118,222 research outputs found
The hippocampal opioid system : role in spatial learning
No full textThe main aim of the present thesis was to study the role of the endogenous hippocampal opioid system, and in particular, the role of dynorphin B and nociceptin, in spatial learning.The effects of bilateral infusion (using chronic cannulae) of dynorphin B into the dorsal hippocampus (CA3-region), an area containing a high number of dynorphin-containing neurons, were examined in the Morris swim-maze, a spatial task dependent on hippocampal functioning. In this test, rats are required to locate a hidden platform in a pool filled with water using extra-maze cues. The results show that dynorphin B impaired spatial learning at all doses tested (1, 3.3 and 10 nmol/rat) and reached its maximum effect already at the 1 nmol/rat dose. Retention performance was not affected indicating that dynorphin B mainly affects acquisition but not memory processes. The impairing effect was blocked by the selective [kappa]-antagonist, nor-binaltorphimine, indicative of [kappa]-receptor involvement. No effect on locomotion could be seen, as examined in a separate experiment. Since the septohippocampal pathway has been shown to play an important role in learning and memory, the effect of dynorphin B on basal acetylcholine relase in the dorsal hippocampus was examined using in vivo microdialysis. The effect of dynorphin B on spatial learning appears not to involve basal ACh release, since dynorphin B perfused via a microdialysis probe did not alter basal hippocampal acetylcholine release. The mechanism by which dynorphin B affects spatial learning (acquisition) probably involves either glutamate- or GABA-transmission or both.The metabolism of dynorphins was examined in tissue homogenates of various brain areas (hippocampus, striatum and substatia nigra) using HPLC and mass spectrometry. It was found that dynorphin B was metabolized into the shorter fragments, Leu-enkephalin and to a smaller extent, Leu-enkephalin-Arg6. The ratio of these formed fragments differed between the tissues tested, which may be of physiological relevance.Nociceptin, infused into the CA3 region of the dorsal hippocampus at a dose of 10 nmol/rat severly impaired spatial learning and decreased exploratory behaviour without affecting swim speed. Nociceptin also impaired retention performance, indicating an effect on both acquisition and memory processes. Using lower doses of nociceptin, it was shown that the peptide had a biphasic dose-effect curve on learning, impairing at a high dose (3.3 nmol/rat) and facilitatory at lower doses (1 and 0.33 nmol/rat). Both the impairing and the facilitatory effect could be blocked by a selective antagonist, showing the involvement of the ORL1-receptor. Nociceptin had no effect on swim speed or on locomotion at these doses. The effects of nociceptin on spatial learning are apparently not mediated by the cholinergic system, since no effect of nociceptin perfusion on basal acetylcholine release was observed. Rather, it probably involves either glutamate- or GABA-transmission or both. In this regard, dynorphin B and nociceptin appear similar in action. However, low doses of nociceptin had the unique property of facilitating spatial learning.The degradation of nociceptin was studied after bilateral infusion of nociceptin (10 nmol/rat) into the rat hippocampus in vivo. Mass spectrometric analysis showed that two fragments were formed by stepwise fragmentation, nociceptin (1-13) and nociceptin (1-9). The nociceptin (1-13) fragment was infused into the dorsal hippocampus and shown to have no effect on spatial learning, suggesting a loss of affinity for the ORL1-receptor, in agreement with receptor binding data.Microinjection of endomorphin-2, a [my]-receptor ligand, into the dorsal hippocampus impaired spatial learning at a high dose (10 nmol/rat) but had no effect at lower doses (3.3 and 1 nmol/rat). No effect on swim speed was observed.On the other hand, Leu-enkephalin, an endogenous [delta]-receptor ligand, had no effect on spatial learning or swim speed at the doses tested (10 and 3.3 nmol/rat). Taken together, the results suggest an important role for hippocampal opioid systems, and dynorphin and nociceptin in particular, in spatial learning. These observations have potential relevance for Alzheimer's disease and age-related disorders of memory.List of scientific papersI. Sandin J, Nylander I, Georgieva J, Schött PA, Ögren SO, Terenius L. (1998). Hippocampal dynorphin B injections impair spatial learning in rats: a kappa-opioid receptor-mediated effect. Neuroscience. 85(2): 375-82. https://pubmed.ncbi.nlm.nih.gov/98283580II. Sandin J, Tan-No K, Kasakov L, Nylander I, Winter A, Silberring J, Terenius L. (1997). Differential metabolism of dynorphins in substantia nigra, striatum, and hippocampus. Peptides. 18(7): 949-56. https://pubmed.ncbi.nlm.nih.gov/98019899III. Sandin J, Georgieva J, Schött PA, Ögren SO, Terenius L. (1997). Nociceptin/orphanin FQ microinjected into hippocampus impairs spatial learning in rats. Eur J Neurosci. 9(1): 194-7. https://pubmed.ncbi.nlm.nih.gov/97195176IV. Sandin J, Ögren SO, Terenius L. (2000). Nociceptin/orphanin FQ modulates spatial learning via NOR-receptors in the CA3-region of the hippocampus. [Submitted]V. Sandin J, Georgieva J, Silberring J, Terenius L. (1999). In vivo metabolism of nociceptin/orphanin FQ in rat hippocampus. Neuroreport. 10(1): 71-6. https://pubmed.ncbi.nlm.nih.gov/99191924VI. Sandin J, Kehr J, Ögren SO, Terenius L. (2000). Nociceptin/orphanin FQ and dynorphin B: effects on spatial learning are not related to acetylcholine release in the hippocampus of the rat. [Manuscript]VII. Sandin J, Ögren SO, Terenius L. (2000). Endomorphin-2 but not leuenkephalin modulates spatial learning when microinjected in the CA3-region of the rat hippocampus. [Submitted]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
No full textIn this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Letter from unknown writer to Jesse L. Boyce
No full textLetter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Cryo-electron tomography of individual protein molecules
No full textAveraging methods of determining structure, such as X-ray diffraction, do not preserve information about the flexibility of molecules. Cryo-electron tomography allows us to reconstruct individual hydrated objects. The method is limited to low-resolution, but it can be used to study dynamic structures, such as very large macromolecular complexes, and to perform in situ analysis of cellular organelles.This thesis explores the expansion of the cryo-electron tomography method to individual protein molecules. Tomographic structures of four proteins, ranging in size from 90 to 150 kDa, are presented in the current thesis.We have analysed the structure and flexibility of the antibody immunoglobulin G (IgG). The tomograms reveal y-shaped IgG molecules with three protruding subunits. We show that the tomographic structures are consistent with X-ray crystallographic structures of IgG and that the three 50 kDa subunits were resolved with accuracy. Each subunit has a similar structure in the tomograms and in the Xray map. Notably, the positions of the subunits differed greatly from one molecule to another. The large flexibility of IgG in solution is most likely of functional significance in antigen recognition. We have investigated a larger number of individual IgG molecules, measured equilibrium distribution of the molecule in terms of the relevant angular coordinates and built a model of the dynamics of IgG in solution.The hepatocyte growth factor/scatter factor (HGF/SF) controls the growth, morphogenesis or migration of epithelial, endothelial and muscle progenitor cells. We have defined the main conformations of inactive single-chain HGF/SF and active two-chain HGF/SF. Furthermore we present structures of the receptor tyrosine kinase MET and of MET bound to two-chain HGF/SF. These structures reveal the mechanism of HGF/SF activation and clarify the mode of binding to MET.Nuclear receptors play important roles in development and tissue homeostasis, and have been implicated in many disease states. We present the structure of the full-length Glucocorticoid Receptor (GR) protein, activated by a synthetic hormone agonist. Three asymmetric domains are clearly defined in the structure of the GR monomer, and two low-density regions, interpreted as hinge regions, connect the domains. The three domains were further characterized by multi-resolution docking procedures and by visualizing GR in complex with a monoclonal antibody.These studies show that cryo-electron tomography can be used to visualize individual proteins molecules with a molecular weight below 200 kDa. Thus, the method can be applied to flexible multi-domain proteins that have not been amenable to high-resolution methods of determining structure.List of scientific papersI. Sandin S, Ofverstedt LG, Wikstrom AC, Wrange O, Skoglund U (2004). Structure and flexibility of individual immunoglobulin G molecules in solution. Structure. 12(3): 409-15. https://pubmed.ncbi.nlm.nih.gov/15016357II. Bongini L, Fanelli D, Piazza F, De Los Rios P, Sandin S, Skoglund U (2004). Freezing immunoglobulins to see them move. Proc Natl Acad Sci U S A. 101(17): 6466-71. https://pubmed.ncbi.nlm.nih.gov/15082830III. Gherardi E, Sandin S, Pethoukov M, Finch J, Ofverstedt LG, Nunez R, Blundell T, Vande Woude G, Skoglund U, Svergun D (2005). Structural basis of hepatocyte growth factor/scatter factor activation, receptor binding and dimerisation. [Submitted]IV. Sandin S, Ofverstedt LG, Wikstrom AC, Wrange O, Skoglund U (2005). Tomographic structures of the full-length glucocorticoid receptor. [Manuscript]</p
Sarah L. Blum Author Visit - Warrior Nurse: PTSD and Healing
No full textHear Sarah L. Blum, author of Women Under Fire: Abuse in the Military, discuss her newest book, Warrior Nurse: PTSD and Healing followed by a Q&A and book signing.
Sarah L. Blum is a decorated Vietnam veteran who served as an operating room nurse during the intense fighting of 1967. In recognition of her service, she was awarded the Army Commendation Medal.
Sponsored by CWU Veterans Center and CWU Libraries.https://digitalcommons.cwu.edu/libraryevents/1252/thumbnail.jp
Lillian L. Lambert, Author, Speaker, and Entrepreneur
No full textLillian L. Lambert, Author, Speaker, and Entrepreneu
Letter to Alfred L. Shoemaker, February 10, 1948
No full textA handwritten letter from an unknown author addressed to Alfred L. Shoemaker, dated February 10, 1948. Within, the author discusses the Pennsylvania Dutch word for Ash Wednesday, along with traditions associated with this day.https://digitalcommons.ursinus.edu/shoemaker_documents/1118/thumbnail.jp
- …
