoma cell line by using chromatin immunoprecipitation (ChIP) cloning. We identified the essential p53 inhibitor and protooncogeneMDM2as a putative target. MDM2 has multiple p53-independent functions modulating cell cycle and transcriptional events. Standard ChIP with MYCN antibodies established the binding of MYCN to a consensus E-box within the humanMDM2promoter. Oligonucleotide pull-down assays further established the capacity of MYCN to bind to this promoter region, confirming the ChIP results. Luciferase reporter assays confirmed the E-box-specific, MYCN-dependent regulation of theMDM2promoter in MYCN-inducible neuroblastoma cell lines. Real-time quantitative PCR and Western blot analysis demonstrated a rapid increase in endogenousMDM2mRNA and MDM2 protein upon induction of MYCN. Targeted inhibition of MYCN in aMYCN-amplified neuroblastoma cell line resulted in decreased MDM2 expression levels with concomitant stabilization of p53 and induction of apoptosis. Our finding that MYCN directly modulates baseline MDM2 levels suggests a mechanism contributing to the pathogenesis of neuroblastoma and other MYC-driven malignancies through inhibition of MYC-stimulated apoptosis.
Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing
Salmonella typhimurium
Authors: Zhao Ming , Yang Meng , Li Xiao-Ming , Jiang Ping , Baranov Eugene , Li Shukuan , Xu Mingxu , Penman Sheldon , Hoffman Robert M.
Published: January 2005

Here we report a genetically modified bacteria strain,
Salmonella typhimurium
A1, selected for anticancer activity
in vivo
. The strain grows in tumor xenografts. In sharp contrast, normal tissue is cleared of these bacteria even in immunodeficient athymic mice.
S
.
typhimurium
A1 is auxotrophic (Leu/Arg-dependent) but apparently receives sufficient support from the neoplastic tissue to grow locally. Whether additional genetic lesions are present is not known. In
in vitro
infection, the GFP-expressing bacteria grew in the cytoplasm of PC-3 human prostate cancer cells and caused nuclear destruction. These effects were visualized in cells labeled with GFP in the nucleus and red fluorescent protein in the cytoplasm.
In vivo
, the bacteria caused tumor inhibition and regression of xenografts visualized by whole-body imaging. The bacteria, introduced i.v. or intratumorally, invaded and replicated intracellularly in PC-3 prostate cancer cells labeled with red fluorescent protein grafted into nude mice. By day 15,
S
.
typhimurium
A1 was undetectable in the liver, lung, spleen, and kidney, but it continued to proliferate in the PC-3 tumor, which stopped growing. When the bacteria were injected intratumorally, the tumor completely regressed by day 20. There were no obvious adverse effects on the host when the bacteria were injected by either route. The
S
.
typhimurium
A1 strain grew throughout the tumor, including viable malignant tissue. This result is in marked contrast to bacteria previously tried for cancer therapy that were confined to necrotic areas of the tumor, which may account, in part, for the strain's unique antitumor efficacy.
Visual extrapolation of contour geometry
Authors: Singh Manish , Fulvio Jacqueline M.
Published: January 2005

Computing the shapes of object boundaries from fragmentary image contours poses a formidable problem for the visual system. We investigated the extrapolation of contour shape by human vision. Measurements of extrapolation position and orientation were taken at six distances from the point of occlusion, thereby yielding a detailed representation of the extrapolated contours. Analyses of these measurements revealed that: (
i
) extrapolation curvature increases linearly with the curvature of the inducing contour, although there is individual bias in the slope; (
ii
) the precision with which an extrapolated contour is represented is roughly constant, in angular terms, with increasing distance from the point of occlusion; (
iii
) there is a substantial cost of curvature, in that the overall precision of an extrapolated contour decreases systematically with curvature; (
iv
) the shapes of visually extrapolated contours are characterized by a nonlinear decrease in curvature, asymptoting to zero; and (
v
) this decaying pattern of curvature is explained by a Bayesian model in which, with increasing distance from the point of occlusion, the prior tendency to minimize curvature gradually dominates the likelihood tendency to minimize variation in curvature.
Profiling the humoral immune response to infection by using proteome microarrays: High-throughput vaccine and diagnostic antigen discovery
Authors: Davies D. Huw , Liang Xiaowu , Hernandez Jenny E. , Randall Arlo , Hirst Siddiqua , Mu Yunxiang , Romero Kimberly M. , Nguyen Toai T. , Kalantari-Dehaghi Mina , Crotty Shane , Baldi Pierre , Villarreal Luis P. , Felgner Philip L.
Published: January 2005

Despite the increasing availability of genome sequences from many human pathogens, the production of complete proteomes remains at a bottleneck. To address this need, a high-throughput PCR recombination cloning and expression platform has been developed that allows hundreds of genes to be batch-processed by using ordinary laboratory procedures without robotics. The method relies on high-throughput amplification of each predicted ORF by using gene specific primers, followed by
in vivo
homologous recombination into a T7 expression vector. The proteins are expressed in an
Escherichia coli
-based cell-free
in vitro
transcription/translation system, and the crude reactions containing expressed proteins are printed directly onto nitrocellulose microarrays without purification. The protein microarrays are useful for determining the complete antigen-specific humoral immune-response profile from vaccinated or infected humans and animals. The system was verified by cloning, expressing, and printing a vaccinia virus proteome consisting of 185 individual viral proteins. The chips were used to determine Ab profiles in serum from vaccinia virus-immunized humans, primates, and mice. Human serum has high titers of anti-
E. coli
Abs that require blocking to unmask vaccinia-specific responses. Naïve humans exhibit reactivity against a subset of 13 antigens that were not associated with vaccinia immunization. Naïve mice and primates lacked this background reactivity. The specific profiles between the three species differed, although a common subset of antigens was reactive after vaccinia immunization. These results verify this platform as a rapid way to comprehensively scan humoral immunity from vaccinated or infected humans and animals.
Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic
Authors: Kang Sohye , Bader Andreas G. , Vogt Peter K.
Published: January 2005

Mutations in genes that encode components of the phosphatidyl-inositol 3-kinase (PI3-kinase) signaling pathway are common in human cancer. The recent discovery of nonrandom somatic mutations in the
PIK3CA
gene of many human tumors suggests an oncogenic role for the mutated enzyme. We have determined the growth-regulatory and signaling properties of the three most frequently observed PI3-kinase mutations: E542K, E545K, and H1047R. Expressed in chicken embryo fibroblasts, all three mutants induce oncogenic transformation with high efficiency. This transforming ability is correlated with elevated catalytic activity in
in vitro
kinase assays. The mutant-transformed cells show constitutive phosphorylation of Akt, of p70 S6 kinase, and of the 4E-binding protein 1. Phosphorylation of S6 kinase and of 4E-binding protein 1 is regulated by the target of rapamycin (TOR) kinase and affects rates of protein synthesis. The inhibitor of TOR, rapamycin, strongly interferes with cellular transformation induced by the PI3-kinase mutants, suggesting that the TOR and its downstream targets are essential components of the transformation process. The oncogenic transforming activity makes the mutated PI3-kinase proteins promising targets for small molecule inhibitors that could be developed into effective and highly specific anticancer drugs.
mtDNA mutations increase tumorigenicity in prostate cancer
Authors: Petros John A. , Baumann Amanda K. , Ruiz-Pesini Eduardo , Amin Mahul B. , Sun Carrie Qi , Hall John , Lim SoDug , Issa Muta M. , Flanders W. Dana , Hosseini Seyed H. , Marshall Fray F. , Wallace Douglas C.
Published: January 2005

Mutations in the mtDNA have been found to fulfill all of the criteria expected for pathogenic mutations causing prostate cancer. Focusing on the cytochrome oxidase subunit I (COI) gene, we found that 11–12% of all prostate cancer patients harbored COI mutations that altered conserved amino acids (mean conservation index = 83%), whereas <2% of no-cancer controls and 7.8% of the general population had COI mutations, the latter altering less conserved amino acids (conservation index = 71%). Four conserved prostate cancer COI mutations were found in multiple independent patients on different mtDNA backgrounds. Three other tumors contained heteroplasmic COI mutations, one of which created a stop codon. This latter tumor also contained a germ-line ATP6 mutation. Thus, both germ-line and somatic mtDNA mutations contribute to prostate cancer. Many tumors have been found to produce increased reactive oxygen species (ROS), and mtDNA mutations that inhibit oxidative phosphorylation can increase ROS production and thus contribute to tumorigenicity. To determine whether mutant tumors had increased ROS and tumor growth rates, we introduced the pathogenic mtDNA ATP6 T8993G mutation into the PC3 prostate cancer cell line through cybrid transfer and tested for tumor growth in nude mice. The resulting mutant (T8993G) cybrids were found to generate tumors that were 7 times larger than the wild-type (T8993T) cybrids, whereas the wild-type cybrids barely grew in the mice. The mutant tumors also generated significantly more ROS. Therefore, mtDNA mutations do play an important role in the etiology of prostate cancer.
Prion protein NMR structures of elk and of mouse/elk hybrids
Authors: Gossert Alvar D. , Bonjour Sophie , Lysek Dominikus A. , Fiorito Francesco , Wüthrich Kurt
Published: January 2005

The NMR structure of the recombinant elk prion protein (ePrP), which represents the cellular isoform (ePrP
C
) in the healthy organism, is described here. As anticipated from the highly conserved amino acid sequence, ePrP
C
has the same global fold as other mammalian prion proteins (PrPs), with a flexibly disordered “tail” of residues 23–124 and a globular domain 125–226 with three α-helices and a short antiparallel β-sheet. However, ePrP
C
shows a striking local structure variation when compared with most other mammalian PrPs, in particular human, bovine, and mouse PrP
C
. A loop of residues 166–175, which links the β-sheet with the α2-helix and is part of a hypothetical “protein X” epitope, is outstandingly well defined, whereas this loop is disordered in the other species. Based on NMR structure determinations of two mouse PrP variants, mPrP[N174T] and mPrP[S170N,N174T], this study shows that the structured loop in ePrP
C
relates to these two local amino acid exchanges, so that mPrP[S170N,N174T] exactly mimics ePrP
C
. These results are evaluated in the context of recent reports on chronic wasting disease (CWD) in captive and free-ranging deer and elk in the U.S. and Canada, and an animal model is proposed for support of future research on CWD.
Inhibited cell growth and protein functional changes from an editing-defective tRNA synthetase
Authors: Bacher Jamie M. , de Crécy-Lagard Valérie , Schimmel Paul R.
Published: January 2005

The genetic code is established in aminoacylation reactions catalyzed by aminoacyl-tRNA synthetases. Many aminoacyl-tRNA synthetases require an additional domain for editing, to correct errors made by the catalytic domain. A nonfunctional editing domain results in an ambiguous genetic code, where a single codon is not translated as a specific amino acid but rather as a statistical distribution of amino acids. Here, wide-ranging consequences of genetic code ambiguity in
Escherichia coli
were investigated with an editing-defective isoleucyl-tRNA synthetase. Ambiguity retarded cell growth at most temperatures in rich and minimal media. These growth rate differences were seen regardless of the carbon source. Inclusion of an amino acid analogue that is misactivated (and not cleared) diminished growth rate by up to 100-fold relative to an isogenic strain with normal editing function. Experiments with target-specific antibiotics for ribosomes, DNA replication, and cell wall biosynthesis, in conjunction with measurements of mutation frequencies, were consistent with global changes in protein function caused by errors of translation and not editing-induced mutational errors. Thus, a single defective editing domain caused translationally generated global effects on protein functions that, in turn, provide powerful selective pressures for maintenance of editing by aminoacyl-tRNA synthetases.
Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice
Authors: Li Shijie , Czubryt Michael P. , McAnally John , Bassel-Duby Rhonda , Richardson James A. , Wiebel Franziska F. , Nordheim Alfred , Olson Eric N.
Published: January 2005

Serum response factor (SRF) controls the transcription of muscle genes by recruiting a variety of partner proteins, including members of the myocardin family of transcriptional coactivators. Mice lacking SRF fail to form mesoderm and die before gastrulation, precluding an analysis of the roles of SRF in muscle tissues. To investigate the functions of SRF in skeletal muscle development, we conditionally deleted the
Srf
gene in mice by skeletal muscle-specific expression of Cre recombinase. In mice lacking skeletal muscle SRF expression, muscle fibers formed, but failed to undergo hypertrophic growth after birth. Consequently, mutant mice died during the perinatal period from severe skeletal muscle hypoplasia. The myopathic phenotype of these mutant mice resembled that of mice expressing a dominant negative mutant of a myocardin family member in skeletal muscle. These findings reveal an essential role for the partnership of SRF and myocardin-related transcription factors in the control of skeletal muscle growth and maturation
in vivo
.
Elevated evolutionary rates in the laboratory strain ofSaccharomyces cerevisiae
Authors: Gu Zhenglong , David Lior , Petrov Dmitri , Jones Ted , Davis Ronald W. , Steinmetz Lars M.
Published: January 2005

By using the maximum likelihood method, we made a genome-wide comparison of the evolutionary rates in the lineages leading to the laboratory strain (S288c) and a wild strain (YJM789) ofSaccharomyces cerevisiaeand found that genes in the laboratory strain tend to evolve faster than in the wild strain. The pattern of elevated evolution suggests that relaxation of selection intensity is the dominant underlying reason, which is consistent with recurrent bottlenecks in theS. cerevisiaelaboratory strain population. Supporting this conclusion are the following observations: (i) the increases in nonsynonymous evolutionary rate occur for genes in all functional categories; (ii) most of the synonymous evolutionary rate increases in S288c occur in genes with strong codon usage bias; (iii) genes under stronger negative selection have a larger increase in nonsynonymous evolutionary rate; and (iv) more genes with adaptive evolution were detected in the laboratory strain, but they do not account for the majority of the increased evolution. The present discoveries suggest that experimental and possible industrial manipulations of the laboratory strain of yeast could have had a strong effect on the genetic makeup of this model organism. Furthermore, they imply an evolution of laboratory model organisms away from their wild counterparts, questioning the relevancy of the models especially when extensive laboratory cultivation has occurred. In addition, these results shed light on the evolution of livestock and crop species that have been under human domestication for years.
Rapid evolution of expression and regulatory divergences after yeast gene duplication
Authors: Gu Xun , Zhang Zhongqi , Huang Wei
Published: January 2005

Although gene duplication is widely believed to be the major source of genetic novelty, how the expression or regulatory network of duplicate genes evolves remains poorly understood. In this article, we propose an additive expression distance between duplicate genes, so that the evolutionary rate of expression divergence after gene duplication can be estimated through phylogenomic analysis. We have analyzed yeast genome sequences, microarrays, and transcriptional regulatory networks, showing a >10-fold increase in the initial rate for both expression and regulatory network evolution after gene duplication but only an ≈20% rate increase in the early stage for protein sequences. Based on the estimated age distribution of yeast duplicate genes, we roughly estimate that the initial rate of expression divergence shortly after gene duplication is 2.9 × 10-9per year, whereas the baseline rate for very ancient gene duplication is 0.14 × 10-9per year. Relative expression rate tests suggest that the expression of duplicate genes tends to evolve asymmetrically, that is, the expression of one copy evolves rapidly, whereas the other one largely maintains the ancestral expression profile. Our study highlights the crucial role of early rapid evolution after gene/genome duplication for continuously increasing the complexity of the yeast regulatory network.
On minimal representations definitions and properties
Authors: Gan Wee Teck , Savin Gordan
Published: January 2005

This paper gives a self-contained exposition of minimal representations. We introduce a notion of weakly minimal representations and prove a global rigidity result for them. We address issues of uniqueness and existence and prove many key properties of minimal representations needed for global applications.
FLR-4, a Novel Serine/Threonine Protein Kinase, Regulates Defecation Rhythm inCaenorhabditis elegans
Authors: Take-uchi Masaya , Kobayashi Yuri , Kimura Koutarou D. , Ishihara Takeshi , Katsura Isao
Published: January 2005

The defecation behavior of the nematode Caenorhabditis elegans is controlled by a 45-s ultradian rhythm. An essential component of the clock that regulates the rhythm is the inositol trisphosphate receptor in the intestine, but other components remain to be discovered. Here, we show that the flr-4 gene, whose mutants exhibit very short defecation cycle periods, encodes a novel serine/threonine protein kinase with a carboxyl terminal hydrophobic region. The expression of functional flr-4::GFP was detected in the intestine, part of pharyngeal muscles and a pair of neurons, but expression of flr-4 in the intestine was sufficient for the wild-type phenotype. Furthermore, laser killing of the flr-4–expressing neurons did not change the defecation phenotypes of wild-type and flr-4 mutant animals. Temperature-shift experiments with a temperature-sensitive flr-4 mutant suggested that FLR-4 acts in a cell-functional rather than developmental aspect in the regulation of defecation rhythms. The function of FLR-4 was impaired by missense mutations in the kinase domain and near the hydrophobic region, where the latter allele seemed to be a weak antimorph. Thus, a novel protein kinase with a unique structural feature acts in the intestine to increase the length of defecation cycle periods.
p27Kip1Acts Downstream of N-Cadherin-mediated Cell Adhesion to Promote Myogenesis beyond Cell Cycle Regulation
Authors: Messina Graziella , Blasi Cristiana , La Rocca Severina Anna , Pompili Monica , Calconi Attilio , Grossi Milena
Published: January 2005

It is widely acknowledged that cultured myoblasts can not differentiate at very low density. Here we analyzed the mechanism through which cell density influences myogenic differentiation in vitro. By comparing the behavior of C2C12 myoblasts at opposite cell densities, we found that, when cells are sparse, failure to undergo terminal differentiation is independent from cell cycle control and reflects the lack of p27Kip1and MyoD in proliferating myoblasts. We show that inhibition of p27Kip1expression impairs C2C12 cell differentiation at high density, while exogenous p27Kip1allows low-density cultured C2C12 cells to enter the differentiative program by regulating MyoD levels in undifferentiated myoblasts. We also demonstrate that the early induction of p27Kip1is a critical step of the N-cadherin-dependent signaling involved in myogenesis. Overall, our data support an active role of p27Kip1in the decision of myoblasts to commit to terminal differentiation, distinct from the regulation of cell proliferation, and identify a pathway that, reasonably, operates in vivo during myogenesis and might be part of the phenomenon known as “community effect”.
Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway
Authors: Terai Masanori , Uyama Taro , Sugiki Tadashi , Li Xiao-Kang , Umezawa Akihiro , Kiyono Tohru
Published: January 2005

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells.
The Roles of Fission Yeast Ase1 in Mitotic Cell Division, Meiotic Nuclear Oscillation, and Cytokinesis Checkpoint Signaling
Authors: Yamashita Akira , Sato Masamitsu , Fujita Akiko , Yamamoto Masayuki , Toda Takashi
Published: January 2005

The Ase1/Prc1 proteins constitute a conserved microtubule-associated protein family that is implicated in central spindle formation and cytokinesis. Here we characterize a role for fission yeast Ase1. Ase1 localizes to microtubule overlapping zones and displays dynamic alterations of localization during the cell cycle. In particular, its spindle localization during metaphase is reduced substantially, followed by robust appearance at the spindle midzone in anaphase. ase1 deletions are viable but defective in nuclear and septum positioning and completion of cytokinesis, which leads to diploidization and chromosome loss. Time-lapse imaging shows that elongating spindles collapse abruptly in the middle of anaphase B. Either absence or overproduction of Ase1 results in profound defects on microtubule bundling in an opposed manner, indicating that Ase1 is a dose-dependent microtubule-bundling factor. In contrast microtubule nucleating activities are not noticeably compromised in ase1 mutants. During meiosis astral microtubules are not bundled and oscillatory nuclear movement is impaired significantly. The Aurora kinase does not correctly localize to central spindles in the absence of Ase1. Finally Ase1 acts as a regulatory component in the cytokinesis checkpoint that operates to inhibit nuclear division when the cytokinesis apparatus is perturbed. Ase1, therefore, couples anaphase completion with cytokinesis upon cell division.
Robert Mallet and the
‘Great Neapolitan earthquake’
of 1857
Authors: Ferrari Graziano , Mcconnell Anita
Published: January 2005

Robert Mallet (1810–81), an Irish civil engineer who had been investigating the passage of artificial seismic waves, sought Royal Society support to test his theories in the field, after a devastating earthquake in Basilicata, a province in the Kingdom of Naples. The earthquake struck on 16 December 1857; in January 1858 Mallet began a month–long trek across this mountainous region, gathering a wealth of data and description. His report, illustrated by maps and diagrams, included several hundred monoscopic and stereoscopic photographs, a remarkably early scientific use of this technique. It was published in 1862 as
Great Neapolitan earthquake of 1857: the first principles of observational seismology
. The acknowledged value of Mallet's report led to its being reprinted in 1987 and, in 2004, its translation into Italian, with supporting materials. While the translation was in progress, a search for related correspondence in Italian and British archives yielded a vivid personal side of Mallet's expedition, absent from his own report.
Homing pigeons develop local route stereotypy
Authors: Meade Jessica , Biro Dora , Guilford Tim
Published: January 2005

The mechanisms used by homing pigeons (Columba livia) to navigate homeward from distant sites have been well studied, yet the mechanisms underlying navigation within, and mapping of, the local familiar area have been largely neglected. In the local area pigeons potentially have access to a powerful navigational aid--a memorized landscape map. Current opinion suggests that landmarks are used only to recognize a familiar start position and that the goalward route is then achieved solely using compass orientation. We used high-resolution global positioning system (GPS) loggers to track homing pigeons as they became progressively familiar with a local homing task. Here, we demonstrate that birds develop highly stereotyped yet individually distinctive routes over the landscape, which remain substantially inefficient. Precise aerial route recapitulation implies close control by localized geocentric cues. Magnetic cues are unlikely to have been used, since recapitulation remains despite magnetic disruption treatment, and olfactory cues would have been positionally unstable under the variable wind conditions, making visual landmarks the most likely cues used.
Are reproductive and somatic senescence coupled in humans? Late, but not early, reproduction correlated with longevity in historical Sami women
Authors: Helle Samuli , Lummaa Virpi , Jokela Jukka
Published: January 2005

Evolutionary theory of senescence emphasizes the importance of intense selection on early reproduction owing to the declining force of natural selection with age that constrains lifespan. In humans, recent studies have, however, suggested that late-life mortality might be more closely related to late rather than early reproduction, although the role of late reproduction on fitness remains unclear. We examined the association between early and late reproduction with longevity in historical post-reproductive Sami women. We also estimated the strength of natural selection on early and late reproduction using path analysis, and the effect of reproductive timing on offspring survival to adulthood and maternal risk of dying at childbirth. We found that natural selection favoured both earlier start and later cessation of reproduction, and higher total fe cundity. Maternal age at childbirth was not related to offspring or maternal survival. Interestingly, females who produced their last offspring at advanced age also lived longest, while age at first reproduction and total fecundity were unrelated to female longevity. Our results thus suggest that reproductive and somatic senescence may have been coupled in these human populations, and that selection could have favoured late reproduction. We discuss alternative hypotheses for the mechanisms which might have promoted the association between late reproduction and longevity.
Black holes, cuspy atmospheres and galaxy formation
Authors: Binney James
Published: January 2005

In cuspy atmospheres, jets driven by supermassive black holes (BHs) offset radiative cooling. The jets fire episodically, but often enough that the cuspy atmosphere does not move very far towards a cooling catastrophe in the intervals of jet inactivity. The ability of energy released on the sub–parsec scale of the BH to balance cooling on scales of several tens of kiloparsecs arises through a combination of the temperature sensitivity of the accretion rate and the way in which the radius of jet disruption varies with ambient density. Accretion of hot gas does not significantly increase BH masses, which are determined by periods of rapid BH growth and star formation when cold gas is briefly abundant at the galactic centre. Hot gas does not accumulate in shallow potential wells. As the Universe ages, deeper wells form, and eventually hot gas accumulates. This gas soon prevents the formation of further stars, since jets powered by the BH prevent it from cooling, and it mops up most cold infalling gas before many stars can form. Thus, BHs set the upper limit to the masses of galaxies. The formation of low–mass galaxies is inhibited by a combination of photoheating and supernova–driven galactic winds. Working in tandem, these mechanisms can probably explain the profound difference between the galaxy luminosity function and the mass function of dark haloes expected in the cold dark matter cosmology.
The connection between the formation of galaxies and that of their central supermassive black holes
Authors: Haehnelt Martin G.
Published: January 2005

Massive black holes appear to be an essential ingredient of massive galactic bulges but little is known yet to what extent massive black holes reside in dwarf galaxies and globular clusters. Massive black holes most likely grow by a mixture of merging and accretion of gas in their hierarchically merging host galaxies. While the hierarchical merging of dark matter structures extends to sub-galactic scales and very high redshift, it is uncertain if the same is true for the build–up of massive black holes. I discuss here some of the relevant problems and open questions.
Implication of membrane localization of target mRNA in the action of a small RNA: mechanism of post-transcriptional regulation of glucose transporter in Escherichia coli
Authors: Kawamoto Hiroshi , Morita Teppei , Shimizu Ayumi , Inada Toshifumi , Aiba Hiroji
Published: January 2005

Accumulation of phosphosugars such as glucose-6-phosphate causes a rapid degradation of ptsG mRNA encoding the major glucose transporter IICBGlc in an RNase E/degradosome-dependent manner. The destabilization of ptsG mRNA is caused by a small antisense RNA (SgrS) that is induced by phosphosugar stress. In this study, we analyzed a series of ptsG-crp translational fusions to identify the mRNA region required for the rapid degradation of ptsG mRNA. We found that the ptsG-crp mRNA is destabilized in response to phosphosugar stress when it contains the 5′ portion of ptsG mRNA corresponding up to the first two transmembrane domains (TM1 and TM2) of IICBGlc. The destabilization of ptsG-crp mRNA was largely eliminated by frameshift mutations in the transmembrane region. The IICBGlc-CRP fusion proteins containing more than two transmembrane domains were localized at the membrane. The efficient destabilization of ptsG-crp mRNA was restored when TM1 and TM2 of IICBGlc were replaced by part of the LacY transmembrane region. We conclude that the membrane-targeting property of IICBGlc protein rather than the particular nucleotide or amino acid sequence is required for the efficient degradation of ptsG mRNA in response to metabolic stress. The stimulation of ptsG-crp mRNA degradation was completely eliminated when either the hfq or sgrS gene is inactivated. The efficient mRNA destabilization was observed in the absence of membrane localization when translation was reduced by introducing a mutation in the ribosome-binding site in the cytoplasmic ptsG-crp mRNA. Taken together, we conclude that mRNA localization to the inner membrane coupled with the membrane insertion of nascent peptide mediates the Hfq/SgrS-dependent ptsG mRNA destabilization presumably by reducing second rounds of translation.
Memory consolidation and gene expression in Periplaneta
americana
Authors: Pintér Marianna , Lent David D. , Strausfeld Nicholas J.
Published: January 2005

A unique behavioral paradigm has been developed for Periplaneta
americana that assesses the timing and success of memory consolidation
leading to long-term memory of visual-olfactory associations. The brains of
trained and control animals, removed at the critical consolidation period,
were screened by two-directional suppression subtractive hybridization.
Screens identified neurobiologically relevant as well as novel genes that are
differentially expressed at the consolidation phase of memory. The
differential expression of six transcripts was confirmed with real-time RT-PCR
experiments. There are mitochondrial DNA encoded transcripts among the
up-regulated ones (COX, ATPase6). One of the confirmed down-regulated
transcripts is RNA polymerase II largest subunit. The mitochondrial genes are
of particular interest because mitochondria represent autonomous DNA at
synapses. These transcripts will be used as one of several tools in the
identification of neuronal circuits, such as in the mushroom bodies, that are
implicated in memory consolidation.
The role of social identity in doctors' experiences of clinical managing
Authors: Hallier Jerry , Forbes Tom
Published: January 2005

Purpose

Aims to illustrate how the use of a social identity approach can help to refine our understanding of how organizational professionals experience the introduction of managerialism and the incorporation of managing specialist roles.

Design/methodology/approach

Draws on theories of social identity and social categorization to examine the process by which clinical directors tackle and assign meaning to their managing roles. Interviews were conducted with a sample of current and previous clinical directors over a five year period. Variations in doctors’ responses were explained by a range of self enhancement strategies that emerged to deal with tensions between prepared management identities and actual role experiences.

Findings

Reveals the importance of multiple self‐enhancement strategies as a way for doctors to protect self definitions in failing identity situations where immediate exit from a new role is not feasible. Concludes that a greater use of social identity and social categorization theory may add much to general explanations of how varied stances towards management interventions emerge and develop among professional workers.

Originality/value

Points to how we might achieve a deeper understanding of the diverse ways that the organizational professionals experience the introduction of managerialism and the incorporation of managing the specialist roles.
HRM and the pursuit of a service culture
Authors: Francis Helen , D'Annunzio‐Green Norma
Published: January 2005

Purpose

Aims to draw attention to how managers actively re‐construct inherent contradictions characterising the employment relationship that in the service sector, are rooted in drives for increased efficiency and customer‐oriented behaviours.

Design/methodology/approach

Presents a case study of the human resource implications of changes taking place within a contract catering firm seeking to attain “world class” service delivery.

Findings

Finds that managers' accounts of “the reality” of change were constructed upon three overlapping and competing discourses – labelled “enagagement”, “enterprise” and “compliance”.

Originality/value

Highlights the active role of discourse in the management of HRM and organisational change.
A biogeographical approach to plant invasions: the importance of studying exotics in their introduced and native range
Authors: HIERRO JOSÉ L. , MARON JOHN L. , CALLAWAY RAGAN M.
Published: January 2005

Most theory and empirical research on exotic invasions is based on the assumption that problematic exotics are much more abundant in the regions where they invade than in the regions where they are native. However, the overwhelming majority of studies on exotic plants have been conducted solely within the introduced range. With few exceptions, ecologists know surprisingly little about the abundance, interaction strengths and ecosystems impacts of even the best‐studied exotics in their native range.

We argue that taking a biogeographical approach is key to understanding exotic plant invasions. On a descriptive level, unambiguous quantification of distributions and abundances of exotics in native and introduced ranges are crucial. Experiments conducted at a biogeographical scale are also necessary to elucidate the mechanisms that enable highly successful exotics to occur at substantially higher abundance in their introduced vs. native communities.

We summarize the leading hypotheses for exotic plant success. We assert that tests of these major hypotheses for invasions (the natural enemies, evolution of invasiveness, empty niche and novel weapons hypotheses) require comparative biogeographical approaches.

In addition to focusing on comparative work in the native and introduced range, we also suggest other approaches that could yield important insight into processes that influence exotic success.

Increased understanding of invasions has the potential to provide unique insight into fundamental ecological theory, including that on individualistic‐holistic structure, the role of trophic interactions in population regulation, and the importance of co‐evolution in communities.
Statistical analysis of the three‐dimensional structure of centromeric heterochromatin in interphase nuclei
Authors: BEIL M. , FLEISCHER F. , PASCHKE S. , SCHMIDT V.
Published: January 2005

Translocation of genes into the pericentromeric heterochromatin occurs during cellular differentiation and leads to a long‐term silencing of these genes. Consequently, a structural remodelling of this heterochromatin compartment is observed during differentiation but this remains to be defined from a topological point of view. In a previous study, we analysed the three‐dimensional (3D) distribution patterns of centromere clusters (chromocentres) by confocal scanning laser microscopy and found that differentiation of the promyelocytic leukaemia cell line NB4 along the neutrophil lineage is associated with a progressive clustering of centromeres. This clustering was reflected by a decreased number of detectable chromocentres, i.e. groups of centromeres with a distance below the diffraction‐limited resolution of optical microscopy. The purpose of this study was to perform a statistical analysis of the 3D distribution of chromocentres in NB4 cells. Several point field characteristics (Ripley's K‐function, L‐function, pair correlation function, nearest‐neighbour distribution function) were investigated to describe the topology of chromocentres during differentiation of NB4 cells. The pair correlation function revealed a higher frequency of chromocentre distances between 350 nm and 800 nm in undifferentiated NB4 cells as compared with differentiated cells. The L‐function and the nearest‐neighbour distribution function confirmed these results. These data imply the existence of intranuclear heterochromatin zones formed by functionally related centromeric regions. In view of the observed decrease in the number of detectable chromocentres during differentiation, we hypothesize that these zones with a diameter of 350–800 nm in undifferentiated NB4 cells contract into zones with a diameter below 350 nm in differentiated cells.
Increased number of CD34+cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid
Authors: Sergejeva S. , Malmhäll C. , Lötvall J. , Pullerits T.
Published: January 2005

Background
Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood.

Objective
We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4‐positive cells (CXCR4+), since the CXCR4 ligand (stromal cell‐derived factor‐1 (SDF‐1)) is a potent chemoattractant for haematopoietic progenitors.

Methods
In a double‐blind, randomized study, pollen‐sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 μg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry.

Results
The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo‐treated patients, but not in FP‐treated patients. The mean pollen season‐induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP‐treated patients was lower compared with placebo‐treated patients.

Conclusion
A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen‐induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen‐induced CXCR4‐mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.