bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic neurons synthesize and secrete pro‐nerve growth factor protein
Authors: Hasan Wohaib , Pedchenko Tetyana , Krizsan‐Agbas Dora , Baum Laura , Smith Peter G. 
Published: September 2003

AbstractPostmitotic sympathetic neuronal survival is dependent upon nerve growth factor (NGF) provided by peripheral targets, and this dependency serves as a central tenet of the neurotrophic hypothesis. In some other systems, NGF has been shown to play an autocrine role, although the pervasiveness and significance of this phenomenon within the nervous system remain unclear. We show here that rat sympathetic neurons synthesize and secrete NGF. NGF mRNA is expressed in nearly half of superior cervical ganglion sympathetic neurons at embryonic day 17, rising to over 90% in the early postnatal period, and declining in the adult. Neuronal immunoreactivity is reduced when retrograde transport is interrupted by axotomy, but persists in a subpopulation of neurons despite diminished mRNA expression, suggesting that intrinsic protein synthesis occurs. Cultured neonatal neurons express NGF mRNA, which is maintained even when they are undergoing apoptosis. To determine which NGF isoforms are secreted, we performed metabolic labeling and immunoprecipitation of NGF‐immunoreactive proteins synthesized by cultured NGF‐dependent and ‐independent neurons. Conditioned medium contained high molecular weight NGF precursor proteins, which varied depending upon the state of NGF dependence. Mature NGF was undetectable by these methods. High molecular weight NGF isoforms were also detected in ganglion homogenates, and persisted at diminished levels following axotomy. We conclude that sympathetic neurons express NGF mRNA, and synthesize and secrete pro‐NGF protein. These findings suggest that a potential NGF‐sympathetic neuron autocrine loop may exist in this prototypic target‐dependent system, but that the secreted forms of this neurotrophin apparently do not support neuronal survival. © 2003 Wiley Periodicals, Inc. J Neurobiol
38–53, 2003
20‐hydroxyecdysone inhibits the mitotic activity of neuronal precursors in the developing mushroom bodies of the honeybee, Apis mellifera
Authors: Malun Dagmar , Moseleit Ariane D. , Grünewald Bernd 
Published: September 2003

AbstractThe mushroom bodies (MBs) within the brain of the honeybee, Apis mellifera, are prominent paired neuropil structures consisting of a lateral and a median subunit. The intrinsic MB neurons (Kenyon cells) of each of these subunits are generated in four distinct proliferation centers, each associated with a calyx. Previous BrdU studies revealed that neurogenesis of Kenyon cells starts at the first larval stage (L1) by symmetrical cell division of Kenyon precursor cells, and ceases abruptly at a midpupal stage (P5). In the present work, we confirmed these results using the antiphospho histone H3 mitosis marker to label mitotically active cells in a cell culture system, in histological sections, and in whole‐mount brain preparations. To elucidate whether the steroid hormone ecdysone plays a role in the termination of Kenyon cell neurogenesis, we manipulated the hormone titer by injecting 20‐hydroxyecdysone (20E) into animals of those pupal stages (P0/1, P3, P4) in which neurogenesis of Kenyon cells was still extensive. The effects of 20E were evaluated by determining the number of mitotically active cells in confocal microscopic images of squash preparations of the MB proliferation centers. In all pupal stages studied, 20E caused a reduction of mitotic activity, indicating its involvement in the cessation of Kenyon cell neurogenesis. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 1‐14, 2003
Aberrant neuronal connectivity in CHL1‐deficient mice is associated with altered information processing‐related immediate early gene expression
Authors: Montag‐Sallaz Monique , Baarke Andrea , Montag Dirk 
Published: September 2003

AbstractIn humans, loss or alteration of the CHL1/CALL gene may contribute to mental impairment associated with the 3p‐syndrome, caused by distal deletions of the short (p) arm of chromosome 3, and schizophrenia. Mice deficient for the Close Homologue of L1 (CHL1) show aberrant connectivity of hippocampal mossy fibers and olfactory sensory axons, suggesting participation of CHL1 in the establishment of neuronal networks. Furthermore, behavioral studies showed that CHL1‐deficient mice react differently towards novel experimental environments. These data raise the hypothesis that processing of information, possibly novel versus familiar, may be altered in the absence of CHL1. To test this hypothesis, brain activities were investigated after presentation of a novel, familiar, or neutral gustatory stimulus using metabolic mapping with (14C)‐2‐deoxyglucose (2‐DG) and analysis of mRNA expression of the immediate early genes (IEGs) c‐fos and arg 3.1/arc by in situ hybridization. 2‐DG labeling revealed only small differences between CHL1‐deficient and wild‐type littermate mice. In contrast, while the specific novelty‐induced increase in c‐fos expression was maintained in most of the brain areas analyzed, c‐fos mRNA expression was similar after the novel and familiar taste in several brain areas of the CHL1‐deficient mice. Furthermore, in these mutants, arg 3.1/arc expression was slightly reduced after the novel taste and increased after the familiar taste, leading to a similar arg 3.1/arc mRNA expression after both stimuli. Our results indicate that, in contrast to controls, CHL1‐deficient mice might process novel and familiar information similarly and suggest that the altered neuronal connectivity in these mutants disturbs information processing at the molecular level. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 67–80, 2003
S100 immunoreactive glial cells in the forebrain and midbrain of the lizard Gallotia galloti during ontogeny
Authors: del Mar Romero‐Alemán María , Monzón‐Mayor Maximina , Yanes Carmen , Arbelo‐Galván Juan Francisco , Lang Dirk , Renau‐Piqueras Jaime , Negrín‐Martínez Ciro 
Published: September 2003

AbstractWe identified S100 immunoreactive cells in the brain of the lizard Gallotia galloti during ontogeny using immunohistochemical techniques for light and electron microscopy. In double labeling experiments with antibodies specific for S100A1 and S100B (anti‐S100) and proliferative cell nuclear antigen (anti‐PCNA), myelin basic protein (anti‐MBP), phosphorylated neurofilaments (SMI‐31), glial fibrillary acidic protein (anti‐GFAP), or glutamine synthetase (anti‐GS), we detected S100‐like immunoreactivity in glial cells but never in neurons. Restricted areas of the ventricular zone were stained in the hypothalamus from E32 to postnatal stages, and in the telencephalon at E35, E36, and in adults. S100 immunoreactivity was observed predominantly in scattered PCNA‐negative cells that increased in number from E35 to the adult stage in the myelinated tracts of the brain and had the appearance of oligodendrocytes. Quantitative analysis revealed that all of the S100‐positive glial cells were GFAP‐negative, whereas most of the S100‐positive glial cells were GS‐positive. Ultrastructurally, most of these S100‐positive/GS‐positive glial cells resembled oligodendrocytes of light and medium electron density. In adult lizards, a small subpopulation of astrocyte‐like cells was also stained in the pretectum. We conclude that in the lizard S100 can be considered a marker of a subpopulation of oligodendrocytes rather than of astrocytes, as is the case in mammals. The S100‐positive subpopulation of oligodendrocytes in the lizard could represent cells actively involved in the process of myelination during development and in the maintenance of myelin sheaths in the adult. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 54–66, 2003
Different regulation of Purkinje cell dendritic development in cerebellar slice cultures by protein kinase Cα and ‐β
Authors: Gundlfinger Anja , Kapfhammer Josef P. , Kruse Friederike , Leitges Michael , Metzger Friedrich 
Published: September 2003

AbstractActivity of protein kinase C (PKC), and in particular the PKCγ‐isoform, has been shown to strongly affect and regulate Purkinje cell dendritic development, suggesting an important role for PKC in activity‐dependent Purkinje cell maturation. In this study we have analyzed the role of two additional Ca2+‐dependent PKC isoforms, PKCα and ‐β, in Purkinje cell survival and dendritic morphology in slice cultures using mice deficient in the respective enzymes. Pharmacological PKC activation strongly reduced basal Purkinje cell dendritic growth in wild‐type mice whereas PKC inhibition promoted branching. Purkinje cells from mice deficient in PKCβ, which is expressed in two splice forms by granule but not Purkinje cells, did not yield measurable morphological differences compared to respective wild‐type cells under either experimental condition. In contrast, Purkinje cell dendrites in cultures from PKCα‐deficient mice were clearly protected from the negative effects on dendritic growth of pharmacological PKC activation and showed an increased branching response to PKC inhibition as compared to wild‐type cells. Together with our previous work on the role of PKCγ, these data support a model predicting that normal Purkinje cell dendritic growth is mainly regulated by the PKCγ‐isoform, which is highly activated by developmental processes. The PKCα isoform in this model forms a reserve pool, which only becomes activated upon strong stimulation and then contributes to the limitation of dendritic growth. The PKCβ isoform appears to not be involved in the signaling cascades regulating Purkinje cell dendritic maturation in cerebellar slice cultures. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 95–109, 2003
Protein profiles of medulloblastoma cell lines DAOY and D283: Identification of tumor‐related proteins and principles
Authors: Peyrl Andreas , Krapfenbauer Kurt , Slavc Irene , Yang Jae‐Won , Strobel Thomas , Lubec Gert 
Published: September 2003

AbstractMedulloblastoma is the most frequent malignant brain tumor in children and is considered to be of neuroectodermal origin. Two main representative cell lines, DAOY and D283, are widely used in studies of medulloblastoma. The former shows expression of neuronal and glial elements whereas the latter is assigned to neuronal lineages. We decided to systematically study the proteome of these cell lines in order to find novel and known proteins that could serve as candidate markers or could be of interest as specific antigens for future vaccines. We studied DAOY and D283 by two‐dimensional gel electrophoresis with subsequent matrix‐assisted laser desorption/ionization identification. A series of identified medulloblastoma proteins were already described in many other malignancies of different origin. An antiapoptotic principle, Ded protein, was observed in both cell lines. Several hypothetical proteins, that were never described at the protein level but only predicted from nucleic acid sequences, could be identified. We conclude that medulloblastoma proteins SYT interacting protein, similar to glucose related protein 58 kDa, hypothetical 37.5 kDa protein, serologically defined colon cancer antigen 10, hepatocellular carcinoma‐associated antigen 59, X‐ray repair complementing defective repair in CHO 5, hypothetical protein Q96ir7, nit protein 2 and hypothetical protein Q96e67, have been described in a series of other malignancies possibly indicating a role for those in tumor biology and pathomechanisms. The antiapoptotic principle, Ded protein, found in both cell lineages may stand for immortalization but could also determine malignancy per se in medulloblastoma.
Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer
Authors: Herrmann Paul C. , Gillespie John W. , Charboneau Lu , Bichsel Verena E. , Paweletz Cloud P. , Calvert Valerie S. , Kohn Elise C. , Emmert‐Buck Michael R. , Liotta Lance A. , Petricoin Emanuel F. 
Published: September 2003

AbstractLaser capture microdissection was combined with reverse phase protein lysate arrays to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I‐III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV–VIII) are synthesized from cellular nuclear DNA. A significant (P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and VIc compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array‐based observations were corroborated with immunohistochemistry, and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome.
Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani
Authors: Bente Meike , Harder Simone , Wiesgigl Martina , Heukeshoven Jochen , Gelhaus Christoph , Krause Eberhard , Clos Joachim , Bruchhaus Iris 
Published: September 2003

AbstractIn order to proceed through their life cycle, protozoan parasites of the genus Leishmania cycle between sandflies and mammals. This change of environment correlates with the differentiation from the promastigote stage (insect form) to the amastigote stage (intracellular mammalian form). The molecular basis underlying this major transformation is poorly understood so far; however, heat shock protein 90 (HSP90) appears to play a pivotal role. To further elucidate this process we identified proteins expressed preferentially in either of the two life cycle stages. By using two‐dimensional (2‐D) gel electrophoresis we observed defined changes in the protein pattern. A total of approximately 2000 protein spots were visualized. Of these, 31 proteins were present only in promastigotes. The abundance of 65 proteins increased during heat‐induced in vitro amastigote differentiation, while a decreased abundance is observed for four proteins late in amastigote differentiation. Further analyses using matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry and peptide mass fingerprinting 67 protein spots were identified representing 41 different proteins known from databases and eight hypothetical proteins. Further studies showed that most of the stage‐specific proteins fall into five groups of functionally related proteins. These functional categories are: (i) stress response (e.g. heat, oxidative stress); (ii) cytoskeleton and cell membrane; (iii) energy metabolism and phosphorylation; (iv) cell cycle and proliferation; and (v) amino acid metabolism. Very similar changes in the 2‐D protein pattern were obtained when in vitro amastigote differentiation was induced either by pharmacological inhibition of HSP90 or by a combination of heat stress and acidic pH supporting the critical role for HSP90 in life cycle control.
Multiple approaches to data‐mining of proteomic data based on statistical and pattern classification methods
Authors: Tatay Jacob W. , Feng Xin , Sobczak Nancy , Jiang Hao , Chen Chin‐Fu , Kirova Roumyana , Struble Craig , Wang Nan Jiang , Tonellato Peter J. 
Published: September 2003

AbstractThe data‐mining challenge presented is composed of two fundamental problems. Problem one is the separation of forty‐one subjects into two classifications based on the data produced by the mass spectrometry of protein samples from each subject. Problem two is to find the specific differences between protein expression data of two sets of subjects. In each problem, one group of subjects has a disease, while the other group is nondiseased. Each problem was approached with the intent to introduce a new and potentially useful tool to analyze protein expression from mass spectrometry data. A variety of methodologies, both conventional and nonconventional were used in the analysis of these problems. The results presented show both overlap and discrepancies. What is important is the breadth of the techniques and the future direction this analysis will create.
Analysis of human serum proteins by liquid phase isoelectric focusing and matrix‐assisted laser desorption/ionization‐mass spectrometry
Authors: Wang Michael Z. , Howard Brandon , Campa Michael J. , Patz Edward F. , Fitzgerald Michael C. 
Published: September 2003

AbstractDirect matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF MS) analysis of human serum yielded ion signals from only a fraction of the total number of peptides and proteins expected to be in the sample. We increased the number of peptide and protein ion signals observed in the MALDI‐TOF mass spectra analysis of human serum by using a prefractionation protocol based on liquid phase isoelectric focusing electrophoresis. This pre‐fractionation technique facilitated the MALDI‐TOF MS detection of as many as 262 different peptide and protein ion signals from human serum. The results obtained from three replicate fractionation experiments on the same serum sample indicated that 148 different peptide and protein ion signals were reproducibly detected using our isoelectric focusing and MALDI‐TOF MS protocol.
Identification and validation of a potential lung cancer serum biomarker detected by matrix‐assisted laser desorption/ionization‐time of flight spectra analysis
Authors: Howard Brandon A. , Wang Michael Z. , Campa Michael J. , Corro Christina , Fitzgerald Michael C. , Patz Edward F. 
Published: September 2003

AbstractMany abnormalities detected in the thorax by routine conventional imaging studies are benign, yet all require further evaluation because of the concern for cancer. To address this deficiency and develop a serum biomarker for lung cancer, we designed a matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF MS) based platform to display the proteins present in the serum of patients with or without lung cancer, and then challenged the scientific community to analyze these data with the aim of determining specific ion signal differences among the resulting spectra. The most statistically significant ion peak identified by the various analysis algorithms that differentiated the serum of patients with lung cancer from the serum of individuals without lung cancer was found at m/z 11 702. We identified the protein responsible for this ion peak as serum amyloid A (SAA; Mr = 11 682.7) by partial purification followed by in‐gel digestion and peptide mapping. By enzyme‐linked immunosorbent assay, we showed SAA to be present at 286 ng/mL in the serum of cancer patients vs. 34.1 ng/mL in the serum of individuals without cancer. These data suggest that the combination of MALDI‐TOF MS and computer analysis can be a powerful tool in the search for serum biomarkers of lung cancer and other diseases.
Megavariate data analysis of mass spectrometric proteomics data using latent variable projection method
Authors: Lee Kwan R. , Lin Xiwu , Park Daniel C. , Eslava Sergio 
Published: September 2003

AbstractThere are many data mining techniques for processing and general learning of multivariate data. However, we believe the wavelet transformation and latent variable projection method are particularly useful for spectroscopic and chromatographic data. Projection based methods are designed to handle hugely multivariate nature of such data effectively. For the actual analysis of the data we have used latent variable projection methods such as principal component analysis (PCA) and partial least squares projection to latent structures based discriminant analysis (PLS‐DA) to analyze the raw data presented to the participants of the First Duke Proteomics Data Mining Conference. PCA was used to solve problem #1 (clustering problem) and the PLS‐DA was used to solve problem #2 (classification problem). The idea of internal and external cross‐validation was used to validate the model obtained from the classification analysis. The simple two‐component PLS‐DA model obtained from the analysis performed well. The model has completely separated the two groups from all the data. The same model applied on two‐thirds of the data showed good performance by external validation with independent test set of remaining 13 specimens obtained by setting aside the spectra of every third specimen (accuracy of 85%).
Generalizable mass spectrometry mining used to identify disease state biomarkers from blood serum
Authors: Neville Padraic , Tan Pei‐Yi , Mann Geoffrey , Wolfinger Russ 
Published: September 2003

AbstractWe bring a “spectrum” of classical data mining and statistical analysis methods to bear on discrimination of two groups of spectra from 24 diseased and 17 normal patients. Our primary goal is to accurately estimate the generalizability of this small dataset. After an aggressive preprocessing step that reduces consideration to only 55 peaks, we conduct over 35 out‐of‐sample cross‐validation simulations of logistic regression, binary decision trees, and linear discriminant analysis. Misclassification rates grow worse as the size of the holdout sample increases, with many exceeding 30 percent. The ability to generalize is clearly tempered by the statistical, instrumentation, and biophysical characteristics of the study.
Clustering mass spectrometry data using order statistics
Authors: Slotta Douglas J. , Heath Lenwood S. , Ramakrishnan Naren , Helm Rich , Potts Malcolm 
Published: September 2003

AbstractMass spectrometry data is inherently uncertain. Rather than compare peak heights across samples, a comparison can be made of the relative ordering of the peak height across samples. Order statistics are used to provide a distance metric between each ordered list of peak heights from the samples. A principal component analysis is performed on the set of distance vectors to highlight to important components.
Discriminant models for high‐throughput proteomics mass spectrometer data
Authors: Purohit Parul V. , Rocke David M. 
Published: September 2003

AbstractWe use several different multivariate analysis methods to discriminate between diseased and healthy patients using protein mass spectrometer data provided by Duke University. Two problems were presented by the university; one in which the responses (diseased or healthy) of the patients were not known and second, when the responses were known. In the latter case, the data can be used as a ‘training’ set. We attempted both problems. In particular, we use principle component analysis along with clustering methods to discriminate for the first problem set and partial least squares coupled with logistic and discriminant methods when the responses were known. In addition, we were able to detect regions of interest in the spectrum where there were differences in the protein patterns between healthy and diseased patients. There was considerable effort involved in the preprocessing of the data. We used a binning approach to reduce the number of variables rather than peak heights or peak areas. We performed a square root transformation on the data to help stabilize the variance; this in turn made a significant improvement in clustering results.