bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical gradients of adult neurogenesis and activity: Young neurons in the ventral dentate gyrus are activated by water maze training
Authors: Snyder Jason S. , Radik Ruvim , Wojtowicz J. Martin , Cameron Heather A. 
Published: November 2008

AbstractHippocampal function varies in a subregion‐specific fashion: spatial processing is thought to rely on the dorsal hippocampus, whereas anxiety‐related behavior relies more on the ventral hippocampus. During development, neurogenesis in the dentate gyrus (DG) proceeds along ventral to dorsal as well as suprapyramidal to infrapyramidal gradients, but it is unclear whether regional differences in neurogenesis are maintained in adulthood. Moreover, it is unknown whether young neurons in the adult exhibit subregion‐specific patterns of activation. We therefore examined the magnitude of neurogenesis and the activation of young and mature granule cells in DG subregions in adult rats that learned a spatial water maze task, swam with no platform, or were left untouched. We found that both adult neurogenesis and granule cell activation, as defined by c‐fos expression in the granule cell population as a whole, were higher in the dorsal than the ventral DG. In contrast, c‐fos expression in adult‐born granule cells, identified by PSA‐NCAM or location in the subgranular zone, occurred at a higher rate in the opposite subregion, the ventral DG. Interestingly, c‐fos expression in the entire granule cell population was equivalent in water maze‐trained rats and swim control rats, but was increased in the young granule cells only in the learning condition. These results provide new evidence that hippocampally‐relevant experience activates young and mature neurons in different DG subregions and with different experiential specificity, and suggest that adult‐born neurons may play a specific role in anxiety‐related behavior or other nonspatial aspects of hippocampal function. © 2008 Wiley‐Liss, Inc.
Viral‐mediated expression of a constitutively active form of CREB in hippocampal neurons increases memory
Authors: Restivo Leonardo , Tafi Elisiana , Ammassari‐Teule Martine , Marie Hélène 
Published: November 2008

AbstractSynaptic activity‐dependent phosphorylation of the transcription factor cAMP response element binding protein (CREB) leads to CREB‐dependent gene transcription, a process thought to underlie long‐term hippocampal synaptic plasticity and memory formation. We previously reported that increasing CREB activity in glutamatergic neurons enhances synaptic plasticity and neuronal excitability. Whether these modifications are sufficient to promote hippocampal‐dependent memory formation was not determined. Here, we provide direct evidence that a brief increase in CREB‐dependent transcription in either CA1 or DG neurons, using in vivo viral vectors, is sufficient to boost memory for contextual representations, as tested in the contextual fear conditioning task, without affecting motor, pain, or anxiety behaviors. © 2008 Wiley‐Liss, Inc.
AMPA receptor trafficking and synaptic plasticity require SQSTM1/p62
Authors: Jiang Jianxiong , Parameshwaran Kodeeswaran , Seibenhener M. Lamar , Kang Myoung‐Goo , Suppiramaniam Vishnu , Huganir Richard L. , Diaz‐Meco Maria T. , Wooten Marie W. 
Published: November 2008

AbstractSQSTM1/p62 is a multidomain/scaffold for the atypical protein kinase Cs (aPKC). Phosphorylation of AMPA receptors by PKC has been shown to regulate their insertion in the postsynaptic membrane. Here, we directly tested whether p62 could interact with AMPA receptor subunits and influence their trafficking and phosphorylation. GluR1 receptor intracellular loop L2–3 and the ZZ‐type zinc finger domain of p62 are essential for the interaction between these two proteins. In this context, both p62 and aPKC‐mediated phosphorylation were necessary for surface delivery of the receptor. Our findings reveal that p62 is the first protein identified that interacts with a region of the GluR receptor other than the C‐terminal tail. Furthermore, mice deficient in p62 displayed impaired hippocampal CA1 long‐term potentiation (LTP), along with diminished surface expression of GluR1 and phosphorylation of S818. Lastly, we identify a conserved sequence (ISExSL) shared by all p62 interacting‐aPKC substrates. These findings support a model where p62 interaction and aPKC phosphorylation act together to mediate AMPA receptor trafficking and long‐term synaptic plasticity in the hippocampus. © 2008 Wiley‐Liss, Inc.
Biological aggressiveness of prostate cancer in the Finnish screening trial
Authors: Laurila Marita , Tammela Teuvo L.J. , Auvinen Anssi , Isola Jorma , Visakorpi Tapio , Luukkaala Tiina , Määttänen Liisa , Ruutu Mirja , Ala‐Opas Martti , Mildh Markus , Martikainen Paula 
Published: November 2008

AbstractProstate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55–67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen‐detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki‐67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high‐grade cancers (Gleason 7 or higher). In the second round, the proportion of low‐grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. © 2008 Wiley‐Liss, Inc.
Dkk3, downregulated in cervical cancer, functions as a negative regulator of β‐catenin
Authors: Lee Eun‐Ju , Jo Minwha , Rho Seung Bae , Park Kyoungsook , Yoo Yae‐Na , Park Junsoo , Chae Myounghee , Zhang Wei , Lee Je‐Ho 
Published: November 2008

AbstractThe Wnt/β‐catenin signaling pathway is activated during the malignant transformation of keratinocytes that originate from the human uterine cervix. Dkk1, 2 and 4 have been shown to modulate the Wnt‐induced stabilization of the β‐catenin signaling pathway. However, the function of Dkk3 in this pathway is unknown. Comparison of the Dkk3 gene expression profiles in cervical cancer and normal cervical tissue by cDNA microarray and subsequent real‐time PCR revealed that the Dkk3 gene is frequently downregulated in the cancer. Methylation studies showed that the promoter of Dkk3 was methylated in cervical cancer cell lines and 22 (31.4%) of 70 cervical cancer tissue specimens. This promoter methylation was associated with reduced expression of Dkk3 mRNA in the paired normal and tumor tissue samples. Further, the reintroduction of Dkk3 into HeLa cervical cancer cells resulted in reduced colony formation and retarded cell growth. The forced expression of Dkk3 markedly attenuated β‐catenin‐responsive luciferase activity in a dose‐dependent manner and decreased the β‐catenin levels. By utilizing a yeast two‐hybrid screen, βTrCP, a negative regulator of β‐catenin was identified as a novel Dkk3‐interacting partner. Coexpression with βTrCP synergistically enhanced the inhibitory function of Dkk3 on β‐catenin. The stable expression of Dkk3 blocks the nuclear translocation of β‐catenin, resulting in downregulation of its downstream targets (VEGF and cylcin D), whereas knockdown of Dkk3 abrogates this blocking. We conclude from our finding that Dkk3 is a negative regulator of β‐catenin and its downregulation contribute to an activation of the β‐catenin signaling pathway. © 2008 Wiley‐Liss, Inc.
Soluble and membrane levels of molecules involved in the interaction between clonal plasma cells and the immunological microenvironment in multiple myeloma and their association with the characteristics of the disease
Authors: Perez‐Andres Martin , Almeida Julia , Martin‐Ayuso Marta , De Las Heras Natalia , Moro Maria Jesus , Martin‐Nuñez Guillermo , Galende Josefina , Cuello Rebeca , Abuín Isabel , Moreno Inmaculada , Domínguez Mercedes , Hernandez Jose , Mateo Gema , San Miguel Jesus F. , Orfao Alberto 
Published: November 2008

AbstractClonal plasma cells (PC) from different types of monoclonal gammopathies (MG) display distinct phenotypes consistent with an increased antigen‐presentation and T‐cell costimulation in MG of undetermined significance that deteriorates in malignant conditions. Expression of other cell surface and soluble molecules (e.g. adhesion/proliferation molecules) involved in the interaction between clonal PC and the bone marrow (BM) microenvironment has also been related to malignant PC, although the exact clinical significance of their expression remains largely unknown. Analysis of cell surface levels of several of these molecules in multiple myeloma (MM) patients shows an association between lower expression on BMPC of the HLA‐I and β2‐microglobulin antigen‐presenting molecules, the CD126 and CD130 IL6 receptor (IL6R) chains, and CD38, and adverse prognostic features of the disease. Likewise, patients showing higher soluble levels of antigen‐presenting molecules (HLA‐I and β2‐microglobulin), IL6R and CD95 tended to be associated with more aggressive disease behavior. In contrast, CD40, CD86, CD56, CD19, and CD45 were not associated with patients' outcome. Interestingly, upon considering the ratio between the soluble and PC membrane expression of each molecule, an increased adverse prognostic impact was observed for both HLA‐I and β2‐microglobulin, but not for the other molecules. Multivariate analysis confirmed the independent prognostic value of cell surface expression of CD126 on BMPC together with serum β2‐microglobulin and LDH. In summary, our results show an abnormal distribution of the cellular and soluble compartments of the HLA‐I, IL6R, and to a lower extent, CD95 molecules, in MM, associated with the clinical characteristics and behavior of the disease. © 2008 Wiley‐Liss, Inc.
Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention
Authors: Andersson Anne , Näslund Ulf , Tavelin Björn , Enblad Gunilla , Gustavsson Anita , Malmer Beatrice 
Published: November 2008

AbstractPrevious studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first‐degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in‐patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in‐patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow‐up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on‐going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept. © 2008 Wiley‐Liss, Inc.
Rapid alterations in cortical protein profiles underlie spontaneous sleep and wake bouts
Authors: Vazquez Jacqueline , Hall Steven C. , Witkowska H. Ewa , Greco Mary Ann 
Published: November 2008

AbstractExisting data indicate that sleep–wakefulness is an essential behavior. The biological function(s) of sleep, however, remains unknown, due, in part, to the lack of information available at the intracellular level. Preliminary microarray analyses show that changes in behavioral state influence regional mRNA profiles; however, the impact of sleep on protein signatures is virtually unexplored. In these studies, cortical protein profiles were examined after timed bouts of spontaneous sleep–wakefulness. Within minutes of each behavioral state examined, a small number of spots showing unique expression were detected. Mass spectroscopy analyses of sleep‐ and wake‐related spots identified proteins associated with multiple functional categories. Two sleep‐associated proteins were further validated using a sleep deprivation paradigm. We found preliminary evidence for two different post‐transcriptional mechanisms—one (GAPDH) in which the amount of protein was increased in the recovery sleep following prolonged waking, while the other (actin) suggested that post‐translational modifications may underlie sleep. The similarities between the effects of sleep on both protein and mRNA profiles indicate that dynamic intracellular changes underlie sleep–wake states and are consistent with roles for sleep in multiple biological functions. J. Cell. Biochem. 105: 1472–1484, 2008. © 2008 Wiley‐Liss, Inc.
Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: Hypothermia as preventive treatment
Authors: Dorfman Verónica Berta , Rey‐Funes Manuel , Bayona Julio César , López Ester María , Coirini Héctor , Loidl César Fabián 
Published: November 2008

AbstractPerinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full‐term fetuses in a water bath at 37°C for 19 or 20 min (PA19 or PA20) or at 15°C for 20 min (hypothermia during PA‐HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA‐HPA). Full‐term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60‐day‐old PA20 rats, with increased NADPH‐d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH‐d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia. © 2008 Wiley‐Liss, Inc.
C1473G polymorphism in mouse tph2 gene is linked to tryptophan hydroxylase‐2 activity in the brain, intermale aggression, and depressive‐like behavior in the forced swim test
Authors: Osipova Daria V. , Kulikov Alexander V. , Popova Nina K. 
Published: November 2008

AbstractTryptophan hydroxylase‐2 (TPH2) is the rate‐limiting enzyme of brain serotonin synthesis. The C1473G polymorphism in the mouse tryptophan hydroxylase‐2 gene affects the enzyme's activity. In the present study, we investigated the linkage between the C1473G polymorphism, enzyme activity in the brain, and behavior in the forced swim, intermale aggression, and open field tests using mice of the C57BL/6 (C/C) and CC57BR/Mv (G/G) strains and the B6‐1473C (C/C) and B6‐1473G (G/G) lines created by three successive backcrossings on C57BL/6. Mice of the CC57BR/Mv strain had decreased brain enzyme activity, aggression intensity, and immobility in the forced swim test, but increased locomotor activity and time spent in the central part of the open field arena compared with animals of the C57BL/6 strain. Mice of the B6‐1473G line homozygous for the 1473G allele had lower TPH2 activity in the brain, aggression intensity, and immobility time in the forced swim test compared with animals of the B6‐1473C line homozygous for the 1473C allele. No differences were found between the B6‐1473G and B6‐1473C mice in locomotor activity and time spent in the central part of the arena in the open field test. Thus, the C1473G polymorphism is involved in the determination of TPH2 activity and is linked to aggression intensity and forced‐swim immobility in mice. At the same time, the polymorphism does not affect locomotion and anxiety‐related behavior in the open field test. The B6‐1473C and B6‐1473G mice represent a valuable experimental model for investigating molecular mechanisms of serotonin‐related behavior. © 2008 Wiley‐Liss, Inc.
Calpain‐mediated truncation of GSK‐3 in post‐mortem brain samples
Authors: Goñi‐Oliver Paloma , Avila Jesús , Hernández Félix 
Published: November 2008

AbstractGSK‐3 activity can be regulated by phosphorylation and through interaction with GSK‐3‐binding proteins. In addition, we have recently demonstrated that calpain activation produces a truncation of GSK‐3 that removes the N‐terminal inhibitory domain (Goñi‐Oliver et al. [2007] J. Biol. Chem. 282:22406). Given that calpain is involved in post‐mortem proteolysis in brain samples, the objective of this investigation was to test whether GSK‐3 is truncated in post‐mortem samples. To achieve this objective, we first investigated the degradation of GSK‐3 during different post‐mortem intervals in mouse brains and found that the conversion of GSK‐3 to proteolytic fragments of 40 and 30 kDa takes place in a way similar that of to p35‐CDK‐5 subunit and spectrin, two well‐known calpain substrates. In addition, we demonstrated that this truncation is mediated by calpain, insofar as pretreatment with MDL 28170, a permeable blood–brain barrier calpain inhibitor, partially inhibited that degradation. When human brain extracts were exposed to calcium, GSK‐3 was truncated, generating two fragments of approximately 40 and 30 kDa, a proteolytic process that was inhibited by calpeptin, a specific calpain inhibitor. Thus, this is the first report of calcium‐dependent truncation of human GSK‐3. These data demonstrate that control samples with similar post‐mortem delay are essential to interpret correctly the changes observed in GSK‐3 levels in human post‐mortem brain, especially when studying human neurodegenerative diseases. © 2008 Wiley‐Liss, Inc.
Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses
Authors: Santafe M.M. , Garcia N. , Lanuza M.A. , Tomàs M. , Besalduch N. , Tomàs J. 
Published: November 2008

AbstractWe studied the relation among calcium inflows, voltage‐dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of thelevator auris longusmuscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q‐, N‐, or L‐type VDCC‐specific block or 500 μM magnesium ions), M1‐ or M4‐type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR‐PKC‐VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block. © 2008 Wiley‐Liss, Inc.
Ultrasound treatment of cutaneous side‐effects of infused apomorphine: A randomized controlled pilot study
Authors: Poltawski Leon , Edwards Hazel , Todd Amy , Watson Tim , Lees Andrew , James Cherry Ann 
Published: November 2008

AbstractApomorphine hydrochloride is a dopamine agonist used in the treatment of advanced Parkinson's disease. Its administration by subcutaneous infusions is associated with the development of nodules that may interfere with absorption of the drug. This pilot study assessed the effectiveness of ultrasound (US) in the treatment of these nodules. Twelve participants were randomly assigned to receive a course of real or sham US on an area judged unsuitable for infusion. Following treatment, no significant change was observed in measures of tissue hardness and tenderness. However, 5 of 6 participants receiving real US rated the treated area suitable for infusion compared with the 1 of 6 receiving sham US. Sonographic appearance improved in both groups, but more substantially in the real US group. Power calculations suggest a total sample size of 30 would be required to establish statistical significance. A full‐scale study of the effectiveness of therapeutic US in the treatment of apomorphine nodules is warranted. © 2008 Movement Disorder Society
Structural elucidation of four new furostanol saponins from Tupistra chinensis by 1D and 2D NMR spectroscopy
Authors: Zou Kun , Wang Jun‐zhi , Guo Zhi‐yong , Du Ming , Wu Jun , Zhou Yuan , Dan Fei‐jun , Liu Chuang 
Published: November 2008

AbstractFour new furostanol saponins (1–4), two pairs of diastereoisomers, were isolated from methanolic extracts of Tupistra chinensis rhizomes and their structures were assigned from 1H and 13C NMR spectra, DEPT, and by 2D COSY, NOESY, HMQC, and HMBC experiments. Copyright © 2008 John Wiley & Sons, Ltd.