bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of maternal-zygotic mutant zebrafish by germ-line replacement
Authors: Ciruna Brian , Weidinger Gilbert , Knaut Holger , Thisse Bernard , Thisse Christine , Raz Erez , Schier Alexander F.
Published: November 2002

We report a generally applicable strategy for transferring zygotic lethal mutations through the zebrafish germ line. By using a morpholino oligonucleotide that blocks primordial germ cell (PGC) development, we generate embryos devoid of endogenous PGCs to serve as hosts for the transplantation of germ cells derived from homozygous mutant donors. Successful transfers are identified by the localization of specifically labeled donor PGCs to the region of the developing gonad in chimeric embryos. This strategy, which results in the complete replacement of the host germ line with donor PGCs, was validated by the generation of maternal and maternal-zygotic mutants for the
miles apart
locus. This germ-line replacement technique provides a powerful tool for studying the maternal effects of zygotic lethal mutations. Furthermore, the ability to generate large clutches of purely mutant embryos will greatly facilitate embryological, genetic, genomic, and biochemical studies.
Site-specific translocation and evidence of postnatal origin of the t(1;19)E2A-PBX1fusion in childhood acute lymphoblastic leukemia
Authors: Wiemels Joseph L. , Leonard Brian C. , Wang Yunxia , Segal Mark R. , Hunger Stephen P. , Smith Martyn T. , Crouse Vonda , Ma Xiaomei , Buffler Patricia A. , Pine Sharon R.
Published: November 2002

The t(1;19) translocation yields a fusion betweenE2AandPBX1genes and occurs in 5% of acute lymphoblastic leukemia in children and adults. We used chromosomal translocations and Ig heavy chain (IGH)/T cell antigen receptor (TCR) rearrangements to develop an understanding of the etiology and natural history of this subtype of leukemia. We sequenced the genomic fusion betweenE2AandPBX1in 22 preB acute lymphoblastic leukemias and two cell lines. The prenatal origin of the leukemia was assessed in 15 pediatric patients by screening for the clonotypicE2A-PBX1translocation in neonatal blood spots, or Guthrie cards, obtained from the children at the time of birth. Two patients were determined to be weakly positive for the fusion at the time of birth, in contrast to previously studied childhood leukemia fusions, t(12;21), t(8;21), and t(4;11), which were predominantly prenatal. The presence of extensiveN-nucleotides at the point of fusion in theE2A-PBX1translocation as well as specific characteristics of theIGH/TCRrearrangements provided additional evidence for a postnatal, preB cell origin. Intriguingly, 16 of 24 breakpoints on the 3.2-kbE2Aintron 14 were located within 5 bp, providing evidence for a site-specific recombination mechanism. Breakpoints on the 232-kbPBX1intron 1 were more dispersed but highly clustered proximal to exon 2. In sum, the translocation breakpoints displayed evidence of unique temporal, ontological, and mechanistic formation than the previously analyzed pediatric leukemia translocation breakpoints and emphasize the need to differentiate cytogenetic and molecular subgroups for studies of leukemia causality.
Drusen proteome analysis: An approach to the etiology of age-related macular degeneration
Authors: Crabb John W. , Miyagi Masaru , Gu Xiaorong , Shadrach Karen , West Karen A. , Sakaguchi Hirokazu , Kamei Motohiro , Hasan Azeem , Yan Lin , Rayborn Mary E. , Salomon Robert G. , Hollyfield Joe G.
Published: November 2002

Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding of drusen formation, we have developed a method for isolating microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid chromatography tandem MS analyses of drusen preparations from 18 normal donors and five AMD donors identified 129 proteins. Immunocytochemical studies have thus far localized ≈16% of these proteins in drusen. Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen. Up to 65% of the proteins identified were found in drusen from both AMD and normal donors. However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely generated from the oxidation of docosahexaenoate-containing lipids. By Western analysis they were found to be more abundant in AMD than in normal Bruch's membrane and were found associated with drusen proteins. Carboxymethyl lysine, another oxidative modification, was also detected in drusen. These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.
RNA-binding protein Musashi family: Roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation
Authors: Sakakibara Shin-ichi , Nakamura Yuki , Yoshida Tetsu , Shibata Shinsuke , Koike Masato , Takano Hiroshi , Ueda Shuichi , Uchiyama Yasuo , Noda Tetsuo , Okano Hideyuki
Published: November 2002

Homologues of the Musashi family of RNA-binding proteins are evolutionarily conserved across species. In mammals, two members of this family, Musashi1 (Msi1) and Musashi2 (Msi2), are strongly coexpressed in neural precursor cells, including CNS stem cells. To address the
in vivo
roles of
msi
in neural development, we generated mice with a targeted disruption of the gene encoding Msi1. Homozygous newborn mice frequently developed obstructive hydrocephalus with aberrant proliferation of ependymal cells in a restricted area surrounding the Sylvius aqueduct. These observations indicate a vital role for
msi1
in the normal development of this subpopulation of ependymal cells, which has been speculated to be a source of postnatal CNS stem cells. On the other hand, histological examination and an
in vitro
neurosphere assay showed that neither the embryonic CNS development nor the self-renewal activity of CNS stem cells in embryonic forebrains appeared to be affected by the disruption of
msi1
, but the diversity of the cell types produced by the stem cells was moderately reduced by the
msi1
deficiency. Therefore, we performed antisense ablation experiments to target both
msi1
and
msi2
in embryonic neural precursor cells. Administration of the antisense peptide-nucleotides, which were designed to specifically down-regulate
msi2
expression, to
msi1
−/−
CNS stem cell cultures drastically suppressed the formation of neurospheres in a dose-dependent manner. Antisense-treated
msi1
−/−
CNS stem cells showed a reduced proliferative activity. These data suggest that
msi1
and
msi2
are cooperatively involved in the proliferation and maintenance of CNS stem cell populations.
Identification of E2A target genes in B lymphocyte development by using a gene tagging-based chromatin immunoprecipitation system
Authors: Greenbaum Stephen , Zhuang Yuan
Published: November 2002

The transcription factors encoded by theE2Agene are known to be essential for B lymphocyte development, and ectopic expression or gene inactivation studies have revealed several potential lineage-specific E2A target genes. However, it remains unknown whether these target genes are directly regulated by E2A at the transcriptional level. We therefore generated mice carrying an affinity-tagged E2A knock-in allele to provide a system for the direct elucidation of E2A target genes based on E2A binding to target regulatory regions. Abelson-transformed pre-B cell lines derived from these mice were used in chromatin immunoprecipitation experiments to identify regulatory sequences bound by E2A in the context of an early B lymphocyte environment. Significant E2A binding was detected at the promoters and enhancers of several essential B-lineage genes, including the Igκ intronic and 3′ enhancers,λ5andVpreBsurrogate light chain promoters, theEBFlocus promoter region, and themb-1(Igα) promoter. Low levels of E2A binding were observed at several other lymphoid-restricted regulatory regions including the Ig heavy chain (IgH) intronic enhancer, theIgH3′ enhancers hs3b/hs4, theRAG-2enhancer, and the 5′ regions of theB29andTdTloci. An E2A target gene, the predicted butyrophilin-like geneNG9(BTL-II), was also identified by using a chromatin immunoprecipitation-based cloning strategy. In summary, our studies have provided evidence that E2A is directly involved in the transcriptional regulation of a number of early B-lineage genes.
Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts
Authors: Lee Cheol-Koo , Allison David B. , Brand Jaap , Weindruch Richard , Prolla Tomas A.
Published: November 2002

To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5- and 30-month-old male B6C3F
1
mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.
Short constrained peptides that inhibit HIV-1 entry
Authors: Sia Samuel K. , Carr Peter A. , Cochran Andrea G. , Malashkevich Vladimir N. , Kim Peter S.
Published: November 2002

Peptides corresponding to the C-terminal heptad repeat of HIV-1 gp41 (C-peptides) are potent inhibitors of HIV-1 entry into cells. Their mechanism of inhibition involves binding in a helical conformation to the central coiled coil of HIV-1 gp41 in a dominant–negative manner. Short C-peptides, however, have low binding affinity for gp41 and poor inhibitory activity, which creates an obstacle to the development of small drug-like C-peptides. To improve the inhibitory potency of short C-peptides that target the hydrophobic pocket region of gp41, we use two strategies to stabilize the C-peptide helix: chemical crosslinking and substitution with unnatural helix-favoring amino acids. In this study, the short linear peptide shows no significant inhibitory activity, but a constrained peptide (C14linkmid) inhibits cell–cell fusion at micromolar potency. Structural studies confirm that the constrained peptides bind to the gp41 hydrophobic pocket. Calorimetry reveals that, of the peptides analyzed, the most potent are those that best balance the changes in binding enthalpy and entropy, and surprisingly not those with the highest helical propensity as measured by circular dichroism spectroscopy. Our study reveals the thermodynamic basis of inhibition of an HIV C-peptide, demonstrates the utility of constraining methods for a short antiviral peptide inhibitor, and has implications for the future design of constrained peptides.
Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal
Authors: Rebel Vivienne I. , Kung Andrew L. , Tanner Elizabeth A. , Yang Hong , Bronson Roderick T. , Livingston David M.
Published: November 2002

Hematopoietic stem cells (HSC) are tightly regulated through, as yet, undefined mechanisms that balance self-renewal and differentiation. We have identified a role for the transcriptional coactivators CREB-binding protein (CBP) and p300 in such HSC fate decisions. A full dose of CBP, but not p300, is crucial for HSC self-renewal. Conversely, p300, but not CBP, is essential for proper hematopoietic differentiation. Furthermore, in chimeric mice, hematologic malignancies emerged from both CBP
−/−
and p300
−/−
cell populations. Thus, CBP and p300 play essential but distinct roles in maintaining normal hematopoiesis, and, in mice, both are required for preventing hematologic tumorigenesis.
Missense models [
Gus

tm(E536A)Sly

,
Gus

tm(E536Q)Sly

, and
Gus

tm(L175F)Sly

] of murine mucopolysaccharidosis type VII produced by targeted mutagenesis
Authors: Tomatsu Shunji , Orii Koji O. , Vogler Carole , Grubb Jeffrey H. , Snella Elizabeth M. , Gutierrez Monica A. , Dieter Tatiana , Sukegawa Kazuko , Orii Tadao , Kondo Naomi , Sly William S.
Published: November 2002

Human mucopolysaccharidosis VII (MPS VII, Sly syndrome) results from a deficiency of β-glucuronidase (GUS) and has been associated with a wide range in severity of clinical manifestations. To study missense mutant models of murine MPS VII with phenotypes of varying severity, we used targeted mutagenesis to produce E536A and E536Q, corresponding to active-site nucleophile replacements E540A and E540Q in human GUS, and L175F, corresponding to the most common human mutation, L176F. The E536A mouse had no GUS activity in any tissue and displayed a severe phenotype like that of the originally described MPS VII mice carrying a deletion mutation (
gus
mps/mps
). E536Q and L175F mice had low levels of residual activity and milder phenotypes. All three mutant MPS models showed progressive lysosomal storage in many tissues but had different rates of accumulation. The amount of urinary glycosaminoglycan excretion paralleled the clinical severity, with urinary glycosaminoglycans remarkably higher in E536A mice than in E536Q or L175F mice. Molecular analysis showed that the
Gus
mRNA levels were quantitatively similar in the three mutant mouse strains and normal mice. These mouse models, which mimic different clinical phenotypes of human MPS VII, should be useful in studying pathogenesis and also provide useful models for studying enzyme replacement therapy and targeted correction of missense mutations.
Mbd4 inactivation increases C→T transition mutations and promotes gastrointestinal tumor formation
Authors: Wong Edmund , Yang Kan , Kuraguchi Mari , Werling Uwe , Avdievich Elena , Fan Kunhua , Fazzari Melissa , Jin Bo , Brown Anthony M. C. , Lipkin Martin , Edelmann Winfried
Published: November 2002

Mbd4 (methyl-CpG binding domain 4) is a novel mammalian repair enzyme that has been implicated biochemically in the repair of mismatched G-T residues at methylated CpG sites. In addition, the human protein has been shown to interact with the DNA mismatch repair protein MLH1. To clarify the role of Mbd4 in DNA repair
in vivo
and to examine the impact of Mbd4 inactivation on gastrointestinal (GI) tumorigenesis, we introduced a null mutation into the murine
Mbd4
gene by gene targeting. Heterozygous and homozygous
Mbd4
mutant mice develop normally and do not show increased cancer susceptibility or reduced survival. Although Mbd4 inactivation did not increase microsatellite instability (MSI) in the mouse genome, it did result in a 2- to 3-fold increase in C→T transition mutations at CpG sequences in splenocytes and epithelial cells of the small intestinal mucosa. The combination of Mbd4 deficiency with a germ line mutation in the adenomatous polyposis coli (
Apc
) gene increased the tumor number in the GI tract and accelerated tumor progression. The change in the GI cancer phenotype was associated with an increase in somatic C→T mutations at CpG sites within the coding region of the wild-type
Apc
allele. These studies indicate that, although inactivation of Mbd4 does not by itself cause cancer predisposition in mice, it can alter the mutation spectrum in cancer cells and modify the cancer predisposition phenotype.
Expression of the antiapoptotic baculovirus p35 gene in tomato blocks programmed cell death and provides broad-spectrum resistance to disease
Authors: Lincoln James E. , Richael Craig , Overduin Bert , Smith Kathy , Bostock Richard , Gilchrist David G.
Published: November 2002

The sphinganine analog mycotoxin, AAL-toxin, induces a death process in plant and animal cells that shows apoptotic morphology. In nature, the AAL-toxin is the primary determinant of the Alternaria stem canker disease of tomato, thus linking apoptosis to this disease caused by
Alternaria alternata
f. sp.
lycopersici
. The product of the baculovirus p35 gene is a specific inhibitor of a class of cysteine proteases termed caspases, and naturally functions in infected insects. Transgenic tomato plants bearing the p35 gene were protected against AAL-toxin-induced death and pathogen infection. Resistance to the toxin and pathogen co-segregated with the expression of the p35 gene through the T3 generation, as did resistance to
A. alternata
,
Colletotrichum coccodes
, and
Pseudomonas syringae
pv.
tomato
. The p35 gene, stably transformed into tomato roots by
Agrobacterium rhizogenes
, protected roots against a 30-fold greater concentration of AAL-toxin than control roots tolerated. Transgenic expression of a p35 binding site mutant (DQMD to DRIL), inactive against animal caspases-3, did not protect against AAL-toxin. These results indicate that plants possess a protease with substrate-site specificity that is functionally equivalent to certain animal caspases. A biological conclusion is that diverse plant pathogens co-opt apoptosis during infection, and that transgenic modification of pathways regulating programmed cell death in plants is a potential strategy for engineering broad-spectrum disease resistance in plants.
A chemoattractant for ascidian spermatozoa is a sulfated steroid
Authors: Yoshida Manabu , Murata Michio , Inaba Kazuo , Morisawa Masaaki
Published: November 2002

Sperm chemotaxis toward eggs before fertilization has been demonstrated in many animals and plants, and several peptides and small organic compounds acting as chemoattractants have been identified. We previously showed that sperm of the ascidians
Ciona intestinalis
and
Ciona savignyi
are activated and then attracted toward the egg by a common factor released from the egg. In this study, we purified sperm-activating and -attracting factor (SAAF) from the egg-conditioning medium of
C. intestinalis
by using several steps of column chromatography. Determination of the molecular structure by NMR and MS/MS analysis revealed that SAAF is a previously uncharacterized sulfated steroid: 3,4,7,26-tetrahydroxycholestane-3,26-disulfate. Furthermore, it was shown that the SAAF of
C. savignyi
was indistinguishable from that of
C. intestinalis
in terms of the chromatographic behavior and molecular weight, indicating that the same compound might be responsible for sperm activation and chemotaxis in both the species. Furthermore, we established a method for quantitative analysis of sperm chemotaxis and showed that the chemotactic behavior of
Ciona
sperm is controlled by the “chemotactic turn” associated with decrease in the concentration of SAAF.
Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein
Authors: Meiering Christopher D. , Linial Maxine L.
Published: November 2002

Spumaviruses, commonly called foamy viruses (FV), are complex retroviruses that establish lifelong persistent infections without any accompanying pathologies. In tissue culture, cells can be either lytically or latently infected, depending on cell type. Regulation of FV replication is controlled by two promoters: the LTR and a second promoter within the
env
gene termed the internal promoter (IP). The IP directs expression of the transcriptional activator, Tas, and a second accessory protein, Bet, whose function has been elusive. In this study, we report that expression of exogenous Tas is sufficient to initiate a switch from latent to lytic replication. We also show that treatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA) can lead to an increase in transcription from the IP, and that Bet protein expression abrogates this effect. Finally, we demonstrate that Bet expression severely limits the ability of PMA to activate transcription of latent FV genomes, and that replication of a Bet(-) virus is more easily activated than wild-type FV. Taken together, these data suggest that viral transcription is regulated by a sensitive switch, and that Bet functions as a negative regulator of basal IP activity.
Protein Kinase MARK/PAR-1 Is Required for Neurite Outgrowth and Establishment of Neuronal Polarity
Authors: Biernat Jacek , Wu Yong-Zhong , Timm Thomas , Zheng-Fischhöfer Qingyi , Mandelkow Eckhard , Meijer Laurent , Mandelkow Eva-Maria
Published: November 2002

Protein kinases of the microtubule affinity-regulating kinase (MARK) family were originally discovered because of their ability to phosphorylate certain sites in tau protein (KXGS motifs in the repeat domain). This type of phosphorylation is enhanced in abnormal tau from Alzheimer brain tissue and causes the detachment of tau from microtubules. MARK-related kinases (PAR-1 and KIN1) occur in various organisms and are involved in establishing and maintaining cell polarity. Herein, we report the ability of MARK2 to affect the differentiation and outgrowth of cell processes from neuroblastoma and other cell models. MARK2 phosphorylates tau protein at the KXGS motifs; this results in the detachment of tau from microtubules and their destabilization. The formation of neurites in N2a cells is blocked if MARK2 is inactivated, either by transfecting a dominant negative mutant, or by MARK2 inhibitors such as hymenialdisine. Alternatively, neurites are blocked if the target KXGS motifs on tau are rendered nonphosphorylatable by point mutations. The results suggest that MARK2 contributes to the plasticity of microtubules needed for neuronal polarity and the growth of neurites.
Localization of Phospholipase D1 to Caveolin-enriched Membrane via Palmitoylation: Implications for Epidermal Growth Factor Signaling
Authors: Han Jung Min , Kim Yong , Lee Jun Sung , Lee Chang Sup , Lee Byoung Dae , Ohba Motoi , Kuroki Toshio , Suh Pann-Ghill , Ryu Sung Ho
Published: November 2002

Phospholipase D (PLD) has been suggested to mediate epidermal growth factor (EGF) signaling. However, the molecular mechanism of EGF-induced PLD activation has not yet been elucidated. We investigated the importance of the phosphorylation and compartmentalization of PLD1 in EGF signaling. EGF treatment of COS-7 cells transiently expressing PLD1 stimulated PLD1 activity and induced PLD1 phosphorylation. The EGF-induced phosphorylation of threonine147 was completely blocked and the activity of PLD1 attenuated by point mutations (S2A/T147A/S561A) of PLD1 phosphorylation sites. The expression of a dominant negative PKCα mutant by adenovirus-mediated gene transfer greatly inhibited the phosphorylation and activation of PLD1 induced by EGF in PLD1-transfected COS-7 cells. EGF-induced PLD1 phosphorylation occurred primarily in the caveolin-enriched membrane (CEM) fraction, and the kinetics of PLD1 phosphorylation in the CEM were strongly correlated with PLD1 phosphorylation in the total membrane. Interestingly, EGF-induced PLD1 phosphorylation and activation and the coimmunoprecipitation of PLD1 with caveolin-1 and the EGF receptor in the CEM were significantly attenuated in the palmitoylation-deficient C240S/C241S mutant, which did not localize to the CEM. Immunocytochemical analysis revealed that wild-type PLD1 colocalized with caveolin-1 and the EGF receptor and that phosphorylated PLD1 was localized exclusively in the plasma membrane, although some PLD1 was also detected in vesicular structures. Transfection of wild-type PLD1 but not of C240S/C241S mutant increased EGF-induced raf-1 translocation to the CEM and ERK phosphorylation. This study shows, for the first time, that EGF-induced PLD1 phosphorylation and activation occur in the CEM and that the correct localization of PLD1 to the CEM via palmitoylation is critical for EGF signaling.
Nucleocytoplasmic Distribution of Human RNA-editing Enzyme ADAR1 Is Modulated by Double-stranded RNA-binding Domains, a Leucine-rich Export Signal, and a Putative Dimerization Domain
Authors: Strehblow Alexander , Hallegger Martina , Jantsch Michael F.
Published: November 2002

The human RNA-editing enzyme adenosine deaminase that acts on RNA (ADAR1) is expressed in two versions. A longer 150-kDa protein is interferon inducible and can be found both in the nucleus and cytoplasm. An amino-terminally truncated 110-kDa version, in contrast, is constitutively expressed and predominantly nuclear. In the absence of transcription, however, the shorter protein is also cytoplasmic and thus displays the hallmarks of a shuttling protein. The nuclear localization signal (NLS) of human hsADAR1 is atypical and overlaps with its third double-stranded RNA-binding domain (dsRBD). Herein, we identify regions in hsADAR1 that interfere with nuclear localization and mediate cytoplasmic accumulation. We show that interferon-inducible hsADAR1 contains a Crm1-dependent nuclear export signal in its amino terminus. Most importantly, we demonstrate that the first dsRBD of hsADAR1 interferes with nuclear localization of a reporter construct containing dsRBD3 as an active NLS. The same effect can be triggered by several other, but not all dsRBDs. Active RNA binding of either the inhibitory dsRBD1 or the NLS bearing dsRBD3 is required for cytoplasmic accumulation. Furthermore, hsADAR1's dsRBD1 has no effect on other NLSs, suggesting RNA-mediated cross talk between dsRBDs, possibly leading to masking of the NLS. A model, incorporating these findings is presented. Finally, we identify a third region located in the C terminus of hsADAR1 that also interferes with nuclear accumulation of this protein.
Modulation of Fibroblast Morphology and Adhesion during Collagen Matrix Remodeling
Authors: Tamariz Elisa , Grinnell Frederick
Published: November 2002

When fibroblasts are placed within a three-dimensional collagen matrix, cell locomotion results in translocation of the flexible collagen fibrils of the matrix, a remodeling process that has been implicated in matrix morphogenesis during development and wound repair. In the current experiments, we studied formation and maturation of cell–matrix interactions under conditions in which we could distinguish local from global matrix remodeling. Local remodeling was measured by the movement of collagen-embedded beads towards the cells. Global remodeling was measured by matrix contraction. Our observations show that no direct relationship occurs between protrusion and retraction of cell extensions and collagen matrix remodeling. As fibroblasts globally remodel the collagen matrix, however, their overall morphology changes from dendritic to stellate/bipolar, and cell–matrix interactions mature from punctate to focal adhesion organization. The less well organized sites of cell–matrix interaction are sufficient for translocating collagen fibrils, and focal adhesions only form after a high degree of global remodeling occurs in the presence of growth factors. Rho kinase activity is required for maturation of fibroblast morphology and formation of focal adhesions but not for translocation of collagen fibrils.
ENTANGLEMENT IN TWO VERTICALLY COUPLED IDENTICAL SINGLE-ELECTRON QUANTUM DOTS
Authors: ZHANG ZHAN-JUN , QIAO HAO-XUE , LI BAI-WEN
Published: November 2002

The evolutions of the von Neumann entropies of the low-lying states in two vertically coupled identical single-electron quantum dot systems with increasing magnetic field and inter-dot separation have been investigated. We show that both the external magnetic field and the inter-dot separation can induce the transition of the entropy of the system. Additionally, a suspicion (that is, the higher the excitation, the larger entropy) has been clarified and proven to be incorrect.
Studying Gene Function in Eukaryotes by Conditional Gene Inactivation
Authors: Gossen Manfred , Bujard Hermann
Published: November 2002

▪ Abstract  The prospect of specifically controlling gene activities in vivo has become a defining hallmark of many model organisms of biological research. Where once the aim was to gain control over gene activities using endogenous control elements, new technologies have emerged that owe their remarkable specificity to heterologous components derived from evolutionarily distant species. This review highlights inducible transcriptional systems and site-specific recombination. Their quantitative and qualitative characteristics are discussed, with examples of how recent developments have expanded the spectrum of cells and organisms that are now accessible to genetic dissection of unprecedented precision. Transgenesis has already converted the mouse into a prime model for mammalian genetics. Combined with the new approaches of conditional activation or inactivation of genes, this model has opened up new horizons for the analysis of gene function in mammals.
The Feline Genome Project
Authors: O'Brien Stephen J. , Menotti-Raymond Marilyn , Murphy William J. , Yuhki Naoya
Published: November 2002

▪ Abstract  The compilation of a dense gene map and eventually a whole genome sequence (WGS) of the domestic cat holds considerable value for human genome annotation, for veterinary medicine, and for insight into the evolution of genome organization among mammals. Human association and veterinary studies of the cat, its domestic breeds, and its charismatic wild relatives of the family Felidae have rendered the species a powerful model for human hereditary diseases, for infectious disease agents, for adaptive evolutionary divergence, for conservation genetics, and for forensic applications. Here we review the advantages, rationale, and present strategy of a feline genome project, and we describe the disease models, comparative genomics, and biological applications posed by the full resolution of the cat's genome.
Genetic Engineering Using Homologous Recombination
Authors: Court Donald L. , Sawitzke James A. , Thomason Lynn C.
Published: November 2002

▪ Abstract  In the past few years, in vivo technologies have emerged that, due to their efficiency and simplicity, may one day replace standard genetic engineering techniques. Constructs can be made on plasmids or directly on the Escherichia coli chromosome from PCR products or synthetic oligonucleotides by homologous recombination. This is possible because bacteriophage-encoded recombination functions efficiently recombine sequences with homologies as short as 35 to 50 base pairs. This technology, termed recombineering, is providing new ways to modify genes and segments of the chromosome. This review describes not only recombineering and its applications, but also summarizes homologous recombination in E. coli and early uses of homologous recombination to modify the bacterial chromosome. Finally, based on the premise that phage-mediated recombination functions act at replication forks, specific molecular models are proposed.
Effect of Diet and Exercise Intervention on Blood Pressure, Insulin, Oxidative Stress, and Nitric Oxide Availability
Authors: Roberts Christian K. , Vaziri Nosratola D. , Barnard R. James
Published: November 2002

Background—

Diet and exercise can affect blood pressure and atherosclerotic risk.

Methods and Results—

The present study was designed to examine the effects of a short-term, rigorous diet and exercise intervention on blood pressure, hyperinsulinemia, and nitric oxide (NO) availability. Men (n=11) were placed on a low-fat, high-fiber diet combined with daily exercise for 45 to 60 minutes for 3 weeks. Pre- and post fasting blood was drawn for serum lipid, insulin, 8-isoprostaglandin F
2α
(8-iso-PGF
2α
), and glucose measurements. Anthropometric parameters, blood pressure (BP), and 24-hour urinary NO metabolite excretion (NO
X
), a marker of NO bioavailability, were measured. Systolic (
P
<0.01) and diastolic BP (
P
<0.01) and 8-iso-PGF
2α
decreased (
P
<0.05), whereas urinary NO
X
increased (
P
<0.05). There was a significant reduction in fasting insulin (
P
<0.01) and a significant correlation between the decrease in serum insulin and the increase in urinary NO
X
(
r
2
=0.68,
P
<0.05). All fasting lipids decreased significantly, and the total cholesterol to high-density lipoprotein cholesterol ratio improved. Although body weight and body mass index (
P
<0.01) decreased, obesity was still present and there were no correlations between the change in body mass index and the change in insulin, BP, or urinary NO
X
.

Conclusions—

This intervention resulted in dramatic improvements in BP, oxidative stress, NO availability, and the metabolic profile within 3 weeks, mitigating the risk for atherosclerosis progression and its clinical sequelae.
Algunas reflexiones sobre la psicosociolingüística: la interrelación entre la lingüística y la psicología social
Authors: Valencia José F.
Published: November 2002

El presente artículo pretende plantear algunas reflexiones sobre la lingüística y la psicología social a raiz de la reciente aparición del texto Psicosociolingüística de la profesora Maria Jose Azurmendi. Aquí se plantea, desde una visión crítica, la necesidad de tener en cuenta los recientes aportes tanto de la lingüística (la búsqueda de lo que hay «mas allá de la sentencia») como de la psicología social (la búsqueda del contexto social) que ya estaban en el origen de ambas disciplinas. A través de la revisión de los cinco apartados de los que consta el texto, se realiza un análisis crítico de dicha interrelación. Finalmente, desde la psicología social, se plantean algunas ideas para superar la «falta de lenguaje» que esta disciplina ha sufrido.
Relación empírica entre el burnout y los estilos de solución de problemas interpersonales en una muestra de terapeutas y preparadores laborales de adultos autistas integrados en un programa de empleo con apoyo
Authors: García-Villamisar Domingo , Muela Carmen
Published: November 2002

En este estudio se analiza la relación empírica entre los estilos de solución de problemas interpersonales y el síndrome de burnout en una muestra de preparadores laborales y terapeutas de adultos con autismo que participan en un programa de empleo apoyado. Se aplicaron los cuestionarios de Maslach Burnout Inventory (Maslach y Jakson, 1997) y el de Social Problem-solving Inventory-Revised (D'Zurilla, Nezu y Maydeu, 1996). Los resultados indicaron que el cansancio emocional y la despersonalización están relacionados con los estilos negativos de solución de problemas. Sin embargo, los estilos de solución de problemas no son predictores de la realización personal.
Rol percibido en la relación del profesional de la salud con el paciente y cumplimiento terapéutico
Authors: Nouvilas Encarnación
Published: November 2002

Dentro del estudio de los procesos sociocognitivos implicados en la conducta de salud, el objetivo de este estudio es obtener la percepción de rol de las personas implicadas en la relación del profesional de la salud con el paciente. Así como su asociación con el cumplimiento terapéutico del paciente. Cien pacientes de hipertensión arterial esencial y cien profesionales de la salud (médicos y de enfermería) respondieron a los cuestionarios especialmente elaborados para este trabajo.

El cumplimiento terapéutico lo valoramos mediante una medida combinada de autoinforme y consecución de los objetivos terapéuticos. Los resultados mostraron que el rol del paciente podría evaluarse por los profesionales sanitarios en función de tres dimensiones fundamentales (obediencia/resistencia hacia la asistencia sanitaria; confianza/desconfianza hacia los profesionales sanitarios y cumplimiento/incumplimiento hacia los tratamientos terapéuticos). El rol de médico percibido por los pacientes se definió de forma más amplia y exigente que el rol de la enfermera. Y por último, observamos diferencias entre los pacientes cumplidores y los incumplidores respecto a algunas características atribuidas al rol del médico.
Análisis de respuestas abiertas en un cuestionario sobre conductas relacionadas con el SIDA
Authors: Sánchez Manuel , Muñoz Alicia
Published: November 2002

El objetivo de este trabajo es, por un lado, analizar y describir las respuestas que 402 alumnos de la Universidad de Huelva dan a una pregunta abierta—a través de análisis de textos—y, por otro, ver en quémedida estas respuestas se relacionan—por el método de las especificidades—con algunas características de los sujetos. Dichas características fueron determinadas a partir de sus respuestas en un cuestionario creado para medir conocimientos, actitudes, norma social percibida y control conductual percibido respecto a una conducta de prevención del SIDA: uso del condón. Los resultados del análisis de textos muestran cómo los sujetos justifican el no uso de condón en base a la estabilidad de sus relaciones sentimentales; además, los autores descubren que el cuestionario tiene efectos no previstos inicialmente por los investigadores sobre los sujetos estudiados: aporta nuevos concocimientos a los alumnos y les lleva a reflexionar sobre—e intentar cambiar—sus conductas de riesgo respecto al SIDA, entre otras consideraciones.
Variables moduladoras de las diferencias de sexo en los celos
Authors: Gómez-Jacinto Luis , Canto-Ortiz Jesús , García-Leiva Patricia
Published: November 2002

Los celos son un mecanismo psicológico clave para los hombres y las mujeres, que se activan en respuesta a la amenaza de una relación valiosa. Hay diferencia en la respuesta de hombres y mujeres ante una situación de celos. En general los hombres se sienten más preocupados que las mujeres por una infidelidad sexual potencial y las mujeres se sienten peor que los hombres ante una hipotética infidelidad emocional. Sin embargo, en las dos investigaciones realizadas se comprueba que algunos factores sociales y culturales—v.g. género y deseabilidad social—modulan esta asimetría sexual y apoyan una perspectiva interaccionista que minimiza la dicotomía causal evolución versus socialización. En ambos estudios se comprobó también que, en buena medida, las respuestas emitidas por los sujetos son debidas al artefacto experimental de elección forzada utilizado habitualmente. No se encontró dependencia entre el sexo y el tipo de celos experimentado cuando se controlaban los factores socioculturales y los sesgos delprocedimiento experimental.
Relaciones de género desde la perspectiva de la mujer y el continuo interpersonal-intergrupal
Authors: Moya Miguel , Montes Beatriz
Published: November 2002

Se presentan dos investigaciones en las que se pretende estudiar cómo las mujeres perciben las relaciones con los hombres. En la primera investigación, de carácter descriptivo, se le pidió a un grupo de mujeres que indicaran aquellas situaciones cotidianas en las que se hubieran sentidos tratadas en virtud de su grupo de género y no en virtud de sus características personales, así como las reacciones que tales situaciones le provocaban. Otro grupo de mujeres evaluó posteriormente las situaciones más representativas. Los resultados se analizan desde la perspectiva del continuo interpersonal-intergrupal. En una segunda investigación, de carácter experimental, mujeres estudiantes de Psicología fueron rechazadas (o elegidas) por un compañero en virtud de sus características personales o de su pertenencia al grupo de género. Se analizó las reacciones de las participantes ante este comportamiento del compañero. Las respuestas fueron mucho más positivas cuando fueron elegidas que cuando fueron rechazadas, y también aparecieron algunas diferencias en virtud de que el comportamiento del compañero tuviera una base interpersonal o intergrupal (mayor aceptación o rechazo en este segundo caso). Los resultados se discuten desde la perspectiva intergrupaly desde las nuevas formulaciones sobre el sexismo.
Burnout y engagement. Relación con el desempeño, madurez profesional y tendencia al abandono de los estudiantes
Authors: Manzano Guadalupe
Published: November 2002

El objetivo de este trabajo es analizar el burnout y su constructo hipotético opuesto “el engagement” en estudiantes universitarios. Además de determinar qué variables influyen en uno u otro, y profundizar en las relaciones entre estos dos constructos, estudiamos hasta qué punto pueden explicar, junto a algunas variables demográficas, el comportamiento de los estudiantes respectoa tres variablesps icosociales: desempeño, madurez profesional y tendencia al abandon.

La muestra esta compuesta por 1284 individuos (33,2% hombres y 66,7% mujeres) que cursan la Licenciatura en Administración y Dirección de Empresas en la Facultad de Ciencias Económicas y Empresariales de la Universidad del País Vasco.

Entre los resultados hallados, cabe destacar: 1. -La relación negativa entre las escalas del burnout agotamiento emocional y cinismo y las del engagement vigor, dedicación y absorción; así como una relación positiva entre la competencia percibida (burnout) y las tres escalas del engagement. 2. -La existencia de diferencias significativasen las dimensiones de burnout y engagement en función del sexo. 3. -La edad es el único factor que se repite en la explicación de las tres variables psicosociales. Las escalas del burnout y engagement contribuyen, de forma diferente, a la explicación de cada una de dichas variables.
Towards a more social Social Psychology: The case of meta-stereotypes
Authors: Otten Sabine
Published: November 2002

Based on the review by Gómez, who summarizes recent social-psychological work about meta-stereotypes, this domain of research will be located and discussed in the broader context of current Social Psychology. It is argued that the current work on meta-stereotyping is a prime example for a truly social-psychological approach, as it includes aspects of perspectivity, context-specificity, and of mutual social influence. By providing a more complete picture of the phenomenon of stereotyping in social contexts, research on meta-stereotypes can offer a good theoretical background to derive more efficient interventions towards reducing negative prejudice and improving intergroup relations.
Presiones internas del ámbito laboral y/o familiar como antecedentes del conflicto trabajo-familia
Authors: Marín Manuel , Infante Eduardo , Rivero Marcos
Published: November 2002

Analizamos los antecedentes en la génesis de percepciones conflicto trabajo-familia y viceversa. De acuerdo con la teoría de rol, se hipotetiza que las tensiones de rol familiar generan percepciones de conflicto familia-trabajo y que las tensiones de rol laboral se asociarán con percepciones de conflicto trabajo-familia. Al mismo tiempo, se analiza el papel modulador del género y de la prioridad de carrera en el trabajador. Un total de 85 trabajadores participaron en la recogida de datos que consistió en medidas autoinforme. En general, los resultados obtenidos confirman las relaciones iniciales. Las mujeres mostraron mayor vulnerabilidad a las tensiones de rol que los hombres. Estos, que mostraron diferencialmente mayor tendencia al equilibrio entre roles laborales y familiares, padecieron índices de interferencia ligeramente menores al de las trabajadoras. Se proponen nuevos trabajos para profundizar en las complejas relaciones entre los ámbitos de desarrollo humano.
Niveles de análisis en el estudio de liderazgo carismático
Authors: López-Zafra Esther , Morales J. Francisco
Published: November 2002

En este artículo revisamos brevemente el concepto de niveles de análisis y nos centramos en su aplicación al estudio de Liderazgo Carismático ya que este enfoque apenas si se ha tenido en cuenta y es prácticamente nulo su empleo en España.

Desde nuestro punto de vista consideramos que Carisma es un fenómeno que se incardina en el grupo, ya que existen diferencias significativas entre grupos de trabajo cuyo líder es carismático y aquellos otros cuyo líder no lo es. Esto nos hace pensar que debe explicarse en el nivel grupal.

Una técnica que sirve para comprobar el nivel de análisis adecuado es el denominado «análisis intra-entre»» (A.I.E. o W.A.B.A. Within-and Between entities analysis) que explicamos brevemente en este artículo. Para realizar nuestro estudio hemos administrado el M.L.Q. (Multifactor Leadership Questionnaire) junto con otras escalas en 39 unidades de producción (N total=199). Los resultados favorecen nuestra hipótesis en la dirección entregrupos en la relación entre Carisma y algunas variables. Por el contrario, otras relaciones se explican en el nivel intragrupo. Al final, ofrecemos una discusión de porqué se producen estos resultados y sus implicaciones.
Una intervención en los valores para la mejora del rendimiento académico
Authors: Ros María , Grad Héctor , Martínez-Sánchez Eva
Published: November 2002

Este trabajo presenta una investigación aplicada para estimar la eficacia de una intervención educativa dirigida a influir en las prioridades valorativas de estudiantes de secundaria como estrategia para lograr la mejora del rendimiento académico. Se describe la adaptación de la técnica de Autoconfrontación de Rokeach (1973) como procedimiento utilizado para influir sobre las prioridades de valores y mejorar las calificaciones escolares. El diseño experimental es pretest-postest sobre el rendimiento académico con grupo de control. La intervención se realizóen 12 grupos de 2' de B.U.P. (N= 301 alumnos), en 6 institutos de Madrid, asignando aleatoriamente un grupo a cada condición en cada instituto. Los resultados muestran que el uso de esta intervención educativa mejora de forma moderada aunque significativa los resultados académicos y que esta mejora es mayor para los alumnos insatisfechos con los resultados obtenidos en sus estudios, especialmente para aquellos insatisfechos con el tiempo que dedican a la tarea de estudiar.
La exploración de tácticas para la resolución de conflictos en relaciones íntimas: reanálisis de un instrumento de investigación
Authors: Bilsky Wolfgang , Borg Ingwer , Wetzels Peter
Published: November 2002

Este artículo surge de una encuesta nacional y representativa a víctimas cuyo fin fue la integración de las ventajas y experiencias tanto de la criminología como de la exploración de la violencia en el seno de las relaciones familiares. Una adaptación de las Escalas de Tácticas empleadas en Conflictos, CTS, de Straus fue uno de los instrumentos centrales utilizados en este estudio. A pesar de su empleo muy frecuente, el análisis de este instrumento ha venido acompañado de muchas dificultades, algunas de las cuales se tratan en este artículo. En primer lugar, vamos a presentar un esquema conceptual del CTS y su estructura. A continuación, describimos nuestro enfoque metodológico prestando atención a problemas particulares de este instrumento. En tercer lugar, resumiremos los resultados principales de nuestro estudio. Y, para finalizar, indicaremos cómo aplicar este enfoque metodológico a otros problemas de investigación.