bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes
Authors: Klug Christopher A. , Morrison Sean J. , Masek Marilyn , Hahm Kyungmin , Smale Stephen T. , Weissman Irving L.
Published: July 2002

The generation of lymphoid cells in mice depends on the function of the Ikaros protein. Ikaros has been characterized as a lymphoid-restricted, zinc-finger transcription factor that is derived from an alternatively spliced message. Ikaros knockout mice have defects in multiple cell lineages, raising the question of whether the protein regulates multiple committed progenitors and/or multipotent stem cells. To address this issue, we examined Ikaros expression in purified populations of multipotent cells and more committed progenitors. We found that the DNA-binding isoforms of Ikaros were localized in the nucleus of the most primitive hematopoietic stem cell subset. Changes in the RNA splicing pattern of Ikaros occurred at two stages: (
i
) as long-term self-renewing stem cells differentiated into short-term self-renewing stem cells and (
ii
) as non-self-renewing multipotent progenitors differentiated into lymphoid-committed progenitors. Unexpectedly, we found Ikaros localized to heterochromatin in Abelson-transformed pre-B lymphocytes by using immunogold electron microscopy. These observations suggest a complex role for Ikaros in lymphoid development.
Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt–Jakob disease
Authors: Cervenáková Larisa , Goldfarb Lev G. , Garruto Ralph , Lee Hee-Suk , Gajdusek D. Carleton , Brown Paul
Published: July 2002

The PRNP polymorphic (methionine/valine) codon 129 genotype influences the phenotypic features of transmissible spongiform encephalopathy. All tested cases of new variant Creutzfeldt–Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future “epidemic curve” of nvCJD. Genotype-phenotype studies of kuru, the only other orally transmitted transmissible spongiform encephalopathy, might be instructive in predicting the answers to these questions. We therefore extracted DNA from blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness and, in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness than was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may begin to occur in older individuals with heterozygous codon 129 genotypes and signal a maturing evolution of the nvCJD “epidemic.” The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least less readily identified) amyloid plaque formation.
Paleoindian large mammal hunters on the plains of North America
Authors: Frison George C.
Published: July 2002

From ≈11,200 to 8,000 years ago, the Great Plains of North America were populated by small Paleoindian hunting groups with well developed weaponry and the expertise to successfully hunt large mammals, especially mammoths and bison. Mammoths became extinct on the Plains by 11,000 years ago, and, although paleoecological conditions were worsening, their demise may have been hastened by human predation. After this, the main target of the Plains Paleoindian hunters consisted of subspecies of bison,
Bison antiquus
and
Bison occidentalis
. As bison populations gradually diminished, apparently because of worsening ecological conditions, by ≈8,000 years ago, human subsistence was forced into a greater dependence on small animal and plant foods. Human paleoecology studies of the Paleoindian time period rely heavily on multidisciplinary efforts. Geomorphologists, botanists, soil scientists, palynologists, biologists, and other specialists aid archaeologists in data recovery and analysis, although, with few exceptions, their contributions are derived from the fringes rather than the mainstream of their disciplines.
Anti-β2 glycoprotein I (β2GPI) autoantibodies recognize an epitope on the first domain of β2GPI
Authors: Iverson G. Michael , Victoria Edward J. , Marquis David M.
Published: July 2002

Anticardiolipin (aCL) autoantibodies are associated with thrombosis, recurrent fetal loss, and thrombocytopenia. Only aCL found in autoimmune disease require the participation of the phospholipid binding plasma protein β2 glycoprotein I (β2GPI) for antibody binding and now are called anti-β2GPI. The antigenic specificity of aCL affinity purified from 11 patients with high titers was evaluated in an effort to better understand the pathophysiology associated with aCL. Seven different recombinant domain-deleted mutants of human β2GPI, and full length human β2GPI (wild-type), were used in competition assays to inhibit the autoantibodies from binding to immobilized wild-type β2GPI. Only those domain-deleted mutants that contained domain 1 inhibited the binding to immobilized wild-type β2GPI from all of the patients. The domain-deleted mutants that contained domain 1 inhibited all aCL in a similar but not identical pattern, suggesting that these aCL recognize a similar, but distinguishable, epitope(s) present on domain 1.
Brain-wave recognition of sentences
Authors: Suppes Patrick , Han Bing , Lu Zhong-Lin
Published: July 2002

Electrical and magnetic brain waves of two subjects were recorded for the purpose of recognizing which one of 12 sentences or seven words auditorily presented was processed. The analysis consisted of averaging over trials to create prototypes and test samples, to each of which a Fourier transform was applied, followed by filtering and an inverse transformation to the time domain. The filters used were optimal predictive filters, selected for each subject. A still further improvement was obtained by taking differences between recordings of two electrodes to obtain bipolar pairs that then were used for the same analysis. Recognition rates, based on a least-squares criterion, varied, but the best were above 90%. The first words of prototypes of sentences also were cut and pasted to test, at least partially, the invariance of a word’s brain wave in different sentence contexts. The best result was above 80% correct recognition. Test samples made up only of individual trials also were analyzed. The best result was 134 correct of 288 (47%), which is promising, given that the expected recognition number by chance is just 24 (or 8.3%). The work reported in this paper extends our earlier work on brain-wave recognition of words only. The recognition rates reported here further strengthen the case that recordings of electric brain waves of words or sentences, together with extensive mathematical and statistical analysis, can be the basis of new developments in our understanding of brain processing of language.
Proteolytic processing of the
Aplysia
egg-laying hormone prohormone
Authors: Garden Rebecca W. , Shippy Scott A. , Li Lingjun , Moroz Tatiana P. , Sweedler Jonathan V.
Published: July 2002

By using matrix-assisted laser desorption/ionization time-of-flight MS, individual peptidergic neurons from
Aplysia
are assayed. A semiquantitative method is developed for comparing single-cell profiles by using spectral normalization, and peptides are localized to specific cells by mass spectrometric cell mapping. In addition to all previously identified products of the egg-laying hormone (ELH) gene, other peptides are formed from proteolytic hydrolysis of Leu-Leu residues within ELH and acidic peptide (AP). AP exhibits further processing to yield AP
1–20
and AP
9–27
. These peptides appear to be colocalized in vesicles with ELH, transported to specific neuronal targets, and released in a Ca
2+
-dependent manner. A differential peptide distribution is observed at a specific target cell, and a low-frequency variation of AP, [Thr
21
]AP, is detected in a single animal.
The helium paradoxes
Authors: Anderson Don L.
Published: July 2002

The ratio
3
He/
4
He (R) plays a central role in models of mantle evolution that propose an undegassed lower mantle, rich in the primordial isotope
3
He. A large primordial volatile-rich reservoir, a feature of recent models, is inconsistent with high-temperature accretion and with estimates of crustal and bulk Earth chemistry. High R can alternatively reflect high integrated
3
He/(U+Th) ratios or low
4
He abundances, as expected in refractory portions of the upper mantle. I show that high R materials are gas-poor and are deficient in radiogenic
4
He compared with midocean ridge basalts. The seemingly primitive (i.e., high R) signatures in “hotspot” magmas may be secondary, derived from CO
2
-rich gases, or residual peridotite, a result of differential partitioning of U and He into magmas. A shallow and low
3
He source explains the spatial variability and the temporal trends of R in ocean islands and is consistent with a volatile-poor planet. A shallow origin for the “primitive” He signature in ocean island basalts, such as at Loihi, reconciles the paradoxical juxtaposition of crustal, seawater, and atmospheric signatures with inferred “primitive” characteristics. High
238
U/
204
Pb components in ocean island basalts are generally attributed to recycled altered oceanic crust. The low
238
U/
3
He component may be in the associated depleted refractory mantle. High
3
He/
4
He ratios are due to low
4
He, not excess
3
He, and do not imply or require a deep or primordial or undegassed reservoir.
40
Ar in the atmosphere also argues against such models.
Dipeptidyl peptidase I is required for the processing and activation of granzymes A and Bin vivo
Authors: Pham Christine T. N. , Ley Timothy J.
Published: July 2002

Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of activated cytotoxic lymphocytes. In this report, we show that cytotoxic lymphocytes derived from DPPI−/− mice contain normal amounts of granzymes A and B, but these molecules retain their prodipeptide domains and are inactive. Cytotoxic assays with DPPI−/− effector cells reveal severe defects in the induction of target cell apoptosis (as measured by [125I]UdR release) at both early and late time points; this defect is comparable to that detected in perforin−/− or granzyme A−/− × B−/− cytotoxic lymphocytes. DPPI therefore plays an essential role in thein vivoprocessing and activation of granzymes A and B, which are required for cytotoxic lymphocyte granule-mediated apoptosis.
Crystal structure and mechanism of CO dehydrogenase, a molybdo iron-sulfur flavoprotein containing
S
-selanylcysteine
Authors: Dobbek Holger , Gremer Lothar , Meyer Ortwin , Huber Robert
Published: July 2002

CO dehydrogenase from the aerobic bacterium
Oligotropha carboxidovorans
catalyzes the oxidation of CO with H
2
O, yielding CO
2
, two electrons, and two H
+
. Its crystal structure in the air-oxidized form has been determined to 2.2 Å. The active site of the enzyme, which contains molybdenum with three oxygen ligands, molybdopterin-cytosine dinucleotide and
S
-selanylcysteine, delivers the electrons to an intramolecular electron transport chain composed of two types of [2Fe–2S] clusters and flavin-adenine dinucleotide. CO dehydrogenase is composed of an 88.7-kDa molybdoprotein (L), a 30.2-kDa flavoprotein (M), and a 17.8-kDa iron-sulfur protein (S). It is organized as a dimer of LMS heterotrimers and resembles xanthine dehydrogenase/oxidase in many, but not all, aspects. A mechanism based on a structure with the bound suicide-substrate cyanide is suggested and displays the necessity of
S
-selanylcysteine for the catalyzed reaction.
Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains
Authors: Kopen Gene C. , Prockop Darwin J. , Phinney Donald G.
Published: July 2002

Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.
Geranyl diphosphate synthase: Cloning, expression, and characterization of this prenyltransferase as a heterodimer
Authors: Burke Charles C. , Wildung Mark R. , Croteau Rodney
Published: July 2002

Geranyl diphosphate synthase, which catalyzes the condensation of dimethylallyl diphosphate and isopentenyl diphosphate to geranyl diphosphate, the key precursor of monoterpene biosynthesis, was purified from isolated oil glands of spearmint. Peptide fragments generated from the pure proteins of 28 and 37 kDa revealed amino acid sequences that matched two cDNA clones obtained by random screening of a peppermint-oil gland cDNA library. The deduced sequences of both proteins showed some similarity to existing prenyltransferases, and both contained a plastid-targeting sequence. Expression of each cDNA individually yielded no detectable prenyltransferase activity; however, coexpression of the two together produced functional geranyl diphosphate synthase. Antibodies raised against each protein were used to demonstrate that both subunits were required to produce catalytically active native and recombinant enzymes, thus confirming that geranyl diphosphate synthase is a heterodimer.
Integrated pararetroviral sequences define a unique class of dispersed repetitive DNA in plants
Authors: Jakowitsch J. , Mette M. F. , van der Winden J. , Matzke M. A. , Matzke A. J. M.
Published: July 2002

Although integration of viral DNA into host chromosomes occurs regularly in bacteria and animals, there are few reported cases in plants, and these involve insertion at only one or a few sites. Here, we report that pararetrovirus-like sequences have integrated repeatedly into tobacco chromosomes, attaining a copy number of ≈10
3
. Insertion apparently occurred by illegitimate recombination. From the sequences of 22 independent insertions recovered from a healthy plant, an 8-kilobase genome encoding a previously uncharacterized pararetrovirus that does not contain an integrase function could be assembled. Preferred boundaries of the viral inserts may correspond to recombinogenic gaps in open circular viral DNA. An unusual feature of the integrated viral sequences is a variable tandem repeat cluster, which might reflect defective genomes that preferentially recombine into plant DNA. The recurrent invasion of pararetroviral DNA into tobacco chromosomes demonstrates that viral sequences can contribute significantly to plant genome evolution.
The onset and extent of genomic instability in sporadic colorectal tumor progression
Authors: Stoler Daniel L. , Chen Neng , Basik Mark , Kahlenberg Morton S. , Rodriguez-Bigas Miguel A. , Petrelli Nicholas J. , Anderson Garth R.
Published: July 2002

Cancer cell genomes contain alterations beyond known etiologic events, but their total number has been unknown at even the order of magnitude level. By sampling colorectal premalignant polyp and carcinoma cell genomes through use of the technique inter-(simple sequence repeat) PCR, we have found genomic alterations to be considerably more abundant than expected, with the mean number of genomic events per carcinoma cell totaling approximately 11,000. Colonic polyps early in the tumor progression pathway showed similar numbers of events. These results indicate that, as with certain hereditary cancer syndromes, genomic destabilization is an early step in sporadic tumor development. Together these results support the model of genomic instability being a cause rather than an effect of malignancy, facilitating vastly accelerated somatic cell evolution, with the observed orderly steps of the colon cancer progression pathway reflecting the consequences of natural selection.
Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans
Authors: Valenzuela David M. , Griffiths Jennifer A. , Rojas Jose , Aldrich Thomas H. , Jones Pamela F. , Zhou Hao , McClain Joyce , Copeland Neal G. , Gilbert Debra J. , Jenkins Nancy A. , Huang Tammy , Papadopoulos Nick , Maisonpierre Peter C. , Davis Samuel , Yancopoulos George D.
Published: July 2002

The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.
Cyclin-dependent kinase control of centrosome duplication
Authors: Lacey Kathleen R. , Jackson Peter K. , Stearns Tim
Published: July 2002

Centrosomes nucleate microtubules and duplicate once per cell cycle. This duplication and subsequent segregation in mitosis results in maintenance of the one centrosome/cell ratio. Centrosome duplication occurs during the G
1
/S transition in somatic cells and must be coupled to the events of the nuclear cell cycle; failure to coordinate duplication and mitosis results in abnormal numbers of centrosomes and aberrant mitoses. Using both
in vivo
and
in vitro
assays, we show that centrosome duplication in
Xenopus laevis
embryos requires cyclin/cdk2 kinase activity. Injection of the cdk (cyclin-dependent kinase) inhibitor p21 into one blastomere of a dividing embryo blocks centrosome duplication in that blastomere; the related cdk inhibitor p27 has a similar effect. An
in vitro
system using
Xenopus
extracts carries out separation of the paired centrioles within the centrosome. This centriole separation activity is dependent on cyclin/cdk2 activity; depletion of either cdk2 or of the two activating cyclins, cyclin A and cyclin E, eliminates centriole separation activity. In addition, centriole separation is inhibited by the mitotic state, suggesting a mechanism of linking the cell cycle to periodic duplication of the centrosome.
RETRACTED: Detecting patterns of protein distribution and gene expression
in silico
Authors: Geraghty Michael T. , Bassett Doug , Morrell James C. , Gatto Gregory J. , Bai Jianwu , Geisbrecht Brian V. , Hieter Phil , Gould Stephen J.
Published: July 2002

Most biological information is contained within gene and genome sequences. However, current methods for analyzing these data are limited primarily to the prediction of coding regions and identification of sequence similarities. We have developed a computer algorithm, CoSMoS (for context sensitive motif searches), which adds context sensitivity to sequence motif searches. CoSMoS was challenged to identify genes encoding peroxisome-associated and oleate-induced genes in the yeast
Saccharomyces cerevisiae
. Specifically, we searched for genes capable of encoding proteins with a type 1 or type 2 peroxisomal targeting signal and for genes containing the oleate-response element, a
cis
-acting element common to fatty acid-regulated genes. CoSMoS successfully identified 7 of 8 known PTS-containing peroxisomal proteins and 13 of 14 known oleate-regulated genes. More importantly, CoSMoS identified an additional 18 candidate peroxisomal proteins and 300 candidate oleate-regulated genes. Preliminary localization studies suggest that these include at least 10 previously unknown peroxisomal proteins. Phenotypic studies of selected gene disruption mutants suggests that several of these new peroxisomal proteins play roles in growth on fatty acids, one is involved in peroxisome biogenesis and at least two are required for synthesis of lysine, a heretofore unrecognized role for peroxisomes. These results expand our understanding of peroxisome content and function, demonstrate the utility of CoSMoS for context-sensitive motif scanning, and point to the benefits of improved
in silico
genome analysis.
Identification of mutations in the
c-mpl
gene in congenital amegakaryocytic thrombocytopenia
Authors: Ihara Kenji , Ishii Eiichi , Eguchi Mariko , Takada Hidetoshi , Suminoe Aiko , Good Robert A. , Hara Toshiro
Published: July 2002

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. Our previous hematological analysis indicated similarities between human CAMT and murine
c-mpl
(thrombopoietin receptor) deficiency. Because the
c-mpl
gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the
c-mpl
gene of a 10-year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10. Both mutations were predicted to result in a prematurely terminated c-Mpl protein, which, if translated, lacks all intracellular domains essential for signal transduction. Each of the mutations was segregated from the patient’s parents. Accordingly, the patient was a compound heterozygote for two mutations of the
c-mpl
gene, each derived from one of the parents. The present study suggests that at least a certain type of CAMT is caused by the
c-mpl
mutation, which disrupts the function of thrombopoietin receptor.
Measures of degeneracy and redundancy in biological networks
Authors: Tononi Giulio , Sporns Olaf , Edelman Gerald M.
Published: July 2002

Degeneracy, the ability of elements that are structurally different to perform the same function, is a prominent property of many biological systems ranging from genes to neural networks to evolution itself. Because structurally different elements may produce different outputs in different contexts, degeneracy should be distinguished from redundancy, which occurs when the same function is performed by identical elements. However, because of ambiguities in the distinction between structure and function and because of the lack of a theoretical treatment, these two notions often are conflated. By using information theoretical concepts, we develop here functional measures of the degeneracy and redundancy of a system with respect to a set of outputs. These measures help to distinguish the concept of degeneracy from that of redundancy and make it operationally useful. Through computer simulations of neural systems differing in connectivity, we show that degeneracy is low both for systems in which each element affects the output independently and for redundant systems in which many elements can affect the output in a similar way but do not have independent effects. By contrast, degeneracy is high for systems in which many different elements can affect the output in a similar way and at the same time can have independent effects. We demonstrate that networks that have been selected for degeneracy have high values of complexity, a measure of the average mutual information between the subsets of a system. These measures promise to be useful in characterizing and understanding the functional robustness and adaptability of biological networks.
Characterization of two chloroplast RNA polymerase sigma factors from
Zea mays
: Photoregulation and differential expression
Authors: Tan Shi , Troxler Robert F.
Published: July 2002

Two distinct cDNAs encoding putative σ factors of plastid RNA polymerase were isolated from
Zea mays
, a C4 plant. The deduced amino acid sequences of both cDNAs possess all four highly conserved domains proposed for recognition of −10 and −35 promoter elements, core complex binding, DNA binding, and melting. These two cDNAs are designated
sig1
and
sig2
.
Phylogenetic analysis of available plastid σ factors indicated that they were probably the descendants of cyanobacterial principal σ factors. Southern blots probed with
sig1
and
sig2
revealed that both genes exist in the maize nuclear genome as single-copy genes, but low-stringency hybridization suggested the presence of a multigene family of maize plastid σ factors. Transcription of
sig1
and
sig2
is light inducible and tissue specific. Transcripts of
sig1
and
sig2
were abundant in greening leaf tissues;
sig2
(but not
sig1
) was barely detectable in etiolated leaves and neither was detectable in roots. Immunological studies using a peptide antibody against an epitope in subdomain 2.4 of Sig1 revealed 50-kDa and 60-kDa immunoreactive proteins in maize chloroplasts. Reduced levels of the 60-kDa immunoreactive protein were detected in etioplasts, and no immunoreactive proteins were observed in roots. Collectively, the data suggest that the nuclear genes,
sig1
and
sig2
, may play a role in differential expression of plastid genes during chloroplast biogenesis.
Diverse karyotypic abnormalities of the c
-myc
locus associated with c
-myc
dysregulation and tumor progression in multiple myeloma
Authors: Shou Yaping , Martelli Maria L. , Gabrea Ana , Qi Ying , Brents Leslie A. , Roschke Anna , Dewald Gordon , Kirsch Ilan R. , Bergsagel P. Leif , Kuehl W. Michael
Published: July 2002

Translocations involving c
-myc
and an Ig locus have been reported rarely in human multiple myeloma (MM). Using specific fluorescence
in situ
hybridization probes, we show complex karyotypic abnormalities of the c
-myc
or L
-myc
locus in 19 of 20 MM cell lines and approximately 50% of advanced primary MM tumors. These abnormalities include unusual and complex translocations and insertions that often juxtapose
myc
with an IgH or IgL locus. For two advanced primary MM tumors, some tumor cells contain a karyotypic abnormality of the c
-myc
locus, whereas other tumor cells do not, indicating that this karyotypic abnormality of c
-myc
occurs as a late event. All informative MM cell lines show monoallelic expression of c
-myc
. For Burkitt's lymphoma and mouse plasmacytoma tumors, balanced translocation that juxtaposes c
-myc
with one of the Ig loci is an early, invariant event that is mediated by B cell-specific DNA modification mechanisms. By contrast, for MM, dysregulation of c
-myc
apparently is caused principally by complex genomic rearrangements that occur during late stages of MM progression and do not involve B cell-specific DNA modification mechanisms.
Acute decrease in net glutamate uptake during energy deprivation
Authors: Jabaudon Denis , Scanziani Massimo , Gähwiler Beat H. , Gerber Urs
Published: July 2002

The extracellular glutamate concentration ([glu]o) rises during cerebral ischemia, reaching levels capable of inducing delayed neuronal death. The mechanisms underlying this glutamate accumulation remain controversial. We usedN-methyl-d-aspartate receptors on CA3 pyramidal neurons as a real-time, on-site, glutamate sensor to identify the source of glutamate release in anin vitromodel of ischemia. Using glutamate andl-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) as substrates anddl-threo-β-benzyloxyaspartate (TBOA) as an inhibitor of glutamate transporters, we demonstrate that energy deprivation decreases net glutamate uptake within 2–3 min and later promotes reverse glutamate transport. This process accounts for up to 50% of the glutamate accumulation during energy deprivation. Enhanced action potential-independent vesicular release also contributes to the increase in [glu]o, by ≈50%, but only once glutamate uptake is inhibited. These results indicate that a significant rise in [glu]oalready occurs during the first minutes of energy deprivation and is the consequence of reduced uptake and increased vesicular and nonvesicular release of glutamate.
Stimulation of glutamate receptor protein synthesis and membrane insertion within isolated neuronal dendrites
Authors: Kacharmina Janet Estee , Job Christy , Crino Peter , Eberwine James
Published: July 2002

The selective subcellular localization of mRNAs to dendrites and
the recent demonstration of local protein synthesis have highlighted
the potential role of postsynaptic sites in modulation of cell–cell
communication. We show that epitope-tagged subunit 2 of the ionotopic
glutamate receptor, GluR2, mRNA transfected into isolated hippocampal
neuronal dendrites is translated in response to pharmacologic
stimulation. Further, confocal imaging of N-terminally labeled GluR2
reveals that the newly synthesized GluR2 protein can integrate into the
dendritic membrane with the N terminus externally localized. These data
demonstrate that integral membrane proteins can be synthesized in
dendrites and can locally integrate into the cell membrane.
Six cloned calves produced from adult fibroblast cells after long-term culture
Authors: Kubota Chikara , Yamakuchi Hiroshi , Todoroki Junichi , Mizoshita Kazunori , Tabara Norio , Barber Michele , Yang Xiangzhong
Published: July 2002

Cloning whole animals with somatic cells as parents offers the
possibility of targeted genetic manipulations
in vitro
such
as “gene knock-out” by homologous recombination. However, such
manipulation requires prolonged culture of nuclear donor cells.
Previous successes in cloning have been limited to the use of cells
collected either fresh or after short-term culture. Therefore,
demonstration of genetic totipotency of cells after prolonged culture
is pivotal to combining site-specific genetic manipulations and
cloning. Here we report birth of six clones of an aged (17-year-old)
Japanese Black Beef bull using ear skin fibroblast cells as nuclear
donor cells after up to 3 months of
in vitro
culture
(10–15 passages). We observed higher developmental rates for embryos
derived from later passages (10 and 15) as compared with those embryos
from an early passage (passage 5). The four surviving clones are now
10–12 months of age and appear normal, similar to their naturally
reproduced peers. These data show that fibroblasts of aged animals
remain competent for cloning, and prolonged culture does not affect the
cloning competence of adult somatic donor cells.
Zygmunt Bauman's poisoned gift of morality*
Authors: Junge Matthias
Published: July 2002

Bauman's attempt to develop a sociological theory of morality turning around fundamental premises of Durkheim's approach fails in the last analysis, since in Bauman's view the ‘moral party of two’ does not constitute a social situation. It is argued that the necessary condition to think sociologically about morality is the concept of reciprocity and thus one can arrive at a view of morality in postmodernity consistent with Bauman's earlier theory of practice. If Bauman's idea about responsibilty as the core of morality is transformed to the idea of an appeal of history to compassion and is supplemented with the idea of reciprocity as an emerging norm it is possible to outline a sociological theory of moral practice according to postmodern conditions.
Political Implications of Psychological Research on Ecological Justice and Proenvironmental Behaviour
Authors: Montada Leo , Kals Elisabeth
Published: July 2002

An empirically corroborated model of proenvironmental commitments is outlined. According to this model, willingness to contribute to the saving of global commons (atmosphere, oceans, etc.) is motivated by the awareness of global ecological risks, by perceived injustices of the distributions of benefits and costs resulting from exploiting and polluting activities, and by the conviction that many actors—ordinary citizens as well as powerful authorities in business and politics—have both effective means and responsibilities to contribute to the protection of the environment. Political implications are drawn from the typical attributional pattern of multi‐responsibility for environmental protection and from the perception of distributive injustices of the current overuse and pollution of commons. Basic issues of ecological justice are discussed.
Les habiletés et régulations motrices au cours de l'escalade et de la descente d'un escalier hélicoïdal chez des enfants de 17 à 27 mois
Authors: Fulcrand Jean , Montagner Hubert , Taule Marguerite
Published: July 2002

Nous rapportons dans cet article des données nouvelles sur les comportements d'escalade et de descente d'un escalier hélicoïdal par 12 enfants, dans un local spécialement aménagé. Âgés entre 17 et 21 mois au début de la recherche, ils ont été répartis en deux groupes: pour l'un, la première marche était triangulaire; pour l'autre, quadrangulaire. Les měmes enfants ont été étudiés entre 23 et 27 mois dans les měmes conditions et selon le měme protocole, mais avec une inversion de la configuration de la première marche. On observe que: (1) dès la classe d'âges de 17 à 21 mois, les enfants des deux groupes privilégient le pied droit pour attaquer la première marche, avec le plus souvent alternance des deux pieds sans diminution du pas et sans arrět; (2) la configuration de la première marche joue un rôle significatif dans la fréquence de choix du pied d'attaque en début d'escalade et en fin de descente; (3) les comportements en fin d'escalade et en début de descente apparaissent influencés par la configuration du sommet de l'escalier et par la configuration de la première marche d'escalade; (4) entre 23 et 27 mois, l'influence des facteurs de développement est particulièrement nette en début d'escalade et en fin de descente; (5) les comportements en fin d'escalade et en début de descente apparaissent influencés par une combinaison de facteurs de développement, de la configuration du sommet de l'escalier, des expériences individuelles au début de l'escalade et des expériences individuelles au cours de la première partie de l'étude.
Antecedent Variables for Sociomoral Reasoning Development: Evidence from Two Cultural Settings
Authors: Markoulis Diomedes , Valanides Nikolaos
Published: July 2002

This study examined the developmental pattern of sociomoral reasoning in two different cultural settings, focusing on factors assumed to influence the course of growth in this particular domain. The specific hypotheses tested concerned the relationships between operational thinking within Piaget's theory and Kohlberg's conceptualization of sociomoral judgement development. Secondary school and university students from Greece and Nigeria aged 15 to 22 years (N = 281) participated in the study. Results indicated that (1) the developmental sequence was similar in the two differing cultural environments, (2) stage endorsement differed significantly in the two samples, and (3) the necessary‐but‐not‐sufficient hypothesis was confirmed in both groups. The possible explanations of the findings are discussed in connection with the basic assumptions of the structural‐developmental approach to socio‐cognitive growth.
Psychological Distress among Immigrant Adolescents: Culture‐specific Factors in the Case of Immigrants from the Former Soviet Union
Authors: Mirsky Julia
Published: July 2002

Studies investigating the effects of immigration on the psychological wellbeing of adolescents have produced variable and inconclusive results: some identify immigrant adolescents as a group of risk whereas others fail to demonstrate higher psychological distress in this group of adolescents. It is suggested in the present paper that cultural factors active in specific ethnic groups of immigrants may in part account for this inconsistency. The present study explores the psychological distress of immigrant adolescents from the Former Soviet Union (FSU) in Israel. The respondents were 560 university students (250 females and 310 males) who had immigrated to Israel from the FSU since 1989. The present report relates to one of the instruments applied in the study: the Brief Symptom Inventory (BSI). Mean BSI scores of the respondents were significantly higher than those of Israeli adolescents and in some categories higher than the American norms. A high percent of the immigrant respondents have reported severely troubling symptoms; however no significant differences were found between the BSI scores of FSU immigrants in Israel and their peers in the FSU. The findings are discussed in light of some sociocultural characteristics of society in the FSU.
An Entrepreneurial City in Action: Hong Kong's Emerging Strategies in and for (Inter)Urban Competition
Authors: Jessop Bob , Sum Ngai-Ling
Published: July 2002

The paper applies a Schumpeterian analysis of entrepreneurial cities to Hong Kong. It argues that the concept of entrepreneurship can be applied to cities as strategic actors, identifies various objects of urban entrepreneurship, and refers to the important role of entrepreneurial discourses, narratives and self-images. Despite its laissez-faire reputation, Hong Kong has a long history of urban entrepreneurship, but its strategies have been adapted to changing circumstances—most recently with its key role in an emerging cross-border region (Greater China) and its favourable insertion into the global economy. This has prompted a debate over the most appropriate strategies for Hong Kong, notably regarding the respective futures of manufacturing, services and the virtual economy. The concept of 'glurbanisation' as one form of the more general phenomenon of 'glocalisation' is introduced to illuminate these issues. The paper concludes by noting the increased importance of 'Siliconisation' as an accumulation strategy in east Asia.
Devolution and User Participation in Public Services: How They Work and What They Do
Authors: Tunstall Rebecca
Published: July 2002

Devolution and user participation have had enduring popularity as initiatives in public services in many countries. The 1997 Labour government renewed interest in the UK. However, how devolution and participation work and what they do, particularly in combination, are still not well understood. Research has been handicapped by key conceptual problems over definition, measurement and the identification of effects, and challenged by gaps between rhetoric and reality. Data on combined devolution and user participation through Tenant Management Organisations in English council housing were used to specify the extent of changes, examine processes and identify the effects. Formal measures alone were insufficient. Other measures and changes in management processes showed that the combination had the potential for significant, but widely varying effects on service performance.
The Role of Development Agencies in Regional Policy: An Academic and Practitioner Approach
Authors: Hughes James T.
Published: July 2002

The increasing importance of Regional Development Agencies creates a need for consideration of how the role and effectiveness of these organisations can be researched in the UK. In their relationship with central government, the informal channels are frequently the most important means of control. Following an acceptable definition, several aspects of their operation are examined, including their scope for independent action, strategy and local contact within their regions. However, the changing strategic priorities must be examined in relation to how they work as organisations. This is a challenge to the disciplines engaged in regional analysis.
Unwrapping Stock Transfers: Applying Discourse Analysis to Landlord Communication Strategies
Authors: Taylor Mary
Published: July 2002

This paper applies the principles of critical discourse analysis to material produced by public landlords to inform tenants about transfer proposals. It refers in particular to the case of Scottish Homes, a quango landlord currently seeking to transfer all its tenanted housing stock to alternative landlords. It starts by setting out some background on the policy context for stock transfer in the UK as a whole and from Scottish Homes in particular. Recent Scottish Homes material is then examined with reference to Fairclough's framework for critical discourse analysis. The paper concludes that it may be too difficult for disposing landlords to counteract the strength of resistant readings from competing informal discourse, however skilful their own marketing, and that discourse analysis is a useful public policy research tool for specific pieces of discourse, particularly in helping to investigate the management of communication.
Language Politics in Education and the Response of the Russians in Ukraine
Authors: Janmaat Jan G.
Published: July 2002

Ukraine's independence signaled the end of the post-war Russification of the school system and the beginning of a large scale Ukrainization of the educational sector. From the 1990–1991 school year to the 1997–1998 school year, the national authorities raised the proportion of Ukrainian-instructed school children from 47.9% to 62.8% nationwide. As the language of instruction in Ukraine's schools almost exclusively is either Ukrainian or Russian, the relative percentage of Russian-instructed school children, conversely, declined from 51.4% to 36.4% during the same period. Ukraine is not the only Soviet successor state that has promoted the language of the titular nationality in the sphere of education at the expense of Russian. In Kazakhstan, for example, the proportion of pupils receiving their education in Kazakh grew from 32.4% in 1990–1991 to 40.1% in 1993–1994, and the percentage of Russian-instructed children, accordingly, fell from 65.0% to 57.2%. In Moldova, the number of pupils studying exclusively in Moldovan increased from 424,000 to 447,000 between 1989–1990 and 1992–1993, while the number of pupils studying exclusively in Russian dropped from 290,000 to 262,000.
The Attachment Doll-play Interview for Preschoolers
Authors: Oppenheim David
Published: July 2002

Children’s narratives about attachment themes were elicited using the Attachment Doll-play Interview (ADI) and compared with measures of attachment based on a separation-reunion observation and on the Waters and Deane (1985) Attachment Q-sort. Two correlates of attachment, self-esteem and attention-seeking strategies, were also measured. Children who were more secure based on the ADI, as reflected in emotional openness and descriptions of positive mother-child interactions, behaved more independently during separations and reunions, and were rated by teachers as having higher levels of self-esteem and age-appropriate attention-seeking strategies. No significant correlations were found between ADI responses and the Attachment Q-sort. The results of this study converge with previous research which has used narratives to assess attachment among young children, and highlight the importance of open communication as an aspect of security.
Immune Responses: Adverse Versus Non-Adverse Effects
Authors: Kimber Ian , Dearman Rebecca J.
Published: July 2002

The adaptive immune system in vertebrates has evolved to provide host resistance to infectious microorganisms and malignant disease. Normal immune function and the induction of specific immune responses require the orchestrated interaction between cells and molecules both within and outside the lymphoid system. Immunotoxicology can be defined as the study of adverse health effects that may result from the interaction of xenobiotics with the immune system. In general terms such effects can take one of two forms. The first of these is immunotoxicity (or immunosuppression) where there is a perturbation of, or damage to, one or more components of the immune system resulting in impaired immune function and reduced host resistance. The design and interpretation of experimental immunotoxicity studies and the investigation of clinical immunosuppression require consideration of the relationship between changes in the structure and/or function of discrete components of the immune system and holistic changes in the susceptibility to infectious and malignant disease. The other main way in which chemicals may cause adverse health effects secondary to interaction with the immune system is through stimulation of specific immune responses that result in allergic disease. Allergy to chemicals and proteins can take many forms, including allergic contact dermatitis, allergic sensitization of the respiratory tract (associated with rhinitis and/or asthma), systemic allergic reactions (associated frequently with drug treatment), and gastrointestinal disease. Here there is a need to distinguish between immunogenic responses per se and those immune responses that are of sufficient vigor and of the quality necessary to provoke allergic sensitization. The purpose of this article is to explore the extent to which distinctions can be drawn between adverse and nonadverse effects in the context of immunotoxicity and allergy.
Safety Assessment and Public Concerns for Genetically Modified Food Products: The Japanese Experience
Authors: Hino Akihiro
Published: July 2002

Therecombinant DNA (rDNA) technique is expected to bring about great progress in the improvement of breeding technology and the development of new plant varieties showing high quality and high yield, such as those with excellent pest and disease resistance, those with environmental stress tolerance, and so forth. In the United States and Canada, many genetically modified (GM) crop plants were commercialized as early as 1994. In Japan, 35 transgenic crop plants, such as herbicide tolerant soybean, cotton, and canola, and insect-resistant corn, cotton, and potatos, were authorized and considered marketable until April 2001. The general public, however, is not familiar with rDNA technology, and some people seem to feel uncomfortable with biotechnology, frequently because of the difficulty of the technology and lacking of sufficient information. New labeling systems were initiated in April 2001 in Japan to provide information regarding the use of GM crops as raw material.