bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound induced improvement in optical coherence tomography (OCT) resolution
Authors: Schenk John O. , Brezinski Mark E.
Published: July 2002

Optical coherence tomography (OCT) is a rapidly emerging technology for high-resolution biomedical imaging. The axial resolution of this technology is determined by the bandwidth of the source. Commercial sources generally provide resolutions of 10–20 μm whereas laboratory-based solid state lasers have resolutions of ≈4 μm. The resolution in tissue depends almost exclusively on detecting single scattered events. However, the phenomenon known as multiple scattering results in a deterioration of resolution as a function of depth. In this study, OCT was combined with ultrasound in an attempt to reduce the effect of multiple scattering. The theory is that, with parallel ultrasound and OCT beams, multiply scattered light with a momentum component significantly perpendicular to the OCT beam will be reduced because the light is Doppler shifted outside the bandpass filter of the OCT detection electronics. A 7.5-MHz ultrasound transducer was used to introduce the photon/phonon interaction. A reflecting metal plate was placed within biological tissue, and the point spread function (PSF) was assessed off the reflector. The PSF was determined in the presence of no ultrasound, pulsed ultrasound, and continuous-wave (CW) ultrasound. CW ultrasound resulted in a 17% improvement (
P
< 0.001) in resolution and pulsed ultrasound resulted in 8% (
P
< 0.01). Image noise reduction could also be noted. Combining OCT with a parallel ultrasound beam results in an improvement in resolution through a reduced effect of multiple scattering due to photon/phonon interaction. With higher frequencies, better control of the acoustical beam, and tests in media with higher rates of multiple scattering, improved results are anticipated.
A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification
Authors: Pallafacchina Giorgia , Calabria Elisa , Serrano Antonio L. , Kalhovde John M. , Schiaffino Stefano
Published: July 2002

Nerve activity controls fiber size and fiber type in skeletal muscle, but the underlying molecular mechanisms remain largely unknown. We have previously shown that Ras–mitogen-activated protein kinase and calcineurin control fiber type but not fiber size in regenerating rat skeletal muscle. Here we report that constitutively active protein kinase B (PKB), also known as Akt, increases fiber size and prevents denervation atrophy in regenerating and adult rat muscles but does not affect fiber type profile. The coexistence of hypertrophic muscle fibers overexpressing activated PKB with normal-size untransfected fibers within the same muscle points to a cell-autonomous control of muscle growth by PKB. The physiological role of this pathway is confirmed by the finding that PKB kinase activity and phosphorylation status are significantly increased in innervated compared with denervated regenerating muscles in parallel with muscle growth. Muscle fiber hypertrophy induced by activated PKB and by a Ras double mutant (RasV12C40) that activates selectively the phosphoinositide 3-kinase–PKB pathway is completely blocked by rapamycin, showing that the mammalian target of rapamycin kinase is the major downstream effector of this pathway in the control of muscle fiber size. On the other hand, nerve activity-dependent growth of regenerating muscle is only partially inhibited by dominant negative PKB and rapamycin, suggesting that other nerve-dependent signaling pathways are involved in muscle growth. The present results support the notion that fiber size and fiber type are regulated by nerve activity through different mechanisms.
An engineered
Escherichia coli
tyrosyl–tRNA synthetase for site-specific incorporation of an unnatural amino acid into proteins in eukaryotic translation and its application in a wheat germ cell-free system
Authors: Kiga Daisuke , Sakamoto Kensaku , Kodama Koichiro , Kigawa Takanori , Matsuda Takayoshi , Yabuki Takashi , Shirouzu Mikako , Harada Yoko , Nakayama Hiroshi , Takio Koji , Hasegawa Yoshinori , Endo Yaeta , Hirao Ichiro , Yokoyama Shigeyuki
Published: July 2002

Tyrosyl–tRNA synthetase (TyrRS) from
Escherichia coli
was engineered to preferentially recognize 3-iodo-
l
-tyrosine rather than
l
-tyrosine for the site-specific incorporation of 3-iodo-
l
-tyrosine into proteins in eukaryotic translation systems. The wild-type TyrRS does not recognize 3-iodo-
l
-tyrosine, because of the bulky iodine substitution. On the basis of the reported crystal structure of
Bacillus stearothermophilus
TyrRS, three residues, Y37, Q179, and Q195, in the
l
-tyrosine-binding site were chosen for mutagenesis. Thirty-four single amino acid replacements and 16 of their combinations were screened by
in vitro
biochemical assays. A combination of the Y37V and Q195C mutations changed the amino acid specificity in such a way that the variant TyrRS activates 3-iodo-
l
-tyrosine 10-fold more efficiently than
l
-tyrosine. This engineered enzyme, TyrRS(V37C195), was tested for use in the wheat germ cell-free translation system, which has recently been significantly improved, and is now as productive as conventional recombinant systems. During the translation in the wheat germ system, an
E. coli
suppressor tRNA
Tyr
was not aminoacylated by the wheat germ enzymes, but was aminoacylated by the
E. coli
TyrRS(V37C195) variant with 3-iodo-
l
-tyrosine. After the use of the 3-iodotyrosyl–tRNA in translation, the resultant uncharged tRNA could be aminoacylated again in the system. A mass spectrometric analysis of the produced protein revealed that more than 95% of the amino acids incorporated for an amber codon were iodotyrosine, whose concentration was only twice that of
l
-tyrosine in the translation. Therefore, the variant enzyme, 3-iodo-
l
-tyrosine, and the suppressor tRNA can serve as an additional set orthogonal to the 20 endogenous sets in eukaryotic
in vitro
translation systems.
Ab initio
/GIAO-MP2-calculated structures and
11
B-
13
C NMR chemical shift relationship in hypercoordinate onium-carbonium dications and isoelectronic onium-boronium cations
Authors: Rasul Golam , Prakash G. K. Surya , Olah George A.
Published: July 2002

The boronium–carbonium ion continuum was extended to include hypercoordinated onium-carbonium dications and the isoelectronic onium-boronium cation analogs. Structures and
13
C and
11
B NMR chemical shifts of the onium-carbonium dications and the corresponding isoelectronic and isostructural onium-boronium cations were calculated with the
ab initio
/GIAO-MP2 method. The data show a good linear correlation between
11
B and
13
C NMR chemical shifts, indicating that the same factors that determine the chemical shifts of the boron nuclei also govern the chemical shifts of carbon nuclei of these hypercoordinated onium ions and dications.
GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis
Authors: Chang Aaron N. , Cantor Alan B. , Fujiwara Yuko , Lodish Maya B. , Droho Steven , Crispino John D. , Orkin Stuart H.
Published: July 2002

The function of GATA transcription factors in diverse developmental contexts depends in part on physical interaction with cofactors of the Friend of GATA (FOG) family. However, previous studies indicate that FOG-1 may play a GATA-1-independent role in early megakaryopoiesis, suggesting that FOG proteins might act in a GATA factor-independent manner. Here, we have generated mouse knock-in (KI) mutants harboring a critical valine-to-glycine substitution in the amino-terminal zinc fingers of GATA-1 and GATA-2 to ablate FOG interaction. In contrast to male GATA-1KI(GATA-1 is located on the X-chromosome) or GATA-2KI/KImice, compound GATA-1KIGATA-2KI/KImutant mice display complete megakaryopoietic failure, a phenocopy of FOG-1−/−mice. We conclude that FOG-1 requires an interaction with either GATA-1 or -2 as part of its essential role in early megakaryopoiesis. On the basis of these and previous reports, we infer that GATA factor dependence is a critical aspect of FOG protein function.
Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds
Authors: Mallick Parag , Boutz Daniel R. , Eisenberg David , Yeates Todd O.
Published: July 2002

Disulfide bonds have only rarely been found in intracellular proteins. That pattern is consistent with the chemically reducing environment inside the cells of well-studied organisms. However, recent experiments and new calculations based on genomic data of archaea provide striking contradictions to this pattern. Our results indicate that the intracellular proteins of certain hyperthermophilic archaea, especially the crenarchaea
Pyrobaculum aerophilum
and
Aeropyrum pernix
, are rich in disulfide bonds. This finding implicates disulfide bonding in stabilizing many thermostable proteins and points to novel chemical environments inside these microbes. These unexpected results illustrate the wealth of biochemical insights available from the growing reservoir of genomic data.
The aging baboon: Comparative demography in a non-human primate
Authors: Bronikowski Anne M. , Alberts Susan C. , Altmann Jeanne , Packer Craig , Carey K. Dee , Tatar Marc
Published: July 2002

Why do closely related primate genera vary in longevity, and what does this teach us about human aging? Life tables of female baboons (
Papio hamadryas
) in two wild populations of East Africa and in a large captive population in San Antonio, Texas, provide striking similarities and contrasts to human mortality patterns. For captive baboons at the Southwest Foundation for Biomedical Research, we estimate the doubling time of adult mortality rate as 4.8 years. Wild females in free-living populations in Tanzania and in Kenya showed doubling times of 3.5 and 3.8 years, respectively. Although these values are considerably faster than the estimates of 7–8 years for humans, these primates share a demographic feature of human aging: within each taxon populations primarily vary in the level of Gompertz mortality intercept (frailty) and vary little in the demographic rate of aging. Environmental and genetic factors within taxa appear to affect the level of frailty underlying senescence. In contrast, primate taxa are differentiated by rates of demographic aging, even if they cannot be characterized by species-specific lifespan.
Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69
Authors: Park Kyung Chan , Kim Jung Hwa , Choi Eun-Jung , Min Sang Won , Rhee Sangmyung , Baek Sung Hee , Chung Sung Soo , Bang Oksun , Park Dongeun , Chiba Tomoki , Tanaka Keiji , Chung Chin Ha
Published: July 2002

Protein modification by ubiquitin is a dynamic and reversible process that is involved in the regulation of a variety of cellular processes. Here, we show that myogenic differentiation of embryonic muscle cells is antagonistically regulated by two deubiquitinating enzymes, UBP45 and UBP69, that are generated by alternative splicing. Both enzymes cleaved off ubiquitin from polyubiquitinated protein conjugates
in vivo
as well as from linear ubiquitin–protein fusions
in vitro
. In cultured myoblasts, the level of UBP69 mRNA markedly but transiently increased before membrane fusion, whereas that of UBP45 mRNA increased as the cells fused to form myotubes. Both myoblast fusion and accumulation of myosin heavy chain were dramatically stimulated by the stable expression of UBP69 but strongly attenuated by that of the catalytically inactive form of the protease, suggesting that the mutant enzyme acts dominant negatively on the function of the wild-type protease. In contrast, stable expression of UBP45 completely blocked both of the myogenic processes but that of inactive enzyme did not, indicating that the catalytic activity of the enzyme is essential for its inhibitory effects. These results indicate that differential expression of UBP45 and UBP69 is involved in the regulation of muscle cell differentiation.
Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis
Authors: Saito Yoshimasa , Kanai Yae , Sakamoto Michiie , Saito Hidetsugu , Ishii Hiromasa , Hirohashi Setsuo
Published: July 2002

DNA hypomethylation on pericentromeric satellite regions is an early and frequent event associated with heterochromatin instability during human hepatocarcinogenesis. A DNA methyltransferase, DNMT3b, is required for methylation on pericentromeric satellite regions during mouse development. To clarify the molecular mechanism underlying DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis, we examined mutations of the
DNMT3b
gene and mRNA expression levels of splice variants of DNMT3b in noncancerous liver tissues showing chronic hepatitis and cirrhosis, which are considered to be precancerous conditions, and in hepatocellular carcinomas (HCCs). Mutation of the
DNMT3b
gene was not found in HCCs. Overexpression of DNMT3b4, a splice variant of DNMT3b lacking conserved methyltransferase motifs IX and X, significantly correlated with DNA hypomethylation on pericentromeric satellite regions in precancerous conditions and HCCs (
P
= 0.0001). In particular, the ratio of expression of DNMT3b4 to that of DNMT3b3, which is the major splice variant in normal liver tissues and retains conserved methyltransferase motifs I, IV, VI, IX, and X, showed significant correlation with DNA hypomethylation (
P
= 0.009). Transfection of human epithelial 293 cells with DNMT3b4 cDNA induced DNA demethylation on satellite 2 in pericentromeric heterochromatin DNA. These results suggest that overexpression of DNMT3b4, which may lack DNA methyltransferase activity and compete with DNMT3b3 for targeting to pericentromeric satellite regions, results in DNA hypomethylation on these regions, even in precancerous stages, and plays a critical role in human hepatocarcinogenesis by inducing chromosomal instability.
Glutathionylation of human thioredoxin: A possible crosstalk between the glutathione and thioredoxin systems
Authors: Casagrande Simona , Bonetto Valentina , Fratelli Maddalena , Gianazza Elisabetta , Eberini Ivano , Massignan Tania , Salmona Mario , Chang Geng , Holmgren Arne , Ghezzi Pietro
Published: July 2002

To identify proteins undergoing glutathionylation (formation of protein-glutathione mixed disulfides) in human T cell blasts, we radiolabeled the glutathione pool with
35
S, exposed cells to the oxidant diamide, and analyzed cellular proteins by two-dimensional electrophoresis. One of the proteins undergoing glutathionylation was identified by molecular weight, isoelectric point, and immunoblotting as thioredoxin (Trx). Incubation of recombinant human Trx with glutathione disulfide or
S
-nitrosoglutathione led to the formation of glutathionylated Trx, identified by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. The glutathionylation site was identified as Cys-72. Glutathionylation of rhTrx abolished its enzymatic activity as insulin disulfide reductase in the presence of NADPH and Trx reductase. Activity was, however, regained with sigmoidal kinetics, indicating a process of autoactivation due to the ability of Trx to de-glutathionylate itself. These data suggest that the intracellular glutathione/glutathione disulfide ratio, an indicator of the redox state of the cell, can regulate Trx functions reversibly through thiol-disulfide exchange reactions.
Single residue modification of only one dimer within the hemoglobin tetramer reveals autonomous dimer function
Authors: Ackers Gary K. , Dalessio Paula M. , Lew George H. , Daugherty Margaret A. , Holt Jo M.
Published: July 2002

The mechanism of cooperativity in the human hemoglobin tetramer (a dimer of αβ dimers) has historically been modeled as a simple two-state system in which a low-affinity structural form (T) switches, on ligation, to a high-affinity form (R), yielding a net loss of hydrogen bonds and salt bridges in the dimer–dimer interface. Modifications that weaken these cross-dimer contacts destabilize the quaternary T tetramer, leading to decreased cooperativity and enhanced ligand affinity, as demonstrated in many studies on symmetric double modifications, i.e., a residue site modified in both α- or both β-subunits. In this work, hybrid tetramers have been prepared with only one modified residue, yielding molecules composed of a wild-type dimer and a modified dimer. It is observed that the cooperative free energy of ligation to the modified dimer is perturbed to the same extent whether in the hybrid tetramer or in the doubly modified tetramer. The cooperative free energy of ligation to the wild-type dimer is unperturbed, even in the hybrid tetramer, and despite the overall destabilization of the T tetramer by the modification. This asymmetric response by the two dimers within the same tetramer shows that loss of dimer–dimer contacts is not communicated across the dimer–dimer interface, but is transmitted through the dimer that bears the modified residue. These observations are interpreted in terms of a previously proposed dimer-based model of cooperativity with an additional quaternary (T/R) component.
mda-
7 (IL-24) mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK
Authors: Sarkar Devanand , Su Zao-Zhong , Lebedeva Irina V. , Sauane Moira , Gopalkrishnan Rahul V. , Valerie Kristoffer , Dent Paul , Fisher Paul B.
Published: July 2002

Subtraction hybridization identified melanoma differentiation-associated gene-7 (
mda
-7) as a gene induced during terminal differentiation in human melanoma cells. On the basis of structure, chromosomal localization and cytokine-like properties,
mda
-7 is classified as IL-24. Administration of
mda
-7/IL-24 by means of a replication-incompetent adenovirus (Ad.
mda
-7) induces apoptosis selectively in diverse human cancer cells without inducing harmful effects in normal fibroblast or epithelial cells. The present studies investigated the mechanism underlying this differential apoptotic effect. Infection of melanoma cells, but not normal immortal melanocytes, with Ad.
mda
-7 induced a time- and dose-dependent increase in expression, mRNA and protein, of a family of growth arrest and DNA damage (GADD)-inducible genes, which correlated with induction of apoptosis. Among the members of the GADD family of genes, GADD153, GADD45α, and GADD34 displayed marked, and GADD45γ showed minimal induction. Treatment of melanoma cells with SB203580, a selective inhibitor of the p38 mitogen-activated protein kinase (MAPK) pathway, effectively inhibited Ad.
mda
-7-induced apoptosis. Additional support for an involvement of the p38 MAPK pathway in Ad.
mda
-7-mediated apoptosis was documented by using an adenovirus expressing a dominant negative mutant of p38 MAPK. Infection with Ad.
mda
-7 increased the phosphorylation of p38 MAPK and heat shock protein 27 in melanoma cells but not in normal immortal melanocytes. In addition, SB203580 effectively inhibited Ad.
mda
-7-mediated induction of the GADD family of genes in a time- and dose-dependent manner, and it effectively blocked Ad.
mda
-7-mediated down-regulation of the antiapoptotic protein BCL-2. Inhibition of GADD genes by an antisense approach either alone or in combination also effectively blocked Ad.
mda
-7-induced apoptosis in melanoma cells. These results support the hypothesis that Ad.
mda
-7 mediates induction of the GADD family of genes by means of the p38 MAPK pathway, thereby resulting in the selective induction of apoptosis in human melanoma cells.
Regional analysis ofp53mutations in rheumatoid arthritis synovium
Authors: Yamanishi Yuji , Boyle David L. , Rosengren Sanna , Green Douglas R. , Zvaifler Nathan J. , Firestein Gary S.
Published: July 2002

The p53 tumor suppressor protein plays a central role in cell cycle regulation, DNA repair, and apoptosis. Recent studies indicate that DNA damage and somatic mutations in thep53gene can occur because of genotoxic stress in many tissues, including the skin, colon, and synovium. Although somatic mutations in thep53gene have been demonstrated in rheumatoid arthritis (RA) synovial tissue and synoviocytes, no information is available on the location or extent ofp53mutations. Using microdissected RA synovial tissue sections, we observed abundantp53transition mutations, which are characteristic DNA damage caused by oxidative stress.p53mutations, as well asp53mRNA expression, were located mainly in the synovial intimal lining rather than the sublining (P< 0.01). Clusters ofp53mutant subclones were observed in some microdissected regions, suggesting oligoclonal expansion. Because IL-6 gene expression is regulated by wild-type p53, IL-6 mRNA expression in microdissected tissues was quantified by using real-time PCR. The regions with high rates ofp53mutations contained significantly greater amounts of IL-6 mRNA compared with the low mutation samples (P< 0.02). The microdissection findings suggest thatp53mutations are induced in RA synovial tissues by inflammatory oxidative stress. This process, as in sun-exposed skin and inflamed colonic epithelium, provides some of the mutant clones with a selective growth advantage. A relatively low percentage of cells containingp53mutations can potentially affect neighboring cells and enhance inflammation through the elaboration of proinflammatory cytokines.
Bcl-XLaffects Ca2+homeostasis by altering expression of inositol 1,4,5-trisphosphate receptors
Authors: Li Chi , Fox Casey J. , Master Stephen R. , Bindokas Vytautas P. , Chodosh Lewis A. , Thompson Craig B.
Published: July 2002

An oligonucleotide-based microarray analysis of 9,500 genes and expressed sequence tags (ESTs) demonstrated that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R) was significantly down-regulated in Bcl-XL-expressing as compared with control cells. This result was confirmed at the mRNA and protein levels by Northern and Western blot analyses of two independent hematopoietic cell lines and murine primary T cells. Bcl-XLexpression resulted in a dose-dependent decrease in IP3R protein. IP3R expression is regulated as part of a mitochondrion-to-nucleus stress-responsive pathway. The uncoupling of mitochondrial oxidative phosphorylation resulted in induction of binding of the transcription factor NFATc2 to the IP3R promoter and transcriptional activation of IP3R. Expression of Bcl-XLled to a decreased induction of both NFATc2 DNA binding to the IP3R promoter and IP3R expression in response to the inhibition of mitochondrial oxidative phosphorylation. The Bcl-XL-dependent decrease in IP3R expression also correlated with a reduced T cell antigen receptor ligation-induced Ca2+flux in Bcl-XLtransgenic murine T cells, and microsomal vesicles prepared from Bcl-XL-overexpressing cells exhibited lower IP3-mediated Ca2+release capacity. Furthermore, reintroducing IP3R into Bcl-XL-transfected cells partially reversed Bcl-XL-dependent anti-apoptotic activity. These results suggest that even under non-apoptotic conditions, expression of Bcl-2-family proteins influences a signaling network that links changes in mitochondrial metabolism to alterations in nuclear gene expression.
Role of the E1A Rb-binding domain in repression of the NF-κB-dependent defense against tumor necrosis factor-α
Authors: Cook James L. , Walker Thomas A. , Worthen G. Scott , Radke Jay R.
Published: July 2002

The adenoviral E1A oncogene sensitizes mammalian cells to tumor necrosis factor-α (TNF-α), in part by repressing the nuclear factor-κ B (NF-κB)-dependent defense against this cytokine. Other E1A activities involve binding to either p300/cyclic AMP response element-binding protein (CBP) or retinoblastoma (Rb)-family proteins, but the roles of E1A interactions with these transcriptional regulators in sensitizing cells to TNF-α are unclear. E1A expression did not block upstream events in TNF-α-induced activation of NF-κB in NIH 3T3 cells, including degradation of IκB-α, nuclear translocation of NF-κB subunits, and their dimeric binding to κB sequences in the nucleus. However, E1A markedly repressed NF-κB-dependent transcription and sensitized cells to TNF-αinduced apoptosis. These E1A effects were selective for κB-dependent transcription and for the function of the NF-κB p65/RelA subunit. A four amino acid E1A deletion that eliminates binding to Rb-family proteins blocked both repression of TNF-α-induced transcription and sensitization to apoptosis. In contrast, mutations that eliminate E1A binding to p300/CBP (coactivators of p65/RelA) did not affect either E1A activity. These data suggest that E1A-Rb-binding blocks the NF-κB-dependent activation response to TNF-α by altering the function of p65/RelA at a stage after formation of the transcription factor-enhancer complex. These observations also open questions about the general role of Rb-family proteins in modulation of NF-κB-dependent transcription.
Evaluating an interpolation approach for modelling spatial variability in pest development
Authors: Jarvis C.H. , Collier R.H.
Published: July 2002

Air temperatures estimated by partial thin plate spline interpolation, or from the ‘nearest station’ (Voronoi polygon method), were used to model the phenology of three pests of horticultural crops throughout England and Wales. Temperatures for a particularly hot (1976) and a particularly cold (1986) year were interpolated to a grid resolution of 1 km. Estimates were made of the timing of spring emergence (Cecidophyopsis ribis (Westwood)), the maximum number of generations completed during the summer (Plutella xylostella (Linnaeus)) and the numbers of days when mating was possible (Merodon equestris (Fabricius)). The relative accuracy of the two temperature estimation methods was compared using jack-knife cross-validation. For C. ribis and P. xylostella, modelling with interpolated temperature input data was more accurate than using data from the ‘nearest station’. Of the three phenology models used, the one that relied on an activity threshold (M. equestris) was the most sensitive to both types of input data. Spatial variability in the activity of M. equestris adults was investigated in the two main areas (south-west peninsula and Lincolnshire) where its host crop (Narcissus) is grown. Modelling at cruder scales (up to 25*25 km) masked local variation, but the degree to which this was important varied from region to region and over time, as did the geography of the variability itself. The results indicate that interpolated data, computed to a resolution of 1 km using the UK synoptic network, have the potential for wider use within agricultural decision support systems for horticultural crops.
How international is psychology?
Authors: Adair John G. , Coělho Angela E. L. , Luna Jesus R.
Published: July 2002

Psychology claims to be an international discipline. This claim has been based upon subjective estimates of attendance at international congresses, status reports from selected countries published within edited volumes, and a survey of the member countries of the International Union of Psychological Science (IUPsyS) (Rosenzweig, 1992). However, to be truly international, the work of psychologists in countries around the world must be internationally disseminated. Systematic examination of international congress presentations and abstracts of published psychological literature indexed on widely available electronic databases (e.g., PsycLIT) provides a more objective means of documenting the international presence of psychology. In this article, counts by country were made of research contributions reported within PsycLIT and on the programs of International Congresses of Applied Psychology over the five years in which the congresses were held from 1982 to 1998. Analyses of these data revealed PsycLIT to be more international in scope than previously assumed—45% of its entries were by authors from outside the US. Coverage of research from developing countries was even more limited within PsycLIT (4.67%), but proportionally greater within international congresses (10%). PsycLIT entries not in the English language were found noticeably to have declined from approximately 12–14% levels in the 1980s to only about 6% in the 1990s. An index of the presence of psychology in each country, based upon presentations at IAAP congresses, memberships in international associations, and the extent of PsycLIT entries over the previous three decades, provided an objective, empirically‐based answer to the question ‘How International is Psychology?' This index indicated that psychology has a significant presence in 47 countries, a presence in another 22 countries, but minimal or no presence in 82 other countries. The meaning of these data for the discipline and ways in which psychology's worldwide presence might be strengthened and extended were discussed.
Psychology in sub‐Saharan Africa: Challenges, prospects and promises
Authors: Mpofu Elias
Published: July 2002

The experiences of African communities are significantly underrepresented in the current psychological literature as compared to those of Western European and North American communities. Professional psychology in sub‐Saharan African is either nonexistent or strongly modeled after practices in North America and Western Europe. The modeling of psychology in sub‐Saharan Africa on the North American and Western European experience is a result of the more extensive marketing of the Western cultural heritage around the globe by national governments, education institutions and international aid agencies vis a vis the marketing of alternative cultural heritages. It is also reflective of the historically unequal intercultural exchanges between Western and African cultural heritages and in favour of the former. A greater representation of the African experience in the psychological literature could add to the richness and global relevance of psychology.
Content and context effects in children's and adults' conditional reasoning
Authors: Barrouillet Pierre , Lecas Jean-François
Published: July 2002

We have recently shown that children interpret conditional sentences with binary terms (e.g., male/female) in both the antecedent and the consequent as biconditionals (Barrouillet & Lecas, 1998). We hypothesized that the same effect can be obtained with conditionals that do not contain binary terms provided that they are embedded in a context that restricts to only two the possible values on both the antecedent and the consequent. In the present experiment, we asked 12-year-old children, 15-year-old children, and adults to draw conclusions from conditional syllogisms that involved three types of conditional sentence: (1) conditionals with binary terms (BB), (2) conditionals with non-binary terms (NN), and (3) conditionals with non-binary terms embedded in a restrictive context (NNR). As we predicted, BB conditionals elicited more biconditional response patterns than did NN conditionals in all age groups. On the other hand, manipulating the context had the same effect in children but not in adults. Content and context constraints on conditional reasoning along with developmental issues are discussed within the framework of the mental models theory.
The effects of endogenous attention and stimulus onsets on encoding target location
Authors: Danziger Shai
Published: July 2002

The effects of endogenously attended and non-attended stimulus onsets on spatial stimulus encoding of a target were explored in a Simon task. In each experiment participants made speeded left or right key-press responses to the colour of a target that followed a cueing display consisting of several shapes. The target appeared within some shapes and not others. The target's spatial code as measured by a Simon task was its location relative to possible target positions and relative to the centre of the display. Target location was not coded relative to the positions of onset shapes that could not contain a target. These spatial coding effects were found at cue-target intervals of 50, 300, and 1000 ms. The data indicate that target location is defined relative to the distribution of endogenous attention and reference frames aligned with the centre of the display and that the spatial code assigned to a target is not affected when attention is shifted in the target's direction.
Localized Ca2+ uncaging reveals polarized distribution of Ca2+-sensitive Ca2+ release sites
Authors: Ashby Michael C. , Craske Madeleine , Park Myoung Kyu , Gerasimenko Oleg V. , Burgoyne Robert D. , Petersen Ole H. , Tepikin Alexei V.
Published: July 2002

Ca2+-induced Ca2+ release (CICR) plays an important role in the generation of cytosolic Ca2+ signals in many cell types. However, it is inherently difficult to distinguish experimentally between the contributions of messenger-induced Ca2+ release and CICR. We have directly tested the CICR sensitivity of different regions of intact pancreatic acinar cells using local uncaging of caged Ca2+. In the apical region, local uncaging of Ca2+ was able to trigger a CICR wave, which propagated toward the base. CICR could not be triggered in the basal region, despite the known presence of ryanodine receptors. The triggering of CICR from the apical region was inhibited by a pharmacological block of ryanodine or inositol trisphosphate receptors, indicating that global signals require coordinated Ca2+ release. Subthreshold agonist stimulation increased the probability of triggering CICR by apical uncaging, and uncaging-induced CICR could activate long-lasting Ca2+ oscillations. However, with subthreshold stimulation, CICR could still not be initiated in the basal region. CICR is the major process responsible for global Ca2+ transients, and intracellular variations in sensitivity to CICR predetermine the activation pattern of Ca2+ waves.
Proximal location of mouse prostate epithelial stem cells
Authors: Tsujimura Akira , Koikawa Yasuhiro , Salm Sarah , Takao Tetsuya , Coetzee Sandra , Moscatelli David , Shapiro Ellen , Lepor Herbert , Sun Tung-Tien , Wilson E. Lynette
Published: July 2002

Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation.
Cytoplasmic p21Cip1/WAF1 regulates neurite remodeling by inhibiting Rho-kinase activity
Authors: Tanaka Hiroyuki , Yamashita Toshihide , Asada Minoru , Mizutani Shuki , Yoshikawa Hideki , Tohyama Masaya
Published: July 2002

p21Cip1/WAF1 has cell cycle inhibitory activity by binding to and inhibiting both cyclin/Cdk kinases and proliferating cell nuclear antigen. Here we show that p21Cip1/WAF1 is induced in the cytoplasm during the course of differentiation of chick retinal precursor cells and N1E-115 cells. Ectopic expression of p21Cip1/WAF1 lacking the nuclear localization signal in N1E-115 cells and NIH3T3 cells affects the formation of actin structures, characteristic of inactivation of Rho. p21Cip1/WAF1 forms a complex with Rho-kinase and inhibits its activity in vitro and in vivo. Neurite outgrowth and branching from the hippocampal neurons are promoted if p21Cip1/WAF1 is expressed abundantly in the cytoplasm. These results suggest that cytoplasmic p21Cip1/WAF1 may contribute to the developmental process of the newborn neurons that extend axons and dendrites into target regions.
T Cell Costimulation through CD28 Depends on Induction of the Bcl-xγ Isoform
Authors: Ye Qunrui , Press Barry , Kissler Stephan , Yang Xiao-Feng , Lu Linrong , Bassing Craig H. , Sleckman Barry P. , Jansson Marianne , Panoutsakopoulou Vily , Trimble Linda A. , Alt Frederick W. , Cantor Harvey
Published: July 2002

The molecular basis of CD28-dependent costimulation of T cells is poorly understood. Bcl-xγ is a member of the Bcl-x family whose expression is restricted to activated T cells and requires CD28-dependent ligation for full expression. We report that Bcl-xγ–deficient (Bcl-xγ−/−) T cells display defective proliferative and cytokine responses to CD28-dependent costimulatory signals, impaired memory responses to proteolipid protein peptide (PLP), and do not develop PLP-induced experimental autoimmune encephalomyelitis (EAE). In contrast, enforced expression of Bcl-xγ largely replaces the requirement for B7-dependent ligation of CD28. These findings identify the Bcl-xγ cytosolic protein as an essential downstream link in the CD28-dependent signaling pathway that underlies T cell costimulation.
PKC Phosphorylation Increases the Ability of AFAP-110 to Cross-link Actin Filaments
Authors: Qian Yong , Baisden Joseph M. , Cherezova Lidia , Summy Justin M. , Guappone-Koay Anne , Shi Xianglin , Mast Tom , Pustula Jennifer , Zot Henry G. , Mazloum Nayef , Lee Marietta Y. , Flynn Daniel C.
Published: July 2002

The actin filament-associated protein and Src-binding partner, AFAP-110, is an adaptor protein that links signaling molecules to actin filaments. AFAP-110 binds actin filaments directly and multimerizes through a leucine zipper motif. Cellular signals downstream of Src527F can regulate multimerization. Here, we determined recombinant AFAP-110 (rAFAP-110)-bound actin filaments cooperatively, through a lateral association. We demonstrate rAFAP-110 has the capability to cross-link actin filaments, and this ability is dependent on the integrity of the carboxy terminal actin binding domain. Deletion of the leucine zipper motif or PKC phosphorylation affected AFAP-110's conformation, which correlated with changes in multimerization and increased the capability of rAFAP-110 to cross-link actin filaments. AFAP-110 is both a substrate and binding partner of PKC. On PKC activation, stress filament organization is lost, motility structures form, and AFAP-110 colocalizes strongly with motility structures. Expression of a deletion mutant of AFAP-110 that is unable to bind PKC blocked the effect of PMA on actin filaments. We hypothesize that upon PKC activation, AFAP-110 can be cooperatively recruited to newly forming actin filaments, like those that exist in cell motility structures, and that PKC phosphorylation effects a conformational change that may enable AFAP-110 to promote actin filament cross-linking at the cell membrane.
Structural Determinants of Ras-Raf Interaction Analyzed in Live Cells
Authors: Bondeva Tzvetanka , Balla András , Várnai Péter , Balla Tamas
Published: July 2002

The minimum structure of the Raf-1 serine/threonine kinase that recognizes active Ras was used to create a green fluorescent fusion protein (GFP) for monitoring Ras activation in live cells. In spite of its ability to bind activated Ras in vitro, the Ras binding domain (RBD) of Raf-1 (Raf-1[51-131]GFP) failed to detect Ras in Ras-transformed NIH 3T3 fibroblasts and required the addition of the cysteine-rich domain (CRD) (Raf-1[51-220]GFP) to show clear localization to plasma membrane ruffles. In normal NIH 3T3 cells, (Raf-1[51-220]GFP) showed minimal membrane localization that was enhanced after stimulation with platelet-derived growth factor or phorbol-12-myristate-13-acetate. Mutations within either the RBD (R89L) or CRD (C168S) disrupted the membrane localization of (Raf-1[51-220]GFP), suggesting that both domains contribute to the recruitment of the fusion protein to Ras at the plasma membrane. The abilities of the various constructs to localize to the plasma membrane closely correlated with their inhibitory effects on mitogen-activated protein kinase kinase1 and mitogen-activated protein kinase activation. Membrane localization of full-length Raf-1-GFP was less prominent than that of (Raf-1[51-220]GFP) in spite of its strong binding to RasV12 and potent activation of mitogen-activated protein kinase. These finding indicate that both RBD and CRD are necessary to recruit Raf-1 to active Ras at the plasma membrane, and that these domains are not fully exposed in the Raf-1 molecule. Visualization of activated Ras in live cells will help to better understand the dynamics of Ras activation under various physiological and pathological conditions.
Exon discovery by genomic sequence alignment
Authors: Morgenstern Burkhard , Rinner Oliver , Abdeddaïm Saïd , Haase Dirk , Mayer Klaus F. X. , Dress Andreas W. M. , Mewes Hans-Werner
Published: July 2002

Motivation: During evolution, functional regions in genomic sequences tend to be more highly conserved than randomly mutating ‘junk DNA’ so local sequence similarity often indicates biological functionality. This fact can be used to identify functional elements in large eukaryotic DNA sequences by cross-species sequence comparison. In recent years, several gene-prediction methods have been proposed that work by comparing anonymous genomic sequences, for example from human and mouse. The main advantage of these methods is that they are based on simple and generally applicable measures of (local) sequence similarity; unlike standard gene-finding approaches they do not depend on species-specific training data or on the presence of cognate genes in data bases. As all comparative sequence-analysis methods, the new comparative gene-finding approaches critically rely on the quality of the underlying sequence alignments.

Results: Herein, we describe a new implementation of the sequence-alignment program DIALIGN that has been developed for alignment of large genomic sequences. We compare our method to the alignment programs PipMaker, WABA and BLAST and we show that local similarities identified by these programs are highly correlated to protein-coding regions. In our test runs, PipMaker was the most sensitive method while DIALIGN was most specific.

Availability: The program is downloadable from the DIALIGN home page at http://bibiserv.techfak.uni-bielefeld.de/dialign/

Contact: burkhard@TechFak.Uni-Bielefeld.DE

* To whom correspondence should be addressed at Universität Bielefeld, Technische Fakultät, Praktische Informatik, Postfach 100131, 33501 Bielefeld, Germany.
A Bayesian network model for protein fold and remote
homologue recognition
Authors: Raval A. , Ghahramani Z. , Wild D. L.
Published: July 2002

Motivation: The Bayesian network approach is a framework which combines graphical representation and probability theory, which includes, as a special case, hidden Markov models. Hidden Markov models trained on amino acid sequence or secondary structure data alone have been shown to have potential for addressing the problem of protein fold and superfamily classification.

Results: This paper describes a novel implementation of a Bayesian network which simultaneously learns amino acid sequence, secondary structure and residue accessibility for proteins of known three-dimensional structure. An awareness of the errors inherent in predicted secondary structure may be incorporated into the model by means of a confusion matrix. Training and validation data have been derived for a number of protein superfamilies from the Structural Classification of Proteins (SCOP) database. Cross validation results using posterior probability classification demonstrate that the Bayesian network performs better in classifying proteins of known structural superfamily than a hidden Markov model trained on amino acid sequences alone.

Contact: alpan_raval@kgi.eduzoubin@gatsby.ucl.ac.ukdavid_wild@kgi.edu

* To whom correspondence should be addressed.
THE ALLOCATION OF FEDERAL FUNDS TO PROMOTE BUREAUCRATIC OBJECTIVES: AN EMPIRICAL TEST
Authors: Svorny Shirley , Marcal Leah
Published: July 2002

This article tests whether Job Training Partnership Act Title III discretionary funds are allocated to meet bureaucratic objectives. These funds are targeted to provide a rapid response to mass layoffs or natural disasters and are therefore well suited for detecting political influence because program distributions are awarded contemporaneously and eligibility is difficult to anticipate. After controlling for worker displacements and disaster declarations, discretionary outlays are higher in states with close congressional races, politically active constituents, and powerful congressional representatives. There is additional evidence of politics in the reduction of aggregate outlays during presidential election years.
BUDGET BALANCE THROUGH SPENDING CUTS OR TAX ADJUSTMENTS?
Authors: Darrat Ali F.
Published: July 2002

This article explores the causal (lead/lag) relation between government spending and taxation in two developing countries (Lebanon and Tunisia). Both countries have suffered from large budget deficit and/or national debt problems, particularly since the early 1990s. Empirical results deduced from a battery of tests suggest that decisions to spend and tax are significantly interdependent in both countries. Moreover, the evidence is consistent with the notion that raising taxes (working primarily through aroused public awareness) provokes spending cuts. Thus, higher taxes seem an optimal resolution to the deficit predicament in both countries.
THEORY AND PRACTICE IN THE CLASSROOM: A REPEATED GAME OF MULTIMARKET OLIGOPOLY
Authors: Sorenson Timothy L.
Published: July 2002

This article describes a repeated game of multimarket contact, designed to be played throughout an entire term. Besides enjoying reciprocal advantages in their home markets, firms are perfectly informed after every round about each other's decisions. For most of the game, it appears there is always a future in which to punish deviations, and (with the game's parameters) zero‐cost punishments can always be implemented. Thus the game provides all the elements for an escape from the prisoner's dilemma. Theoretical foundations, predictions, and some results are also discussed.
Optimal Deterrence with Legal Defense Expenditure
Authors: Gravelle Hugh , Garoupa Nuno
Published: July 2002

Legal defense expenditure by honest and dishonest accused can increase or reduce the amount of crime, and deterrence can decrease when punishment is increased. Unregulated expenditure of innocent and guilty defendants is inefficient whether or not there is a direct social harm from type I and II errors. The circumstances in which the optimal fine bankrupts convicted dishonest or honest defendants, regulation to limit defense expenditure and a tax‐financed public defender system are also investigated.
Safety and Soundness and the CRA: Is There a Conflict?
Authors: Gunther Jeffery W.
Published: July 2002

Ordered probit regressions of the supervisory ratings assigned to banks point to a conflict between the credit enhancement objectives associated with the Community Reinvestment Act (CRA) and financial safety and soundness standards. Aggressive banking strategies tend to help CRA ratings but hurt safety and soundness ratings. In addition, banks with financial problems are more likely to receive substandard CRA ratings, even though their condition may require a retrenchment from CRA objectives. Finally, there is some limited evidence to suggest that a greater focus on lending in low‐income neighborhoods helps CRA ratings but at the expense of safety and soundness.