bluuebunny/crossref_metadata_2025 huggingface dataset:
Algae displaying the diadinoxanthin cycle also possess the violaxanthin cycle
Authors: Lohr Martin , Wilhelm Christian
Published: July 2002

According to general agreement, all photosynthetic organisms using xanthophyll cycling for photoprotection contain either the violaxanthin (Vx) cycle or the diadinoxanthin (Ddx) cycle instead. Here, we report the temporal accumulation of substantial amounts of pigments of the Vx cycle under prolonged high-light stress in several microalgae thought to possess only the Ddx cycle. In the diatom
Phaeodactylum tricornutum
, used as a model organism, these pigments also participate in xanthophyll cycling, and their accumulation depends on
de novo
synthesis of carotenoids and on deepoxidase activity. Furthermore, our data strongly suggest a biosynthetic sequence from Vx via Ddx to fucoxanthin in
P. tricornutum
. This gives experimental support to the long-stated hypothesis that Vx is a common precursor of all carotenoids with an allenic or acetylenic group, including the main light-harvesting carotenoids in most chlorophyll a/c-containing algae. Thus, another important function for xanthophyll cycling may be to optimize the biosynthesis of light-harvesting xanthophylls under fluctuating light conditions.
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region
Authors: Georgescu Maria-Magdalena , Kirsch Kathrin H. , Akagi Tsuyoshi , Shishido Tomoyuki , Hanafusa Hidesaburo
Published: July 2002

PTEN is a recently identified tumor suppressor inactivated in a variety of cancers such as glioblastoma and endometrial and prostate carcinoma. It contains an amino-terminal phosphatase domain and acts as a phosphatidylinositol 3,4,5-trisphosphate phosphatase antagonizing the activity of the phosphatidylinositol 3-OH kinase. PTEN also contains a carboxyl-terminal domain, and we addressed the role of this region that, analogous to the amino-terminal phosphatase domain, is the target of many mutations identified in tumors. Expression of carboxyl-terminal mutants in PTEN-deficient glioblastoma cells permitted the anchorage-independent growth of the cells that otherwise was suppressed by wild-type PTEN. The stability of these mutants in cells was reduced because of rapid degradation. Although the carboxyl-terminal region contains regulatory PEST sequences and a PDZ-binding motif, these specific elements were dispensable for the tumor-suppressor function. The study of carboxyl-terminal point mutations affecting the stability of PTEN revealed that these were located in strongly predicted β-strands. Surprisingly, the phosphatase activity of these mutants was affected in correlation with the degree of disruption of these structural elements. We conclude that the carboxyl-terminal region is essential for regulating PTEN stability and enzymatic activity and that mutations in this region are responsible for the reversion of the tumor-suppressor phenotype. We also propose that the molecular conformational changes induced by these mutations constitute the mechanism for PTEN inactivation.
Replicated evolution of trophic specializations in an endemic cichlid fish lineage from Lake Tanganyika
Authors: Rüber Lukas , Verheyen Erik , Meyer Axel
Published: July 2002

The current phylogenetic hypothesis for the endemic Lake Tanganyika cichlid fishes of the tribe Eretmodini is based solely on morphology and suggests that more complex trophic morphologies derived only once from a less specialized ancestral condition. A molecular phylogeny of eretmodine cichlids based on partial mitochondrial DNA cytochromeband control-region sequences was used to reconstruct the evolutionary sequence of trophic adaptations and to test alternative models of morphological divergence. The six mitochondrial lineages found disagree with the current taxonomy and the morphology-based phylogeny. Mitochondrial lineages with similar trophic morphologies are not grouped monophyletically but are typically more closely related to lineages with different trophic phenotypes currently assigned to other genera. Our results indicate multiple independent origins of similar trophic specializations in these cichlids. A pattern of repeated divergent morphological evolution becomes apparent when the phylogeography of the mitochondrial haplotypes is analyzed in the context of the geological and paleoclimatological history of Lake Tanganyika. In more than one instance within Lake Tanganyika, similar morphological divergence of dentitional traits occurred in sympatric species pairs. Possibly, resource-based divergent selective regimes led to resource partitioning and brought about similar trophic morphologies independently and repeatedly.
Ultrafast electron diffraction and direct observation of transient structures in a chemical reaction
Authors: Cao Jianming , Ihee Hyotcherl , Zewail Ahmed H.
Published: July 2002

Ultrafast electron diffraction is a unique method for the studies of structural changes of complex molecular systems. In this contribution, we report direct ultrafast electron diffraction study of the evolution of short-lived intermediates in the course of a chemical change. Specifically, we observe the transient intermediate in the elimination reaction of 1,2-diiodotetrafluoroethane (C
2
F
4
I
2
) to produce the corresponding ethylene derivative by the breakage of two carbon–iodine, C—I, bonds. The evolution of the ground-state intermediate (C
2
F
4
I radical) is directly revealed in the population change of a single chemical bond, namely the second C—I bond. The elimination of two iodine atoms was shown to be nonconcerted, with reaction time of the second C—I bond breakage being 17 ± 2 ps. The structure of the short-lived C
2
F
4
I radical is more favorable to the classical radical structure than to the bridged radical structure. This leap in our ability to record structural changes on the ps and shorter time scales bodes well for many future applications in complex molecular systems.
IL-1β differentially regulates calcium wave propagation between primary human fetal astrocytes via pathways involving P2 receptors and gap junction channels
Authors: John Gareth R. , Scemes Eliana , Suadicani Sylvia O. , Liu Judy S. H. , Charles Peter C. , Lee Sunhee C. , Spray David C. , Brosnan Celia F.
Published: July 2002

In mammalian astrocytes, calcium waves are transmitted between cells via both a gap junction-mediated pathway and an extracellular, P2 receptor-mediated pathway, which link the cells into a syncytium. Calcium waves in astrocytes have also been shown to evoke calcium transients in neurons, and activity in neurons can elicit calcium waves in astrocytes. In this study, we show that in primary human fetal astrocytes, the P2 receptor-mediated and gap junction-mediated pathways are differentially regulated by the cytokine IL-1β. Confocal microscopy of astrocytes loaded with Indo-1 demonstrated that intercellular calcium wave transmission in IL-1β-treated cultures was potentiated compared with controls. However, transmission of calcium waves via the gap junction-mediated pathway was strikingly reduced. The major component of functional gap junctions in human fetal astrocytes was demonstrated to be connexin43 (Cx43), and there was a marked reduction of junctional conductance, loss of dye coupling, loss of Cx43 protein, and down-regulation of Cx43 mRNA expression after IL-1β treatment of cultures. Conversely, transmission of calcium waves via the P2 receptor-mediated pathway was potentiated in IL-1β-treated cultures compared with controls. This potentiation was associated with an increase in the number of cells responsive to UTP, and with a transient increase in expression of the P2Y2purinoceptor mRNA. Because in inflammatory conditions of the human central nervous system IL-1β is produced both by resident glia and by invading cells of the immune system, our results suggest that inflammatory events may have a significant impact on coordination of astrocytic function and on information processing in the central nervous system.
Oogenic function of the myogenic factor D-MEF2: Negative regulation of the Decapentaplegic receptor gene
thick veins
Authors: Mantrova Ekaterina Y. , Schulz Robert A. , Hsu Tien
Published: July 2002

The myogenic factor D-MEF2 is required for the proper differentiation of muscle cells during
Drosophila
embryogenesis and the correct patterning of indirect flight muscles assembled during later metamorphosis. In addition to these essential myogenic functions, mutant
D-mef2
adult females are weakly fertile and produce defective eggs. D-MEF2 is expressed in nurse and follicle cells of the wild-type egg chamber. We have analyzed the
D-mef2
oogenic phenotype and show that the gene is required for the normal patterning and differentiation of the centripetally migrating follicle cells that are crucial for development of the anterior chorionic structures.
D-mef2
alleles exhibit a genetic interaction with a dominant-negative allele of
thick veins
(
tkv
), which encodes a type I receptor of the Decapentaplegic-signaling pathway.
tkv
RNA is overexpressed in
D-mef2
mutant egg chambers, and, conversely, forced expression of
D-mef2
represses
tkv
expression. These results indicate a role for D-MEF2 in the regulation of
tkv
gene expression and Decapentaplegic signal transduction that are essential for proper determination and/or differentiation of the anterior follicle cells. Additionally, they demonstrate a vital function for the D-MEF2 transcription factor in multiple genetic pathways during
Drosophila
development.
Pain modulation by release of the endogenous cannabinoid anandamide
Authors: Walker J. Michael , Huang Susan M. , Strangman Nicole M. , Tsou Kang , Sañudo-Peña M. Clara
Published: July 2002

Synthetic cannabinoids produce behavioral analgesia and suppress pain neurotransmission, raising the possibility that endogenous cannabinoids serve naturally to modulate pain. Here, the development of a sensitive method for measuring cannabinoids by atmospheric pressure-chemical ionization mass spectrometry permitted measurement of the release of the endogenous cannabinoid anandamide in the periaqueductal gray (PAG) by
in vivo
microdialysis in the rat. Electrical stimulation of the dorsal and lateral PAG produced CB1 cannabinoid receptor-mediated analgesia accompanied by a marked increase in the release of anandamide in the PAG, suggesting that endogenous anandamide mediates the behavioral analgesia. Furthermore, pain triggered by subcutaneous injections of the chemical irritant formalin substantially increased the release of anandamide in the PAG. These findings indicate that the endogenous cannabinoid anandamide plays an important role in a cannabinergic pain-suppression system existing within the dorsal and lateral PAG. The existence of a cannabinergic pain-modulatory system may have relevance for the treatment of pain, particularly in instances where opiates are ineffective.
Stimulation of the blue light phototropic receptor NPH1 causes a transient increase in cytosolic Ca
2+
Authors: Baum Gideon , Long Joanne C. , Jenkins Gareth I. , Trewavas Anthony J.
Published: July 2002

Blue light regulates plant growth and development, and three photoreceptors, CRY1, CRY2, and NPH1, have been identified. The transduction pathways of these receptors are poorly understood. Transgenic plants containing aequorin have been used to dissect the involvement of these three receptors in the regulation of intracellular Ca
2+
. Pulses of blue light induce cytosolic Ca
2+
transients lasting about 80 s in
Arabidopsis
and tobacco seedlings. Use of organelle-targeted aequorins shows that Ca
2+
increases are limited to the cytoplasm. Blue light treatment of
cry1
,
cry2
, and
nph1
mutants showed that NPH1, which regulates phototropism, is largely responsible for the Ca
2+
transient. The spectral response of the Ca
2+
transient is similar to that of phototropism, supporting NPH1 involvement. Furthermore, known interactions between red and blue light and between successive blue light pulses on phototropic sensitivity are mirrored in the blue light control of cytosolic Ca
2+
in these seedlings. Our observations raise the possibility that physiological responses regulated by NPH1, such as phototropism, may be transduced through cytosolic Ca
2+
.
An
in vivo
membrane fusion assay implicates SpoIIIE in the final stages of engulfment during
Bacillus subtilis
sporulation
Authors: Sharp Marc D. , Pogliano Kit
Published: July 2002

Shortly after the synthesis of the two cells required for sporulation in
Bacillus subtilis
, the membranes of the larger mother cell begin to migrate around and engulf the smaller forespore cell. At the completion of this process the leading edges of the migrating membrane meet and fuse, releasing the forespore into the mother cell cytoplasm. We developed a fluorescent membrane stain-based assay for this membrane fusion event, and we isolated mutants defective in the final stages of engulfment or membrane fusion. All had defects in
spoIIIE,
which is required for translocation of the forespore chromosome across the polar septum. We isolated one
spoIIIE
mutant severely defective in chromosome translocation, but not in membrane fusion; this mutation disrupts the ATP/GTP-binding site of SpoIIIE, suggesting that ATP binding and hydrolysis are required for DNA translocation but not for the late engulfment function of SpoIIIE. We also correlated relocalization of SpoIIIE-green fluorescent protein from the sporulation septum to the forespore pole with the completion of membrane fusion and engulfment. We suggest that SpoIIIE is required for the final steps of engulfment and that it may regulate or catalyze membrane fusion events.
Neuropeptide release by efficient recruitment of diffusing cytoplasmic secretory vesicles
Authors: Han Weiping , Ng Yuen-Keng , Axelrod Daniel , Levitan Edwin S.
Published: July 2002

Neuropeptides are slowly released from a limited pool of secretory vesicles. Despite decades of research, the composition of this pool has remained unknown. Endocrine cell studies support the hypothesis that a population of docked vesicles supports the first minutes of hormone release. However, it has been proposed that mobile cytoplasmic vesicles dominate the releasable neuropeptide pool. Here, to determine the cellular basis of the releasable pool, single green fluorescent protein-labeled secretory vesicles were visualized in neuronal growth cones with the use of an inducible construct or total internal reflection fluorescence microscopy. We report that vesicle movement follows the diffusion equation. Furthermore, rapidly moving secretory vesicles are used more efficiently than stationary vesicles near the plasma membrane to support stimulated release. Thus, randomly moving cytoplasmic vesicles participate in the first minutes of neuropeptide release. Importantly, the preferential recruitment of diffusing cytoplasmic secretory vesicles contributes to the characteristic slow kinetics and limited extent of sustained neuropeptide release.
DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes
Authors: Bailey Susan M. , Meyne Julianne , Chen David J. , Kurimasa Akihiro , Li Gloria C. , Lehnert Bruce E. , Goodwin Edwin H.
Published: July 2002

Recent findings intriguingly place DNA double-strand break repair proteins at chromosome ends in yeast, where they help maintain normal telomere length and structure. In the present study, an essential telomere function, the ability to cap and thereby protect chromosomes from end-to-end fusions, was assessed in repair-deficient mouse cell lines. By using fluorescence
in situ
hybridization with a probe to telomeric DNA, spontaneously occurring chromosome aberrations were examined for telomere signal at the points of fusion, a clear indication of impaired end-capping. Telomeric fusions were not observed in any of the repair-proficient controls and occurred only rarely in a p53 null mutant. In striking contrast, chromosomal end fusions that retained telomeric sequence were observed in nontransformed DNA-PK
cs
-deficient cells, where they were a major source of chromosomal instability. Metacentric chromosomes created by telomeric fusion became even more abundant in these cells after spontaneous immortalization. Restoration of repair proficiency through transfection with a functional cDNA copy of the human

DNA-PK
cs

gene reduced the number of fusions compared with a negative transfection control. Virally transformed cells derived from Ku70 and Ku80 knockout mice also displayed end-to-end fusions. These studies demonstrate that DNA double-strand break repair genes play a dual role in maintaining chromosomal stability in mammalian cells, the known role in repairing incidental DNA damage, as well as a new protective role in telomeric end-capping.
MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1
Authors: Bellacosa Alfonso , Cicchillitti Lucia , Schepis Filippo , Riccio Antonio , Yeung Anthony T. , Matsumoto Yoshihiro , Golemis Erica A. , Genuardi Maurizio , Neri Giovanni
Published: July 2002

The DNA mismatch repair (MMR) is a specialized system, highly conserved throughout evolution, involved in the maintenance of genomic integrity. To identify novel human genes that may function in MMR, we employed the yeast interaction trap. Using the MMR protein MLH1 as bait, we cloned
MED1.
The MED1 protein forms a complex with MLH1, binds to methyl-CpG-containing DNA, has homology to bacterial DNA repair glycosylases/lyases, and displays endonuclease activity. Transfection of a MED1 mutant lacking the methyl-CpG-binding domain (MBD) is associated with microsatellite instability (MSI). These findings suggest that MED1 is a novel human DNA repair protein that may be involved in MMR and, as such, may be a candidate eukaryotic homologue of the bacterial MMR endonuclease, MutH. In addition, these results suggest that cytosine methylation may play a role in human DNA repair.
Distinguishing surface effects of calcium ion from pore-occupancy effects in Na
+
channels
Authors: Armstrong C. M.
Published: July 2002

The effects of calcium ion on the Na
+
activation gate were studied in squid giant axons. Saxitoxin (STX) was used to block ion entry into Na
+
channels without hindering access to the membrane surface, making it possible to distinguish surface effects of calcium from pore-occupancy effects. In the presence of STX, gating kinetics were measured from gating current (
I
g
). The kinetic effects of external calcium concentration changes were small when STX was present. In the absence of STX, lowering the calcium concentration (from 100 to 10 mM) slowed the closing of Na
+
channels (measured from
I
Na
tails) by more than a factor of 2. Surprisingly, the voltage sensitivity of closing kinetics changed with calcium concentration, and it was modified by STX. Voltage sensitivity apparently depends in part on the ability of calcium to enter and block the channels as voltage is driven negative. In external medium with no added calcium,
I
Na
tail current initially increases in amplitude severalfold with the relief of calcium block, then progressively slows and gets smaller, as calcium diffuses out of the layers investing the axon.
I
Na
tails seen just before the current disappears suggest that closing in the absence of channel block is very slow or does not occur.
I
Na
amplitude and kinetics are completely restored when calcium is returned. The results strongly suggest that calcium occupancy is a requirement for channel closing and that nonoccupied channels fold reversibly into a nonfunctional conformation.
Supernovae, an accelerating universe and the cosmological constant
Authors: Kirshner Robert P.
Published: July 2002

Observations of supernova explosions
halfway back to the Big Bang give plausible evidence that the expansion
of the universe has been accelerating since that epoch, approximately 8
billion years ago and suggest that energy associated with the vacuum
itself may be responsible for the acceleration.
The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance
Authors: Schwartz Donald R. , Homanics Gregg E. , Hoyt Dale G. , Klein Ed , Abernethy John , Lazo John S.
Published: July 2002

The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent, is deaminated
in vitro
by Blmh. We used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is the sole enzyme required for BLM deamination. Although some Blmh null mice were viable and reproduced, only about 65% of the expected number survived the neonatal period, revealing an important role for Blmh in neonatal survival. Mice lacking Blmh exhibited variably penetrant tail dermatitis that resembled rodent ringtail. The histopathology of the tail dermatitis was similar to skin lesions in humans with pellagra, necrolytic migratory erythema, and acrodermatitis enteropathica. Compared with controls, Blmh null mice were more sensitive to acute BLM lethality and developed pulmonary fibrosis more readily following BLM treatment. Thus, we have established that Blmh is an essential protectant against BLM-induced death and has an important role in neonatal survival and in maintaining epidermal integrity.
The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors
Authors: Klapper Leah N. , Glathe Stefanie , Vaisman Nora , Hynes Nancy E. , Andrews Glenn C. , Sela Michael , Yarden Yosef
Published: July 2002

The
erbB-2
/
HER2
oncogene is overexpressed in a significant fraction of human carcinomas of the breast, ovary, and lung in a manner that correlates with poor prognosis. Although the encoded protein resembles several receptors for growth factors, no high affinity ligand of ErbB-2 has so far been fully characterized. However, several lines of evidence have raised the possibility that ErbB-2 can augment signal transduction initiated by binding of certain growth factors to their direct receptors. Here, we contrasted these two models of ErbB-2 function: First, examination of a large series of epidermal growth factor (EGF)-like ligands and neuregulins, including virus-encoded ligands as well as related motifs derived from the precursor of EGF, failed to detect interactions with ErbB-2 when this protein was singly expressed. Second, by using antibodies that block inter-ErbB interactions and cells devoid of surface ErbB-2, we learned that signaling by all ligands examined, except those derived from the precursor of EGF, was enhanced by the oncoprotein. These results imply that ErbB-2 evolved as a shared receptor subunit of all ErbB-specific growth factors. Thus, oncogenicity of ErbB-2 in human epithelia may not rely on the existence of a specific ligand but rather on its ability to act as a coreceptor for multiple stroma-derived growth factors.
Induction of a secreted protein by the myxoid liposarcoma oncogene
Authors: Kuroda Masahiko , Wang XiaoZhong , Sok John , Yin Yin , Chung Peter , Giannotti JoAnn W. , Jacobs Kenneth A. , Fitz Lori J. , Murtha-Riel Patricia , Turner Katherine J. , Ron David
Published: July 2002

The TLS-CHOP oncoprotein, found in the majority of human myxoid liposarcomas, consists of a fusion between the transcription factor CHOP/GADD153 and the N terminus of an RNA-binding protein TLS/FUS. Clinical correlation and
in vitro
transformation assays indicate that the N terminus of TLS plays an important role in oncogenesis by TLS-CHOP. Until now, however, the only activity attributed to the oncoprotein is that of inhibiting the binding of transcription factors of the C/EBP class to certain adipogenic target genes, a function that TLS-CHOP shares with the nononcogenic CHOP protein. Here we report the isolation of a gene, DOL54, that is activated in primary fibroblasts by the expression of TLS-CHOP. DOL54 is expressed in the neoplastic component of human myxoid liposarcomas and increases the tumorigenicity of cells injected in nude mice. Activation of
DOL54
requires an intact DNA-binding and dimerization domain in TLS-CHOP, a suitable cellular dimerization partner, and depends on the TLS N terminus. Normal adipocytic differentiation is associated with an early and transient expression of
DOL54,
and the gene encodes a secreted protein that is tightly associated with the cell surface or extracellular matrix. TLS-CHOP thus leads to the unscheduled expression of a gene that is normally associated with adipocytic differentiation.
The adhesion ofPlasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated byP. falciparumerythrocyte membrane protein 1
Authors: Reeder John C. , Cowman Alan F. , Davern Kathleen M. , Beeson James G. , Thompson Jennifer K. , Rogerson Stephen J. , Brown Graham V.
Published: July 2002

Chondroitin sulfate A (CSA) is an important receptor for the sequestration ofPlasmodium falciparumin the placenta, but the parasite ligand involved in adhesion has not previously been identified. Here we report the identification of avargene transcribed in association with binding to CSA and present evidence that theP. falciparumerythrocyte membrane protein 1 product of the gene is the parasite ligand mediating CSA binding. Description of this gene and the implication ofP. falciparumerythrocyte membrane protein 1 as the parasite ligand paves the way to a more detailed understanding of the pathogenesis of placental infection and potential therapeutic strategies targeting the interaction.
Complementary roles of neurotrophin 3 and a
N-
methyl-
d
-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity
Authors: Duan Maoli , Agerman Karin , Ernfors Patrik , Canlon Barbara
Published: July 2002

Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by
N-
methyl-
d
-aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity.
The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium
Authors: Strobl Stefan , Fernandez-Catalan Carlos , Braun Marianne , Huber Robert , Masumoto Hajime , Nakagawa Kazuhiro , Irie Akihiro , Sorimachi Hiroyuki , Bourenkow Gleb , Bartunik Hans , Suzuki Koichi , Bode Wolfram
Published: July 2002

Calpains (calcium-dependent cytoplasmic cysteine proteinases) are implicated in processes such as cytoskeleton remodeling and signal transduction. The 2.3-Å crystal structure of full-length heterodimeric [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the absence of calcium reveals an oval disc-like shape, with the papain-like catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying opposite poles, and the tumor necrosis factor α-like β-sandwich domain dIII and the N-terminal segments dI+dV located between. Compared with papain, the two subdomains dIIa+dIIb of the catalytic unit are rotated against one another by 50°, disrupting the active site and the substrate binding site, explaining the inactivity of calpains in the absence of calcium. Calcium binding to an extremely negatively charged loop of domain dIII (an electrostatic switch) could release the adjacent barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop could also mediate membrane binding, thereby explaining calpains' strongly reduced calcium requirements
in vivo
. The activity status at the catalytic center might be further modulated by calcium binding to the calmodulin domains via the N-terminal linkers.
Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins
Authors: Adcock Gregory J. , Dennis Elizabeth S. , Easteal Simon , Huttley Gavin A. , Jermiin Lars S. , Peacock W. James , Thorne Alan
Published: July 2002

DNA from ancient human remains provides perspectives on the origin
of our species and the relationship between molecular and morphological
variation. We report analysis of mtDNA from the remains of 10 ancient
Australians. These include the morphologically
gracile
Lake Mungo 3 [≈60 thousand years (ka) before present] and three
other
gracile
individuals from Holocene deposits at
Willandra Lakes (<10 ka), all within the skeletal range of living
Australians, and six Pleistocene/early Holocene individuals (15 to
<8 ka) from Kow Swamp with
robust
morphologies outside
the skeletal range of contemporary indigenous Australians. Lake Mungo 3
is the oldest (Pleistocene) “anatomically modern” human from whom
DNA has been recovered. His mtDNA belonged to a lineage that only
survives as a segment inserted into chromosome 11 of the nuclear
genome, which is now widespread among human populations. This lineage
probably diverged before the most recent common ancestor of
contemporary human mitochondrial genomes. This timing of divergence
implies that the deepest known mtDNA lineage from an anatomically
modern human occurred in Australia; analysis restricted to living
humans places the deepest branches in East Africa. The other ancient
Australian individuals we examined have mtDNA sequences descended from
the most recent common ancestor of living humans. Our results indicate
that anatomically modern humans were present in Australia before the
complete fixation of the mtDNA lineage now found in all living people.
Sequences from additional ancient humans may further challenge current
concepts of modern human origins.
My company or my career: managerial achievement and loyalty
Authors: Wajcman Judy , Martin Bill
Published: July 2002

This article examines the objective and subjective aspects of managerial careers in six large firms that have experienced organizational restructuring. We begin by assessing the dominant models of change in career structures, particularly those which emphasize the ‘portfolio’ route to career success. Although elements of the bureaucratic career remain, we find some evidence of the shift predicted by these models amongst the younger generation of managers. However, it is striking that not all young managers are able to take advantage of the opportunities offered by the new career model. Indeed, cultural capital has an increasing impact on career achievement. Younger managers are responding by reorienting away from organizational loyalty towards a concern with individual career projects.
A Comparative Evaluation of Approaches to Urban Crime Pattern Analysis
Authors: Craglia Massimo , Haining Robert , Wiles Paul
Published: July 2002

The increased availability of digital data and the increased scrutiny of public expenditure are opening new opportunities for detailed spatial analysis of social behaviour and policy initiatives to target resources where they are most needed. Two such policy areas in which the use of GIS combined with spatial analysis tools has made significant progress are health and police services, which are at the top of the political agenda due to increasing 'demand' and spiralling costs. Against this background, this paper presents the results of a collaborative research project carried out in Sheffield on the use of GIS for crime pattern analysis. The research described is significant in a number of respects: it is based on high-quality detailed crime data and geographical data for the whole of Sheffield; it compares two different methodologies for crime pattern analysis, one developed specifically for crime, the other for health research; and it demonstrates the policy value of this transfer of methodologies across disciplines.
Correlating the Knowledge-base of Cities with Economic Growth
Authors: Lever W.F.
Published: July 2002

The competitive advantage of cities in the developed world is increasingly thought to lie in their superior access to the knowledge-base. The generation of new knowledge through investment in research and development leads to new products, services and processes which form the basis of the new economy. Attempts to correlate knowledge creation with economic growth have therefore tended to use R&D measures such as the numbers of research establishments in a rather narrow sense. This paper develops a much wider measure of the knowledge-base comprising tacit knowledge, codified knowledge and knowledge infrastructure for 19 European cities. With the exception of the two world cities, London and Paris, which significantly underperform, there is a broad relationship between the quality of the knowledge-base and economic change as measured by the competitive shift-share residual.
Employment Centres in Greater Cleveland: Evidence of Evolution in a Formerly Monocentric City
Authors: Bogart William T. , Ferry William C.
Published: July 2002

This paper uses US Census Bureau data from 1990 to identify employment centres in the five counties surrounding Cleveland, Ohio. The results indicate the extent to which the former dominance of downtown Cleveland has been eroded by the growth of suburban employment centres. Location quotient analysis is used to identify the specialisations of each of the employment centres. The results illustrate the extent to which the changes in urban form identified by researchers examining cities such as Los Angeles and Chicago have become the norm for cities throughout the US.
Cross-cultural views on human development in the third millennium
Authors: Dasen Pierre R. , Mishra Ramesh C.
Published: July 2002

The authors examine the prospects of a cross-cultural approach for research in human development. They first examine the apparent conflict between the positivistic and the constructionist paradigms, and examine their methodological implications. They argue for a midline position, seeing the seemingly opposed paradigms as complementary rather than antithetical. The major part of the paper lists the further developments needed in the field, in particular taking new theories to the cross-cultural test more quickly, and working out culturally appropriate applications to social issues. Shorter sections are devoted to the choice of appropriate theoretical frameworks, to the development of “indigenous psychologies” and to the working conditions of researchers in different contexts. The authors conclude that the situation of a cross-cultural approach to human development has improved significantly in the last two decades, but that there is still a lot to be done to completely disengage developmental psychology from its inherent ethnocentrism by “taking culture seriously”.
The Connection Between Syntactic Awareness and Reading: Evidence from Portuguese-speaking Children Taught by a Phonic Method
Authors: Rego Lucia Lins Browne
Published: July 2002

Most studies that have investigated the connection between syntactic awareness and reading acquisition involved English-speaking subjects and have not considered the influence of the teaching method. These studies have consistently reported strong connections between performance in syntactic awareness tasks and measures of decoding. The purpose of the present study was to investigate the connection between syntactic awareness and reading acquisition in a group of 48 Brazilian children who were taught to read by a phonic method. The children were given syntactic awareness and phonological awareness tasks before they began to read and were evaluated in contextual facilitation, decoding skills, and reading comprehension during their first year of reading instruction. The results suggest that although the connection between syntactic awareness and contextual facilitation is an essential one, the link between syntactic awareness and the development of decoding skills is sensitive to how often children are encouraged to use contextual strategies in learning to read. Children learning a regular orthography through explicit teaching of letter-sound correspondences can make considerable progress in decoding which is not dependent on syntactic awareness.
Tutoring Interactions between Young Children: How Symmetry can Modify Asymmetrical Interactions
Authors: Verba Mina
Published: July 2002

The constructivist and interactionist approach to cognitive development emphasises the importance of the active participation of children in social interactions and their contribution to knowledge acquisition. Peer tutoring is one way of making such a contribution. During the preschool period, children develop specific skills that allow them to assist and guide less competent peers through the learning process. This study was aimed at gaining insight into the potentials of tutoring in young children, and at demonstrating the role of the symmetrical relationship which prevails in peer interaction in expert-novice problem-solving activity. An adult trained 24 boys and girls for a building task. The young “experts” were then observed with 48 same- and different-age novices of the same sex. The results showed that already at this young age, the experts and novices exhibited asymmetric interactions fulfilling the essential functions of tutoring. The tutors geared their actions to the task demands but were not yet sensitive to the novice’s needs. Qualitative analysis of interactive episodes indicate that the symmetrical nature of the two partners’ skills and statuses brought the tutoring closer to several forms of co-operation or to specific parallel work: While guiding the partner, the expert child shared the problem-solving activity with the novice, consolidating his/her own know-how at the same time. The shift—under some circumstances—from asymmetrical interactions to symmetrical co-elaboration suggests a new conception of sociocognitive functioning in the construction of knowledge.
Children’s Play Preferences, Construction Play with Blocks, and Visual-spatial Skills: Are they Related?
Authors: Caldera Yvonne M. , Culp Anne McDonald , O’Brien Marion , Truglio Rosemarie T. , Alvarez Mildred , Huston Aletha C.
Published: July 2002

Fifty-one preschoolers’ play preferences, skills at assembling block structures, and spatial abilities were recorded in this study. There were no sex differences in children’s visual-spatial skills, and play with art materials and children’s free and structured play with blocks were related to spatial visualisation. Two patterns emerged from the findings: (1) activity and performance representing skills in spatial visualisation and visual-motor coordination; and (2) creativity, or the ability to break set and to produce varied solutions using visual materials. Future research might examine the extent to which children’s play activities and experiences predict these types of skills.
Application of Cognitive Theory to Training and Design Solutions for Age-related Computer Use
Authors: Mead Sherry E. , Batsakes Peter , Fisk Arthur D. , Mykityshyn Amy
Published: July 2002

As the prevalence of computer-based technologies increases throughout society, so does the likelihood that older adults will be required to interact with them. Unfortunately, such systems often appear to older adults to be too hard to use and too hard to learn. We provide examples highlighting the opportunities available to behavioural science to affect training and system design through practically relevant research. We focus on our research on ageing, computer use, and training to support our assertion that applied research aimed at designing training materials and system interfaces to enhance the performance of older adults can and should be driven by psychological theory. The data presented and studies reviewed here clearly demonstrate that theory is critical for predicting age differences in computer use, for guiding the development of both training and design interventions for older computer users, and for reconciling conflicting findings in the design-evaluation literature.
Genetic Disposition for Global Maturity: An Explanation for Genetic Effects on Parental Report on ADHD
Authors: Steffensson Birgitta , Larsson Jan-Olov , Fried Ingegärd , El-Sayed Eman , Rydelius Per-Anders , Lichtenstein Paul
Published: July 2002

Attention deficit hyperactivity disorder (ADHD) has been shown to be substantially influenced by genetic factors. However it is still not known how these effects are mediated. The aim of this study is to evaluate whether genetic disposition for global maturity could be a mediator of the well-known findings of genetic factors for ADHD symptoms. A total of 1480 pairs of twins aged 8-9 years were identified through the population-based Swedish Twin Registry. A mailed questionnaire with items from DSM-III-R for ADHD and items concerning global maturity were completed by the parents. The results showed that global maturity mediated part of genetic effects for ADHD for both boys and girls. There were also genetic, shared environmental, as well as nonshared environmental effects unique to ADHD not in common with global maturity. Thus, there are at least two pathways through which genetic effects can influence ADHD: one through predisposition for maturational lag and one unique to ADHD, possibly mediated by personality. The results indicate that maturational lag could be of importance for treatment and prognosis of ADHD.
Children’s Spontaneous Correction of False Beliefs in a Conversation Partner
Authors: Terwogt Mark Meerum , Rieffe Carolien , Tuijn Anne H. , Harris Paul L. , Mant Isobel
Published: July 2002

Preschool children were tested for their ability to vary the verbal information they offered regarding an object’s location depending on whether the person searching for that object was likely to infer or misinfer its location. Older children (mean age: 5 years 3 months) offered information in a selective fashion: If the location of the hidden object could be readily inferred by their conversation partner, they indicated its location only when explicitly asked but if its location was likely to be misinferred, they often indicated that location prior to being explicitly asked. The response pattern of younger children (mean age: 3 years 6 months) was less conclusive. A relatively large number of younger children took matters “into their own hands” and immediately grasped for the concealed object, irrespective of whether its location could be readily inferred. However, the reactions of the remaining 3-year-olds suggest that even at this age children may be sensitive to the likely beliefs of their conversation partner.
An Ordinal Scale for Transitive Reasoning by Means of a Deductive Strategy
Authors: Verweij Anton C. , Sijtsma Klaas , Koops Willem
Published: July 2002

Transitivity tasks with either equality or inequality relations between three, four, or five objects were presented by means of a successive and a simultaneous presentation procedure to 124 third-grade primary schoolchildren. Equality tasks were easier than inequality tasks. Inequality tasks were more difficult when presented successively than simultaneously. Difficulty of equality tasks was not affected by presentation procedure. These findings were interpreted in terms of the Fuzzy Trace Theory. Successively presented inequality tasks induced more deductive reasoning strategies, and simultaneously presented tasks induced both positional and reductional strategies. As perceptual differences between objects increased, more visual strategies were used.

These conclusions were used to construct a series of nine tasks geared at inducing transitive reasoning by means of a deductive strategy. Mokken scale analysis was used to construct an ordinal scale for transitive reasoning. Data were collected from 417 second- through fourth-grade primary school children. The scale score correlated highly with arithmetic skills and insight into the quantity concept. Possibilities for future transitivity research, supported by advanced psychometric methods, are discussed.
Pedagogy, information and communications technology and teachers' professional knowledge
Authors: Leach Jenny , Moon Bob
Published: July 2002

In this article UK governmental policy imperatives to apply new forms of information and communications technology (ICT) to school improvement are explored, with particular reference to the National Curriculum for England and Wales. The analysis juxtaposes the piecemeal, random way in which ICT is used in National Curriculum programmes of study and schemes of work with the government rhetoric that requires coherent planning and integration of ICT within all aspects of teaching learning. The article argues that this contradiction within the policy process could be overcome if a stronger conceptualization of teachers' professional knowledge was embraced. An example of such a conceptualization is presented and this is exemplified by accounts of teachers' development of ICT within their pedagogic practice.
Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis‐inducing activity
Authors: Yui Satoru , Nakatani Yuichi , Hunter Michael J. , Chazin Walter J. , Yamazaki Masatoshi
Published: July 2002

Background: Calprotectin is a calcium‐binding and zinc‐binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor‐related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc‐reversible manner.

Aim: The present study was undertaken to elucidate which subunit is responsible for the apoptosis‐inducing activity, and to explore the mechanism of zinc‐reversible apoptosis induction.

Methods: The apoptosis‐inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL‐4 lymphoma cells in vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut‐off dialysis membrane.

Results: The cytotoxicity of rhMRP14 against EL‐4 cells was first detected at 10 μM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 μM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 μM). When the cells were cultured in divalent cation‐depleted medium, each dose‐response curve was shifted to about a four‐fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane‐impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time‐course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions.

Conclusion: These data indicate that calprotectin has higher specific activity to induce apoptosis than the individual subunits, and that the mechanism is exclusion of zinc from target cells.