bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase inhibitor trichostatin a potentiates doxorubicin‐induced apoptosis by up‐regulating PTEN expression
Authors: Pan Lina , Lu Jun , Wang Xiuli , Han Liping , Zhang Yu , Han Songyan , Huang Baiqu 
Published: March 2007

AbstractBACKGROUND.The tumor suppressor gene PTEN is a major negative regulator of the PI3K/Akt cellular survival pathway. Overexpression of PTEN by adenoviral transfection increases doxorubicin‐induced apoptosis. Whereas doxorubicin‐induced apoptosis can be potentiated by the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), the mechanisms underlying this process remain unclear. The aim of this work was to investigate whether changes in PTEN expression are involved in TSA/doxorubicin‐induced apoptosis.METHODS.We treated 293 T cells with TSA and doxorubicin, detected apoptosis by using Hoechst 33342 staining, and examined changes of PTEN and Egr‐1 expression by quantitative real‐time polymerase chain reaction (PCR). Luciferase reporter assay was used to evaluate the promoter activity of PTEN and Western blot and enzyme‐linked immunosorbent assay (ELISA) were used to confirm changes in the expression of PTEN. The chromatin immunoprecipitation (ChIP) assay was performed to estimate the acetylation level of PTEN promoter.RESULTS.Doxorubicin‐induced apoptosis was enhanced by TSA, whereas small interfering RNA (siRNA) targeting PTEN inhibited TSA/doxorubicin‐induced apoptosis. Also, TSA promoted Egr‐1 expression, which is the main transcription factor of PTEN, and this resulted in up‐regulation of PTEN expression, which consequently potentiated apoptosis. Moreover, histone acetyltransferase p300 was able to synergistically activate PTEN transcription with Egr‐1, implicating the role of histone acetylation in the regulation of PTEN expression.CONCLUSIONS.TSA promoted doxorubicin‐induced apoptosis through a mechanism that involved the stimulation of Egr‐1 expression, acetylation of core histones at the PTEN promoter, and consequently induction of PTEN transcription. These findings provide a theoretical basis for the therapeutic application of combined treatment of TSA/doxorubicin for cancer. Cancer 2007. © 2007 American Cancer Society.
Ferric and Ferrous Iron in Nitroso‐Myoglobin: Computer Simulations of Stable and Metastable States and Their Infrared Spectra
Authors: Nutt David R. , Meuwly Markus 
Published: March 2007

AbstractThe binding of NO to iron is involved in the biological function of many heme proteins. Contrary to ligands like CO and O2, which only bind to ferrous (FeII) iron, NO binds to both ferrous and ferric (FeIII) iron. In a particular protein, the natural oxidation state can therefore be expected to be tailored to the required function. Herein, we present an ab initio potential‐energy surface for ferric iron interacting with NO. This potential‐energy surface exhibits three minima corresponding to η1‐NO coordination (the global minimum), η1‐ON coordination and η2 coordination. This contrasts with the potential‐energy surface for FeII–NO, which exhibits only two minima (the η2 coordination mode for FeII is a transition state, not a minimum). In addition, the binding energies of NO are substantially larger for FeIII than for FeII. We have performed molecular dynamics simulations for NO bound to ferric myoglobin (MbIII) and compare these with results obtained for MbII. Over the duration of our simulations (1.5 ns), all three binding modes are found to be stable at 200 K and transiently stable at 300 K, with eventual transformation to the η1‐NO global‐minimum conformation. We discuss the implication of these results related to studies of rebinding processes in myoglobin.
Neurotrophic rationale in glaucoma: A TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cellsin vivo
Authors: Shi ZhiHua , Birman Elena , Saragovi H. Uri 
Published: March 2007

AbstractGlaucoma is a major cause of vision impairment, which arises from the sustained and progressive apoptosis of retinal ganglion cells (RGC), with ocular hypertension being a major risk or co‐morbidity factor. Because RGC death often continues after normalization of ocular hypertension, growth factor‐mediated protection of compromised neurons may be useful. However, the therapeutic use of nerve growth factor (NGF) has not proven effective at delaying RGC death in glaucoma. We postulated that one cause for the failure of NGF may be related to its binding to two receptors, TrkA and p75. These receptors have distinct cellular distribution in the retina and in neurons they induce complex and sometimes opposing activities. Here, we show in anin vivotherapeutic model of glaucoma that a selective agonist of the pro‐survival TrkA receptor was effective at preventing RGC death. RGC loss was fully prevented by combining the selective agonist of TrkA with intraocular pressure‐lowering drugs. In contrast, neither NGF nor an antagonist of the pro‐apoptotic p75 receptor protected RGCs. These results further a neurotrophic rationale for glaucoma. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Expression of FOS, EGR‐1, and ARC in the amygdala and hippocampus of female rats during formation of the intromission mnemonic of pseudopregnancy
Authors: Yang Jasmine J. , Oberlander Joseph G. , Erskine Mary S. 
Published: March 2007

AbstractPseudopregnancy (PSP) in the female rat is a neuroendocrine condition that is induced by repeated and intermittent vaginocervical stimulation received during mating and involves the expression of bicircadian prolactin surges and cessation of normal estrous cyclicity for 10–12 days postmating. The temporal patterning and number of intromissions received by the female are critical for PSP initiation, and thus, short‐term encoding of VCS occurs during transduction of intromissions into PSP. In this experiment, we characterized and compared the mating‐induced neural activation patterns within amygdalar and hippocampal regions using expression of the immediate early genes FOS, EGR‐1, and ARC. Cycling female rats mated on proestrus received 15 or 5 intromissions under paced or nonpaced mating conditions. High numbers of intromissions during nonpaced mating or low numbers received during paced mating are sufficient to induce PSP, while five nonpaced intromissions and mounts without intromission are insufficient. Here we demonstrate that the CA1 region of the hippocampus was selectively sensitive to PSP‐sufficient but not PSP‐insufficient mating stimulation by showing significant effects of paced mating for all three IEGs. Paced mating also stimulated the expression of ARC within the basolateral, cortical, and central nuclei of the amygdala. The posterodorsal medial amygdala also showed selective EGR‐1 responses to PSP‐sufficient mating stimulation. There was no effect of hemisphere on IEG expression. The postmating expression profiles of these IEGs provide evidence that limbic areas involved in encoding and consolidation of memory are involved in initiating the neuroendocrine memory of PSP. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Interaction between hindbrain and spinal networks during the development of locomotion in zebrafish
Authors: Chong Mabel , Drapeau Pierre 
Published: March 2007

AbstractLittle is known about the role of the hindbrain during development of spinal network activity. We set out to identify the activity patterns of reticulospinal (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae. Simultaneous recordings of RS neurons and spinal motoneurons revealed that these were coactive during spontaneous fictive swim episodes. We characterized four types of RS activity patterns during fictive swimming: (i) a spontaneous pattern of discharges resembling evoked high‐frequency spiking during startle responses to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim episodes, and (iv) RS cell activity uncorrelated with motoneuron activity. Despite lesions to the rostral spinal cord that prevented ascending spinal axons from entering the hindbrain (normally starting at ∼20 h), RS neurons continued to display the aforementioned activity patterns at day 3. However, removal of the caudal portion of the hindbrain prior to the descent of RS axons left the spinal cord network unable to generate the rhythmic oscillations normally elicited by application of N‐methyl‐D‐aspartate (NMDA), but in ∼40% of cases chronic incubation in NMDA maintained rhythmic activity. We conclude that there is an autonomous embryonic hindbrain network that is necessary for proper development of the spinal central pattern generator, and that the hindbrain network can partially develop independently of ascending input. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
BDNF‐mediated modulation of GABA and glycine release in dorsal horn lamina II from postnatal rats
Authors: Bardoni Rita , Ghirri Alessia , Salio Chiara , Prandini Massimiliano , Merighi Adalberto 
Published: March 2007

AbstractRecent studies show that excitatory glutamatergic transmission is potentiated by BDNF in superficial dorsal horn, both at the pre‐ and the postsynaptic site. The role of BDNF in modulating GABA and glycine‐mediated inhibitory transmission has not been fully investigated. To determine whether the neurotrophin is effective in regulating the spontaneous release of the two neurotransmitters, we have recorded miniature inhibitory postsynaptic currents (mIPSCs) in lamina II of post‐natal rats. We show that application of BDNF enhanced the spontaneous release of GABA and glycine, in presence of tetrodotoxin. The effect was blocked by the trk‐receptor inhibitor k‐252a. Amplitude and kinetics of mIPSCs were not altered. Evoked GABA and glycine IPSCs (eIPSCs) were depressed by BDNF and the coefficient of variation of eIPSC amplitude was significantly increased. By recording glycine eIPSCs with the paired‐pulse protocol, an increase of paired‐pulse ratio during BDNF application was observed. We performed parallel ultrastructural studies to unveil the circuitry involved in the effects of BDNF. These studies show that synaptic interactions between full length functional trkB receptors and GABA‐containing profiles only occur at non peptidergic synaptic glomeruli of types I and II. Expression of trkB in presynaptic vesicle‐containing dendrites originating from GABAergic islet cells, indicates these profiles as key structures in the modulation of inhibitory neurotransmission by the neurotrophin. Our results thus describe a yet uncharacterized effect of BDNF in lamina II, giving further strength to the notion that the neurotrophin plays an important role in pain neurotransmission. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Extracellular ATP in activity‐dependent remodeling of the neuromuscular junction
Authors: Jia Min , Li Min‐Xu , Fields R. Douglas , Nelson Phillip G. 
Published: March 2007

AbstractElectrical activity during early development affects the development and maintenance of synapses (Spitzer [2006]: Nature 4447:707–712), but the intercellular signals regulating maintenance of synapses are not well identified. At the neuromuscular junction, adenosine 5‐triphosphate (ATP) is coreleased with acetylcholine at activated nerve terminals to modulate synaptic function. Here we use cocultured mouse motor neurons and muscle cells in a three‐compartment cell culture chamber to test whether endogenously released ATP plays a role in activity‐dependent maintenance of neuromuscular synapses. The results suggest that ATP release at the synapse counters the negative effect of electrical activity, thus stabilizing activated synapses. Confirming our previous work (Li et al. [2001]: Nat Neurosci 4:871–872), we found that in doubly innervated muscles, electrical stimulation induced heterosynaptic downregulation of the nonstimulated convergent input to the muscle fiber with no or little change of the stimulated inputs. However, in preparations that were stimulated in the presence of apyrase, an enzyme that degrades extracellular ATP, synapse downregulation of stimulated inputs was substantial and significant, and end plate potentials were reduced. Apyrase treatment for 20 h in the absence of stimulation did result in moderate diminution, but this was prevented by blocking spontaneous neural activity with tetrodotoxin. The P2 receptor blocker, suramin, also induced activity‐dependent synapse diminution. The decrease in synaptic efficacy produced by prolonged stimulation in the presence of apyrase persisted for greater than 20 h, consistent with a developmental time‐course and distinct from the rapid neuromodulatory actions of ATP that have been demonstrated by others. We conclude that extracellular ATP promotes stabilization of the neuromuscular junction and may play a role in activity‐dependent synaptic modification during development. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
The G‐protein coupling properties of the human sweet and amino acid taste receptors
Authors: Sainz Eduardo , Cavenagh Margaret M. , LopezJimenez Nelson D. , Gutierrez Joanne C. , Battey James F. , Northup John K. , Sullivan Susan L. 
Published: March 2007

AbstractThe human T1R taste receptors are family C G‐protein‐coupled receptors (GPCRs) that act as heterodimers to mediate sweet (hT1R2 + hT1R3) and umami (hT1R1 + hT1R3) taste modalities. Each T1R has a large extracellular ligand‐binding domain linked to a seven transmembrane‐spanning core domain (7TMD). We demonstrate that the 7TMDs of hT1R1 and hT1R2 display robust ligand‐independent constitutive activity, efficiently catalyzing the exchange of GDP for GTP on Gα subunits. In contrast, relative to the 7TMDs of hT1R1 and hT1R2, the 7TMD of hT1R3 couples poorly to G‐proteins, suggesting that in vivo signaling may proceed primarily through hT1R1 and hT1R2. In addition, we provide direct evidence that the hT1Rs selectively signal through Gαi/o pathways, coupling to multiple Gαi/o subunits as well as the taste cell specific Gβ1γ13 dimer. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Effect of lipopolysaccharide on intracellular killing of Leishmania enriettii and correlation with macrophage oxidative metabolism
Authors: Mauël Jacques , Buchmüller‐Rouiller Yolande 
Published: March 2007

AbstractThe effect of lipopolysaccharide (LPS) on the lymphokine (LK)‐dependent activation of murine peritoneal macrophages for intracellular killing of Leishmania enriettii parasites was investigated. Exposure to LPS alone did not induce macrophages to kill the parasite. In the presence of LK or recombinant interferon‐γ, however, which by themselves rendered the macrophages only weakly cytotoxic, considerable stimulation of intracellular parasite killing was achieved already at a LPS concentration of 1 ng/ml. The response to LPS was of the same magnitude in macrophages tested for intracellular killing as in parallel assays of extracellular cytolysis of target cells. Acquisition of leishmanicidal activity by macrophages exposed to LK and LPS correlated with stimulation of the respiratory burst, as shown by increased hexose monophosphate shunt levels, and priming for elevated chemiluminescence and O2− and H2O2 production. Polymyxin B blocked both this LPS‐dependent metabolic activity and intracellular parasite destruction. Intracellular killing was, however, not solely dependent on oxidative metabolism of macrophages since (a) in the absence of LK, LPS stimulated respiratory burst activity, yet no intracellular killing was observed, and (b) triggering of the respiratory burst by phorbol myristate acetate or zymosan did not affect intracellular parasite survival. These results suggest that, in this experimental model, efficient intracellular parasite killing depends both on increased production of oxygen metabolites and on the availability of so far unidentified factor(s), the synthesis of which requires exposure of macrophages to both LK and LPS.
Specific lysis of Listeria monocytogenes‐infected macrophages by class II‐restricted L3T4+ T cells
Authors: Kaufmann Stefan H. E. , Hug Erika , Väth Ulla , De Libero Gennaro 
Published: March 2007

AbstractMice were infected with the intracellular bacterium, Listeria monocytogenes, and T cell clones from spleens, lymph nodes and peritoneal exudates were established. The capacity of L3T4+, Lyt2− T‐cell clones to specifically lyse L. monocytogenes‐infected macrophages was analyzed. As a source of target cells, bone marrow macrophages (BMMΦ) after 9 days of culture in hydrophobic teflon bags were used. These BMMΦ were totally Ia−; however, significant Ia‐expression could be induced by interferon‐γ (IFN‐γ). IFN‐γ‐stimulated BMMΦ, after priming with live or killed L. monocytogenes organisms were effectively lysed by the vast majority of L3T4+ T cell clones. In the absence of either IFN‐γ stimulation or antigen priming, no lysis occurred. Cytolysis was demonstrable in a conventional 4‐h 51Cr‐release assay and in an 18‐h neutral red uptake assay and was antigen specific and class II restricted. Native T cells from L. monocytogenes‐infected mice failed to lyse stimulated, L. monocytogenes‐primed BMMΦ and gained their cytolytic activity after antigenic restimulation in vitro. These data demonstrate that L. monocytogenes‐specific L3T4+ T cells could lyse MΦ presenting listerial antigens provided that Ia antigen expression had been induced. L3T4+ T cell clones produced IFN‐γ after restimulation with antigen plus accessory cells in vitro and IFN‐γ secretion could be increased by costimulation with recombinant IL 2. These T cell clones conferred significant protection upon recipient mice which was more pronounced in the liver. The possible relevance of lysis by L3T4+ T cells of infected MΦ to protection against and pathogenesis of intracellular bacterial infections is discussed.
Sequence analysis of a cDNA clone of a gene encoding a component of a putative phosphorylcholine‐specific T suppressor factor and functional property of its gene product
Authors: Yamasaki Noriyuki , Sugimura Kazuhisa , Hiida Megumi , Naito Tsutomu , Watanabe Takeshi 
Published: March 2007

AbstractWe have isolated a putative phosphorylcholine (PC)‐T cell suppressor factor (TsF) cDNA clone, p6‐5, from a cDNA library of a T hybridoma which constitutively secretes a PC‐TsF in vitro [8]. In the present study, we determined the nucleotide sequence of the p6‐5 gene and found that the p6‐5 sequence is 86% homologous to rat preproelastase 1 gene, one of the serine protease genes. An oligopeptide (14 mer, TsF14) deduced from the p6‐5 sequence was synthesized and antisera against TsF14 were prepared in rabbits. Anti‐TsF14‐conjugated Sepharose 4B specifically absorbed the PC‐TsF activity from the culture supernatant of PC‐TsF‐secreting T hybridomas. In contrast, the binding molecule eluted from the anti‐TsF14‐conjugated Sepharose suppressed the antibody response PC specifically. These results indicated that the p6‐5 polypeptide is a component of the PC‐TsF molecule.
Isogeneic monoclonal antibodies against anti‐α(1 → 3)dextran idiotypes I. Isotypes, idiotope specificity and representation of idiotopes in antisera from mice of various genetic constitutions
Authors: Wilke Joachim , Weiler Eberhardt 
Published: March 2007

AbstractEight isogeneic anti‐idiotypic hybridomas were raised against BALB/c myeloma protein MOPC104E and one against J558. Both myelomas react specifically with the α(1 → 3) glucosidic linkage of dextran B1355 fraction S (Dex). Six anti‐MOPC 104E proteins were IgG1, one was IgG2b and one IgM. The anti‐J558 protein was IgG1. Competitive interactions of the anti‐idiotopes and antigen with anti‐Dex proteins were measured. Dex itself was effective, but also an α(1→3) glucosidic heptasaccharide (N7‐CHO).In order to assess the anti‐idiotope specificity of hybridoma proteins, three anti‐Dex molecules were used: MOPC 104E, J558 and hybridoma protein Hdex14. These differed from each other in VH amino acid positions 54–55, or 100–101, respectively. By their serological reaction pattern our anti‐idiotope proteins could be divided into 3 groups: cross‐reactive, partially cross‐reactive and strictly specific for the immunogen. The latter ones were in the majority, and were called “private”, in contrast to the cross‐reactive “public” anti‐idiotopes. The serological pattern was followed, in general, by the mouse‐to‐mouse distribution of idiotopes in physiological anti‐Dex sera. Public idiotopes were closely correlated in their expression with anti‐Dex activity. “Private” idiotopes showed no correlation, and displayed a characteristically high degree of fluctuation from mouse to mouse.Among the different mouse strains that were compared with respect to idiotope expression in anti‐Dex sera, two stand out: C57BL‐Igha, which carries chromosome 12 of BALB/c, (as selected through allotype) on the C57BL/6 genome, and BALB‐Ighb, dex+, a recombinant in chromosome 12 linking the dex+ trait from BALB/c to the CH allotype from C57BL/6. The latter strain expressed significantly more of the private idiotopes than the former. This observation is discussed in terms of the position effect of classical genetics and network concepts.
Cyclosporin A does not affect the in vitro induction of antigen‐specific delayed‐type hypersensitivity‐mediating T cells
Authors: Shidani Babak , Motta Iris , Truffa‐Bachi Paolo 
Published: March 2007

AbstractThe effect of cyclosporin A (CsA) on the in vitro induction of sheep red blood cell (SRBC)‐specific T cells mediating the delayed‐type hypersensitivity (DTH) reaction was studied. CsA (1 μg/ml) addition to the culture medium totally inhibits the in vitro anti‐SRBC humoral response but does not interfere with the generation of anti‐SRBC DTH‐mediating T (TDTH) cells. The induction of TDTH requires the presence of antigen and their expression is mediated selectively by the antigen used in the culture. The TDTH cells generated are Lyt‐1+, 2− and their induction occurs with a similar efficiency in CsA‐treated and untreated cultures: the frequency of the TDTH cells increases by a factor of 10 to 20 during the 6‐day incubation period. Lyt‐2+ suppressor cells are also generated in CsA‐treated or untreated cultures. Our results suggest that a small fraction of T cells can be driven into the proliferative pathway by antigen even in presence of CsA.
Long‐lived B cells: mitogen reactivity as a tool for studying their life‐spans
Authors: Lévy Martine , Coutinho António 
Published: March 2007

AbstractA population of noncycling small lymphocytes has been selectively enriched in mice by treatment with hydroxyurea (HU) over 4 consecutive days. This cell population, present in the spleen of HU‐treated mice, contained a high frequency of lipopolysac‐charide (LPS)‐reactive cells and this could be used as a functional marker to follow their persistence after transfer to LPS‐nonresponder recipient mice. The results reported here show that cells selected after a long‐term HU treatment have considerably less decay, after transfer in recipient mice, than normal spleen cells. Furthermore, they demonstrate that HU‐selected B cells survive in the recipient mice for periods up to 3 months, and are, consequently, true long‐lived lymphocytes.