bluuebunny/crossref_metadata_2025 huggingface dataset:
The mechanism of isoluminant chromatic motion perception
Authors: Lu Zhong-Lin , Lesmes Luis A. , Sperling George
Published: July 2002

An isoluminant chromatic display is a color display in which the component colors have been so carefully equated in luminance that they stimulate only color-sensitive perceptual mechanisms and not luminance-sensitive mechanisms. The nature of the mechanism by which isoluminant chromatic motion is perceived is an important issue because color and motion processing historically have been associated with different neural pathways. Here we show that isoluminant chromatic motion (
i
) fails a pedestal test, (
ii
) has a temporal tuning function that declines to half-amplitude at 3–6 Hz, and (
iii
) is perceived equally well when the entire motion sequence is presented monocularly (entire motion sequence to one eye) versus interocularly (the frames of motion sequence alternate between eyes so that neither eye individually could perceive motion). These three characteristics indicate that chromatic motion is detected by the third-order motion system. Based on this theory, it was possible to take a moving isoluminant red–green grating and, by simply increasing the chromatic contrast of the green component, to generate the full gamut of motion percepts, from compelling smooth motion to motion standstill. The perception of motion standstill when the third-order mechanism is nullified indicates that there is no other motion computation available for purely chromatic motion. It follows that isoluminant chromatic motion is not computed by specialized chromatic motion mechanisms within a color pathway but by the third-order motion system at a brain level where binocular inputs of form, color, depth, and texture are simultaneously available and where selective attention can exert a major influence.
Basonuclin, a zinc finger protein of keratinocytes and reproductive germ cells, binds to the rRNA gene promoter
Authors: Iuchi Shiro , Green Howard
Published: July 2002

Basonuclin is a protein containing three pairs of C
2
H
2
zinc fingers. The protein has been found in the basal (germinal) cell layer of stratified squamous epithelia, such as the epidermis, and in germ cells of the testis and ovary. We show here that the human protein has specific affinity for a segment of the promoter of the gene for rRNA. Basonuclin interacts with two separate parts of the promoter, each possessing dyad symmetry. The upstream part, but not the downstream part, is known to bind UBF1, a transcription factor for rDNA. Basonuclin is likely to be a cell-type-specific regulatory protein for rDNA transcription.
Pathways for proton release during ubihydroquinone oxidation by the
bc
1
complex
Authors: Crofts Antony R. , Hong Sangjin , Ugulava Natalia , Barquera Blanca , Gennis Robert , Guergova-Kuras Mariana , Berry Edward A.
Published: July 2002

Quinol oxidation by the
bc
1
complex of
Rhodobacter sphaeroides
occurs from an enzyme–substrate complex formed between quinol bound at the Q
o
site and the iron–sulfur protein (ISP) docked at an interface on cytochrome
b
. From the structure of the stigmatellin-containing mitochondrial complex, we suggest that hydrogen bonds to the two quinol hydroxyl groups, from Glu-272 of cytochrome
b
and His-161 of the ISP, help to stabilize the enzyme–substrate complex and aid proton release. Reduction of the oxidized ISP involves H transfer from quinol. Release of the proton occurs when the acceptor chain reoxidizes the reduced ISP, after domain movement to an interface on cytochrome
c
1
. Effects of mutations to the ISP that change the redox potential and/or the pK on the oxidized form support this mechanism. Structures for the complex in the presence of inhibitors show two different orientations of Glu-272. In stigmatellin-containing crystals, the side chain points into the site, to hydrogen bond with a ring hydroxyl, while His-161 hydrogen bonds to the carbonyl group. In the native structure, or crystals containing myxothiazol or β-methoxyacrylate-type inhibitors, the Glu-272 side chain is rotated to point out of the site, to the surface of an external aqueous channel. Effects of mutation at this residue suggest that this group is involved in ligation of stigmatellin and quinol, but not quinone, and that the carboxylate function is essential for rapid turnover. H
+
transfer from semiquinone to the carboxylate side chain and rotation to the position found in the myxothiazol structure provide a pathway for release of the second proton.
Multijurisdictional economies, the Tiebout Hypothesis, and sorting
Authors: Wooders Myrna H.
Published: July 2002

The Tiebout Hypothesis asserts that, when it
is efficient to have multiple jurisdictions providing local public
goods, then competition between jurisdictions for residents will lead
to a near-optimal outcome. Research from cooperative game theory both
provides a foundation for the hypothesis and extends the hypothesis to
diverse situations where small groups of participants are effective.
Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: Expression of
15
N-lysine- and
13
C-glycine-labeled opsin in a stable cell line
Authors: Eilers Markus , Reeves Philip J. , Ying Weiwen , Khorana H. Gobind , Smith Steven O.
Published: July 2002

The apoprotein corresponding to the mammalian photoreceptor rhodopsin has been expressed by using suspension cultures of HEK293S cells in defined media that contained 6-
15
N-lysine and 2-
13
C-glycine. Typical yields were 1.5–1.8 mg/liter. Incorporation of 6-
15
N-lysine was quantitative, whereas that of 2-
13
C-glycine was about 60%. The rhodopsin pigment formed by binding of 11-
cis
retinal was spectrally indistinguishable from native bovine rhodopsin. Magic angle spinning (MAS) NMR spectra of labeled rhodopsin were obtained after its incorporation into liposomes. The
15
N resonance corresponding to the protonated retinylidene Schiff base nitrogen was observed at 156.8 ppm in the MAS spectrum of 6-
15
N-lysine-labeled rhodopsin. This chemical shift corresponds to an effective Schiff base-counterion distance of greater than 4 Å, consistent with structural water in the binding site hydrogen bonded with the Schiff base nitrogen and the Glu-113 counterion. The present study demonstrates that structural studies of rhodopsin and other G protein-coupled receptors by using MAS NMR are feasible.
Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis
Authors: Hamza Iqbal , Schaefer Mark , Klomp Leo W. J. , Gitlin Jonathan D.
Published: July 2002

The delivery of copper to specific sites within the cell is mediated by distinct intracellular carrier proteins termed copper chaperones. Previous studies in
Saccharomyces cerevisiae
suggested that the human copper chaperone HAH1 may play a role in copper trafficking to the secretory pathway of the cell. In this current study, HAH1 was detected in lysates from multiple human cell lines and tissues as a single-chain protein distributed throughout the cytoplasm and nucleus. Studies with a glutathione
S
-transferase-HAH1 fusion protein demonstrated direct protein–protein interaction between HAH1 and the Wilson disease protein, which required the cysteine copper ligands in the amino terminus of HAH1. Consistent with these
in vitro
observations, coimmunoprecipitation experiments revealed that HAH1 interacts with both the Wilson and Menkes proteins
in vivo
and that this interaction depends on available copper. When these studies were repeated utilizing three disease-associated mutations in the amino terminus of the Wilson protein, a marked diminution in HAH1 interaction was observed, suggesting that impaired copper delivery by HAH1 constitutes the molecular basis of Wilson disease in patients harboring these mutations. Taken together, these data provide a mechanism for the function of HAH1 as a copper chaperone in mammalian cells and demonstrate that this protein is essential for copper homeostasis.
Global GacA-steered control of cyanide and exoprotease production in
Pseudomonas fluorescens
involves specific ribosome binding sites
Authors: Blumer Caroline , Heeb Stephan , Pessi Gabriella , Haas Dieter
Published: July 2002

The conserved two-component regulatory system GacS/GacA determines the expression of extracellular products and virulence factors in a variety of Gram-negative bacteria. In the biocontrol strain CHA0 of
Pseudomonas fluorescens
, the response regulator GacA is essential for the synthesis of extracellular protease (AprA) and secondary metabolites including hydrogen cyanide. GacA was found to exert its control on the hydrogen cyanide biosynthetic genes (
hcnABC
) and on the
aprA
gene indirectly via a posttranscriptional mechanism. Expression of a translational
hcnA
′-′
lacZ
fusion was GacA-dependent whereas a transcriptional
hcnA-lacZ
fusion was not. A distinct recognition site overlapping with the ribosome binding site appears to be primordial for GacA-steered regulation. GacA-dependence could be conferred to the
Escherichia coli lacZ
mRNA by a 3-bp substitution in the ribosome binding site. The gene coding for the global translational repressor RsmA of
P. fluorescens
was cloned. RsmA overexpression mimicked partial loss of GacA function and involved the same recognition site, suggesting that RsmA is a downstream regulatory element of the GacA control cascade. Mutational inactivation of the chromosomal
rsmA
gene partially suppressed a
gacS
defect. Thus, a central, GacA-dependent switch from primary to secondary metabolism may operate at the level of translation.
Dynamin-dependent endocytosis of ionotropic glutamate receptors
Authors: Carroll Reed C. , Beattie Eric C. , Xia Houhui , Lüscher Christian , Altschuler Yoram , Nicoll Roger A. , Malenka Robert C. , von Zastrow Mark
Published: July 2002

Little is known about the mechanisms that regulate the number of ionotropic glutamate receptors present at excitatory synapses. Herein, we show that GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) are removed from the postsynaptic plasma membrane of cultured hippocampal neurons by rapid, ligand-induced endocytosis. Although endocytosis of AMPARs can be induced by high concentrations of AMPA without concomitant activation of
N
-methyl-
d
-aspartate (NMDA) receptors (NMDARs), NMDAR activation is required for detectable endocytosis induced by synaptically released glutamate. Activated AMPARs colocalize with AP2, a marker of endocytic coated pits, and endocytosis of AMPARs is blocked by biochemical inhibition of clathrin-coated pit function or overexpression of a dominant-negative mutant form of dynamin. These results establish that ionotropic receptors are regulated by dynamin-dependent endocytosis and suggest an important role of endocytic membrane trafficking in the postsynaptic modulation of neurotransmission.
Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors
Authors: Járai Zoltán , Wagner Jens A. , Varga Károly , Lake Kristy D. , Compton David R. , Martin Billy R. , Zimmer Anne M. , Bonner Tom I. , Buckley Nancy E. , Mezey Eva , Razdan Raj K. , Zimmer Andreas , Kunos George
Published: July 2002

Cannabinoids, including the endogenous ligand arachidonyl ethanolamide (anandamide), elicit not only neurobehavioral but also cardiovascular effects. Two cannabinoid receptors, CB1 and CB2, have been cloned, and studies with the selective CB1 receptor antagonist SR141716A have implicated peripherally located CB1 receptors in the hypotensive action of cannabinoids. In rat mesenteric arteries, anandamide-induced vasodilation is inhibited by SR141716A, but other potent CB1 receptor agonists, such as HU-210, do not cause vasodilation, which implicates an as-yet-unidentified receptor in this effect. Here we show that “abnormal cannabidiol” (Abn-cbd) is a neurobehaviorally inactive cannabinoid that does not bind to CB1 receptors, yet causes SR141716A-sensitive hypotension and mesenteric vasodilation in wild-type mice and in mice lacking CB1 receptors or both CB1 and CB2 receptors. Hypotension by Abn-cbd is also inhibited by cannabidiol (20 μg/g), which does not influence anandamide- or HU-210-induced hypotension. In the rat mesenteric arterial bed, Abn-cbd-induced vasodilation is unaffected by blockade of endothelial NO synthase, cyclooxygenase, or capsaicin receptors, but it is abolished by endothelial denudation. Mesenteric vasodilation by Abn-cbd, but not by acetylcholine, sodium nitroprusside, or capsaicine, is blocked by SR141716A (1 μM) or by cannabidiol (10 μM). Abn-cbd-induced vasodilation is also blocked in the presence of charybdotoxin (100 nM) plus apamin (100 nM), a combination of K
+
-channel toxins reported to block the release of an endothelium-derived hyperpolarizing factor (EDHF). These findings suggest that Abn-cbd and cannabidiol are a selective agonist and antagonist, respectively, of an as-yet-unidentified endothelial receptor for anandamide, activation of which elicits NO-independent mesenteric vasodilation, possibly by means of the release of EDHF.
Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: An efficient mechanism for the regulation of angiogenesis
Authors: Struman Ingrid , Bentzien Frauke , Lee Hsinyu , Mainfroid Véronique , D’Angelo Gisela , Goffin Vincent , Weiner Richard I. , Martial Joseph A.
Published: July 2002

Angiogenesis, the process of development of a new microvasculature, is regulated by a balance of positive and negative factors. We show bothin vivoandin vitrothat the members of the human prolactin/growth hormone family, i.e., human prolactin, human growth hormone, human placental lactogen, and human growth hormone variant are angiogenic whereas their respective 16-kDa N-terminal fragments are antiangiogenic. The opposite actions are regulated in part via activation or inhibition of mitogen-activated protein kinase signaling pathway. In addition, the N-terminal fragments stimulate expression of type 1 plasminogen activator inhibitor whereas the intact molecules have no effect, an observation consistent with the fragments acting via separate receptors. The concept that a single molecule encodes both angiogenic and antiangiogenic peptides represents an efficient model for regulating the balance of positive and negative factors controlling angiogenesis. This hypothesis has potential physiological importance for the control of the vascular connection between the fetal and maternal circulations in the placenta, where human prolactin, human placental lactogen, and human growth hormone variant are expressed.
Ligand-dependent activation of transcription
in vitro
by retinoic acid receptor α/retinoid X receptor α heterodimers that mimics transactivation by retinoids
in vivo
Authors: Dilworth F. Jeffrey , Fromental-Ramain Catherine , Remboutsika Eumorphia , Benecke Arndt , Chambon Pierre
Published: July 2002

All-trans and 9-cis retinoic acids (RA) signals are transduced by
retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers
that act as functional units controlling the transcription of
RA-responsive genes. With the aim of elucidating the underlying
molecular mechanisms, we have developed an
in vitro
transcription system using a chromatin template made up of a minimal
promoter and a direct repeat with 5-spacing-based RA response element.
RARα and RXRα were expressed in and purified from
baculovirus-infected
Sf9
cells, and transcription was
carried out by using naked DNA or chromatin templates. Transcription
from naked templates was not affected by the presence of RA and/or
RAR/RXR heterodimers. In contrast, very little transcription occurred
from chromatin templates in the absence of RA or RAR/RXR heterodimers
whereas their addition resulted in a dosage-dependent stimulation of
transcription that never exceeded that occurring on naked DNA
templates. Most importantly, the addition of synthetic agonistic or
antagonistic retinoids to the chromatin transcription system mimicked
their stimulatory or inhibitory action
in vivo
, and
activation by a RXR-specific retinoid was subordinated to the binding
of an agonist ligand to the RAR partner. Moreover, the addition of the
p300 coactivator generated a synergistic enhancement of transcription.
Thus, the dissection of this transcription system ultimately should
lead to the elucidation of the molecular mechanisms by which RAR/RXR
heterodimers control transcription in a ligand-dependent manner.
A strategy for rapid sequencing of heparan sulfate and heparin saccharides
Authors: Turnbull Jeremy E. , Hopwood John J. , Gallagher John T.
Published: July 2002

Sulfated glycosaminoglycans (GAGs) are
linear polysaccharides of repeating disaccharide sequences on which are
superimposed highly complex and variable patterns of sulfation,
especially in heparan sulfate (HS). HS and the structurally related
heparin exert important biological functions, primarily by interacting
with proteins and regulating their activities. Evidence is accumulating
that these interactions depend on specific saccharide sequences, but
the lack of simple, direct techniques for sequencing GAG saccharides
has been a major obstacle to progress. We describe how HS and heparin
saccharides can be sequenced rapidly by using an integrated strategy
with chemical and enzymic steps. Attachment of a reducing-end
fluorescent tag establishes a reading frame. Partial selective chemical
cleavage at internal
N
-sulfoglucosamine residues with
nitrous acid then creates a set of fragments of defined sizes.
Subsequent digestion of these fragments with combinations of
exosulfatases and exoglycosidases permits the selective removal of
specific sulfates and monosaccharides from their nonreducing ends. PAGE
of the products yields a pattern of fluorescent bands from which the
saccharide sequence can be read directly. Data are presented on
sequencing of heparin tetrasaccharides and hexasaccharides of known
structure; these data show the accuracy and versatility of this
sequencing strategy. Data also are presented on the application of the
strategy to the sequencing of an HS decasaccharide of unknown
structure. Application and further development of this sequencing
strategy, called integral glycan sequencing, will accelerate progress
in defining the structure–activity relationships of these complex GAGs
and lead to important insights into their biological functions.
Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression
Authors: McGregor Lisa M. , McCune Bryan K. , Graff Jeremy R. , McDowell Philip R. , Romans Katherine E. , Yancopoulos George D. , Ball Douglas W. , Baylin Stephen B. , Nelkin Barry D.
Published: July 2002

Although initiating mutations in the ret protooncogene have been found in familial and sporadic medullary thyroid carcinoma (MTC), the molecular events underlying subsequent tumor progression stages are unknown. We now report that changes in trk family neurotrophin receptor expression appear to be involved in both preneoplastic thyroid C cell hyperplasia and later tumor progression. Only a subset of normal C cells expresses trk family receptors, but, in C cell hyperplasia, the affected cells consistently express trkB, with variable expression of trkA and trkC. In later stages of gross MTC tumors, trkB expression was substantially reduced, while trkC expression was increased and often intense. In a cell culture model of MTC, exogenous trkB expression resulted in severely impaired tumorigenicity and was associated with 11-fold lower levels of the angiogenesis factor vascular endothelial growth factor. These results suggest that trk family receptor genes participate in MTC development and progression, and, in particular, that trkB may limit MTC tumor growth by inhibition of angiogenesis.
A synthetic inhibitor of histone deacetylase, MS-27-275, with marked
in vivo
antitumor activity against human tumors
Authors: Saito Akiko , Yamashita Takashi , Mariko Yukiyasu , Nosaka Yasuhito , Tsuchiya Katsutoshi , Ando Tomoyuki , Suzuki Tsuneji , Tsuruo Takashi , Nakanishi Osamu
Published: July 2002

Synthetic benzamide derivatives were investigated for their ability to inhibit histone deacetylase (HDA). In this study, one of the most active benzamide derivatives, MS-27-275, was examined with regard to its biological properties and antitumor efficacy. MS-27-275 inhibited partially purified human HDA and caused hyperacetylation of nuclear histones in various tumor cell lines. It behaved in a manner similar to other HDA inhibitors, such as sodium butyrate and trichostatin A; MS-27-275 induced p21
WAF1/CIP1
and gelsolin and changed the cell cycle distribution, decrease of S-phase cells, and increase of G
1
-phase cells. The
in vitro
sensitivity spectrum of MS-27-275 against various human tumor cell lines showed a pattern different than that of a commonly used antitumor agent, 5-fluorouracil, and, of interest, the accumulation of p21
WAF1/CIP1
tended to be faster and greater in the cell lines sensitive to MS-27-275. MS-27-275 administered orally strongly inhibited the growth in seven of eight tumor lines implanted into nude mice, although most of these did not respond to 5-fluorouracil. A structurally analogous compound to MS-27-275 without HDA-inhibiting activity showed neither the biological effects in cell culture nor the
in vivo
therapeutic efficacy. These results suggest that MS-27-275 acts as an antitumor agent through HDA inhibition and may provide a novel chemotherapeutic strategy for cancers insensitive to traditional antitumor agents.
Potent antimalarial activity of clotrimazole in
in vitro
cultures of
Plasmodium falciparum
Authors: Tiffert Teresa , Ginsburg Hagai , Krugliak Miriam , Elford Barry C. , Lew Virgilio L.
Published: July 2002

The increasing resistance of the malaria parasite
Plasmodium falciparum
to currently available drugs demands a continuous effort to develop new antimalarial agents. In this quest, the identification of antimalarial effects of drugs already in use for other therapies represents an attractive approach with potentially rapid clinical application. We have found that the extensively used antimycotic drug clotrimazole (CLT) effectively and rapidly inhibited parasite growth in five different strains of
P. falciparum
,
in vitro
, irrespective of their chloroquine sensitivity. The concentrations for 50% inhibition (IC
50
), assessed by parasite incorporation of [
3
H]hypoxanthine, were between 0.2 and 1.1 μM. CLT concentrations of 2 μM and above caused a sharp decline in parasitemia, complete inhibition of parasite replication, and destruction of parasites and host cells within a single intraerythrocytic asexual cycle (≈48 hr). These concentrations are within the plasma levels known to be attained in humans after oral administration of the drug. The effects were associated with distinct morphological changes. Transient exposure of ring-stage parasites to 2.5 μM CLT for a period of 12 hr caused a delay in development in a fraction of parasites that reverted to normal after drug removal; 24-hr exposure to the same concentration caused total destruction of parasites and parasitized cells. Chloroquine antagonized the effects of CLT whereas mefloquine was synergistic. The present study suggests that CLT holds much promise as an antimalarial agent and that it is suitable for a clinical study in
P. falciparum
malaria.
Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice
Authors: Schönbeck U. , Sukhova G. K. , Shimizu K. , Mach F. , Libby P.
Published: July 2002

Interruption of inflammatory pathways may provide a novel approach to the therapy of atherosclerosis. Recently, we and others have implicated the immune mediator dyad CD40/CD40L (CD40 ligand), which is expressed on endothelial and smooth muscle cells, macrophages, and T lymphocytes within human atherosclerotic lesions, in aspects of atherogenesis and the acute coronary syndromes, including regulation of matrix metalloproteinases, procoagulant activity, cytokines, etc.In vivo, interruption of CD40 signaling reduced the initiation and early phases of atheroma formation in hypercholesterolemic mice. However, whether interruption of CD40 signaling can retard the progression or even regress established lesions remains unknown. We report here that anti-CD40L antibody treatment of randomly assigned low-density lipoprotein receptor-deficient mice during the second half of a 26-week regimen of high-cholesterol diet did not regress, but did significantly reduce further evolution of established atherosclerotic lesions within the aortic arch and particularly the thoracic and abdominal aorta, as compared with control treatment (application of rat-IgG or saline; 13 weeks, continued high-cholesterol diet). In addition to limiting lesion progression, anti-CD40L treatment changed the composition of atheroma in manners thought to favor plaque stability, e.g., reduced relative content of macrophages and lipid, as well as increased relative content of smooth muscle cells and collagen. These data implicate CD40/CD40L as crucial mediators not only in the initial events of atherogenesis but also during the evolution of established atheroma. This study lends further support to the importance of this specific inflammatory signaling pathway in atherosclerosis and its complications.
Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch for the destruction of p27
Xic1
Authors: Swanson Craig , Ross John , Jackson Peter K.
Published: July 2002

The action of cyclin-dependent kinases (CDKs) is regulated by phosphorylation, cyclin levels, the abundance of CDK inhibitors, and, as recently has been shown for cyclin B/cdc2, their localization. It is unclear how localization regulates the action of cyclin E/Cdk2 and its inhibitors. Here, we show that the closest known
Xenopus
laevis
homolog of mammalian Cdk2 inhibitors p27
Kip1
and p21
CIP1
, Xic1, is concentrated, ubiquitinated, and destroyed in the nucleus. Furthermore, Xic1 destruction requires nuclear import, but not nuclear export, and requires the formation of a transport-competent nuclear envelope, but not interactions between the lamina and chromatin. We show that (
i
) cyclin E/Cdk2 and Xic1 are transported into the nucleus as a complex and that Xic1 destruction requires the activity of cyclin E, (
ii
) that phosphorylation of Xic1 by cyclin E/Cdk2 bypasses the requirement for nuclear formation, and (
iii
) that the phosphorylation of Xic1 by cyclin E/Cdk2 is concentration dependent and likely realized through second-order interactions between stable cyclin E/Cdk2/Xic1 ternary complexes. Based on these results we propose a model wherein nuclear accumulation of the cyclin E/Cdk2/Xic1 complex triggers a concentration-dependent switch that promotes the phosphorylation of Xic1 and, consequently, its ubiquitination and destruction, thus allowing subsequent activation of cyclin E/Cdk2.
Increased discrimination of “false memories” in autism spectrum disorder
Authors: Beversdorf David Q. , Smith Brian W. , Crucian Gregory P. , Anderson Jeffrey M. , Keillor Jocelyn M. , Barrett Anna M. , Hughes John D. , Felopulos Gretchen J. , Bauman Margaret L. , Nadeau Stephen E. , Heilman Kenneth M.
Published: July 2002

Individuals with autism spectrum disorder (ASD) have impaired ability to use context, which may manifest as alterations of relatedness within the semantic network. However, impairment in context use may be more difficult to detect in high-functioning adults with ASD. To test context use in this population, we examined the influence of context on memory by using the “false memory” test. In the false memory task, lists of words were presented to high-functioning subjects with ASD and matched controls. Each list consists of words highly related to an index word not on the list. Subjects are then given a recognition test. Positive responses to the index words represent false memories. We found that individuals with ASD are able to discriminate false memory items from true items significantly better than are control subjects. Memory in patients with ASD may be more accurate than in normal individuals under certain conditions. These results also suggest that semantic representations comprise a less distributed network in high-functioning adults with ASD. Furthermore, these results may be related to the unusually high memory capacities found in some individuals with ASD. Research directed at defining the range of tasks performed superiorly by high-functioning individuals with ASD will be important for optimal vocational rehabilitation.
Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development
Authors: Dunn Karen J. , Williams Bart O. , Li Yi , Pavan William J.
Published: July 2002

Wnt1 signaling has been implicated as one factor involved in neural crest-derived melanocyte (NC-M) development. Mice deficient for both Wnt1 and Wnt3a have a marked deficiency in trunk neural crest derivatives including NC-Ms. We have used cell lineage-directed gene targeting of Wnt signaling genes to examine the effects of Wnt signaling in mouse neural crest development. Gene expression was directed to cell lineages by infection with subgroup A avian leukosis virus vectors in lines of transgenic mice that express the retrovirus receptor
tv-a
. Transgenic mice with
tva
in either nestin-expressing neural precursor cells (line
Ntva
) or dopachrome tautomerase (DCT)-expressing melanoblasts (line DCT
tva
) were analyzed. We overstimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to
Ntva
+
cells and transfer of β-catenin to DCT
tva
+
NC-M precursor cells. In both methods, NC-M expansion and differentiation were effected. Significant increases were observed in the number of NC-Ms [melanin
+
and tyrosinase-related protein 1 (TYRP1)
+
cells], the differentiation of melanin
−
TYRP1
+
cells to melanin
+
TYRP1
+
NC-Ms, and the intensity of pigmentation per NC-M. These data are consistent with Wnt1 signaling being involved in both expansion and differentiation of migrating NC-Ms in the developing mouse embryo. The use of lineage-directed gene targeting will allow the dissection of signaling molecules involved in NC development and is adaptable to other mammalian developmental systems.
A
Ufd2/D4Cole1e
chimeric protein and overexpression of
Rbp7
in the slow Wallerian degeneration (
Wld
S
) mouse
Authors: Conforti Laura , Tarlton Andrea , Mack Till G. A. , Mi Weiqian , Buckmaster E. Anne , Wagner Diana , Perry V. Hugh , Coleman Michael P.
Published: July 2002

Exons of three genes were identified within the 85-kilobase tandem
triplication unit of the slow Wallerian degeneration mutant mouse,
C57BL/
Wld
S
. Ubiquitin fusion
degradation protein 2 (
Ufd2
) and a previously
undescribed gene,
D4Cole1e
, span the proximal and distal
boundaries of the repeat unit, respectively. They have the same
chromosomal orientation and form a chimeric gene when brought together
at the boundaries between adjacent repeat units in
Wld
S
. The chimeric mRNA is
abundantly expressed in the nervous system and encodes an in-frame
fusion protein consisting of the N-terminal 70 amino acids of
Ufd2
, the C-terminal 302 amino acids of
D4Cole1e
, and an aspartic acid formed at the junction.
Antisera raised against synthetic peptides detect the expected 43-kDa
protein specifically in
Wld
S
brain.
This expression pattern, together with the previously established role
of ubiquitination in axon degeneration, makes the chimeric gene a
promising candidate for
Wld
. The third gene altered by
the triplication,
Rbp7
, is a novel member of the
cellular retinoid-binding protein family and is highly expressed in
white adipose tissue and mammary gland. The whole gene lies within the
repeat unit leading to overexpression of the normal transcript in
Wld
S
mice. However, it is
undetectable on Northern blots of
Wld
S
brain and seems unlikely to be
the
Wld
gene. These data reveal both a candidate gene
for
Wld
and the potential of the
Wld
S
mutant for studies of ubiquitin
and retinoid metabolism.
Sexual selection and speciation in field crickets
Authors: Gray David A. , Cade William H.
Published: July 2002

Recent theoretical work has shown that sexual selection may cause speciation under a much wider range of conditions than previously supposed. There are, however, no empirical studies capable of simultaneously evaluating several key predictions that contrast this with other speciation models. We present data on male pulse rates and female phonotactic responses to pulse rates for the field cricketGryllus texensis; pulse rate is the key feature distinguishingG. texensisfrom its cryptic sister speciesG. rubens. We show (i) genetic variation in male song and in female preference for song, (ii) a genetic correlation between the male trait and the female preference, and (iii) no character displacement in male song, female song recognition, female species-level song discrimination, or female song preference. Combined with previous work demonstrating a lack of hybrid inviability, these results suggest that divergent sexual selection may have caused speciation between these taxa.
Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain
Authors: Forsberg E. Camilla , Downs Karen M. , Christensen Heather M. , Im Hogune , Nuzzi Paul A. , Bresnick Emery H.
Published: July 2002

We have defined the histone acetylation pattern of the
endogenous murine β-globin domain, which contains the
erythroidspecific β-globin genes. The β-globin locus control
region (LCR) and transcriptionally active promoters were enriched in
acetylated histones in fetal liver relative to fetal brain, whereas the
inactive promoters were hypoacetylated. In contrast, the LCR and both
active and inactive promoters were hyperacetylated in yolk sac.
Hypersensitive site two of the LCR was also hyperacetylated in murine
embryonic stem cells, whereas β-globin promoters were hypoacetylated.
Thus, the acetylation pattern varied at different developmental stages.
Histone deacetylase inhibition selectively increased acetylation at a
hypoacetylated promoter in fetal liver, suggesting that active
deacetylation contributes to silencing of promoters. We propose that
dynamic histone acetylation and deacetylation play an important role in
the developmental control of β-globin gene expression.
Enhanced association of mutant triosephosphate isomerase to red cell membranes and to brain microtubules
Authors: Orosz F. , Wágner G. , Liliom K. , Kovács J. , Baróti K. , Horányi M. , Farkas T. , Hollán S. , Ovádi J.
Published: July 2002

In a Hungarian family with triosephosphate isomerase (TPI;
d
-glyceraldehyde-3-phosphate keto-isomerase, EC
5.3.1.1
) deficiency, two germ-line identical, but phenotypically differing compound heterozygote brothers (one of them with neurological disorder) have been identified with the same very low (<5%) TPI activity and 20- or 40-fold higher erythrocyte dihydroxyacetone phosphate levels as compared with normal controls. Our present studies with purified TPI and hemolysates revealed the binding of TPI, and the binding of human wild-type and mutant TPIs in hemolysate, to the red cell membrane, and the interference of binding with other hemolysate proteins. The binding of the mutant TPI is enhanced as compared with the wild-type enzyme. The increased binding is influenced by both the altered structure of the mutant and the changes in the red cell membrane. Compared with binding of glyceraldehyde-3-phosphate dehydrogenase, the isomerase binding is much less sensitive to ionic strength or blocking of the N-terminal tail of the band-3 transmembrane protein. The binding of TPIs to the membrane decreases the isomerase activity, resulting in extremely high dihydroxyacetone phosphate levels in deficient cells. In cell-free brain extract, tubulin copolymerizes with TPI and with other cytosolic proteins forming highly decorated microtubules as shown by immunoblot analysis with anti-TPI antibody and by electron microscopic images. The efficacy order of TPI binding to microtubules is propositus > brother without neurological disorder > normal control. This distinct microcompartmentation of mutant proteins may be relevant in the development of the neurodegenerative process in TPI deficiency and in other, more common neurological diseases.
Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: Cleavage of proteins with aspartate vs. glutamate at position 298
Authors: Tesauro M. , Thompson W. C. , Rogliani P. , Qi L. , Chaudhary P. P. , Moss J.
Published: July 2002

An endothelial nitric oxide synthase (eNOS) polymorphism in exon 7 (894 G/T) resulting in glutamate or aspartate, respectively, at position 298 on the protein is correlated with severity of cardiopulmonary diseases. Because glutamate and aspartate are considered to be conservative replacements, the polymorphism was thought to be a marker for a functional locus elsewhere in the gene. We now show in transfected cells, primary human endothelial cells, and human hearts, that eNOS with aspartate, but not glutamate, at position 298 is cleaved, resulting in the generation of 100-kDa and 35-kDa products. Recombinant or native eNOS was examined by immunoblotting either in lysates (COS7) or after partial purification over 2′,5′-ADP-Sepharose and calmodulin-Sepharose. Immunoblotting after SDS/PAGE with a carboxyl-terminal antibody showed a single major protein band in the predicted position for eNOS at 135 kDa. An additional band at approximately 100 kDa was present only in the recombinant 298Asp eNOS and in the eNOS synthesized by primary cells and heart tissue with a G/T genotype. Using an eNOS amino-terminal-specific antibody, an immunoreactive band at approximately 35 kDa, corresponding to the residual N-terminal cleavage fragment, was observed in those cells with a T genotype. Thus, eNOS with aspartate but not glutamate at position 298 is cleaved, resulting in the generation of N-terminal 35-kDa and C-terminal 100-kDa fragments. Thus, the eNOS gene with polymorphisms at nucleotide 894 generates protein products with differing susceptibility to cleavage, suggesting that, in contrast to prior predictions, this polymorphism has a functional effect on the eNOS protein.
Are variations in cuticular hydrocarbons of queens and workers a reliable signal of fertility in the antHarpegnathos saltator?
Authors: Liebig Jürgen , Peeters Christian , Oldham Neil J. , Markstädter Claus , Hölldobler Bert
Published: July 2002

One of the key features of insect societies is the division of labor in reproduction between one or a few fertile individuals and many sterile nestmates that function as helpers. The behavioral and physiological mechanisms regulating reproduction in ant societies are still not very well understood, especially in species in which all colony members are reproductively totipotent. In the ponerine antHarpegnathos saltator, queen-worker dimorphism is very limited, and a few mated workers reproduce (“gamergates”) once the founding queen becomes senescent. Worker oviposition is regulated by highly directed aggressive interactions among nestmates, who can recognize different levels of ovarian activity. We show that variations in cuticular hydrocarbons (CHC) correlate with oogenesis, both for queens and workers. 13,23-Dimethylheptatriacontane is present in egg-layers, but not in infertile workers and queens. Proportions of other CHCs vary as well, resulting in clear separation of the ants in a multivariate analysis. Egg-layers are characterized by an elongation of the chain length of CHCs. We used solid-phase microextraction to measure CHCs in live ants that were experimentally induced to start producing eggs. Over a period of 118 days, CHC profiles of infertile workers changed completely to that of reproductives. The effect of age can be excluded in this modification. This striking correlation of ovarian activity with CHC variation and its correspondence with the observed recognition behavior exhibited by the workers toward egg-laying nestmates suggests that CHCs serve as a fertility signal in the antH. saltator, a reliable basis for regulating reproduction.
Uncoupling proteins 2 and 3 are highly active H
+
transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)
Authors: Echtay Karim S. , Winkler Edith , Frischmuth Karina , Klingenberg Martin
Published: July 2002

Based on the discovery of coenzyme Q (CoQ) as an obligatory
cofactor for H
+
transport by uncoupling protein 1 (UCP1)
[Echtay, K. S., Winkler, E. & Klingenberg, M. (2000)
Nature (London)
408, 609–613] we show here that UCP2
and UCP3 are also highly active H
+
transporters and require
CoQ and fatty acid for H
+
transport, which is inhibited by
low concentrations of nucleotides. CoQ is proposed to facilitate
injection of H
+
from fatty acid into UCP. Human UCP2 and 3
expressed in
Escherichia coli
inclusion bodies are
solubilized, and by exchange of sarcosyl against digitonin, nucleotide
binding as measured with
2′-
O
-[5-(dimethylamino)naphthalene-1-sulfonyl]-GTP
can be restored. After reconstitution into vesicles, Cl
−
but no H
+
are transported. The addition of CoQ initiates
H
+
transport in conjunction with fatty acids. This increase
is fully sensitive to nucleotides. The rates are as high as with
reconstituted UCP1 from mitochondria. Maximum activity is at a molar
ratio of 1:300 of CoQ:phospholipid. In UCP2 as in UCP1, ATP is a
stronger inhibitor than ADP, but in UCP3 ADP inhibits more strongly
than ATP. Thus UCP2 and UCP3 are regulated differently by nucleotides,
in line with their different physiological contexts. These results
confirm the regulation of UCP2 and UCP3 by the same factors CoQ, fatty
acids, and nucleotides as UCP1. They supersede reports that UCP2 and
UCP3 may not be H
+
transporters.
Acid House and Thatcherism: noise, the mob, and the English countryside
Authors: Hill Andrew
Published: July 2002

This paper examines why the late 1980s youth subculture Acid House provoked a moral panic of the scale and intensity that it did. The subculture is conceived as presenting a disruptive presence to Thatcherism as an hegemonic project. The terms under which this occurred are examined through the themes of noise, the mob, and the disruption of bureaucratic authority. The presence of Acid House within the English countryside, and in particular the Home Counties, is situated as enhancing the problematic status of the subculture. The scale of measures taken against Acid House is related to Thatcherism's ‘authoritarian populism’. Acid House is located in terms of a history of similar forms of popular cultural activity. The coverage of Acid House in The Sun and The Daily Mail, and the parliamentary debate around the second reading of the Entertainments (Increased Penalties) Act, are drawn upon throughout.
Prediction of performance among West African male farmers: Natural and supernatural factors
Authors: Ouédraogo Aminata , Mullet Etienne
Published: July 2002

The goal of the present study was to study the performance schema in a male farmer population with very limited contacts with Western media and living in the North of Burkina Faso. The methodology was an application of the theory of functional cognition. The first experiment was aimed at testing a device through which participants could express their quantitative judgements. The second experiment was aimed at uncovering the integration rule used. The data supported the independence schema already found in Indian and Chinese samples. Experiment 3 extended the performance schema by incorporating a new factor currently present in Burkinabè culture: supernatural power.
William Grigsby and the Analysis of Housing Sub-markets and Filtering
Authors: Galster George
Published: July 2002

The paper reviews post-war developments in the theory of housing sub-markets and filtering, emphasising the seminal conceptual and empirical contributions provided by William Grigsby. The study discusses the implications associated with these models with respect to formulating housing policy in a market-dominated economy.
Urban Design and City Regeneration: Social Representations of Entrepreneurial Landscapes
Authors: Hubbard Phil
Published: July 2002

Recent accounts of urban political change have been seemingly preoccupied with demonstrating the existence of a transition from managerial to entrepreneurial forms of governance, typified by the speculative deployment of resources to attract investment. Within such processes, the construction of spectacular urban landscapes has become a requisite strategy for making the city attractive as a site for investment, yet, with a few notable exceptions, the meanings projected by these landscapes have been given little attention. This paper sets out to rectify this omission by developing ideas from European social psychology, particularly that of the social representation, to explore the process by which the meaning and symbolism of these new urban landscapes is imposed by dominant interests in such a way as to make them appear legitimate. Using Birmingham as a case study, interviews with local residents are drawn on to demonstrate that even when opposition to the city's entrepreneurial policies was articulated, it relied on the existence of a shared representation of its entrepreneurial landscapes, one which acknowledged their spectacular and post-modern appearance. The paper thus concludes by suggesting that such urban landscapes can potentially play a crucial role in forging a new cultural politics of place conducive to the legitimation of entrepreneurial policies.
The Role of Inward Investment in Urban Economic Development: The Cases of Bristol, Cardiff and Plymouth
Authors: Gripaios Peter , Gripaios Rose , Munday Max
Published: July 2002

This paper examines the role of manufacturing and services foreign direct investment (FDI) in the restructuring of the three large cities in the South West and Wales: Bristol, Plymouth and Cardiff. Key differences in the FDI stock of each city are analysed, with special attention given to location rationale and quality of investments. Bristol is found to be comparatively successful in attracting high-grade manufacturing, regional service centres of manufacturing companies, and financial and computer services firms. Location and policy influences have meant that Cardiff and Plymouth have been more dependent on 'production only' facilities; and Plymouth, in particular, has had difficulty attracting financial and business services investment. Policy and practical ramifications of the study are explained.
Mapping a Pedagogy for Special Educational Needs
Authors: Norwich Brahm , Lewis Anne
Published: July 2002

Abstract Recent curriculum initiatives, such as the National Literacy and Numeracy Hours, assume the validity of a broadly common curriculum for all pupils. This article synthesises a review which set out to subject that assumption to critical scrutiny, addressing the ensuing question: can differences between learners (by particular special educational needs [SEN] group) be identified and systematically linked with learners’ needs for differential teaching? Generic teaching effectiveness studies have assumed that what works with most pupils would also work for all pupils. However, little direct evidence for this position has been presented in the areas of learning difficulties which are covered in this review. Similarly, some papers by SEN specialists make calls, which were also mostly unsubstantiated by empirical evidence, for what the authors call, the ‘unique differences’ position. This rejects distinctive SEN teaching strategies and accepts that there are common pedagogic principles which are relevant to the unique differences between all pupils, including those considered to be designated as having SEN. This position is qualified by some recognition of the need for more intense and focused teaching for those with SEN. Support for a common pedagogy also comes from the authors’ analyses of pedagogy by SEN group. They conclude that the notion of continua of teaching approaches is useful as it makes it possible to distinguish between the ‘normal’ adaptations in class teaching for most pupils and the greater degree of adaptations required for those with more severe difficulties in learning, those designated as having SEN. These are adaptations to common teaching approaches, what have been called specialised adaptations, or ‘high density’ teaching.