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school:SOM

Department/Unit:Cell Biology

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14086


Nicotine and epibatidine triggered prolonged rise in calcium and TH gene transcription in PC12 cells

Gueorguiev, Volodia D; Frenz, Christopher M; Ronald, Kimberly M; Sabban, Esther L
The effect of epibatidine on regulation of [Ca2+]i and tyrosine hydroxylase (TH) transcription was examined. Epibatidine triggers a biphasic rise in [Ca2+]i in PC12 cells similar to that observed with nicotine. There was an immediate transient increase in [Ca2+]i and a subsequent sustained second elevation. In contrast to nicotine, the epibatidine-triggered increase in [Ca2+]i was independent of activation of alpha7 nicotinic acetylcholine receptors, as it was not altered by either methyllycaconitine or alpha-bungarotoxin. The second [Ca2+]i elevation involves calcium release from intracellular stores and is inhibited by dantrolene or xestospongin C. Epibatidine, like nicotine, elevated TH promoter driven reporter transcription, mostly mediated by the cyclic-AMP responsive motifs. Elevation in TH promoter activity requires Ca2+ and cAMP since it is inhibited by 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'-tetraacetic Acid Tetra (acetoxymethyl ester) (BAPTA-AM) or 2',5'-dideoxyadenosine (DDA). The results reveal that epibatidine can elevate [Ca2+]i in an alpha7 independent manner and nevertheless induce TH transcription.
PMID: 15588622
ISSN: 0014-2999
CID: 606822

Noise sensitivity analysis of statistically consistent optimal structure from motion

Chapter by: Park, F. C.; Park, Byungsoo; Kim, Munsang; Mishra, Bhubaneswar
in: 2004 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS) by
[S.l.] : Springer Verlagservice@springer.de, 2004
pp. 3698-3703
ISBN: 9780780384637
CID: 2852162

Turning CARTwheels: An alternating algorithm for mining redescriptions

Chapter by: Ramakrishnan, Naren; Kumar, Deept; Mishra, Bud; Potts, Malcolm; Helm, Richard F.
in: KDD-2004 - Proceedings of the Tenth ACM SIGKDD International Conference on Knowledge Discovery and Data Mining by
[S.l.] : Springer Verlagservice@springer.de, 2004
pp. 266-275
ISBN: 9781581138887
CID: 2852192

Novel approach for food safety evaluation. Results of a pilot experiment to evaluate organic and conventional foods

Finamore, Alberto; Britti, Maria Serena; Roselli, Marianna; Bellovino, Diana; Gaetani, Sancia; Mengheri, Elena
There is evidence that organic food often contains relatively high amounts of natural toxic compounds produced by fungi or plants, whereas corresponding conventional food tends to contain more synthetic toxins such as pesticide residues, but only a few studies have evaluated the impact of their consumption on health. This study proposes a novel approach to evaluate the potential health risk of organic compared to conventional food consumption, that is, the assay of sensitive markers of cell function in vulnerable conditions. The markers utilized were intestinal and splenic lymphocyte proliferative capacity and liver acute-phase reaction, both responding to the presence of toxins. The vulnerable conditions in which body defenses can be less efficient were weaning and protein-energy malnutrition. This study reports the results of a pilot experiment on one sample of eight varieties of organically and conventionally grown wheat. Weaned rats were assigned to two groups fed conventional (CV) or organic (ORG) wheat for 30 days. Each group was divided in two subgroups of well-nourished (WN) or protein-energy-malnourished (PEM) rats. For each rat, the lymphocyte proliferation was assayed by [(3)H]thymidine incorporation after stimulation of cells with a mitogen, in a culture medium containing either commercial fetal calf serum (FCS) or the corresponding rat serum (RS) to mimic the in vivo proliferative response. The acute-phase proteins (albumin, transthyretin, transferrin, ceruloplasmin, retinol-binding protein) were measured in plasma by Western blotting and immunostaining with specific antibodies. The proliferative response of lymphocytes cultured with FCS and the amount of acute-phase proteins of rats fed the ORG wheat sample, either WN or PEM, did not differ from those of rats fed the CV wheat sample. However, the proliferative response of lymphocytes cultured with RS was inhibited in PEM-CV compared with PEM-ORG. The content of mycotoxins was highest in the organic sample, and therefore the immunotoxic effect was probably due to other contaminants in the CV wheat. In conclusion, these results indicate that the conventional wheat sample tested represented a higher risk for lymphocyte function than the wheat sample organically grown, at least in vulnerable conditions.
PMID: 15563230
ISSN: 0021-8561
CID: 1368352

Neurotrophin survival signaling mechanisms

Chao, Moses V; Lee, Francis S
PMID: 15665417
ISSN: 1387-2877
CID: 55906

Autophagic vacuoles are enriched in amyloid precursor protein-secretase activities: implications for beta-amyloid peptide over-production and localization in Alzheimer's disease

Yu, W H; Kumar, A; Peterhoff, C; Shapiro Kulnane, L; Uchiyama, Y; Lamb, B T; Cuervo, A M; Nixon, R A
In Alzheimer's disease (AD), the neuropathologic hallmarks of beta-amyloid deposition and neurofibrillary degeneration are associated with early and progressive pathology of the endosomal-lysosomal system. Abnormalities of autophagy, a major pathway to lysosomes for protein and organelle turnover, include marked accumulations of autophagy-related vesicular compartments (autophagic vacuoles or AVs) in affected neurons. Here, we investigated the possibility that AVs contain the proteases and substrates necessary to cleave the amyloid precursor protein (APP) to A beta peptide that forms beta-amyloid, a key pathogenic factor in AD. AVs were highly purified using a well-established metrizamide gradient procedure from livers of transgenic YAC mice overexpressing wild-type human APP. By Western blot analysis, AVs contained APP, beta C
PMID: 15325590
ISSN: 1357-2725
CID: 61278

Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2

Deng, Jing; Lu, Phoebe D; Zhang, Yuhong; Scheuner, Donalyn; Kaufman, Randal J; Sonenberg, Nahum; Harding, Heather P; Ron, David
Numerous stressful conditions activate kinases that phosphorylate the alpha subunit of translation initiation factor 2 (eIF2alpha), thus attenuating mRNA translation and activating a gene expression program known as the integrated stress response. It has been noted that conditions associated with eIF2alpha phosphorylation, notably accumulation of unfolded proteins in the endoplasmic reticulum (ER), or ER stress, are also associated with activation of nuclear factor kappa B (NF-kappaB) and that eIF2alpha phosphorylation is required for NF-kappaB activation by ER stress. We have used a pharmacologically activable version of pancreatic ER kinase (PERK, an ER stress-responsive eIF2alpha kinase) to uncouple eIF2alpha phosphorylation from stress and found that phosphorylation of eIF2alpha is both necessary and sufficient to activate both NF-kappaB DNA binding and an NF-kappaB reporter gene. eIF2alpha phosphorylation-dependent NF-kappaB activation correlated with decreased levels of the inhibitor IkappaBalpha protein. Unlike canonical signaling pathways that promote IkappaBalpha phosphorylation and degradation, eIF2alpha phosphorylation did not increase phosphorylated IkappaBalpha levels or affect the stability of the protein. Pulse-chase labeling experiments indicate instead that repression of IkappaBalpha translation plays an important role in NF-kappaB activation in cells experiencing high levels of eIF2alpha phosphorylation. These studies suggest a direct role for eIF2alpha phosphorylation-dependent translational control in activating NF-kappaB during ER stress
PMCID:529034
PMID: 15542827
ISSN: 0270-7306
CID: 47770

[Effects of two test-meals on transient lower esophageal sphincter relaxation in patients with gastroesophageal reflux disease and mechanism of gastroesophageal reflux]

Sun, Xiao-Hong; Ke, Mei-Yun; Wang, Zhi-Feng; Liu, Xiao-Hong
OBJECTIVE: To investigate the effects of standard meal and fat meal distending the fundus on transient lower esophageal sphincter relaxation (TLESR) and esophageal motility and to explore the mechanism of gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). METHODS: Eight patients with GERD (3 male, 5 female; median age: 43.5 ys) were enrolled in the study. All received 2 times of esophageal manometry and pH monitoring simultaneously for 30 min during fasting and 2 h after two different test-meals, including standard meal (SM) and fat meal (FM) on separate day at least 1 week apart. RESULTS: The frequency of TLESR significantly increased after 2 test-meals (P < 0.05). There were no significant difference in the frequency and duration of TLESR between SM group and FM group 1 h after meal (P > 0.05). However, the frequency of TLESR in FM group 2 h after meal was more than that in SM group and during fasting (P < 0.05). Lower esophageal sphincter pressure (LESP) significantly decreased in FM group than in SM group (P < 0.05). The contractive amplitude of post lower esophageal sphincter relaxation and the contractive amplitude of the distal esophagus had no difference after FM and SM. Acid reflux episodes and duration of pH < 4 were larger after FM than after SM (P < 0.05). A total of 50.2% of GER occurred during decreased LESP and 37.8% during TLESR after FM, while 61.7% of GER occurred during TLESR after SM. CONCLUSIONS: Both the SM and FM can increase the frequency of TLESR in patients with GERD. Decreased LESP and increased frequency of TLESR after FM are the major mechanism of GER, while reflux after SM may attribute to the increased frequency of TLESR.
PMID: 15663221
ISSN: 1000-503x
CID: 830802

How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?

Sato, Tatsuya; Joyner, Alexandra L; Nakamura, Harukazu
The mesencephalic/rhombomere 1 border (isthmus) is an organizing center for early development of midbrain and cerebellum. In this review, we summarize recent progress in studies of Fgf signaling in the isthmus and discuss how the isthmus instructs the differentiation of the midbrain versus cerebellum. Fgf8 is shown to play a pivotal role in isthmic organizer activity. Only a strong Fgf signal mediated by Fgf8b activates the Ras-extracellular signal-regulated kinase (ERK) pathway, and this is sufficient to induce cerebellar development. A lower level of signaling transduced by Fgf8a, Fgf17 and Fgf18 induce midbrain development. Numerous feedback loops then maintain appropriate mesencephalon/rhombomere1 and organizer gene expression
PMID: 15610138
ISSN: 0012-1592
CID: 56066

Oxidative stress activates FUS1 and RLM1 transcription in the yeast Saccharomyces cerevisiae in an oxidant-dependent Manner

Staleva, Liliana; Hall, Andrea; Orlow, Seth J
Mating in haploid Saccharomyces cerevisiae occurs after activation of the pheromone response pathway. Biochemical components of this pathway are involved in other yeast signal transduction networks. To understand more about the coordination between signaling pathways, we used a 'chemical genetic' approach, searching for compounds that would activate the pheromone-responsive gene FUS1 and RLM1, a reporter for the cell integrity pathway. We found that catecholamines (l-3,4-hydroxyphenylalanine [l-dopa], dopamine, adrenaline, and noradrenaline) elevate FUS1 and RLM1 transcription. N-Acetyl-cysteine, a powerful antioxidant in yeast, completely reversed this effect, suggesting that FUS1 and RLM1 activation in response to catecholamines is a result of oxidative stress. The oxidant hydrogen peroxide also was found to activate transcription of an RLM1 reporter. Further genetic analysis combined with immunoblotting revealed that Kss1, one of the mating mitogen-activated protein kinases (MAPKs), and Mpk1, an MAPK of the cell integrity pathway, participated in l-dopa-induced stimulation of FUS1 and RLM1 transcription. We also report that Mpk1 and Hog1, the high osmolarity MAPK, were phosphorylated upon induction by hydrogen peroxide. Together, our results demonstrate that cells respond to oxidative stress via different signal transduction machinery dependent upon the nature of the oxidant
PMCID:532035
PMID: 15385622
ISSN: 1059-1524
CID: 49632