bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells
Authors: Liang Ying , Van Zant Gary , Szilvassy Stephen J.
Published: April 2005

To test the hypothesis that aging has negative effects on stem-cell homing and engraftment, young or old C57BL/6 bone marrow (BM) cells were injected, using a limiting-dilution, competitive transplantation method, into old or young Ly5 congenic mice. Numbers of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) recovered from BM or spleen were measured and compared with the numbers initially transplanted. Although the frequency of marrow competitive repopulation units (CRUs) increased approximately 2-fold from 2 months to 2 years of age, the BM homing efficiency of old CRUs was approximately 3-fold lower than that of young CRUs. Surprisingly, the overall size of individual stem-cell clones generated in recipients receiving a single CRU was not affected by donor age. However, the increased ages of HSC donors and HSC transplant recipients caused marked skewing of the pattern of engraftment toward the myeloid lineage, indicating that HSC-intrinsic and HSC-extrinsic (microenvironmental) age-related changes favor myelopoiesis. This correlated with changes after transplantation in the rate of recovery of circulating leukocytes, erythrocytes, and platelets. Recovery of the latter was especially blunted in aged recipients. Collectively, these findings may have implications for clinical HSC transplantation in which older persons increasingly serve as donors for elderly patients. (Blood. 2005; 106:1479-1487)
Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report
Authors: Galbusera Miriam , Bresin Elena , Noris Marina , Gastoldi Sara , Belotti Daniela , Capoferri Cristina , Daina Erica , Perseghin Paolo , Scheiflinger Friedrich , Fakhouri Fadi , Grünfeld Jean-Pierre , Pogliani Enrico , Remuzzi Giuseppe
Published: April 2005

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor–cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.
Identification of a truncated nucleoprotein in avian metapneumovirus-infected cells encoded by a second AUG, in-frame to the full-length gene
Authors: Alvarez Rene , Seal Bruce S
Published: April 2005

Background

Avian metapneumoviruses (aMPV) cause an upper respiratory disease with low mortality, but high morbidity primarily in commercial turkeys. There are three types of aMPV (A, B, C) of which the C type is found only in the United States. Viruses related to aMPV include human, bovine, ovine, and caprine respiratory syncytial viruses and pneumonia virus of mice, as well as the recently identified human metapneumovirus (hMPV). The aMPV and hMPV have become the type viruses of a new genus within the Metapneumovirus. The aMPV nucleoprotein (N) amino acid sequences of serotypes A, B, and C were aligned for comparative analysis. Based on predicted antigenicity of consensus protein sequences, five aMPV-specific N peptides were synthesized for development of peptide-antigens and antisera.

Results

The presence of two aMPV nucleoprotein (N) gene encoded polypeptides was detected in aMPV/C/US/Co and aMPV/A/UK/3b infected Vero cells. Nucleoprotein 1 (N1) encoded from the first open reading frame (ORF) was predicted to be 394 amino acids in length for aMPV/C/US/Co and 391 amino acids in length for aMPV/A/UK/3b with approximate molecular weights of 43.3 kilodaltons and 42.7 kilodaltons, respectively. Nucleoprotein 2 (N2) was hypothesized to be encoded by a second downstream ORF in-frame with ORF1 and encoded a protein predicted to contain 328 amino acids for aMPV/C/US/Co or 259 amino acids for aMPV/A/UK/3b with approximate molecular weights of 36 kilodaltons and 28.3 kilodaltons, respectively. Peptide antibodies to the N-terminal and C-terminal portions of the aMPV N protein confirmed presence of these products in both aMPV/C/US/Co- and aMPV/A/UK/3b-infected Vero cells. N1 and N2 for aMPV/C/US/Co ORFs were molecularly cloned and expressed in Vero cells utilizing eukaryotic expression vectors to confirm identity of the aMPV encoded proteins.

Conclusion

This is the first reported identification of potential, accessory in-frame N2 ORF gene products among members of the Paramyxoviridae. Genomic sequence analyses of related members of the Pneumovirinae other than aMPV, including human respiratory syncytial virus and bovine respiratory syncytial virus demonstrated the presence of this second potential ORF among these agents.
Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells
Authors: Camirand Anne , Zakikhani Mahvash , Young Fiona , Pollak Michael
Published: April 2005

Introduction

Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas.

Methods

AG1024 (an inhibitor of IGF-1R) was used with gefitinib for treatment of MDA468, MDA231, SK-BR-3, and MCF-7 breast cancer lines, which express similar levels of IGF-1R but varying levels of EGFR. Proliferation assays, apoptosis induction studies, and Western blot analyses were conducted with cells treated with AG1024 and gefitinib as single agents and in combination.

Results

Gefitinib and AG1024 reduced proliferation in all lines when used as single agents, and when used in combination revealed an additive-to-synergistic effect on cell growth inhibition. Flow cytometry measurements of cells stained with annexin V-propidium iodide and cells stained for caspase-3 activation indicated that adding an IGF-1R-targeting strategy to gefitinib results in higher levels of apoptosis than are achieved with gefitinib alone. Gefitinib either reduced or completely inhibited p42/p44 Erk kinase phosphorylation, depending on the cell line, while Akt phosphorylation was reduced by a combination of the two agents. Overexpression of IGF-1R in SK-BR-3 cells was sufficient to cause a marked enhancement in gefitinib resistance.

Conclusion

These results indicate that IGF-1R signaling reduces the antiproliferative effects of gefitinib in several breast cancer cell lines, and that the addition of an anti-IGF-1R strategy to gefitinib treatment may be more effective than a single-agent approach.
Cortical Mechanisms of Saccade Generation from Execution to Decision
Authors: MILEA DAN , LOBEL ELIE , LEHÉRICY STÉPHANE , PIERROT‐DESEILLIGNY CHARLES , BERTHOZ ALAIN
Published: April 2005

Abstract: Several cortical areas are involved in the control of ocular motor behavior, but little is known about the cognitive processes occurring prior to saccade triggering. The use of functional brain imaging allows a better understanding of the networks involved specifically in distinct processes of saccade generation. The use of sophisticated visual stimulation paradigms in functional imaging studies suggests that the decision process of where to look when faced with visual alternatives is subserved by a prefrontoparietal network, including the dorsolateral prefrontal cortex.
Pontine Lesions May Cause Selective Deficits of “Slow” Vergence Eye Movements
Authors: RAMBOLD H. , NEUMANN G , SANDER T , HELMCHEN C
Published: April 2005

Abstract: To address the role of pontine nuclei in vergence control, eye movements to ramp (‘slow vergence’) and step targets (‘fast vergence’) were recorded in two patients with unilateral mediolateral pontine infarctions and in ten healthy controls. ‘Slow’ vergence and conjugate smooth pursuit eye movements were impaired while ‘fast’ vergence was not. We conclude that like smooth pursuit signals, vergence signals are distributed in the pontine nuclei.
Nuclear re-organisation of theHoxbcomplex during mouse embryonic development
Authors: Chambeyron Séverine , Da Silva Nelly R. , Lawson Kirstie A. , Bickmore Wendy A.
Published: April 2005

The spatial and temporal co-linear expression of Hox genes during development is an exquisite example of programmed gene expression. The precise mechanisms underpinning this are not known. Analysis of Hoxbchromatin structure and nuclear organisation, during the differentiation of murine ES cells, has lent support to the idea that there is a progressive`opening' of chromatin structure propagated through Hox clusters from 3′to 5′, which contributes to the sequential activation of gene expression. Here, we show that similar events occur in vivo in at least two stages of development. The first changes in chromatin structure and nuclear organisation were detected during gastrulation in the Hoxb1-expressing posterior primitive streak region: Hoxbchromatin was decondensed and the Hoxb1 locus looped out from its chromosome territory, in contrast to non-expressing Hoxb9, which remained within the chromosome territory. At E9.5, when differential Hox expression along the anteroposterior axis is being established, we found concomitant changes in the organisation of Hoxb. Hoxb organisation differed between regions of the neural tube that had never expressed Hoxb [rhombomeres (r) 1 and 2], strongly expressed Hoxb1 but not b9 (r4), had downregulated Hoxb1 (r5), expressed Hoxb9 but not Hoxb1 (spinal cord), and expressed both genes(tail bud). We conclude that Hoxb chromatin decondensation and nuclear re-organisation is regulated in different parts of the developing embryo, and at different developmental stages. The differential nuclear organisation of Hoxb along the anteroposterior axis of the developing neural tube is coherent with co-linear Hox gene expression. In early development nuclear re-organisation is coupled to Hoxb expression,but does not anticipate it.
Nef induces apoptosis by activating JNK signaling pathway and inhibits NF-κB-dependent immune responses in Drosophila
Authors: Lee Sung Bae , Park Jeehye , Jung Jae U. , Chung Jongkyeong
Published: April 2005

The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial. The present study illuminated the in vivo functions of Nef using Drosophila, in which genetic analyses can be conveniently conducted. Using Drosophila transgenic lines for wild-type Nef, we demonstrated that Nef is not involved in the regulation of cell proliferation but rather specifically induces caspase-dependent apoptosis in wings in a cell-autonomous manner. Interestingly, myristoylation-defective Nef completely failed to induce the apoptotic wing phenotypes, consistent with previous reports demonstrating a crucial role for membrane localization of Nef in vivo. Further genetic and immunohistochemical studies revealed that Nef-dependent JNK activation is responsible for apoptosis. Furthermore, we found that ectopic expression of Nef inhibits Drosophila innate immune responses including Relish NF-κB activation with subsequent induction of an antimicrobial peptide, diptericin. The in vivo functions of Nef in Drosophila are highly consistent with those found in mammals and so we propose that Nef regulates evolutionarily highly conserved signaling molecules of the JNK and NF-κB signaling pathways at the plasma membrane, and consequently modulates apoptosis and immune responses in HIV target cells.
RasGEF-containing proteins GbpC and GbpD have differential effects on cell polarity and chemotaxis in Dictyostelium
Authors: Bosgraaf Leonard , Waijer Arjen , Engel Ruchira , Visser Antonie J. W. G. , Wessels Deborah , Soll David , van Haastert Peter J. M.
Published: April 2005

The regulation of cell polarity plays an important role in chemotaxis. Previously, two proteins termed GbpC and GbpD were identified in Dictyostelium, which contain RasGEF and cyclic nucleotide binding domains. Here we show that gbpC-null cells display strongly reduced chemotaxis, because they are unable to polarise effectively in a chemotactic gradient. However, gbpD-null mutants exhibit the opposite phenotype: cells display improved chemotaxis and appear hyperpolar, because cells make very few lateral pseudopodia, whereas the leading edge is continuously remodelled. Overexpression of GbpD protein results in severely reduced chemotaxis. Cells extend many bifurcated and lateral pseudopodia, resulting in the absence of a leading edge. Furthermore, cells are flat and adhesive owing to an increased number of substrate-attached pseudopodia. This GbpD phenotype is not dependent on intracellular cGMP or cAMP, like its mammalian homolog PDZ-GEF. Previously we showed that GbpC is a high-affinity cGMP-binding protein that acts via myosin II. We conclude that cGMP activates GbpC, mediating the chemoattractant-induced establishment of cell polarity through myosin. GbpD induces the formation of substrate-attached pseudopodia, resulting in increased attachment and suppression of polarity.
Serotonin Toxicity Associated with Concomitant Use of Linezolid
Authors: Bergeron Luc , Boulé Martin , Perreault Sébastien
Published: April 2005

OBJECTIVE:

To report 2 cases of serotonin toxicity (ST) associated with concomitant use of linezolid and serotonergic drugs and review previously published case reports.

CASE SUMMARIES:

Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped.

DISCUSSION:

The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1–3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases.

CONCLUSIONS:

Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.
Attitude change and the public–private attitude distinction
Authors: MacDonald Geoff , Nail Paul R.
Published: April 2005

In this paper, we highlight the importance of the distinction between public and private attitudes in research on attitude change. First, we clarify the definitions of public and private attitudes by locating the researcher as a potential source of influence. In a test of this definition, we compare participant reports of potentially embarrassing behaviour and the study's importance between participants responding when a researcher has potential access to their reports (public condition), and participants whose reports the researcher has no potential access to (private condition). Participants high in public self‐focus or low in defensive self‐presentation reported the study to be more important in the public condition than the private condition. Further, participants in the public condition reported less frequency of engaging in embarrassing behaviours than those in the private condition, an effect not moderated by individual differences. We conclude that the public–private distinction is an essential element in attitude change theory.
The effect of anxiety on impression formation: Affect‐congruent or stereotypic biases?
Authors: Curtis Guy J. , Locke Vance
Published: April 2005

Two classes of theories propose that anxious individuals will form either more affect‐congruent or more stereotypic impressions of others. These theories' predictions are not mutually exclusive. Eighty‐one participants were examined to determine if either class of theories was more descriptive of the effect of anxiety on impression formation or whether a theory combining elements of both was more appropriate. Anxious participants read behavioural descriptions about an Australian Aboriginal target that were stereotypic, non‐stereotypic, threatening, and non‐threatening, and rated the target on traits that corresponded to the behavioural descriptions. Anxious participants formed impressions that were more affect‐congruent, but not more stereotypic, than those formed by control participants. This result was replicated in a field study with 61 participants who were waiting to see a dentist. Future studies should examine the cognitive mechanisms that influence and underlie anxious affect‐congruent impression formation.
Modular Organization of Excitatory Circuits between Neurons of the Spinal Superficial Dorsal Horn (Laminae I and II)
Authors: Lu Yan , Perl Edward R.
Published: April 2005

Neural circuitry of the spinal superficial dorsal horn (SDH) (laminae I and II) and its relationship to pain and other somatosensory phenomena remain poorly understood. To gain information on this issue, synaptic connections between identified SDH neurons were studied in rat spinal cord slices by simultaneous whole-cell recordings from pairs of cells. Both excitatory and inhibitory connections were noted. This report focuses on the observed excitatory linkages. Synaptic excitatory connections between SDH neurons proved highly selective and consistently were unidirectional. Two patterns repeatedly appeared (for neuron classification, see Materials and Methods) (Grudt and Perl, 2002). Lamina II central neurons, with dorsal root (DR) C-fiber input, monosynaptically excited lamina II vertical neurons with DR Aδ input. Lamina II outer vertical neurons with DR Aδ input monosynaptically excited lamina I neurons. Some of the postsynaptic lamina I cells were shown to project rostrally. In contrast to the usual case for connected neurons, in unconnected pairs, primary afferent input to the same type of neuron proved closely similar. Together, these observations indicate that the neural circuitry in the SDH, including its substantia gelatinosa (lamina II), has an explicit organization in which particular combinations of neurons comprise modules arranged to modify and transmit sensory information arriving from Aδ and C primary afferent fibers.
c-Jun NH2-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-β Precursor Protein
Authors: Muresan Zoia , Muresan Virgil
Published: April 2005

Abnormal phosphorylation of amyloid-β precursor protein (APP) is a pathologic feature of Alzheimer's disease. To begin to understand the mechanism of APP phosphorylation, we studied this process in differentiating neurons under normal physiological conditions. We found that c-Jun NH2-terminal kinase (JNK), not cyclin-dependent kinase 5, is required for APP phosphorylation, leading to localized accumulation of phosphorylated APP (pAPP) in neurites. We show that JNK-interacting protein-3 (JIP-3), a JNK scaffolding protein that does not bind APP, selectively increases APP phosphorylation, accumulation of pAPP into processes, and stimulates process extension in both neurons and COS-1 cells. Downregulation of JIP-3 by small interfering RNA impairs neurite extension and reduces the amount of localized pAPP. Finally, whereas stress-activated JNK generates pAPP only in the cell body, concomitant expression of JIP-3 restores pAPP accumulation into neurites. Thus, APP phosphorylation, transport of the generated pAPP into neurites, and neurite extension are interdependent processes regulated by JIP-3/JNK, in a pathway distinct from stress-activated JNK signaling.
Sharing Receptive Fields with Your Neighbors: Tuning the Vertical System Cells to Wide Field Motion
Authors: Farrow Karl , Borst Alexander , Haag Juergen
Published: April 2005

In the blowfly, the direction-selective response of the 60 lobula-plate tangential cells has been ascribed to the integration of local motion information across their extensive dendritic trees. Because the lobula plate is organized retinotopically, the receptive fields of the tangential cells ought to be determined by their dendritic architecture. However, this appears not always to be the case. One compelling example is the exceptionally wide receptive fields of the vertical system (VS) tangential cells. Using dual-intracellular recordings, Haag and Borst (2004) found VS cells to be mutually coupled in such a way that each VS cell is connected exclusively to its immediate neighbors. This coupling may form the basis of the broad receptive fields of VS cells. Here, we tested this hypothesis directly by photoablating individual VS cells. The receptive field width of VS cells indeed narrowed after the ablation of single VS cells, specifically depending on whether the receptive field of the ablated cell was more frontal or more posterior to the recorded cell. In particular, the responses changed as if the neuron lost access to visual information from the ablated neuron and those VS cells more distal than it from the recorded neuron. These experiments provide strong evidence that the lateral connections among VS cells are a crucial component in the mechanism underlying their complex receptive fields, augmenting the direct columnar input to their dendrites.
Timing of Conditioned Eyeblink Responses Is Impaired in Cerebellar Patients
Authors: Gerwig Marcus , Hajjar Karim , Dimitrova Albena , Maschke Matthias , Kolb Florian P. , Frings Markus , Thilmann Alfred F. , Forsting Michael , Diener Hans Christoph , Timmann Dagmar
Published: April 2005

In the present study, timing of conditioned eyeblink responses (CRs) was investigated in cerebellar patients and age-matched controls using a standard delay paradigm. Findings were compared with previously published data of CR incidences in the same patient population (Gerwig et al., 2003; Timmann et al., 2005). Sixteen patients with pure cortical cerebellar degeneration (spinocerebellar ataxia type 6 and idiopathic cerebellar ataxia), 14 patients with lesions within the territory of the superior cerebellar artery, and 13 patients with infarctions within the territory of the posterior inferior cerebellar artery were included. The affected cerebellar lobules and possible involvement of cerebellar nuclei were determined by three-dimensional magnetic resonance imaging (MRI) in patients with focal lesions (n= 27). Based on a voxel-by-voxel analysis, MRI lesion data were related to eyeblink conditioning data. CR incidence was significantly reduced, and CRs occurred significantly earlier in patients with cortical cerebellar degeneration and lesions of the superior cerebellum compared with controls. Incidence and timing of CRs was not impaired in patients with lesions restricted to the posterior and inferior cerebellum. Voxel-based MRI analysis revealed that cortical areas within the anterior lobe (Larsell lobule HV) were most significantly related to timing deficits, whereas reduced CR incidences were related to more caudal parts (lobule HVI) of the superior cerebellar cortex. The present data suggest that different parts of the superior cerebellar cortex may be involved in the formation of the stimulus association and appropriate timing of conditioned eyeblink responses in humans. Extracerebellar premotoneuronal disinhibition, however, is another possible explanation for changes in CR timing.
Downregulation of Activating Transcription Factor 5 Is Required for Differentiation of Neural Progenitor Cells into Astrocytes
Authors: Angelastro James M. , Mason Jeffrey L. , Ignatova Tatyana N. , Kukekov Valery G. , Stengren George B. , Goldman James E. , Greene Lloyd A.
Published: April 2005

The mechanisms that regulate neural progenitor cell differentiation are primarily unknown. The transcription factor activating transcription factor 5 (ATF5) is expressed in neural progenitors of developing brain but is absent from mature astrocytes and neurons. Here, we demonstrate that ATF5 regulates the conversion of ventricular zone (VZ) and subventricular zone (SVZ) neural progenitors into astrocytes. Constitutive ATF5 expression maintains neural progenitor cell proliferation and blocks theirin vitroandin vivodifferentiation into astrocytes. Conversely, loss of ATF5 function promotes cell-cycle exit and allows astrocytic differentiationin vitroandin vivo. CNTF, a promoter of astrocytic differentiation, downregulates endogenous ATF5, whereas constitutively expressed ATF5 suppresses CNTF-promoted astrocyte genesis. Unexpectedly, constitutive ATF5 expression in neonatal SVZ cells bothin vitroandin vivocauses them to acquire properties and anatomic distributions of VZ cells. These findings identify ATF5 as a key regulator of astrocyte formation and potentially of the VZ to SVZ transition.
Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development
Authors: Stepanek Laurie , Stoker Andrew W. , Stoeckli Esther , Bixby John L.
Published: April 2005

Receptor-type protein tyrosine phosphatases (RPTPs) are required for appropriate growth of axons during nervous system development inDrosophila. In the vertebrate, type IIa RPTPs [protein tyrosine phosphatase (PTP)-δ, PTP-σ, and LAR (leukocyte common-antigen-related)] and the type III RPTP, PTP receptor type O (PTPRO), have been implicated in the regulation of axon growth, but their roles in developmental axon guidance are unclear. PTPRO, PTP-δ, and PTP-σ are each expressed in chick motor neurons during the period of axonogenesis. To examine potential roles of RPTPs in axon growth and guidancein vivo, we used double-stranded RNA (dsRNA) interference combined within ovoelectroporation to knock down RPTP expression levels in the embryonic chick lumbar spinal cord. Although most branches of the developing limb nerves appeared grossly normal, a dorsal nerve identified as the anterior iliotibialis was clearly affected by dsRNA knock-down of RPTPs. In experimental embryos treated with dsRNA targeting PTP-δ, PTP-σ, or PTPRO, this nerve showed abnormal fasciculation, was reduced in size, or was missing entirely; interference with PTPRO produced the most severe phenotypes. Control embryos electroporated with vehicle, or with dsRNA targeting choline acetyltransferase or axonin-1, did not exhibit this phenotype. Surprisingly, embryos electroporated with dsRNA targeting PTP-δ together with PTPRO, or all three RPTPs combined, had less severe phenotypes than embryos treated with PTPRO alone. This result suggests that competition between type IIa and type III RPTPs can regulate motor axon outgrowth, consistent with findings inDrosophila. Our results indicate that RPTPs, and especially PTPRO, are required for axon growth and guidance in the developing vertebrate limb.
Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons
Authors: Voulalas Pamela J. , Holtzclaw Lynne , Wolstenholme Jennifer , Russell James T. , Hyman Steven E.
Published: April 2005

Striatal medium spiny neurons are an important site of convergence for signaling mediated by the neurotransmitters dopamine and glutamate. We report that in striatal neurons in primary culture, signaling through group I metabotropic glutamate receptors (mGluRs) 1/5 and the D1class of dopamine receptors (DRs) 1/5 converges to increase phosphorylation of the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase 2). Induction of mitogen-activated protein kinase kinase-dependent signaling cascades by either mGluR1/5 or DR1/5 gave rise to increases in phosphorylation of ERK2. Coactivation of mGluR1/5 and DR1/5 with (S)-3,5-dihydroxyphenylglycine and (+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride enhanced the phosphorylation of ERK2. This interaction between mGluR1/5 and DR1/5 required protein kinase C (PKC), because the PKC inhibitors calphostin C, bisindolylmaleimide I, and Gö6976 blocked DR1/5-enhanced phosphorylation of ERK2. Use of the phosphatase inhibitors calyculin and okadaic acid indicated that inhibition of protein phosphatases 1 and 2A dramatically enhanced ERK2 phosphorylation by mGluR1/5. Coactivation of mGluR1/5 and DR1/5 also enhanced cAMP-response element binding protein (CREB) phosphorylation (compared with each receptor agonist alone) but did not enhance CREB-mediated transcriptional activity. Thus, signal transduction pathways activated by DR1/5 and mGluR5 interact to modify downstream events in striatal neurons while retaining numerous regulatory checkpoints.
Torsin-Mediated Protection from Cellular Stress in the Dopaminergic Neurons ofCaenorhabditis elegans
Authors: Cao Songsong , Gelwix Christopher C. , Caldwell Kim A. , Caldwell Guy A.
Published: April 2005

Parkinson's disease (PD) is linked genetically to proteins that function in the management of cellular stress resulting from protein misfolding and oxidative damage. Overexpression or mutation of α-synuclein results in the formation of Lewy bodies and neurodegeneration of dopaminergic (DA) neurons. Human torsinA, mutations in which cause another movement disorder termed early-onset torsion dystonia, is highly expressed in DA neurons and is also a component of Lewy bodies. Previous work has established torsins as having molecular chaperone activity. Thus, we examined the ability of torsinA to manage cellular stress within DA neurons of the nematodeCaenorhabditis elegans.Worm DA neurons undergo a reproducible pattern of neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), a neurotoxin commonly used to model PD. Overexpression of torsins inC. elegansDA neurons results in dramatic suppression of neurodegeneration after 6-OHDA treatment. In contrast, expression of either dystonia-associated mutant torsinA or combined overexpression of wild-type and mutant torsinA yielded greatly diminished neuroprotection against 6-OHDA. We further demonstrated that torsins seem to protect DA neurons from 6-OHDA through downregulating protein levels of the dopamine transporter (DAT-1)in vivo. Additionally, we determined that torsins protect robustly against DA neurodegeneration caused by overexpression of α-synuclein. Using mutant nematodes lacking DAT-1 function, we also showed that torsin neuroprotection from α-synuclein-induced degeneration occurs in a manner independent of this transporter. Together, these data have mechanistic implications for movement disorders, because our results demonstrate that torsin proteins have the capacity to manage sources of cellular stress within DA neurons.
Constitutively Active G-Protein-Gated Inwardly Rectifying K+Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons
Authors: Chen Xixi , Johnston Daniel
Published: April 2005

A diversity of ion channels contributes to the active properties of neuronal dendrites. From the apical dendrites of hippocampal CA1 pyramidal neurons, we recorded inwardly rectifying K+channels with a single-channel conductance of 33 pS. The inwardly rectifying K+channels were constitutively active at the resting membrane potential. The amount of constitutive channel activity was significantly larger in the apical dendrites than in the soma. Activities of these inwardly rectifying K+channels were inhibited by Ba2+(200 μm) and tertiapin (10 nm), both of which are believed to block G-protein-coupled inwardly rectifying K+(GIRK) channels. Intracellularly applied GTPγS (20 μm) during dual dendritic recordings significantly increased constitutive channel activity. Baclofen (20 μm), an agonist for the G-protein-coupled GABABreceptor, also significantly increased the level of channel activity. Therefore, these channels are GIRK channels, which are constitutively active at rest in the apical dendrites of CA1 pyramidal neurons and can be further activated via G-protein-coupled neurotransmitter receptors.
Prevalence of the Metabolic Syndrome using the Modified ATP III Definitions for Workers in Japan, Korea and Mongolia
Authors: Shiwaku Kuninori , Nogi Akiko , Kitajima Keiko , Anuurad Erdembileg , Enkhmaa Byambaa , Yamasaki Masayuki , Kim Jung‐Man , Kim In‐Shik , Lee Sung‐Kook , Oyunsuren Tsendsuren , Yamane Yosuke
Published: April 2005

Prevalence of the Metabolic Syndrome using the Modified ATP III Definitions for Workers in Japan, Korea and Mongolia: Kuninori Shiwaku, et al. Department of Environmental and Preventive Medicine, Shimane University School of Medicine— A clustering of insulin resistance, hypertension and dyslipidemia has been labeled as the metabolic syndrome. Asians have a lower frequency of obesity than do Caucasians, but have an increasing tendency toward metabolic syndrome. Most data on metabolic syndrome are based on studies from Western countries with only limited information derived from Asian populations. We conducted a cross‐sectional study of individuals aged 30–60 yr in workplace settings. We examined and analyzed the health data of 1,384 Japanese, Koreans and Mongolians for metabolic syndrome based on the modified definitions of the working definition proposed by the Third Report of the National Cholesterol Educational Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III definition). The prevalence of metabolic syndrome using the ATP III‐BMI30 and ATP III‐BMI25 definitions was 7% and 12% for Japanese, 7% and 13% for Koreans, and 12% and 16% for Mongolians, respectively. With the exception of obesity, the prevalences of individual metabolic abnormalities within each of the three Asian groups were similar to each other and to reported rates of prevalence in the U.S.A. Nevertheless, the values of sensitivity and specificity by the metabolic syndrome definitions are remarkably different relative to ethnicity. A universal metabolic syndrome definition is inappropriate for comparisons of metabolic syndrome among Asian ethnic groups. We believe that the ATP III‐BMI25 definition is suitable for the determination of metabolic syndrome among Japanese and Koreans, and that the ATP III‐BMI30 is more appropriate for Mongolians.
Merkel Cell Carcinoma in Patients with Long‐Term Ingestion of Arsenic
Authors: Ho Sheng‐Yow , Tsai Yi‐Chang , Lee Ming‐Chin , Guo How‐Ran
Published: April 2005

Merkel Cell Carcinoma in Patients with Long‐Term Ingestion of Arsenic: Sheng‐Yow HO, et al. Departments of Radiation Oncology, Sin‐Lau Christian Hospital, Taiwan—Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, mostly occurring late in life on sun‐exposed body parts. Little is known about the specific etiological factors in the pathogenesis of MCC. A previous report indicated that arsenic exposure might cause MCC, which might be another specific type of skin cancer associated with arsenic exposure. On the southwest coast of Taiwan, high arsenic levels in artesian well water have been documented, and various diseases associated with arsenic exposure have been found to be prevalent in this area. We report two pathologically confirmed cases of MCC in patients who had histories of long‐term ingestion of arsenic from drinking water. The tumors were on the anterior chest wall, an area less exposed to the sun, in both cases. The literature on the dose‐response relationship between arsenic exposure and MCC is limited. We estimated that the total arsenic ingested by these two cases was around 14.7 and 2.6 gm, respectively. We also tried to assess the cancer risk on the basis of the estimated doses of arsenic exposure and the cancer risk model developed by the U.S. Environmental Protection Agency (EPA). The estimated lifetime target cancer risk was 1.3 × 10–2 in Case 1 and 2.3 × 10–3 in Case 2. Both are much higher than the 10–6 upper limit on lifetime cancer risk put forth by the U.S. EPA health protection standard. We believe that arsenic intoxication played an important role in the carcinogenic process of MCC in our cases.
Lefschetz-Pontrjagin duality for differential characters
Authors: HARVEY REESE , LAWSON BLAINE
Published: April 2005

A theory of differential characters is developed for manifolds with boundary. This is done from both the Cheeger-Simons and the deRham-Federer viewpoints. The central result of the paper is the formulation and proof of a Lefschetz-Pontrjagin Duality Theorem, which asserts that the pairing  given by (alpha, beta)  (alpha * beta) [X] induces isomorphisms   onto the smooth Pontrjagin duals. In particular,  and  are injective with dense range in the group of all continuous homomorphisms into the circle. A coboundary map is introduced which yields a long sequence for the character groups associated to the pair (X, X). The relation of the sequence to the duality mappings is analyzed.
Non-holonomic connections following Élie Cartan
Authors: KOILLER JAIR , RODRIGUES PAULO R. , PITANGA PAULO
Published: April 2005

In this note we revisit E. Cartan's address at the 1928 International Congress of Mathematicians at Bologna, Italy. The distributions considered here will be of the same class as those considered by Cartan, a special type which we call strongly or maximally non-holonomic. We set up the groundwork for using Cartan's method of equivalence (a powerful tool for obtaining invariants associated to geometrical objects), to more general non-holonomic distributions.
Coherent soliton propagation through doped optical fibers: cloning, breakup, and soliton interactions
Authors: CAVALCANTI SOLANGE B. , FONSECA EDUARDO J. DA S. , CAETANO DILSON P. , HICKMANN JANDIR M.
Published: April 2005

The simultaneous propagation of two optical pulses through a doped nonlinear dispersive medium modelled by a resonant three-level system was investigated numerically, within the framework of a pair of coupled extended nonlinear Schrödinger equations. These included the contribution of the dopant resonances whose dynamics is governed by Bloch equations. In this work, we review the interesting possibilities on the manipulation of fields such as cloning, breakup and soliton interactions, that the combination of coherent population trapping with nonlinear dispersive media offers.
Sr and Nd isotopic characteristics of 1.77-1.58 Ga rift-related granites and volcanics of the Goiás tin province, central Brazil
Authors: PIMENTEL MÁRCIO M. , BOTELHO NILSON F.
Published: April 2005

Supracrustal rocks of the Araí Group, together with coeval A-type granites represent a ca. 1.77-1.58 Ga old continental rift in Brazil. Two granite families are identified: the older (1.77 Ga) group forms small undeformed plutons, and the younger granites (ca. 1.58 Ga) constitute larger, deformed plutons. Sr-Nd isotopic data for these rocks indicate that the magmatism is mostly product of re-melting of Paleoproterozoic sialic crust. Initial Sr ratios for both granite families are ca 0.726 and 0.720. Most TDM model ages are between 2.58 and 1.80 Ga. epsilonND(T) values are between +3.6 and -11.9. Araí volcanics are bimodal, with basalts and dacites/rhyolites interlayered with continental sediments. The felsic volcanics show Nd isotopic characteristics which are very similar to the granites, and are also interpreted as reworking of Paleoproterozoic crust. Detrital sediments of the Araí Group revealed T DM model ages between 2.4 and 2.16 Ga, indicating that they are the product of erosion of Paleoproterozoic crust. The data indicate that the Araí rift system was established on crust that had just become stable after the Paleoproterozoic orogeny.
U-Pb SHRIMP and Sm-Nd geochronology of the Silvânia Volcanics and Jurubatuba Granite: juvenile Paleoproterozoic crust in the basement of the Neoproterozoic Brasília Belt, Goiás, central Brazil
Authors: FISCHEL DANIELLE P. , PIMENTEL MÁRCIO M. , FUCK REINHARDT A. , ARMSTRONG RICHARD
Published: April 2005

U-Pb SHRIMP and Sm-Nd isotopic ages were determined for felsic metavolcanic rocks from the Silvânia Sequence and Jurubatuba Granite in the central part of the Brasília Belt. Zircon grains from a metavolcanic sample yielded 2115 ± 23 Ma and from the granite yielded 2089 ± 14 Ma, interpreted as crystallization ages of these rocks. Six metavolcanic samples of the Silvânia Sequence yielded a six-point whole-rock Sm-Nd isochron indicating a crystallization age of 2262 ± 110 Ma and positive epsilonNd(T) = +3.0 interpreted as a juvenile magmatic event. Nd isotopic analyses on samples from the Jurubatuba Granite have Paleoproterozoic T DM model ages between 2.30 and 2.42 Ga and epsilonNd(T) values vary between -0.22 and -0.58. The oldest T DM value refers to a sedimentary xenolith in the granite. These results suggest crystallization ages of Silvânia volcanics and Jurubatuba Granite are the first evidence of a ca. 2.14-2.08 juvenile magmatic event in the basement of the central part of the Brasília Belt that implies the presence of arc/suture hidden in reworked basement of the Brasília Belt.
Spectrophotometric determination of phenol in the presence of congeners by multivariated calibration
Authors: SOUZA KELY VIVIANE DE , PERALTA-ZAMORA PATRICIO
Published: April 2005

The generation of poly-hydroxilated transient species during the photochemical treatment of phenol usually impedes the spectrophotmetric monitoring of its degradation process. Frequently, the appearance of compounds such as pyrocatechol, hydroquinone and benzoquinone produces serious spectral interference, which hinder the use of the classical univariate calibration process. In this work, the use of multivariate calibration is proposed to permit the spectrophotometric determination of phenol in the presence of these intermediates. Using 20 synthetic mixtures containing phenol and the interferents, a calibration model was developed by using a partial least square regression process (PLSR) and processing the absorbance signal between 180 and 300 nm. The model was validated by using 3 synthetic mixtures. In this operation, typical errors lower than 3% were observed. Close correlation between the results obtained by liquid chromatography and the proposed method was also observed.
Synthesis of calcium-phosphate and chitosan bioceramics for bone regeneration
Authors: FINISIE MELLATIE R. , JOSUÉ ATCHE , FÁVERE VALFREDO T. , LARANJEIRA MAURO C. M.
Published: April 2005

Bioceramic composites were obtained from chitosan and hydroxyapatite pastes synthesized at physiological temperature according to two different syntheses approaches. Usual analytical techniques (X-ray diffraction analysis, Fourier transformed infrared spectroscopy, Thermo gravimetric analysis, Scanning electron microscopy, X-ray dispersive energy analysis and Porosimetry) were employed to characterize the resulting material. The aim of this investigation was to study the bioceramic properties of the pastes with non-decaying behavior from chitosan-hydroxyapatite composites. Chitosan, which also forms a water-insoluble gel in the presence of calcium ions, and has been reported to have pharmacologically beneficial effects on osteoconductivity, was added to the solid phase of the hydroxyapatite powder. The properties exhibited by the chitosan-hydroxyapatite composites were characteristic of bioceramics applied as bone substitutes. Hydroxyapatite contents ranging from 85 to 98% (w/w) resulted in suitable bioceramic composites for bone regeneration, since they showed a non-decaying behavior, good mechanical properties and suitable pore sizes.
About periodic and quasi-periodic orbits of a new type for twist maps of the torus
Authors: ADDAS-ZANATA SALVADOR
Published: April 2005

We prove that for a large and important class of C¹ twist maps of the torus periodic and quasi-periodic orbits of a new type exist, provided that there are no rotational invariant circles (R.I.C's). These orbits have a non-zero "vertical rotation number'' (V.R.N.), in contrast to what happens to Birkhoff periodic orbits and Aubry-Mather sets. The V.R.N. is rational for a periodic orbit and irrational for a quasi-periodic. We also prove that the existence of an orbit with a V.R.N = a > 0, implies the existence of orbits with V.R.N = b, for all 0 < b < a. And as a consequence of the previous results we get that a twist map of the torus with no R.I.C's has positive topological entropy, which is a very classical result. In the end of the paper we present some applications and examples, like the Standard map, such that our results apply.
Morphology and sedimentology of the Itaipú Embayment - Niterói/RJ
Authors: SALVADOR MARCUS VINICIUS S. , SILVA MARIA AUGUSTA M. DA
Published: April 2005

Bathymetric and sedimentological data from water depths between 3 and 28 meters are the basis of a detailed bathymetric map of the Itaipú Embayment and an understanding of its sedimentary dynamics. Shallower than 16 meters the contours are parallel to the shoreline whereas the morphology of the deeper bottom is influenced by the Menina, Mãe, and Pai islands. Medium sand is prevalent, with local variations in more protected or less protected areas. Minor amount of black mud possibly derives from the Itaipú Lagoon. Siliciclastic granules and pebbles may be relict. The Itaipú Embayment’s bottom morphology is controlled by stormy waves and the calmer easternmost part of the embayment presents a tendency to accumulate finer sediments.
Pharmaceuticals from natural products: current trends
Authors: SEIDL PETER R.
Published: April 2005

The use of products extracted from plants for medicinal purposes can be traced to the beginnings of civilization and up until the end of the nineteenth century natural products were the principal source of medicines. Since then their relative importance has oscillated according to the strategies of large pharmaceutical companies. Now that these strategies are changing, there are new opportunities for countries like Brazil, in which a large proportion of the world's biodiversity is located. There are, however, new circumstances that must be taken into consideration: material must be collected by groups which are formally authorized to do so and under the conditions of the Convention of Biological Diversity, the discovery process is being successively outsourced to smaller specialized firms and there is a growing integration with producers of cosmetics and phytomedicines.