Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins

PubMed Central

Imamura, Morikazu; Kato, Nobuko; Okada, Hiroyuki; Yoshioka, Miyako; Iwamaru, Yoshifumi; Shimizu, Yoshihisa; Mohri, Shirou; Yokoyama, Takashi; Murayama, Yuichi

2013-01-01

The central event in prion infection is the conformational conversion of host-encoded cellular prion protein (PrPC) into the pathogenic isoform (PrPSc). Diverse mammalian species possess the cofactors required for in vitro replication of PrPSc by protein-misfolding cyclic amplification (PMCA), but lower organisms, such as bacteria, yeasts, and insects, reportedly lack the essential cofactors. Various cellular components, such as RNA, lipids, and other identified cofactor molecules, are commonly distributed in both eukaryotes and prokaryotes, but the reasons for the absence of cofactor activity in lower organisms remain to be elucidated. Previously, we reported that brain-derived factors were necessary for the in vitro replication of glycosylphosphatidylinositol-anchored baculovirus-derived recombinant PrP (Bac-PrP). Here, we demonstrate that following protease digestion and heat treatment, insect cell lysates had the functional cofactor activity required for Bac-PrP replication by PMCA. Mammalian PrPSc seeds and Bac-PrPSc generated by PMCA using Bac-PrP and insect cell-derived cofactors showed similar pathogenicity and produced very similar lesions in the brains of inoculated mice. These results suggested that the essential cofactors required for the high-fidelity replication of mammalian PrPSc were present in the insect cells but that the cofactor activity was masked or inhibited in the native state. We suggest that not only RNA, but also DNA, are the key components of PMCA, although other cellular factors were necessary for the expression of the cofactor activity of nucleic acids. PMCA using only insect cell-derived substances (iPMCA) was highly useful for the ultrasensitive detection of PrPSc of some prion strains. PMID:24367521

Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains)

USDA-ARS?s Scientific Manuscript database

A prion (PrPSc) is a conformer of a normal cellular prion protein (PrPC). Although they are isosequential, PrPSc is an infectious protein able to convert PrPC into the prion conformation and thereby propagate an infection. PrPC is monomeric while PrPSc is a multimer. PrPSc can adopt more than one co...

Mechanism of Scrapie Prion Precipitation with Phosphotungstate Anions

PubMed Central

2015-01-01

The phosphotungstate anion (PTA) is widely used to facilitate the precipitation of disease-causing prion protein (PrPSc) from infected tissue for applications in structural studies and diagnostic approaches. However, the mechanism of this precipitation is not understood. In order to elucidate the nature of the PTA interaction with PrPSc under physiological conditions, solutions of PTA were characterized by NMR spectroscopy at varying pH. At neutral pH, the parent [PW12O40]3– ion decomposes to give a lacunary [PW11O39]7– (PW11) complex and a single orthotungstate anion [WO4]2– (WO4). To measure the efficacy of each component of PTA, increasing concentrations of PW11, WO4, and mixtures thereof were used to precipitate PrPSc from brain homogenates of scrapie prion-infected mice. The amount of PrPSc isolated, quantified by ELISA and immunoblotting, revealed that both PW11 and WO4 contribute to PrPSc precipitation. Incubation with sarkosyl, PTA, or individual components of PTA resulted in separation of higher-density PrP aggregates from the neuronal lipid monosialotetrahexosylganglioside (GM1), as observed by sucrose gradient centrifugation. These experiments revealed that yield and purity of PrPSc were greater with polyoxometalates (POMs), which substantially supported the separation of lipids from PrPSc in the samples. Interaction of POMs and sarkosyl with brain homogenates promoted the formation of fibrillar PrPSc aggregates prior to centrifugation, likely through the separation of lipids like GM1 from PrPSc. We propose that this separation of lipids from PrP is a major factor governing the facile precipitation of PrPSc by PTA from tissue and might be optimized further for the detection of prions. PMID:25695325

The strain-encoded relationship between PrP replication, stability and processing in neurons is predictive of the incubation period of disease.

PubMed

Ayers, Jacob I; Schutt, Charles R; Shikiya, Ronald A; Aguzzi, Adriano; Kincaid, Anthony E; Bartz, Jason C

2011-03-01

Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrP(Sc), is an essential component of the infectious agent, the strain-specific relationship between PrP(Sc) properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrP(Sc) from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrP(Sc) in neurons and glia. We found that short incubation period strains were characterized by more efficient PrP(Sc) amplification and higher PrP(Sc) conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrP(Sc) in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrP(Sc) did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrP(Sc) in neurons.

Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.

PubMed

Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

2016-07-07

Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N-glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans.

Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains

PubMed Central

Vey, Martin; Pilkuhn, Susanne; Wille, Holger; Nixon, Randal; DeArmond, Stephen J.; Smart, Eric J.; Anderson, Richard G. W.; Taraboulos, Albert; Prusiner, Stanley B.

1996-01-01

Results of transgenetic studies argue that the scrapie isoform of the prion protein (PrPSc) interacts with the substrate cellular PrP (PrPC) during conversion into nascent PrPSc. While PrPSc appears to accumulate primarily in lysosomes, caveolae-like domains (CLDs) have been suggested to be the site where PrPC is converted into PrPSc. We report herein that CLDs isolated from scrapie-infected neuroblastoma (ScN2a) cells contain PrPC and PrPSc. After lysis of ScN2a cells in ice-cold Triton X-100, both PrP isoforms and an N-terminally truncated form of PrPC (PrPC-II) were found concentrated in detergent-insoluble complexes resembling CLDs that were isolated by flotation in sucrose gradients. Similar results were obtained when CLDs were purified from plasma membranes by sonication and gradient centrifugation; with this procedure no detergents are used, which minimizes artifacts that might arise from redistribution of proteins among subcellular fractions. The caveolar markers ganglioside GM1 and H-ras were found concentrated in the CLD fractions. When plasma membrane proteins were labeled with the impermeant reagent sulfo-N-hydroxysuccinimide-biotin, both PrPC and PrPSc were found biotinylated in CLD fractions. Similar results on the colocalization of PrPC and PrPSc were obtained when CLDs were isolated from Syrian hamster brains. Our findings demonstrate that both PrPC and PrPSc are present in CLDs and, thus, support the hypothesis that the PrPSc formation occurs within this subcellular compartment. PMID:8962161

A New Method for the Characterization of Strain-Specific Conformational Stability of Protease-Sensitive and Protease-Resistant PrPSc

PubMed Central

Pirisinu, Laura; Di Bari, Michele; Marcon, Stefano; Vaccari, Gabriele; D'Agostino, Claudia; Fazzi, Paola; Esposito, Elena; Galeno, Roberta; Langeveld, Jan; Agrimi, Umberto; Nonno, Romolo

2010-01-01

Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrPSc, a disease-associated isoform of the host-encoded cellular protein (PrPC). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrPSc. However, PrPSc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrPSc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrPC and PrPSc by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrPSc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl]1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl]1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrPSc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrPSc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrPSc conformational stabilities of protease-resistant and protease-sensitive PrPSc and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep. PMID:20856860

Co-existence of Distinct Prion Types Enables Conformational Evolution of Human PrPSc by Competitive Selection*

PubMed Central

Haldiman, Tracy; Kim, Chae; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Qing, Liuting; Cohen, Mark L.; Langeveld, Jan; Telling, Glenn C.; Kong, Qingzhong; Safar, Jiri G.

2013-01-01

The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrPSc). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier remains unsolved. Using biophysical techniques and conformation-dependent immunoassays in tandem, we isolated two distinct populations of PrPSc particles with different conformational stabilities and aggregate sizes, which frequently co-exist in the most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein misfolding cyclic amplification replicates each of the PrPSc particle types independently and leads to the competitive selection of those with lower initial conformational stability. In serial propagation with a nonglycosylated mutant PrPC substrate, the dominant PrPSc conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to its lowest stability. Cumulatively, the data show that sporadic Creutzfeldt-Jakob disease PrPSc is not a single conformational entity but a dynamic collection of two distinct populations of particles. This implies the co-existence of different prions, whose adaptation and evolution are governed by the selection of progressively less stable, faster replicating PrPSc conformers. PMID:23974118

Does methionine oxidation influence the progression of classical or atypical scrapie

USDA-ARS?s Scientific Manuscript database

Introduction Prions are pathological proteins that propagate by converting a normal cellular prion protein (PrPC) into a prion (PrPSc). PrPC and PrPSc possess identical covalent structures and only differ in their conformations. The conversion of the PrPC conformation to the PrPSc one is template ...

Biochemical Characterization of Prion Strains in Bank Voles

PubMed Central

Pirisinu, Laura; Marcon, Stefano; Di Bari, Michele Angelo; D’Agostino, Claudia; Agrimi, Umberto; Nonno, Romolo

2013-01-01

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrPSc biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrPSc biochemical characteristics and if it was possible to univocally identify strains through PrPSc biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived) and analyzed PrPSc from individual voles by epitope mapping of protease resistant core of PrPSc (PrPres) and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrPSc types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed. PMID:25437201

High-resolution structure of infectious prion protein: the final frontier

PubMed Central

Diaz-Espinoza, Rodrigo; Soto, Claudio

2014-01-01

Prions are the proteinaceous infectious agents responsible for the transmission of prion diseases. The main or sole component of prions is the misfolded prion protein (PrPSc), which is able to template the conversion of the host’s natively folded form of the protein (PrPC). The detailed mechanism of prion replication and the high-resolution structure of PrPSc are unknown. The currently available information on PrPSc structure comes mostly from low-resolution biophysical techniques, which have resulted in quite divergent models. Recent advances in the production of infectious prions, using very pure recombinant protein, offer new hope for PrPSc structural studies. This review highlights the importance of, challenges for and recent progress toward elucidating the elusive structure of PrPSc, arguably the major pending milestone to reach in understanding prions. PMID:22472622

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

PubMed

Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

2017-07-01

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

Pathogenesis of bovine spongiform encephalopathy in sheep.

PubMed

van Keulen, L J M; Vromans, M E W; Dolstra, C H; Bossers, A; van Zijderveld, F G

2008-01-01

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrP(Sc) accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrP(Sc) was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7-L1. At subsequent time points, PrP(Sc) was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrP(Sc) involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord.

Pathogenesis of bovine spongiform encephalopathy in sheep

PubMed Central

Vromans, M. E. W.; Dolstra, C. H.; Bossers, A.; van Zijderveld, F. G.

2007-01-01

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was detected after 6 months in the tonsil and the ileal Peyer’s patches. At 9 months postinfection, PrPSc accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrPSc accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrPSc was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7–L1. At subsequent time points, PrPSc was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrPSc involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord. PMID:18092124

Detergents modify proteinase K resistance of PrPSc in different transmissible spongiform encephalopathies (TSEs)

PubMed Central

Breyer, Johanna; Wemheuer, Wiebke M.; Wrede, Arne; Graham, Catherine; Benestad, Sylvie L.; Brenig, Bertram; Richt, Jürgen A.; Schulz-Schaeffer, Walter J.

2012-01-01

Prion diseases are diagnosed by the detection of their proteinase K-resistant prion protein fragment (PrPSc). Various biochemical protocols use different detergents for the tissue preparation. We found that the resistance of PrPSc against proteinase K may vary strongly with the detergent used. In our study, we investigated the influence of the most commonly used detergents on eight different TSE agents derived from different species and distinct prion disease forms. For a high throughput we used a membrane adsorbtion assay to detect small amounts of prion aggregates, as well as Western blotting. Tissue lysates were prepared using DOC, SLS, SDS or Triton X-100 in different concentrations and these were digested with various amounts of proteinase K. Detergents are able to enhance or diminish the detectability of PrPSc after proteinase K digestion. Depending on the kind of detergent, its concentration - but also on the host species that developed the TSE and the disease form or prion type - the detectability of PrPSc can be very different. The results obtained here may be helpful during the development or improvement of a PrPSc detection method and they point towards a detergent effect that can be additionally used for decontamination purposes. A plausible explanation for the detergent effects described in this article could be an interaction with the lipids associated with PrPSc that may stabilize the aggregates. PMID:22226540

The multivesicular body is the major internal site of prion conversion

PubMed Central

Yim, Yang-In; Park, Bum-Chan; Yadavalli, Rajgopal; Zhao, Xiaohong; Eisenberg, Evan; Greene, Lois E.

2015-01-01

ABSTRACT The conversion of the properly folded prion protein, PrPc, to its misfolded amyloid form, PrPsc, occurs as the two proteins traffic along the endocytic pathway and PrPc is exposed to PrPsc. To determine the specific site of prion conversion, we knocked down various proteins in the endocytic pathway including Rab7a, Tsg101 and Hrs (also known as HGS). PrPsc was markedly reduced in two chronically infected cell lines by preventing the maturation of the multivesicular body, a process that begins in the early endosome and ends with the sorting of cargo to the lysosome. By contrast, knocking down proteins in the retromer complex, which diverts cargo away from the multivesicular body caused an increase in PrPsc levels. These results suggest that the multivesicular body is the major site for intracellular conversion of PrPc to PrPsc. PMID:25663703

Experimental transmission of U.S. scrapie agent to neonatal sheep by oral route

USDA-ARS?s Scientific Manuscript database

Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. This study documents incubation periods, pathological findings and distribution of abnormal prion proteins (PrP**Sc) by immunohistochemistry and Western blot in tiss...

Prions Adhere to Soil Minerals and Remain Infectious

PubMed Central

Johnson, Christopher J; Phillips, Kristen E; Schramm, Peter T; McKenzie, Debbie; Aiken, Judd M; Pedersen, Joel A

2006-01-01

An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrPSc) with common soil minerals. In this study, we demonstrated substantial PrPSc adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrPSc-binding capacities of each mineral. Furthermore, we observed that PrPSc desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrPSc and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrPSc bound to Mte remained infectious. Results from our study suggest that PrPSc released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent. PMID:16617377

PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

PubMed Central

Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

2007-01-01

We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

Pathological findings in retina and visual pathways associated to natural Scrapie in sheep.

PubMed

Hortells, Paloma; Monzón, Marta; Monleón, Eva; Acín, Cristina; Vargas, Antonia; Bolea, Rosa; Luján, Lluís; Badiola, Juan José

2006-09-07

This work represents a comprehensive pathological description of the retina and visual pathways in naturally affected Scrapie sheep. Twenty naturally affected Scrapie sheep and 6 matched controls were used. Eyes, optic nerves and brain from each animal were fixed and histologically processed using hematoxylin-eosin, followed by immunohistochemical staining for prion protein (PrPsc) and glial fibrillar acidic protein (GFAP). Retinal histopathological changes were observed in only 7 clinically affected animals and mainly consisted of loss of outer limitant layer definition, outer plexiform layer atrophy, disorganization and loss of nuclei in both nuclear layers, and Müller glia hypertrophy. PrPsc was detected in the retina of 19 of the 20 sheep and characterized by a disseminated granular deposit across layers and intraneuronally in ganglion cells. The inner plexiform and the ganglion cell layers were the structures most severely affected by PrPsc deposits. PrPsc exhibited a tendency to spread from these two layers to the others. A marked increase in the number and intensity of GFAP-expressing Müller cells was observed in the clinical stage, especially at the terminal stage of the disease. Spongiosis and PrPsc were detected within the visual pathways at the preclinical stage, their values increasing during the course of the disease but varying between the areas examined. PrPsc was detected in only 3 optic nerves. The results suggest that the presence of PrPsc in the retina correlates with disease progression during the preclinical and clinical stages, perhaps using the inner plexiform layer as a first entry site and diffusing from the brain using a centrifugal model.

Experimental infection of meadow voles (Microtus pennsylvanicus) with sheep scrapie

USGS Publications Warehouse

Carlson, CM; Schneider, Jay R.; Pedersen, Janice C.; Heisey, Dennis M.; Johnson, Christopher J.

2015-01-01

Meadow voles (Microtus pennsylvanicus) are permissive to chronic wasting disease (CWD) infection, but their susceptibility to other transmissible spongiform encephalopathies (TSEs) is poorly characterized. In this initial study, we intracerebrally challenged 6 meadow voles with 2 isolates of sheep scrapie. Three meadow voles acquired a TSE after the scrapie challenge and an extended incubation period. The glycoform profile of proteinase K-resistant prion protein (PrP(res)) in scrapie-sick voles remained similar to the sheep inocula, but differed from that of voles clinically affected by CWD. Vacuolization patterns and disease-associated prion protein (PrP(Sc)) deposition were generally similar in all scrapie-affected voles, except in the hippocampus, where PrP(Sc) staining varied markedly among the animals. Our results demonstrate that meadow voles can acquire a TSE after intracerebral scrapie challenge and that this species could therefore prove useful for characterizing scrapie isolates.

Temporal resolution of PrPSc transport, PrPSc accumulation, activation of glia and neuronal death in retinas from C57Bl/6 mice inoculated with RML scrapie: Relevance to biomarkers of prion disease progression

USDA-ARS?s Scientific Manuscript database

Currently, there is a lack of pathologic landmarks to objectively evaluate the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between transport of misfolded prion protein to the retina from the brain, accumulation of PrPSc in the retina, the re...

Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.

PubMed

Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Satoh, Katsuya; Sano, Kazunori; Atarashi, Ryuichiro; Nishida, Noriyuki

2014-03-28

Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP(Sc), forming a large aggregate in the perinuclear region, hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP(Sc). Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.

Recombinant human prion protein inhibits prion propagation in vitro.

PubMed

Yuan, Jue; Zhan, Yi-An; Abskharon, Romany; Xiao, Xiangzhu; Martinez, Manuel Camacho; Zhou, Xiaochen; Kneale, Geoff; Mikol, Jacqueline; Lehmann, Sylvain; Surewicz, Witold K; Castilla, Joaquín; Steyaert, Jan; Zhang, Shulin; Kong, Qingzhong; Petersen, Robert B; Wohlkonig, Alexandre; Zou, Wen-Quan

2013-10-09

Prion diseases are associated with the conformational conversion of the cellular prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc), but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune response side effects.

Transmission of chronic wasting disease of white-tailed deer to Suffolk sheep following intracranial inoculation

USDA-ARS?s Scientific Manuscript database

Background: Interspecies transmission studies are an opportunity to better understand the potential host ranges of prion diseases. Chronic wasting disease (CWD) of cervids and scrapie of sheep and goats have a similar tissue distribution of abnormal prion protein (PrPSc) and prion disease exposure a...

The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease.

PubMed

Peden, Alexander H; Sarode, Deep P; Mulholland, Carl R; Barria, Marcelo A; Ritchie, Diane L; Ironside, James W; Head, Mark W

2014-10-21

Variably protease sensitive prionopathy (VPSPr) is a recently described, sporadic human prion disease that is pathologically and biochemically distinct from the currently recognised sporadic Creutzfeldt-Jakob disease (sCJD) subtypes. The defining biochemical features of the abnormal form of the prion protein (PrPSc) in VPSPr are increased sensitivity to proteolysis and the presence of an N- and C-terminally cleaved ~8 kDa protease resistant PrPSc (PrPres) fragment. The biochemical and neuropathological profile of VPSPr has been proposed to resemble either Gerstmann-Sträussler-Scheinker syndrome (GSS) or familial CJD with the PRNP-V180I mutation. However, in some cases of VPSPr two protease resistant bands have been observed in Western blots that co-migrate with those of type 2 PrPres, suggesting that a proportion of the PrPSc present in VPSPr has properties similar to those of sCJD. Here, we have used conformation dependent immunoassay to confirm the presence of PrPSc in VPSPr that is more protease sensitive compared with sCJD. However, CDI also shows that a proportion of PrPSc in VPSPr resists PK digestion of its C-terminus, distinguishing it from GSS associated with ~8 kDa PrPres, and showing similarity to sCJD. Intensive investigation of a single VPSPr case with frozen tissue from multiple brain regions shows a broad, region-specific spectrum of protease sensitivity and differential stability of PrPSc in the absence of PK treatment. Finally, using protein misfolding cyclic amplification and real-time quaking induced conversion, we show that VPSPr PrPSc has the potential to seed conversion in vitro and that seeding activity is dispersed through a broad range of aggregate sizes. We further propose that seeding activity is associated with the ~19 and ~23 kDa PrPres rather than the ~8 kDa fragment. Therefore, PrPSc in VPSPr is heterogeneous in terms of protease sensitivity and stability to denaturation with the chaotrope GdnHCl and includes a proportion with similar properties to that found in sCJD.

Piperazine derivatives inhibit PrP/PrP(res) propagation in vitro and in vivo.

PubMed

Leidel, Fabienne; Eiden, Martin; Geissen, Markus; Hirschberger, Thomas; Tavan, Paul; Giese, Armin; Kretzschmar, Hans A; Schätzl, Hermann; Groschup, Martin H

2014-02-28

Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPc(C) into a disease-associated isoform PrP(Sc). PrP(Sc) accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrP(Sc) species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrP(Sc) formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10,000 compounds (DIVERset 2, ChemBridge). We could detect six different classes of highly potent inhibitors of PrP(Sc) propagation in vitro and identified piperazine derivatives as a new inhibitory lead structure, which increased incubation time of scrapie infected mice. Copyright © 2014 Elsevier Inc. All rights reserved.

A short purification process for quantitative isolation of PrPSc from naturally occurring and experimental transmissible spongiform encephalopathies

PubMed Central

Polymenidou, Magdalini; Verghese-Nikolakaki, Susan; Groschup, Martin; Chaplin, Melanie J; Stack, Mick J; Plaitakis, Andreas; Sklaviadis, Theodoros

2002-01-01

Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases affecting both humans and animals. They are associated with post-translational conversion of the normal cellular prion protein (PrPC) into a heat- and protease-resistant abnormal isoform (PrPSc). Detection of PrPSc in individuals is widely utilized for the diagnosis of prion diseases. Methods TSE brain tissue samples have been processed in order to quantitatively isolate PrPSc. The protocol includes an initial homogenization, digestion with proteinase K and salt precipitation. Results Here we show that over 97 percent of the PrPSc present can be precipitated from infected brain material using this simple salting-out procedure for proteins. No chemically harsh conditions are used during the process in order to conserve the native quality of the isolated protein. Conclusion The resulting PrPSc-enriched preparation should provide a suitable substrate for analyzing the structure of the prion agent and for scavenging for other molecules with which it may associate. In comparison with most methods that exist today, the one described in this study is rapid, cost-effective and does not demand expensive laboratory equipment. PMID:12370086

Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie

USDA-ARS?s Scientific Manuscript database

Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to co...

Evidence of scrapie transmission to sheep via goat milk.

PubMed

Konold, Timm; Thorne, Leigh; Simmons, Hugh A; Hawkins, Steve A C; Simmons, Marion M; González, Lorenzo

2016-09-17

Previous studies confirmed that classical scrapie can be transmitted via milk in sheep. The current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [sPMCA] on milk samples). In an initial pilot study, new-born lambs of two different prion protein gene (PRNP) genotypes (six VRQ/VRQ and five ARQ/ARQ) were orally challenged with 5 g brain homogenate from two scrapie-affected goats to determine susceptibility of sheep to goat scrapie. All sheep challenged with goat scrapie brain became infected based on the immunohistochemical detection of disease-associated PrP (PrP(sc)) in lymphoid tissue, with an ARQ/ARQ sheep being the first to succumb. Subsequent feeding of milk to eight pairs of new-born ARQ/ARQ lambs, with each pair receiving milk from a different scrapie-affected goat, resulted in scrapie in the six pairs that received the largest volume of milk (38-87 litres per lamb), whereas two pairs fed 8-9 litres per lamb, and an environmental control group raised on sheep milk from healthy ewes, did not show evidence of infection when culled at up to 1882 days of age. Infection in those 12 milk recipients occurred regardless of the clinical status, PrP(sc) distribution, caprine arthritis-encephalitis virus infection status and PRNP polymorphisms at codon 142 (II or IM) of the donor goats, but survival time was influenced by PRNP polymorphisms at codon 141. Serial PMCA applied to a total of 32 milk samples (four each from the eight donor goats collected throughout lactation) detected PrP(sc) in one sample each from two goats. The scrapie agent was present in the milk from infected goats and was able to transmit to susceptible species even at early preclinical stage of infection, when PrP(sc) was undetectable in the brain of the donor goats. Serial PMCA as a PrP(sc) detection method to assess the risk of scrapie transmission via milk in goats proved inefficient compared to the bioassay.

Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type.

PubMed

Hannaoui, Samia; Maatouk, Layal; Privat, Nicolas; Levavasseur, Etienne; Faucheux, Baptiste A; Haïk, Stéphane

2013-03-01

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrP(Sc)) of the host-encoded prion protein (PrP(C)), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrP(Sc) distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate in vitro studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess in vitro neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated in vitro; (ii) the cytotoxic effect varied among strains and neuronal cell types; (iii) prion propagation and toxicity occurred in two kinetic phases, a replicative phase followed by a toxic phase; and (iv) neurotoxicity peaked when abnormal PrP accumulation reached a plateau.

Prion Propagation and Toxicity Occur In Vitro with Two-Phase Kinetics Specific to Strain and Neuronal Type

PubMed Central

Hannaoui, Samia; Maatouk, Layal; Privat, Nicolas; Levavasseur, Etienne; Faucheux, Baptiste A.

2013-01-01

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrPSc) of the host-encoded prion protein (PrPC), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrPSc distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate in vitro studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess in vitro neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated in vitro; (ii) the cytotoxic effect varied among strains and neuronal cell types; (iii) prion propagation and toxicity occurred in two kinetic phases, a replicative phase followed by a toxic phase; and (iv) neurotoxicity peaked when abnormal PrP accumulation reached a plateau. PMID:23255799

Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells.

PubMed Central

Rogers, M; Yehiely, F; Scott, M; Prusiner, S B

1993-01-01

The only known component of the infectious prion is a posttranslationally modified protein known as the scrapie isoform of the prion protein, PrPSc. Upon limited proteolysis, a protease-resistant fragment designated PrP 27-30 is formed. Using in vitro mutagenesis, we examined the role of the N and C termini in the formation of PrPSc in persistently infected, mouse neuroblastoma (ScN2a) cells. Neither deletion of amino acids 23-88, which are also removed by proteinase K in the formation of PrP 27-30, nor deletion of the five octapeptide repeats within this region altered synthesis of PrPSc. Elongation of PrP with one, two, four, or six octapeptide repeats in addition to the five found in wild-type PrP did not alter the synthesis of PrPSc. Truncation of the C terminus was accomplished by substituting a translation stop codon for the predicted glycosylinositol phospholipid (GPI) anchor-attachment signal corresponding to amino acids 231-254. Expression of this C-terminal PrP mutant in ScN2a cells produced PrPSc that appeared to lack a GPI anchor. We conclude that neither the GPI anchor nor the N-terminal 66 amino acids are required for the synthesis of PrPSc as measured by the acquisition of limited resistance to proteinase K digestion. Whether these truncated or elongated PrP molecules are competent to participate in the formation of infectious prions remains to be established. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8475059

Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.

PubMed

Akasaka, Kazuyuki; Maeno, Akihiro; Murayama, Taichi; Tachibana, Hideki; Fujita, Yuzo; Yamanaka, Hitoki; Nishida, Noriyuki; Atarashi, Ryuichiro

2014-01-01

The crucial step for the fatal neurodegenerative prion diseases involves the conversion of a normal cellular protein, PrP(C), into a fibrous pathogenic form, PrP(Sc), which has an unusual stability against heat and resistance against proteinase K digestion. A successful challenge to reverse the reaction from PrP(Sc) into PrP(C) is considered valuable, as it would give a key to dissolving the complex molecular events into thermodynamic and kinetic analyses and may also provide a means to prevent the formation of PrP(Sc) from PrP(C) eventually in vivo. Here we show that, by applying pressures at kbar range, the "proteinase K-resistant" fibrils (rHaPrP(res)) prepared from hamster prion protein (rHaPrP [23-231]) by seeding with brain homogenate of scrapie-infected hamster, becomes easily digestible. The result is consistent with the notion that rHaPrP(res) fibrils are dissociated into rHaPrP monomers under pressure and that the formation of PrP(Sc) from PrP(C) is thermodynamically controlled. Moreover, the efficient degradation of prion fibrils under pressure provides a novel means of eliminating infectious PrP(Sc) from various systems of pathogenic concern.

Endogenous proteolytic cleavage of disease-associated prion protein to produce C2 fragments is strongly cell- and tissue-dependent.

PubMed

Dron, Michel; Moudjou, Mohammed; Chapuis, Jérôme; Salamat, Muhammad Khalid Farooq; Bernard, Julie; Cronier, Sabrina; Langevin, Christelle; Laude, Hubert

2010-04-02

The abnormally folded form of the prion protein (PrP(Sc)) accumulating in nervous and lymphoid tissues of prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about the identity of the cellular proteases involved in this process and its possible role in prion biology has remained limited and controversial. We investigated PrP(Sc) N-terminal trimming in different cell lines and primary cultured nerve cells, and in the brain and spleen tissue from transgenic mice infected by ovine and mouse prions. We found the following: (i) the full-length to C2 ratio varies considerably depending on the infected cell or tissue. Thus, in primary neurons and brain tissue, PrP(Sc) accumulated predominantly as untrimmed species, whereas efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii) Although C2 is generally considered to be the counterpart of the PrP(Sc) proteinase K-resistant core, the N termini of the fragments cleaved in vivo and in vitro can actually differ, as evidenced by a different reactivity toward the Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of full-length versus C2 species dramatically increased, yet efficient prion propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced PrP(Sc) fragments lacking the Pc248 epitope, strongly arguing for the primary involvement of acidic hydrolases of the endolysosomal compartment. These findings have implications on the molecular analysis of PrP(Sc) and cell pathogenesis of prion infection.

Endogenous Proteolytic Cleavage of Disease-associated Prion Protein to Produce C2 Fragments Is Strongly Cell- and Tissue-dependent*

PubMed Central

Dron, Michel; Moudjou, Mohammed; Chapuis, Jérôme; Salamat, Muhammad Khalid Farooq; Bernard, Julie; Cronier, Sabrina; Langevin, Christelle; Laude, Hubert

2010-01-01

The abnormally folded form of the prion protein (PrPSc) accumulating in nervous and lymphoid tissues of prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about the identity of the cellular proteases involved in this process and its possible role in prion biology has remained limited and controversial. We investigated PrPSc N-terminal trimming in different cell lines and primary cultured nerve cells, and in the brain and spleen tissue from transgenic mice infected by ovine and mouse prions. We found the following: (i) the full-length to C2 ratio varies considerably depending on the infected cell or tissue. Thus, in primary neurons and brain tissue, PrPSc accumulated predominantly as untrimmed species, whereas efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii) Although C2 is generally considered to be the counterpart of the PrPSc proteinase K-resistant core, the N termini of the fragments cleaved in vivo and in vitro can actually differ, as evidenced by a different reactivity toward the Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of full-length versus C2 species dramatically increased, yet efficient prion propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced PrPSc fragments lacking the Pc248 epitope, strongly arguing for the primary involvement of acidic hydrolases of the endolysosomal compartment. These findings have implications on the molecular analysis of PrPSc and cell pathogenesis of prion infection. PMID:20154089

Recombinant Prion Protein Refolded with Lipid and RNA Has the Biochemical Hallmarks of a Prion but Lacks In Vivo Infectivity

PubMed Central

Timmes, Andrew G.; Moore, Roger A.; Fischer, Elizabeth R.; Priola, Suzette A.

2013-01-01

During prion infection, the normal, protease-sensitive conformation of prion protein (PrPC) is converted via seeded polymerization to an abnormal, infectious conformation with greatly increased protease-resistance (PrPSc). In vitro, protein misfolding cyclic amplification (PMCA) uses PrPSc in prion-infected brain homogenates as an initiating seed to convert PrPC and trigger the self-propagation of PrPSc over many cycles of amplification. While PMCA reactions produce high levels of protease-resistant PrP, the infectious titer is often lower than that of brain-derived PrPSc. More recently, PMCA techniques using bacterially derived recombinant PrP (rPrP) in the presence of lipid and RNA but in the absence of any starting PrPSc seed have been used to generate infectious prions that cause disease in wild-type mice with relatively short incubation times. These data suggest that lipid and/or RNA act as cofactors to facilitate the de novo formation of high levels of prion infectivity. Using rPrP purified by two different techniques, we generated a self-propagating protease-resistant rPrP molecule that, regardless of the amount of RNA and lipid used, had a molecular mass, protease resistance and insolubility similar to that of PrPSc. However, we were unable to detect prion infectivity in any of our reactions using either cell-culture or animal bioassays. These results demonstrate that the ability to self-propagate into a protease-resistant insoluble conformer is not unique to infectious PrP molecules. They suggest that the presence of RNA and lipid cofactors may facilitate the spontaneous refolding of PrP into an infectious form while also allowing the de novo formation of self-propagating, but non-infectious, rPrP-res. PMID:23936256

Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation

PubMed Central

Alleaume-Butaux, Aurélie; Nicot, Simon; Pietri, Mathéa; Baudry, Anne; Dakowski, Caroline; Tixador, Philippe; Ardila-Osorio, Hector; Haeberlé, Anne-Marie; Bailly, Yannick; Peyrin, Jean-Michel; Launay, Jean-Marie; Kellermann, Odile; Schneider, Benoit

2015-01-01

In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc) and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1) activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases. PMID:26241960

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

USDA-ARS?s Scientific Manuscript database

Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

Divergent prion strain evolution driven by PrPC expression level in transgenic mice

PubMed Central

Le Dur, Annick; Laï, Thanh Lan; Stinnakre, Marie-George; Laisné, Aude; Chenais, Nathalie; Rakotobe, Sabine; Passet, Bruno; Reine, Fabienne; Soulier, Solange; Herzog, Laetitia; Tilly, Gaëlle; Rézaei, Human; Béringue, Vincent; Vilotte, Jean-Luc; Laude, Hubert

2017-01-01

Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPC into PrPSc. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Constrained interactions between PrPC and different PrPSc strains can in turn lead to certain PrPSc (sub)populations being selected for cross-species transmission, or even produce mutation-like events. By contrast, prion strains are generally conserved when transmitted within the same species, or to transgenic mice expressing homologous PrPC. Here, we compare the strain properties of a representative sheep scrapie isolate transmitted to a panel of transgenic mouse lines expressing varying levels of homologous PrPC. While breeding true in mice expressing PrPC at near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPC overexpression. Our results support the view that PrPC gene dosage can influence prion evolution on homotypic transmission. PMID:28112164

Semi-purification procedures of prions from a prion-infected brain using sucrose has no influence on the nonenzymatic glycation of the disease-associated prion isoform.

PubMed

Choi, Yeong-Gon; Kim, Jae-Il; Choi, Eun-Kyoung; Carp, Richard I; Kim, Yong-Sun

2016-01-01

Previous studies have shown that the Nε-carboxymethyl group is linked to not only one or more N-terminal Lys residues but also to one or more Lys residues of the protease-resistant core region of the pathogenic prion isoform (PrPSc) in prion-infected brains. Using an anti-advanced glycation end product (AGE) antibody, we detected nonenzymatically glycated PrPSc (AGE-PrPSc) in prion-infected brains following concentration by a series of ultracentrifugation steps with a sucrose cushion. In the present study, the levels of in vitro nonenzymatic glycation of PrPSc using sucrose were investigated to determine whether sucrose cushion can artificially and nonenzymatically induce in vitro glycation during ultracentrifugation. The first insoluble pellet fraction following the first ultracentrifugation (PU1st) collected from 263K scrapie-infected brains was incubated with sucrose, glucose or colloidal silica coated with polyvinylpyrrolidone (percoll). None of the compounds in vitro resulted in AGE-PrPSc. Nonetheless, glucose and percoll produced AGEs in vitro from other proteins within PU1st of the infected brains. This reaction could lead to the AGE-modified polymer(s) of nonenzymatic glycation-prone protein(s). This study showed that PrPSc is not nonenzymatically glycated in vitro with sucrose, glucose or percoll and that AGE-modified PrPSc can be isolated and enriched from prion-infected brains.

Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.

PubMed

Cali, Ignazio; Miller, Cathleen J; Parisi, Joseph E; Geschwind, Michael D; Gambetti, Pierluigi; Schonberger, Lawrence B

2015-06-25

The present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1). The index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1. Our study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.

Quantifying the relative amounts of PrP polymorphisms present in prions isolated from heterozygous prion-infected animals

USDA-ARS?s Scientific Manuscript database

Prions cause protein misfolding diseases, such as transmissible spongiform encephalopathy. They propagate infections by converting a normal cellular prion protein into a prion (PrPSc). PrPC and PrPSc are isosequential and differ only in their respective conformations. PrPC is monomeric and sensit...

Inoculation of Scrapie with the Self-Assembling RADA-Peptide Disrupts Prion Accumulation and Extends Hamster Survival

USDA-ARS?s Scientific Manuscript database

Intercerebral inoculation of 263K Scrapie brain homogenate (PrPsc) with a self-assembling RADA-peptide (RADA) significantly delayed disease onset and increased hamster survival. Time of survival was dependent on the dose of RADA and pre-incubation with PrPsc prior to inoculation. RADA treatment resu...

Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

PubMed Central

2010-01-01

Background Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" Methods Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. Results Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrPSc positive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC). Conclusions Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2) that the amount of PrPSc in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD. PMID:21108848

Prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (S/D)-treated plasma OctaplasLG.

PubMed

Neisser-Svae, A; Bailey, A; Gregori, L; Heger, A; Jordan, S; Behizad, M; Reichl, H; Römisch, J; Svae, T-E

2009-10-01

A new chromatographic step for the selective binding of abnormal prion protein (PrP(Sc)) was developed, and optimization for PrP(Sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. This step was implemented into the manufacturing process of the solvent/detergent (S/D)-treated biopharmaceutical quality plasma Octaplas to further improve the safety margin in terms of risk for variant Creutzfeldt-Jakob disease (vCJD) transmission. Intermediates and Octaplas final container material, spiked with hamster brain-derived PrP(Sc)-containing fractions, were used for experiments to establish the feasibility of introducing this novel chromatography step. The binding capacity per millilitre of ligand gel was determined under the selected manufacturing conditions. In addition, the specificity of the ligand gel to bind PrP(Sc) from human sources was investigated. A validated Western blot test was used for the identification and quantification of PrP(Sc). A reduction factor of > or = 3.0 log(10) could be demonstrated by Western blotting, utilizing the relevant Octaplas matrix from manufacturing. In this particular cell-free plasma solution, the PrP(Sc) binding capacity of the selected gel was very high (> or = 6 log(10) ID(50)/ml, equivalent to roughly 10 log(10) ID(50)/column at manufacturing scale). The gel binds specifically PrP(Sc) from both animal (hamster and mouse) and human (sporadic and variant CJD) sources. This new single-use, disposable PrP(Sc)-harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG, in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.

Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases.

PubMed

Kabir, M Enamul; Safar, Jiri G

2014-01-01

There is a growing body of evidence indicating that number of human neurodegenerative diseases, including Alzheimer disease, Parkinson disease, fronto-temporal dementias, and amyotrophic lateral sclerosis, propagate in the brain via prion-like intercellular induction of protein misfolding. Prions cause lethal neurodegenerative diseases in humans, the most prevalent being sporadic Creutzfeldt-Jakob disease (sCJD); they self-replicate and spread by converting the cellular form of prion protein (PrP(C)) to a misfolded pathogenic conformer (PrP(Sc)). The extensive phenotypic heterogeneity of human prion diseases is determined by polymorphisms in the prion protein gene, and by prion strain-specific conformation of PrP(Sc). Remarkably, even though informative nucleic acid is absent, prions may undergo rapid adaptation and evolution in cloned cells and upon crossing the species barrier. In the course of our investigation of this process, we isolated distinct populations of PrP(Sc) particles that frequently co-exist in sCJD. The human prion particles replicate independently and undergo competitive selection of those with lower initial conformational stability. Exposed to mutant substrate, the winning PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to the lowest stability. Thus, the evolution and adaptation of human prions is enabled by a dynamic collection of distinct populations of particles, whose evolution is governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers. This fundamental biological mechanism may explain the drug resistance that some prions gained after exposure to compounds targeting PrP(Sc). Whether the phenotypic heterogeneity of other neurodegenerative diseases caused by protein misfolding is determined by the spectrum of misfolded conformers (strains) remains to be established. However, the prospect that these conformers may evolve and adapt by a prion-like mechanism calls for the reevaluation of therapeutic strategies that target aggregates of misfolded proteins, and argues for new therapeutic approaches that will focus on prior pathogenetic steps.

Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

PubMed

Bessen, Richard A; Robinson, Cameron J; Seelig, Davis M; Watschke, Christopher P; Lowe, Diana; Shearin, Harold; Martinka, Scott; Babcock, Alex M

2011-01-01

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc), prion infection of the central and peripheral neuroendocrine system, and PrP(Sc) deposition in cardiac muscle. There was also prominent PrP(Sc) deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

Relationships between PrPSc stability and incubation time for United States scrapie strains in a natural host system

USDA-ARS?s Scientific Manuscript database

Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP**C) into a beta-rich conformer (PrP**Sc) that accumulates into higher-order structures in the brain and other ti...

Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

USDA-ARS?s Scientific Manuscript database

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

Accumulation of PrP-Sc in hemal nodes of naturally and experimentally scrapie-infected sheep

USDA-ARS?s Scientific Manuscript database

Classical scrapie is a naturally occurring fatal disease of sheep and goats which is caused by prions, a novel class of infectious agent. Infection is accompanied by accumulation of abnormal isoforms of the prion protein (PrP-Sc) in certain neural and lymphoid tissues. Hemal nodes, which are unique ...

In vitro replication highlights the mutability of prions.

PubMed

Vanni, Ilaria; Di Bari, Michele Angelo; Pirisinu, Laura; D'Agostino, Claudia; Agrimi, Umberto; Nonno, Romolo

2014-01-01

Prions exist as strains, which are thought to reflect PrP(Sc) conformational variants. Prion strains can mutate and it has been proposed that prion mutability depends on an intrinsic heterogeneity of prion populations that would behave as quasispecies. We investigated in vitro prion mutability of 2 strains, by following PrP(Sc) variations of populations serially propagated in PMCA under constant environmental pressure. Each strain was propagated either at low dilution of the seed, i.e., by large population passages, or at limiting dilution, mimicking bottleneck events. In both strains, PrP(Sc) conformational variants were identified only after large population passages, while repeated bottleneck events caused a rapid decline in amplification rates. These findings support the view that mutability is an intrinsic property of prions.

Proximity of SCG10 and prion protein in membrane rafts.

PubMed

Iwamaru, Yoshifumi; Kitani, Hiroshi; Okada, Hiroyuki; Takenouchi, Takato; Shimizu, Yoshihisa; Imamura, Morikazu; Miyazawa, Kohtaro; Murayama, Yuichi; Hoover, Edward A; Yokoyama, Takashi

2015-12-10

The conversion of normal cellular prion protein (PrPC) into its pathogenic isoform (PrPSc) is an essential event in prion pathogenesis. In culture models, membrane rafts are suggested to play a critical role in PrPSc formation. To identify the candidate molecules capable of interacting with PrPC and facilitating PrPSc formation in membrane rafts, we applied a novel biochemical labelling method termed 'enzyme-mediated activation of radical sources (EMARS)'. EMARS was applied to the Lubrol WX insoluble detergent-resistant membrane fractions from mouse neuroblastoma (N2a) cells in which the surface PrPC was labeled with HRP-conjugated anti-PrP antibody. Two-dimensional Western blots of these preparations revealed biotinylated spots of approximately 20 kDa with an isoelectric point of 8.0-9.0. Liquid chromatography-tandem mass spectrometry analysis resulted in the identification of peptides containing SCG10, the neuron-specific microtubule regulator. Proximity of SCG10 and PrPC was confirmed using proximity ligation assay and co-immunoprecipitation assay. Transfection of persistently 22L prion infected N2a cells with SCG10 small interfering RNA reduced SCG10 expression but did not prevent PrPSc accumulation, indicating that SCG10 appears to be unrelated to PrPSc formation of 22L prion. Immunofluorescence and Western blot analyses showed reduced levels of SCG10 in the hippocampus of prion-infected mice, suggesting a possible association between SCG10 levels and the prion neuropathogenesis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles

USDA-ARS?s Scientific Manuscript database

The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (I...

Covalent surface modification of prions: a mass spectrometry-based means of detecting distinctive structural features of prion strains

USDA-ARS?s Scientific Manuscript database

Prions (PrPSc) are molecular pathogens that are able to convert the isosequential normal cellular prion protein (PrPC) into a prion. The only demonstrated differences between PrPC and PrPSc is conformational, they are isoforms. A given host can be infected by more than one kind or strain of prion. F...

Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates*

PubMed Central

Margalith, Ilan; Suter, Carlo; Ballmer, Boris; Schwarz, Petra; Tiberi, Cinzia; Sonati, Tiziana; Falsig, Jeppe; Nyström, Sofie; Hammarström, Per; Åslund, Andreas; Nilsson, K. Peter R.; Yam, Alice; Whitters, Eric; Hornemann, Simone; Aguzzi, Adriano

2012-01-01

Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23–231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23–231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits. PMID:22493452

Octarepeat region flexibility impacts prion function, endoproteolysis and disease manifestation

PubMed Central

Lau, Agnes; McDonald, Alex; Daude, Nathalie; Mays, Charles E; Walter, Eric D; Aglietti, Robin; Mercer, Robert CC; Wohlgemuth, Serene; van der Merwe, Jacques; Yang, Jing; Gapeshina, Hristina; Kim, Chae; Grams, Jennifer; Shi, Beipei; Wille, Holger; Balachandran, Aru; Schmitt-Ulms, Gerold; Safar, Jiri G; Millhauser, Glenn L; Westaway, David

2015-01-01

The cellular prion protein (PrPC) comprises a natively unstructured N-terminal domain, including a metal-binding octarepeat region (OR) and a linker, followed by a C-terminal domain that misfolds to form PrPSc in Creutzfeldt-Jakob disease. PrPC β-endoproteolysis to the C2 fragment allows PrPSc formation, while α-endoproteolysis blocks production. To examine the OR, we used structure-directed design to make novel alleles, ‘S1’ and ‘S3’, locking this region in extended or compact conformations, respectively. S1 and S3 PrP resembled WT PrP in supporting peripheral nerve myelination. Prion-infected S1 and S3 transgenic mice both accumulated similar low levels of PrPSc and infectious prion particles, but differed in their clinical presentation. Unexpectedly, S3 PrP overproduced C2 fragment in the brain by a mechanism distinct from metal-catalysed hydrolysis reported previously. OR flexibility is concluded to impact diverse biological endpoints; it is a salient variable in infectious disease paradigms and modulates how the levels of PrPSc and infectivity can either uncouple or engage to drive the onset of clinical disease. PMID:25661904

Use of an ELISA-based stability assay to examine host genotype, PrP**Sc stability, and incubation time relationships in U.S. livestock prion strains

USDA-ARS?s Scientific Manuscript database

Transmissible spongiform encephalopathies (TSEs) are caused by the misfolding of the cellular prion protein (PrP**C) into a disease-associated version (PrP**Sc) that accumulates in certain tissues, leading to pathological changes in the brain and eventual death. Different strains of TSEs have been d...

Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrPSc accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype

USDA-ARS?s Scientific Manuscript database

Background Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. Findings This study reports the failure to detect PrPSc in nervous or lymphoid tis...

The architecture of PrPSc: Threading secondary structure elements into the 4-rung ß-solenoid scaffold

USDA-ARS?s Scientific Manuscript database

Aims: We propose to exploit the wealth of theoretical and experimental constraints to develop a structure of the infectious prion (hamster PrP27-30). Recent cryo-EM based evidence has determined that PrPSc is a 4-rung ß-solenoid (Vázquez-Fernández et al. 2016, PLoS Pathog. 12(9): e1005835). This ev...

Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

PubMed

Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

2015-01-01

Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using growth media supplemented with FBS.

Removal of Transmissible Spongiform Encephalopathy Prion from Large Volumes of Cell Culture Media Supplemented with Fetal Bovine Serum by Using Hollow Fiber Anion-Exchange Membrane Chromatography

PubMed Central

Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

2015-01-01

Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco’s modified Eagle’s medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using growth media supplemented with FBS. PMID:25874629

Relationship of PrPSc molecular properties with incubation time in a natural prion disease host: a characterization of three isolates of U.S. sheep scrapie

USDA-ARS?s Scientific Manuscript database

Determination of aspects of tertiary and quaternary structure of PrPSc associated with differences in disease presentation in the host is a key area of interest in the prion field. Previously, we determined that a U.S. scrapie isolate (136-VDEP) with a short incubation time upon passage in sheep als...

Kinetics of Ozone Inactivation of Infectious Prion Protein

PubMed Central

Ding, Ning; Price, Luke M.; Braithwaite, Shannon L.; Balachandran, Aru; Mitchell, Gordon; Belosevic, Miodrag

2013-01-01

The kinetics of ozone inactivation of infectious prion protein (PrPSc, scrapie 263K) was investigated in ozone-demand-free phosphate-buffered saline (PBS). Diluted infectious brain homogenates (IBH) (0.01%) were exposed to a predetermined ozone dose (10.8 ± 2.0 mg/liter) at three pHs (pH 4.4, 6.0, and 8.0) and two temperatures (4°C and 20°C). The inactivation of PrPSc was quantified by determining the in vitro destruction of PrPSc templating properties using the protein misfolding cyclic amplification (PMCA) assay and bioassay, which were shown to correlate well. The inactivation kinetics were characterized by both Chick-Watson (CW) and efficiency factor Hom (EFH) models. It was found that the EFH model fit the experimental data more appropriately. The efficacy of ozone inactivation of PrPSc was both pH and temperature dependent. Based on the EFH model, CT (disinfectant concentration multiplied by contact time) values were determined for 2-log10, 3-log10, and 4-log10 inactivation at the conditions under which they were achieved. Our results indicated that ozone is effective for prion inactivation in ozone-demand-free water and may be applied for the inactivation of infectious prion in prion-contaminated water and wastewater. PMID:23416994

Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease.

PubMed

Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce

2016-07-03

Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model.

Enzymatic Formulation Capable of Degrading Scrapie Prion under Mild Digestion Conditions

PubMed Central

Okoroma, Emeka A.; Purchase, Diane; Garelick, Hemda; Morris, Roger; Neale, Michael H.; Windl, Otto; Abiola, Oduola O.

2013-01-01

The prion agent is notoriously resistant to common proteases and conventional sterilisation procedures. The current methods known to destroy prion infectivity such as incineration, alkaline and thermal hydrolysis are harsh, destructive, environmentally polluting and potentially hazardous, thus limit their applications for decontamination of delicate medical and laboratory devices, remediation of prion contaminated environment and for processing animal by-products including specified risk materials and carcases. Therefore, an environmentally friendly, non-destructive enzymatic degradation approach is highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has been isolated which degraded scrapie prion to undetectable level of PrPSc signals as determined by Western Blot analysis. Prion infectivity was verified by ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrPSc at 65°C in 10 min to undetectable level -. A time-course degradation analysis carried out at 50°C over 2 h revealed the progressive attenuation of PrPSc intensity. Test of residual infectivity by standard cell culture assay confirmed that the enzymatic formulation reduced PrPSc infectivity to undetectable levels as compared to cells challenged with untreated standard scrapie sheep prion (SSBP/1) (p-value = 0.008 at 95% confidence interval). This novel enzymatic formulation has significant potential application for prion decontamination in various environmentally friendly systems under mild treatment conditions. PMID:23874511

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice

PubMed Central

Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1–4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain. PMID:29220360

Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein.

PubMed

Leske, Henning; Hornemann, Simone; Herrmann, Uli Simon; Zhu, Caihong; Dametto, Paolo; Li, Bei; Laferriere, Florent; Polymenidou, Magdalini; Pelczar, Pawel; Reimann, Regina Rose; Schwarz, Petra; Rushing, Elisabeth Jane; Wüthrich, Kurt; Aguzzi, Adriano

2017-01-01

Resistance to proteolytic digestion has long been considered a defining trait of prions in tissues of organisms suffering from transmissible spongiform encephalopathies. Detection of proteinase K-resistant prion protein (PrPSc) still represents the diagnostic gold standard for prion diseases in humans, sheep and cattle. However, it has become increasingly apparent that the accumulation of PrPSc does not always accompany prion infections: high titers of prion infectivity can be reached also in the absence of protease resistant PrPSc. Here, we describe a structural basis for the phenomenon of protease-sensitive prion infectivity. We studied the effect on proteinase K (PK) resistance of the amino acid substitution Y169F, which removes a single oxygen atom from the β2-α2 loop of the cellular prion protein (PrPC). When infected with RML or the 263K strain of prions, transgenic mice lacking wild-type (wt) PrPC but expressing MoPrP169F generated prion infectivity at levels comparable to wt mice. The newly generated MoPrP169F prions were biologically indistinguishable from those recovered from prion-infected wt mice, and elicited similar pathologies in vivo. Surprisingly, MoPrP169F prions showed greatly reduced PK resistance and density gradient analyses showed a significant reduction in high-density aggregates. Passage of MoPrP169F prions into mice expressing wt MoPrP led to full recovery of protease resistance, indicating that no strain shift had taken place. We conclude that a subtle structural variation in the β2-α2 loop of PrPC affects the sensitivity of PrPSc to protease but does not impact prion replication and infectivity. With these findings a specific structural feature of PrPC can be linked to a physicochemical property of the corresponding PrPSc.

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

PubMed

Stenland, Christopher J; Lee, Douglas C; Brown, Paul; Petteway, Stephen R; Rubenstein, Richard

2002-11-01

Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

Rapid Typing of Transmissible Spongiform Encephalopathy Strains with Differential ELISA

PubMed Central

Simon, Stéphanie; Nugier, Jérôme; Morel, Nathalie; Boutal, Hervé; Créminon, Christophe; Benestad, Sylvie L.; Andréoletti, Olivier; Lantier, Frédéric; Bilheude, Jean-Marc; Feyssaguet, Muriel; Biacabe, Anne-Gaëlle; Baron, Thierry

2008-01-01

The bovine spongiform encephalopathy (BSE) agent has been transmitted to humans, leading to variant Creutzfeldt-Jakob disease. Sheep and goats can be experimentally infected by BSE and have been potentially exposed to natural BSE; however, whether BSE can be transmitted to small ruminants is not known. Based on the particular biochemical properties of the abnormal prion protein (PrPsc) associated with BSE, and particularly the increased degradation induced by proteinase K in the N terminal part of PrPsc, we have developed a rapid ELISA designed to distinguish BSE from other scrapie strains. This assay clearly discriminates experimental ovine BSE from other scrapie strains and was used to screen 260 transmissible spongiform encephalopathy (TSE)–infected small ruminant samples identified by the French active surveillance network (2002/2003). In this context, this test has helped to identify the first case of natural BSE in a goat and can be used to classify TSE isolates based on the proteinase K sensitivity of PrPsc. PMID:18394279

Semiautomated cell-free conversion of prion protein: applications for high-throughput screening of potential antiprion drugs.

PubMed

Breydo, Leonid; Bocharova, Olga V; Baskakov, Ilia V

2005-04-01

Transmissible spongiform encephalitis (TSE) is a lethal illness with no known treatment. Conversion of the cellular prion protein (PrP(C)) into the infectious isoform (PrP(Sc)) is believed to be the central event in the development of this disease. Recombinant PrP (rPrP) protein folded into the amyloid conformation was shown to cause the transmissible form of prion disease in transgenic mice and can be used as a surrogate model for PrP(Sc). Here, we introduced a semiautomated assay of in vitro conversion of rPrP protein to the amyloid conformation. We have examined the effect of known inhibitors of prion propagation on this conversion and found good correlation between their activity in this assay and that in other in vitro assays. We thus propose that the conversion of rPrP to the amyloid isoform can serve as a high-throughput screen for possible inhibitors of PrP(Sc) formation and potential anti-TSE drugs.

Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches

PubMed Central

Hyeon, Jae Wook; Choi, Jiwon; Kim, Su Yeon; Govindaraj, Rajiv Gandhi; Jam Hwang, Kyu; Lee, Yeong Seon; An, Seong Soo A.; Lee, Myung Koo; Joung, Jong Young; No, Kyoung Tai; Lee, Jeongmin

2015-01-01

Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds. PMID:26449325

A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

PubMed Central

Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai

2015-01-01

Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623

Plasminogen stimulates propagation of protease-resistant prion protein in vitro.

PubMed

Mays, Charles E; Ryou, Chongsuk

2010-12-01

To clarify the role of plasminogen as a cofactor for prion propagation, we conducted functional assays using a cell-free prion protein (PrP) conversion assay termed protein misfolding cyclic amplification (PMCA) and prion-infected cell lines. Here, we report that plasminogen stimulates propagation of the protease-resistant scrapie PrP (PrP(Sc)). Compared to control PMCA conducted without plasminogen, addition of plasminogen in PMCA using wild-type brain material significantly increased PrP conversion, with an EC(50) = ∼56 nM. PrP conversion in PMCA was substantially less efficient with plasminogen-deficient brain material than with wild-type material. The activity stimulating PrP conversion was specific for plasminogen and conserved in its kringle domains. Such activity was abrogated by modification of plasminogen structure and interference of PrP-plasminogen interaction. Kinetic analysis of PrP(Sc) generation demonstrated that the presence of plasminogen in PMCA enhanced the PrP(Sc) production rate to ∼0.97 U/μl/h and reduced turnover time to ∼1 h compared to those (∼0.4 U/μl/h and ∼2.5 h) obtained without supplementation. Furthermore, as observed in PMCA, plasminogen and kringles promoted PrP(Sc) propagation in ScN2a and Elk 21(+) cells. Our results demonstrate that plasminogen functions in stimulating conversion processes and represents the first cellular protein cofactor that enhances the hypothetical mechanism of prion propagation.

Stochastic Modeling Approach to the Incubation Time of Prionic Diseases

NASA Astrophysics Data System (ADS)

Ferreira, A. S.; da Silva, M. A.; Cressoni, J. C.

2003-05-01

Transmissible spongiform encephalopathies are neurodegenerative diseases for which prions are the attributed pathogenic agents. A widely accepted theory assumes that prion replication is due to a direct interaction between the pathologic (PrPSc) form and the host-encoded (PrPC) conformation, in a kind of autocatalytic process. Here we show that the overall features of the incubation time of prion diseases are readily obtained if the prion reaction is described by a simple mean-field model. An analytical expression for the incubation time distribution then follows by associating the rate constant to a stochastic variable log normally distributed. The incubation time distribution is then also shown to be log normal and fits the observed BSE (bovine spongiform encephalopathy) data very well. Computer simulation results also yield the correct BSE incubation time distribution at low PrPC densities.

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

PubMed Central

Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

PubMed Central

Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J.

2016-01-01

We examined the brains of 266 patients with prion diseases (PrionD) and found that 46 (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (Hu BrnAggs) to brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease (CJD) and found that the neurons in the Hu BrnAggs produced many β-amyloid (β42) inclusions, whereas uninfected, control-exposed Hu BrnAggs did not. Western blots of 20-pooled CJD-infected BrnAggs verified higher Aβ42 levels than controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many Aβ42 intraneuronal inclusions, low APOE-4, and no significant nerve cell loss. Seven patients had high levels of PrPSc, low Aβ42, high APOE-4 and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls and 2 controls had a few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to AD and suggest that PrionD are diseases of PrPSc, Aβ42, APOE-4 and abnormal tau. PMID:26226132

Dominant-Negative Inhibition of Prion Formation Diminished by Deletion Mutagenesis of the Prion Protein

PubMed Central

Zulianello, Laurence; Kaneko, Kiyotoshi; Scott, Michael; Erpel, Susanne; Han, Dong; Cohen, Fred E.; Prusiner, Stanley B.

2000-01-01

Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nuclear magnetic resonance and mutagenesis studies indicate that specific substitutions at the C-terminal residues 167, 171, 214, and 218 of PrPC act as dominant-negative, inhibitors of PrPSc formation (K. Kaneko et al., Proc. Natl. Acad. Sci. USA 94:10069–10074, 1997). Trafficking of substituted PrPC to caveaola-like domains or rafts by the glycolipid anchor was required for the dominant-negative phenotype; interestingly, amino acid replacements at multiple sites were less effective than single-residue substitutions. To elucidate which domains of PrPC are responsible for dominant-negative inhibition of PrPSc formation, we analyzed whether N-terminally truncated PrP(Q218K) molecules exhibited dominant-negative effects in the conversion of full-length PrPC to PrPSc. We found that the C-terminal domain of PrP is not sufficient to impede the conversion of the full-length PrPC molecule and that N-terminally truncated molecules (with residues 23 to 88 and 23 to 120 deleted) have reduced dominant-negative activity. Whether the N-terminal region of PrP acts by stabilizing the C-terminal domain of the molecule or by modulating the binding of PrPC to an auxiliary molecule that participates in PrPSc formation remains to be established. PMID:10756050

Mitigation of Prion Infectivity and Conversion Capacity by a Simulated Natural Process—Repeated Cycles of Drying and Wetting

PubMed Central

Yuan, Qi; Eckland, Thomas; Telling, Glenn; Bartz, Jason; Bartelt-Hunt, Shannon

2015-01-01

Prions enter the environment from infected hosts, bind to a wide range of soil and soil minerals, and remain highly infectious. Environmental sources of prions almost certainly contribute to the transmission of chronic wasting disease in cervids and scrapie in sheep and goats. While much is known about the introduction of prions into the environment and their interaction with soil, relatively little is known about prion degradation and inactivation by natural environmental processes. In this study, we examined the effect of repeated cycles of drying and wetting on prion fitness and determined that 10 cycles of repeated drying and wetting could reduce PrPSc abundance, PMCA amplification efficiency and extend the incubation period of disease. Importantly, prions bound to soil were more susceptible to inactivation by repeated cycles of drying and wetting compared to unbound prions, a result which may be due to conformational changes in soil-bound PrPSc or consolidation of the bonding between PrPSc and soil. This novel finding demonstrates that naturally-occurring environmental process can degrade prions. PMID:25665187

Prion propagation in cells expressing PrP glycosylation mutants.

PubMed

Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Highly Efficient Protein Misfolding Cyclic Amplification

PubMed Central

Ostapchenko, Valeriy G.; Savtchenk, Regina; Alexeeva, Irina; Rohwer, Robert G.; Baskakov, Ilia V.

2011-01-01

Protein misfolding cyclic amplification (PMCA) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research. However, the low efficiency of conversion of PrPC into PrPSc in PMCA limits the applicability of PMCA for many uses including structural studies of infectious prions. It also implies that only a small sub-fraction of PrPC may be available for conversion. Here we show that the yield, rate, and robustness of prion conversion and the sensitivity of prion detection are significantly improved by a simple modification of the PMCA format. Conducting PMCA reactions in the presence of Teflon beads (PMCAb) increased the conversion of PrPC into PrPSc from ∼10% to up to 100%. In PMCAb, a single 24-hour round consistently amplified PrPSc by 600-700-fold. Furthermore, the sensitivity of prion detection in one round (24 hours) increased by 2-3 orders of magnitude. Using serial PMCAb, a 1012-fold dilution of scrapie brain material could be amplified to the level detectible by Western blotting in 3 rounds (72 hours). The improvements in amplification efficiency were observed for the commonly used hamster 263K strain and for the synthetic strain SSLOW that otherwise amplifies poorly in PMCA. The increase in the amplification efficiency did not come at the expense of prion replication specificity. The current study demonstrates that poor conversion efficiencies observed previously have not been due to the scarcity of a sub-fraction of PrPC susceptible to conversion nor due to limited concentrations of essential cellular cofactors required for conversion. The new PMCAb format offers immediate practical benefits and opens new avenues for developing fast ultrasensitive assays and for producing abundant quantities of PrPSc in vitro. PMID:21347353

Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time.

PubMed

Heger, A; Svae, T-E; Neisser-Svae, A; Jordan, S; Behizad, M; Römisch, J

2009-10-01

A new chromatographic step for the selective binding of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas. Pilot batches of Octaplas with the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. The incorporation of this novel chromatography into the large-scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas and OctaplasLG produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin inhibitor. The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.

Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.

PubMed

Hwang, Soyoun; Greenlee, Justin J; Nicholson, Eric M

2017-01-01

Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to differentiate types of bovine spongiform encephalopathy (BSE) in samples from cattle. We evaluated whether PrPSc from TME and BSE infected cattle can be detected with RT-QuIC using recombinant bovine prion proteins, and optimized the reaction conditions to specifically detect cattle TME and to discriminate between classical and atypical BSE by conversion efficiency. We also found that substrate composed of the disease associated E211K mutant protein can be effective for the detection of TME in cattle and that wild type prion protein appears to be a practical substrate to discriminate between the different types of BSEs.

Application of “omics” to Prion Biomarker Discovery

PubMed Central

Huzarewich, Rhiannon L. C. H.; Siemens, Christine G.; Booth, Stephanie A.

2010-01-01

The advent of genomics and proteomics has been a catalyst for the discovery of biomarkers able to discriminate biological processes such as the pathogenesis of complex diseases. Prompt detection of prion diseases is particularly desirable given their transmissibility, which is responsible for a number of human health risks stemming from exogenous sources of prion protein. Diagnosis relies on the ability to detect the biomarker PrPSc, a pathological isoform of the host protein PrPC, which is an essential component of the infectious prion. Immunochemical detection of PrPSc is specific and sensitive enough for antemortem testing of brain tissue, however, this is not the case in accessible biological fluids or for the detection of recently identified novel prions with unique biochemical properties. A complementary approach to the detection of PrPSc itself is to identify alternative, “surrogate” gene or protein biomarkers indicative of disease. Biomarkers are also useful to track the progress of disease, especially important in the assessment of therapies, or to identify individuals “at risk”. In this review we provide perspective on current progress and pitfalls in the use of “omics” technologies to screen body fluids and tissues for biomarker discovery in prion diseases. PMID:20224650

Mammalian prions

PubMed Central

Salamat, Muhammad Khalid; Munoz-Montesino, Carola; Moudjou, Mohammed; Rezaei, Human; Laude, Hubert; Béringue, Vincent; Dron, Michel

2013-01-01

Upon prion infection, abnormal prion protein (PrPSc) self-perpetuate by conformational conversion of α-helix-rich PrPC into β sheet enriched form, leading to formation and deposition of PrPSc aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrPSc and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region. PMID:23232499

Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

NASA Astrophysics Data System (ADS)

Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

2017-12-01

Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

Amyloid-specific fluorophores for the rapid, sensitive in situ detection of prion contamination on surgical instruments.

PubMed

Lipscomb, I P; Hervé, R; Harris, K; Pinchin, H; Collin, R; Keevil, C W

2007-09-01

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of rare, transmissible and fatal neurodegenerative diseases associated with the protein agent (PrP(Sc)). As such, the sensitive and rapid detection of prion PrP(Sc) amyloid on the surface of suspect surgical instruments is of great importance and may even allow remedial action to be taken prior to any further operative intervention and possible iatrogenic transmission. However, conventional PrP(Sc) detection methodologies tend to rely on the inefficient and unreliable removal of suspect material from a surface using swabs or wipes prior to antibody analysis. Here we show how the combination of an advanced light microscope technique, episcopic differential interference contrast/epifluorescence (EDIC/EF) microscopy, and the application of beta-amyloid fluorescent thiazole markers (thioflavin T, thioflavin S) can be used to detect, in situ, submicron (attomole) levels of prion protein amyloid contamination in brain and spleen sections, smears and homogenate on surgical stainless steel surfaces and surgical instruments. This technique, although not specific to an amyloid type, can be used to verify that surgical instruments are substantially free from prion amyloid protein soiling and hence reduce the risk of iatrogenic transmission.

Mechanisms of triggering H1 helix in prion proteins unfolding revealed by molecular dynamic simulation

NASA Astrophysics Data System (ADS)

Tseng, Chih-Yuan; Lee, H. C.

2006-03-01

In template-assistance model, normal Prion protein (PrP^C), the pathogen to cause several prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrP^Sc) through a transient interaction with PrP^Sc. Furthermore, conventional studies showed S1-H1-S2 region in PrP^C to be the template of S1-S2 β-sheet in PrP^Sc, and Prion protein's conformational conversion may involve an unfolding of H1 and refolding into β-sheet. Here we prepare several mouse prion peptides that contain S1-H1-S2 region with specific different structures, which are corresponding to specific interactions, to investigate possible mechanisms to trigger H1 α-helix unfolding process via molecular dynamic simulation. Three properties, conformational transition, salt-bridge in H1, and hydrophobic solvent accessible surface (SAS) are analyzed. From these studies, we found the interaction that triggers H1 unfolding to be the one that causes dihedral angle at residue Asn^143 changes. Whereas interactions that cause S1 segment's conformational changes play a minor in this process. These studies offers an additional evidence for template-assistance model.

Prion disease tempo determined by host-dependent substrate reduction

PubMed Central

Mays, Charles E.; Kim, Chae; Haldiman, Tracy; van der Merwe, Jacques; Lau, Agnes; Yang, Jing; Grams, Jennifer; Di Bari, Michele A.; Nonno, Romolo; Telling, Glenn C.; Kong, Qingzhong; Langeveld, Jan; McKenzie, Debbie; Westaway, David; Safar, Jiri G.

2014-01-01

The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains. PMID:24430187

Evidence that bank vole PrP is a universal acceptor for prions.

PubMed

Watts, Joel C; Giles, Kurt; Patel, Smita; Oehler, Abby; DeArmond, Stephen J; Prusiner, Stanley B

2014-04-01

Bank voles are uniquely susceptible to a wide range of prion strains isolated from many different species. To determine if this enhanced susceptibility to interspecies prion transmission is encoded within the sequence of the bank vole prion protein (BVPrP), we inoculated Tg(M109) and Tg(I109) mice, which express BVPrP containing either methionine or isoleucine at polymorphic codon 109, with 16 prion isolates from 8 different species: humans, cattle, elk, sheep, guinea pigs, hamsters, mice, and meadow voles. Efficient disease transmission was observed in both Tg(M109) and Tg(I109) mice. For instance, inoculation of the most common human prion strain, sporadic Creutzfeldt-Jakob disease (sCJD) subtype MM1, into Tg(M109) mice gave incubation periods of ∼200 days that were shortened slightly on second passage. Chronic wasting disease prions exhibited an incubation time of ∼250 days, which shortened to ∼150 days upon second passage in Tg(M109) mice. Unexpectedly, bovine spongiform encephalopathy and variant CJD prions caused rapid neurological dysfunction in Tg(M109) mice upon second passage, with incubation periods of 64 and 40 days, respectively. Despite the rapid incubation periods, other strain-specified properties of many prion isolates--including the size of proteinase K-resistant PrPSc, the pattern of cerebral PrPSc deposition, and the conformational stability--were remarkably conserved upon serial passage in Tg(M109) mice. Our results demonstrate that expression of BVPrP is sufficient to engender enhanced susceptibility to a diverse range of prion isolates, suggesting that BVPrP may be a universal acceptor for prions.

The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

PubMed

Vázquez-Fernández, Ester; Vos, Matthijn R; Afanasyev, Pavel; Cebey, Lino; Sevillano, Alejandro M; Vidal, Enric; Rosa, Isaac; Renault, Ludovic; Ramos, Adriana; Peters, Peter J; Fernández, José Jesús; van Heel, Marin; Young, Howard S; Requena, Jesús R; Wille, Holger

2016-09-01

The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC) into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding.

Changes in Protein Structure and Distribution Observed at Pre-Clinical Stages of Scrapie Pathogenesis

PubMed Central

Kretlow, Ariane; Wang, Qi; Beekes, Michael; Naumann, Dieter; Miller, Lisa M.

2011-01-01

Scrapie is a neurodegenerative disorder that involves the misfolding, aggregation and accumulation of the prion protein (PrP). The normal cellular PrP (PrPC) is rich in α-helical secondary structure, whereas the disease-associated pathogenic form of the protein (PrPSc) has an anomalously high β-sheet content. In this study, protein structural changes were examined in situ in the dorsal root ganglia from perorally 263K scrapie-infected and mock-infected hamsters using synchrotron Fourier Transform InfraRed Microspectroscopy (FTIRM) at four time points over the course of the disease (preclinical, 100 & 130 days post-infection (dpi); first clinical signs (~145 dpi); and terminal (~170 dpi)). Results showed clear changes in the total protein content, structure, and distribution as the disease progressed. At pre-clinical time points, the scrapie-infected animals exhibited a significant increase in protein expression, but the β-sheet protein content was significantly lower than controls. Based on these findings, we suggest that the pre-clinical stages of scrapie are characterized by an overexpression of proteins low in β-sheet content. As the disease progressed, the β-sheet content increased significantly. Immunostaining with a PrP-specific antibody, 3F4, confirmed that this increase was partly – but not solely – due to the formation of PrPSc in the tissue and indicated that other proteins high in β-sheet were produced, either by overexpression or misfolding. Elevated β-sheet was observed near the cell membrane at pre-clinical time points and also in the cytoplasm of infected neurons at later stages of infection. At the terminal stage of the disease, the protein expression declined significantly, likely due to degeneration and death of neurons. These dramatic changes in protein content and structure, especially at pre-clinical time points, emphasize the possibility for identifying other proteins involved in early pathogenesis, which are important for further understanding the disease. PMID:18625306

Inactivation of Template-Directed Misfolding of Infectious Prion Protein by Ozone

PubMed Central

Ding, Ning; Price, Luke M.; Braithwaite, Shannon L.; Balachandran, Aru; Belosevic, Miodrag

2012-01-01

Misfolded prions (PrPSc) are well known for their resistance to conventional decontamination processes. The potential risk of contamination of the water environment, as a result of disposal of specified risk materials (SRM), has raised public concerns. Ozone is commonly utilized in the water industry for inactivation of microbial contaminants and was tested in this study for its ability to inactivate prions (263K hamster scrapie = PrPSc). Treatment variables included initial ozone dose (7.6 to 25.7 mg/liter), contact time (5 s and 5 min), temperature (4°C and 20°C), and pH (pH 4.4, 6.0, and 8.0). Exposure of dilute suspensions of the infected 263K hamster brain homogenates (IBH) (0.01%) to ozone resulted in the in vitro destruction of the templating properties of PrPSc, as measured by the protein misfolding cyclic amplification (PMCA) assay. The highest levels of prion inactivation (≥4 log10) were observed with ozone doses of 13.0 mg/liter, at pH 4.4 and 20°C, resulting in a CT (the product of residual ozone concentration and contact time) value as low as 0.59 mg · liter−1 min. A comparison of ozone CT requirements among various pathogens suggests that prions are more susceptible to ozone degradation than some model bacteria and protozoa and that ozone treatment may be an effective solution for inactivating prions in water and wastewater. PMID:22138993

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

PubMed Central

Concha-Marambio, Luis; Pritzkow, Sandra; Moda, Fabio; Tagliavini, Fabrizio; Ironside, James W.; Schulz, Paul E.; Soto, Claudio

2017-01-01

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrPSc) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrPSc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrPSc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology. PMID:28003548

PrP(C) signalling in neurons: from basics to clinical challenges.

PubMed

Hirsch, Théo Z; Hernandez-Rapp, Julia; Martin-Lannerée, Séverine; Launay, Jean-Marie; Mouillet-Richard, Sophie

2014-09-01

The cellular prion protein PrP(C) was identified over twenty-five years ago as the normal counterpart of the scrapie prion protein PrP(Sc), itself the main if not the sole component of the infectious agent at the root of Transmissible Spongiform Encephalopathies (TSEs). PrP(C) is a ubiquitous cell surface protein, abundantly expressed in neurons, which constitute the targets of PrP(Sc)-mediated toxicity. Converging evidence have highlighted that neuronal, GPI-anchored PrP(C) is absolutely required for prion-induced neuropathogenesis, which warrants investigating into the normal function exerted by PrP(C) in a neuronal context. It is now well-established that PrP(C) can serve as a cell signalling molecule, able to mobilize transduction cascades in response to interactions with partners. This function endows PrP(C) with the capacity to participate in multiple neuronal processes, ranging from survival to synaptic plasticity. A diverse array of data have allowed to shed light on how this function is corrupted by PrP(Sc). Recently, amyloid Aβ oligomers, whose accumulation is associated with Alzheimer's disease (AD), were shown to similarly instigate toxic events by deviating PrP(C)-mediated signalling. Here, we provide an overview of the various signal transduction cascades ascribed to PrP(C) in neurons, summarize how their subversion by PrP(Sc) or Aβ oligomers contributes to TSE or AD neuropathogenesis and discuss the ensuing clinical implications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.

PubMed

Aguilar-Calvo, Patricia; Fast, Christine; Tauscher, Kerstin; Espinosa, Juan-Carlos; Groschup, Martin H; Nadeem, Muhammad; Goldmann, Wilfred; Langeveld, Jan; Bossers, Alex; Andreoletti, Olivier; Torres, Juan-María

2015-08-15

The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months). These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Neutral Sphingomyelinase Pathway Regulates Packaging of the Prion Protein into Exosomes*

PubMed Central

Guo, Belinda B.; Bellingham, Shayne A.; Hill, Andrew F.

2015-01-01

Prion diseases are a group of transmissible, fatal neurodegenerative disorders associated with the misfolding of the host-encoded prion protein, PrPC, into a disease-associated form, PrPSc. The transmissible prion agent is principally formed of PrPSc itself and is associated with extracellular vesicles known as exosomes. Exosomes are released from cells both in vitro and in vivo, and have been proposed as a mechanism by which prions spread intercellularly. The biogenesis of exosomes occurs within the endosomal system, through formation of intraluminal vesicles (ILVs), which are subsequently released from cells as exosomes. ILV formation is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) machinery, although an alternative neutral sphingomyelinase (nSMase) pathway has been suggested to also regulate this process. Here, we investigate a role for the nSMase pathway in exosome biogenesis and packaging of PrP into these vesicles. Inhibition of the nSMase pathway using GW4869 revealed a role for the nSMase pathway in both exosome formation and PrP packaging. In agreement, targeted knockdown of nSMase1 and nSMase2 in mouse neurons using lentivirus-mediated RNAi also decreases exosome release, demonstrating the nSMase pathway regulates the biogenesis and release of exosomes. We also demonstrate that PrPC packaging is dependent on nSMase2, whereas the packaging of disease-associated PrPSc into exosomes occurs independently of nSMase2. These findings provide further insight into prion transmission and identify a pathway which directly assists exosome-mediated transmission of prions. PMID:25505180

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

NASA Astrophysics Data System (ADS)

Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

2005-02-01

Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

PubMed

Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

2016-02-05

Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of sporadic CJD upon homologous and heterologous transmission. The notion that the environment or matrix where replication is occurring is key to the selection and preferential amplification of prion substrain components raises new questions on the determinants of prion replication within and between species. These data also further interrogate on the interplay between animal and human prions.

Incongruity between Prion Conversion and Incubation Period following Coinfection.

PubMed

Langenfeld, Katie A; Shikiya, Ronald A; Kincaid, Anthony E; Bartz, Jason C

2016-06-15

When multiple prion strains are inoculated into the same host, they can interfere with each other. Strains with long incubation periods can suppress conversion of strains with short incubation periods; however, nothing is known about the conversion of the long-incubation-period strain during strain interference. To investigate this, we inoculated hamsters in the sciatic nerve with long-incubation-period strain 139H prior to superinfection with the short-incubation-period hyper (HY) strain of transmissible mink encephalopathy (TME). First, we found that 139H is transported along the same neuroanatomical tracks as HY TME, adding to the growing body of evidence indicating that PrP(Sc) favors retrograde transneuronal transport. In contrast to a previous report, we found that 139H interferes with HY TME infection, which is likely due to both strains targeting the same population of neurons following sciatic nerve inoculation. Under conditions where 139H blocked HY TME from causing disease, the strain-specific properties of PrP(Sc) corresponded with the strain that caused disease, consistent with our previous findings. In the groups of animals where incubation periods were not altered, we found that the animals contained a mixture of 139H and HY TME PrP(Sc) This finding expands the definition of strain interference to include conditions where PrP(Sc) formation is altered yet disease outcome is unaltered. Overall, these results contradict the premise that prion strains are static entities and instead suggest that strain mixtures are dynamic regardless of incubation period or clinical outcome of disease. Prions can exist as a mixture of strains in naturally infected animals, where they are able to interfere with the conversion of each other and to extend incubation periods. Little is known, however, about the dynamics of strain conversion under conditions where incubation periods are not affected. We found that inoculation of the same animal with two strains can result in the alteration of conversion of both strains under conditions where the resulting disease was consistent with infection with only a single strain. These data challenge the idea that prion strains are static and suggests that strain mixtures are more dynamic than previously appreciated. This observation has significant implications for prion adaptation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes.

PubMed

Guo, Belinda B; Bellingham, Shayne A; Hill, Andrew F

2015-02-06

Prion diseases are a group of transmissible, fatal neurodegenerative disorders associated with the misfolding of the host-encoded prion protein, PrP(C), into a disease-associated form, PrP(Sc). The transmissible prion agent is principally formed of PrP(Sc) itself and is associated with extracellular vesicles known as exosomes. Exosomes are released from cells both in vitro and in vivo, and have been proposed as a mechanism by which prions spread intercellularly. The biogenesis of exosomes occurs within the endosomal system, through formation of intraluminal vesicles (ILVs), which are subsequently released from cells as exosomes. ILV formation is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) machinery, although an alternative neutral sphingomyelinase (nSMase) pathway has been suggested to also regulate this process. Here, we investigate a role for the nSMase pathway in exosome biogenesis and packaging of PrP into these vesicles. Inhibition of the nSMase pathway using GW4869 revealed a role for the nSMase pathway in both exosome formation and PrP packaging. In agreement, targeted knockdown of nSMase1 and nSMase2 in mouse neurons using lentivirus-mediated RNAi also decreases exosome release, demonstrating the nSMase pathway regulates the biogenesis and release of exosomes. We also demonstrate that PrP(C) packaging is dependent on nSMase2, whereas the packaging of disease-associated PrP(Sc) into exosomes occurs independently of nSMase2. These findings provide further insight into prion transmission and identify a pathway which directly assists exosome-mediated transmission of prions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

PRNP variants in goats reduce sensitivity of detection of PrPSc by immunoassay

USDA-ARS?s Scientific Manuscript database

Immunoassays are extensively utilized in disease diagnostics with monoclonal antibodies serving as critical tools within the assay. Detection of scrapie in sheep and goats relies heavily on immunoassays including immunohistochemistry, western blotting, and ELISA. In the United States, regulatory tes...

Computational Calculation Of The Ionization Energies Of The Human Prion Protein By The Coarse-grain Method

NASA Astrophysics Data System (ADS)

Lyu, Justin; Andrianarijaona, V. M.

2016-05-01

The causes of the misfolding of prion protein -i.e. the transformation of PrPC to PrPSc - have not been clearly elucidated. Many studies have focused on identifying possible chemical conditions, such as pH, temperature and chemical denaturation, that may trigger the pathological transformation of prion proteins (Weiwei Tao, Gwonchan Yoon, Penghui Cao, `` β-sheet-like formation during the mechanical unfolding of prion protein'', The Journal of Chemical Physics, 2015, 143, 125101). Here, we attempt to calculate the ionization energies of the prion protein, which will be able to shed light onto the possible causes of the misfolding. We plan on using the coarse-grain method which allows for a more feasible calculation time by means of approximation. We believe that by being able to approximate the ionization potential, particularly that of the regions known to form stable β-strands of the PrPSc form, the possible sources of denaturation, be it chemical or mechanical, may be narrowed down.

Perturbation of the Secondary Structure of the Scrapie Prion Protein Under Conditions that Alter Infectivity

NASA Astrophysics Data System (ADS)

Gasset, Maria; Baldwin, Michael A.; Fletterick, Robert J.; Prusiner, Stanley B.

1993-01-01

Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% β-sheet, 25% α-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the β-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency β-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from α-helical, random coil, or turn into β-sheet remains to be established.

Using small molecule reagents to help distinguish among prion structural models

USDA-ARS?s Scientific Manuscript database

The only demonstrated difference between infectious prions (PrPSc) and the isosequential normal cellular prion protein (PrPC) is conformation. The structure of PrPC has been determined by a variety of instrumental techniques. The structure of prions remains uncertain. Recent instrumental analysis h...

Determining the relative susceptibility of four prion protein genotypes to atypical scrapie

USDA-ARS?s Scientific Manuscript database

Atypical scrapie is a sheep prion (PrPSc) disease whose epidemiology is consistent with a sporadic origin and is associated with specific polymorphisms of the normal cellular prion protein (PrPC). We describe a mass spectrometry-based method of detecting and quantifying the polymorphisms of sheep P...

The chemistry of prions: small molecules, protein conformers and mass spectrometry

USDA-ARS?s Scientific Manuscript database

Background/Introduction. Prions propagate by converting a normal cellular isoform (PrPC) into the prion isoform (PrPSc) in a template-driven process. The lysines in PrPC are highly conserved and strongly influence prion propagation, based on studies using natural polymorphisms of PrPC and transg...

Principal network analysis: identification of subnetworks representing major dynamics using gene expression data

PubMed Central

Kim, Yongsoo; Kim, Taek-Kyun; Kim, Yungu; Yoo, Jiho; You, Sungyong; Lee, Inyoul; Carlson, George; Hood, Leroy; Choi, Seungjin; Hwang, Daehee

2011-01-01

Motivation: Systems biology attempts to describe complex systems behaviors in terms of dynamic operations of biological networks. However, there is lack of tools that can effectively decode complex network dynamics over multiple conditions. Results: We present principal network analysis (PNA) that can automatically capture major dynamic activation patterns over multiple conditions and then generate protein and metabolic subnetworks for the captured patterns. We first demonstrated the utility of this method by applying it to a synthetic dataset. The results showed that PNA correctly captured the subnetworks representing dynamics in the data. We further applied PNA to two time-course gene expression profiles collected from (i) MCF7 cells after treatments of HRG at multiple doses and (ii) brain samples of four strains of mice infected with two prion strains. The resulting subnetworks and their interactions revealed network dynamics associated with HRG dose-dependent regulation of cell proliferation and differentiation and early PrPSc accumulation during prion infection. Availability: The web-based software is available at: http://sbm.postech.ac.kr/pna. Contact: dhhwang@postech.ac.kr; seungjin@postech.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21193522

Time-course study of retinal pathology in C57BL/6 mice infected with RML scrapie

USDA-ARS?s Scientific Manuscript database

Prions are proteinaceous pathogens that cause transmissible spongiform encephalopathies (TSEs). These diseases develop slowly as the misfolded and protease-resistant prion protein, PrP**Sc, interacts with the normal cellular form, PrP**C, a cell-surface protein found throughout the nervous system. T...

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

USDA-ARS?s Scientific Manuscript database

Classical scrapie is a form of transmissible spongiform encephalopathies (TSE) affecting domestic goats and sheep and disease is characterized by the accumulation of abnormal conformational isoform (PrP-Sc) of normal cellular prion protein (PrP-C) in the central nervous system and, in most cases, ly...

Antiprion activity of DB772 and related monothiophene-and furan-based analogs in a persistently infected ovine microglia culture system

USDA-ARS?s Scientific Manuscript database

The transmissible spongiform encephalopathies are fatal neurodegenerative disorders characterized by the misfolding of the native cellular prion protein (PrP-C) into the accumulating, disease-associated isoform (PrP-Sc). Despite extensive research into the inhibition of prion accumulation, no effect...

Comparative aspects of bovine spongiform encephalopathy isolates found in the U.S.

USDA-ARS?s Scientific Manuscript database

Bovine spongiform encephalopathy (BSE) can be subdivided into at least three groups: classical, H-type, and L-type. The latter 2 designations are based on higher or lower apparent molecular mass profiles of the unglycosylated PrP**Sc band in a western blot and are collectively referred to as atypica...

Classical natural ovine scrapie prions are detected in practical volumes of blood by lamb and transgenic mouse bioassay

USDA-ARS?s Scientific Manuscript database

In vitro ligand-based immunoassay studies revealed abnormal isoforms of prion protein (PrP-Sc) are primarily associated with B lymphocytes of scrapie-infected sheep. Our recent study also demonstrated efficient transmission of scrapie to lambs following a transfusion of B lymphocytes isolated from 5...

Detection of BSE prions by RT-QuIC in cattle with subclinical BSE

USDA-ARS?s Scientific Manuscript database

Bovine spongiform encephalopathy (BSE) belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrPC) into a pathogenic form (PrPSc) that accumulates in the brain and some lymphoid tissues. In vitro assays such as serial protein misfolding amplificati...

Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

USDA-ARS?s Scientific Manuscript database

Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study,...

Prion search and cellular prion protein expression in stranded dolphins.

PubMed

Di Guardo, G; Cocumelli, C; Meoli, R; Barbaro, K; Terracciano, G; Di Francesco, C E; Mazzariol, S; Eleni, C

2012-01-01

The recent description of a prion disease (PD) case in a free-ranging bottlenose dolphin (Tursiops truncatus) prompted us to carry out an extensive search for the disease-associated isoform (PrPSc) of the cellular prion protein (PrPC) in the brain and in a range of lymphoid tissues from 23 striped dolphins (Stenella coeruleoalba), 5 bottlenose dolphins and 2 Risso s dolphins (Grampus griseus) found stranded between 2007 and 2012 along the Italian coastline. Three striped dolphins and one bottlenose dolphin showed microscopic lesions of encephalitis, with no evidence of spongiform brain lesions being detected in any of the 30 free-ranging cetaceans investigated herein. Nevertheless, we could still observe a prominent PrPC immunoreactivity in the brain as well as in lymphoid tissues from these dolphins. Although immunohistochemical and Western blot investigations yielded negative results for PrPSc deposition in all tissues from the dolphins under study, the reported occurrence of a spontaneous PD case in a wild dolphin is an intriguing issue and a matter of concern for both prion biology and intra/inter-species transmissibility, as well as for cetacean conservation medicine.

Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.

PubMed

Sorrentino, Sacha; Bucciarelli, Tonino; Corsaro, Alessandro; Tosatto, Alessio; Thellung, Stefano; Villa, Valentina; Schininà, M Eugenia; Maras, Bruno; Galeno, Roberta; Scotti, Luca; Creati, Francesco; Marrone, Alessandro; Re, Nazzareno; Aceto, Antonio; Florio, Tullio; Mazzanti, Michele

2012-01-01

The pathological form of prion protein (PrP(Sc)), as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrP(Sc) extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90-231 (hPrP₉₀₋₂₃₁) increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrP(Sc). In the present study we demonstrate that hPrP₉₀₋₂₃₁, pre-incubated with 10 mM Ca⁺⁺ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP₉₀₋₂₃₁ bearing pathogenic mutations (D202N and E200K). We also report that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP₉₀₋₂₃₁ cytotoxicity. Finally, by in silico structural analysis, we propose that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity.

Calcium Binding Promotes Prion Protein Fragment 90–231 Conformational Change toward a Membrane Destabilizing and Cytotoxic Structure

PubMed Central

Corsaro, Alessandro; Tosatto, Alessio; Thellung, Stefano; Villa, Valentina; Schininà, M. Eugenia; Maras, Bruno; Galeno, Roberta; Scotti, Luca; Creati, Francesco; Marrone, Alessandro; Re, Nazzareno; Aceto, Antonio; Florio, Tullio; Mazzanti, Michele

2012-01-01

The pathological form of prion protein (PrPSc), as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrPSc extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90–231 (hPrP90–231) increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrPSc. In the present study we demonstrate that hPrP90–231, pre-incubated with 10 mM Ca++ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP90–231 bearing pathogenic mutations (D202N and E200K). We also report that Ca++ binding to hPrP90–231 induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP90–231 cytotoxicity. Finally, by in silico structural analysis, we propose that Ca++ binding to hPrP90–231 modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity. PMID:22811758

Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

PubMed

Asante, Emmanuel A; Linehan, Jacqueline M; Smidak, Michelle; Tomlinson, Andrew; Grimshaw, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Powell, Caroline; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2013-01-01

Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion.

PubMed

Dassanayake, Rohana P; Orrú, Christina D; Hughson, Andrew G; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A; Knowles, Donald P; Schneider, David A

2016-03-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200  mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15  h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion

PubMed Central

Dassanayake, Rohana P.; Orrú, Christina D.; Hughson, Andrew G.; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A.; Knowles, Donald P.; Schneider, David A.

2016-01-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10− 3 dilution within 15 h. Our findings indicate that RT-QuIC was at least 10 000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples. PMID:26653410

Experimental approaches to the interaction of the prion protein with nucleic acids and glycosaminoglycans: Modulators of the pathogenic conversion.

PubMed

Silva, Jerson L; Vieira, Tuane C R G; Gomes, Mariana P B; Rangel, Luciana P; Scapin, Sandra M N; Cordeiro, Yraima

2011-03-01

The concept that transmissible spongiform encephalopathies (TSEs) are caused only by proteins has changed the traditional paradigm that disease transmission is due solely to an agent that carries genetic information. The central hypothesis for prion diseases proposes that the conversion of a cellular prion protein (PrP(C)) into a misfolded, β-sheet-rich isoform (PrP(Sc)) accounts for the development of (TSE). There is substantial evidence that the infectious material consists chiefly of a protein, PrP(Sc), with no genomic coding material, unlike a virus particle, which has both. However, prions seem to have other partners that chaperone their activities in converting the PrP(C) into the disease-causing isoform. Nucleic acids (NAs) and glycosaminoglycans (GAGs) are the most probable accomplices of prion conversion. Here, we review the recent experimental approaches that have been employed to characterize the interaction of prion proteins with nucleic acids and glycosaminoglycans. A PrP recognizes many nucleic acids and GAGs with high affinities, and this seems to be related to a pathophysiological role for this interaction. A PrP binds nucleic acids and GAGs with structural selectivity, and some PrP:NA complexes can become proteinase K-resistant, undergoing amyloid oligomerization and conversion to a β-sheet-rich structure. These results are consistent with the hypothesis that endogenous polyanions (such as NAs and GAGs) may accelerate the rate of prion disease progression by acting as scaffolds or lattices that mediate the interaction between PrP(C) and PrP(Sc) molecules. In addition to a still-possible hypothesis that nucleic acids and GAGs, especially those from the host, may modulate the conversion, the recent structural characterization of the complexes has raised the possibility of developing new diagnostic and therapeutic strategies. Copyright © 2010 Elsevier Inc. All rights reserved.

Differential effects of divalent cations on elk prion protein fibril formation and stability

USDA-ARS?s Scientific Manuscript database

Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of different diseases, from scrapie in sheep to bovine spongiform encephalopathy in cattle to chronic wasting disease (CWD) in deer and elk. The misfolded form of PrPC, termed PrPSc, or in this...

Detecting and discriminating among pathogenic protein conformers(prions), using mass spectrometry-based and antibody-based approaches(Abstract)

USDA-ARS?s Scientific Manuscript database

A set of fatal neurological diseases that includes scrapie and chronic wasting disease (CWD) are caused by a pathological protein referred to as a prion (PrPSc). A prion propagates an infection by converting a normal cellular protein (PrPC) into a prion. Unlike viral, bacterial, or fungal pathogens,...

Probing structural differences between PrPC and PrPSc by surface nitration and acetylation: evidence of conformational change in the C-terminus

USDA-ARS?s Scientific Manuscript database

We used two chemical modifiers, tetranitromethane (TNM) and acetic anhydride, which specifically target accessible tyrosine and lysine residues, respectively, to modify Syrian hamster recombinant PrP(90-231) (rPrP) and PrP27-30, aiming at finding locations of conformational change. Modified proteins...

Quantitating PrP polymorphisms present in prions from heterozygous scrapie-infected sheep

USDA-ARS?s Scientific Manuscript database

Scrapie is a prion (PrPSc) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep’s normal cellular prion protein (PrPC). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic pept...

Elucidation of Prion Protein Conformational Changes Associated with Infectivity by Fluorescence Spectroscopy

DTIC Science & Technology

2006-06-01

This work was supported by grants to MAM from the US Army Research (DAMD17- 03-1-0342) and the NIH COBRE program (P20 RR020185-01). Authors...and more tractable model for PrPSc. This is further supported by an intriguing discovery made by Caughey and coworkers in their search to

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelets-rich plasma

USDA-ARS?s Scientific Manuscript database

Classical scrapie is a naturally occurring fatal brain disease of sheep and goats which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood...

Lack of Prion Accumulation in Lymphoid Tissues of Scrapie-affected Sheep with the AA136, QR171 Prion Protein Genotype

USDA-ARS?s Scientific Manuscript database

Background: Sheep scrapie is a transmissible spongiform encephalopathy which can be transmitted horizontally through the shedding of an infectious conformer (PrP**Sc) of the normal cellular prion protein (PrP**c). Genetics profoundly influence the susceptibility of sheep to scrapie. PrP**c amino-aci...

Novel epitopes identified by Anti-PrP monoclonal antibodies produced following immunization of Prnp0/0 Balb/cJ mice with purified scrapie prions

USDA-ARS?s Scientific Manuscript database

Prions, or infectious proteins, cause a class of uniformly fatal neurodegenerative diseases. Prions are composed solely of an aberrantly folded isoform(PrPSc)of a normal cellular protein (PrPC). Shared sequence identity of PrPSc with PrPC has limited the detection sensitivity of immunochemical assay...

Cell surface expression of PrP-c and the presence of scrapie prions in the blood of goats

USDA-ARS?s Scientific Manuscript database

Classical scrapie is a naturally occurring fatal brain disease of goats and sheep which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood...

Pathologic and biochemical characterization of PrPSc from elk with PRNP polymorphisms at codon 132 after experimental infection with the chronic wasting disease agent

USDA-ARS?s Scientific Manuscript database

The Rocky Mountain elk (Cervus elaphus nelsoni) prion protein gene (PRNP) is polymorphic at codon 132, with leucine (L132) and methionine (M132) allelic variants present in the population. In elk experimentally inoculated with the chronic wasting disease (CWD) agent, different incubation periods are...

Sensitive and specific detection of classical scrapie prions in the brain of goats by real-time quaking-induced conversion

USDA-ARS?s Scientific Manuscript database

The real-time quaking-induced conversion (RT-QuIC) is a rapid, specific, and sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect sub-infectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully us...

Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.

PubMed

Bacot, Silvia M; Feldman, Gerald M; Yamada, Kenneth M; Dhawan, Subhash

2015-02-01

Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis. Published by Elsevier Inc.

Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease

USDA-ARS?s Scientific Manuscript database

The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (I...

Temporal resolution of misfolded prion protein transport, accumulation, glial activation, and neuronal death in the retinas of mice inoculated with scrapie

USDA-ARS?s Scientific Manuscript database

Currently, there is a lack of pathologic landmarks to describe the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between the transport of misfolded prion protein from the brain to the retina, the accumulation of PrPSc in the retina, the respon...

Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Chiovitti, Katia; Villa, Valentina; Simi, Alessandro; Raggi, Federica; Paludi, Domenico; Russo, Claudio; Aceto, Antonio; Florio, Tullio

2009-02-01

Several in vitro and in vivo studies addressed the identification of molecular determinants of the neuronal death induced by PrP(Sc) or related peptides. We developed an experimental model to assess PrP(Sc) neurotoxicity using a recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231) that corresponds to the protease-resistant core of PrP(Sc) identified in prion-infected brains. By means of mild thermal denaturation, we can convert hPrP90-231 from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells, inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix-rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on minocycline, a tetracycline with known neuroprotective activity. hPrP90-231 caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic factors, removing a tonic inhibition of p38 activity and resulting in caspase 3 activation. Minocycline prevented hPrP90-231-induced toxicity interfering with this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity and reverted p38 and caspase 3 activities. The effects of minocycline were not mediated by the prevention of hPrP90-231 structural changes or cell internalization (differently from Congo Red). In conclusion, minocycline elicits anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase activities.

Protein Adhesion and Ion Substitution (on/in)to Minerals

NASA Astrophysics Data System (ADS)

Charlet, L.; Fernandez Martinez, A.; Chapron, Y.; Sahai, N.; Cuello, G.; Brendle, J.; Marichal, C.

2008-12-01

Arsenic and pathogenic prion protein-scrapie (PrPsc) are important contaminants which may soil and water for decades, unless they are removed by sorption. Two sorption mechanisms will be discussed, namely the organics (Prp and single aminoacid) adsorption on clay and the arsenic substitution in gypsum. The elucidation of these contrasted mechanisms will be shown to request complementary molecular-mechanical simulations with experimental spectroscopic investigations. As first example, structural studies performed at ILL/ESRF on As-doped gypsum (CaSO4 2H2O) using neutron and X-ray diffraction data and EXAFS were performed to determine how As fits into the bulk of gypsum structure. The combined Rietveld analysis of neutron and X-ray diffraction data shows an expansion of the unit cell volume proportional to the As concentration within the samples. to-sulfate substitution mechanisms were used as simulation starting hypotheses. DFT-based simulations (Mulliken analysis) were used to interpret charge distribution and to show that among the possible mechanisms, a sulphate substitution by either protonated, or fully deprotonated, arsenate ion, only the protonated arsenate substitution could best fit the EXAFS data. In the second example, we used Molecular Dynamics to understand the mechanism of strong binding of the pathogenic PrP peptide with clay mineral surfaces. We modeled only the infectious moiety, PrP92-138, of the whole PrPsc structure, with explicitly solvating water molecules in contact with the cleavage plane of pyrophillite, as a model for montmorillonite without any cationic substitution. Partial residual negative charges on the cleavage plane were balanced with K+ ions. The peptide anchored to the clay surface via up to 10 hydrogen bonds from lysine and histidine residues to oxygen atoms of the siloxane cavities, and a total adsorption energy of 3465 KJ.mol-1 was obtained. Our results were compared to the one obtained by chemical and thermal analysis, 23Na, 1H, 13C solid state NMR and MD computation on sorption of single lysine amino acid on model synthetic Na-montmorillonite. Our data provide further insight about interactions between lysine and montmorillonite which depend strongly on lysine concentration.

Prion disease susceptibility is affected by β-structure folding propensity and local side-chain interactions in PrP

PubMed Central

Khan, M. Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R.; Pai, Emil F.; Chakrabartty, Avijit

2010-01-01

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrPSc). Exposure to PrPSc from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer–octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease. PMID:21041683

Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP.

PubMed

Khan, M Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R; Pai, Emil F; Chakrabartty, Avijit

2010-11-16

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer-octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease.

Neuropathology of italian cats in feline spongiform encephalopathy surveillance.

PubMed

Iulini, B; Cantile, C; Mandara, M T; Maurella, C; Loria, G R; Castagnaro, M; Salvadori, C; Porcario, C; Corona, C; Perazzini, A Z; Maroni, A; Caramelli, M; Casalone, C

2008-09-01

Feline spongiform encephalopathy (FSE) is a transmissible spongiform encephalopathy associated with the consumption of feedstuffs contaminated with tissue from bovine spongiform encephalopathy-affected cattle and characterized by the accumulation in the central nervous system of an abnormal isoform of the prion protein (PrP(sc)). Clinically, it presents as a progressive fatal neurologic syndrome that is not easily distinguished from other feline neurologic conditions. Most cases of FSE have been reported in England, where it was first detected in 1990, but a few cases have been reported from other European countries. To identify possible cases of FSE in Italy, the Italian Ministry of Health funded a 2-year surveillance project during which the brains from 110 domestic cats with neurologic signs were evaluated histologically for spongiform encephalopathy and immunohistochemically to detect PrP(sc). Although no cases of FSE were found, the study proved useful in monitoring the Italian cat population for other neurologic diseases: neoplasia (21.8%), toxic-metabolic encephalopathy (18.2%), granulomatous encephalitis (15.5%), suppurative encephalitis (4.6%), trauma (3.6%), circulatory disorders (3.6%), degeneration (2.7%), nonsuppurative encephalitis (2.7%), and neuromuscular diseases (1.8%). No histologic lesions were found in 20% of the brains, and samples from 5.5% of the cats were rejected as unsuitable.

Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

PubMed Central

Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

2014-01-01

Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

Propagation of prion strains through specific conformers of the prion protein.

PubMed Central

Scott, M R; Groth, D; Tatzelt, J; Torchia, M; Tremblay, P; DeArmond, S J; Prusiner, S B

1997-01-01

Two prion strains with identical incubation periods in mice exhibited distinct incubation periods and different neuropathological profiles upon serial transmission to transgenic mice expressing chimeric Syrian hamster/mouse (MH2M) prion protein (PrP) genes [Tg(MH2M) mice] and subsequent transmission to Syrian hamsters. After transmission to Syrian hamsters, the Me7 strain was indistinguishable from the previously established Syrian hamster strain Sc237, despite having been derived from an independent ancestral source. This apparent convergence suggests that prion diversity may be limited. The Me7 mouse strain could also be transmitted directly to Syrian hamsters, but when derived in this way, its properties were distinct from those of Me7 passaged through Tg(MH2M) mice. The Me7 strain did not appear permanently altered in either case, since the original incubation period could be restored by effectively reversing the series of passages. Prion diversity enciphered in the conformation of the scrapie isoform of PrP (PrP(Sc)) (G. C. Telling et al., Science 274:2079-2082, 1996) seems to be limited by the sequence of the PrP substrates serially converted into PrP(Sc), while prions are propagated through interactions between the cellular and scrapie isoforms of PrP. PMID:9371560

In Vitro Approach To Identify Key Amino Acids in Low Susceptibility of Rabbit Prion Protein to Misfolding

PubMed Central

Eraña, Hasier; Fernández-Borges, Natalia; Elezgarai, Saioa R.; Harrathi, Chafik; Charco, Jorge M.; Chianini, Francesca; Dagleish, Mark P.; Ortega, Gabriel; Millet, Óscar

2017-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of rare progressive neurodegenerative disorders caused by an abnormally folded prion protein (PrPSc). This is capable of transforming the normal cellular prion protein (PrPC) into new infectious PrPSc. Interspecies prion transmissibility studies performed by experimental challenge and the outbreak of bovine spongiform encephalopathy that occurred in the late 1980s and 1990s showed that while some species (sheep, mice, and cats) are readily susceptible to TSEs, others are apparently resistant (rabbits, dogs, and horses) to the same agent. To study the mechanisms of low susceptibility to TSEs of certain species, the mouse-rabbit transmission barrier was used as a model. To identify which specific amino acid residues determine high or low susceptibility to PrPSc propagation, protein misfolding cyclic amplification (PMCA), which mimics PrPC-to-PrPSc conversion with accelerated kinetics, was used. This allowed amino acid substitutions in rabbit PrP and accurate analysis of misfolding propensities. Wild-type rabbit recombinant PrP could not be misfolded into a protease-resistant self-propagating isoform in vitro despite seeding with at least 12 different infectious prions from diverse origins. Therefore, rabbit recombinant PrP mutants were designed to contain every single amino acid substitution that distinguishes rabbit recombinant PrP from mouse recombinant PrP. Key amino acid residue substitutions were identified that make rabbit recombinant PrP susceptible to misfolding, and using these, protease-resistant misfolded recombinant rabbit PrP was generated. Additional studies characterized the mechanisms by which these critical amino acid residue substitutions increased the misfolding susceptibility of rabbit PrP. IMPORTANCE Prion disorders are invariably fatal, untreatable diseases typically associated with long incubation periods and characteristic spongiform changes associated with neuronal loss in the brain. Development of any treatment or preventative measure is dependent upon a detailed understanding of the pathogenesis of these diseases, and understanding the mechanism by which certain species appear to be resistant to TSEs is critical. Rabbits are highly resistant to naturally acquired TSEs, and even under experimental conditions, induction of clinical disease is not easy. Using recombinant rabbit PrP as a model, this study describes critical molecular determinants that confer this high resistance to transmissible spongiform encephalopathies. PMID:28978705

Characterization of the human analogue of a Scrapie-responsive gene.

PubMed

Dron, M; Dandoy-Dron, F; Guillo, F; Benboudjema, L; Hauw, J J; Lebon, P; Dormont, D; Tovey, M G

1998-07-17

We have recently described a novel mRNA denominated ScRG-1, the level of which is increased in the brains of Scrapie-infected mice (Dandoy-Dron, F., Guillo, F., Benboudjema, L., Deslys, J.-P., Lasmézas, C., Dormont, D., Tovey, M. G., and Dron, M. (1998) J. Biol. Chem. 273, 7691-7697). The increase in ScRG-1 mRNA in the brain follows the accumulation of PrPSc, the proteinase K-resistant form of the prion protein (PrP), and precedes the widespread neuronal death that occurs in late stage disease. In the present study, we have isolated a cDNA encoding the human counterpart of ScRG-1. Comparison of the human and mouse transcripts firmly established that both sequences encode a highly conserved protein of 98 amino acids that contains a signal peptide, suggesting that the protein may be secreted. Examination of the distribution of human ScRG-1 mRNA in adult and fetal tissues revealed that the gene was expressed primarily in the central nervous system as a 0.7-kilobase message and was under strict developmental control.

Elucidation of Prion Protein Conformational Changes Associated with Infectivity by Fluorescence Spectroscopy

DTIC Science & Technology

2007-06-01

developed the β-spiral model for PrPSc structure by using molecular dynamics simulations with the sequence of human PrPC (residues 90-231) under...SUPPLEMENTARY NOTES exerpts from thesis of Jessica Gilbert 14. ABSTRACT Steady state and lifetime fluorescence measurements were made on 12...lieu of F. We tried both methods. See Ms. Jessica Gilbert’s MS thesis for details, which is included. 6 Figure 4. Acrylamide quenching of Trp

Tricyclic antidepressants, quinacrine and a novel, synthetic chimera thereof clear prions by destabilizing detergent-resistant membrane compartments.

PubMed

Klingenstein, Ralf; Löber, Stefan; Kujala, Pekka; Godsave, Susan; Leliveld, S Rutger; Gmeiner, Peter; Peters, Peter J; Korth, Carsten

2006-08-01

Prion diseases are invariably fatal, neurodegenerative diseases transmitted by an infectious agent, PrPSc, a pathogenic, conformational isoform of the normal prion protein (PrPC). Heterocyclic compounds such as acridine derivatives like quinacrine abolish prion infectivity in a cell culture model of prion disease. Here, we report that these compounds execute their antiprion activity by redistributing cholesterol from the plasma membrane to intracellular compartments, thereby destabilizing membrane domains. Our findings are supported by the fact that structurally unrelated compounds with known cholesterol-redistributing effects - U18666A, amiodarone, and progesterone - also possessed high antiprion potency. We show that tricyclic antidepressants (e.g. desipramine), another class of heterocyclic compounds, displayed structure-dependent antiprion effects and enhanced the antiprion effects of quinacrine, allowing lower doses of both drugs to be used in combination. Treatment of ScN2a cells with quinacrine or desipramine induced different ultrastructural and morphological changes in endosomal compartments. We synthesized a novel drug from quinacrine and desipramine, termed quinpramine, that led to a fivefold increase in antiprion activity compared to quinacrine with an EC50 of 85 nm. Furthermore, simvastatin, an inhibitor of cholesterol biosynthesis, acted synergistically with both heterocyclic compounds to clear PrPSc. Our data suggest that a cocktail of drugs targeting the lipid metabolism that controls PrP conversion may be the most efficient in treating Creutzfeldt-Jakob disease.

Prion protein β2–α2 loop conformational landscape

PubMed Central

Caldarulo, Enrico; Wüthrich, Kurt; Parrinello, Michele

2017-01-01

In transmissible spongiform encephalopathies (TSEs), which are lethal neurodegenerative diseases that affect humans and a wide range of other mammalian species, the normal “cellular” prion protein (PrPC) is transformed into amyloid aggregates representing the “scrapie form” of the protein (PrPSc). Continued research on this system is of keen interest, since new information on the physiological function of PrPC in healthy organisms is emerging, as well as new data on the mechanism of the transformation of PrPC to PrPSc. In this paper we used two different approaches: a combination of the well-tempered ensemble (WTE) and parallel tempering (PT) schemes and metadynamics (MetaD) to characterize the conformational free-energy surface of PrPC. The focus of the data analysis was on an 11-residue polypeptide segment in mouse PrPC(121–231) that includes the β2–α2 loop of residues 167–170, for which a correlation between structure and susceptibility to prion disease has previously been described. This study includes wild-type mouse PrPC and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an integrative manner the available experimental data on PrPC, providing quantitative insights into the nature of the structural transition-related function of the β2–α2 loop. PMID:28827331

Infrared Microspectroscopy: A Multiple-Screening Platform for Investigating Single-Cell Biochemical Perturbations upon Prion Infection

PubMed Central

2011-01-01

Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of prions in the central nervous system. The pathogenic prion (PrPSc) possesses the capability to convert the host-encoded cellular isoform of the prion protein, PrPC, into nascent PrPSc. The present work aims at providing novel insight into cellular response upon prion infection evidenced by synchrotron radiation infrared microspectroscopy (SR-IRMS). This non-invasive, label-free analytical technique was employed to investigate the biochemical perturbations undergone by prion infected mouse hypothalamic GT1-1 cells at the cellular and subcellular level. A decrement in total cellular protein content upon prion infection was identified by infrared (IR) whole-cell spectra and validated by bicinchoninic acid assay and single-cell volume analysis by atomic force microscopy (AFM). Hierarchical cluster analysis (HCA) of IR data discriminated between infected and uninfected cells and allowed to deduce an increment of lysosomal bodies within the cytoplasm of infected GT1-1 cells, a hypothesis further confirmed by SR-IRMS at subcellular spatial resolution and fluorescent microscopy. The purpose of this work, therefore, consists of proposing IRMS as a powerful multiscreening platform, drawing on the synergy with conventional biological assays and microscopy techniques in order to increase the accuracy of investigations performed at the single-cell level. PMID:22778865

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

PubMed

Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

Enzymatic activity of a subtilisin homolog, Tk-SP, from Thermococcus kodakarensis in detergents and its ability to degrade the abnormal prion protein

PubMed Central

2013-01-01

Background Tk-SP is a member of subtilisin-like serine proteases from a hyperthermophilic archaeon Thermococcus kodakarensis. It has been known that the hyper-stable protease, Tk-SP, could exhibit enzymatic activity even at high temperature and in the presence of chemical denaturants. In this work, the enzymatic activity of Tk-SP was measured in the presence of detergents and EDTA. In addition, we focused to demonstrate that Tk-SP could degrade the abnormal prion protein (PrPSc), a protease-resistant isoform of normal prion protein (PrPC). Results Tk-SP was observed to maintain its proteolytic activity with nonionic surfactants and EDTA at 80°C. We optimized the condition in which Tk-SP functions efficiently, and demonstrated that the enzyme is highly stable in the presence of 0.05% (w/v) nonionic surfactants and 0.01% (w/v) EDTA, retaining up to 80% of its activity. Additionally, we also found that Tk-SP can degrade PrPSc to a level undetectable by western-blot analysis. Conclusions Our results indicate that Tk-SP has a great potential for technological applications, such as thermo-stable detergent additives. In addition, it is also suggested that Tk-SP-containing detergents can be developed to decrease the secondary infection risks of transmissible spongiform encephalopathies (TSE). PMID:23448268

Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD.

PubMed

Mizrahi, Michal; Friedman-Levi, Yael; Larush, Liraz; Frid, Kati; Binyamin, Orli; Dori, Dvir; Fainstein, Nina; Ovadia, Haim; Ben-Hur, Tamir; Magdassi, Shlomo; Gabizon, Ruth

2014-08-01

Neurodegenerative diseases generate the accumulation of specific misfolded proteins, such as PrP(Sc) prions or A-beta in Alzheimer's diseases, and share common pathological features, like neuronal death and oxidative damage. To test whether reduced oxidation alters disease manifestation, we treated TgMHu2ME199K mice, modeling for genetic prion disease, with Nano-PSO, a nanodroplet formulation of pomegranate seed oil (PSO). PSO comprises large concentrations of a unique polyunsaturated fatty acid, Punicic acid, among the strongest natural antioxidants. Nano-PSO significantly delayed disease presentation when administered to asymptomatic TgMHu2ME199K mice and postponed disease aggravation in already sick mice. Analysis of brain samples revealed that Nano-PSO treatment did not decrease PrP(Sc) accumulation, but rather reduced lipid oxidation and neuronal loss, indicating a strong neuroprotective effect. We propose that Nano-PSO and alike formulations may be both beneficial and safe enough to be administered for long years to subjects at risk or to those already affected by neurodegenerative conditions. This team of authors report that a nanoformulation of pomegranade seed oil, containing high levels of a strong antioxidant, can delay disease onset in a mouse model of genetic prion diseases, and the formulation also indicates a direct neuroprotective effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Sporadic Creutzfeldt-Jakob Disease in a Woman Married Into a Gerstmann-Sträussler-Scheinker Family: An Investigation of Prions Transmission via Microchimerism.

PubMed

Areškeviciute, Aušrine; Melchior, Linea Cecilie; Broholm, Helle; Krarup, Lars-Henrik; Granhøj Lindquist, Suzanne; Johansen, Peter; McKenzie, Neil; Green, Alison; Nielsen, Jørgen Erik; Laursen, Henning; Løbner Lund, Eva

2018-06-07

This is the first report of presumed sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS) with the prion protein gene c.305C>T mutation (p.P102L) occurring in one family. The father and son were affected with GSS and the mother had a rapidly progressive form of CJD. Diagnosis of genetic, variant, and iatrogenic CJD was ruled out based on the mother's clinical history, genetic tests, and biochemical investigations, all of which supported the diagnosis of sCJD. However, given the low incidence of sCJD and GSS, their co-occurrence in one family is extraordinary and challenging. Thus, a hypothesis for the transmission of infectious prion proteins (PrPSc) via microchimerism was proposed and investigated. DNA from 15 different brain regions and plasma samples of the CJD patient was subjected to PCR and shallow sequencing for detection of a male sex-determining chromosome Y (chr. Y). However, no trace of chr. Y was found. A long CJD incubation period or presumed small concentrations of chr. Y may explain the obtained results. Further studies of CJD and GSS animal models with controlled genetic and proteomic features are needed to determine whether maternal CJD triggered via microchimerism by a GSS fetus might present a new PrPSc transmission route.

Infrared microspectroscopy: a multiple-screening platform for investigating single-cell biochemical perturbations upon prion infection.

PubMed

Didonna, Alessandro; Vaccari, Lisa; Bek, Alpan; Legname, Giuseppe

2011-03-16

Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of prions in the central nervous system. The pathogenic prion (PrP(Sc)) possesses the capability to convert the host-encoded cellular isoform of the prion protein, PrP(C), into nascent PrP(Sc). The present work aims at providing novel insight into cellular response upon prion infection evidenced by synchrotron radiation infrared microspectroscopy (SR-IRMS). This non-invasive, label-free analytical technique was employed to investigate the biochemical perturbations undergone by prion infected mouse hypothalamic GT1-1 cells at the cellular and subcellular level. A decrement in total cellular protein content upon prion infection was identified by infrared (IR) whole-cell spectra and validated by bicinchoninic acid assay and single-cell volume analysis by atomic force microscopy (AFM). Hierarchical cluster analysis (HCA) of IR data discriminated between infected and uninfected cells and allowed to deduce an increment of lysosomal bodies within the cytoplasm of infected GT1-1 cells, a hypothesis further confirmed by SR-IRMS at subcellular spatial resolution and fluorescent microscopy. The purpose of this work, therefore, consists of proposing IRMS as a powerful multiscreening platform, drawing on the synergy with conventional biological assays and microscopy techniques in order to increase the accuracy of investigations performed at the single-cell level.

Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure.

PubMed

Cobb, Nathan J; Sönnichsen, Frank D; McHaourab, Hassane; Surewicz, Witold K

2007-11-27

Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative diseases that are associated with conformational conversion of the normally monomeric and alpha-helical prion protein, PrP(C), to the beta-sheet-rich PrP(Sc). This latter conformer is believed to constitute the main component of the infectious TSE agent. In contrast to high-resolution data for the PrP(C) monomer, structures of the pathogenic PrP(Sc) or synthetic PrP(Sc)-like aggregates remain elusive. Here we have used site-directed spin labeling and EPR spectroscopy to probe the molecular architecture of the recombinant PrP amyloid, a misfolded form recently reported to induce transmissible disease in mice overexpressing an N-terminally truncated form of PrP(C). Our data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrP(C) involves major refolding of the C-terminal alpha-helical region. The core of the amyloid maps to C-terminal residues from approximately 160-220, and these residues form single-molecule layers that stack on top of one another with parallel, in-register alignment of beta-strands. This structural insight has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases, most of which are associated with point mutations in the region found to undergo a refolding to beta-structure.

Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

PubMed

Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

2014-01-01

Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

Mouse-Hamster Chimeric Prion Protein (PrP) Devoid of N-Terminal Residues 23-88 Restores Susceptibility to 22L Prions, but Not to RML Prions in PrP-Knockout Mice

PubMed Central

Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

2014-01-01

Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice, compared with RML- and 22L-inoculated Prnp0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc. PMID:25330286

Protein folding, misfolding and aggregation: The importance of two-electron stabilizing interactions

PubMed Central

2017-01-01

Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in yet another one via divergent aggregation pathways that yield broad diversity of aggregates’ morphology. A thorough understanding of this behaviour may be necessary to develop a treatment for Alzheimer’s and related disorders. Unfortunately, our present comprehension of folding and misfolding is limited for want of a physicochemical theory of protein secondary and tertiary structure. Here we demonstrate that electronic configuration and hyperconjugation of the peptide amide bonds ought to be taken into account to advance such a theory. To capture the effect of polarization of peptide linkages on conformational and H-bonding propensity of the polypeptide backbone, we introduce a function of shielding tensors of the Cα atoms. Carrying no information about side chain-side chain interactions, this function nonetheless identifies basic features of the secondary and tertiary structure, establishes sequence correlates of the metamorphic and pH-driven equilibria, relates binding affinities and folding rate constants to secondary structure preferences, and manifests common patterns of backbone density distribution in amyloidogenic regions of Alzheimer’s amyloid β and tau, Parkinson’s α-synuclein and prions. Based on those findings, a split-intein like mechanism of molecular recognition is proposed to underlie dimerization of Aβ, tau, αS and PrPC, and divergent pathways for subsequent association of dimers are outlined; a related mechanism is proposed to underlie formation of PrPSc fibrils. The model does account for: (i) structural features of paranuclei, off-pathway oligomers, non-fibrillar aggregates and fibrils; (ii) effects of incubation conditions, point mutations, isoform lengths, small-molecule assembly modulators and chirality of solid-liquid interface on the rate and morphology of aggregation; (iii) fibril-surface catalysis of secondary nucleation; and (iv) self-propagation of infectious strains of mammalian prions. PMID:28922400

Sex effects in mouse prion disease incubation time.

PubMed

Akhtar, Shaheen; Wenborn, Adam; Brandner, Sebastian; Collinge, John; Lloyd, Sarah E

2011-01-01

Prion disease incubation time in mice is determined by many factors including PrP expression level, Prnp alleles, genetic background, prion strain and route of inoculation. Sex differences have been described in age of onset for vCJD and in disease duration for both vCJD and sporadic CJD and have also been shown in experimental models. The sex effects reported for mouse incubation times are often contradictory and detail only one strain of mice or prions, resulting in broad generalisations and a confusing picture. To clarify the effect of sex on prion disease incubation time in mice we have compared male and female transmission data from twelve different inbred lines of mice inoculated with at least two prion strains, representing both mouse-adapted scrapie and BSE. Our data show that sex can have a highly significant difference on incubation time. However, this is limited to particular mouse and prion strain combinations. No sex differences were seen in endogenous PrP(C) levels nor in the neuropathological markers of prion disease: PrP(Sc) distribution, spongiosis, neuronal loss and gliosis. These data suggest that when comparing incubation times between experimental groups, such as testing the effects of modifier genes or therapeutics, single sex groups should be used.

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

PubMed Central

Giles, Kurt; Glidden, David V.; Beckwith, Robyn; Seoanes, Rose; Peretz, David; DeArmond, Stephen J.; Prusiner, Stanley B.

2008-01-01

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used. PMID:19008948

Recombinant human prion protein fragment 90-231, a useful model to study prion neurotoxicity.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Nizzari, Mario; Aceto, Antonio; Florio, Tullio

2012-01-01

Transmissible spongiform encephalopathies (TSE), or prion diseases, are a group of fatal neurodegenerative disorders of animals and humans. Human diseases include Creutzfeldt-Jakob (CJD) and Gerstmann-Straussler-Scheinker (GSSD) diseases, fatal familial insomnia, and Kuru. Human and animal TSEs share a common histopathology with a pathognomonic triad: spongiform vacuolation of the grey matter, neuronal death, glial proliferation, and, more inconstantly, amyloid deposition. According to the "protein only" hypothesis, TSEs are caused by a unique post-translational conversion of normal, host-encoded, protease-sensitive prion protein (PrP(sen) or PrP(C)) to an abnormal disease-associated isoform (PrP(res) or PrP(Sc)). To investigate the molecular mechanism of neurotoxicity induced by PrP(Sc) we developed a protocol to obtain millimolar amounts of soluble recombinant polypeptide encompassing the amino acid sequence 90-231 of human PrP (hPrP90-231). This protein corresponds to the protease-resistant prion protein fragment that originates after amino-terminal truncation. Importantly, hPrP90-231 has a flexible backbone that, similar to PrP(C), can undergo to structural rearrangement. This peptide, structurally resembling PrP(C), can be converted in a PrP(Sc)-like conformation, and thus represents a valuable model to study prion neurotoxicity. In this article we summarized our experimental evidence on the molecular and structural mechanisms responsible of hPrP90-231 neurotoxicity on neuroectodermal cell line SHSY5Y and the effects of some PrP pathogen mutations identified in familial TSE.

Methods and Protocols for Developing Prion Vaccines.

PubMed

Marciniuk, Kristen; Taschuk, Ryan; Napper, Scott

2016-01-01

Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation.

PubMed

Dassanayake, Rohana P; Zhuang, Dongyue; Truscott, Thomas C; Madsen-Bouterse, Sally A; O'Rourke, Katherine I; Schneider, David A

2016-03-03

To assess scrapie infectivity associated with caprine-origin tissues, bioassay can be performed using kids, lambs or transgenic mice expressing caprine or ovine prion (PRNP) alleles, but the incubation periods are fairly long. Although several classical ovine scrapie prion permissive cell lines with the ability to detect brain-derived scrapie prion have been available, no classical caprine scrapie permissive cell line is currently available. Therefore, the aims of this study were to generate a rabbit kidney epithelial cell line (RK13) stably expressing caprine wild-type PRNP (cpRK13) and then to assess permissiveness of cpRK13 cells to classical caprine scrapie prion propagation. The cpRK13 and plasmid control RK13 (pcRK13) cells were incubated with brain-derived classical caprine scrapie inocula prepared from goats or ovinized transgenic mice (Tg338, express ovine VRQ allele) infected with caprine scrapie. Significant PrP(Sc) accumulation, which is indicative of scrapie prion propagation, was detected by TSE ELISA and immunohistochemistry in cpRK13 cells inoculated with classical caprine scrapie inocula. Western blot analysis revealed the typical proteinase K-resistant 3 PrP(res) isoforms in the caprine scrapie prion inoculated cpRK13 cell lysate. Importantly, PrP(Sc) accumulation was not detected in similarly inoculated pcRK13 cells, whether by TSE ELISA, immunohistochemistry, or western blot. These findings suggest that caprine scrapie prions can be propagated in cpRK13 cells, thus this cell line may be a useful tool for the assessment of classical caprine prions in the brain tissues of goats.

Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease

PubMed Central

Cortez, Leonardo M.; Campeau, Jody; Norman, Grant; Kalayil, Marian; Van der Merwe, Jacques; McKenzie, Debbie

2015-01-01

ABSTRACT Prion diseases are fatal neurodegenerative disorders associated with the conversion of cellular prion protein (PrPC) into its aberrant infectious form (PrPSc). There is no treatment available for these diseases. The bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) have been recently shown to be neuroprotective in other protein misfolding disease models, including Parkinson's, Huntington's and Alzheimer's diseases, and also in humans with amyotrophic lateral sclerosis. Here, we studied the therapeutic efficacy of these compounds in prion disease. We demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures. This effect was mediated through reduction of PrPSc seeding ability, rather than an effect on PrPC. We also demonstrated the ability of TUDCA and UDCA to reduce neuronal loss in prion-infected cerebellar slice cultures. UDCA treatment reduced astrocytosis and prolonged survival in RML prion-infected mice. Interestingly, these effects were limited to the males, implying a gender-specific difference in drug metabolism. Beyond effects on PrPSc, we found that levels of phosphorylated eIF2α were increased at early time points, with correlated reductions in postsynaptic density protein 95. As demonstrated for other neurodegenerative diseases, we now show that TUDCA and UDCA may have a therapeutic role in prion diseases, with effects on both prion conversion and neuroprotection. Our findings, together with the fact that these natural compounds are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans, make these compounds promising alternatives for the treatment of prion diseases. IMPORTANCE Prion diseases are fatal neurodegenerative diseases that are transmissible to humans and other mammals. There are no disease-modifying therapies available, despite decades of research. Treatment targets have included inhibition of protein accumulation, clearance of toxic aggregates, and prevention of downstream neurodegeneration. No one target may be sufficient; rather, compounds which have a multimodal mechanism, acting on different targets, would be ideal. TUDCA and UDCA are bile acids that may fulfill this dual role. Previous studies have demonstrated their neuroprotective effects in several neurodegenerative disease models, and we now demonstrate that this effect occurs in prion disease, with an added mechanistic target of upstream prion seeding. Importantly, these are natural compounds which are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans with primary biliary cirrhosis. They have recently been proven efficacious in human amyotrophic lateral sclerosis. Therefore, these compounds are promising options for the treatment of prion diseases. PMID:25972546

Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

PubMed Central

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-01-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

PubMed

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-06-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90-231 fragment.

PubMed

Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Corsaro, Alessandro; Villa, Valentina; Vassalli, Massimo; Robello, Mauro; Florio, Tullio

2013-05-01

Prion diseases recognize, as a unique molecular trait, the misfolding of CNS-enriched prion protein (PrP(C)) into an aberrant isoform (PrP(Sc)). In this work, we characterize the in vitro toxicity of amino-terminally truncated recombinant PrP fragment (amino acids 90-231, PrP90-231), on rat cerebellar granule neurons (CGN), focusing on glutamatergic receptor activation and Ca(2+) homeostasis impairment. This recombinant fragment assumes a toxic conformation (PrP90-231(TOX)) after controlled thermal denaturation (1 h at 53 °C) acquiring structural characteristics identified in PrP(Sc) (enrichment in β-structures, increased hydrophobicity, partial resistance to proteinase K, and aggregation in amyloid fibrils). By annexin-V binding assay, and evaluation of the percentage of fragmented and condensed nuclei, we show that treatment with PrP90-231(TOX), used in pre-fibrillar aggregation state, induces CGN apoptosis. This effect was associated with a delayed, but sustained elevation of [Ca(2+)]i. Both CGN apoptosis and [Ca(2+)]i increase were not observed using PrP90-231 in PrP(C)-like conformation. PrP90-231(TOX) effects were significantly reduced in the presence of ionotropic glutamate receptor antagonists. In particular, CGN apoptosis and [Ca(2+)]i increase were largely reduced, although not fully abolished, by pre-treatment with the NMDA antagonists APV and memantine, while the AMPA antagonist CNQX produced a lower, although still significant, effect. In conclusion, we report that CGN apoptosis induced by PrP90-231(TOX) correlates with a sustained elevation of [Ca(2+)]i mediated by the activation of NMDA and AMPA receptors.

The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie.

PubMed

Di Bari, Michele Angelo; Chianini, Francesca; Vaccari, Gabriele; Esposito, Elena; Conte, Michela; Eaton, Samantha L; Hamilton, Scott; Finlayson, Jeanie; Steele, Philip J; Dagleish, Mark P; Reid, Hugh W; Bruce, Moira; Jeffrey, Martin; Agrimi, Umberto; Nonno, Romolo

2008-12-01

Despite intensive studies on sheep scrapie, a number of questions remain unanswered, such as the natural mode of transmission and the amount of infectivity which accumulates in edible tissues at different stages of scrapie infection. Studies using the mouse model proved to be useful for recognizing scrapie strain diversity, but the low sensitivity of mice to some natural scrapie isolates hampered further investigations. To investigate the sensitivity of bank voles (Myodes glareolus) to scrapie, we performed end-point titrations from two unrelated scrapie sources. Similar titres [10(5.5) ID50 U g(-1) and 10(5.8) ID50 U g(-1), both intracerebrally (i.c.)] were obtained, showing that voles can detect infectivity up to 3-4 orders of magnitude lower when compared with laboratory mice. We further investigated the relationships between PrPSc molecular characteristics, strain and prion titre in the brain and tonsil of the same scrapie-affected sheep. We found that protease-resistant PrPSc fragments (PrPres) from brain and tonsil had different molecular features, but induced identical disease phenotypes in voles. The infectivity titre of the tonsil estimated by incubation time assay was 10(4.8) i.c. ID50 U g(-1), i.e. fivefold less than the brain. This compared well with the relative PrPres content, which was 8.8-fold less in tonsil than in brain. Our results suggest that brain and tonsil harboured the same prion strain showing different glycoprofiles in relation to the different cellular/tissue types in which it replicated, and that a PrPSc-based estimate of scrapie infectivity in sheep tissues could be achieved by combining sensitive PrPres detection methods and bioassay in voles.

Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years

PubMed Central

Groschup, Martin H.; Peters, Rainer; Beekes, Michael; Terytze, Konstantin

2007-01-01

The persistence of infectious biomolecules in soil constitutes a substantial challenge. This holds particularly true with respect to prions, the causative agents of transmissible spongiform encephalopathies (TSEs) such as scrapie, bovine spongiform encephalopathy (BSE), or chronic wasting disease (CWD). Various studies have indicated that prions are able to persist in soil for years without losing their pathogenic activity. Dissemination of prions into the environment can occur from several sources, e.g., infectious placenta or amniotic fluid of sheep. Furthermore, environmental contamination by saliva, excrements or non-sterilized agricultural organic fertilizer is conceivable. Natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. These findings point to a sustained contagion in the environment, and notably the soil. By using outdoor lysimeters, we simulated a contamination of standard soil with hamster-adapted 263K scrapie prions, and analyzed the presence and biological activity of the soil-associated PrPSc and infectivity by Western blotting and hamster bioassay, respectively. Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrPSc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field. PMID:17502917

The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of PRNP Genotypes

PubMed Central

Gough, Kevin C.; Baker, Claire A.; Rees, Helen C.; Terry, Linda A.; Spiropoulos, John; Thorne, Leigh

2012-01-01

Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ PRNP genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of PRNP genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the PRNP genotype and any associated high-level accumulation of PrPSc within lymphoreticular tissues. PrPSc was present in buccal swabs from a large proportion of sheep with PRNP genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie. PMID:22013047

Sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease.

PubMed

Landolt, H-P; Glatzel, M; Blättler, T; Achermann, P; Roth, C; Mathis, J; Weis, J; Tobler, I; Aguzzi, A; Bassetti, C L

2006-05-09

The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration was estimated by brain autopsy in six patients. Western blot analyses enabling classification and quantification of the protease-resistant isoform of the prion protein, PrPSc, in thalamus and occipital cortex was available in four patients. Sleep-wake symptoms were observed in all patients, and were prominent in four of them. All patients had severe sleep EEG abnormalities with loss of sleep spindles, very low sleep efficiency, and virtual absence of REM sleep. The correlation between different methods to assess sleep-wake functions (history, polysomnography, actigraphy, videography) was generally poor. Brain autopsy revealed prominent changes in cortical areas, but only mild changes in the thalamus. No mutation of the PRNP gene was found. This study demonstrates in sporadic Creutzfeldt-Jakob disease, first, the existence of sleep-wake disturbances similar to those reported in fatal familial insomnia in the absence of prominent and isolated thalamic neuronal loss, and second, the need of a multimodal approach for the unambiguous assessment of sleep-wake functions in these patients.

Interaction between a recombinant prion protein and organo-mineral complexes as evidenced by CPMAS 13C-NMR

NASA Astrophysics Data System (ADS)

Russo, F.; Scotti, R.; Gianfreda, L.; Conte, P.; Rao, M. A.

2009-04-01

Prion proteins (PrP) are the main responsible for Transmissible Spongiform Encephalopathies (TSE). The TSE etiological agent is a misfolded form of the normal cellular prion protein. The amyloidal aggregates accumulated in the brain of infected animals and mainly composed of PrPSc exhibit resistance to protease attack and many conventional inactivating procedures. The prion protein diseases cause an environmental issue because the environment and in particular the soil compartment can be contaminated and then become a potential reservoir and diffuser of TSEs infectivity as a consequence of (i) accidental dispersion from storage plants of meat and bone meal, (ii) incorporation of contaminated material in fertilizers, (iii) possible natural contamination of pasture soils by grazing herds, and (v) burial of carcasses. The environmental problem can be even more relevant because very low amounts of PrPSc are able to propagate the disease. Several studies evidenced that infectious prion protein remains active in soils for years. Contaminated soils result, thus, a possible critical route of TSE transmission in wild animals. Soil can also protect prion protein toward degradation processes due to the presence of humic substances and inorganic components such as clays. Mineral and organic colloids and the more common association between clay minerals and humic substances can contribute to the adsorption/entrapment of molecules and macromolecules. The polymerization of organic monomeric humic precursors occurring in soil in the presence of oxidative enzymes or manganese and iron oxides, is considered one of the most important processes contributing to the formation of humic substances. The process is very fast and produces a population of polymeric products of different molecular structures, sizes, shapes and complexity. Other molecules and possibly biomacromolecules such as proteins may be involved. The aim of the present work was to study by CPMAS 13C-NMR the interactions between a non pathogenic ovine recombinant prion protein and a model soil system represented by a manganese oxide in the form of birnessite (δ-MnO2), coated with a polymerized catechol. To better understand the effect of the polymerization process, PrP was added to the birnessite-cathecol system either before or after the polymerization processes. The NMR spectra of the prion protein interacting directly with birnessite revealed disappearance of the signals due to the paramagnetic nature of manganese oxide or abiotic degradation. Conversely, the signal pattern of the protein re-appeared as it is mixed to the soil-like system either during or after the catechol polymerization process. Results suggested that the possible interactions of the prion protein on soil systems can be mediated by natural organic matter. However, deeper studies on more complex real soil systems are needed to definitely confirm such hypothesis.

Amyloid-beta-sheet formation at the air-water interface.

PubMed Central

Schladitz, C; Vieira, E P; Hermel, H; Möhwald, H

1999-01-01

An amyloid(1-40) solution rich in coil, turn, and alpha-helix, but poor in beta-sheet, develops monolayers with a high beta-sheet content when spread at the air-water interface. These monolayers are resistant to repeated compression-dilatation cycles and interaction with trifluoroethanol. The secondary structure motifs were detected by circular dichroism (CD) in solution and with infrared reflection-absorption spectroscopy (IRRAS) at the interface. Hydrophobic influences are discussed for the structure conversion in an effort to understand the completely unknown reason for the natural change of the normal prion protein cellular (PrP(C)) into the abnormal prion protein scrapie (PrP(Sc)). PMID:10585952

High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

DTIC Science & Technology

2007-07-01

malarial drug),31 curcumin (unpublished results), and a number of other CNS-permeable com- pounds that potently inhibit PrPSc formation in cell culture.32...759-761. (35) Hambright, P. Chemistry of Water Soluble Porphyrins. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic...No 10 lM Amodiaquine 264 ± 11 No 10 lM Minocycline 276 ± 2 No 10 lM Mefloquine 257 ± 4 No 10 lM Curcumin NAc NA 10 lM NiPCTS 50 ± 3 Yes 10 lM PCTS 56

A novel copper-hydrogen peroxide formulation for prion decontamination.

PubMed

Solassol, Jerome; Pastore, Manuela; Crozet, Carole; Perrier, Veronique; Lehmann, Sylvain

2006-09-15

With the appearance of variant Creutzfeldt-Jakob disease (CJD) and the detection of infectious prions in the peripheral organs of persons with sporadic CJD, the development of decontamination methods that are compatible with medical equipment has become a major issue. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide dramatically reduces the level of prion protein (PrP)(Sc) (the scrapie isoform of PrP) present in homogenates of samples from prion-infected brains, including brain samples from humans with CJD. An animal bioassay confirmed the reduction in prion infectivity, indicating that this novel Cu(2+)-H(2)O(2) formulation has great potential for prion decontamination.

Theoretical and computational studies in protein folding, design, and function

NASA Astrophysics Data System (ADS)

Morrissey, Michael Patrick

2000-10-01

In this work, simplified statistical models are used to understand an array of processes related to protein folding and design. In Part I, lattice models are utilized to test several theories about the statistical properties of protein-like systems. In Part II, sequence analysis and all-atom simulations are used to advance a novel theory for the behavior of a particular protein. Part I is divided into five chapters. In Chapter 2, a method of sequence design for model proteins, based on statistical mechanical first-principles, is developed. The cumulant design method uses a mean-field approximation to expand the free energy of a sequence in temperature. The method successfully designs sequences which fold to a target lattice structure at a specific temperature, a feat which was not possible using previous design methods. The next three chapters are computational studies of the double mutant cycle, which has been used experimentally to predict intra-protein interactions. Complete structure prediction is demonstrated for a model system using exhaustive, and also sub-exhaustive, double mutants. Nonadditivity of enthalpy, rather than of free energy, is proposed and demonstrated to be a superior marker for inter-residue contact. Next, a new double mutant protocol, called exchange mutation, is introduced. Although simple statistical arguments predict exchange mutation to be a more accurate contact predictor than standard mutant cycles, this hypothesis was not upheld in lattice simulations. Reasons for this inconsistency will be discussed. Finally, a multi-chain folding algorithm is introduced. Known as LINKS, this algorithm was developed to test a method of structure prediction which utilizes chain-break mutants. While structure prediction was not successful, LINKS should nevertheless be a useful tool for the study of protein-protein and protein-ligand interactions. The last chapter of Part I utilizes the lattice to explore the differences between standard folding, from the fully denatured state, and cotranslational folding, whereby one end of a protein is synthesized and released before the other. Cotranslational folding is shown to accelerate folding kinetics, particularly when the target backbone contains many local contacts. Additionally, cotranslation is shown capable of "guiding" a model protein into a metastable, local contact-rich state, despite the existence of a true native state of much lower energy. In Part II, a model is developed for the behavior of PrP, a unique mammalian protein which has been shown to possess two native states. The pathogenic "scrapie" state PrPSc, which has not been structurally characterized, is known to trigger conversion of the characterized endogenous conformation PrPC into additional PrPSc, Residues 144--153 are shown to form the most hydrophilic naturally occurring alpha-helix, out of a broad database with more than 10,000 candidates. The novel beta-nucleation model proposes that PrPSc, is not a distinct mono-molecular state, but is rather a beta-sheet-like aggregate centered around helix-1 components of multiple PrP molecules. The remainder of Part II uses molecular dynamics simulations to support the beta-nucleation hypothesis, and to propose a system of peptide ligands which may arrest the process of prion propagation.

Copper and the Prion Protein: Methods, Structures, Function, and Disease

NASA Astrophysics Data System (ADS)

Millhauser, Glenn L.

2007-05-01

The transmissible spongiform encephalopathies (TSEs) arise from conversion of the membrane-bound prion protein from PrPC to PrPSc. Examples of the TSEs include mad cow disease, chronic wasting disease in deer and elk, scrapie in goats and sheep, and kuru and Creutzfeldt-Jakob disease in humans. Although the precise function of PrPC in healthy tissues is not known, recent research demonstrates that it binds Cu(II) in an unusual and highly conserved region of the protein termed the octarepeat domain. This review describes recent connections between copper and PrPC, with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrPC function, and emerging connections between copper and prion disease.

Progress on low susceptibility mechanisms of transmissible spongiform encephalopathies

PubMed Central

QING, Li-Li; ZHAO, Hui; LIU, Lin-Lin

2014-01-01

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative diseases detected in a wide range of mammalian species. The “protein-only” hypothesis of TSE suggests that prions are transmissible particles devoid of nucleic acid and the primary pathogenic event is thought to be the conversion of cellular prion protein (PrPC) into the disease-associated isoform (PrPSc). According to susceptibility to TSEs, animals can be classified into susceptible species and low susceptibility species. In this review we focus on several species with low susceptibility to TSEs: dogs, rabbits, horses and buffaloes. We summarize recent studies into the characteristics of low susceptibility regarding protein structure, and biochemical and genetic properties. PMID:25297084

The Amino-Terminal PrP Domain Is Crucial to Modulate Prion Misfolding and Aggregation

PubMed Central

Cordeiro, Yraima; Kraineva, Julia; Gomes, Mariana P. B.; Lopes, Marilene H.; Martins, Vilma R.; Lima, Luís M. T. R.; Foguel, Débora; Winter, Roland; Silva, Jerson L.

2005-01-01

The main hypothesis for prion diseases is that the cellular protein (PrPC) can be altered into a misfolded, β-sheet-rich isoform (PrPSc), which undergoes aggregation and triggers the onset of transmissible spongiform encephalopathies. Here, we investigate the effects of amino-terminal deletion mutations, rPrPΔ51–90 and rPrPΔ32–121, on the stability and the packing properties of recombinant murine PrP. The region lacking in rPrPΔ51–90 is involved physiologically in copper binding and the other construct lacks more amino-terminal residues (from 32 to 121). The pressure stability is dramatically reduced with decreasing N-domain length and the process is not reversible for rPrPΔ51–90 and rPrPΔ32–121, whereas it is completely reversible for the wild-type form. Decompression to atmospheric pressure triggers immediate aggregation for the mutants in contrast to a slow aggregation process for the wild-type, as observed by Fourier-transform infrared spectroscopy. The temperature-induced transition leads to aggregation of all rPrPs, but the unfolding temperature is lower for the rPrP amino-terminal deletion mutants. The higher susceptibility to pressure of the amino-terminal deletion mutants can be explained by a change in hydration and cavity distribution. Taken together, our results show that the amino-terminal region has a pivotal role on the development of prion misfolding and aggregation. PMID:16040743

An Enzymatic Treatment of Soil-Bound Prions Effectively Inhibits Replication ▿

PubMed Central

Saunders, Samuel E.; Bartz, Jason C.; Vercauteren, Kurt C.; Bartelt-Hunt, Shannon L.

2011-01-01

Chronic wasting disease (CWD) and scrapie can be transmitted through indirect environmental routes, possibly via soil, and a practical decontamination strategy for prion-contaminated soil is currently unavailable. In the laboratory, an enzymatic treatment under environmentally relevant conditions (22°C, pH 7.4) can degrade soil-bound PrPSc below the limits of Western blot detection. We developed and used a quantitative serial protein misfolding cyclic amplification (PMCA) protocol to characterize the amplification efficiency of treated soil samples relative to controls of known infectious titer. Our results suggest large (104- to >106-fold) decreases in soil-bound prion infectivity following enzyme treatment, demonstrating that a mild enzymatic treatment could effectively reduce the risk of prion disease transmission via soil or other environmental surfaces. PMID:21571886

The application of a sparse, distributed memory to the detection, identification and manipulation of physical objects

NASA Technical Reports Server (NTRS)

Kanerva, P.

1986-01-01

To determine the relation of the sparse, distributed memory to other architectures, a broad review of the literature was made. The memory is called a pattern memory because they work with large patterns of features (high-dimensional vectors). A pattern is stored in a pattern memory by distributing it over a large number of storage elements and by superimposing it over other stored patterns. A pattern is retrieved by mathematical or statistical reconstruction from the distributed elements. Three pattern memories are discussed.

Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie

PubMed Central

2014-01-01

Background Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease. PMID:24450868

Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach

PubMed Central

Toni, Mattia; Massimino, Maria L.; De Mario, Agnese; Angiulli, Elisa; Spisni, Enzo

2017-01-01

Metal ions are key elements in organisms' life acting like cofactors of many enzymes but they can also be potentially dangerous for the cell participating in redox reactions that lead to the formation of reactive oxygen species (ROS). Any factor inducing or limiting a metal dyshomeostasis, ROS production and cell injury may contribute to the onset of neurodegenerative diseases or play a neuroprotective action. Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative disorders affecting the central nervous system (CNS) of human and other mammalian species. The causative agent of TSEs is believed to be the scrapie prion protein PrPSc, the β sheet-rich pathogenic isoform produced by the conformational conversion of the α-helix-rich physiological isoform PrPC. The peculiarity of PrPSc is its ability to self-propagate in exponential fashion in cells and its tendency to precipitate in insoluble and protease-resistance amyloid aggregates leading to neuronal cell death. The expression “prion-like diseases” refers to a group of neurodegenerative diseases that share some neuropathological features with prion diseases such as the involvement of proteins (α-synuclein, amyloid β, and tau) able to precipitate producing amyloid deposits following conformational change. High social impact diseases such as Alzheimer's and Parkinson's belong to prion-like diseases. Accumulating evidence suggests that the exposure to environmental metals is a risk factor for the development of prion and prion-like diseases and that metal ions can directly bind to prion and prion-like proteins affecting the amount of amyloid aggregates. The diet, source of metal ions but also of natural antioxidant and chelating agents such as polyphenols, is an aspect to take into account in addressing the issue of neurodegeneration. Epidemiological data suggest that the Mediterranean diet, based on the abundant consumption of fresh vegetables and on low intake of meat, could play a preventive or delaying role in prion and prion-like neurodegenerative diseases. In this review, metal role in the onset of prion and prion-like diseases is dealt with from a nutritional, cellular, and molecular point of view. PMID:28154522

Exploring the cause of initially reactive bovine brains on rapid tests for BSE

PubMed Central

Dudas, Sandor; James, Jace; Anderson, Renee; Czub, Stefanie

2015-01-01

ABSTRACT Bovine spongiform encephalopathy (BSE) is an invariably fatal prion disease of cattle. The identification of the zoonotic potential of BSE prompted safety officials to initiate surveillance testing for this disease. In Canada, BSE surveillance is primarily focused on high risk cattle including animals which are dead, down and unable to rise, diseased or distressed. This targeted surveillance results in the submission of brain samples with a wide range of tissue autolysis and associated contaminants. These contaminants have the potential to interfere with important steps of surveillance tests resulting in initially positive test results requiring additional testing to confirm the disease status of the animal. The current tests used for BSE screening in Canada utilize the relative protease resistance of the prion protein gained when it misfolds from PrPC to PrPSc as part of the disease process. Proteinase K completely digests PrPC in normal brains, but leaves most of the PrPSc in BSE positive brains intact which is detected using anti-prion antibodies. These tests are highly reliable but occasionally give rise to initially reactive/false positive results. Test results for these reactive samples were close to the positive/negative cut-off on a sub set of test platforms. This is in contrast to all of the previous Canadian positive samples whose numeric values on these same test platforms were 10 to 100 fold greater than the test positive/negative cut-off. Here we explore the potential reason why a sample is repeatedly positive on a sub-set of rapid surveillance tests, but negative on other test platforms. In order to better understand and identify what might cause these initial reactions, we have conducted a variety of rapid and confirmatory assays as well as bacterial isolation and identification on BSE positive, negative and initially reactive samples. We observed high levels of viable bacterial contamination in initially reactive samples suggesting that the reactivity may be related to bacterial factors. Several bacteria isolated from the initially reactive samples have characteristics of biofilm forming bacteria and this extracellular matrix might play a role in preventing complete digestion of PrPC in these samples. PMID:26689488

Distributional properties of relative phase in bimanual coordination.

PubMed

James, Eric; Layne, Charles S; Newell, Karl M

2010-10-01

Studies of bimanual coordination have typically estimated the stability of coordination patterns through the use of the circular standard deviation of relative phase. The interpretation of this statistic depends upon the assumption of a von Mises distribution. The present study tested this assumption by examining the distributional properties of relative phase in three bimanual coordination patterns. There were significant deviations from the von Mises distribution due to differences in the kurtosis of distributions. The kurtosis depended upon the relative phase pattern performed, with leptokurtic distributions occurring in the in-phase and antiphase patterns and platykurtic distributions occurring in the 30° pattern. Thus, the distributional assumptions needed to validly and reliably use the standard deviation are not necessarily present in relative phase data though they are qualitatively consistent with the landscape properties of the intrinsic dynamics.

Inputs and spatial distribution patterns of Cr in Jiaozhou Bay

NASA Astrophysics Data System (ADS)

Yang, Dongfang; Miao, Zhenqing; Huang, Xinmin; Wei, Linzhen; Feng, Ming

2018-03-01

Cr pollution in marine bays has been one of the critical environmental issues, and understanding the input and spatial distribution patterns is essential to pollution control. In according to the source strengths of the major pollution sources, the input patterns of pollutants to marine bay include slight, moderate and heavy, and the spatial distribution are corresponding to three block models respectively. This paper analyzed input patterns and distributions of Cr in Jiaozhou Bay, eastern China based on investigation on Cr in surface waters during 1979-1983. Results showed that the input strengths of Cr in Jiaozhou Bay could be classified as moderate input and slight input, and the input strengths were 32.32-112.30 μg L-1 and 4.17-19.76 μg L-1, respectively. The input patterns of Cr included two patterns of moderate input and slight input, and the horizontal distributions could be defined by means of Block Model 2 and Block Model 3, respectively. In case of moderate input pattern via overland runoff, Cr contents were decreasing from the estuaries to the bay mouth, and the distribution pattern was parallel. In case of moderate input pattern via marine current, Cr contents were decreasing from the bay mouth to the bay, and the distribution pattern was parallel to circular. The Block Models were able to reveal the transferring process of various pollutants, and were helpful to understand the distributions of pollutants in marine bay.

NEUROPATHOLOGIC FINDINGS IN CETACEANS STRANDED IN ITALY (2002-14).

PubMed

Pintore, Maria Domenica; Mignone, Walter; Di Guardo, Giovanni; Mazzariol, Sandro; Ballardini, Marco; Florio, Caterina Lucia; Goria, Maria; Romano, Angelo; Caracappa, Santo; Giorda, Federica; Serracca, Laura; Pautasso, Alessandra; Tittarelli, Cristiana; Petrella, Antonio; Lucifora, Giuseppe; Di Nocera, Fabio; Uberti, Barbara Degli; Corona, Cristiano; Casalone, Cristina; Iulini, Barbara

2018-04-01

  We summarized the neuropathologic findings in 60 cetaceans stranded along the Italian coastline from 2002 to 2014. The following neuropathologic changes were detected in 45% (27/60) of animals: nonsuppurative meningo-encephalitides (30%, 18/60), nonspecific lesions (12%, 7/60), suppurative encephalitis (2%, 1/60), and neoplasm (2%, 1/60). No histologic lesions were found in 47% (28/60) of the specimens. Five (8%, 5/60) samples were unsuitable for analysis. Analysis with PCR detected Brucella spp., morbillivirus, and Toxoplasma gondii infection in one, six, and seven individuals, respectively. Immunohistochemical analysis confirmed positivity for morbillivirus and for T. gondii infection in three cases each. No evidence of the scrapie-associated prion protein PrPSc was detected. Our findings underscore the importance of an adequate surveillance system for monitoring aquatic mammal pathologies and for protecting both animal and human health.

The many shades of prion strain adaptation.

PubMed

Baskakov, Ilia V

2014-01-01

In several recent studies transmissible prion disease was induced in animals by inoculation with recombinant prion protein amyloid fibrils produced in vitro. Serial transmission of amyloid fibrils gave rise to a new class of prion strains of synthetic origin. Gradual transformation of disease phenotypes and PrP(Sc) properties was observed during serial transmission of synthetic prions, a process that resembled the phenomenon of prion strain adaptation. The current article discusses the remarkable parallels between phenomena of prion strain adaptation that accompanies cross-species transmission and the evolution of synthetic prions occurring within the same host. Two alternative mechanisms underlying prion strain adaptation and synthetic strain evolution are discussed. The current article highlights the complexity of the prion transmission barrier and strain adaptation and proposes that the phenomenon of prion adaptation is more common than previously thought.

Clinical, pathological, and molecular features of classical and L-type atypical-BSE in goats

PubMed Central

D’Angelo, Antonio; Mazza, Maria; Meloni, Daniela; Baioni, Elisa; Maurella, Cristiana; Colussi, Silvia; Martinelli, Nicola; Lo Faro, Monica; Favole, Alessandra; Grifoni, Silvia; Gallo, Marina; Lombardi, Guerino; Iulini, Barbara; Casalone, Cristina; Corona, Cristiano

2018-01-01

Monitoring of small ruminants for transmissible spongiform encephalopathies (TSEs) has recently become more relevant after two natural scrapie suspected cases of goats were found to be positive for classical BSE (C-BSE). C-BSE probably established itself in this species unrecognized, undermining disease control measures. This opens the possibility that TSEs in goats may remain an animal source for human prion diseases. Currently, there are no data regarding the natural presence of the atypical BSE in caprines. Here we report that C-BSE and L-type atypical BSE (L-BSE) isolates from bovine species are intracerebrally transmissible to goats, with a 100% attack rate and a significantly shorter incubation period and survival time after C-BSE than after L-BSE experimental infection, suggesting a lower species barrier for classical agentin goat. All animals showed nearly the same clinical features of disease characterized by skin lesions, including broken hair and alopecia, and abnormal mental status. Histology and immunohistochemistry showed several differences between C-BSE and L-BSE infection, allowing discrimination between the two different strains. The lymphoreticular involvement we observed in the C-BSE positive goats argues in favour of a peripheral distribution of PrPSc similar to classical scrapie. Western blot and other currently approved screening tests detected both strains in the goats and were able to classify negative control animals. These data demonstrate that active surveillance of small ruminants, as applied to fallen stock and/or healthy slaughter populations in European countries, is able to correctly identify and classify classical and L-BSE and ultimately protect public health. PMID:29795663

Differential display detects host nucleic acid motifs altered in scrapie-infected brain.

PubMed

Lathe, Richard; Harris, Alyson

2009-09-25

The transmissible spongiform encephalopathies (TSEs) including scrapie have been attributed to an infectious protein or prion. Infectivity is allied to conversion of the endogenous nucleic-acid-binding protein PrP to an infectious modified form known as PrP(sc). The protein-only theory does not easily explain the enigmatic properties of the agent including strain variation. It was previously suggested that a short nucleic acid, perhaps host-encoded, might contribute to the pathoetiology of the TSEs. No candidate host molecules that might explain transmission of strain differences have yet been put forward. Differential display is a robust technique for detecting nucleic acid differences between two populations. We applied this technique to total nucleic acid preparations from scrapie-infected and control brain. Independent RNA preparations from eight normal and eight scrapie-infected (strain 263K) hamster brains were randomly amplified and visualized in parallel. Though the nucleic acid patterns were generally identical in scrapie-infected versus control brain, some rare bands were differentially displayed. Molecular species consistently overrepresented (or underrepresented) in all eight infected brain samples versus all eight controls were excised from the display, sequenced, and assembled into contigs. Only seven ros contigs (RNAs over- or underrepresented in scrapie) emerged, representing <4 kb from the transcriptome. All contained highly stable regions of secondary structure. The most abundant scrapie-only ros sequence was homologous to a repetitive transposable element (LINE; long interspersed nuclear element). Other ros sequences identified cellular RNA 7SL, clathrin heavy chain, visinin-like protein-1, and three highly specific subregions of ribosomal RNA (ros1-3). The ribosomal ros sequences accurately corresponded to LINE; retrotransposon insertion sites in ribosomal DNA (p<0.01). These differential motifs implicate specific host RNAs in the pathoetiology of the TSEs.

PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells

PubMed Central

Arkhipenko, Alexander; Syan, Sylvie; Victoria, Guiliana Soraya

2016-01-01

The Prion Protein (PrP) is an ubiquitously expressed glycosylated membrane protein attached to the external leaflet of the plasma membrane via a glycosylphosphatidylinositol anchor (GPI). While the misfolded PrPSc scrapie isoform is the infectious agent of prion disease, the cellular isoform (PrPC) is an enigmatic protein with unclear function. Of interest, PrP localization in polarized MDCK cells is controversial and its mechanism of trafficking is not clear. Here we investigated PrP traffic in MDCK cells polarized on filters and in three-dimensional MDCK cysts, a more physiological model of polarized epithelia. We found that, unlike other GPI-anchored proteins (GPI-APs), PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells. Following this event full-length PrP and its cleavage fragments are segregated in different domains of the plasma membrane in polarized cells in both 2D and 3D cultures. PMID:27389581

Molecular modeling of the conformational dynamics of the cellular prion protein

NASA Astrophysics Data System (ADS)

Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

2014-03-01

Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

Amino acid sequence of the Amur tiger prion protein.

PubMed

Wu, Changde; Pang, Wanyong; Zhao, Deming

2006-10-01

Prion diseases are fatal neurodegenerative disorders in human and animal associated with conformational conversion of a cellular prion protein (PrP(C)) into the pathologic isoform (PrP(Sc)). Various data indicate that the polymorphisms within the open reading frame (ORF) of PrP are associated with the susceptibility and control the species barrier in prion diseases. In the present study, partial Prnp from 25 Amur tigers (tPrnp) were cloned and screened for polymorphisms. Four single nucleotide polymorphisms (T423C, A501G, C511A, A610G) were found; the C511A and A610G nucleotide substitutions resulted in the amino acid changes Lysine171Glutamine and Alanine204Threoine, respectively. The tPrnp amino acid sequence is similar to house cat (Felis catus ) and sheep, but differs significantly from other two cat Prnp sequences that were previously deposited in GenBank.

Crop yield response to climate change varies with crop spatial distribution pattern

DOE PAGES

Leng, Guoyong; Huang, Maoyi

2017-05-03

The linkage between crop yield and climate variability has been confirmed in numerous studies using statistical approaches. A crucial assumption in these studies is that crop spatial distribution pattern is constant over time. Here, we explore how changes in county-level corn spatial distribution pattern modulate the response of its yields to climate change at the state level over the Contiguous United States. Our results show that corn yield response to climate change varies with crop spatial distribution pattern, with distinct impacts on the magnitude and even the direction at the state level. Corn yield is predicted to decrease by 20~40%more » by 2050s when considering crop spatial distribution pattern changes, which is 6~12% less than the estimates with fixed cropping pattern. The beneficial effects are mainly achieved by reducing the negative impacts of daily maximum temperature and strengthening the positive impacts of precipitation. Our results indicate that previous empirical studies could be biased in assessing climate change impacts by ignoring the changes in crop spatial distribution pattern. As a result, this has great implications for understanding the increasing debates on whether climate change will be a net gain or loss for regional agriculture.« less

Crop yield response to climate change varies with crop spatial distribution pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leng, Guoyong; Huang, Maoyi

The linkage between crop yield and climate variability has been confirmed in numerous studies using statistical approaches. A crucial assumption in these studies is that crop spatial distribution pattern is constant over time. Here, we explore how changes in county-level corn spatial distribution pattern modulate the response of its yields to climate change at the state level over the Contiguous United States. Our results show that corn yield response to climate change varies with crop spatial distribution pattern, with distinct impacts on the magnitude and even the direction at the state level. Corn yield is predicted to decrease by 20~40%more » by 2050s when considering crop spatial distribution pattern changes, which is 6~12% less than the estimates with fixed cropping pattern. The beneficial effects are mainly achieved by reducing the negative impacts of daily maximum temperature and strengthening the positive impacts of precipitation. Our results indicate that previous empirical studies could be biased in assessing climate change impacts by ignoring the changes in crop spatial distribution pattern. As a result, this has great implications for understanding the increasing debates on whether climate change will be a net gain or loss for regional agriculture.« less

Multi-port valve

DOEpatents

Lewin, Keith F.

1997-04-15

A multi-port valve for regulating, as a function of ambient air having varying wind velocity and wind direction in an open-field control area, the distribution of a fluid, particularly carbon dioxide (CO.sub.2) gas, in a fluid distribution system so that the control area remains generally at an elevated fluid concentration or level of said fluid. The multi-port valve generally includes a multi-port housing having a plurality of outlets therethrough disposed in a first pattern of outlets and at least one second pattern of outlets, and a movable plate having a plurality of apertures extending therethrough disposed in a first pattern of apertures and at least one second pattern of apertures. The first pattern of apertures being alignable with the first pattern of outlets and the at least one second pattern of apertures being alignable with the second pattern of outlets. The first pattern of apertures has a predetermined orientation with the at least one second pattern of apertures. For an open-field control area subject to ambient wind having a low velocity from any direction, the movable plate is positioned to equally distribute the supply of fluid in a fluid distribution system to the open-field control area. For an open-field control area subject to ambient wind having a high velocity from a given direction, the movable plate is positioned to generally distribute a supply of fluid in a fluid distribution system to that portion of the open-field control area located upwind.

Multi-port valve

DOEpatents

Lewin, K.F.

1997-04-15

A multi-port valve is described for regulating, as a function of ambient air having varying wind velocity and wind direction in an open-field control area, the distribution of a fluid, particularly carbon dioxide (CO{sub 2}) gas, in a fluid distribution system so that the control area remains generally at an elevated fluid concentration or level of said fluid. The multi-port valve generally includes a multi-port housing having a plurality of outlets there through disposed in a first pattern of outlets and at least one second pattern of outlets, and a movable plate having a plurality of apertures extending there through disposed in a first pattern of apertures and at least one second pattern of apertures. The first pattern of apertures being alignable with the first pattern of outlets and the at least one second pattern of apertures being alignable with the second pattern of outlets. The first pattern of apertures has a predetermined orientation with the at least one second pattern of apertures. For an open-field control area subject to ambient wind having a low velocity from any direction, the movable plate is positioned to equally distribute the supply of fluid in a fluid distribution system to the open-field control area. For an open-field control area subject to ambient wind having a high velocity from a given direction, the movable plate is positioned to generally distribute a supply of fluid in a fluid distribution system to that portion of the open-field control area located upwind. 7 figs.

The Cluster Variation Method: A Primer for Neuroscientists.

PubMed

Maren, Alianna J

2016-09-30

Effective Brain-Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables , is defined in terms of a single interaction enthalpy parameter ( h ) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found.

Intermodal transport and distribution patterns in ports relationship to hinterland

NASA Astrophysics Data System (ADS)

Dinu, O.; Dragu, V.; Ruscă, F.; Ilie, A.; Oprea, C.

2017-08-01

It is of great importance to examine all interactions between ports, terminals, intermodal transport and logistic actors of distribution channels, as their optimization can lead to operational improvement. Proposed paper starts with a brief overview of different goods types and allocation of their logistic costs, with emphasis on storage component. Present trend is to optimize storage costs by means of port storage area buffer function, by making the best use of free storage time available, most of the ports offer. As a research methodology, starting point is to consider the cost structure of a generic intermodal transport (storage, handling and transport costs) and to link this to intermodal distribution patterns most frequently cast-off in port relationship to hinterland. The next step is to evaluate storage costs impact on distribution pattern selection. For a given value of port free storage time, a corresponding value of total storage time in the distribution channel can be identified, in order to substantiate a distribution pattern shift. Different scenarios for transport and handling costs variation, recorded when distribution pattern shift, are integrated in order to establish the reaction of the actors involved in port related logistic and intermodal transport costs evolution is analysed in order to optimize distribution pattern selection.

The Cluster Variation Method: A Primer for Neuroscientists

PubMed Central

Maren, Alianna J.

2016-01-01

Effective Brain–Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables, is defined in terms of a single interaction enthalpy parameter (h) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found. PMID:27706022

Patterns in Calabi-Yau Distributions

NASA Astrophysics Data System (ADS)

He, Yang-Hui; Jejjala, Vishnu; Pontiggia, Luca

2017-09-01

We explore the distribution of topological numbers in Calabi-Yau manifolds, using the Kreuzer-Skarke dataset of hypersurfaces in toric varieties as a testing ground. While the Hodge numbers are well-known to exhibit mirror symmetry, patterns in frequencies of combination thereof exhibit striking new patterns. We find pseudo-Voigt and Planckian distributions with high confidence and exact fit for many substructures. The patterns indicate typicality within the landscape of Calabi-Yau manifolds of various dimension.

In silico studies and fluorescence binding assays of potential anti-prion compounds reveal an important binding site for prion inhibition from PrP(C) to PrP(Sc).

PubMed

Pagadala, Nataraj S; Perez-Pineiro, Rolando; Wishart, David S; Tuszynski, Jack A

2015-02-16

To understand the pharmacophore properties of 2-aminothiazoles and design novel inhibitors against the prion protein, a highly predictive 3D quantitative structure-activity relationship (QSAR) has been developed by performing comparative molecular field analysis (CoMFA) and comparative similarity analysis (CoMSIA). Both CoMFA and CoMSIA maps reveal the presence of the oxymethyl groups in meta and para positions on the phenyl ring of compound 17 (N-[4-(3,4-dimethoxyphenyl)-1,3-thiazol-2-yl]quinolin-2-amine), is necessary for activity while electro-negative nitrogen of quinoline is highly favorable to enhance activity. The blind docking results for these compounds show that the compound with quinoline binds with higher affinity than isoquinoline and naphthalene groups. Out of 150 novel compounds retrieved using finger print analysis by pharmacophoric model predicted based on five test sets of compounds, five compounds with diverse scaffolds were selected for biological evaluation as possible PrP inhibitors. Molecular docking combined with fluorescence quenching studies show that these compounds bind to pocket-D of SHaPrP near Trp145. The new antiprion compounds 3 and 6, which bind with the interaction energies of -12.1 and -13.2 kcal/mol, respectively, show fluorescence quenching with binding constant (Kd) values of 15.5 and 44.14 μM, respectively. Further fluorescence binding assays with compound 5, which is similar to 2-aminothiazole as a positive control, also show that the molecule binds to the pocket-D with the binding constant (Kd) value of 84.7 μM. Finally, both molecular docking and a fluorescence binding assay of noscapine as a negative control reveals the same binding site on the surface of pocket-A near a rigid loop between β2 and α2 interacting with Arg164. This high level of correlation between molecular docking and fluorescence quenching studies confirm that these five compounds are likely to act as inhibitors for prion propagation while noscapine might act as a prion accelerator from PrP(C) to PrP(Sc). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Solution structure of Syrian hamster prion protein rPrP(90-231).

PubMed

Liu, H; Farr-Jones, S; Ulyanov, N B; Llinas, M; Marqusee, S; Groth, D; Cohen, F E; Prusiner, S B; James, T L

1999-04-27

NMR has been used to refine the structure of Syrian hamster (SHa) prion protein rPrP(90-231), which is commensurate with the infectious protease-resistant core of the scrapie prion protein PrPSc. The structure of rPrP(90-231), refolded to resemble the normal cellular isoform PrPC spectroscopically and immunologically, has been studied using multidimensional NMR; initial results were published [James et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 10086-10091]. We now report refinement with better definition revealing important structural and dynamic features which can be related to biological observations pertinent to prion diseases. Structure refinement was based on 2778 unambiguously assigned nuclear Overhauser effect (NOE) connectivities, 297 ambiguous NOE restraints, and 63 scalar coupling constants (3JHNHa). The structure is represented by an ensemble of 25 best-scoring structures from 100 structures calculated using ARIA/X-PLOR and further refined with restrained molecular dynamics using the AMBER 4.1 force field with an explicit shell of water molecules. The rPrP(90-231) structure features a core domain (residues 125-228), with a backbone atomic root-mean-square deviation (RMSD) of 0.67 A, consisting of three alpha-helices (residues 144-154, 172-193, and 200-227) and two short antiparallel beta-strands (residues 129-131 and 161-163). The N-terminus (residues 90-119) is largely unstructured despite some sparse and weak medium-range NOEs implying the existence of bends or turns. The transition region between the core domain and flexible N-terminus, i.e., residues 113-128, consists of hydrophobic residues or glycines and does not adopt any regular secondary structure in aqueous solution. There are about 30 medium- and long-range NOEs within this hydrophobic cluster, so it clearly manifests structure. Multiple discrete conformations are evident, implying the possible existence of one or more metastable states, which may feature in conversion of PrPC to PrPSc. To obtain a more comprehensive picture of rPrP(90-231), dynamics have been studied using amide hydrogen-deuterium exchange and 15N NMR relaxation times (T1 and T2) and 15N{1H} NOE measurements. Comparison of the structure with previous reports suggests sequence-dependent features that may be reflected in a species barrier to prion disease transmission.

Prospect for the development of salted egg agro industry: an analysis on marketing distribution aspect

NASA Astrophysics Data System (ADS)

Sumekar, W.; Al-Baarri, A. N.; Kurnianto, E.

2018-01-01

Marketing distribution is an important of the strategy in business development in agroindustries. The aim of the research was to introduce marketing (distribution pattern, margin and marketing efficiency) at the salted egg agro industries in Brebes Regency. Survey method had been conducted on 52 salted egg agro industries which had active PIRT certificate. The data collection was conducted by means of interview and observation. Descriptive analysis was used to determine the marketing distribution of salted eggs. Marketing efficiency was obtained by calculating marketing margin and farmer share. The results show that the salted egg agro industries implemented two marketing distribution patterns; direct marketing pattern (consumer→producers) and indirect marketing pattern (producer→retailer→consumer). The number of the salted egg agro industries which apply indirect marketing pattern is 57.69%. The implementation of direct and indirect marketing patterns was classified as efficient according to the farmer’s share values of 87.13% and 78.21%. It can be recommended the direct marketing.

Distribution of Total Depressive Symptoms Scores and Each Depressive Symptom Item in a Sample of Japanese Employees.

PubMed

Tomitaka, Shinichiro; Kawasaki, Yohei; Ide, Kazuki; Yamada, Hiroshi; Miyake, Hirotsugu; Furukawa, Toshiaki A; Furukaw, Toshiaki A

2016-01-01

In a previous study, we reported that the distribution of total depressive symptoms scores according to the Center for Epidemiologic Studies Depression Scale (CES-D) in a general population is stable throughout middle adulthood and follows an exponential pattern except for at the lowest end of the symptom score. Furthermore, the individual distributions of 16 negative symptom items of the CES-D exhibit a common mathematical pattern. To confirm the reproducibility of these findings, we investigated the distribution of total depressive symptoms scores and 16 negative symptom items in a sample of Japanese employees. We analyzed 7624 employees aged 20-59 years who had participated in the Northern Japan Occupational Health Promotion Centers Collaboration Study for Mental Health. Depressive symptoms were assessed using the CES-D. The CES-D contains 20 items, each of which is scored in four grades: "rarely," "some," "much," and "most of the time." The descriptive statistics and frequency curves of the distributions were then compared according to age group. The distribution of total depressive symptoms scores appeared to be stable from 30-59 years. The right tail of the distribution for ages 30-59 years exhibited a linear pattern with a log-normal scale. The distributions of the 16 individual negative symptom items of the CES-D exhibited a common mathematical pattern which displayed different distributions with a boundary at "some." The distributions of the 16 negative symptom items from "some" to "most" followed a linear pattern with a log-normal scale. The distributions of the total depressive symptoms scores and individual negative symptom items in a Japanese occupational setting show the same patterns as those observed in a general population. These results show that the specific mathematical patterns of the distributions of total depressive symptoms scores and individual negative symptom items can be reproduced in an occupational population.

On the diffraction pattern of bundled rare-earth silicide nanowires on Si(0 0 1).

PubMed

Timmer, F; Bahlmann, J; Wollschläger, J

2017-11-01

Motivated by the complex diffraction pattern observed for bundled rare-earth silicide nanowires on the Si(0 0 1) surface, we investigate the influence of the width and the spacing distribution of the nanowires on the diffraction pattern. The diffraction pattern of the bundled rare-earth silicide nanowires is analyzed by the binary surface technique applying a kinematic approach to diffraction. Assuming a categorical distribution for the (individual) nanowire size and a Poisson distribution for the size of the spacing between adjacent nanowire-bundles, we are able to determine the parameters of these distributions and derive an expression for the distribution of the nanowire-bundle size. Additionally, the comparison of our simulations to the experimental diffraction pattern reveal that a (1  ×  1)-periodicity on top of the nanowires has to be assumed for a good match.

Fate of prions in soil: trapped conformation of full-length ovine prion protein induced by adsorption on clays.

PubMed

Revault, M; Quiquampoix, H; Baron, M H; Noinville, S

2005-08-05

Studying the mechanism of retention of ovine prion protein in soils will tackle the environmental aspect of potential dissemination of scrapie infectious agent. We consider the surface-induced conformational changes that the recombinant ovine prion protein (ovPrP) may undergo under different pH conditions when interacting with soil minerals of highly adsorptive capacities such as montmorillonite. The conformational states of the full-length ovine prion protein adsorbed on the electronegative clay surface are compared to its solvated state in deuterated buffer in the pD range 3.5-9, using FTIR spectroscopy. The in vitro pH-induced conversion of the alpha-helical monomer of ovPrP into oligomers of beta-like structure prone to self-aggregation does not occur when the protein is adsorbed on the clay surface. The conformation of the trapped ovPrP molecules on montmorillonite is pH-independent and looks like that of the ovPrP solvated state at pD higher than 7, suggesting the major role of Arg and Lys residues in the electrostatic origin of adsorption. The uneven distribution of positively and negatively charged residues of the ovPrP protein would promote a favored orientation of the protein towards the clay, so that not only the basic residues embedded in the N-terminal flexible part but also external basic residues in the globular part of the protein might participate to the attractive interaction. From these results, it appears unlikely that the interaction of normal prions (PrP(C)) with soil clay surfaces could induce a change of conformation leading to the pathogenic form of prions (PrP(Sc)).

Origin of heterogeneous spiking patterns from continuously distributed ion channel densities: a computational study in spinal dorsal horn neurons.

PubMed

Balachandar, Arjun; Prescott, Steven A

2018-05-01

Distinct spiking patterns may arise from qualitative differences in ion channel expression (i.e. when different neurons express distinct ion channels) and/or when quantitative differences in expression levels qualitatively alter the spike generation process. We hypothesized that spiking patterns in neurons of the superficial dorsal horn (SDH) of spinal cord reflect both mechanisms. We reproduced SDH neuron spiking patterns by varying densities of K V 1- and A-type potassium conductances. Plotting the spiking patterns that emerge from different density combinations revealed spiking-pattern regions separated by boundaries (bifurcations). This map suggests that certain spiking pattern combinations occur when the distribution of potassium channel densities straddle boundaries, whereas other spiking patterns reflect distinct patterns of ion channel expression. The former mechanism may explain why certain spiking patterns co-occur in genetically identified neuron types. We also present algorithms to predict spiking pattern proportions from ion channel density distributions, and vice versa. Neurons are often classified by spiking pattern. Yet, some neurons exhibit distinct patterns under subtly different test conditions, which suggests that they operate near an abrupt transition, or bifurcation. A set of such neurons may exhibit heterogeneous spiking patterns not because of qualitative differences in which ion channels they express, but rather because quantitative differences in expression levels cause neurons to operate on opposite sides of a bifurcation. Neurons in the spinal dorsal horn, for example, respond to somatic current injection with patterns that include tonic, single, gap, delayed and reluctant spiking. It is unclear whether these patterns reflect five cell populations (defined by distinct ion channel expression patterns), heterogeneity within a single population, or some combination thereof. We reproduced all five spiking patterns in a computational model by varying the densities of a low-threshold (K V 1-type) potassium conductance and an inactivating (A-type) potassium conductance and found that single, gap, delayed and reluctant spiking arise when the joint probability distribution of those channel densities spans two intersecting bifurcations that divide the parameter space into quadrants, each associated with a different spiking pattern. Tonic spiking likely arises from a separate distribution of potassium channel densities. These results argue in favour of two cell populations, one characterized by tonic spiking and the other by heterogeneous spiking patterns. We present algorithms to predict spiking pattern proportions based on ion channel density distributions and, conversely, to estimate ion channel density distributions based on spiking pattern proportions. The implications for classifying cells based on spiking pattern are discussed. © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

A Holarctic Biogeographical Analysis of the Collembola (Arthropoda, Hexapoda) Unravels Recent Post-Glacial Colonization Patterns

PubMed Central

Ávila-Jiménez, María Luisa; Coulson, Stephen James

2011-01-01

We aimed to describe the main Arctic biogeographical patterns of the Collembola, and analyze historical factors and current climatic regimes determining Arctic collembolan species distribution. Furthermore, we aimed to identify possible dispersal routes, colonization sources and glacial refugia for Arctic collembola. We implemented a Gaussian Mixture Clustering method on species distribution ranges and applied a distance- based parametric bootstrap test on presence-absence collembolan species distribution data. Additionally, multivariate analysis was performed considering species distributions, biodiversity, cluster distribution and environmental factors (temperature and precipitation). No clear relation was found between current climatic regimes and species distribution in the Arctic. Gaussian Mixture Clustering found common elements within Siberian areas, Atlantic areas, the Canadian Arctic, a mid-Siberian cluster and specific Beringian elements, following the same pattern previously described, using a variety of molecular methods, for Arctic plants. Species distribution hence indicate the influence of recent glacial history, as LGM glacial refugia (mid-Siberia, and Beringia) and major dispersal routes to high Arctic island groups can be identified. Endemic species are found in the high Arctic, but no specific biogeographical pattern can be clearly identified as a sign of high Arctic glacial refugia. Ocean currents patterns are suggested as being an important factor shaping the distribution of Arctic Collembola, which is consistent with Antarctic studies in collembolan biogeography. The clear relations between cluster distribution and geographical areas considering their recent glacial history, lack of relationship of species distribution with current climatic regimes, and consistency with previously described Arctic patterns in a series of organisms inferred using a variety of methods, suggest that historical phenomena shaping contemporary collembolan distribution can be inferred through biogeographical analysis. PMID:26467728

Riverscape patterns among years of juvenile coho salmon in midcoastal Oregon: implications for conservation

Treesearch

R. Flitcroft; K. Burnett; J. Snyder; G. Reeves; L. Ganio

2014-01-01

Patterns of salmon distribution throughout a riverscape may be expected to change over time in response to environmental conditions and population sizes. Changing patterns of use, including identification of consistently occupied locations, are informative for conservation and recovery planning. We explored interannual patterns of distribution by juvenile Coho Salmon...

High Energy Conversion Efficiency with 3-D Micro-Patterned Photoanode for Enhancement Diffusivity and Modification of Photon Distribution in Dye-Sensitized Solar Cells.

PubMed

Yun, Min Ju; Sim, Yeon Hyang; Cha, Seung I; Seo, Seon Hee; Lee, Dong Y

2017-11-08

Dye sensitize solar cells (DSSCs) have been considered as the promising alternatives silicon based solar cell with their characteristics including high efficiency under weak illumination and insensitive power output to incident angle. Therefore, many researches have been studied to improve the energy conversion efficiency of DSSCs. However the efficiency of DSSCs are still trapped at the around 10%. In this study, micro-scale hexagonal shape patterned photoanode have proposed to modify light distribution of photon. In the patterned electrode, the appearance efficiency have been obtained from 7.1% to 7.8% considered active area and the efficiency of 12.7% have been obtained based on the photoanode area. Enhancing diffusion of electrons and modification of photon distribution utilizing the morphology of the electrode are major factors to improving the performance of patterned electrode. Also, finite element method analyses of photon distributions were conducted to estimate morphological effect that influence on the photon distribution and current density. From our proposed study, it is expecting that patterned electrode is one of the solution to overcome the stagnant efficiency and one of the optimized geometry of electrode to modify photon distribution. Process of inter-patterning in photoanode has been minimized.

Spatial and temporal statistical analysis of bycatch data: Patterns of sea turtle bycatch in the North Atlantic

USGS Publications Warehouse

Gardner, B.; Sullivan, P.J.; Morreale, S.J.; Epperly, S.P.

2008-01-01

Loggerhead (Caretta caretta) and leatherback (Dermochelys coriacea) sea turtle distributions and movements in offshore waters of the western North Atlantic are not well understood despite continued efforts to monitor, survey, and observe them. Loggerhead and leatherback sea turtles are listed as endangered by the World Conservation Union, and thus anthropogenic mortality of these species, including fishing, is of elevated interest. This study quantifies spatial and temporal patterns of sea turtle bycatch distributions to identify potential processes influencing their locations. A Ripley's K function analysis was employed on the NOAA Fisheries Atlantic Pelagic Longline Observer Program data to determine spatial, temporal, and spatio-temporal patterns of sea turtle bycatch distributions within the pattern of the pelagic fishery distribution. Results indicate that loggerhead and leatherback sea turtle catch distributions change seasonally, with patterns of spatial clustering appearing from July through October. The results from the space-time analysis indicate that sea turtle catch distributions are related on a relatively fine scale (30-200 km and 1-5 days). The use of spatial and temporal point pattern analysis, particularly K function analysis, is a novel way to examine bycatch data and can be used to inform fishing practices such that fishing could still occur while minimizing sea turtle bycatch. ?? 2008 NRC.

Spatial dynamics of warehousing and distribution in California : METRANS UTC draft 15-27.

DOT National Transportation Integrated Search

2017-01-01

The purpose of this research is to document and analyze the location patterns of warehousing and distribution activity in California. The growth of California's warehousing and distribution (W&D) activities and their spatial patterns is affected by s...

Lubricant distribution and its effect on slider air bearing performance over bit patterned media disk of disk drives

NASA Astrophysics Data System (ADS)

Wu, Lin

2011-04-01

The distribution dynamics of a thin lubricant film on a bit-patterned media disk and its effect on the performance of the ultralow flying air bearing slider of disk drives are studied by direct numerical simulations. Our analysis shows that the physics governing lubricant distribution dynamics changes when deep enough sub-100-nm nanostructures are patterned on the disk surface. Air shearing under the slider that dominates lubricant flow on a flat disk may become negligible on a bit-patterned media disk. Surface tension and disjoining pressure become dominant factors instead. Our results show that disks with nanoscale patterns/roughness may no longer be treated as flat, and the air bearing load may strongly depend not only on the geometric detail of disk patterns but also on how lubricants are distributed on the patterns when slider-disk clearance is reduced to sub-10-nm. Air bearing load and consequently the slider's flying attitude are affected by disk pattern geometry, average lubricant thickness, and material properties of lubricant such as the surface tension coefficient and Hamaker constant. The significantly expanded parameter space, upon which ultralow flying slider's dynamics depends, has to be seriously considered in evaluating the head/disk interface tribology performance of next generation patterned media magnetic recording systems.

Improved block copolymer domain dispersity on chemical patterns via homopolymer-blending and molecular transfer printing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guoliang; Nealey, Paul F.

Herein we have investigated the domain width distributions of block copolymers and their ternary blends after directed assembly on chemically patterned surfaces with and without density multiplication. On chemical patterns with density multiplication, the width of the interpolated block copolymer domains was bimodal. Once blended with the corresponding homopolymers, the block copolymers exhibited unimodal distributions of domain width due to the redistribution of homopolymers in the block copolymer domains. When the block copolymers were blended with hydroxyl-terminated homopolymers, the homopolymers with functional end-groups healed the chemical patterns and facilitated the formation of nanostructures with further improved domain width distributions. Lastly,more » it is demonstrated that the block copolymers achieved the most improved domain width distributions when directed to assemble without density multiplication on one-to-one chemical patterns generated by molecular transfer printing.« less

Explaining the power-law distribution of human mobility through transportation modality decomposition.

PubMed

Zhao, Kai; Musolesi, Mirco; Hui, Pan; Rao, Weixiong; Tarkoma, Sasu

2015-03-16

Human mobility has been empirically observed to exhibit Lévy flight characteristics and behaviour with power-law distributed jump size. The fundamental mechanisms behind this behaviour has not yet been fully explained. In this paper, we propose to explain the Lévy walk behaviour observed in human mobility patterns by decomposing them into different classes according to the different transportation modes, such as Walk/Run, Bike, Train/Subway or Car/Taxi/Bus. Our analysis is based on two real-life GPS datasets containing approximately 10 and 20 million GPS samples with transportation mode information. We show that human mobility can be modelled as a mixture of different transportation modes, and that these single movement patterns can be approximated by a lognormal distribution rather than a power-law distribution. Then, we demonstrate that the mixture of the decomposed lognormal flight distributions associated with each modality is a power-law distribution, providing an explanation to the emergence of Lévy Walk patterns that characterize human mobility patterns.

Explaining the power-law distribution of human mobility through transportation modality decomposition

NASA Astrophysics Data System (ADS)

Zhao, Kai; Musolesi, Mirco; Hui, Pan; Rao, Weixiong; Tarkoma, Sasu

2015-03-01

Human mobility has been empirically observed to exhibit Lévy flight characteristics and behaviour with power-law distributed jump size. The fundamental mechanisms behind this behaviour has not yet been fully explained. In this paper, we propose to explain the Lévy walk behaviour observed in human mobility patterns by decomposing them into different classes according to the different transportation modes, such as Walk/Run, Bike, Train/Subway or Car/Taxi/Bus. Our analysis is based on two real-life GPS datasets containing approximately 10 and 20 million GPS samples with transportation mode information. We show that human mobility can be modelled as a mixture of different transportation modes, and that these single movement patterns can be approximated by a lognormal distribution rather than a power-law distribution. Then, we demonstrate that the mixture of the decomposed lognormal flight distributions associated with each modality is a power-law distribution, providing an explanation to the emergence of Lévy Walk patterns that characterize human mobility patterns.

Explaining the power-law distribution of human mobility through transportation modality decomposition

PubMed Central

Zhao, Kai; Musolesi, Mirco; Hui, Pan; Rao, Weixiong; Tarkoma, Sasu

2015-01-01

Human mobility has been empirically observed to exhibit Lévy flight characteristics and behaviour with power-law distributed jump size. The fundamental mechanisms behind this behaviour has not yet been fully explained. In this paper, we propose to explain the Lévy walk behaviour observed in human mobility patterns by decomposing them into different classes according to the different transportation modes, such as Walk/Run, Bike, Train/Subway or Car/Taxi/Bus. Our analysis is based on two real-life GPS datasets containing approximately 10 and 20 million GPS samples with transportation mode information. We show that human mobility can be modelled as a mixture of different transportation modes, and that these single movement patterns can be approximated by a lognormal distribution rather than a power-law distribution. Then, we demonstrate that the mixture of the decomposed lognormal flight distributions associated with each modality is a power-law distribution, providing an explanation to the emergence of Lévy Walk patterns that characterize human mobility patterns. PMID:25779306

Analysis of Geographical Distribution Patterns in Plants Using Fractals

NASA Astrophysics Data System (ADS)

Bari, A.; Ayad, G.; Padulosi, S.; Hodgkin, T.; Martin, A.; Gonzalez-Andujar, J. L.; Brown, A. H. D.

Geographical distribution patterns in plants have been observed since primeval times and have been used by plant explorers to trace the origin of plants species. These patterns embody the effects of fundamental law-like processes. Diversity in plants has also been found to be proportionate with the area, and this scaling behavior is also known as fractal behavior. In the present study, we use fractal geometry to analyze the distribution patterns of wild taxa of cowpea with the objective to locate where their diversity would be the highest to aid in the planning of targeted explorations and conservation measures.

Distributed representations in memory: Insights from functional brain imaging

PubMed Central

Rissman, Jesse; Wagner, Anthony D.

2015-01-01

Forging new memories for facts and events, holding critical details in mind on a moment-to-moment basis, and retrieving knowledge in the service of current goals all depend on a complex interplay between neural ensembles throughout the brain. Over the past decade, researchers have increasingly leveraged powerful analytical tools (e.g., multi-voxel pattern analysis) to decode the information represented within distributed fMRI activity patterns. In this review, we discuss how these methods can sensitively index neural representations of perceptual and semantic content, and how leverage on the engagement of distributed representations provides unique insights into distinct aspects of memory-guided behavior. We emphasize that, in addition to characterizing the contents of memories, analyses of distributed patterns shed light on the processes that influence how information is encoded, maintained, or retrieved, and thus inform memory theory. We conclude by highlighting open questions about memory that can be addressed through distributed pattern analyses. PMID:21943171

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

PubMed

Smid, Jerusa; Studart, Adalberto; Landemberger, Michele Christine; Machado, Cleiton Fagundes; Nóbrega, Paulo Ribeiro; Canedo, Nathalie Henriques Silva; Schultz, Rodrigo Rizek; Naslavsky, Michel Satya; Rosemberg, Sérgio; Kok, Fernando; Chimelli, Leila; Martins, Vilma Regina; Nitrini, Ricardo

2017-06-01

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

Distribution pattern of phthirapterans infesting certain common Indian birds.

PubMed

Saxena, A K; Kumar, Sandeep; Gupta, Nidhi; Mitra, J D; Ali, S A; Srivastava, Roshni

2007-08-01

The prevalence and frequency distribution patterns of 10 phthirapteran species infesting house sparrows, Indian parakeets, common mynas, and white breasted kingfishers were recorded in the district of Rampur, India, during 2004-05. The sample mean abundances, mean intensities, range of infestations, variance to mean ratios, values of the exponent of the negative binomial distribution, and the indices of discrepancy were also computed. Frequency distribution patterns of all phthirapteran species were skewed, but the observed frequencies did not correspond to the negative binomial distribution. Thus, adult-nymph ratios varied in different species from 1:0.53 to 1:1.25. Sex ratios of different phthirapteran species ranged from 1:1.10 to 1:1.65 and were female biased.

Tree species exhibit complex patterns of distribution in bottomland hardwood forests

Treesearch

Luben D Dimov; Jim L Chambers; Brian R. Lockhart

2013-01-01

& Context Understanding tree interactions requires an insight into their spatial distribution. & Aims We looked for presence and extent of tree intraspecific spatial point pattern (random, aggregated, or overdispersed) and interspecific spatial point pattern (independent, aggregated, or segregated). & Methods We established twelve 0.64-ha plots in natural...

Spatial patterns of distribution and abundance of Harrisia portoricensis, an endangered Caribbean cactus

Treesearch

J. Rojas-Sandoval; E. J. Melendez-Ackerman; NO-VALUE

2013-01-01

Aims The spatial distribution of biotic and abiotic factors may play a dominant role in determining the distribution and abundance of plants in arid and semiarid environments. In this study, we evaluated how spatial patterns of microhabitat variables and the degree of spatial dependence of these variables influence the distribution and abundance of the endangered...

Efficient packing of patterns in sparse distributed memory by selective weighting of input bits

NASA Technical Reports Server (NTRS)

Kanerva, Pentti

1991-01-01

When a set of patterns is stored in a distributed memory, any given storage location participates in the storage of many patterns. From the perspective of any one stored pattern, the other patterns act as noise, and such noise limits the memory's storage capacity. The more similar the retrieval cues for two patterns are, the more the patterns interfere with each other in memory, and the harder it is to separate them on retrieval. A method is described of weighting the retrieval cues to reduce such interference and thus to improve the separability of patterns that have similar cues.

Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia.

PubMed

Cropley, Vanessa L; Bartholomeusz, Cali F; Wu, Peter; Wood, Stephen J; Proffitt, Tina; Brewer, Warrick J; Desmond, Patricia M; Velakoulis, Dennis; Pantelis, Christos

2015-11-30

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Declines in moose population density at Isle Royle National Park, MI, USA and accompanied changes in landscape patterns

USGS Publications Warehouse

De Jager, N. R.; Pastor, J.

2009-01-01

Ungulate herbivores create patterns of forage availability, plant species composition, and soil fertility as they range across large landscapes and consume large quantities of plant material. Over time, herbivore populations fluctuate, producing great potential for spatio-temporal landscape dynamics. In this study, we extend the spatial and temporal extent of a long-term investigation of the relationship of landscape patterns to moose foraging behavior at Isle Royale National Park, MI. We examined how patterns of browse availability and consumption, plant basal area, and soil fertility changed during a recent decline in the moose population. We used geostatistics to examine changes in the nature of spatial patterns in two valleys over 18 years and across short-range and long-range distance scales. Landscape patterns of available and consumed browse changed from either repeated patches or randomly distributed patches in 1988-1992 to random point distributions by 2007 after a recent record high peak followed by a rapid decline in the moose population. Patterns of available and consumed browse became decoupled during the moose population low, which is in contrast to coupled patterns during the earlier high moose population. Distributions of plant basal area and soil nitrogen availability also switched from repeated patches to randomly distributed patches in one valley and to random point distributions in the other valley. Rapid declines in moose population density may release vegetation and soil fertility from browsing pressure and in turn create random landscape patterns. ?? Springer Science+Business Media B.V. 2009.

Coherent diffraction imaging: consistency of the assembled three-dimensional distribution.

PubMed

Tegze, Miklós; Bortel, Gábor

2016-07-01

The short pulses of X-ray free-electron lasers can produce diffraction patterns with structural information before radiation damage destroys the particle. From the recorded diffraction patterns the structure of particles or molecules can be determined on the nano- or even atomic scale. In a coherent diffraction imaging experiment thousands of diffraction patterns of identical particles are recorded and assembled into a three-dimensional distribution which is subsequently used to solve the structure of the particle. It is essential to know, but not always obvious, that the assembled three-dimensional reciprocal-space intensity distribution is really consistent with the measured diffraction patterns. This paper shows that, with the use of correlation maps and a single parameter calculated from them, the consistency of the three-dimensional distribution can be reliably validated.

The Relationship between Distributed Leadership and Teachers' Academic Optimism

ERIC Educational Resources Information Center

Mascall, Blair; Leithwood, Kenneth; Straus, Tiiu; Sacks, Robin

2008-01-01

Purpose: The goal of this study was to examine the relationship between four patterns of distributed leadership and a modified version of a variable Hoy et al. have labeled "teachers' academic optimism." The distributed leadership patterns reflect the extent to which the performance of leadership functions is consciously aligned across…

Spray Distribution of Boomless Nozzles: The Boomjet 5880, Radiarc and Boom Buster

Treesearch

James H. Miller

1990-01-01

Abstract. The patterns of spray distribution are described for three boomless nozzlesthat arc commonly used, or have promise, for forestry applications: The BoomJet5880 cluster nozzle (Spraying Systems Co.), the Radiarc (Waldrum specialties ), and the Boom Buster (Evergreen Products). Spray distribution patterns were determined using regularly...

Legal and Illegal Patterns of Drug Distribution in the United States

ERIC Educational Resources Information Center

Caliguri, Joseph P.

1976-01-01

Along with large supply sources of legal and illegal drug substances, diversion and distribution systems have developed to feed and maintain the demand. This presentation provides information on the diverting of drugs from legal and illegal sources as well as the characteristics of the distribution patterns. (Author)

A view of Kanerva's sparse distributed memory

NASA Technical Reports Server (NTRS)

Denning, P. J.

1986-01-01

Pentti Kanerva is working on a new class of computers, which are called pattern computers. Pattern computers may close the gap between capabilities of biological organisms to recognize and act on patterns (visual, auditory, tactile, or olfactory) and capabilities of modern computers. Combinations of numeric, symbolic, and pattern computers may one day be capable of sustaining robots. The overview of the requirements for a pattern computer, a summary of Kanerva's Sparse Distributed Memory (SDM), and examples of tasks this computer can be expected to perform well are given.

Projected distributions and diversity of flightless ground beetles within the Australian Wet Tropics and their environmental correlates.

PubMed

Staunton, Kyran M; Robson, Simon K A; Burwell, Chris J; Reside, April E; Williams, Stephen E

2014-01-01

With the impending threat of climate change, greater understanding of patterns of species distributions and richness and the environmental factors driving them are required for effective conservation efforts. Species distribution models enable us to not only estimate geographic extents of species and subsequent patterns of species richness, but also generate hypotheses regarding environmental factors determining these spatial patterns. Projected changes in climate can then be used to predict future patterns of species distributions and richness. We created distribution models for most of the flightless ground beetles (Carabidae) within the Wet Tropics World Heritage Area of Australia, a major component of regionally endemic invertebrates. Forty-three species were modelled and the environmental correlates of these distributions and resultant patterns of species richness were examined. Flightless ground beetles generally inhabit upland areas characterised by stable, cool and wet environmental conditions. These distribution and richness patterns are best explained using the time-stability hypothesis as this group's primary habitat, upland rainforest, is considered to be the most stable regional habitat. Projected changes in distributions indicate that as upward shifts in distributions occur, species currently confined to lower and drier mountain ranges will be more vulnerable to climate change impacts than those restricted to the highest and wettest mountains. Distribution models under projected future climate change suggest that there will be reductions in range size, population size and species richness under all emission scenarios. Eighty-eight per cent of species modelled are predicted to decline in population size by over 80%, for the most severe emission scenario by the year 2080. These results suggest that flightless ground beetles are among the most vulnerable taxa to climate change impacts so far investigated in the Wet Tropics World Heritage Area. These findings have dramatic implications for all other flightless insect taxa and the future biodiversity of this region.

Projected Distributions and Diversity of Flightless Ground Beetles within the Australian Wet Tropics and Their Environmental Correlates

PubMed Central

Staunton, Kyran M.; Robson, Simon K. A.; Burwell, Chris J.; Reside, April E.; Williams, Stephen E.

2014-01-01

With the impending threat of climate change, greater understanding of patterns of species distributions and richness and the environmental factors driving them are required for effective conservation efforts. Species distribution models enable us to not only estimate geographic extents of species and subsequent patterns of species richness, but also generate hypotheses regarding environmental factors determining these spatial patterns. Projected changes in climate can then be used to predict future patterns of species distributions and richness. We created distribution models for most of the flightless ground beetles (Carabidae) within the Wet Tropics World Heritage Area of Australia, a major component of regionally endemic invertebrates. Forty-three species were modelled and the environmental correlates of these distributions and resultant patterns of species richness were examined. Flightless ground beetles generally inhabit upland areas characterised by stable, cool and wet environmental conditions. These distribution and richness patterns are best explained using the time-stability hypothesis as this group’s primary habitat, upland rainforest, is considered to be the most stable regional habitat. Projected changes in distributions indicate that as upward shifts in distributions occur, species currently confined to lower and drier mountain ranges will be more vulnerable to climate change impacts than those restricted to the highest and wettest mountains. Distribution models under projected future climate change suggest that there will be reductions in range size, population size and species richness under all emission scenarios. Eighty-eight per cent of species modelled are predicted to decline in population size by over 80%, for the most severe emission scenario by the year 2080. These results suggest that flightless ground beetles are among the most vulnerable taxa to climate change impacts so far investigated in the Wet Tropics World Heritage Area. These findings have dramatic implications for all other flightless insect taxa and the future biodiversity of this region. PMID:24586362

Elemental distribution patterns in the skins of false killer whales (Pseudorca crassidens) from a mass stranding in South Africa, analysed using micro-PIXE

NASA Astrophysics Data System (ADS)

Mouton, M.; Botha, A.; Thornton, M.; Mesjasz-Przybyłowicz, J.; Przybyłowicz, W. J.

2015-11-01

Several studies revealed that anthropogenic activities often cause toxic concentrations of some elements, such as mercury, which bio-accumulate through the marine food chain, impacting negatively on the health of animals in the top trophic levels, such as a variety of marine mammals. Moreover, analysis of cetacean skin has been reported to be a reliable, long-term and mostly non-invasive method to monitor bio-accumulation of chemicals in cetacean populations. Several elements, including trace elements, occur naturally in cetacean skin, although nothing is known about their distribution patterns and little about safe base line concentrations. In May 2009, 42 false killer whales (FKWs) beached and died at Kommetjie in the Western Cape of South Africa. Skin samples of these FKWs were collected and analysed to determine elemental distribution patterns. The concentrations and distribution patterns of the major, as well as detectable trace elements were determined in skin samples from ten randomly selected FKW individuals, using micro-PIXE (particle-induced X-ray emission) analysis. Results revealed differences between the distribution patterns of elements in the skin sections. Fe, for example, was found to be concentrated in the dermal papillae, whereas the highest Zn concentrations occurred in the epidermis and particularly in the epidermal papillae. Since these essential elements mediate factors such as host immunity, from skin integrity to humoral immunity, knowledge of their typical distribution patterns can be of great value in studies of bio-accumulation. This is the first report of micro-PIXE being employed to study elemental distribution in cetacean skin and the resulting elemental distribution maps can serve as reference in future environmental pollution studies.

Contrasting elevational diversity patterns for soil bacteria between two ecosystems divided by the treeline.

PubMed

Li, Guixiang; Xu, Guorui; Shen, Congcong; Tang, Yong; Zhang, Yuxin; Ma, Keming

2016-11-01

Above- and below-ground organisms are closely linked, but how elevational distribution pattern of soil microbes shifting across the treeline still remains unknown. Sampling of 140 plots with transect, we herein investigated soil bacterial distribution pattern from a temperate forest up to a subalpine meadow along an elevational gradient using Illumina sequencing. Our results revealed distinct elevational patterns of bacterial diversity above and below the treeline in responding to changes in soil conditions: a hollow elevational pattern in the forest (correlated with soil temperature, pH, and C:N ratio) and a significantly decreasing pattern in the meadow (correlated with soil pH, and available phosphorus). The bacterial community structure was also distinct between the forest and meadow, relating to soil pH in the forest and soil temperature in the meadow. Soil bacteria did not follow the distribution pattern of herb diversity, but bacterial community structure could be predicted by herb community composition. These results suggest that plant communities have an important influence on soil characteristics, and thus change the elevational distribution of soil bacteria. Our findings are useful for future assessments of climate change impacts on microbial community.

Biogeography of Anurans from the Poorly Known and Threatened Coastal Sandplains of Eastern Brazil.

PubMed

Xavier, Ariane Lima; Guedes, Thaís Barreto; Napoli, Marcelo Felgueiras

2015-01-01

The east coast of Brazil comprises an extensive area inserted in the Tropical Atlantic Domain and is represented by sandy plains of beach ridges commonly known as Restingas. The coastal environments are unique and house a rich amphibian fauna, the geographical distribution patterns of which are incipient. Biogeographical studies can explain the current distributional patterns and provide the identification of natural biogeographical units. These areas are important in elucidating the evolutionary history of the taxa and the areas where they occur. The aim of this study was to seek natural biogeographical units in the Brazilian sandy plains of beach ridges by means of distribution data of amphibians and to test the main predictions of the vicariance model to explain the patterns found. We revised and georeferenced data on the geographical distribution of 63 anuran species. We performed a search for latitudinal distribution patterns along the sandy coastal plains of Brazil using the non-metric multidimensional scaling method (NMDS) and the biotic element analysis to identify natural biogeographical units. The results showed a monotonic variation in anuran species composition along the latitudinal gradient with a break in the clinal pattern from 23°S to 25°S latitude (states of Rio de Janeiro to São Paulo). The major predictions of the vicariance model were corroborated by the detection of four biotic elements with significantly clustered distribution and by the presence of congeneric species distributed in distinct biotic elements. The results support the hypothesis that vicariance could be one of the factors responsible for the distribution patterns of the anuran communities along the sandy coastal plains of eastern Brazil. The results of the clusters are also congruent with the predictions of paleoclimatic models made for the Last Glacial Maximum of the Pleistocene, such as the presence of historical forest refugia and biogeographical patterns already detected for amphibians in the Atlantic Rainforest.

Relationship between Item Responses of Negative Affect Items and the Distribution of the Sum of the Item Scores in the General Population

PubMed Central

Kawasaki, Yohei; Ide, Kazuki; Akutagawa, Maiko; Yamada, Hiroshi; Furukawa, Toshiaki A.; Ono, Yutaka

2016-01-01

Background Several studies have shown that total depressive symptom scores in the general population approximate an exponential pattern, except for the lower end of the distribution. The Center for Epidemiologic Studies Depression Scale (CES-D) consists of 20 items, each of which may take on four scores: “rarely,” “some,” “occasionally,” and “most of the time.” Recently, we reported that the item responses for 16 negative affect items commonly exhibit exponential patterns, except for the level of “rarely,” leading us to hypothesize that the item responses at the level of “rarely” may be related to the non-exponential pattern typical of the lower end of the distribution. To verify this hypothesis, we investigated how the item responses contribute to the distribution of the sum of the item scores. Methods Data collected from 21,040 subjects who had completed the CES-D questionnaire as part of a Japanese national survey were analyzed. To assess the item responses of negative affect items, we used a parameter r, which denotes the ratio of “rarely” to “some” in each item response. The distributions of the sum of negative affect items in various combinations were analyzed using log-normal scales and curve fitting. Results The sum of the item scores approximated an exponential pattern regardless of the combination of items, whereas, at the lower end of the distributions, there was a clear divergence between the actual data and the predicted exponential pattern. At the lower end of the distributions, the sum of the item scores with high values of r exhibited higher scores compared to those predicted from the exponential pattern, whereas the sum of the item scores with low values of r exhibited lower scores compared to those predicted. Conclusions The distributional pattern of the sum of the item scores could be predicted from the item responses of such items. PMID:27806132

Biogeography of Anurans from the Poorly Known and Threatened Coastal Sandplains of Eastern Brazil

PubMed Central

Xavier, Ariane Lima; Guedes, Thaís Barreto; Napoli, Marcelo Felgueiras

2015-01-01

The east coast of Brazil comprises an extensive area inserted in the Tropical Atlantic Domain and is represented by sandy plains of beach ridges commonly known as Restingas. The coastal environments are unique and house a rich amphibian fauna, the geographical distribution patterns of which are incipient. Biogeographical studies can explain the current distributional patterns and provide the identification of natural biogeographical units. These areas are important in elucidating the evolutionary history of the taxa and the areas where they occur. The aim of this study was to seek natural biogeographical units in the Brazilian sandy plains of beach ridges by means of distribution data of amphibians and to test the main predictions of the vicariance model to explain the patterns found. We revised and georeferenced data on the geographical distribution of 63 anuran species. We performed a search for latitudinal distribution patterns along the sandy coastal plains of Brazil using the non-metric multidimensional scaling method (NMDS) and the biotic element analysis to identify natural biogeographical units. The results showed a monotonic variation in anuran species composition along the latitudinal gradient with a break in the clinal pattern from 23°S to 25°S latitude (states of Rio de Janeiro to São Paulo). The major predictions of the vicariance model were corroborated by the detection of four biotic elements with significantly clustered distribution and by the presence of congeneric species distributed in distinct biotic elements. The results support the hypothesis that vicariance could be one of the factors responsible for the distribution patterns of the anuran communities along the sandy coastal plains of eastern Brazil. The results of the clusters are also congruent with the predictions of paleoclimatic models made for the Last Glacial Maximum of the Pleistocene, such as the presence of historical forest refugia and biogeographical patterns already detected for amphibians in the Atlantic Rainforest. PMID:26047484

Age distribution patterns of human gene families: divergent for Gene Ontology categories and concordant between different subcellular localizations.

PubMed

Liu, Gangbiao; Zou, Yangyun; Cheng, Qiqun; Zeng, Yanwu; Gu, Xun; Su, Zhixi

2014-04-01

The age distribution of gene duplication events within the human genome exhibits two waves of duplications along with an ancient component. However, because of functional constraint differences, genes in different functional categories might show dissimilar retention patterns after duplication. It is known that genes in some functional categories are highly duplicated in the early stage of vertebrate evolution. However, the correlations of the age distribution pattern of gene duplication between the different functional categories are still unknown. To investigate this issue, we developed a robust pipeline to date the gene duplication events in the human genome. We successfully estimated about three-quarters of the duplication events within the human genome, along with the age distribution pattern in each Gene Ontology (GO) slim category. We found that some GO slim categories show different distribution patterns when compared to the whole genome. Further hierarchical clustering of the GO slim functional categories enabled grouping into two main clusters. We found that human genes located in the duplicated copy number variant regions, whose duplicate genes have not been fixed in the human population, were mainly enriched in the groups with a high proportion of recently duplicated genes. Moreover, we used a phylogenetic tree-based method to date the age of duplications in three signaling-related gene superfamilies: transcription factors, protein kinases and G-protein coupled receptors. These superfamilies were expressed in different subcellular localizations. They showed a similar age distribution as the signaling-related GO slim categories. We also compared the differences between the age distributions of gene duplications in multiple subcellular localizations. We found that the distribution patterns of the major subcellular localizations were similar to that of the whole genome. This study revealed the whole picture of the evolution patterns of gene functional categories in the human genome.

Kanerva's sparse distributed memory with multiple hamming thresholds

NASA Technical Reports Server (NTRS)

Pohja, Seppo; Kaski, Kimmo

1992-01-01

If the stored input patterns of Kanerva's Sparse Distributed Memory (SDM) are highly correlated, utilization of the storage capacity is very low compared to the case of uniformly distributed random input patterns. We consider a variation of SDM that has a better storage capacity utilization for correlated input patterns. This approach uses a separate selection threshold for each physical storage address or hard location. The selection of the hard locations for reading or writing can be done in parallel of which SDM implementations can benefit.

Habitat-based constraints on food web structure and parasite life cycles.

PubMed

Rossiter, Wayne; Sukhdeo, Michael V K

2014-04-01

Habitat is frequently implicated as a powerful determinant of community structure and species distributions, but few studies explicitly evaluate the relationship between habitat-based patterns of species' distributions and the presence or absence of trophic interactions. The complex (multi-host) life cycles of parasites are directly affected by these factors, but almost no data exist on the role of habitat in constraining parasite-host interactions at the community level. In this study the relationship(s) between species abundances, distributions and trophic interactions (including parasitism) were evaluated in the context of habitat structure (classic geomorphic designations of pools, riffles and runs) in a riverine community (Raritan River, Hunterdon County, NJ, USA). We report 121 taxa collected over a 2-year period, and compare the observed food web patterns to null model expectations. The results show that top predators are constrained to particular habitat types, and that species' distributions are biased towards pool habitats. However, our null model (which incorporates cascade model assumptions) accurately predicts the observed patterns of trophic interactions. Thus, habitat strongly dictates species distributions, and patterns of trophic interactions arise as a consequence of these distributions. Additionally, we find that hosts utilized in parasite life cycles are more overlapping in their distributions, and this pattern is more pronounced among those involved in trophic transmission. We conclude that habitat structure may be a strong predictor of parasite transmission routes, particularly within communities that occupy heterogeneous habitats.

[Biomass distribution patterns of Alnus hirsuta and Betula platyphylla-swamp ecotone communities in Changbai Mountains].

PubMed

Mu, Changcheng; Wan, Shucheng; Su, Ping; Song, Hongwen; Sun, Zhihu

2004-12-01

In order to reveal the growth patterns of dominant tree species and the distribution patterns of community biomass along the horizontal environmental gradients or among the vertical layers of communities in Changbai Mountains, this paper studied the biomass distribution patterns of Alnus hirsuta-swamp and Betula platyphylla-swamp ecotone communities. The results showed that there were some differences in growth rate and in adaptability to habitats between A. hirsuta and B. platyphylla. In the wetland habitats of the ecotone, A. hirsuta grew 1-2 times faster than B. platyphylla, but along the gradient from swamp to forest, it grew slowly, while B. platyphylla grew fast. Therefore, A. hirsuta was a favorite tree species in wetland habitats. The distribution pattern of organ biomass was similar between A. hirsute and B. platyphylla, the trunk being 1/2, tree root 1/4, branch 1/10, bark 1.5/20, and leaf 1/20. The vertical distribution pattern of biomass was also similar between A. hirsute-swamp and B. platyphylla-swamp ecotone communities, the tree, shrub, and herbage layer accounted for 87%-90%, 7%-9%, and 2%-3%, respectively in the whole ecotone communities. The community biomass increased linearly from swamp to forest with the change of environment factors.

Simulation of speckle patterns with pre-defined correlation distributions.

PubMed

Song, Lipei; Zhou, Zhen; Wang, Xueyan; Zhao, Xing; Elson, Daniel S

2016-03-01

We put forward a method to easily generate a single or a sequence of fully developed speckle patterns with pre-defined correlation distribution by utilizing the principle of coherent imaging. The few-to-one mapping between the input correlation matrix and the correlation distribution between simulated speckle patterns is realized and there is a simple square relationship between the values of these two correlation coefficient sets. This method is demonstrated both theoretically and experimentally. The square relationship enables easy conversion from any desired correlation distribution. Since the input correlation distribution can be defined by a digital matrix or a gray-scale image acquired experimentally, this method provides a convenient way to simulate real speckle-related experiments and to evaluate data processing techniques.

Simulation of speckle patterns with pre-defined correlation distributions

PubMed Central

Song, Lipei; Zhou, Zhen; Wang, Xueyan; Zhao, Xing; Elson, Daniel S.

2016-01-01

We put forward a method to easily generate a single or a sequence of fully developed speckle patterns with pre-defined correlation distribution by utilizing the principle of coherent imaging. The few-to-one mapping between the input correlation matrix and the correlation distribution between simulated speckle patterns is realized and there is a simple square relationship between the values of these two correlation coefficient sets. This method is demonstrated both theoretically and experimentally. The square relationship enables easy conversion from any desired correlation distribution. Since the input correlation distribution can be defined by a digital matrix or a gray-scale image acquired experimentally, this method provides a convenient way to simulate real speckle-related experiments and to evaluate data processing techniques. PMID:27231589

Evaluation of Potential Infectivity of Alzheimer and Parkinson Disease Proteins in Recipients of Cadaver-Derived Human Growth Hormone

PubMed Central

Irwin, David J.; Abrams, Joseph Y.; Schonberger, Lawrence B.; Leschek, Ellen Werber; Mills, James L.; Lee, Virginia M.-Y.; Trojanowski, John Q.

2013-01-01

Importance Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)–associated proteins (NDAPs) (ie, tau, Aβ, and α-synuclein) suggests possible similarities in the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND. Objective To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients. Design We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature. Setting University-based academic center and agencies of the US Department of Health and Human Services. Participants Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP. Main Outcome Measures Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database. Results We found mild amounts of pathological tau, Aβ, and α-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database. Conclusions and Relevance Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions. PMID:23380910

The Distributed Nature of Pattern Generalization

ERIC Educational Resources Information Center

Rivera, Ferdinand

2015-01-01

Drawing on a review of recent work conducted in the area of pattern generalization (PG), this paper makes a case for a distributed view of PG, which basically situates processing ability in terms of convergences among several different factors that influence PG. Consequently, the distributed nature leads to different types of PG that depend on the…

Mitochondrial distribution and activity in human mature oocytes: gonadotropin-releasing hormone agonist versus antagonist for pituitary down-regulation.

PubMed

Dell'Aquila, Maria Elena; Ambruosi, Barbara; De Santis, Teresa; Cho, Yoon Sung

2009-01-01

To analyze the effects of GnRH agonists versus antagonists on mitochondrial distribution and activity in human mature oocytes. Randomized research experimental study. Academic basic research laboratory and hospital-based fertility center. Two hundred twenty-five supernumerary mature oocytes from 44 patients. Fluorescent staining and confocal laser scanning microscopy on oocytes after the use of either GnRH agonist (group A) or GnRH antagonist (group B). Oocyte mitochondrial distribution pattern and activity using MitoTracker Orange CMTM Ros. More oocytes showing polarized mitochondrial distribution pattern were found in group A than in group B (35% vs. 14%). In group B, hCG rather than GnRH agonist, for ovulation induction, resulted in more oocytes showing heterogeneous (57% vs. 14%), in particular polarized (24% vs. 0) mitochondrial distribution. In groups A and B, fluorescence intensity did not vary according to mitochondrial distribution pattern. However, fluorescence intensity was higher in oocytes with polarized and large granules configurations in group B compared to group A. The GnRH agonist and antagonist may have different effects on oocyte mitochondrial distribution pattern and activity. The GnRH antagonist may induce mitochondrial hyperactivity, which may be detrimental to the oocyte.

Using ordinal partition transition networks to analyze ECG data

NASA Astrophysics Data System (ADS)

Kulp, Christopher W.; Chobot, Jeremy M.; Freitas, Helena R.; Sprechini, Gene D.

2016-07-01

Electrocardiogram (ECG) data from patients with a variety of heart conditions are studied using ordinal pattern partition networks. The ordinal pattern partition networks are formed from the ECG time series by symbolizing the data into ordinal patterns. The ordinal patterns form the nodes of the network and edges are defined through the time ordering of the ordinal patterns in the symbolized time series. A network measure, called the mean degree, is computed from each time series-generated network. In addition, the entropy and number of non-occurring ordinal patterns (NFP) is computed for each series. The distribution of mean degrees, entropies, and NFPs for each heart condition studied is compared. A statistically significant difference between healthy patients and several groups of unhealthy patients with varying heart conditions is found for the distributions of the mean degrees, unlike for any of the distributions of the entropies or NFPs.

Magnitude and Spatial Distribution of Impact Intensity Under the Foot Relates to Initial Foot Contact Pattern.

PubMed

Breine, Bastiaan; Malcolm, Philippe; Segers, Veerle; Gerlo, Joeri; Derie, Rud; Pataky, Todd; Frederick, Edward C; De Clercq, Dirk

2017-12-01

In running, foot contact patterns (rear-, mid-, or forefoot contact) influence impact intensity and initial ankle and foot kinematics. The aim of the study was to compare impact intensity and its spatial distribution under the foot between different foot contact patterns. Forty-nine subjects ran at 3.2 m·s -1 over a level runway while ground reaction forces (GRF) and shoe-surface pressures were recorded and foot contact pattern was determined. A 4-zone footmask (forefoot, midfoot, medial and lateral rearfoot) assessed the spatial distribution of the vertical GRF under the foot. We calculated peak vertical instantaneous loading rate of the GRF (VILR) per foot zone as the impact intensity measure. Midfoot contact patterns were shown to have the lowest, and atypical rearfoot contact patterns the highest impact intensities, respectively. The greatest local impact intensity was mainly situated under the rear- and midfoot for the typical rearfoot contact patterns, under the midfoot for the atypical rearfoot contact patterns, and under the mid- and forefoot for the midfoot contact patterns. These findings indicate that different foot contact patterns could benefit from cushioning in different shoe zones.

Sharpness of interference pattern of the 3-pole wiggler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dejus, Roger J., E-mail: dejus@aps.anl.gov; Kim, Kwang-Je

2016-07-27

Due to the small emittance, radiation from neighboring poles of a strong wiggler in future multi-bend achromat-based storage rings can exhibit sharp interference patterns. The spectral-angular distributions of the 3-pole wiggler for the proposed Advanced Photon Source (APS) upgrade were computed and prominent interference patterns were found. In this paper we provide an understanding of such interference patterns. The equations governing the interference pattern are described and computed spectral-angular distributions of a modeled 3-pole wiggler magnetic field using these equations are presented.

Sharpness of Interference Pattern of the 3-Pole Wiggler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dejus, Roger J.; Kim, Kwang-Je

2016-07-02

Due to the small emittance, radiation from neighboring poles of a strong wiggler in future multi-bend achromat-based storage rings can exhibit sharp interference patterns. The spectral-angular distributions of the 3-pole wiggler for the proposed Advanced Photon Source (APS) upgrade were computed and prominent interference patterns were found. In this paper we provide an understanding of such interference patterns. The equations governing the interference pattern are described and computed spectral-angular distributions of a modeled 3-pole wiggler magnetic field using these equations are presented.

[Effects of topography on the diversity and distribution pattern of ground plants in karst montane forests in Southwest Guangxi, China].

PubMed

Yuan, Tie-Xiang; Zhang, He-Ping; Ou, Zhi-Yang; Tan, Yi-Bo

2014-10-01

Covariance analysis, curve-fitting, and canonical correspondence analysis (CCA) were used to explore the effects of topographic factors on the plant diversity and distribution patterns of ground flora with different growth forms in the karst mountains of Southwest Guangxi, China. A total of 152 ground plants were recorded. Among them, 37 species were ferns, 44 species herbs, 9 species lianas, and 62 species shrubs. Covariance analysis revealed that altitude significantly correlated with the individual number and richness of ground plants, and slope aspect had a significant effect on richness. Statistical analyses showed a highly significant nonlinear correlation between the individual number or richness of ground plants and altitude. Results of CCA revealed that slope aspect had a significant effect on the distribution pattern of ferns, and slope had a significant effect on the distribution patterns of herbs, lianas and shrubs. Ferns were more sensitive than herbs, lianas and shrubs to changes in heat and soil water caused by aspect. The effect of slope was stronger than that of elevation on soil water and nutrients, and it was the most important topographic factor that affected the distribution patterns of herbs, lianas and shrubs in this region.

The impact of fracking on freight distribution patterns.

DOT National Transportation Integrated Search

2016-11-01

The increasing production of domestic energy through the use of fracking will likely alter local/regional/national economies and corresponding freight distribution patterns (highway, rail, marine, pipeline) in the United States. The proposed project ...

Spatial distribution patterns of soil mite communities and their relationships with edaphic factors in a 30-year tillage cornfield in northeast China.

PubMed

Liu, Jie; Gao, Meixiang; Liu, Jinwen; Guo, Yuxi; Liu, Dong; Zhu, Xinyu; Wu, Donghui

2018-01-01

Spatial distribution is an important topic in community ecology and a key to understanding the structure and dynamics of populations and communities. However, the available information related to the spatial patterns of soil mite communities in long-term tillage agroecosystems remains insufficient. In this study, we examined the spatial patterns of soil mite communities to explain the spatial relationships between soil mite communities and soil parameters. Soil fauna were sampled three times (August, September and October 2015) at 121 locations arranged regularly within a 400 m × 400 m monitoring plot. Additionally, we estimated the physical and chemical parameters of the same sampling locations. The distribution patterns of the soil mite community and the edaphic parameters were analyzed using a range of geostatistical tools. Moran's I coefficient showed that, during each sampling period, the total abundance of the soil mite communities and the abundance of the dominant mite populations were spatially autocorrelated. The soil mite communities demonstrated clear patchy distribution patterns within the study plot. These patterns were sampling period-specific. Cross-semivariograms showed both negative and positive cross-correlations between soil mite communities and environmental factors. Mantel tests showed a significant and positive relationship between soil mite community and soil organic matter and soil pH only in August. This study demonstrated that in the cornfield, the soil mite distribution exhibited strong or moderate spatial dependence, and the mites formed patches with sizes less than one hundred meters. In addition, in this long-term tillage agroecosystem, soil factors had less influence on the observed pattern of soil mite communities. Further experiments that take into account human activity and spatial factors should be performed to study the factors that drive the spatial distribution of soil microarthropods.

Sediment-hosted contaminants and distribution patterns in the Mississippi and Atchafalaya River Deltas

USGS Publications Warehouse

Flocks, James G.; Kindinger, Jack G.; Ferina, Nicholas; Dreher, Chandra

2002-01-01

The Mississippi and Atchafalaya Rivers transport very large amounts of bedload and suspended sediments to the deltaic and coastal environments of the northern Gulf of Mexico. Absorbed onto these sediments are contaminants that may be detrimental to the environment. To adequately assess the impact of these contaminants it is first necessary to develop an understanding of sediment distribution patterns in these deltaic systems. The distribution patterns are defined by deltaic progradational cycles. Once these patterns are identified, the natural and industrial contaminant inventories and their depositional histories can be reconstructed. Delta progradation is a function of sediment discharge, as well as channel and receiving-basin dimensions. Fluvial energy controls the sediment distribution pattern, resulting in a coarse grained or sandy framework, infilled with finer grained material occupying the overbank, interdistributary bays, wetlands and abandoned channels. It has been shown that these fine-grained sediments can carry contaminants through absorption and intern them in the sediment column or redistribute them depending on progradation or degradation of the delta deposit. Sediment distribution patterns in delta complexes can be determined through high-resolution geophysical surveys and groundtruthed with direct sampling. In the Atchafalaya and Mississippi deltas, remote sensing using High-Resolution Single-Channel Seismic Profiling (HRSP) and Sidescan Sonar was correlated to 20-ft vibracores to develop a near-surface geologic framework that identifies variability in recent sediment distribution patterns. The surveys identified bedload sand waves, abandoned-channel back-fill, prodelta and distributary mouth bars within the most recently active portions of the deltas. These depositional features respond to changes in deltaic processes and through their response may intern or transport absorbed contaminants. Characterizing these features provides insight into the fate of sediment-hosted contaminants.

PCI bus content-addressable-memory (CAM) implementation on FPGA for pattern recognition/image retrieval in a distributed environment

NASA Astrophysics Data System (ADS)

Megherbi, Dalila B.; Yan, Yin; Tanmay, Parikh; Khoury, Jed; Woods, C. L.

2004-11-01

Recently surveillance and Automatic Target Recognition (ATR) applications are increasing as the cost of computing power needed to process the massive amount of information continues to fall. This computing power has been made possible partly by the latest advances in FPGAs and SOPCs. In particular, to design and implement state-of-the-Art electro-optical imaging systems to provide advanced surveillance capabilities, there is a need to integrate several technologies (e.g. telescope, precise optics, cameras, image/compute vision algorithms, which can be geographically distributed or sharing distributed resources) into a programmable system and DSP systems. Additionally, pattern recognition techniques and fast information retrieval, are often important components of intelligent systems. The aim of this work is using embedded FPGA as a fast, configurable and synthesizable search engine in fast image pattern recognition/retrieval in a distributed hardware/software co-design environment. In particular, we propose and show a low cost Content Addressable Memory (CAM)-based distributed embedded FPGA hardware architecture solution with real time recognition capabilities and computing for pattern look-up, pattern recognition, and image retrieval. We show how the distributed CAM-based architecture offers a performance advantage of an order-of-magnitude over RAM-based architecture (Random Access Memory) search for implementing high speed pattern recognition for image retrieval. The methods of designing, implementing, and analyzing the proposed CAM based embedded architecture are described here. Other SOPC solutions/design issues are covered. Finally, experimental results, hardware verification, and performance evaluations using both the Xilinx Virtex-II and the Altera Apex20k are provided to show the potential and power of the proposed method for low cost reconfigurable fast image pattern recognition/retrieval at the hardware/software co-design level.

Flexible Micro-and Nano-Patterning Tools for Photonics

DTIC Science & Technology

2016-03-10

AFRL-AFOSR-VA-TR-2016-0125 Flexible Micro- and Nano -Patterning Tools for Photonics Henry Smith LUMARRAY INC. 15 WARD ST. SOMERVILLE, MA 21434228 03...14-01-2015 4.  TITLE AND SUBTITLE Flexible Micro- and Nano -Patterning Tools for Photonics - OSD STTR Phase 2 5a.  CONTRACT NUMBER FA9550-12-C-0082 5b...2016https://livelink.ebs.afrl.af.mil/livelink/llisapi.dll DISTRIBUTION A: Distribution approved for public release. FLEXIBLE MICRO- AND NANO - PATTERNING

Species richness of Eurasian Zephyrus hairstreaks (Lepidoptera: Lycaenidae: Theclini) with implications on historical biogeography: An NDM/VNDM approach

PubMed Central

Yago, Masaya; Settele, Josef; Li, Xiushan; Ueshima, Rei; Grishin, Nick V.; Wang, Min

2018-01-01

Aim A database based on distributional records of Eurasian Zephyrus hairstreaks (Lepidoptera: Lycaenidae: Theclini) was compiled to analyse their areas of endemism (AoEs), species richness and distribution patterns, to explore their locations of past glacial refugia and dispersal routes. Methods Over 2000 Zephyrus hairstreaks occurrences are analysed using the NDM/VNDM algorithm, for the recognition of AoEs. Species richness was calculated by using the option ‘Number of different classes’ to count the different classes of a variable presented in each 3.0°×3.0° grid cell, and GIS software was used to visualize distribution patterns of endemic species. Results Centres of species richness of Zephyrus hairstreaks are situated in the eastern Qinghai-Tibet Plateau (EQTP), Hengduan Mountain Region (HDMR) and the Qinling Mountain Region (QLMR). Latitudinal gradients in species richness show normal distribution with the peak between 25° N and 35° N in the temperate zone, gradually decreasing towards the poles. Moreover, most parts of central and southern China, especially the area of QLMR-EQTP-HDMR, were identified as AoEs that may have played a significant role as refugia during Quaternary global cooling. There are four major distributional patterns of Zephyrus hairstreaks in Eurasia: Sino-Japanese, Sino-Himalayan, high-mountain and a combined distribution covering all three patterns. Conclusions Zephyrus hairstreaks probably originated at least 23–24 Myr ago in E. Asia between 25° N to 35° N in the temperate zone. Cenozoic orogenies caused rapid speciation of this tribe and extrusion of the Indochina block resulted in vicariance between the Sino-Japanese and the Sino-Himalayan patterns. The four distribution patterns provided two possible dispersal directions: Sino-Japanese dispersal and Sino-Himalayan dispersal. PMID:29351314

Species richness of Eurasian Zephyrus hairstreaks (Lepidoptera: Lycaenidae: Theclini) with implications on historical biogeography: An NDM/VNDM approach.

PubMed

Zhuang, Hailing; Yago, Masaya; Settele, Josef; Li, Xiushan; Ueshima, Rei; Grishin, Nick V; Wang, Min

2018-01-01

A database based on distributional records of Eurasian Zephyrus hairstreaks (Lepidoptera: Lycaenidae: Theclini) was compiled to analyse their areas of endemism (AoEs), species richness and distribution patterns, to explore their locations of past glacial refugia and dispersal routes. Over 2000 Zephyrus hairstreaks occurrences are analysed using the NDM/VNDM algorithm, for the recognition of AoEs. Species richness was calculated by using the option 'Number of different classes' to count the different classes of a variable presented in each 3.0°×3.0° grid cell, and GIS software was used to visualize distribution patterns of endemic species. Centres of species richness of Zephyrus hairstreaks are situated in the eastern Qinghai-Tibet Plateau (EQTP), Hengduan Mountain Region (HDMR) and the Qinling Mountain Region (QLMR). Latitudinal gradients in species richness show normal distribution with the peak between 25° N and 35° N in the temperate zone, gradually decreasing towards the poles. Moreover, most parts of central and southern China, especially the area of QLMR-EQTP-HDMR, were identified as AoEs that may have played a significant role as refugia during Quaternary global cooling. There are four major distributional patterns of Zephyrus hairstreaks in Eurasia: Sino-Japanese, Sino-Himalayan, high-mountain and a combined distribution covering all three patterns. Zephyrus hairstreaks probably originated at least 23-24 Myr ago in E. Asia between 25° N to 35° N in the temperate zone. Cenozoic orogenies caused rapid speciation of this tribe and extrusion of the Indochina block resulted in vicariance between the Sino-Japanese and the Sino-Himalayan patterns. The four distribution patterns provided two possible dispersal directions: Sino-Japanese dispersal and Sino-Himalayan dispersal.

Distribution patterns of microcalcifications in suspected thyroid carcinoma: a classification method helpful for diagnosis.

PubMed

Ning, Chun-Ping; Ji, Qing-Lian; Fang, Shi-Bao; Wang, Hong-Qiao; Zhong, Yan-Mi; Niu, Hai-Tao

2018-06-01

The aim of this study was to compare the distribution patterns of microcalcifications in thyroid cancers with benign cases. In total, 358 patients having microcalcifications on ultrasonography were analysed. Microcalcifications were categorised according to the distribution patterns: (I) microcalcifications inside one (a) or more (b) suspected nodules, (II) microcalcifications not only inside but also surrounding a suspected single (a) or multiple (b) nodules, and (III) focal (a) or diffuse (b) microcalcifications in the absence of any suspected nodule. Differences in distribution patterns of microcalcifications in benign and malignant thyroid lesions were compared. We found that the distribution patterns of microcalcifications differed between malignant (n = 325) and benign lesions (n = 117) (X 2 = 9.926, p < 0.01). Benign lesions were classified as type Ia (66.7%), type Ib (29.1%) or type IIIa (4.3%). The specificity of type II and type IIIb in diagnosing malignant cases was 100%. Among malignant lesions, 172 locations were classified as type Ia, 106 as type Ib, 12 as type IIa, 7 as IIb, 7 as type IIIa and 19 as type IIIb. Accompanying Hashimoto thyroiditis was most frequent in type III (51.6%). Types II and IIIb are highly specific for cancer detection. Microcalcifications outside a nodule and those detected in the absence of any nodule should therefore be reviewed carefully in clinical practice. • A method to classify distribution patterns of thyroid microcalcifications is presented. • Distribution features of microcalcifications are useful for diagnosing thyroid cancers. • Microcalcifications outside a suspicious nodule are highly specific for thyroid cancers. • Microcalcifications without suspicious nodules should also alert the physician to thyroid cancers.

Distribution of Articles in Written Composition among Malaysian ESL Learners

ERIC Educational Resources Information Center

Rahim, Mia Emily Abdul; Rahim, Emma Marini Abdul; Ning, Chia Han

2013-01-01

The study aimed to investigate the distribution patterns of the English grammar articles (a, an, and the) as well as the distributions of their colligation patterns in written compositions of English among Malaysian ESL learners. This paper reports the results of a corpus-based study on articles used by these learners. The method used in this…

Algorithms for Hidden Markov Models Restricted to Occurrences of Regular Expressions

PubMed Central

Tataru, Paula; Sand, Andreas; Hobolth, Asger; Mailund, Thomas; Pedersen, Christian N. S.

2013-01-01

Hidden Markov Models (HMMs) are widely used probabilistic models, particularly for annotating sequential data with an underlying hidden structure. Patterns in the annotation are often more relevant to study than the hidden structure itself. A typical HMM analysis consists of annotating the observed data using a decoding algorithm and analyzing the annotation to study patterns of interest. For example, given an HMM modeling genes in DNA sequences, the focus is on occurrences of genes in the annotation. In this paper, we define a pattern through a regular expression and present a restriction of three classical algorithms to take the number of occurrences of the pattern in the hidden sequence into account. We present a new algorithm to compute the distribution of the number of pattern occurrences, and we extend the two most widely used existing decoding algorithms to employ information from this distribution. We show experimentally that the expectation of the distribution of the number of pattern occurrences gives a highly accurate estimate, while the typical procedure can be biased in the sense that the identified number of pattern occurrences does not correspond to the true number. We furthermore show that using this distribution in the decoding algorithms improves the predictive power of the model. PMID:24833225

[Spatial point patterns of Antarctic krill fishery in the northern Antarctic Peninsula].

PubMed

Yang, Xiao Ming; Li, Yi Xin; Zhu, Guo Ping

2016-12-01

As a key species in the Antarctic ecosystem, the spatial distribution of Antarctic krill (thereafter krill) often tends to present aggregation characteristics, which therefore reflects the spatial patterns of krill fishing operation. Based on the fishing data collected from Chinese krill fishing vessels, of which vessel A was professional krill fishing vessel and Vessel B was a fishing vessel which shifted between Chilean jack mackerel (Trachurus murphyi) fishing ground and krill fishing ground. In order to explore the characteristics of spatial distribution pattern and their ecological effects of two obvious different fishing fleets under a high and low nominal catch per unit effort (CPUE), from the viewpoint of spatial point pattern, the present study analyzed the spatial distribution characteristics of krill fishery in the northern Antarctic Peninsula from three aspects: (1) the two vessels' point pattern characteristics of higher CPUEs and lower CPUEs at different scales; (2) correlation of the bivariate point patterns between these points of higher CPUE and lower CPUE; and (3) correlation patterns of CPUE. Under the analysis derived from the Ripley's L function and mark correlation function, the results showed that the point patterns of the higher/lo-wer catch available were similar, both showing an aggregation distribution in this study windows at all scale levels. The aggregation intensity of krill fishing was nearly maximum at 15 km spatial scale, and kept stably higher values at the scale of 15-50 km. The aggregation intensity of krill fishery point patterns could be described in order as higher CPUE of vessel A > lower CPUE of vessel B >higher CPUE of vessel B > higher CPUE of vessel B. The relationship of the higher and lo-wer CPUEs of vessel A showed positive correlation at the spatial scale of 0-75 km, and presented stochastic relationship after 75 km scale, whereas vessel B showed positive correlation at all spatial scales. The point events of higher and lower CPUEs were synchronized, showing significant correlations at most of spatial scales because of the dynamics nature and complex of krill aggregation patterns. The distribution of vessel A's CPUEs was positively correlated at scales of 0-44 km, but negatively correlated at the scales of 44-80 km. The distribution of vessel B's CPUEs was negatively correlated at the scales of 50-70 km, but no significant correlations were found at other scales. The CPUE mark point patterns showed a negative correlation, which indicated that intraspecific competition for space and prey was significant. There were significant differences in spatial point pattern distribution between vessel A with higher fishing capacity and vessel B with lower fishing capacity. The results showed that the professional krill fishing vessel is suitable to conduct the analysis of spatial point pattern and scientific fishery survey.

Distribution pattern of public transport passenger in Yogyakarta, Indonesia

NASA Astrophysics Data System (ADS)

Narendra, Alfa; Malkhamah, Siti; Sopha, Bertha Maya

2018-03-01

The arrival and departure distribution pattern of Trans Jogja bus passenger is one of the fundamental model for simulation. The purpose of this paper is to build models of passengers flows. This research used passengers data from January to May 2014. There is no policy that change the operation system affecting the nature of this pattern nowadays. The roads, buses, land uses, schedule, and people are relatively still the same. The data then categorized based on the direction, days, and location. Moreover, each category was fitted into some well-known discrete distributions. Those distributions are compared based on its AIC value and BIC. The chosen distribution model has the smallest AIC and BIC value and the negative binomial distribution found has the smallest AIC and BIC value. Probability mass function (PMF) plots of those models were compared to draw generic model from each categorical negative binomial distribution models. The value of accepted generic negative binomial distribution is 0.7064 and 1.4504 of mu. The minimum and maximum passenger vector value of distribution are is 0 and 41.

[Spatial distribution pattern of Chilo suppressalis analyzed by classical method and geostatistics].

PubMed

Yuan, Zheming; Fu, Wei; Li, Fangyi

2004-04-01

Two original samples of Chilo suppressalis and their grid, random and sequence samples were analyzed by classical method and geostatistics to characterize the spatial distribution pattern of C. suppressalis. The limitations of spatial distribution analysis with classical method, especially influenced by the original position of grid, were summarized rather completely. On the contrary, geostatistics characterized well the spatial distribution pattern, congregation intensity and spatial heterogeneity of C. suppressalis. According to geostatistics, the population was up to Poisson distribution in low density. As for higher density population, its distribution was up to aggregative, and the aggregation intensity and dependence range were 0.1056 and 193 cm, respectively. Spatial heterogeneity was also found in the higher density population. Its spatial correlativity in line direction was more closely than that in row direction, and the dependence ranges in line and row direction were 115 and 264 cm, respectively.

Time of Day and Day of Week Trends in EMS Demand.

PubMed

Cantwell, Kate; Morgans, Amee; Smith, Karen; Livingston, Michael; Spelman, Tim; Dietze, Paul

2015-01-01

We examined temporal variations in overall Emergency Medical Services (EMS) demand, as well as medical and trauma cases separately. We analyzed cases according to time of day and day of week to determine whether population level demand demonstrates temporal patterns that will increase baseline knowledge for EMS planning. We conducted a secondary analysis of data from the Ambulance Victoria data warehouse covering the period 2008-2011. We included all cases of EMS attendance which resulted in 1,203,803 cases for review. Data elements comprised age, gender, date and time of call to the EMS emergency number along with the clinical condition of the patient. We employed Poisson regression to analyze case numbers and trigonometric regression to quantify distribution patterns. EMS demand exhibited a bimodal distribution with the highest peak at 10:00 and a second smaller peak at 19:00. The highest number of cases occurred on Fridays, and the lowest on Tuesdays and Wednesdays. However, the distribution of cases throughout the day differed by day of week. Distribution patterns on Fridays, Saturdays and Sundays differed significantly from the rest of the week (p < 0.001). When categorized into medical or trauma cases, medical cases were more frequent during working hours and involved patients of higher mean age (57 years vs. 49 years for trauma, p < 0.001). Trauma cases peaked on Friday and Saturday nights around midnight. Day of week EMS demand distribution patterns reveal differences that can be masked in aggregate data. Day of week EMS demand distribution patterns showed not only which days have differences in demand but the times of day at which the demand changes. Patterns differed by case type as well. These differences in distribution are important for EMS demand planning. Increased understanding of EMS demand patterns is imperative in a climate of ever-increasing demand and fiscal constraints. Further research is needed into the effect of age and case type on EMS demand.

Ceramic matrix composite article and process of fabricating a ceramic matrix composite article

DOEpatents

Cairo, Ronald Robert; DiMascio, Paul Stephen; Parolini, Jason Robert

2016-01-12

A ceramic matrix composite article and a process of fabricating a ceramic matrix composite are disclosed. The ceramic matrix composite article includes a matrix distribution pattern formed by a manifold and ceramic matrix composite plies laid up on the matrix distribution pattern, includes the manifold, or a combination thereof. The manifold includes one or more matrix distribution channels operably connected to a delivery interface, the delivery interface configured for providing matrix material to one or more of the ceramic matrix composite plies. The process includes providing the manifold, forming the matrix distribution pattern by transporting the matrix material through the manifold, and contacting the ceramic matrix composite plies with the matrix material.

Spatial pattern of Baccharis platypoda shrub as determined by sex and life stages

NASA Astrophysics Data System (ADS)

Fonseca, Darliana da Costa; de Oliveira, Marcio Leles Romarco; Pereira, Israel Marinho; Gonzaga, Anne Priscila Dias; de Moura, Cristiane Coelho; Machado, Evandro Luiz Mendonça

2017-11-01

Spatial patterns of dioecious species can be determined by their nutritional requirements and intraspecific competition, apart from being a response to environmental heterogeneity. The aim of the study was to evaluate the spatial pattern of populations of a dioecious shrub reporting to sex and reproductive stage patterns of individuals. Sampling was carried out in three areas located in the meridional portion of Serra do Espinhaço, where in individuals of the studied species were mapped. The spatial pattern was determined through O-ring analysis and Ripley's K-function and the distribution of individuals' frequencies was verified through x2 test. Populations in two areas showed an aggregate spatial pattern tending towards random or uniform according to the observed scale. Male and female adults presented an aggregate pattern at smaller scales, while random and uniform patterns were verified above 20 m for individuals of both sexes of the areas A2 and A3. Young individuals presented an aggregate pattern in all areas and spatial independence in relation to adult individuals, especially female plants. The interactions between individuals of both genders presented spatial independence with respect to spatial distribution. Baccharis platypoda showed characteristics in accordance with the spatial distribution of savannic and dioecious species, whereas the population was aggregated tending towards random at greater spatial scales. Young individuals showed an aggregated pattern at different scales compared to adults, without positive association between them. Female and male adult individuals presented similar characteristics, confirming that adult individuals at greater scales are randomly distributed despite their distinct preferences for environments with moisture variation.

Research on the Spatial-Temporal Distribution Pattern of the Network Attention of Fog and Haze in China

NASA Astrophysics Data System (ADS)

Weng, Lingyan; Han, Xugao

2018-01-01

Understanding the spatial-temporal distribution pattern of fog and haze is the base to deal with them by adjusting measures to local conditions. Taking 31 provinces in China mainland as the research areas, this paper collected data from Baidu index on the network attention of fog and haze in relevant areas from 2011 to 2016, and conducted an analysis of their spatial-temporal distribution pattern by using autocorrelation analysis. The results show that the network attention of fog and haze has an overall spatial distribution pattern of “higher in the eastern and central, lower in the western China”. There are regional differences in different provinces in terms of network attention. Network attention of fog and haze indicates an obvious geographical agglomeration phenomenon, which is a gradual enlargement of the agglomeration area of higher value with a slight shrinking of those lower value agglomeration areas.

Comparative study of cocoa black ants temporal population distribution utilizing geospatial analysis

NASA Astrophysics Data System (ADS)

Adnan, N. A.; Bakar, S.; Mazlan, A. H.; Yusoff, Z. Mohd; Rasam, A. R. Abdul

2018-02-01

Cocoa plantation also subjected to diseases and pests infestation. Some pests not only reduced the yield but also inhibit the growth of trees. Therefore, the Malaysia Cocoa Board (MCB) has explored Cocoa Black Ants (CBA) as one of their biological control mechanism to reduce the pest infestation of the Cocoa Pod Borer (CPB). CPB is capable to cause damage to cocoa beans, and later on will reduce the quality of dried cocoa beans. This study tries to integrate the use of geospatial analysis in understanding population distribution pattern of CBA to enhance its capability in controlling CPB infestation. Two objectives of the study are i) to generate temporal CBA distribution of cocoa plantation for two different blocks, and ii) to compare visually the CBA population distribution pattern with the aid of geospatial technique. This study managed to find the CBA population pattern which indicated spatially modest amount of low pattern distribution in February of 2007 until reaching the highest levels of ant populations in September 2007 and decreasing by the end of the year in 2009 for two different blocks (i.e 10B and 18A). Therefore, the usage of GIS is important to explain the CBA pattern population in the mature cocoa field. This finding might to be used as an indicator to examine the optimum distribution of CBA, which needed as a biological control agent against the CPB in the future.

Pattern analysis of total item score and item response of the Kessler Screening Scale for Psychological Distress (K6) in a nationally representative sample of US adults

PubMed Central

Kawasaki, Yohei; Ide, Kazuki; Akutagawa, Maiko; Yamada, Hiroshi; Yutaka, Ono; Furukawa, Toshiaki A.

2017-01-01

Background Several recent studies have shown that total scores on depressive symptom measures in a general population approximate an exponential pattern except for the lower end of the distribution. Furthermore, we confirmed that the exponential pattern is present for the individual item responses on the Center for Epidemiologic Studies Depression Scale (CES-D). To confirm the reproducibility of such findings, we investigated the total score distribution and item responses of the Kessler Screening Scale for Psychological Distress (K6) in a nationally representative study. Methods Data were drawn from the National Survey of Midlife Development in the United States (MIDUS), which comprises four subsamples: (1) a national random digit dialing (RDD) sample, (2) oversamples from five metropolitan areas, (3) siblings of individuals from the RDD sample, and (4) a national RDD sample of twin pairs. K6 items are scored using a 5-point scale: “none of the time,” “a little of the time,” “some of the time,” “most of the time,” and “all of the time.” The pattern of total score distribution and item responses were analyzed using graphical analysis and exponential regression model. Results The total score distributions of the four subsamples exhibited an exponential pattern with similar rate parameters. The item responses of the K6 approximated a linear pattern from “a little of the time” to “all of the time” on log-normal scales, while “none of the time” response was not related to this exponential pattern. Discussion The total score distribution and item responses of the K6 showed exponential patterns, consistent with other depressive symptom scales. PMID:28289560

Current and Future Patterns of Global Marine Mammal Biodiversity

PubMed Central

Kaschner, Kristin; Tittensor, Derek P.; Ready, Jonathan; Gerrodette, Tim; Worm, Boris

2011-01-01

Quantifying the spatial distribution of taxa is an important prerequisite for the preservation of biodiversity, and can provide a baseline against which to measure the impacts of climate change. Here we analyse patterns of marine mammal species richness based on predictions of global distributional ranges for 115 species, including all extant pinnipeds and cetaceans. We used an environmental suitability model specifically designed to address the paucity of distributional data for many marine mammal species. We generated richness patterns by overlaying predicted distributions for all species; these were then validated against sightings data from dedicated long-term surveys in the Eastern Tropical Pacific, the Northeast Atlantic and the Southern Ocean. Model outputs correlated well with empirically observed patterns of biodiversity in all three survey regions. Marine mammal richness was predicted to be highest in temperate waters of both hemispheres with distinct hotspots around New Zealand, Japan, Baja California, the Galapagos Islands, the Southeast Pacific, and the Southern Ocean. We then applied our model to explore potential changes in biodiversity under future perturbations of environmental conditions. Forward projections of biodiversity using an intermediate Intergovernmental Panel for Climate Change (IPCC) temperature scenario predicted that projected ocean warming and changes in sea ice cover until 2050 may have moderate effects on the spatial patterns of marine mammal richness. Increases in cetacean richness were predicted above 40° latitude in both hemispheres, while decreases in both pinniped and cetacean richness were expected at lower latitudes. Our results show how species distribution models can be applied to explore broad patterns of marine biodiversity worldwide for taxa for which limited distributional data are available. PMID:21625431

Thin-section computed tomography findings in 104 immunocompetent patients with adenovirus pneumonia.

PubMed

Park, Chan Kue; Kwon, Hoon; Park, Ji Young

2017-08-01

Background To date, there has been no computed tomography (CT) evaluation of adenovirus pneumonia in a large number of immunocompetent patients. Purpose To describe the thin-section CT findings of immunocompetent patients with adenovirus pneumonia. Material and Methods We prospectively enrolled 104 patients with adenovirus pneumonia from a military hospital. CT scans of each patient were retrospectively and independently assessed by two radiologists for the presence of abnormalities, laterality and zonal predominance of the parenchymal abnormalities, and dominant imaging patterns and their anatomic distributions. Results CT findings included consolidation (n = 92), ground-glass opacity (GGO; n = 82), septal thickening (n = 34), nodules (n = 46), bronchial wall thickening (n = 32), pleural effusion (n = 16), and lymphadenopathy (n = 3). Eighty-four patients (81%) exhibited unilateral parenchymal abnormalities and 57 (57%) exhibited lower lung zone abnormalities. The most frequently dominant CT pattern was consolidation with surrounding GGO (n = 50), with subpleural (70%) and peribronchovascular (94%) distributions. Consolidation-the second-most common pattern (n = 33)-also exhibited subpleural (79%) and peribronchovascular (97%) distributions. The dominant nodule pattern (n = 14) exhibited mixed (64%) and peribronchovascular (100%) distributions. A dominant GGO pattern was only observed in four patients; none had central distribution. Conclusion Although the manifestations of adenovirus pneumonia on CT are varied, we found the most frequent pattern was consolidation with or without surrounding GGO, with subpleural and peribronchovascular distributions. Parenchymal abnormalities were predominantly unilateral and located in the lower lung zone. If dominant consolidation findings are present in immunocompetent patients during the early stages, adenovirus pneumonia should be considered.

Computation of the intensities of parametric holographic scattering patterns in photorefractive crystals.

PubMed

Schwalenberg, Simon

2005-06-01

The present work represents a first attempt to perform computations of output intensity distributions for different parametric holographic scattering patterns. Based on the model for parametric four-wave mixing processes in photorefractive crystals and taking into account realistic material properties, we present computed images of selected scattering patterns. We compare these calculated light distributions to the corresponding experimental observations. Our analysis is especially devoted to dark scattering patterns as they make high demands on the underlying model.

Links of the significant wave height distribution in the Mediterranean sea with the Northern Hemisphere teleconnection patterns

NASA Astrophysics Data System (ADS)

Lionello, P.; Galati, M. B.

2008-06-01

This study analyzes the link between the SWH (Significant Wave Height) distribution in the Mediterranean Sea during the second half of the 20th century and the Northern Hemisphere SLP (Sea Level Pressure) teleconnection patterns. The SWH distribution is computed using the WAM (WAve Model) forced by the surface wind fields provided by the ERA-40 reanalysis for the period 1958-2001. The time series of mid-latitude teleconnection patterns are downloaded from the NOAA web site. This study shows that several mid-latitude patterns are linked to the SWH field in the Mediterranean, especially in its western part during the cold season: East Atlantic Pattern (EA), Scandinavian Pattern (SCA), North Atlantic Oscillation (NAO), East Atlantic/West Russia Pattern (EA/WR) and East Pacific/ North Pacific Pattern (EP/NP). Though the East Atlantic pattern exerts the largest influence, it is not sufficient to characterize the dominant variability. NAO, though relevant, has an effect smaller than EA and comparable to other patterns. Some link results from possibly spurious structures. Patterns which have a very different global structure are associated to similar spatial features of the wave variability in the Mediterranean Sea. These two problems are, admittedly, shortcomings of this analysis, which shows the complexity of the response of the Mediterranean SWH to global scale SLP teleconnection patterns.

Within-twig leaf distribution patterns differ among plant life-forms in a subtropical Chinese forest.

PubMed

Meng, Fengqun; Cao, Rui; Yang, Dongmei; Niklas, Karl J; Sun, Shucun

2013-07-01

In theory, plants can alter the distribution of leaves along the lengths of their twigs (i.e., within-twig leaf distribution patterns) to optimize light interception in the context of the architectures of their leaves, branches and canopies. We hypothesized that (i) among canopy tree species sharing similar light environments, deciduous trees will have more evenly spaced within-twig leaf distribution patterns compared with evergreen trees (because deciduous species tend to higher metabolic demands than evergreen species and hence require more light), and that (ii) shade-adapted evergreen species will have more evenly spaced patterns compared with sun-adapted evergreen ones (because shade-adapted species are generally light-limited). We tested these hypotheses by measuring morphological traits (i.e., internode length, leaf area, lamina mass per area, LMA; and leaf and twig inclination angles to the horizontal) and physiological traits (i.e., light-saturated net photosynthetic rates, Amax; light saturation points, LSP; and light compensation points, LCP), and calculated the 'evenness' of within-twig leaf distribution patterns as the coefficient of variation (CV; the higher the CV, the less evenly spaced leaves) of within-twig internode length for 9 deciduous canopy tree species, 15 evergreen canopy tree species, 8 shade-adapted evergreen shrub species and 12 sun-adapted evergreen shrub species in a subtropical broad-leaved rainforest in eastern China. Coefficient of variation was positively correlated with large LMA and large leaf and twig inclination angles, which collectively specify a typical trait combination adaptive to low light interception, as indicated by both ordinary regression and phylogenetic generalized least squares analyses. These relationships were also valid within the evergreen tree species group (which had the largest sample size). Consistent with our hypothesis, in the canopy layer, deciduous species (which were characterized by high LCP, LSP and Amax) had more even leaf distribution patterns than evergreen species (which had low LCP, LSP and Amax); shade-adapted evergreen species had more even leaf distribution patterns than sun-adapted evergreen species. We propose that the leaf distribution pattern (i.e., 'evenness' CV, which is an easily measured functional trait) can be used to distinguish among life-forms in communities similar to the one examined in this study.

Two-state Markov-chain Poisson nature of individual cellphone call statistics

NASA Astrophysics Data System (ADS)

Jiang, Zhi-Qiang; Xie, Wen-Jie; Li, Ming-Xia; Zhou, Wei-Xing; Sornette, Didier

2016-07-01

Unfolding the burst patterns in human activities and social interactions is a very important issue especially for understanding the spreading of disease and information and the formation of groups and organizations. Here, we conduct an in-depth study of the temporal patterns of cellphone conversation activities of 73 339 anonymous cellphone users, whose inter-call durations are Weibull distributed. We find that the individual call events exhibit a pattern of bursts, that high activity periods are alternated with low activity periods. In both periods, the number of calls are exponentially distributed for individuals, but power-law distributed for the population. Together with the exponential distributions of inter-call durations within bursts and of the intervals between consecutive bursts, we demonstrate that the individual call activities are driven by two independent Poisson processes, which can be combined within a minimal model in terms of a two-state first-order Markov chain, giving significant fits for nearly half of the individuals. By measuring directly the distributions of call rates across the population, which exhibit power-law tails, we purport the existence of power-law distributions, via the ‘superposition of distributions’ mechanism. Our findings shed light on the origins of bursty patterns in other human activities.

Using Citizen Science Observations to Model Species Distributions Over Space, Through Time, and Across Scales

NASA Astrophysics Data System (ADS)

Kelling, S.

2017-12-01

The goal of Biodiversity research is to identify, explain, and predict why a species' distribution and abundance vary through time, space, and with features of the environment. Measuring these patterns and predicting their responses to change are not exercises in curiosity. Today, they are essential tasks for understanding the profound effects that humans have on earth's natural systems, and for developing science-based environmental policies. To gain insight about species' distribution patterns requires studying natural systems at appropriate scales, yet studies of ecological processes continue to be compromised by inadequate attention to scale issues. How spatial and temporal patterns in nature change with scale often reflects fundamental laws of physics, chemistry, or biology, and we can identify such basic, governing laws only by comparing patterns over a wide range of scales. This presentation will provide several examples that integrate bird observations made by volunteers, with NASA Earth Imagery using Big Data analysis techniques to analyze the temporal patterns of bird occurrence across scales—from hemisphere-wide views of bird distributions to the impact of powerful city lights on bird migration.

[Spatial distribution pattern of Pontania dolichura larvae and sampling technique].

PubMed

Zhang, Feng; Chen, Zhijie; Zhang, Shulian; Zhao, Huiyan

2006-03-01

In this paper, the spatial distribution pattern of Pontania dolichura larvae was analyzed with Taylor's power law, Iwao's distribution function, and six aggregation indexes. The results showed that the spatial distribution pattern of P. dolichura larvae was of aggregated, and the basic component of the distribution was individual colony, with the aggregation intensity increased with density. On branches, the aggregation was caused by the adult behavior of laying eggs and the spatial position of leaves, while on leaves, the aggregation was caused by the spatial position of news leaves in spring when m < 2.37, and by the spatial position of news leaves in spring and the behavior of eclosion and laying eggs when m > 2.37. By using the parameters alpha and beta in Iwao's m * -m regression equation, the optimal and sequential sampling numbers were determined.

Detecting diffusion-diffraction patterns in size distribution phantoms using double-pulsed field gradient NMR: Theory and experiments.

PubMed

Shemesh, Noam; Ozarslan, Evren; Basser, Peter J; Cohen, Yoram

2010-01-21

NMR observable nuclei undergoing restricted diffusion within confining pores are important reporters for microstructural features of porous media including, inter-alia, biological tissues, emulsions and rocks. Diffusion NMR, and especially the single-pulsed field gradient (s-PFG) methodology, is one of the most important noninvasive tools for studying such opaque samples, enabling extraction of important microstructural information from diffusion-diffraction phenomena. However, when the pores are not monodisperse and are characterized by a size distribution, the diffusion-diffraction patterns disappear from the signal decay, and the relevant microstructural information is mostly lost. A recent theoretical study predicted that the diffusion-diffraction patterns in double-PFG (d-PFG) experiments have unique characteristics, such as zero-crossings, that make them more robust with respect to size distributions. In this study, we theoretically compared the signal decay arising from diffusion in isolated cylindrical pores characterized by lognormal size distributions in both s-PFG and d-PFG methodologies using a recently presented general framework for treating diffusion in NMR experiments. We showed the gradual loss of diffusion-diffraction patterns in broadening size distributions in s-PFG and the robustness of the zero-crossings in d-PFG even for very large standard deviations of the size distribution. We then performed s-PFG and d-PFG experiments on well-controlled size distribution phantoms in which the ground-truth is well-known a priori. We showed that the microstructural information, as manifested in the diffusion-diffraction patterns, is lost in the s-PFG experiments, whereas in d-PFG experiments the zero-crossings of the signal persist from which relevant microstructural information can be extracted. This study provides a proof of concept that d-PFG may be useful in obtaining important microstructural features in samples characterized by size distributions.

Voronoi cell patterns: Theoretical model and applications

NASA Astrophysics Data System (ADS)

González, Diego Luis; Einstein, T. L.

2011-11-01

We use a simple fragmentation model to describe the statistical behavior of the Voronoi cell patterns generated by a homogeneous and isotropic set of points in 1D and in 2D. In particular, we are interested in the distribution of sizes of these Voronoi cells. Our model is completely defined by two probability distributions in 1D and again in 2D, the probability to add a new point inside an existing cell and the probability that this new point is at a particular position relative to the preexisting point inside this cell. In 1D the first distribution depends on a single parameter while the second distribution is defined through a fragmentation kernel; in 2D both distributions depend on a single parameter. The fragmentation kernel and the control parameters are closely related to the physical properties of the specific system under study. We use our model to describe the Voronoi cell patterns of several systems. Specifically, we study the island nucleation with irreversible attachment, the 1D car-parking problem, the formation of second-level administrative divisions, and the pattern formed by the Paris Métro stations.

Lineament and polygon patterns on Europa

NASA Technical Reports Server (NTRS)

Pieri, D. C.

1981-01-01

A classification scheme is presented for the lineaments and associated polygonal patterns observed on the surface of Europa, and the frequency distribution of the polygons is discussed in terms of the stress-relief fracturing of the surface. The lineaments are divided on the basis of albedo, morphology, orientation and characteristic geometry into eight groups based on Voyager 2 images taken at a best resolution of 4 km. The lineaments in turn define a system of polygons varying in size from small reticulate patterns the limit of resolution to 1,000,000 sq km individuals. Preliminary analysis of polygon side frequency distributions reveals a class of polygons with statistics similar to those found in complex terrestrial terrains, particularly in areas of well-oriented stresses, a class with similar statistics around the antijovian point, and a class with a distribution similar to those seen in terrestrial tensional fracture patterns. Speculations concerning the processes giving rise to the lineament patterns are presented.

A Dictionary Approach to Electron Backscatter Diffraction Indexing.

PubMed

Chen, Yu H; Park, Se Un; Wei, Dennis; Newstadt, Greg; Jackson, Michael A; Simmons, Jeff P; De Graef, Marc; Hero, Alfred O

2015-06-01

We propose a framework for indexing of grain and subgrain structures in electron backscatter diffraction patterns of polycrystalline materials. We discretize the domain of a dynamical forward model onto a dense grid of orientations, producing a dictionary of patterns. For each measured pattern, we identify the most similar patterns in the dictionary, and identify boundaries, detect anomalies, and index crystal orientations. The statistical distribution of these closest matches is used in an unsupervised binary decision tree (DT) classifier to identify grain boundaries and anomalous regions. The DT classifies a pattern as an anomaly if it has an abnormally low similarity to any pattern in the dictionary. It classifies a pixel as being near a grain boundary if the highly ranked patterns in the dictionary differ significantly over the pixel's neighborhood. Indexing is accomplished by computing the mean orientation of the closest matches to each pattern. The mean orientation is estimated using a maximum likelihood approach that models the orientation distribution as a mixture of Von Mises-Fisher distributions over the quaternionic three sphere. The proposed dictionary matching approach permits segmentation, anomaly detection, and indexing to be performed in a unified manner with the additional benefit of uncertainty quantification.

Design Flexibility for Uncertain Distributed Generation from Photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Krishnamurthy, Dheepak; Wu, Hongyu

2016-12-12

Uncertainty in the future adoption patterns for distributed energy resources (DERs) introduces a challenge for electric distribution system planning. This paper explores the potential for flexibility in design - also known as real options - to identify design solutions that may never emerge when future DER patterns are treated as deterministic. A test case for storage system design with uncertain distributed generation for solar photovoltaics (DGPV) demonstrates this approach and is used to study sensitivities to a range of techno-economic assumptions.

Photosynthate distribution patterns in cherrybark oak seedling sprouts

Treesearch

Brian Roy Lockhart; John D. Hodges; Emile S. Gardiner; Andrew W. Ezell

2003-01-01

Summary We used 14C tracers to determine photosynthate distribution in cherrybark oak (Quercus pagoda Raf.) seedling sprouts following release from competing mid-story vegetation. Fall acquisition of labeled photosynthates by seedlings followed expected source--sink patterns, with root and basal stem tissues...

Does the Australian desert ant Melophorus bagoti approximate a Lévy search by an intrinsic bi-modal walk?

PubMed

Reynolds, Andy M; Schultheiss, Patrick; Cheng, Ken

2014-01-07

We suggest that the Australian desert ant Melophorus bagoti approximates a Lévy search pattern by using an intrinsic bi-exponential walk and does so when a Lévy search pattern is advantageous. When attempting to locate its nest, M. bagoti adopt a stereotypical search pattern. These searches begin at the location where the ant expects to find the nest, and comprise loops that start and end at this location, and are directed in different azimuthal directions. Loop lengths are exponentially distributed when searches are in visually familiar surroundings and are well described by a mixture of two exponentials when searches are in unfamiliar landscapes. The latter approximates a power-law distribution, the hallmark of a Lévy search. With the aid of a simple analytically tractable theory, we show that an exponential loop-length distribution is advantageous when the distance to the nest can be estimated with some certainty and that a bi-exponential distribution is advantageous when there is considerable uncertainty regarding the nest location. The best bi-exponential search patterns are shown to be those that come closest to approximating advantageous Lévy looping searches. The bi-exponential search patterns of M. bagoti are found to approximate advantageous Lévy search patterns. Copyright © 2013. Published by Elsevier Ltd.

Patterns of oribatid mite species diversity: testing the effects of elevation, area and sampling effort.

PubMed

Mumladze, Levan; Murvanidze, Maka; Maraun, Mark

2017-07-01

Elevational gradients in species diversity and species area relationships are two well established patterns that are not mutually exclusive in space and time. Elevation and area are both considered as good proxies to detect and characterize the patterns of species diversity distribution. However, such studies are hampered by the incomplete biodiversity data available for ecologists, which may affect the pattern perceptions. Using the large dataset of oribatid mite communities sampled in Georgia, we tested the effects of altitude and area on species distribution using various approaches, while explicitly considering the biases from sampling effort. Our results showed that elevation and area are strongly correlated (with increasing absolute elevation, land area decreases) and both have strong linear effects on species diversity distribution when studied separately. Approaches based on multiple regression and direct removal of co-varied factors, indicated that the effect of area can actually override the effect of elevation in describing the oribatid species diversity distribution along with elevation. On the other hand, the bias of sampling proved significant in perception of elevational species richness pattern with less effect on elevational species area relationship. We suggest that the sampling alone may be responsible for patterns observed and thus should be considered in ecological studies when eligible.

Mistaking geography for biology: inferring processes from species distributions.

PubMed

Warren, Dan L; Cardillo, Marcel; Rosauer, Dan F; Bolnick, Daniel I

2014-10-01

Over the past few decades, there has been a rapid proliferation of statistical methods that infer evolutionary and ecological processes from data on species distributions. These methods have led to considerable new insights, but they often fail to account for the effects of historical biogeography on present-day species distributions. Because the geography of speciation can lead to patterns of spatial and temporal autocorrelation in the distributions of species within a clade, this can result in misleading inferences about the importance of deterministic processes in generating spatial patterns of biodiversity. In this opinion article, we discuss ways in which patterns of species distributions driven by historical biogeography are often interpreted as evidence of particular evolutionary or ecological processes. We focus on three areas that are especially prone to such misinterpretations: community phylogenetics, environmental niche modelling, and analyses of beta diversity (compositional turnover of biodiversity). Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Patterns of particle distribution in multiparticle systems by random walks with memory enhancement and decay

NASA Astrophysics Data System (ADS)

Tan, Zhi-Jie; Zou, Xian-Wu; Huang, Sheng-You; Zhang, Wei; Jin, Zhun-Zhi

2002-07-01

We investigate the pattern of particle distribution and its evolution with time in multiparticle systems using the model of random walks with memory enhancement and decay. This model describes some biological intelligent walks. With decrease in the memory decay exponent α, the distribution of particles changes from a random dispersive pattern to a locally dense one, and then returns to the random one. Correspondingly, the fractal dimension Df,p characterizing the distribution of particle positions increases from a low value to a maximum and then decreases to the low one again. This is determined by the degree of overlap of regions consisting of sites with remanent information. The second moment of the density ρ(2) was introduced to investigate the inhomogeneity of the particle distribution. The dependence of ρ(2) on α is similar to that of Df,p on α. ρ(2) increases with time as a power law in the process of adjusting the particle distribution, and then ρ(2) tends to a stable equilibrium value.

The use of decision tree induction and artificial neural networks for recognizing the geochemical distribution patterns of LREE in the Choghart deposit, Central Iran

NASA Astrophysics Data System (ADS)

Zaremotlagh, S.; Hezarkhani, A.

2017-04-01

Some evidences of rare earth elements (REE) concentrations are found in iron oxide-apatite (IOA) deposits which are located in Central Iranian microcontinent. There are many unsolved problems about the origin and metallogenesis of IOA deposits in this district. Although it is considered that felsic magmatism and mineralization were simultaneous in the district, interaction of multi-stage hydrothermal-magmatic processes within the Early Cambrian volcano-sedimentary sequence probably caused some epigenetic mineralizations. Secondary geological processes (e.g., multi-stage mineralization, alteration, and weathering) have affected on variations of major elements and possible redistribution of REE in IOA deposits. Hence, the geochemical behaviors and distribution patterns of REE are expected to be complicated in different zones of these deposits. The aim of this paper is recognizing LREE distribution patterns based on whole-rock chemical compositions and automatic discovery of their geochemical rules. For this purpose, the pattern recognition techniques including decision tree and neural network were applied on a high-dimensional geochemical dataset from Choghart IOA deposit. Because some data features were irrelevant or redundant in recognizing the distribution patterns of each LREE, a greedy attribute subset selection technique was employed to select the best subset of predictors used in classification tasks. The decision trees (CART algorithm) were pruned optimally to more accurately categorize independent test data than unpruned ones. The most effective classification rules were extracted from the pruned tree to describe the meaningful relationships between the predictors and different concentrations of LREE. A feed-forward artificial neural network was also applied to reliably predict the influence of various rock compositions on the spatial distribution patterns of LREE with a better performance than the decision tree induction. The findings of this study could be effectively used to visualize the LREE distribution patterns as geochemical maps.

Microsatellite analysis of genotype distribution patterns of Candida albicans vulvovaginal candidiasis in Nanjing, China and its association with pregnancy, age and clinical presentation.

PubMed

Li, Caixia; Wang, Le; Tong, Hua; Ge, Yiping; Mei, Huan; Chen, Liangyu; Lv, Guixia; Liu, Weida

2016-08-01

To characterize the genotype distribution pattern of Candida albicans associated with vulvovaginal candidiasis (VVC) in Nanjing, China by microsatellite genotyping. A questionnaire was completed by each patient diagnosed with VVC. A total of 208 independent C. albicans was isolated from 208 patients. Microsatellite genotyping characterized the genotype distribution by analysis of the CAI locus marker. PCR of CAI fragments showed the three major genotypes contained 30:45, 21:21 and 32:46 alleles among the 51 genotypes detected, accounting for 29.3, 13.0 and 12.0 % of 208 clinical isolates. Genotype distributions had a similar pattern among different clinical presentations (P = 0.219). In both groups of the (21-30) and (31-40) years, 30:45 was the most frequent genotype allele detected. In the (21-30) year females, 16.5 % of the isolated strains had the genotype 21:21, while the same genotype in the group of (31-40) years was 6.9 %. Genotype distributions were significant difference between the pregnant and non-pregnant women (P < 0.001). 30:45 was detected only one in the 23 pregnant women. The results indicated a unique genotype distribution of C. albicans associated with VVC in Nanjing, eastern China and a different distribution pattern was also detected in pregnant women compared to non-pregnant women.

Dynamic Patterns of Modern Epidemics

NASA Astrophysics Data System (ADS)

Brockmann, Dirk; Hufnagel, Lars; Geisel, Theo

2004-03-01

We investigate the effects of scale-free travelling of humans and their inhomogeneous geographic distribution on the dynamic patterns of spreading epidemics. Our approach combines the susceptible/infected/recovered paradigm for the infection dynamics with superdiffusive dispersion of individuals and their inhomogeneous spatial distribution. We show that scale-free motion of individuals and their variable spatial distribution leads to the absence of wavefronts in dynamic epidemic patterns which are typical for the limiting cases of ordinary diffusion and spatially homogeneous populations. Instead, patterns emerge with isolated hotspots on highly populated areas from which regional epidemic outbursts are triggered. Hotspot sizes are independent of the correlation length in the spatial distribution of individuals and occur on all scales. Our theory predicts that highly populated areas are reached by an epidemic in advance and must receive special attention in control measure strategies. Furthermore, our analysis predicts strong fluctuations in the time course of the total infection which cannot be accounted for by ordinary reaction-diffusion models for epidemics.

Computation of spanwise distribution of circulation and lift coefficient for flapped wings of arbitrary planform

NASA Technical Reports Server (NTRS)

Razak, K.

1980-01-01

The question of the effect of distribution and magnitude of spanwise circulation and shed vorticity from an airplane wing on the distribution pattern of agricultural products distributed from an airplane was studied. The first step in an analysis of this question is the determination of the actual distribution of lift along an airplane wing, from which the pattern of shed vorticity can be determined. A procedure is developed to calculate the span loading for flapped and unflapped wings of arbitrary aspect ratio and taper ratio. The procedure was programmed on a small programmable calculator, the Hewlett Packard HP-97, and also was programmed in BASIC language. They could be used to explore the variations in span loading that can be secured by variable flap deflections or the effect of flying at varying air speeds at different airplane gross weights. Either an absolute evaluation of span loading can be secured or comparative span loading can be evaluated to determine their effect on swath width and swath distribution pattern. The programs are intended to assist the user in evaluating the effect of a given spanload distribution.

Processing and statistical analysis of soil-root images

NASA Astrophysics Data System (ADS)

Razavi, Bahar S.; Hoang, Duyen; Kuzyakov, Yakov

2016-04-01

Importance of the hotspots such as rhizosphere, the small soil volume that surrounds and is influenced by plant roots, calls for spatially explicit methods to visualize distribution of microbial activities in this active site (Kuzyakov and Blagodatskaya, 2015). Zymography technique has previously been adapted to visualize the spatial dynamics of enzyme activities in rhizosphere (Spohn and Kuzyakov, 2014). Following further developing of soil zymography -to obtain a higher resolution of enzyme activities - we aimed to 1) quantify the images, 2) determine whether the pattern (e.g. distribution of hotspots in space) is clumped (aggregated) or regular (dispersed). To this end, we incubated soil-filled rhizoboxes with maize Zea mays L. and without maize (control box) for two weeks. In situ soil zymography was applied to visualize enzymatic activity of β-glucosidase and phosphatase at soil-root interface. Spatial resolution of fluorescent images was improved by direct application of a substrate saturated membrane to the soil-root system. Furthermore, we applied "spatial point pattern analysis" to determine whether the pattern (e.g. distribution of hotspots in space) is clumped (aggregated) or regular (dispersed). Our results demonstrated that distribution of hotspots at rhizosphere is clumped (aggregated) compare to control box without plant which showed regular (dispersed) pattern. These patterns were similar in all three replicates and for both enzymes. We conclude that improved zymography is promising in situ technique to identify, analyze, visualize and quantify spatial distribution of enzyme activities in the rhizosphere. Moreover, such different patterns should be considered in assessments and modeling of rhizosphere extension and the corresponding effects on soil properties and functions. Key words: rhizosphere, spatial point pattern, enzyme activity, zymography, maize.

Decapod larvae distribution and species composition off the southern Portuguese coast

NASA Astrophysics Data System (ADS)

Pochelon, Patricia N.; Pires, Rita F. T.; Dubert, Jesús; Nolasco, Rita; Santos, A. Miguel P.; Queiroga, Henrique; dos Santos, Antonina

2017-12-01

For decapod crustaceans, the larval phase is the main responsible for dispersal, given the direct emission from adult habitats into the water column. Circulation patterns and behavioural mechanisms control the dispersal distance and connectivity between different areas. Information on larval distribution and abundance is required to predict the size and location of breeding populations, and correctly manage marine resources. Spatial distribution and abundance data of decapod larvae, and environmental parameters were assessed in winter surveys off the southern Portuguese coast. To better understand the oceanic structures driving larval distribution patterns, in situ physical parameters were measured and a hydrodynamical model used. Inter-annual, cross-shore and alongshore differences on decapod larvae distribution were found. Brachyuran crabs dominated the samples and similar taxa composition was observed in the most dynamic areas. Coastal taxa dominated the nearshore survey and were almost absent in the more offshore one, that registered much lower abundances. An upwelling front allowed a clear cross-shore species separation, also evident in the abundance values and number of taxa. Hydrodynamical conditions and adult habitats were the main factors explaining the observed patterns. Important missing information to understand the distribution patterns of decapod larval communities and the mechanisms behind them is given for the region.

Woodland type and spatial distribution of nymphal Ixodes scapularis (Acari: Ixodidae)

USGS Publications Warehouse

Ginsberg, Howard S.; Zhioua, Elyes; Mitra, Shaibal; Fischer, Jason L.; Buckley, P.A.; Verret, Frank; Underwood, H. Brian; Buckley, Francine G.

2004-01-01

Spatial distribution patterns of black-legged ticks, Ixodes scapularis, in deciduous and coniferous woodlands were studied by sampling ticks in different woodland types and at sites from which deer had been excluded and by quantifying movement patterns of tick host animals (mammals and birds) at the Lighthouse Tract, Fire Island, NY, from 1994 to 2000. Densities of nymphal ticks were greater in deciduous than coniferous woods in 3 of 7 yr. Only engorged ticks survived the winter, and overwintering survival of engorged larvae in experimental enclosures did not differ between deciduous and coniferous woods. Nymphs were not always most abundant in the same forest type as they had been as larvae, and the habitat shift between life stages differed in direction in different years. Therefore, forest type by itself did not account for tick distribution patterns. Nymphal densities were lower where deer had been excluded compared with areas with deer present for 3 yr after exclusion, suggesting that movement patterns of vertebrate hosts influenced tick distribution, but nymphal densities increased dramatically in one of the enclosures in the fourth year. Therefore, movements of ticks on animal hosts apparently contribute substantially to tick spatial distribution among woodland types, but the factor(s) that determine spatial distribution of nymphal I. scapularis shift from year to year.

Resistance of Soil-Bound Prions to Rumen Digestion

PubMed Central

Saunders, Samuel E.; Bartelt-Hunt, Shannon L.; Bartz, Jason C.

2012-01-01

Before prion uptake and infection can occur in the lower gastrointestinal system, ingested prions are subjected to anaerobic digestion in the rumen of cervids and bovids. The susceptibility of soil-bound prions to rumen digestion has not been evaluated previously. In this study, prions from infectious brain homogenates as well as prions bound to a range of soils and soil minerals were subjected to in vitro rumen digestion, and changes in PrP levels were measured via western blot. Binding to clay appeared to protect noninfectious hamster PrPc from complete digestion, while both unbound and soil-bound infectious PrPSc proved highly resistant to rumen digestion. In addition, no change in intracerebral incubation period was observed following active rumen digestion of unbound hamster HY TME prions and HY TME prions bound to a silty clay loam soil. These results demonstrate that both unbound and soil-bound prions readily survive rumen digestion without a reduction in infectivity, further supporting the potential for soil-mediated transmission of chronic wasting disease (CWD) and scrapie in the environment. PMID:22937149

3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

NASA Astrophysics Data System (ADS)

Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

2014-02-01

Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

Prion pathogenesis and secondary lymphoid organs (SLO)

PubMed Central

Mabbott, Neil A.

2012-01-01

Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases. PMID:22895090

Lack of prion transmission by sexual or parental routes in experimentally infected hamsters.

PubMed

Morales, Rodrigo; Pritzkow, Sandra; Hu, Ping Ping; Duran-Aniotz, Claudia; Soto, Claudio

2013-01-01

Prion diseases are a group of neurodegenerative disorders affecting humans as well as captive and wild animals. The mechanisms and routes governing the natural spread of prions are not completely understood and several hypotheses have been proposed. In this study, we analyzed the effect of gender in prion incubation period, as well as the possibility of prion transmission by sexual and parental contact using 263K infected hamsters as a model. Our results show that males have significantly longer incubation periods compared with females when exposed to the same quantity of infectious material. Importantly, no evidence of sexual or parental prion transmission was found, even 500 d after sexual contact or birth, respectively. Western blotting and PMCA were unable to detect sub-clinical levels of PrP(Sc) in experimental subjects, suggesting a complete absence of prion transmission by these routes. Our results show that sexual and parental transmission of prions does not occur in this model. It remains to be studied whether this conclusion is valid also for other prion strains and species.

Statistical detection of patterns in unidimensional distributions by continuous wavelet transforms

NASA Astrophysics Data System (ADS)

Baluev, R. V.

2018-04-01

Objective detection of specific patterns in statistical distributions, like groupings or gaps or abrupt transitions between different subsets, is a task with a rich range of applications in astronomy: Milky Way stellar population analysis, investigations of the exoplanets diversity, Solar System minor bodies statistics, extragalactic studies, etc. We adapt the powerful technique of the wavelet transforms to this generalized task, making a strong emphasis on the assessment of the patterns detection significance. Among other things, our method also involves optimal minimum-noise wavelets and minimum-noise reconstruction of the distribution density function. Based on this development, we construct a self-closed algorithmic pipeline aimed to process statistical samples. It is currently applicable to single-dimensional distributions only, but it is flexible enough to undergo further generalizations and development.

Transferrin receptors in human tissues: their distribution and possible clinical relevance.

PubMed

Gatter, K C; Brown, G; Trowbridge, I S; Woolston, R E; Mason, D Y

1983-05-01

The distribution of transferrin receptors (TR) has been studied in a range of normal and malignant tissues using four monoclonal antibodies, BK19.9, B3/25, T56/14 and T58/1. In normal tissues TR was found in a limited number of sites, notably basal epidermis, the endocrine pancreas, hepatocytes, Kupffer cells, testis and pituitary. This restricted pattern of distribution may be relevant to the characteristic pattern of iron deposition in primary haemachromatosis. In contrast to this limited pattern of expression in normal tissue, the receptor was widely distributed in carcinomas, sarcomas and in samples from cases of Hodgkin's disease. This malignancy-associated expression of the receptor may play a role in the anaemia of advanced malignancy by competing with the bone marrow for serum iron.

Transferrin receptors in human tissues: their distribution and possible clinical relevance.

PubMed Central

Gatter, K C; Brown, G; Trowbridge, I S; Woolston, R E; Mason, D Y

1983-01-01

The distribution of transferrin receptors (TR) has been studied in a range of normal and malignant tissues using four monoclonal antibodies, BK19.9, B3/25, T56/14 and T58/1. In normal tissues TR was found in a limited number of sites, notably basal epidermis, the endocrine pancreas, hepatocytes, Kupffer cells, testis and pituitary. This restricted pattern of distribution may be relevant to the characteristic pattern of iron deposition in primary haemachromatosis. In contrast to this limited pattern of expression in normal tissue, the receptor was widely distributed in carcinomas, sarcomas and in samples from cases of Hodgkin's disease. This malignancy-associated expression of the receptor may play a role in the anaemia of advanced malignancy by competing with the bone marrow for serum iron. Images PMID:6302135

Some considerations on the use of ecological models to predict species' geographic distributions

USGS Publications Warehouse

Peterjohn, B.G.

2001-01-01

Peterson (2001) used Genetic Algorithm for Rule-set Prediction (GARP) models to predict distribution patterns from Breeding Bird Survey (BBS) data. Evaluations of these models should consider inherent limitations of BBS data: (1) BBS methods may not sample species and habitats equally; (2) using BBS data for both model development and testing may overlook poor fit of some models; and (3) BBS data may not provide the desired spatial resolution or capture temporal changes in species distributions. The predictive value of GARP models requires additional study, especially comparisons with distribution patterns from independent data sets. When employed at appropriate temporal and geographic scales, GARP models show considerable promise for conservation biology applications but provide limited inferences concerning processes responsible for the observed patterns.

Two dimensional Fourier transform methods for fringe pattern analysis

NASA Astrophysics Data System (ADS)

Sciammarella, C. A.; Bhat, G.

An overview of the use of FFTs for fringe pattern analysis is presented, with emphasis on fringe patterns containing displacement information. The techniques are illustrated via analysis of the displacement and strain distributions in the direction perpendicular to the loading, in a disk under diametral compression. The experimental strain distribution is compared to the theoretical, and the agreement is found to be excellent in regions where the elasticity solution models well the actual problem.

Ichthyoplankton spatial pattern in the inner shelf off Bahía Blanca Estuary, SW Atlantic Ocean

NASA Astrophysics Data System (ADS)

Hoffmeyer, Mónica Susana; Clara, Menéndez María; Florencia, Biancalana; Mabel, Nizovoy Alicia; Ramón, Torres Eduardo

2009-09-01

This study focuses on the composition, abundance and distribution of ichthyoplankton in the inner shelf area off Bahía Blanca Estuary on the SW Atlantic Ocean during late spring. Eggs and larvae of Brevoortia aurea, Engraulis anchoita, Parona signata, Sciaenidae spp. - such as Cynoscion guatucupa and Micropogonias furnieri -, and Odontesthes argentinensis were found. Species richness was low probably as a result of season and shallow depths. Ichthyoplankton abundance reached values close to 10 000 per 10 m -3 (eggs) and 4000 per 10 m -3 (larvae) and displayed a spatial distribution pattern with maximum abundance values restricted to a band parallel to the coast. Differences between egg and larval patterns, probably derived from a different displacement and hydrodynamic behavior, were observed. Egg and larvae distribution patterns were found related with spawning areas and to directly depend on salinity and mesozooplankton. The larvae distribution pattern, in particular, was found to inversely depend on particulate organic carbon. In addition, the geographic location of egg and larvae maxima strongly coincided with a saline front reported for this area in springtime, thus suggesting a direct relationship with it.

Consistent role of Quaternary climate change in shaping current plant functional diversity patterns across European plant orders.

PubMed

Ordonez, Alejandro; Svenning, Jens-Christian

2017-02-23

Current and historical environmental conditions are known to determine jointly contemporary species distributions and richness patterns. However, whether historical dynamics in species distributions and richness translate to functional diversity patterns remains, for the most part, unknown. The geographic patterns of plant functional space size (richness) and packing (dispersion) for six widely distributed orders of European angiosperms were estimated using atlas distribution data and trait information. Then the relative importance of late-Quaternary glacial-interglacial climate change and contemporary environmental factors (climate, productivity, and topography) as determinants of functional diversity of evaluated orders was assesed. Functional diversity patterns of all evaluated orders exhibited prominent glacial-interglacial climate change imprints, complementing the influence of contemporary environmental conditions. The importance of Quaternary glacial-interglacial climate change factors was comparable to that of contemporary environmental factors across evaluated orders. Therefore, high long-term paleoclimate variability has imposed consistent supplementary constraints on functional diversity of multiple plant groups, a legacy that may permeate to ecosystem functioning and resilience. These findings suggest that strong near-future anthropogenic climate change may elicit long-term functional disequilibria in plant functional diversity.

Multivariate pattern analysis of fMRI data reveals deficits in distributed representations in schizophrenia

PubMed Central

Yoon, Jong H.; Tamir, Diana; Minzenberg, Michael J.; Ragland, J. Daniel; Ursu, Stefan; Carter, Cameron S.

2009-01-01

Background Multivariate pattern analysis is an alternative method of analyzing fMRI data, which is capable of decoding distributed neural representations. We applied this method to test the hypothesis of the impairment in distributed representations in schizophrenia. We also compared the results of this method with traditional GLM-based univariate analysis. Methods 19 schizophrenia and 15 control subjects viewed two runs of stimuli--exemplars of faces, scenes, objects, and scrambled images. To verify engagement with stimuli, subjects completed a 1-back matching task. A multi-voxel pattern classifier was trained to identify category-specific activity patterns on one run of fMRI data. Classification testing was conducted on the remaining run. Correlation of voxel-wise activity across runs evaluated variance over time in activity patterns. Results Patients performed the task less accurately. This group difference was reflected in the pattern analysis results with diminished classification accuracy in patients compared to controls, 59% and 72% respectively. In contrast, there was no group difference in GLM-based univariate measures. In both groups, classification accuracy was significantly correlated with behavioral measures. Both groups showed highly significant correlation between inter-run correlations and classification accuracy. Conclusions Distributed representations of visual objects are impaired in schizophrenia. This impairment is correlated with diminished task performance, suggesting that decreased integrity of cortical activity patterns is reflected in impaired behavior. Comparisons with univariate results suggest greater sensitivity of pattern analysis in detecting group differences in neural activity and reduced likelihood of non-specific factors driving these results. PMID:18822407

Integrating satellite actual evapotranspiration patterns into distributed model parametrization and evaluation for a mesoscale catchment

NASA Astrophysics Data System (ADS)

Demirel, M. C.; Mai, J.; Stisen, S.; Mendiguren González, G.; Koch, J.; Samaniego, L. E.

2016-12-01

Distributed hydrologic models are traditionally calibrated and evaluated against observations of streamflow. Spatially distributed remote sensing observations offer a great opportunity to enhance spatial model calibration schemes. For that it is important to identify the model parameters that can change spatial patterns before the satellite based hydrologic model calibration. Our study is based on two main pillars: first we use spatial sensitivity analysis to identify the key parameters controlling the spatial distribution of actual evapotranspiration (AET). Second, we investigate the potential benefits of incorporating spatial patterns from MODIS data to calibrate the mesoscale Hydrologic Model (mHM). This distributed model is selected as it allows for a change in the spatial distribution of key soil parameters through the calibration of pedo-transfer function parameters and includes options for using fully distributed daily Leaf Area Index (LAI) directly as input. In addition the simulated AET can be estimated at the spatial resolution suitable for comparison to the spatial patterns observed using MODIS data. We introduce a new dynamic scaling function employing remotely sensed vegetation to downscale coarse reference evapotranspiration. In total, 17 parameters of 47 mHM parameters are identified using both sequential screening and Latin hypercube one-at-a-time sampling methods. The spatial patterns are found to be sensitive to the vegetation parameters whereas streamflow dynamics are sensitive to the PTF parameters. The results of multi-objective model calibration show that calibration of mHM against observed streamflow does not reduce the spatial errors in AET while they improve only the streamflow simulations. We will further examine the results of model calibration using only multi spatial objective functions measuring the association between observed AET and simulated AET maps and another case including spatial and streamflow metrics together.

Distributional pattern of planktonic foraminifers and pteropods in surface waters and top core sediments of the Red Sea, and adjacent areas controlled by the monsoonal regime and other ecological factors

NASA Astrophysics Data System (ADS)

Auras-Schudnagies, Anabelle; Kroon, Dick; Ganssen, Gerald; Hemleben, Christoph; Van Hinte, Jan E.

1989-10-01

Living planktonic foraminiferal and pteropod distribution patterns in the western Arabian Sea, Gulf of Aden and Red Sea, collected during two summer cruises (1984, 1985), reflect the hydrographical system that is mainly controlled by a combination of monsoonal winds and evaporation rates. Spinose species constitute the majority of the planktonic foraminiferal assemblages in the Red Sea during both monsoonal seasons. The non-spinose species Globorotalia menardii, Neogloboquadrina dutertrei and Pulleniatina obliquiloculata, which are always abundant in the Arabian Sea, are present only during winter inflow. The intensity and duration of these inflowing surface currents control their distribution pattern. Stable oxygen isotope ratios show that G. menardii survives but ceases to grow north of Bab el Mandeb, while N. dutertrei continues to grow. Trends in the foraminiferal distribution in surface waters compare well with those of the sea floor, as far as larger specimens (>250 μm) are concerned, but differ for the small ones. Surface distribution patterns of small-sized specimens and juvenile/neanic stages of large-sized fully grown species do not correspond to those in the core top samples. The distribution pattern of living pteropods in the Red Sea is closely related to distinct water masses and corresponds to the distribution in top core sediments. Pteropods are absent in the sediments of the Gulf of Aden and the western Arabian Sea due to dissolution. Peak abundances of various pteropods and foraminifers indicate the presence of local upwelling processes in the Bab el Mandeb area. Determining these dynamics allows for the reconstruction of ancient oceanic environments and climatic interactions in the area.

Determinants of Spatial Distribution in a Bee Community: Nesting Resources, Flower Resources, and Body Size

PubMed Central

Torné-Noguera, Anna; Rodrigo, Anselm; Arnan, Xavier; Osorio, Sergio; Barril-Graells, Helena; da Rocha-Filho, Léo Correia; Bosch, Jordi

2014-01-01

Understanding biodiversity distribution is a primary goal of community ecology. At a landscape scale, bee communities are affected by habitat composition, anthropogenic land use, and fragmentation. However, little information is available on local-scale spatial distribution of bee communities within habitats that are uniform at the landscape scale. We studied a bee community along with floral and nesting resources over a 32 km2 area of uninterrupted Mediterranean scrubland. Our objectives were (i) to analyze floral and nesting resource composition at the habitat scale. We ask whether these resources follow a geographical pattern across the scrubland at bee-foraging relevant distances; (ii) to analyze the distribution of bee composition across the scrubland. Bees being highly mobile organisms, we ask whether bee composition shows a homogeneous distribution or else varies spatially. If so, we ask whether this variation is irregular or follows a geographical pattern and whether bees respond primarily to flower or to nesting resources; and (iii) to establish whether body size influences the response to local resource availability and ultimately spatial distribution. We obtained 6580 specimens belonging to 98 species. Despite bee mobility and the absence of environmental barriers, our bee community shows a clear geographical pattern. This pattern is mostly attributable to heterogeneous distribution of small (<55 mg) species (with presumed smaller foraging ranges), and is mostly explained by flower resources rather than nesting substrates. Even then, a large proportion (54.8%) of spatial variability remains unexplained by flower or nesting resources. We conclude that bee communities are strongly conditioned by local effects and may exhibit spatial heterogeneity patterns at a scale as low as 500–1000 m in patches of homogeneous habitat. These results have important implications for local pollination dynamics and spatial variation of plant-pollinator networks. PMID:24824445

Determinants of spatial distribution in a bee community: nesting resources, flower resources, and body size.

PubMed

Torné-Noguera, Anna; Rodrigo, Anselm; Arnan, Xavier; Osorio, Sergio; Barril-Graells, Helena; da Rocha-Filho, Léo Correia; Bosch, Jordi

2014-01-01

Understanding biodiversity distribution is a primary goal of community ecology. At a landscape scale, bee communities are affected by habitat composition, anthropogenic land use, and fragmentation. However, little information is available on local-scale spatial distribution of bee communities within habitats that are uniform at the landscape scale. We studied a bee community along with floral and nesting resources over a 32 km2 area of uninterrupted Mediterranean scrubland. Our objectives were (i) to analyze floral and nesting resource composition at the habitat scale. We ask whether these resources follow a geographical pattern across the scrubland at bee-foraging relevant distances; (ii) to analyze the distribution of bee composition across the scrubland. Bees being highly mobile organisms, we ask whether bee composition shows a homogeneous distribution or else varies spatially. If so, we ask whether this variation is irregular or follows a geographical pattern and whether bees respond primarily to flower or to nesting resources; and (iii) to establish whether body size influences the response to local resource availability and ultimately spatial distribution. We obtained 6580 specimens belonging to 98 species. Despite bee mobility and the absence of environmental barriers, our bee community shows a clear geographical pattern. This pattern is mostly attributable to heterogeneous distribution of small (<55 mg) species (with presumed smaller foraging ranges), and is mostly explained by flower resources rather than nesting substrates. Even then, a large proportion (54.8%) of spatial variability remains unexplained by flower or nesting resources. We conclude that bee communities are strongly conditioned by local effects and may exhibit spatial heterogeneity patterns at a scale as low as 500-1000 m in patches of homogeneous habitat. These results have important implications for local pollination dynamics and spatial variation of plant-pollinator networks.

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-10-22

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners.

Optimal pattern distributions in Rete-based production systems

NASA Technical Reports Server (NTRS)

Scott, Stephen L.

1994-01-01

Since its introduction into the AI community in the early 1980's, the Rete algorithm has been widely used. This algorithm has formed the basis for many AI tools, including NASA's CLIPS. One drawback of Rete-based implementation, however, is that the network structures used internally by the Rete algorithm make it sensitive to the arrangement of individual patterns within rules. Thus while rules may be more or less arbitrarily placed within source files, the distribution of individual patterns within these rules can significantly affect the overall system performance. Some heuristics have been proposed to optimize pattern placement, however, these suggestions can be conflicting. This paper describes a systematic effort to measure the effect of pattern distribution on production system performance. An overview of the Rete algorithm is presented to provide context. A description of the methods used to explore the pattern ordering problem area are presented, using internal production system metrics such as the number of partial matches, and coarse-grained operating system data such as memory usage and time. The results of this study should be of interest to those developing and optimizing software for Rete-based production systems.

Dynamics of DDT in the terrestrial snail Otala lactea (Stylommatophora:Helicidae)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurzinger, K.H.; Dindal, D.L.

1975-01-01

Seventy specimens of Otala lactea (Mueller) were fed 40 ..mu..g radiolabelled DDT.gram/sup -1/ body weight and analyzed by liquid scintillation spectrometry to determine the body distribution and dynamics of the DDT within the snail's tissues. More than 50% of the pesticide fed to the animals was excreted in the feces after 1 to 2 days. Residues in the body accumulated mostly in the hepatopancreas. All tissues assayed contained measureable quantities of DDT. Five patterns of residue distribution/time were apparent. Pattern I, exhibited by the buccal mass, esophagus, crop, stomach and intestine, showed a general decrease in residue concentrations over themore » 14 day test period. Pattern II, exhibited by the hepatopancreas, kidney, ovotestis, sperm-oviduct, albumen gland and mucous gland, showed a general increase in residue concentrations. Pattern III, exhibited by the salivary gland, spermatheca, circumesophageal nerve ring, lung, collar (mantle edge), foot and vagina + dart sack, showed a fairly constant level of residues. Pattern IV, exhibited by the retractor muscles, epidermis and heart, showed a cyclical distribution of residue levels. Pattern V, exhibited by the penis, showed a cyclical distribution of residue levels that were different from Pattern IV. A double compartment scheme was utilized to explain those trends. Period A, corresponding to the fast compartment, is due to the initial ingestionof insecticide. Periods B and C, corresponding to the slow compartment, are due to the redistribution of residues within the organism.« less

Effects of defoliation in the developing leaf zone on young Populus Xeuramericana plants. II. Distribution of UC-photosynthate after defoliation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bassman, J.H.; Dickmann, D.I.

Patterns of UC-photosynthate distribution in growth chamber-grown Populus xeuramericana cv. Negrito de Granada were determined 24 h, 3 weeks, and 5 weeks after defoliation in the developing leaf zone. Translocation patterns were determined by exposing leaves below, within, or above the defoliated zone to UCO2 and determining UC distribution within the plant after 48 h. Translocation patterns were altered within 24 h after defoliation. When leaves below or remaining tissue of leaves within the zone of defoliation were exposed to UCO2, a greater percentage of UC-photosynthate was transported to the expanding shoot and lateral branches and less to the rootsmore » in defoliated plants compared to controls. Little difference between defoliated and control plants and UC distribution occurred when new leaves produced subsequent to defoliation were exposed to UCO2. By 5 weeks after defoliation there was little difference in patterns of UC distribution between defoliated and control plants. These results substantiate biomass partitioning data which showed that a single defoliation of young poplar plants did not affect diameter or height growth, whereas leaf growth was stimulated and root growth reduced.« less

Distributional patterns of arsenic concentrations in contaminant plumes offer clues to the source of arsenic in groundwater at landfills

USGS Publications Warehouse

Harte, Philip T.

2015-01-01

The distributional pattern of dissolved arsenic concentrations from landfill plumes can provide clues to the source of arsenic contamination. Under simple idealized conditions, arsenic concentrations along flow paths in aquifers proximal to a landfill will decrease under anthropogenic sources but potentially increase under in situ sources. This paper presents several conceptual distributional patterns of arsenic in groundwater based on the arsenic source under idealized conditions. An example of advanced subsurface mapping of dissolved arsenic with geophysical surveys, chemical monitoring, and redox fingerprinting is presented for a landfill site in New Hampshire with a complex flow pattern. Tools to assist in the mapping of arsenic in groundwater ultimately provide information on the source of contamination. Once an understanding of the arsenic contamination is achieved, appropriate remedial strategies can then be formulated.

Understanding User Behavioral Patterns in Open Knowledge Communities

ERIC Educational Resources Information Center

Yang, Xianmin; Song, Shuqiang; Zhao, Xinshuo; Yu, Shengquan

2018-01-01

Open knowledge communities (OKCs) have become popular in the era of knowledge economy. This study aimed to explore how users collaboratively create and share knowledge in OKCs. In particular, this research identified the behavior distribution and behavioral patterns of users by conducting frequency distribution and lag sequential analyses. Some…

School Finance Equalization Management System: An Overview.

ERIC Educational Resources Information Center

Educational Testing Service, Princeton, NJ. Education Policy Research Institute.

This overview acquaints prospective users with the School Finance Equalization Management System (SFEMS), a computer-based system designed to answer questions about state aid distribution. SFEMS can determine such things as the current pattern of aid distribution, the current pattern of tax effort, or the effect of alternative expenditure and…

Equilibrium theory of island biogeography: A review

Treesearch

Angela D. Yu; Simon A. Lei

2001-01-01

The topography, climatic pattern, location, and origin of islands generate unique patterns of species distribution. The equilibrium theory of island biogeography creates a general framework in which the study of taxon distribution and broad island trends may be conducted. Critical components of the equilibrium theory include the species-area relationship, island-...

Forest regions of Montana

Treesearch

Stephen F. Arno

1979-01-01

In this paper, Montana is divided into eight geographic subdivisions called "forest regions," based on distributions of tree and undergrowth species and the relationship of these patterns to climate and topography. The regions serve as a geographic reference for describing patterns of forest vegetation across the State. Data on the distributions of plant...

Antagonism Between Luminal and Caffeine, Studied by the Use of Radioisotopes; RECHERCHES SUR LES BARBITURIQUES RADIOACTIFS: LA DISTRIBUTION DU LUMINAL DANS L'ORGANISME ANIMAL EN PRESENCE DE CAFEINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aliprandi, B.; Masironi, R.

1959-10-31

The normal pattern of distribution of luminal in the animal organism was determined in mice using a tracer technique. The effect of an antagonistic drug, e.g., caffeine, on this normal distribution pattern was studied. The results confirmed the hypothesis of the in vivo breaking of the barbituric ring. (J.S.R.)

Empirical analysis on the runners' velocity distribution in city marathons

NASA Astrophysics Data System (ADS)

Lin, Zhenquan; Meng, Fan

2018-01-01

In recent decades, much researches have been performed on human temporal activity and mobility patterns, while few investigations have been made to examine the features of the velocity distributions of human mobility patterns. In this paper, we investigated empirically the velocity distributions of finishers in New York City marathon, American Chicago marathon, Berlin marathon and London marathon. By statistical analyses on the datasets of the finish time records, we captured some statistical features of human behaviors in marathons: (1) The velocity distributions of all finishers and of partial finishers in the fastest age group both follow log-normal distribution; (2) In the New York City marathon, the velocity distribution of all male runners in eight 5-kilometer internal timing courses undergoes two transitions: from log-normal distribution at the initial stage (several initial courses) to the Gaussian distribution at the middle stage (several middle courses), and to log-normal distribution at the last stage (several last courses); (3) The intensity of the competition, which is described by the root-mean-square value of the rank changes of all runners, goes weaker from initial stage to the middle stage corresponding to the transition of the velocity distribution from log-normal distribution to Gaussian distribution, and when the competition gets stronger in the last course of the middle stage, there will come a transition from Gaussian distribution to log-normal one at last stage. This study may enrich the researches on human mobility patterns and attract attentions on the velocity features of human mobility.

Pattern detection in stream networks: Quantifying spatialvariability in fish distribution

USGS Publications Warehouse

Torgersen, Christian E.; Gresswell, Robert E.; Bateman, Douglas S.

2004-01-01

Biological and physical properties of rivers and streams are inherently difficult to sample and visualize at the resolution and extent necessary to detect fine-scale distributional patterns over large areas. Satellite imagery and broad-scale fish survey methods are effective for quantifying spatial variability in biological and physical variables over a range of scales in marine environments but are often too coarse in resolution to address conservation needs in inland fisheries management. We present methods for sampling and analyzing multiscale, spatially continuous patterns of stream fishes and physical habitat in small- to medium-size watersheds (500–1000 hectares). Geospatial tools, including geographic information system (GIS) software such as ArcInfo dynamic segmentation and ArcScene 3D analyst modules, were used to display complex biological and physical datasets. These tools also provided spatial referencing information (e.g. Cartesian and route-measure coordinates) necessary for conducting geostatistical analyses of spatial patterns (empirical semivariograms and wavelet analysis) in linear stream networks. Graphical depiction of fish distribution along a one-dimensional longitudinal profile and throughout the stream network (superimposed on a 10-metre digital elevation model) provided the spatial context necessary for describing and interpreting the relationship between landscape pattern and the distribution of coastal cutthroat trout (Oncorhynchus clarki clarki) in western Oregon, U.S.A. The distribution of coastal cutthroat trout was highly autocorrelated and exhibited a spherical semivariogram with a defined nugget, sill, and range. Wavelet analysis of the main-stem longitudinal profile revealed periodicity in trout distribution at three nested spatial scales corresponding ostensibly to landscape disturbances and the spacing of tributary junctions.

Temporal patterns of mental model convergence: implications for distributed teams interacting in electronic collaboration spaces.

PubMed

McComb, Sara; Kennedy, Deanna; Perryman, Rebecca; Warner, Norman; Letsky, Michael

2010-04-01

Our objective is to capture temporal patterns in mental model convergence processes and differences in these patterns between distributed teams using an electronic collaboration space and face-to-face teams with no interface. Distributed teams, as sociotechnical systems, collaborate via technology to work on their task. The way in which they process information to inform their mental models may be examined via team communication and may unfold differently than it does in face-to-face teams. We conducted our analysis on 32 three-member teams working on a planning task. Half of the teams worked as distributed teams in an electronic collaboration space, and the other half worked face-to-face without an interface. Using event history analysis, we found temporal interdependencies among the initial convergence points of the multiple mental models we examined. Furthermore, the timing of mental model convergence and the onset of task work discussions were related to team performance. Differences existed in the temporal patterns of convergence and task work discussions across conditions. Distributed teams interacting via an electronic interface and face-to-face teams with no interface converged on multiple mental models, but their communication patterns differed. In particular, distributed teams with an electronic interface required less overall communication, converged on all mental models later in their life cycles, and exhibited more linear cognitive processes than did face-to-face teams interacting verbally. Managers need unique strategies for facilitating communication and mental model convergence depending on teams' degrees of collocation and access to an interface, which in turn will enhance team performance.

Graded bit patterned magnetic arrays fabricated via angled low-energy He ion irradiation.

PubMed

Chang, L V; Nasruallah, A; Ruchhoeft, P; Khizroev, S; Litvinov, D

2012-07-11

A bit patterned magnetic array based on Co/Pd magnetic multilayers with a binary perpendicular magnetic anisotropy distribution was fabricated. The binary anisotropy distribution was attained through angled helium ion irradiation of a bit edge using hydrogen silsesquioxane (HSQ) resist as an ion stopping layer to protect the rest of the bit. The viability of this technique was explored numerically and evaluated through magnetic measurements of the prepared bit patterned magnetic array. The resulting graded bit patterned magnetic array showed a 35% reduction in coercivity and a 9% narrowing of the standard deviation of the switching field.

Palmar dermatoglyphic patterns in twins.

PubMed

Jacques, S M; Salzano, F M; Penña, H F

1977-01-01

The role of genetic factors in the determination of palmar dermatoglyphic patterns was investigated in a series of 49 MZ and 51 DZ twins, using Spearman's rank correlation and analysis of variance. Both methods indicated that the genetic effect in the distribution of patterns is highest in the interdigital III and lowest in the interdigital IV regions, the hypothenar and thenar showing intermediate values. As for interdigital II, no evaluation of genetic effects was possible using the nonparametric test, but the estimates of genetic variance indicate that inherited factors may play a relatively minor role in the pattern distribution of this area.

Temperature distribution and heat radiation of patterned surfaces at short wavelengths.

PubMed

Emig, Thorsten

2017-05-01

We analyze the equilibrium spatial distribution of surface temperatures of patterned surfaces. The surface is exposed to a constant external heat flux and has a fixed internal temperature that is coupled to the outside heat fluxes by finite heat conductivity across the surface. It is assumed that the temperatures are sufficiently high so that the thermal wavelength (a few microns at room temperature) is short compared to all geometric length scales of the surface patterns. Hence the radiosity method can be employed. A recursive multiple scattering method is developed that enables rapid convergence to equilibrium temperatures. While the temperature distributions show distinct dependence on the detailed surface shapes (cuboids and cylinder are studied), we demonstrate robust universal relations between the mean and the standard deviation of the temperature distributions and quantities that characterize overall geometric features of the surface shape.

Temperature distribution and heat radiation of patterned surfaces at short wavelengths

NASA Astrophysics Data System (ADS)

Emig, Thorsten

2017-05-01

We analyze the equilibrium spatial distribution of surface temperatures of patterned surfaces. The surface is exposed to a constant external heat flux and has a fixed internal temperature that is coupled to the outside heat fluxes by finite heat conductivity across the surface. It is assumed that the temperatures are sufficiently high so that the thermal wavelength (a few microns at room temperature) is short compared to all geometric length scales of the surface patterns. Hence the radiosity method can be employed. A recursive multiple scattering method is developed that enables rapid convergence to equilibrium temperatures. While the temperature distributions show distinct dependence on the detailed surface shapes (cuboids and cylinder are studied), we demonstrate robust universal relations between the mean and the standard deviation of the temperature distributions and quantities that characterize overall geometric features of the surface shape.

Distribution and foraging patterns of common loons on Lake Michigan with implications for exposure to type E avian botulism

USGS Publications Warehouse

Kenow, Kevin P.; Houdek, Steven C.; Fara, Luke; Gray, Brian R.; Lubinski, Brian R.; Heard, Darryl J.; Meyer, Michael W.; Fox, Timothy J.; Kratt, Robert

2018-01-01

Common loons (Gavia immer) staging on the Great Lakes during fall migration are at risk to episodic outbreaks of type E botulism. Information on distribution, foraging patterns, and exposure routes of loons are needed for understanding the physical and ecological factors that contribute to avian botulism outbreaks. Aerial surveys were conducted to document the spatiotemporal distribution of common loons on Lake Michigan during falls 2011–2013. In addition, satellite telemetry and archival geolocator tags were used to determine the distribution and foraging patterns of individual common loons while using Lake Michigan during fall migration. Common loon distribution observed during aerial surveys and movements of individual radiomarked and/or geotagged loons suggest a seasonal pattern of use, with early fall use of Green Bay and northern Lake Michigan followed by a shift in distribution to southern Lake Michigan before moving on to wintering areas. Common loons tended to occupy offshore areas of Lake Michigan and, on average, spent the majority of daylight hours foraging. Dive depths were as deep as 60 m and dive characteristics suggested that loons were primarily foraging on benthic prey. A recent study concluded that round gobies (Neogobius melanostomus) are an important prey item of common loons and may be involved in transmission of botulinum neurotoxin type E. Loon distribution coincides with the distribution of dreissenid mussel biomass, an important food resource for round gobies. Our observations support speculation that energy transfer to higher trophic levels via gobies may occur in deep-water habitats, along with transfer of botulinum neurotoxin.

Individual analyses of Lévy walk in semi-free ranging Tonkean macaques (Macaca tonkeana).

PubMed

Sueur, Cédric; Briard, Léa; Petit, Odile

2011-01-01

Animals adapt their movement patterns to their environment in order to maximize their efficiency when searching for food. The Lévy walk and the Brownian walk are two types of random movement found in different species. Studies have shown that these random movements can switch from a Brownian to a Lévy walk according to the size distribution of food patches. However no study to date has analysed how characteristics such as sex, age, dominance or body mass affect the movement patterns of an individual. In this study we used the maximum likelihood method to examine the nature of the distribution of step lengths and waiting times and assessed how these distributions are influenced by the age and the sex of group members in a semi free-ranging group of ten Tonkean macaques. Individuals highly differed in their activity budget and in their movement patterns. We found an effect of age and sex of individuals on the power distribution of their step lengths and of their waiting times. The males and old individuals displayed a higher proportion of longer trajectories than females and young ones. As regards waiting times, females and old individuals displayed higher rates of long stationary periods than males and young individuals. These movement patterns resembling random walks can probably be explained by the animals moving from one location to other known locations. The power distribution of step lengths might be due to a power distribution of food patches in the enclosure while the power distribution of waiting times might be due to the power distribution of the patch sizes.

Establishing Functional Relationships between Abiotic Environment, Macrophyte Coverage, Resource Gradients and the Distribution of Mytilus trossulus in a Brackish Non-Tidal Environment.

PubMed

Kotta, Jonne; Oganjan, Katarina; Lauringson, Velda; Pärnoja, Merli; Kaasik, Ants; Rohtla, Liisa; Kotta, Ilmar; Orav-Kotta, Helen

2015-01-01

Benthic suspension feeding mussels are an important functional guild in coastal and estuarine ecosystems. To date we lack information on how various environmental gradients and biotic interactions separately and interactively shape the distribution patterns of mussels in non-tidal environments. Opposing to tidal environments, mussels inhabit solely subtidal zone in non-tidal waterbodies and, thereby, driving factors for mussel populations are expected to differ from the tidal areas. In the present study, we used the boosted regression tree modelling (BRT), an ensemble method for statistical techniques and machine learning, in order to explain the distribution and biomass of the suspension feeding mussel Mytilus trossulus in the non-tidal Baltic Sea. BRT models suggested that (1) distribution patterns of M. trossulus are largely driven by separate effects of direct environmental gradients and partly by interactive effects of resource gradients with direct environmental gradients. (2) Within its suitable habitat range, however, resource gradients had an important role in shaping the biomass distribution of M. trossulus. (3) Contrary to tidal areas, mussels were not competitively superior over macrophytes with patterns indicating either facilitative interactions between mussels and macrophytes or co-variance due to common stressor. To conclude, direct environmental gradients seem to define the distribution pattern of M. trossulus, and within the favourable distribution range, resource gradients in interaction with direct environmental gradients are expected to set the biomass level of mussels.

Establishing Functional Relationships between Abiotic Environment, Macrophyte Coverage, Resource Gradients and the Distribution of Mytilus trossulus in a Brackish Non-Tidal Environment

PubMed Central

Kotta, Jonne; Oganjan, Katarina; Lauringson, Velda; Pärnoja, Merli; Kaasik, Ants; Rohtla, Liisa; Kotta, Ilmar; Orav-Kotta, Helen

2015-01-01

Benthic suspension feeding mussels are an important functional guild in coastal and estuarine ecosystems. To date we lack information on how various environmental gradients and biotic interactions separately and interactively shape the distribution patterns of mussels in non-tidal environments. Opposing to tidal environments, mussels inhabit solely subtidal zone in non-tidal waterbodies and, thereby, driving factors for mussel populations are expected to differ from the tidal areas. In the present study, we used the boosted regression tree modelling (BRT), an ensemble method for statistical techniques and machine learning, in order to explain the distribution and biomass of the suspension feeding mussel Mytilus trossulus in the non-tidal Baltic Sea. BRT models suggested that (1) distribution patterns of M. trossulus are largely driven by separate effects of direct environmental gradients and partly by interactive effects of resource gradients with direct environmental gradients. (2) Within its suitable habitat range, however, resource gradients had an important role in shaping the biomass distribution of M. trossulus. (3) Contrary to tidal areas, mussels were not competitively superior over macrophytes with patterns indicating either facilitative interactions between mussels and macrophytes or co-variance due to common stressor. To conclude, direct environmental gradients seem to define the distribution pattern of M. trossulus, and within the favourable distribution range, resource gradients in interaction with direct environmental gradients are expected to set the biomass level of mussels. PMID:26317668

Is the nestedness of metazoan parasite assemblages of marine fishes from the southeastern Pacific coast a pattern associated with the geographical distributional range of the host?

PubMed

González, M T; Oliva, M E

2009-04-01

Nested structure is a pattern originally described in island biogeography to characterize how a set of species is distributed among a set of islands. In parasite communities, nestedness has been intensively studied among individual fish from a locality. However, nested patterns among parasite assemblages from different host populations (localities) have scarcely been investigated. We recorded the occurrence of parasites in 9 fish species widely distributed along the southeastern Pacific coast to determine whether the ecto- and endoparasite assemblages of marine fishes show a nested structure associated with host distributional range. Nestedness was tested using Brualdi-Sanderson index of discrepancy (BR); and 5 null models incorporated in a 'Nestedness' programme (Ulrich, 2006). The ecto- and endoparasite richness do not show similar patterns of latitudinal gradients among fish hosts, with 33-66% of analysed ectoparasite assemblages, and 25-75% of endoparasite assemblages showing nested structures through the host distributional range. For ectoparasites, species richness gradients and nested structure (when present) might be associated with decreased host densities or could reflect negative environmental conditions in the distributional border of the host species, whereas for endoparasites might be caused by geographical breaks of prey or changes in prey availability (intermediate hosts). The sampled extension of the distributional range of the host species, as well as the lack of specificity of some parasites, could influence the detection of nestedness.

Envelope: interactive software for modeling and fitting complex isotope distributions.

PubMed

Sykes, Michael T; Williamson, James R

2008-10-20

An important aspect of proteomic mass spectrometry involves quantifying and interpreting the isotope distributions arising from mixtures of macromolecules with different isotope labeling patterns. These patterns can be quite complex, in particular with in vivo metabolic labeling experiments producing fractional atomic labeling or fractional residue labeling of peptides or other macromolecules. In general, it can be difficult to distinguish the contributions of species with different labeling patterns to an experimental spectrum and difficult to calculate a theoretical isotope distribution to fit such data. There is a need for interactive and user-friendly software that can calculate and fit the entire isotope distribution of a complex mixture while comparing these calculations with experimental data and extracting the contributions from the differently labeled species. Envelope has been developed to be user-friendly while still being as flexible and powerful as possible. Envelope can simultaneously calculate the isotope distributions for any number of different labeling patterns for a given peptide or oligonucleotide, while automatically summing these into a single overall isotope distribution. Envelope can handle fractional or complete atom or residue-based labeling, and the contribution from each different user-defined labeling pattern is clearly illustrated in the interactive display and is individually adjustable. At present, Envelope supports labeling with 2H, 13C, and 15N, and supports adjustments for baseline correction, an instrument accuracy offset in the m/z domain, and peak width. Furthermore, Envelope can display experimental data superimposed on calculated isotope distributions, and calculate a least-squares goodness of fit between the two. All of this information is displayed on the screen in a single graphical user interface. Envelope supports high-quality output of experimental and calculated distributions in PNG or PDF format. Beyond simply comparing calculated distributions to experimental data, Envelope is useful for planning or designing metabolic labeling experiments, by visualizing hypothetical isotope distributions in order to evaluate the feasibility of a labeling strategy. Envelope is also useful as a teaching tool, with its real-time display capabilities providing a straightforward way to illustrate the key variable factors that contribute to an observed isotope distribution. Envelope is a powerful tool for the interactive calculation and visualization of complex isotope distributions for comparison to experimental data. It is available under the GNU General Public License from http://williamson.scripps.edu/envelope/.

Extreme deconstruction supports niche conservatism driving New World bird diversity

NASA Astrophysics Data System (ADS)

Diniz-Filho, José Alexandre Felizola; Rangel, Thiago Fernando; dos Santos, Mariana Rocha

2012-08-01

It is expected that if environment fully establishes the borders of species geographic distribution, then richness patterns will arise simple by changing parameters on how environment affect each of the species. However, if other mechanisms (i.e., non-equilibrium of species' distributions with climate and historical contingency, shifts in adaptive peaks or biotic interactions) are driving species geographic distribution, models for species distribution and richness will not entirely match. Here we used the extreme deconstruction principle to test how niche conservatism keeping species geographic distributions in certain parts of environmental space drives richness patterns in New World birds, under tropical niche conservatism. Eight environmental variables were used to model the geographic distribution of 2790 species within 28 bird families using a GLM. Spatial patterns in richness for each of these families were also modeled as a function of these same variables using a standard OLS regression. Fit of these two types of models (mean MacFadden's ρ2 for GLM and R2 of OLS) across families and the match between GLM and OLS standardized slopes within and among bird families were then compared. We found a positive and significant correlation between GLM and OLS model fit (r = 0.601; P < 0.01), indicating that when environment strongly determine richness of a family, it also explains its species geographic distributions. The match between GLM and OLS slopes is significantly correlated with families' phylogenetic root distance (r = -0.467; P = 0.012), so that more basal families tend to have a better match between environmental drivers of richness and geographic distribution models. This is expected under tropical niche conservatism model and provides an integrated explanation on how processes at a lower hierarchical level (species' geographic distribution) drive diversity patterns.

Constraining ejecta particle size distributions with light scattering

NASA Astrophysics Data System (ADS)

Schauer, Martin; Buttler, William; Frayer, Daniel; Grover, Michael; Lalone, Brandon; Monfared, Shabnam; Sorenson, Daniel; Stevens, Gerald; Turley, William

2017-06-01

The angular distribution of the intensity of light scattered from a particle is strongly dependent on the particle size and can be calculated using the Mie solution to Maxwell's equations. For a collection of particles with a range of sizes, the angular intensity distribution will be the sum of the contributions from each particle size weighted by the number of particles in that size bin. The set of equations describing this pattern is not uniquely invertible, i.e. a number of different distributions can lead to the same scattering pattern, but with reasonable assumptions about the distribution it is possible to constrain the problem and extract estimates of the particle sizes from a measured scattering pattern. We report here on experiments using particles ejected by shockwaves incident on strips of triangular perturbations machined into the surface of tin targets. These measurements indicate a bimodal distribution of ejected particle sizes with relatively large particles (median radius 2-4 μm) evolved from the edges of the perturbation strip and smaller particles (median radius 200-600 nm) from the perturbations. We will briefly discuss the implications of these results and outline future plans.

A gossip based information fusion protocol for distributed frequent itemset mining

NASA Astrophysics Data System (ADS)

Sohrabi, Mohammad Karim

2018-07-01

The computational complexity, huge memory space requirement, and time-consuming nature of frequent pattern mining process are the most important motivations for distribution and parallelization of this mining process. On the other hand, the emergence of distributed computational and operational environments, which causes the production and maintenance of data on different distributed data sources, makes the parallelization and distribution of the knowledge discovery process inevitable. In this paper, a gossip based distributed itemset mining (GDIM) algorithm is proposed to extract frequent itemsets, which are special types of frequent patterns, in a wireless sensor network environment. In this algorithm, local frequent itemsets of each sensor are extracted using a bit-wise horizontal approach (LHPM) from the nodes which are clustered using a leach-based protocol. Heads of clusters exploit a gossip based protocol in order to communicate each other to find the patterns which their global support is equal to or more than the specified support threshold. Experimental results show that the proposed algorithm outperforms the best existing gossip based algorithm in term of execution time.

Patterns of Drug Distribution: Implications and Issues#

PubMed Central

Johnson, Bruce D.

2007-01-01

This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years, including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for “drug abuse” to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues. PMID:14582578

Patterns of drug distribution: implications and issues.

PubMed

Johnson, Bruce D

2003-01-01

This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years. including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for "drug abuse" to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues.

Inhomogeneity Based Characterization of Distribution Patterns on the Plasma Membrane

PubMed Central

Paparelli, Laura; Corthout, Nikky; Wakefield, Devin L.; Sannerud, Ragna; Jovanovic-Talisman, Tijana; Annaert, Wim; Munck, Sebastian

2016-01-01

Cell surface protein and lipid molecules are organized in various patterns: randomly, along gradients, or clustered when segregated into discrete micro- and nano-domains. Their distribution is tightly coupled to events such as polarization, endocytosis, and intracellular signaling, but challenging to quantify using traditional techniques. Here we present a novel approach to quantify the distribution of plasma membrane proteins and lipids. This approach describes spatial patterns in degrees of inhomogeneity and incorporates an intensity-based correction to analyze images with a wide range of resolutions; we have termed it Quantitative Analysis of the Spatial distributions in Images using Mosaic segmentation and Dual parameter Optimization in Histograms (QuASIMoDOH). We tested its applicability using simulated microscopy images and images acquired by widefield microscopy, total internal reflection microscopy, structured illumination microscopy, and photoactivated localization microscopy. We validated QuASIMoDOH, successfully quantifying the distribution of protein and lipid molecules detected with several labeling techniques, in different cell model systems. We also used this method to characterize the reorganization of cell surface lipids in response to disrupted endosomal trafficking and to detect dynamic changes in the global and local organization of epidermal growth factor receptors across the cell surface. Our findings demonstrate that QuASIMoDOH can be used to assess protein and lipid patterns, quantifying distribution changes and spatial reorganization at the cell surface. An ImageJ/Fiji plugin of this analysis tool is provided. PMID:27603951

The numerical model of the sediment distribution pattern at Lampulo National fisheries port

NASA Astrophysics Data System (ADS)

Irham, M.; Setiawan, I.

2018-01-01

The spatial distribution of sediment pattern was studied at Lampulo Fisheries Port, Krueng Aceh estuarial area, Banda Aceh. The research was conducted using the numerical model of wave-induced currents at shallow water area. The study aims to understand how waves and currents react to the pattern of sediment distribution around the beach structure in that region. The study demonstrated that the port pool area had no sedimentation and erosion occurred because the port was protected by the jetty as the breakwater to defend the incoming waves toward the pool. The protected pool created a weak current circulation to distribute the sediments. On the other hand, the sediments were heavily distributed along the beach due to the existence of longshore currents near the shoreline (outside the port pool area). Meanwhile, at the estuarial area, the incoming fresh water flow responded to the coastal shallow water currents, generating Eddy-like flow at the mouth of the river.

Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study.

PubMed

Jiang, Xi Zhuo; Feng, Muye; Ventikos, Yiannis; Luo, Kai H

2018-04-10

Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.

The pattern of the arterial supply of the pancreas in anthropoid apes, catarrhine monkeys and platyrrhine monkeys.

PubMed

Shawuti, Alimujiang; Miyaki, Takayoshi; Saito, Toshiyuki; Itoh, Masahiro

2009-11-01

To get the full understanding of the arterial distribution to the pancreas, the analysis of the distribution of the variety of monkey species would be helpful. In this study, we studied the layout of the pancreatic artery in anthropoids (1 gorilla, 3 chimpanzees and 2 white-handed gibbons), in catarrhine monkeys (1 hamadryas baboon, 2 anubid baboons, 10 savannah monkeys) and in platyrrhine monkeys (6 squirrel monkeys). The pancreas of the monkeys was supplied by the arteries originating from the celiac trunk and/or superior mesenteric artery. There were three patterns in the arterial distribution; (1) the celiac artery supplied the major area of the pancreas. (2) the superior mesenteric artery supplied the major area of the pancreas. (3) the celiac artery supplied the whole pancreas. The pattern of the arterial distribution to the monkey pancreas had a wide variety. The result would be helpful for the elucidation of the development of the vascular distribution in the pancreas.

Distribution pattern of rare earth ions between water and montmorillonite and its relation to the sorbed species of the ions.

PubMed

Takahashi, Yoshio; Tada, Akisa; Shimizu, Hiroshi

2004-09-01

REE (rare earth element) distribution coefficients (Kd) between the aqueous phase and montmorillonite surface were obtained to investigate the relation between the REE distribution patterns and the species of REE sorbed on the solid-water interface. It was shown that the features in the REE patterns, such as the slope of the REE patterns, the tetrad effect, and the Y/Ho ratio, were closely related to the REE species at the montmorillonite-water interface. In a binary system (REE-montmorillonite) below pH 5, three features (a larger Kd value for a lighter REE, the absence of the tetrad effect, and the Y/Ho ratio being unchanged from its initial value) suggest that hydrated REE are directly sorbed as an outer-sphere complex at the montmorillonite-water interface. Above pH 5.5, the features in the REE patterns, the larger Kd value for heavier REE, the M-type tetrad effect, and the reduced Y/Ho ratio, showed the formation of an inner-sphere complex of REE with -OH group at the montmorillonite surface. In addition, the REE patterns in the presence of humic acid at pH 5.9 were also studied, where the REE patterns became flat, suggesting that the humate complex is dominant as both dissolved and sorbed species of REE in the ternary system. All of these results were consistent with the spectroscopic data (laser-induced fluorescence spectroscopy) showing the local structure of Eu(III) conducted in the same experimental system. The present results suggest that the features in the REE distribution patterns include information on the REE species at the solid-water interface.

Recent human history governs global ant invasion dynamics

Treesearch

Cleo Bertelsmeier; Sébastien Ollier; Andrew Liebhold; Laurent Keller

2017-01-01

Human trade and travel are breaking down biogeographic barriers, resulting in shifts in the geographical distribution of organisms, yet it remains largely unknown whether different alien species generally follow similar spatiotemporal colonization patterns and how such patterns are driven by trends in global trade. Here, we analyse the global distribution of 241 alien...

Sex-Biased Ratio of Avoidant/Ambivalent Attachment in Middle Childhood

ERIC Educational Resources Information Center

Del Giudice, Marco

2008-01-01

In this study, new evidence is presented of marked sex differences in the distribution of insecure attachment patterns in middle childhood. Attachment was assessed with the Manchester Child Attachment Story Task (MCAST) in a sample of 122 Italian 7-year-olds. The four-way distribution of attachment patterns was significantly unbalanced, with…

Arthropod vertical stratification in temperate deciduous forests: Implications for conservation oriented management

Treesearch

Ulyshen Michael

2011-01-01

Studies on the vertical distribution patterns of arthropods in temperate deciduous forests reveal highly stratified (i.e., unevenly vertically distributed) communities. These patterns are determined by multiple factors acting simultaneously, including: (1) time (forest age, season, time of day); (2) forest structure (height, vertical foliage complexity, plant surface...

Within-band spray distribution of nozzles used for herbaceous plant control

Treesearch

James H. Miller

1994-01-01

Abstract. Described are the spray patterns of nozzles setup for banded herbaceous plant control treatments. Spraying Systems Company nozzles. were tested, but similar nozzles are available from other manufacturers. Desirable traits were considered to be as follows: an even distribution pattern, low volume, low height, large droplets, and a single...

Distributed and Relative Nature of Professional Expertise

ERIC Educational Resources Information Center

Pillay, Hitendra; McCrindle, Andrea R.

2005-01-01

This exploratory study investigates the distributed nature and complexity of professional expertise by examining the patterns of cognitive processes in novices and experts who are using ultrasound technology to make diagnoses. The study aims to identify and provide an explanation for such patterns in light of the recent debate on the locus of…

The biomass, abundance, and distribution pattern of starfish Asterias sp. (Echinodermata: Asteroidea) in East Coast of Surabaya

NASA Astrophysics Data System (ADS)

Dewi, N. N.; Pursetyo, K. T.; Aprilianitasari, L.; Zakaria, M. H.; Ramadhan, M. R.; Triatmaja, R. A.

2018-04-01

This study aims to determine the biomass, density, and distribution patterns of Asterias sp. Samples were collected from three locations such as Wonokromo, Dadapan and Juanda, each divided into 3 zones. In each zone, samples were taken as many as 5 repetitions using swept area method. Temporarily, the highest biomass of starfish was 2.95 gr/m2 in Dadapan Zone on January. Spatially, biomass of starfish was found in Dadapan Zone (3,35 gr/m2). Similarly, the high density was also found in Dadapan Zone on January (9 ind/10 m2). In general, the distributionpattern of starfish in East Coast Surabaya throughspatial and temporal showed that the pattern of starfish was grouping distribution (Id value > 1) for Dadapan and Juanda, and uniform for Wonokromo. Oceanographic condition, antropogenic activity, and water quality in East Cost of Surabaya become important things which is affected the biomass, densityand distribution pattern of starfish. The knowledge of starfish biomass and density is very important given that this biota has ecological value as a balancing ecosystem in the waters.

Fractionation and mobility of Cu, Fe, Mn, Pb and Zn in the road dust retained on noise barriers along expressway - a potential tool for determining the effects of driving conditions on speciation of emitted particulate metals.

PubMed

Świetilik, Ryszard; Trojanowska, Marzena; Strzelecka, Monika; Bocho-Janiszewska, Anita

2015-01-01

Road dust (RD) retained on noise barriers was used as a monitor of emission of traffic-related metals from expressway. By using SEM/EDX analysis it has been revealed that the main components of this particulate were irregular fine aggregates and tire debris with a ragged porous structure and with inclusions derived from the road surface. The results of chemical fractionation showed that driving conditions influence strongly a distribution pattern of Cu, whereas the atmospheric corrosion process affects a distribution pattern of Zn. The distribution pattern of Cu originating only from vehicle braking emission was “isolated” from the distribution pattern of road traffic copper. The predicted comparative mobilities of the emitted metals form the order: Zn > Cu ≈ Mn > Pb > Fe. The high mobility of zinc (K = 0.61)may create a current inhalation hazard and may be a source of future environmental hazard in the areas adjacent to heavily trafficked roads.

Atmospheric water distribution in a midlatitude cyclone observed by the Seasat Scanning Multichannel Microwave Radiometer

NASA Technical Reports Server (NTRS)

Mcmurdie, L. A.; Katsaros, K. B.

1985-01-01

Patterns in the horizontal distribution of integrated water vapor, integrated liquid water and rainfall rate derived from the Seasat Scanning Multichannel Microwave Radiometer (SMMR) during a September 10-12, 1978 North Pacific cyclone are studied. These patterns are compared with surface analyses, ship reports, radiosonde data, and GOES-West infrared satellite imagery. The SMMR data give a unique view of the large mesoscale structure of a midlatitude cyclone. The water vapor distribution is found to have characteristic patterns related to the location of the surface fronts throughout the development of the cyclone. An example is given to illustrate that SMMR data could significantly improve frontal analysis over data-sparse oceanic regions. The distribution of integrated liquid water agrees qualitatively well with corresponding cloud patterns in satellite imagery and appears to provide a means to distinguish where liquid water clouds exist under a cirrus shield. Ship reports of rainfall intensity agree qualitatively very well with SMMR-derived rainrates. Areas of mesoscale rainfall, on the order of 50 km x 50 km or greater are detected using SMMR derived rainrates.

Global marine bacterial diversity peaks at high latitudes in winter

PubMed Central

Ladau, Joshua; Sharpton, Thomas J; Finucane, Mariel M; Jospin, Guillaume; Kembel, Steven W; O'Dwyer, James; Koeppel, Alexander F; Green, Jessica L; Pollard, Katherine S

2013-01-01

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms. PMID:23514781

Towards multifocal ultrasonic neural stimulation: pattern generation algorithms

NASA Astrophysics Data System (ADS)

Hertzberg, Yoni; Naor, Omer; Volovick, Alexander; Shoham, Shy

2010-10-01

Focused ultrasound (FUS) waves directed onto neural structures have been shown to dynamically modulate neural activity and excitability, opening up a range of possible systems and applications where the non-invasiveness, safety, mm-range resolution and other characteristics of FUS are advantageous. As in other neuro-stimulation and modulation modalities, the highly distributed and parallel nature of neural systems and neural information processing call for the development of appropriately patterned stimulation strategies which could simultaneously address multiple sites in flexible patterns. Here, we study the generation of sparse multi-focal ultrasonic distributions using phase-only modulation in ultrasonic phased arrays. We analyse the relative performance of an existing algorithm for generating multifocal ultrasonic distributions and new algorithms that we adapt from the field of optical digital holography, and find that generally the weighted Gerchberg-Saxton algorithm leads to overall superior efficiency and uniformity in the focal spots, without significantly increasing the computational burden. By combining phased-array FUS and magnetic-resonance thermometry we experimentally demonstrate the simultaneous generation of tightly focused multifocal distributions in a tissue phantom, a first step towards patterned FUS neuro-modulation systems and devices.

Predicting spiral wave patterns from cell properties in a model of biological self-organization.

PubMed

Geberth, Daniel; Hütt, Marc-Thorsten

2008-09-01

In many biological systems, biological variability (i.e., systematic differences between the system components) can be expected to outrank statistical fluctuations in the shaping of self-organized patterns. In principle, the distribution of single-element properties should thus allow predicting features of such patterns. For a mathematical model of a paradigmatic and well-studied pattern formation process, spiral waves of cAMP signaling in colonies of the slime mold Dictyostelium discoideum, we explore this possibility and observe a pronounced anticorrelation between spiral waves and cell properties (namely, the firing rate) and particularly a clustering of spiral wave tips in regions devoid of spontaneously firing (pacemaker) cells. Furthermore, we observe local inhomogeneities in the distribution of spiral chiralities, again induced by the pacemaker distribution. We show that these findings can be explained by a simple geometrical model of spiral wave generation.

Agricultural Aircraft Aid

NASA Technical Reports Server (NTRS)

1982-01-01

Farmers are increasingly turning to aerial applications of pesticides, fertilizers and other materials. Sometimes uneven distribution of the chemicals is caused by worn nozzles, improper alignment of spray nozzles or system leaks. If this happens, job must be redone with added expense to both the pilot and customer. Traditional pattern analysis techniques take days or weeks. Utilizing NASA's wind tunnel and computer validation technology, Dr. Roth, Oklahoma State University (OSU), developed a system for providing answers within minutes. Called the Rapid Distribution Pattern Evaluation System, the OSU system consists of a 100-foot measurement frame tied in to computerized analysis and readout equipment. System is mobile, delivered by trailer to airfields in agricultural areas where OSU conducts educational "fly-ins." A fly-in typically draws 50 to 100 aerial applicators, researchers, chemical suppliers and regulatory officials. An applicator can have his spray pattern checked. A computerized readout, available in five to 12 minutes, provides information for correcting shortcomings in the distribution pattern.

Predicting spiral wave patterns from cell properties in a model of biological self-organization

NASA Astrophysics Data System (ADS)

Geberth, Daniel; Hütt, Marc-Thorsten

2008-09-01

In many biological systems, biological variability (i.e., systematic differences between the system components) can be expected to outrank statistical fluctuations in the shaping of self-organized patterns. In principle, the distribution of single-element properties should thus allow predicting features of such patterns. For a mathematical model of a paradigmatic and well-studied pattern formation process, spiral waves of cAMP signaling in colonies of the slime mold Dictyostelium discoideum, we explore this possibility and observe a pronounced anticorrelation between spiral waves and cell properties (namely, the firing rate) and particularly a clustering of spiral wave tips in regions devoid of spontaneously firing (pacemaker) cells. Furthermore, we observe local inhomogeneities in the distribution of spiral chiralities, again induced by the pacemaker distribution. We show that these findings can be explained by a simple geometrical model of spiral wave generation.

Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

1997-01-01

The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

1998-01-01

The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids.

PubMed

Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C; Reinheimer, Renata; Zuloaga, Fernando O

2016-01-01

Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.

Establishment of a finite element model of a neonate's skull to evaluate the stress pattern distribution resulting during nasoalveolar molding therapy of cleft lip and palate patients.

PubMed

Bauer, Franz X; Heinrich, Veronika; Grill, Florian D; Wölfle, Felix; Hedderich, Dennis M; Rau, Andrea; Wolff, Klaus-Dietrich; Ritschl, Lucas M; Loeffelbein, Denys J

2018-04-01

Nasoalveolar Molding (NAM) is associated with ambivalent acceptance regarding effectiveness and unknown long-term results. Our purpose was to analyze the stress distribution patterns within the viscero- and neurocranium of neonates during the first phase of NAM therapy. A finite element (FE) model of a healthy four-week-old neonate was generated, derived from a computed tomography scan allowing the implementation of a bone-density-dependent material model. The influence of dental germs with variable material properties, the cleft width and area of expected force application were analyzed in a worst-case scenario. The resulting stress distribution patterns for each situation were analyzed using the software Ansys APDL. The established FE model was verified with a convergence analysis. Overall, stress patterns at the age of four weeks showed von Mises stress values below 60.000 Pa in the viscero- and neurocranium. The influences of the allocation of material properties for the dental germs, the area of force application, and the cleft width were negligible. A workflow to simulate the stress distribution and deformation in neonates attributable to various areas of force application has been established. Further analyses of the skulls of younger and older neonates are needed to describe the stress distribution patterns during NAM therapy. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The force synergy of human digits in static and dynamic cylindrical grasps.

PubMed

Kuo, Li-Chieh; Chen, Shih-Wei; Lin, Chien-Ju; Lin, Wei-Jr; Lin, Sheng-Che; Su, Fong-Chin

2013-01-01

This study explores the force synergy of human digits in both static and dynamic cylindrical grasping conditions. The patterns of digit force distribution, error compensation, and the relationships among digit forces are examined to quantify the synergetic patterns and coordination of multi-finger movements. This study recruited 24 healthy participants to perform cylindrical grasps using a glass simulator under normal grasping and one-finger restricted conditions. Parameters such as the grasping force, patterns of digit force distribution, and the force coefficient of variation are determined. Correlation coefficients and principal component analysis (PCA) are used to estimate the synergy strength under the dynamic grasping condition. Specific distribution patterns of digit forces are identified for various conditions. The compensation of adjacent fingers for the force in the normal direction of an absent finger agrees with the principle of error compensation. For digit forces in anti-gravity directions, the distribution patterns vary significantly by participant. The forces exerted by the thumb are closely related to those exerted by other fingers under all conditions. The index-middle and middle-ring finger pairs demonstrate a significant relationship. The PCA results show that the normal forces of digits are highly coordinated. This study reveals that normal force synergy exists under both static and dynamic cylindrical grasping conditions.

The Force Synergy of Human Digits in Static and Dynamic Cylindrical Grasps

PubMed Central

Kuo, Li-Chieh; Chen, Shih-Wei; Lin, Chien-Ju; Lin, Wei-Jr; Lin, Sheng-Che; Su, Fong-Chin

2013-01-01

This study explores the force synergy of human digits in both static and dynamic cylindrical grasping conditions. The patterns of digit force distribution, error compensation, and the relationships among digit forces are examined to quantify the synergetic patterns and coordination of multi-finger movements. This study recruited 24 healthy participants to perform cylindrical grasps using a glass simulator under normal grasping and one-finger restricted conditions. Parameters such as the grasping force, patterns of digit force distribution, and the force coefficient of variation are determined. Correlation coefficients and principal component analysis (PCA) are used to estimate the synergy strength under the dynamic grasping condition. Specific distribution patterns of digit forces are identified for various conditions. The compensation of adjacent fingers for the force in the normal direction of an absent finger agrees with the principle of error compensation. For digit forces in anti-gravity directions, the distribution patterns vary significantly by participant. The forces exerted by the thumb are closely related to those exerted by other fingers under all conditions. The index-middle and middle-ring finger pairs demonstrate a significant relationship. The PCA results show that the normal forces of digits are highly coordinated. This study reveals that normal force synergy exists under both static and dynamic cylindrical grasping conditions. PMID:23544151

The preferential accumulation of cadmium in the head portion of the freshwater planarian, Dugesia japonica (Platyhelminthes: Turbellaria).

PubMed

Wu, Jui-Pin; Chen, Hon-Cheng; Li, Mei-Hui

2011-12-01

Free-living freshwater planarians are considered to have the potential for development as an experimental model for toxicological studies on xenobiotics, including metals. However, little was known about the distribution patterns of metals in the body of treated planarians. This study was conducted to determine the tissue distribution patterns of cadmium (Cd) in different body portions of the treated planarian, Dugesia japonica. Results showed that Cd accumulated in the head of planarians at a significantly higher concentration than in the tail. After examining the level of metallothionein (MT), we suggested that the tissue distribution pattern of Cd might be related to MT induction patterns. In contrast, in planarians treated with copper (Cu), neither the tissue accumulation of Cu nor the multiples of induction of MTs significantly differed between different portions. Furthermore, a higher Cd accumulation rate in the head of planarians caused more-severe oxidative stress to appear in this portion and also a higher susceptibility to a lethal concentration of Cd. Finally, both in vitro and in vivo acetylcholinesterase activities in both body portions of planarians were inhibited by Cd. The present study provides the first report that different metals are distributed in various body portions with different patterns in the planarian.

Changes in the pattern of distribution of von Willebrand factor in rat aortic endothelial cells following thrombin generation in vivo.

PubMed

Senis, Y A; Richardson, M; Tinlin, S; Maurice, D H; Giles, A R

1996-04-01

The pattern of distribution of von Willebrand factor (VWF) in relatively large sheets of rat aortic endothelial cells (EC) obtained by the Häutchen technique were analysed by immunocytochemistry and light microscopy. EC were examined pre and post administration of a procoagulant mixture of factor Xa (F.Xa) and phosphotidylcholine/phosphotidylserine (PCPS) vesicles which was demonstrated to result in the selective loss of high molecular weight multimers (HMWM) of plasma VWF in the rat. In placebo animals the pattern was heterogenous both in overall distribution and in individual cells which showed both a diffuse and granular pattern. Groups of intensely stained EC were oriented parallel to the longitudinal axis of the aorta and staining was particularly prominent around the orifices of the intercostal arteries, implicating shear-stress as a possible factor in VWF expression by EC. Changes in the pattern of distribution of staining were observed at various time points post-infusion of F.Xa/PCPS, suggesting the immediate release of VWF from EC stores followed by the recruitment of EC to synthesize and store VWF. These changes are consistent with the decrease in EC Weibel-Palade Body (WPB) content observed by EM in previously reported studies using this model.

Characterization of traffic-related PM concentration distribution and fluctuation patterns in near-highway urban residential street canyons.

PubMed

Hahn, Intaek; Brixey, Laurie A; Wiener, Russell W; Henkle, Stacy W; Baldauf, Richard

2009-12-01

Analyses of outdoor traffic-related particulate matter (PM) concentration distribution and fluctuation patterns in urban street canyons within a microscale distance of less than 500 m from a highway source are presented as part of the results from the Brooklyn Traffic Real-Time Ambient Pollutant Penetration and Environmental Dispersion (B-TRAPPED) study. Various patterns of spatial and temporal changes in the street canyon PM concentrations were investigated using time-series data of real-time PM concentrations measured during multiple monitoring periods. Concurrent time-series data of local street canyon wind conditions and wind data from the John F. Kennedy (JFK) International Airport National Weather Service (NWS) were used to characterize the effects of various wind conditions on the behavior of street canyon PM concentrations.Our results suggest that wind direction may strongly influence time-averaged mean PM concentration distribution patterns in near-highway urban street canyons. The rooftop-level wind speeds were found to be strongly correlated with the PM concentration fluctuation intensities in the middle sections of the street blocks. The ambient turbulence generated by shifting local wind directions (angles) showed a good correlation with the PM concentration fluctuation intensities along the entire distance of the first and second street blocks only when the wind angle standard deviations were larger than 30 degrees. Within-canyon turbulent shearing, caused by fluctuating local street canyon wind speeds, showed no correlation with PM concentration fluctuation intensities. The time-averaged mean PM concentration distribution along the longitudinal distances of the street blocks when wind direction was mostly constantly parallel to the street was found to be similar to the distribution pattern for the entire monitoring period when wind direction fluctuated wildly. Finally, we showed that two different PM concentration metrics-time-averaged mean concentration and number of concentration peaks above a certain threshold level-can possibly lead to different assessments of spatial concentration distribution patterns.

Pattern of occurrence of leukemia at a teaching hospital in eastern region of Nepal - a six year study.

PubMed

Kulshrestha, R; Sah, S P

2009-01-01

Pattern of leukemia is known to vary widely throughout the world. The characterization of distribution patterns of different subtypes of leukemia in Nepal needs further study. We wanted to study the leukemia pattern in our institute. A retrospective study of 196 cases of leukemia, diagnosed at BPKIHS, between January 1997 to December 2002 was done. We analyzed the pattern of leukemia at BPKIHS by morphological subtype, gender, age at diagnosis, time period of diagnosis (seasonality), and geographic distribution. Morphological sub typing showed that 121 cases were of acute leukemia and 75 of chronic leukemia. Chronic myeloid leukemia constituted the single largest group comprising 35.2 % of all cases, followed by acute myeloid leukemia (28.57 %) and acute lymphoid leukemia (19.9 %). Maximum numbers of cases were from the lowlands while least number of cases were from the mountain districts. Results were compared with literature from Nepal and other countries. This is the second series of leukemia from Nepal. The data published in this study reflects the leukemia pattern in the eastern region of Nepal. The pattern and distribution of AML, CML, ALL was similar to that in the developed western countries while the lesser frequency of CLL was similar to that in Southeast Asian region.

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed Central

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-01-01

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners. PMID:12396487

Spatio-temporal patterns of bacteria caused by collective motion

NASA Astrophysics Data System (ADS)

Kitsunezaki, So

2006-04-01

In incubation experiments on bacterial colonies of Proteus mirabilis, collective motion of bacteria is found to generate macroscopic turbulent patterns on the surface of agar media. We propose a mathematical model to describe the time evolution of the positional and directional distributions of motile bacteria in such systems, and investigate this model both numerically and analytically. It is shown that as the average density of bacteria increases, nonuniform swarming patterns emerge from a uniform stationary state. For a sufficient large density, we find that spiral patterns are caused by interactions between the local bacteria densities and the rotational mode of the collective motion. Unidirectional spiral patterns similar to those observed in experiments appear in the case in which the equilibrium directional distribution is asymmetric.

The spatial distribution of umbral dots and granules

NASA Astrophysics Data System (ADS)

Lawrence, J. K.

1983-08-01

It is pointed out that the study of point patterns in two dimensions is of extremely broad interest in both the natural and social sciences. The subjects to which this study has been applied include tree distributions in forests, bird nesting patterns, the growth of towns, crystal formation in rocks, and the distribution of galaxies on the sky. The present investigation is concerned with the particular example of the distribution of umbral dots and their similarity, or dissimilarity, to photospheric granules. Attention is given to a collection of N points in an area A, statistical comparisons of distributions, and studies conducted by Bumba and Suda (1980) and Adjabshirzadeh and Koutchmy (1980, 1982).

Spatial Distribution Patterns in the Very Rare and Species-Rich Picea chihuahuana Tree Community (Mexico).

PubMed

Wehenkel, Christian; Brazão-Protázio, João Marcelo; Carrillo-Parra, Artemio; Martínez-Guerrero, José Hugo; Crecente-Campo, Felipe

2015-01-01

The very rare Mexican Picea chihuahuana tree community covers an area of no more than 300 ha in the Sierra Madre Occidental. This special tree community has been the subject of several studies aimed at learning more about the genetic structure and ecology of the species and the potential effects of climate change. The spatial distribution of trees is a result of many ecological processes and can affect the degree of competition between neighbouring trees, tree density, variability in size and distribution, regeneration, survival, growth, mortality, crown formation and the biological diversity within forest communities. Numerous scale-dependent measures have been established in order to describe spatial forest structure. The overall aim of most of these studies has been to obtain data to help design preservation and conservation strategies. In this study, we examined the spatial distribution pattern of trees in the P. chihuahuana tree community in 12 localities, in relation to i) tree stand density, ii) diameter distribution (vertical structure), iii) tree species diversity, iv) geographical latitude and v) tree dominance at a fine scale (in 0.25 ha plots), with the aim of obtaining a better understanding of the complex ecosystem processes and biological diversity. Because of the strongly mixed nature of this tree community, which often produces low population densities of each tree species and random tree fall gaps caused by tree death, we expect aggregated patterns in individual Picea chihuahuana trees and in the P. chihuahuana tree community, repulsive Picea patterns to other tree species and repulsive patterns of young to adult trees. Each location was represented by one plot of 50 x 50 m (0.25 ha) established in the centre of the tree community. The findings demonstrate that the hypothesis of aggregated tree pattern is not applicable to the mean pattern measured by Clark-Evans index, Uniform Angle index and Mean Directional index of the uneven-aged P. chihuahuana trees and P. chihuahuana tree community and but to specific spatial scales measured by the univariate L-function. The spatial distribution pattern of P. chihuahuana trees was found to be independent of patches of other tree species measured by the bivariate L-function. The spatial distribution was not significantly related to tree density, diameter distribution or tree species diversity. The index of Clark and Evans decreased significantly from the southern to northern plots containing all tree species. Self-thinning due to intra and inter-specific competition-induced mortality is probably the main cause of the decrease in aggregation intensity during the course of population development in this tree community. We recommend the use of larger sampling plots (> 0.25 ha) in uneven-aged and species-rich forest ecosystems to detect less obvious, but important, relationships between spatial tree pattern and functioning and diversity in these forests.

Spatial Distribution Patterns in the Very Rare and Species-Rich Picea chihuahuana Tree Community (Mexico)

PubMed Central

Wehenkel, Christian; Brazão-Protázio, João Marcelo; Carrillo-Parra, Artemio; Martínez-Guerrero, José Hugo; Crecente-Campo, Felipe

2015-01-01

The very rare Mexican Picea chihuahuana tree community covers an area of no more than 300 ha in the Sierra Madre Occidental. This special tree community has been the subject of several studies aimed at learning more about the genetic structure and ecology of the species and the potential effects of climate change. The spatial distribution of trees is a result of many ecological processes and can affect the degree of competition between neighbouring trees, tree density, variability in size and distribution, regeneration, survival, growth, mortality, crown formation and the biological diversity within forest communities. Numerous scale-dependent measures have been established in order to describe spatial forest structure. The overall aim of most of these studies has been to obtain data to help design preservation and conservation strategies. In this study, we examined the spatial distribution pattern of trees in the P. chihuahuana tree community in 12 localities, in relation to i) tree stand density, ii) diameter distribution (vertical structure), iii) tree species diversity, iv) geographical latitude and v) tree dominance at a fine scale (in 0.25 ha plots), with the aim of obtaining a better understanding of the complex ecosystem processes and biological diversity. Because of the strongly mixed nature of this tree community, which often produces low population densities of each tree species and random tree fall gaps caused by tree death, we expect aggregated patterns in individual Picea chihuahuana trees and in the P. chihuahuana tree community, repulsive Picea patterns to other tree species and repulsive patterns of young to adult trees. Each location was represented by one plot of 50 x 50 m (0.25 ha) established in the centre of the tree community. The findings demonstrate that the hypothesis of aggregated tree pattern is not applicable to the mean pattern measured by Clark-Evans index, Uniform Angle index and Mean Directional index of the uneven-aged P. chihuahuana trees and P. chihuahuana tree community and but to specific spatial scales measured by the univariate L-function. The spatial distribution pattern of P. chihuahuana trees was found to be independent of patches of other tree species measured by the bivariate L-function. The spatial distribution was not significantly related to tree density, diameter distribution or tree species diversity. The index of Clark and Evans decreased significantly from the southern to northern plots containing all tree species. Self-thinning due to intra and inter-specific competition-induced mortality is probably the main cause of the decrease in aggregation intensity during the course of population development in this tree community. We recommend the use of larger sampling plots (> 0.25 ha) in uneven-aged and species-rich forest ecosystems to detect less obvious, but important, relationships between spatial tree pattern and functioning and diversity in these forests. PMID:26496189

Quantifying the pattern of beta/A4 amyloid protein distribution in Alzheimer's disease by image analysis.

PubMed

Bruce, C V; Clinton, J; Gentleman, S M; Roberts, G W; Royston, M C

1992-04-01

We have undertaken a study of the distribution of the beta/A4 amyloid deposited in the cerebral cortex in Alzheimer's disease. Previous studies which have examined the differential distribution of amyloid in the cortex in order to determine the laminar pattern of cortical pathology have not proved to be conclusive. We have developed an alternative method for the solution of this problem. It involves the immunostaining of sections followed by computer-enhanced image analysis. A mathematical model is then used to describe both the amount and the pattern of amyloid across the cortex. This method is both accurate and reliable and also removes many of the problems concerning inter and intra-rater variability in measurement. This method will provide the basis for further quantitative studies on the differential distribution of amyloid in Alzheimer's disease and other cases of dementia where cerebral amyloidosis occurs.

Patterns of 11C-PIB cerebral retention in mild cognitive impairment patients.

PubMed

Banzo, I; Jiménez-Bonilla, J F; Martínez-Rodríguez, I; Quirce, R; de Arcocha-Torres, M; Bravo-Ferrer, Z; Lavado-Pérez, C; Sánchez-Juan, P; Rodríguez, E; Jiménez-Alonso, M; López-Defilló, J; Carril, J M

2016-01-01

To evaluate the patterns of cerebral cortical distribution of (11)C-PIB in patients with mild cognitive impairment (MCI). The study included 69 patients (37 male, age range 42-79 years) with MCI, sub-classified as 53 with amnestic-MCI (A-MCI), and 16 with non-amnestic-MCI (NA-MCI). Patients underwent (11)C-PIB PET/CT scan 60min after intravenous injection of the radiotracer. A visual analysis of the images was performed by 2 experienced physicians. (11)C-PIB-positive studies were considered when gray matter uptake was equal to or greater than white matter. According to the regions involved, (11)C-PIB-positive studies were classified into A-pattern (predominant retention in frontal, anterior cingulate, lateral temporal, and basal ganglia) and B-pattern (generalized retention). Thirty-nine of the 69 (56%) patients with MCI showed (11)C-PIB retention. Of the 53 A-MCI patients, 36 (68%) showed (11)C-PIB retention. Eleven out of 36 (30%) positive scans in A-MCI patients showed A-pattern, and 25 out of 36 (70%) patients had a B-pattern. Positive (11)C-PIB was observed in 3 out of 16 (19%) patients with NA-MCI. Regional distribution in these 3 patients showed A-pattern in 1, and B-pattern in 2 patients. Cortical retention of (11)C-PIB was more frequent in A-MCI than in NA-MCI patients, and also B-pattern than A-pattern in the (11)C-PIB positive group. The recognition of (11)C-PIB distribution patterns allows MCI patients to be classified, and the A-pattern may offer a therapeutic window for potential future treatments. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Scene-based nonuniformity correction using local constant statistics.

PubMed

Zhang, Chao; Zhao, Wenyi

2008-06-01

In scene-based nonuniformity correction, the statistical approach assumes all possible values of the true-scene pixel are seen at each pixel location. This global-constant-statistics assumption does not distinguish fixed pattern noise from spatial variations in the average image. This often causes the "ghosting" artifacts in the corrected images since the existing spatial variations are treated as noises. We introduce a new statistical method to reduce the ghosting artifacts. Our method proposes a local-constant statistics that assumes that the temporal signal distribution is not constant at each pixel but is locally true. This considers statistically a constant distribution in a local region around each pixel but uneven distribution in a larger scale. Under the assumption that the fixed pattern noise concentrates in a higher spatial-frequency domain than the distribution variation, we apply a wavelet method to the gain and offset image of the noise and separate out the pattern noise from the spatial variations in the temporal distribution of the scene. We compare the results to the global-constant-statistics method using a clean sequence with large artificial pattern noises. We also apply the method to a challenging CCD video sequence and a LWIR sequence to show how effective it is in reducing noise and the ghosting artifacts.

Secure information transport by transverse localization of light

PubMed Central

Leonetti, Marco; Karbasi, Salman; Mafi, Arash; DelRe, Eugenio; Conti, Claudio

2016-01-01

A single-photon beating with itself can produce even the most elaborate optical fringe pattern. However, the large amount of information enclosed in such a pattern is typically inaccessible, since the complete distribution can be visualized only after many detections. In fact this limitation is only true for delocalized patterns. Here we demonstrate how reconfigurable localized optical patterns allow to encode up to 6 bits of information in disorder-induced high transmission channels, even using a small number of photon counts. We developed a quantum key distribution scheme for fiber communication in which high information capacity is achieved through position and momentum complementarity. PMID:27436283

Secure information transport by transverse localization of light.

PubMed

Leonetti, Marco; Karbasi, Salman; Mafi, Arash; DelRe, Eugenio; Conti, Claudio

2016-07-20

A single-photon beating with itself can produce even the most elaborate optical fringe pattern. However, the large amount of information enclosed in such a pattern is typically inaccessible, since the complete distribution can be visualized only after many detections. In fact this limitation is only true for delocalized patterns. Here we demonstrate how reconfigurable localized optical patterns allow to encode up to 6 bits of information in disorder-induced high transmission channels, even using a small number of photon counts. We developed a quantum key distribution scheme for fiber communication in which high information capacity is achieved through position and momentum complementarity.

Regional mantle upwelling on Venus: The Beta-Atla-Themis anomaly and correlation with global tectonic patterns

NASA Technical Reports Server (NTRS)

Crumpler, L. S.; Head, J. W.; Aubele, Jayne C.

1993-01-01

The morphology and global distribution of volcanic centers and their association with other geological characteristics offers significant insight into the global patterns of geology, tectonic style, thermal state, and interior dynamics of Venus. Magellan data permit the detailed geological interpretation necessary to address questions about interior dynamics of Venus particularly as they reflect relatively physical, chemical, and thermal conditions of the interior. This paper focuses on the distribution of anomalous concentrations of volcanic centers on Venus and regional patterns of tectonic deformation as it may relate to the identification of global internal anomalies, including mantle dynamic, petrological, or thermal patterns.

Comparison between wavelet transform and moving average as filter method of MODIS imagery to recognize paddy cropping pattern in West Java

NASA Astrophysics Data System (ADS)

Dwi Nugroho, Kreshna; Pebrianto, Singgih; Arif Fatoni, Muhammad; Fatikhunnada, Alvin; Liyantono; Setiawan, Yudi

2017-01-01

Information on the area and spatial distribution of paddy field are needed to support sustainable agricultural and food security program. Mapping or distribution of cropping pattern paddy field is important to obtain sustainability paddy field area. It can be done by direct observation and remote sensing method. This paper discusses remote sensing for paddy field monitoring based on MODIS time series data. In time series MODIS data, difficult to direct classified of data, because of temporal noise. Therefore wavelet transform and moving average are needed as filter methods. The Objective of this study is to recognize paddy cropping pattern with wavelet transform and moving average in West Java using MODIS imagery (MOD13Q1) from 2001 to 2015 then compared between both of methods. The result showed the spatial distribution almost have the same cropping pattern. The accuracy of wavelet transform (75.5%) is higher than moving average (70.5%). Both methods showed that the majority of the cropping pattern in West Java have pattern paddy-fallow-paddy-fallow with various time planting. The difference of the planting schedule was occurs caused by the availability of irrigation water.

Diversity and Distribution Patterns in High Southern Latitude Sponges

PubMed Central

Downey, Rachel V.; Griffiths, Huw J.; Linse, Katrin; Janussen, Dorte

2012-01-01

Sponges play a key role in Antarctic marine benthic community structure and dynamics and are often a dominant component of many Southern Ocean benthic communities. Understanding the drivers of sponge distribution in Antarctica enables us to understand many of general benthic biodiversity patterns in the region. The sponges of the Antarctic and neighbouring oceanographic regions were assessed for species richness and biogeographic patterns using over 8,800 distribution records. Species-rich regions include the Antarctic Peninsula, South Shetland Islands, South Georgia, Eastern Weddell Sea, Kerguelen Plateau, Falkland Islands and north New Zealand. Sampling intensity varied greatly within the study area, with sampling hotspots found at the Antarctic Peninsula, South Georgia, north New Zealand and Tierra del Fuego, with limited sampling in the Bellingshausen and Amundsen seas in the Southern Ocean. In contrast to previous studies we found that eurybathy and circumpolar distributions are important but not dominant characteristics in Antarctic sponges. Overall Antarctic sponge species endemism is ∼43%, with a higher level for the class Hexactinellida (68%). Endemism levels are lower than previous estimates, but still indicate the importance of the Polar Front in isolating the Southern Ocean fauna. Nineteen distinct sponge distribution patterns were found, ranging from regional endemics to cosmopolitan species. A single, distinct Antarctic demosponge fauna is found to encompass all areas within the Polar Front, and the sub-Antarctic regions of the Kerguelen Plateau and Macquarie Island. Biogeographical analyses indicate stronger faunal links between Antarctica and South America, with little evidence of links between Antarctica and South Africa, Southern Australia or New Zealand. We conclude that the biogeographic and species distribution patterns observed are largely driven by the Antarctic Circumpolar Current and the timing of past continent connectivity. PMID:22911840

Are species photosynthetic characteristics good predictors of seedling post-hurricane demographic patterns and species spatiotemporal distribution in a hurricane impacted wet montane forest?

NASA Astrophysics Data System (ADS)

Luke, Denneko; McLaren, Kurt

2018-05-01

In situ measurements of leaf level photosynthetic response to light were collected from seedlings of ten tree species from a tropical montane wet forest, the John Crow Mountains, Jamaica. A model-based recursive partitioning ('mob') algorithm was then used to identify species associations based on their fitted photosynthetic response curves. Leaf area dark respiration (RD) and light saturated maximum photosynthetic (Amax) rates were also used as 'mob' partitioning variables, to identify species associations based on seedling demographic patterns (from June 2007 to May 2010) following a hurricane (Aug. 2007) and the spatiotemporal distribution patterns of stems in 2006 and 2012. RD and Amax rates ranged from 1.14 to 2.02 μmol (CO2) m-2s-1 and 2.97-5.87 μmol (CO2) m-2s-1, respectively, placing the ten species in the range of intermediate shade tolerance. Several parsimonious species 'mob' groups were formed based on 1) interspecific differences among species response curves, 2) variations in post-hurricane seedling demographic trends and 3) RD rates and species spatiotemporal distribution patterns at aspects that are more or less exposed to hurricanes. The composition of parsimonious groupings based on photosynthetic curves was not concordant with the groups based on demographic trends but was partially concordant with the RD - species spatiotemporal distribution groups. Our results indicated that the influence of photosynthetic characteristics on demographic traits and species distributions was not straightforward. Rather, there was a complex pattern of interaction between ecophysiological and demographic traits, which determined species successional status, post-hurricane response and ultimately, species distribution at our study site.

Are anesthesia start and end times randomly distributed? The influence of electronic records.

PubMed

Deal, Litisha G; Nyland, Michael E; Gravenstein, Nikolaus; Tighe, Patrick

2014-06-01

To perform a frequency analysis of start minute digits (SMD) and end minute digits (EMD) taken from the electronic, computer-assisted, and manual anesthesia billing-record systems. Retrospective cross-sectional review. University medical center. This cross-sectional review was conducted on billing records from a single healthcare institution over a 15-month period. A total of 30,738 cases were analyzed. For each record, the start time and end time were recorded. Distributions of SMD and EMD were tested against the null hypothesis of a frequency distribution equivalently spread between zero and nine. SMD and EMD aggregate distributions each differed from equivalency (P < 0.0001). When stratified by type of anesthetic record, no differences were found between the recorded and expected equivalent distribution patterns for electronic anesthesia records for start minute (P < 0.98) or end minute (P < 0.55). Manual and computer-assisted records maintained nonequivalent distribution patterns for SMD and EMD (P < 0.0001 for each comparison). Comparison of cumulative distributions between SMD and EMD distributions suggested a significant difference between the two patterns (P < 0.0001). An electronic anesthesia record system, with automated time capture of events verified by the user, produces a more unified distribution of billing times than do more traditional methods of entering billing times. Copyright © 2014 Elsevier Inc. All rights reserved.

Point pattern analysis of FIA data

Treesearch

Chris Woodall

2002-01-01

Point pattern analysis is a branch of spatial statistics that quantifies the spatial distribution of points in two-dimensional space. Point pattern analysis was conducted on stand stem-maps from FIA fixed-radius plots to explore point pattern analysis techniques and to determine the ability of pattern descriptions to describe stand attributes. Results indicate that the...

Biogeographic distribution patterns and their correlates in the diverse frog fauna of the Atlantic Forest hotspot.

PubMed

Vasconcelos, Tiago S; Prado, Vitor H M; da Silva, Fernando R; Haddad, Célio F B

2014-01-01

Anurans are a highly diverse group in the Atlantic Forest hotspot (AF), yet distribution patterns and species richness gradients are not randomly distributed throughout the biome. Thus, we explore how anuran species are distributed in this complex and biodiverse hotspot, and hypothesize that this group can be distinguished by different cohesive regions. We used range maps of 497 species to obtain a presence/absence data grid, resolved to 50×50 km grain size, which was submitted to k-means clustering with v-fold cross-validation to determine the biogeographic regions. We also explored the extent to which current environmental variables, topography, and floristic structure of the AF are expected to identify the cluster patterns recognized by the k-means clustering. The biogeographic patterns found for amphibians are broadly congruent with ecoregions identified in the AF, but their edges, and sometimes the whole extent of some clusters, present much less resolved pattern compared to previous classification. We also identified that climate, topography, and vegetation structure of the AF explained a high percentage of variance of the cluster patterns identified, but the magnitude of the regression coefficients shifted regarding their importance in explaining the variance for each cluster. Specifically, we propose that the anuran fauna of the AF can be split into four biogeographic regions: a) less diverse and widely-ranged species that predominantly occur in the inland semideciduous forests; b) northern small-ranged species that presumably evolved within the Pleistocene forest refugia; c) highly diverse and small-ranged species from the southeastern Brazilian mountain chain and its adjacent semideciduous forest; and d) southern species from the Araucaria forest. Finally, the high congruence among the cluster patterns and previous eco-regions identified for the AF suggests that preserving the underlying habitat structure helps to preserve the historical and ecological signals that underlie the geographic distribution of AF anurans.

Hierarchical species distribution models

USGS Publications Warehouse

Hefley, Trevor J.; Hooten, Mevin B.

2016-01-01

Determining the distribution pattern of a species is important to increase scientific knowledge, inform management decisions, and conserve biodiversity. To infer spatial and temporal patterns, species distribution models have been developed for use with many sampling designs and types of data. Recently, it has been shown that count, presence-absence, and presence-only data can be conceptualized as arising from a point process distribution. Therefore, it is important to understand properties of the point process distribution. We examine how the hierarchical species distribution modeling framework has been used to incorporate a wide array of regression and theory-based components while accounting for the data collection process and making use of auxiliary information. The hierarchical modeling framework allows us to demonstrate how several commonly used species distribution models can be derived from the point process distribution, highlight areas of potential overlap between different models, and suggest areas where further research is needed.

Antenna with distributed strip and integrated electronic components

DOEpatents

Rodenbeck, Christopher T [Albuquerque, NM; Payne, Jason A [Albuquerque, NM; Ottesen, Cory W [Albuquerque, NM

2008-08-05

An antenna comprises electrical conductors arranged to form a radiating element including a folded line configuration and a distributed strip configuration, where the radiating element can be in proximity to a ground conductor and/or arranged as a dipole. Embodiments of the antenna include conductor patterns formed on a printed wiring board, having a ground plane, spacedly adjacent to and coplanar with the radiating element. An antenna can comprise a distributed strip patterned on a printed wiring board, integrated with electronic components mounted on top of or below the distributed strip, and substantially within the extents of the distributed strip. Mounting of electronic components on top of or below the distributed strip has little effect on the performance of the antenna, and allows for realizing the combination of the antenna and integrated components in a compact form. An embodiment of the invention comprises an antenna including a distributed strip, integrated with a battery mounted on the distributed strip.

Distributed bearing fault diagnosis based on vibration analysis

NASA Astrophysics Data System (ADS)

Dolenc, Boštjan; Boškoski, Pavle; Juričić, Đani

2016-01-01

Distributed bearing faults appear under various circumstances, for example due to electroerosion or the progression of localized faults. Bearings with distributed faults tend to generate more complex vibration patterns than those with localized faults. Despite the frequent occurrence of such faults, their diagnosis has attracted limited attention. This paper examines a method for the diagnosis of distributed bearing faults employing vibration analysis. The vibrational patterns generated are modeled by incorporating the geometrical imperfections of the bearing components. Comparing envelope spectra of vibration signals shows that one can distinguish between localized and distributed faults. Furthermore, a diagnostic procedure for the detection of distributed faults is proposed. This is evaluated on several bearings with naturally born distributed faults, which are compared with fault-free bearings and bearings with localized faults. It is shown experimentally that features extracted from vibrations in fault-free, localized and distributed fault conditions form clearly separable clusters, thus enabling diagnosis.

Macroecology of unicellular organisms - patterns and processes.

PubMed

Soininen, Janne

2012-02-01

Macroecology examines the relationship between organisms and their environment at large spatial (and temporal) scales. Typically, macroecologists explain the large-scale patterns of abundance, distribution and diversity. Despite the difficulties in sampling and characterizing microbial diversity, macroecologists have recently also been interested in unicellular organisms. Here, I review the current advances made in microbial macroecology, as well as discuss related ecosystem functions. Overall, it seems that microorganisms suit surprisingly well to known species abundance distributions and show positive relationship between distribution and adundance. Microbial species-area and distance-decay relationships tend to be weaker than for macroorganisms, but nonetheless significant. Few findings on altitudinal gradients in unicellular taxa seem to differ greatly from corresponding findings for larger taxa, whereas latitudinal gradients among microorganisms have either been clearly evident or absent depending on the context. Literature also strongly emphasizes the role of spatial scale for the patterns of diversity and suggests that patterns are affected by species traits as well as ecosystem characteristics. Finally, I discuss the large role of local biotic and abiotic variables driving the community assembly in unicellular taxa and eventually dictating how multiple ecosystem processes are performed. Present review highlights the fact that most microorganisms may not differ fundamentally from larger taxa in their large-scale distribution patterns. Yet, review also shows that many aspects of microbial macroecology are still relatively poorly understood and specific patterns depend on focal taxa and ecosystem concerned. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

COMPARISON OF SPATIAL PATTERNS OF POLLUTANT DISTRIBUTION WITH CMAQ PREDICTIONS

EPA Science Inventory

One indication of model performance is the comparison of spatial patterns of pollutants, either as concentration or deposition, predicted by the model with spatial patterns derived from measurements. If the spatial patterns produced by the model are similar to the observations i...

Diversity and distribution of Archaea in global estuarine ecosystems.

PubMed

Liu, Xiaobo; Pan, Jie; Liu, Yang; Li, Meng; Gu, Ji-Dong

2018-05-09

Estuarine ecosystem is a unique geographical transitional zone between freshwater and seawater, harboring a wide range of microbial communities including Archaea. Although a large number of Archaea have been detected in such ecosystem, the global patterns in archaeal diversity and distribution are extremely scarce. To bridge this gap, we carried out a comprehensive survey of archaeal communities using ca. 4000 publicly available archaeal 16S rRNA gene sequences (>300 bp) collected from 24 estuaries in different latitude regions. These sequences were divided into 1450 operational taxonomic units (OTUs) at 97% identity, suggesting a high biodiversity that increased gradually from the high- to low-latitude estuaries. Phylogenetic analysis showed that estuarine ecosystem was a large biodiversity pool of Archaea that was mainly composed of 12 phyla. Among them, the predominant groups were Bathyarchaeota, Euryarchaeota and Thaumarchaeota. Interestingly, archaeal distribution demonstrated a geographical differentiation in that Thaumarchaeota was dominated in the low-latitude estuaries, Bathyarchaeota in the mid-latitude estuaries, and Euryarchaeota in the high-latitude estuaries, respectively. Furthermore, the majority of the most abundant 20 OTUs demonstrated an overrepresented or underrepresented distribution pattern in some specific estuaries or latitude regions while a few were evenly distributed throughout the estuaries. This pattern indicates a potential selectivity of geographical distribution. In addition, the analysis of environmental parameters suggested that latitude would be one of the major factors driving the distribution of archaeal communities in estuarine ecosystem. This study profiles a clear framework on the diversity and distribution of Archaea in the global estuarine ecosystem and explores the general environmental factors that influence these patterns. Our findings constitute an important part of the exploration of the global ecology of Archaea. Copyright © 2018 Elsevier B.V. All rights reserved.

Geological Substrates Shape Tree Species and Trait Distributions in African Moist Forests

PubMed Central

Fayolle, Adeline; Engelbrecht, Bettina; Freycon, Vincent; Mortier, Frédéric; Swaine, Michael; Réjou-Méchain, Maxime; Doucet, Jean-Louis; Fauvet, Nicolas; Cornu, Guillaume; Gourlet-Fleury, Sylvie

2012-01-01

Background Understanding the factors that shape the distribution of tropical tree species at large scales is a central issue in ecology, conservation and forest management. The aims of this study were to (i) assess the importance of environmental factors relative to historical factors for tree species distributions in the semi-evergreen forests of the northern Congo basin; and to (ii) identify potential mechanisms explaining distribution patterns through a trait-based approach. Methodology/Principal Findings We analyzed the distribution patterns of 31 common tree species in an area of more than 700,000 km2 spanning the borders of Cameroon, the Central African Republic, and the Republic of Congo using forest inventory data from 56,445 0.5-ha plots. Spatial variation of environmental (climate, topography and geology) and historical factors (human disturbance) were quantified from maps and satellite records. Four key functional traits (leaf phenology, shade tolerance, wood density, and maximum growth rate) were extracted from the literature. The geological substrate was of major importance for the distribution of the focal species, while climate and past human disturbances had a significant but lesser impact. Species distribution patterns were significantly related to functional traits. Species associated with sandy soils typical of sandstone and alluvium were characterized by slow growth rates, shade tolerance, evergreen leaves, and high wood density, traits allowing persistence on resource-poor soils. In contrast, fast-growing pioneer species rarely occurred on sandy soils, except for Lophira alata. Conclusions/Significance The results indicate strong environmental filtering due to differential soil resource availability across geological substrates. Additionally, long-term human disturbances in resource-rich areas may have accentuated the observed patterns of species and trait distributions. Trait differences across geological substrates imply pronounced differences in population and ecosystem processes, and call for different conservation and management strategies. PMID:22905127

The Use of Compressive Sensing to Reconstruct Radiation Characteristics of Wide-Band Antennas from Sparse Measurements

DTIC Science & Technology

2015-06-01

of uniform- versus nonuniform -pattern reconstruction, of transform function used, and of minimum randomly distributed measurements needed to...the radiation-frequency pattern’s reconstruction using uniform and nonuniform randomly distributed samples even though the pattern error manifests...5 Fig. 3 The nonuniform compressive-sensing reconstruction of the radiation

Interannual consistency in fractal snow depth patterns at two Colorado mountain sites

Treesearch

Jeffrey S. Deems; Steven R. Fassnacht; Kelly J. Elder

2008-01-01

Fractal dimensions derived from log-log variograms are useful for characterizing spatial structure and scaling behavior in snow depth distributions. This study examines the temporal consistency of snow depth scaling features at two sites using snow depth distributions derived from lidar datasets collected in 2003 and 2005. The temporal snow accumulation patterns in...

Spatiotemporal distribution patterns of forest fires in northern Mexico

Treesearch

Gustavo Pérez-Verdin; M. A. Márquez-Linares; A. Cortes-Ortiz; M. Salmerón-Macias

2013-01-01

Using the 2000-2011 CONAFOR databases, a spatiotemporal analysis of the occurrence of forest fires in Durango, one of the most affected States in Mexico, was conducted. The Moran's index was used to determine a spatial distribution pattern; also, an analysis of seasonal and temporal autocorrelation of the data collected was completed. The geographically weighted...

Contrasting distribution patterns of invasive and naturalized non-native species along environmental gradients in a semi-arid montane ecosystem

Treesearch

Kelly M. Andersen; Bridgett J. Naylor; Bryan A. Endress; Catherine G. Parks

2015-01-01

Questions: Mountain systems have high abiotic heterogeneity over local spatial scales, offering natural experiments for examining plant species invasions. We ask whether functional groupings explain non-native species spread into native vegetation and up elevation gradients.We examine whether non-native species distribution patterns are related to environmental...

Parallel processing for pitch splitting decomposition

NASA Astrophysics Data System (ADS)

Barnes, Levi; Li, Yong; Wadkins, David; Biederman, Steve; Miloslavsky, Alex; Cork, Chris

2009-10-01

Decomposition of an input pattern in preparation for a double patterning process is an inherently global problem in which the influence of a local decomposition decision can be felt across an entire pattern. In spite of this, a large portion of the work can be massively distributed. Here, we discuss the advantages of geometric distribution for polygon operations with limited range of influence. Further, we have found that even the naturally global "coloring" step can, in large part, be handled in a geometrically local manner. In some practical cases, up to 70% of the work can be distributed geometrically. We also describe the methods for partitioning the problem into local pieces and present scaling data up to 100 CPUs. These techniques reduce DPT decomposition runtime by orders of magnitude.

Potential effects of climate change on the risk of accidents with poisonous species of the genus Tityus (Scorpiones, Buthidae) in Argentina.

PubMed

Martinez, Pablo Ariel; Andrade, Mayane Alves; Bidau, Claudio Juan

2018-06-01

The temporal pattern of co-occurrence of human beings and venomous species (scorpions, spiders, snakes) is changing. Thus, the temporal pattern of areas with risk of accidents with such species tends to become dynamic in time. We analyze the areas of occurrence of species of Tityus in Argentina and assess the impact of global climate change on their area of distribution by the construction of risk maps. Using data of occurrence of the species and climatic variables, we constructed models of species distribution (SMDs) under current and future climatic conditions. We also created maps that allow the detection of temporal shifts in the distribution patterns of each Tityus species. Finally, we developed risk maps for the analyzed species. Our results predict that climate change will have an impact on the distribution of Tityus species which will clearly expand to more southern latitudes, with the exception of T. argentinus. T. bahiensis, widely distributed in Brazil, showed a considerable increase of its potential area (ca. 37%) with future climate change. The species T. confluens and T. trivittatus that cause the highest number of accidents in Argentina are expected to show significant changes of their distributions in future scenarios. The former fact is worrying because Buenos Aires province is the more densely populated district in Argentina thus iable to become the most affected by T. trivittatus. These alterations of distributional patterns can lead to amplify the accident risk zones of venomous species, becoming an important subject of concern for public health policies. Copyright © 2018 Elsevier Ltd. All rights reserved.

RipleyGUI: software for analyzing spatial patterns in 3D cell distributions

PubMed Central

Hansson, Kristin; Jafari-Mamaghani, Mehrdad; Krieger, Patrik

2013-01-01

The true revolution in the age of digital neuroanatomy is the ability to extensively quantify anatomical structures and thus investigate structure-function relationships in great detail. To facilitate the quantification of neuronal cell patterns we have developed RipleyGUI, a MATLAB-based software that can be used to detect patterns in the 3D distribution of cells. RipleyGUI uses Ripley's K-function to analyze spatial distributions. In addition the software contains statistical tools to determine quantitative statistical differences, and tools for spatial transformations that are useful for analyzing non-stationary point patterns. The software has a graphical user interface making it easy to use without programming experience, and an extensive user manual explaining the basic concepts underlying the different statistical tools used to analyze spatial point patterns. The described analysis tool can be used for determining the spatial organization of neurons that is important for a detailed study of structure-function relationships. For example, neocortex that can be subdivided into six layers based on cell density and cell types can also be analyzed in terms of organizational principles distinguishing the layers. PMID:23658544

An analysis of dinosaurian biogeography: evidence for the existence of vicariance and dispersal patterns caused by geological events.

PubMed

Upchurch, Paul; Hunn, Craig A; Norman, David B

2002-03-22

As the supercontinent Pangaea fragmented during the Mesozoic era, dinosaur faunas were divided into isolated populations living on separate continents. It has been predicted, therefore, that dinosaur distributions should display a branching ('vicariance') pattern that corresponds with the sequence and timing of continental break-up. Several recent studies, however, minimize the importance of plate tectonics and instead suggest that dispersal and regional extinction were the main controls on dinosaur biogeography. Here, in order to test the vicariance hypothesis, we apply a cladistic biogeographical method to a large dataset on dinosaur relationships and distributions. We also introduce a methodological refinement termed 'time-slicing', which is shown to be a key step in the detection of ancient biogeographical patterns. These analyses reveal biogeographical patterns that closely correlate with palaeogeography. The results provide the first statistically robust evidence that, from Middle Jurassic to mid-Cretaceous times, tectonic events had a major role in determining where and when particular dinosaur groups flourished. The fact that evolutionary trees for extinct organisms preserve such distribution patterns opens up a new and fruitful direction for palaeobiogeographical research.

Distribution patterns of MCA-coated granules aerially applied to corn fields of Southern Hungary between 2000 and 2002.

PubMed

Wennemann, L; Hummel, H E

2003-01-01

Field studies in corn (Zea mays L.) were conducted to evaluate distribution patterns of 4-methoxy-cinnamaldehyde (MCA) coated corn grits after aerial application with a Dromader fixed wing aircraft. The kairomone mimic MCA is synthetically available and a quite specific and efficient adult attractant for the invasive alien maize pest western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte. Orientation disruptive properties of MCA for WCR when applied at unphysiologically high concentrations are currently under investigation. For successful implementation of the MCA disruption technique, the distribution patterns of MCA coated corn granules ('grits') in the field are important. Grits are degrained corn cobs, shredded to different sizes, coated with MCA and used as a carrier material to disseminate MCA vapors into corn fields. Granules of 10-12 mesh size were aerially applied eight times at rates ranging from 12.4 to 25.0 kg/ha. The goal is to evaluate distribution patterns of corn grits treated with MCA in three fields located at Csanadpalota, Kardoskút and Mezöhegyes in Southern Hungary between 2000 and 2002. Increasing rates reflect our attempts in finding and optimising the most even distribution of granules in the field. Field experiments were evaluated by collecting grits in 30-cm plastic saucers and by counting grits accumulated on corn plant parts. Variation in grit number per unit area and frequency of corn granule number per plant showed some transient technical application problems. Analysis of grits collected in the saucers revealed some statistical difference between the different application dates as well as differences in rates applied. Altogether grits in saucers were more evenly distributed in comparison to the grits collected on plant parts. As the corn plants age, their leaves and whorls present a smaller and smaller surface area where granules can accumulate. Altogether, however, grit distribution patterns indicate that aerial application is a viable tool for disseminating MCA in corn fields.

Glenoid subchondral bone density distribution in male total shoulder arthroplasty subjects with eccentric and concentric wear.

PubMed

Simon, Peter; Gupta, Anil; Pappou, Ioannis; Hussey, Michael M; Santoni, Brandon G; Inoue, Nozomu; Frankle, Mark A

2015-03-01

Glenoid component loosening in total shoulder arthroplasty may be prevented by component placement on a congruent and adequate bony surface. Glenoid subchondral bone density (SBD) variability may be correlated with this concept. This study analyzed the 3-dimensional distribution of glenoid SBD in total shoulder arthroplasty patients with osteoarthritis. Three-dimensional computed tomography osteoabsorptiometry (CT-OAM) was performed in 42 men (21 with eccentric and 21 with concentric wear patterns) with glenohumeral arthritis. Glenoid SBD was measured from the joint surface based on 5 clinically relevant topographic zones. The correlation of the wear pattern with the SBD distribution was investigated. The glenoid subarticular layers could be separated into distinct regions: calcified cartilage (≤ 1.5 mm), subchondral plate (2-4.5 mm) and cancellous bone (≥ 5 mm). There were significant differences in SBD among these layers within and between patients with concentric and eccentric wear patterns. In concentric glenoids, the SBD distribution was homogeneous, with greater mineralization in the central zone, 1,749.1 ± 162.3 Hounsfield units (HU) (at 2.5 mm), compared with the posterior, anterior, and superior zones (P < .001). In the eccentric group, the SBD distribution was inhomogeneous. Mineralization was greatest in the posterior zone, 1,739.0 ± 172.6 HU (at 2.5 mm), followed by the inferior zone, 1,722.1 ± 186.6 HU (at 3 mm). This study represents the first study using CT-OAM to evaluate the 3-dimensional SBD distribution of the glenoid vault for different arthritic wear patterns. The study findings indicate that the SBD distribution is dependent on (1) depth from the articular surface, (2) topographic zone, and (3) wear pattern. CT-OAM may be an effective tool to assist in preoperative planning for shoulder arthroplasty. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

CDU improvement technology of etching pattern using photo lithography

NASA Astrophysics Data System (ADS)

Tadokoro, Masahide; Shinozuka, Shinichi; Jyousaka, Megumi; Ogata, Kunie; Morimoto, Tamotsu; Konishi, Yoshitaka

2008-03-01

Semiconductor manufacturing technology has shifted towards finer design rules, and demands for critical dimension uniformity (CDU) of resist patterns have become greater than ever. One of the methods for improving Resist Pattern CDU is to control post-exposure bake (PEB) temperature. When ArF resist is used, there is a certain relationship between critical dimension (CD) and PEB temperature. By utilizing this relationship, Resist Pattern CDU can be improved through control of within-wafer temperature distribution in the PEB process. Resist Pattern CDU improvement contributes to Etching Pattern CDU improvement to a certain degree. To further improve Etching Pattern CDU, etcher-specific CD variation needs to be controlled. In this evaluation, 1. We verified whether etcher-specific CD variation can be controlled and consequently Etching Pattern CDU can be further improved by controlling resist patterns through PEB control. 2. Verifying whether Etching Pattern CDU improvement through has any effect on the reduction in wiring resistance variation. The evaluation procedure is as follows.1. Wafers with base film of Doped Poly-Si (D-Poly) were prepared. 2. Resist patterns were created on them. 3. To determine etcher-specific characteristics, the first etching was performed, and after cleaning off the resist and BARC, CD of etched D-Poly was measured. 4. Using the obtained within-wafer CD distribution of the etching patterns, within-wafer temperature distribution in the PEB process was modified. 5. Resist patterns were created again, followed by the second etching and cleaning, which was followed by CD measurement. We used Optical CD Measurement (OCD) for measurement of resist patterns and etching patterns as OCD is minimally affected by Line Edge Roughness (LER). As a result, 1. We confirmed the effect of Resist Pattern CD control through PEB control on the reduction in etcher-specific CD variation and the improvement in Etching Pattern CDU. 2. The improvement in Etching Pattern CDU has an effect on the reduction in wiring resistance variation. The method for Etching Pattern CDU improvement through PEB control reduces within-wafer variation of MOS transistor's gate length. Therefore, with this method, we can expect to observe uniform within-wafer MOS transistor characteristics.

Distributed Storage Algorithm for Geospatial Image Data Based on Data Access Patterns.

PubMed

Pan, Shaoming; Li, Yongkai; Xu, Zhengquan; Chong, Yanwen

2015-01-01

Declustering techniques are widely used in distributed environments to reduce query response time through parallel I/O by splitting large files into several small blocks and then distributing those blocks among multiple storage nodes. Unfortunately, however, many small geospatial image data files cannot be further split for distributed storage. In this paper, we propose a complete theoretical system for the distributed storage of small geospatial image data files based on mining the access patterns of geospatial image data using their historical access log information. First, an algorithm is developed to construct an access correlation matrix based on the analysis of the log information, which reveals the patterns of access to the geospatial image data. Then, a practical heuristic algorithm is developed to determine a reasonable solution based on the access correlation matrix. Finally, a number of comparative experiments are presented, demonstrating that our algorithm displays a higher total parallel access probability than those of other algorithms by approximately 10-15% and that the performance can be further improved by more than 20% by simultaneously applying a copy storage strategy. These experiments show that the algorithm can be applied in distributed environments to help realize parallel I/O and thereby improve system performance.

Experimental Verification of Modeled Thermal Distribution Produced by a Piston Source in Physiotherapy Ultrasound

PubMed Central

Lopez-Haro, S. A.; Leija, L.

2016-01-01

Objectives. To present a quantitative comparison of thermal patterns produced by the piston-in-a-baffle approach with those generated by a physiotherapy ultrasonic device and to show the dependency among thermal patterns and acoustic intensity distributions. Methods. The finite element (FE) method was used to model an ideal acoustic field and the produced thermal pattern to be compared with the experimental acoustic and temperature distributions produced by a real ultrasonic applicator. A thermal model using the measured acoustic profile as input is also presented for comparison. Temperature measurements were carried out with thermocouples inserted in muscle phantom. The insertion place of thermocouples was monitored with ultrasound imaging. Results. Modeled and measured thermal profiles were compared within the first 10 cm of depth. The ideal acoustic field did not adequately represent the measured field having different temperature profiles (errors 10% to 20%). Experimental field was concentrated near the transducer producing a region with higher temperatures, while the modeled ideal temperature was linearly distributed along the depth. The error was reduced to 7% when introducing the measured acoustic field as the input variable in the FE temperature modeling. Conclusions. Temperature distributions are strongly related to the acoustic field distributions. PMID:27999801

Impact of various factors on radioactivity distribution in different DBS papers.

PubMed

Ren, Xiao; Paehler, Tobias; Zimmer, Manfred; Guo, Zuyu; Zane, Patricia; Emmons, Gary T

2010-08-01

Dried blood spot (DBS) sampling could potentially become the preferred blood collection technique in toxicological and clinical studies. Autoradiography was performed to study compound distribution within a dbs under different conditions using five papers, 31ETF, Grade 226, 903(®), FTA(®) and FTA(®) Elute. The results showed an uneven distribution in all papers with common distribution patterns regardless of compounds: decreased concentrations along the edge, the volcano effect in the middle and the speckle pattern in the center. Treated papers were more readily influenced by environmental factors. Autoradiography enables visualization of a compound's distribution and can guide bioanalytical assay development by allowing convenient evaluation of factors, such as choice of paper, spotting volume, punch size, punch location, temperature and humidity.

Spatial Distribution of Cyanobacteria in Modern Stromatolites

NASA Technical Reports Server (NTRS)

Prufert-Bebout, Lee; Dacles-Mariani, Jennifer; Herbert, Alice; DeVincenzi, Donald (Technical Monitor)

2001-01-01

Living stromatolites consist of complex microbial communities with distinct distribution patterns for different microbial groups. The cyanobacterial populations of Highborne Cay Bahamas exemplify this phenomenon. Field observations reveal distinct distribution patterns for several of these cyanobacterial species. To date 10 different cyanobacterial cultures, including both filamentous and endolithic species, have been isolated from these stromatolites. We will present data on the growth and motility characteristics as well as on the nutritional requirements of these isolates. These data will then be correlated with the field observed distributions for these species. Lastly laboratory simulations of stromatolites grown under various conditions of irradiance, flow and cyanobacterial community composition will be presented. These experiments allow us to evaluate our predictions regarding controls on cyanobacterial distribution.

Patterns across multiple memories are identified over time.

PubMed

Richards, Blake A; Xia, Frances; Santoro, Adam; Husse, Jana; Woodin, Melanie A; Josselyn, Sheena A; Frankland, Paul W

2014-07-01

Memories are not static but continue to be processed after encoding. This is thought to allow the integration of related episodes via the identification of patterns. Although this idea lies at the heart of contemporary theories of systems consolidation, it has yet to be demonstrated experimentally. Using a modified water-maze paradigm in which platforms are drawn stochastically from a spatial distribution, we found that mice were better at matching platform distributions 30 d compared to 1 d after training. Post-training time-dependent improvements in pattern matching were associated with increased sensitivity to new platforms that conflicted with the pattern. Increased sensitivity to pattern conflict was reduced by pharmacogenetic inhibition of the medial prefrontal cortex (mPFC). These results indicate that pattern identification occurs over time, which can lead to conflicts between new information and existing knowledge that must be resolved, in part, by computations carried out in the mPFC.

Optical proximity correction (OPC) in near-field lithography with pixel-based field sectioning time modulation

NASA Astrophysics Data System (ADS)

Oh, Seonghyeon; Han, Dandan; Shim, Hyeon Bo; Hahn, Jae W.

2018-01-01

Subwavelength features have been successfully demonstrated in near-field lithography. In this study, the point spread function (PSF) of a near-field beam spot from a plasmonic ridge nanoaperture is discussed with regard to the complex decaying characteristic of a non-propagating wave and the asymmetry of the field distribution for pattern design. We relaxed the shape complexity of the field distribution with pixel-based optical proximity correction (OPC) for simplifying the pattern image distortion. To enhance the pattern fidelity for a variety of arbitrary patterns, field-sectioning structures are formulated via convolutions with a time-modulation function and a transient PSF along the near-field dominant direction. The sharpness of corners and edges, and line shortening can be improved by modifying the original target pattern shape using the proposed approach by considering both the pattern geometry and directionality of the field decay for OPC in near-field lithography.

Optical proximity correction (OPC) in near-field lithography with pixel-based field sectioning time modulation.

PubMed

Oh, Seonghyeon; Han, Dandan; Shim, Hyeon Bo; Hahn, Jae W

2018-01-26

Subwavelength features have been successfully demonstrated in near-field lithography. In this study, the point spread function (PSF) of a near-field beam spot from a plasmonic ridge nanoaperture is discussed with regard to the complex decaying characteristic of a non-propagating wave and the asymmetry of the field distribution for pattern design. We relaxed the shape complexity of the field distribution with pixel-based optical proximity correction (OPC) for simplifying the pattern image distortion. To enhance the pattern fidelity for a variety of arbitrary patterns, field-sectioning structures are formulated via convolutions with a time-modulation function and a transient PSF along the near-field dominant direction. The sharpness of corners and edges, and line shortening can be improved by modifying the original target pattern shape using the proposed approach by considering both the pattern geometry and directionality of the field decay for OPC in near-field lithography.

Fish distribution during smolt migration in the Penobscot Estuary, ME

NASA Astrophysics Data System (ADS)

Volkel, S. L.

2016-02-01

Estuaries are complex and dynamic ecosystems. The Penobscot Estuary is particularly important because it harbors a suite of imperiled diadromous fish species. In order to properly manage these populations, it is imperative to understand their distribution and ecology. My study focuses on May because endangered Atlantic salmon migrate seaward then. Successful emigration of these smolts is important to the population's overall fitness. One potential way to increase the likelihood of migratory success (survival) is to decrease their risk of predation. Assuming that predators in this system are generalists, overall smolt predation may be reduced by having a larger selection of alternative prey (other fish species). We hypothesize that diadromous fish abundance is increasing as a result of recent (2012-2013) dam removals. To explore this hypothesis, I used hydroacoustic methods to characterize the distribution patterns of alternative prey (TL=10-30 cm). I found that peak fish abundances occurred in the mid-estuary, especially during mid-May, and depth distribution patterns varied weekly. By understanding these seasonal, longitudinal, and vertical distribution patterns, I explored potential interactions of other fish populations as prey buffers to emigrating smolts.

Voronoi Cell Patterns: theoretical model and application to submonolayer growth

NASA Astrophysics Data System (ADS)

González, Diego Luis; Einstein, T. L.

2012-02-01

We use a simple fragmentation model to describe the statistical behavior of the Voronoi cell patterns generated by a homogeneous and isotropic set of points in 1D and in 2D. In particular, we are interested in the distribution of sizes of these Voronoi cells. Our model is completely defined by two probability distributions in 1D and again in 2D, the probability to add a new point inside an existing cell and the probability that this new point is at a particular position relative to the preexisting point inside this cell. In 1D the first distribution depends on a single parameter while the second distribution is defined through a fragmentation kernel; in 2D both distributions depend on a single parameter. The fragmentation kernel and the control parameters are closely related to the physical properties of the specific system under study. We apply our model to describe the Voronoi cell patterns of island nucleation for critical island sizes i=0,1,2,3. Experimental results for the Voronoi cells of InAs/GaAs quantum dots are also described by our model.

Performance analysis of a brushless dc motor due to magnetization distribution in a continuous ring magnet

NASA Astrophysics Data System (ADS)

Hur, Jin; Jung, In-Soung; Sung, Ha-Gyeong; Park, Soon-Sup

2003-05-01

This paper represents the force performance of a brushless dc motor with a continuous ring-type permanent magnet (PM), considering its magnetization patterns: trapezoidal, trapezoidal with dead zone, and unbalanced trapezoidal magnetization with dead zone. The radial force density in PM motor causes vibration, because vibration is induced the traveling force from the rotating PM acting on the stator. Magnetization distribution of the PM as well as the shape of the teeth determines the distribution of force density. In particular, the distribution has a three-dimensional (3-D) pattern because of overhang, that is, it is not uniform in axial direction. Thus, the analysis of radial force density required dynamic analysis considering the 3-D shape of the teeth and overhang. The results show that the force density as a source of vibration varies considerably depending on the overhang and magnetization distribution patterns. In addition, the validity of the developed method, coupled 3-D equivalent magnetic circuit network method, with driving circuit and motion equation, is confirmed by comparison of conventional method using 3D finite element method.

Pedagogical Implications of Score Distribution Pattern and Learner Satisfaction in an Intensive TOEIC Course

ERIC Educational Resources Information Center

Kang, Che Chang

2014-01-01

The study aimed at investigating TOEIC score distribution patterns and learner satisfaction in an intensive TOEIC course and drew implications for pedagogical practice. A one-group pre-test post-test experiment and a survey on learner satisfaction were conducted on Taiwanese college EFL students (n = 50) in a case study. Results showed that the…

Evolutionary history of the little fire ant Wasmannia auropunctata before global invasion: inferring dispersal patterns, niche requirements, and past and present distribution within its native range

USDA-ARS?s Scientific Manuscript database

The evolutionary history of invasive species within their native range may involve key processes that allow them to colonize new habitats. We integrated classic and Bayesian phylogeographic methods with a paleodistribution modeling approach to study the demographic patterns that shaped the distribut...

Earthworm abundance and distribution pattern in contrasting plant communities within a tropical wet forest in Puerto Rico

Treesearch

G. Gonzalez; X. Zou; A. Sabat; N. Fetcher

1999-01-01

Plant communities may impose strong control on soil fauna properties. We examined the abundance and distribution pattern of earthworms in two contrasting plant communities within a tropical wet forest in Puerto Rico. The Dacryodes community occurs in well-drained soils and is dominated by Dacryodes excels, Manilkara bidentata, Guarea guidonea, and Sloanea berteriana....

Large scale patterns in vertical distribution and behaviour of mesopelagic scattering layers

NASA Astrophysics Data System (ADS)

Klevjer, T. A.; Irigoien, X.; Røstad, A.; Fraile-Nuez, E.; Benítez-Barrios, V. M.; Kaartvedt., S.

2016-01-01

Recent studies suggest that previous estimates of mesopelagic biomasses are severely biased, with the new, higher estimates underlining the need to unveil behaviourally mediated coupling between shallow and deep ocean habitats. We analysed vertical distribution and diel vertical migration (DVM) of mesopelagic acoustic scattering layers (SLs) recorded at 38 kHz across oceanographic regimes encountered during the circumglobal Malaspina expedition. Mesopelagic SLs were observed in all areas covered, but vertical distributions and DVM patterns varied markedly. The distribution of mesopelagic backscatter was deepest in the southern Indian Ocean (weighted mean daytime depth: WMD 590 m) and shallowest at the oxygen minimum zone in the eastern Pacific (WMD 350 m). DVM was evident in all areas covered, on average ~50% of mesopelagic backscatter made daily excursions from mesopelagic depths to shallow waters. There were marked differences in migrating proportions between the regions, ranging from ~20% in the Indian Ocean to ~90% in the Eastern Pacific. Overall the data suggest strong spatial gradients in mesopelagic DVM patterns, with implied ecological and biogeochemical consequences. Our results suggest that parts of this spatial variability can be explained by horizontal patterns in physical-chemical properties of water masses, such as oxygen, temperature and turbidity.

Large scale patterns in vertical distribution and behaviour of mesopelagic scattering layers.

PubMed

Klevjer, T A; Irigoien, X; Røstad, A; Fraile-Nuez, E; Benítez-Barrios, V M; Kaartvedt, S

2016-01-27

Recent studies suggest that previous estimates of mesopelagic biomasses are severely biased, with the new, higher estimates underlining the need to unveil behaviourally mediated coupling between shallow and deep ocean habitats. We analysed vertical distribution and diel vertical migration (DVM) of mesopelagic acoustic scattering layers (SLs) recorded at 38 kHz across oceanographic regimes encountered during the circumglobal Malaspina expedition. Mesopelagic SLs were observed in all areas covered, but vertical distributions and DVM patterns varied markedly. The distribution of mesopelagic backscatter was deepest in the southern Indian Ocean (weighted mean daytime depth: WMD 590 m) and shallowest at the oxygen minimum zone in the eastern Pacific (WMD 350 m). DVM was evident in all areas covered, on average ~50% of mesopelagic backscatter made daily excursions from mesopelagic depths to shallow waters. There were marked differences in migrating proportions between the regions, ranging from ~20% in the Indian Ocean to ~90% in the Eastern Pacific. Overall the data suggest strong spatial gradients in mesopelagic DVM patterns, with implied ecological and biogeochemical consequences. Our results suggest that parts of this spatial variability can be explained by horizontal patterns in physical-chemical properties of water masses, such as oxygen, temperature and turbidity.

Survey on aedes mosquito density and pattern distribution of aedes aegypti and aedes albopictus in high and low incidence districts in north sumatera province

NASA Astrophysics Data System (ADS)

Siregar, Fazidah A.; Makmur, Tri

2018-03-01

Transmission and control of dengue hemorrhagic fever are related to its vectors. This study investigated vector density and distribution patterns of Aedes aegypty and Aedes albopictus in Medan and Langkat as high and low incidence district, respectively. An entomological survey was carried out in 304 households both in Medan and Langkat. The results showed that adult Ae. aegypti were predominantly in Medan, while adult Ae. albopictus was only in Langkat. Larvae indices (HI, CI, BI) for Aedes in Medan ( 35,13 and 43) were higher than langkat ( 22,8 and 30). Adult indices (AHI, AD, RR) for Ae. aegypti in Medan and for Ae. albopictus in Langkat were 20,38,24 and 3,5, and 5, respectively. Pattern distribution of Aedes larvae and adult mosquitoes in both district had similar pattern. Aedes larval indices and adult indices both in HIDs and LIDs were above the critical level, indicating potential high risk for DHF transmission. By multiple regression analysis, HI is predictor for DHF transmission in North Sumatera. Thus, in designing an effective control measures for dengue hemorrhagic fever, monitoring distribution and vector density is crucial.

The Ability of Atmospheric Data to Reduce Disagreements in Wetland Methane Flux Estimates over North America

NASA Astrophysics Data System (ADS)

Miller, S. M.; Andrews, A. E.; Benmergui, J. S.; Commane, R.; Dlugokencky, E. J.; Janssens-Maenhout, G.; Melton, J. R.; Michalak, A. M.; Sweeney, C.; Worthy, D. E. J.

2015-12-01

Existing estimates of methane fluxes from wetlands differ in both magnitude and distribution across North America. We discuss seven different bottom-up methane estimates in the context of atmospheric methane data collected across the US and Canada. In the first component of this study, we explore whether the observation network can even detect a methane pattern from wetlands. We find that the observation network can identify a methane pattern from Canadian wetlands but not reliably from US wetlands. Over Canada, the network can even identify spatial patterns at multi-provence scales. Over the US, by contrast, anthropogenic emissions and modeling errors obscure atmospheric patterns from wetland fluxes. In the second component of the study, we then use these observations to reconcile disagreements in the magnitude, seasonal cycle, and spatial distribution of existing estimates. Most existing estimates predict fluxes that are too large with a seasonal cycle that is too narrow. A model known as LPJ-Bern has a spatial distribution most consistent with atmospheric observations. By contrast, a spatially-constant model outperforms the distribution of most existing flux estimates across Canada. The results presented here provide several pathways to reduce disagreements among existing wetland flux estimates across North America.

Understanding taxi travel patterns

NASA Astrophysics Data System (ADS)

Cai, Hua; Zhan, Xiaowei; Zhu, Ji; Jia, Xiaoping; Chiu, Anthony S. F.; Xu, Ming

2016-09-01

Taxis play important roles in modern urban transportation systems, especially in mega cities. While providing necessary amenities, taxis also significantly contribute to traffic congestion, urban energy consumption, and air pollution. Understanding the travel patterns of taxis is thus important for addressing many urban sustainability challenges. Previous research has primarily focused on examining the statistical properties of passenger trips, which include only taxi trips occupied with passengers. However, unoccupied trips are also important for urban sustainability issues because they represent potential opportunities to improve the efficiency of the transportation system. Therefore, we need to understand the travel patterns of taxis as an integrated system, instead of focusing only on the occupied trips. In this study we examine GPS trajectory data of 11,880 taxis in Beijing, China for a period of three weeks. Our results show that taxi travel patterns share similar traits with travel patterns of individuals but also exhibit differences. Trip displacement distribution of taxi travels is statistically greater than the exponential distribution and smaller than the truncated power-law distribution. The distribution of short trips (less than 30 miles) can be best fitted with power-law while long trips follow exponential decay. We use radius of gyration to characterize individual taxi's travel distance and find that it does not follow a truncated power-law as observed in previous studies. Spatial and temporal regularities exist in taxi travels. However, with increasing spatial coverage, taxi trips can exhibit dual high probability density centers.

Patterns of Spatial Variation of Assemblages Associated with Intertidal Rocky Shores: A Global Perspective

PubMed Central

Cruz-Motta, Juan José; Miloslavich, Patricia; Palomo, Gabriela; Iken, Katrin; Konar, Brenda; Pohle, Gerhard; Trott, Tom; Benedetti-Cecchi, Lisandro; Herrera, César; Hernández, Alejandra; Sardi, Adriana; Bueno, Andrea; Castillo, Julio; Klein, Eduardo; Guerra-Castro, Edlin; Gobin, Judith; Gómez, Diana Isabel; Riosmena-Rodríguez, Rafael; Mead, Angela; Bigatti, Gregorio; Knowlton, Ann; Shirayama, Yoshihisa

2010-01-01

Assemblages associated with intertidal rocky shores were examined for large scale distribution patterns with specific emphasis on identifying latitudinal trends of species richness and taxonomic distinctiveness. Seventy-two sites distributed around the globe were evaluated following the standardized sampling protocol of the Census of Marine Life NaGISA project (www.nagisa.coml.org). There were no clear patterns of standardized estimators of species richness along latitudinal gradients or among Large Marine Ecosystems (LMEs); however, a strong latitudinal gradient in taxonomic composition (i.e., proportion of different taxonomic groups in a given sample) was observed. Environmental variables related to natural influences were strongly related to the distribution patterns of the assemblages on the LME scale, particularly photoperiod, sea surface temperature (SST) and rainfall. In contrast, no environmental variables directly associated with human influences (with the exception of the inorganic pollution index) were related to assemblage patterns among LMEs. Correlations of the natural assemblages with either latitudinal gradients or environmental variables were equally strong suggesting that neither neutral models nor models based solely on environmental variables sufficiently explain spatial variation of these assemblages at a global scale. Despite the data shortcomings in this study (e.g., unbalanced sample distribution), we show the importance of generating biological global databases for the use in large-scale diversity comparisons of rocky intertidal assemblages to stimulate continued sampling and analyses. PMID:21179546

Digital holographic tomography method for 3D observation of domain patterns in ferroelectric single crystals

NASA Astrophysics Data System (ADS)

Mokrý, Pavel; Psota, Pavel; Steiger, Kateřina; Václavík, Jan; Vápenka, David; Doleček, Roman; Vojtíšek, Petr; Sládek, Juraj; Lédl, Vít.

2016-11-01

We report on the development and implementation of the digital holographic tomography for the three-dimensio- nal (3D) observations of the domain patterns in the ferroelectric single crystals. Ferroelectric materials represent a group of materials, whose macroscopic dielectric, electromechanical, and elastic properties are greatly in uenced by the presence of domain patterns. Understanding the role of domain patterns on the aforementioned properties require the experimental techniques, which allow the precise 3D measurements of the spatial distribution of ferroelectric domains in the single crystal. Unfortunately, such techniques are rather limited at this time. The most frequently used piezoelectric atomic force microscopy allows 2D observations on the ferroelectric sample surface. Optical methods based on the birefringence measurements provide parameters of the domain patterns averaged over the sample volume. In this paper, we analyze the possibility that the spatial distribution of the ferroelectric domains can be obtained by means of the measurement of the wavefront deformation of the transmitted optical wave. We demonstrate that the spatial distribution of the ferroelectric domains can be determined by means of the measurement of the spatial distribution of the refractive index. Finally, it is demonstrated that the measurements of wavefront deformations generated in ferroelectric polydomain systems with small variations of the refractive index provide data, which can be further processed by means of the conventional tomographic methods.

Combining satellite data and appropriate objective functions for improved spatial pattern performance of a distributed hydrologic model

NASA Astrophysics Data System (ADS)

Demirel, Mehmet C.; Mai, Juliane; Mendiguren, Gorka; Koch, Julian; Samaniego, Luis; Stisen, Simon

2018-02-01

Satellite-based earth observations offer great opportunities to improve spatial model predictions by means of spatial-pattern-oriented model evaluations. In this study, observed spatial patterns of actual evapotranspiration (AET) are utilised for spatial model calibration tailored to target the pattern performance of the model. The proposed calibration framework combines temporally aggregated observed spatial patterns with a new spatial performance metric and a flexible spatial parameterisation scheme. The mesoscale hydrologic model (mHM) is used to simulate streamflow and AET and has been selected due to its soil parameter distribution approach based on pedo-transfer functions and the build in multi-scale parameter regionalisation. In addition two new spatial parameter distribution options have been incorporated in the model in order to increase the flexibility of root fraction coefficient and potential evapotranspiration correction parameterisations, based on soil type and vegetation density. These parameterisations are utilised as they are most relevant for simulated AET patterns from the hydrologic model. Due to the fundamental challenges encountered when evaluating spatial pattern performance using standard metrics, we developed a simple but highly discriminative spatial metric, i.e. one comprised of three easily interpretable components measuring co-location, variation and distribution of the spatial data. The study shows that with flexible spatial model parameterisation used in combination with the appropriate objective functions, the simulated spatial patterns of actual evapotranspiration become substantially more similar to the satellite-based estimates. Overall 26 parameters are identified for calibration through a sequential screening approach based on a combination of streamflow and spatial pattern metrics. The robustness of the calibrations is tested using an ensemble of nine calibrations based on different seed numbers using the shuffled complex evolution optimiser. The calibration results reveal a limited trade-off between streamflow dynamics and spatial patterns illustrating the benefit of combining separate observation types and objective functions. At the same time, the simulated spatial patterns of AET significantly improved when an objective function based on observed AET patterns and a novel spatial performance metric compared to traditional streamflow-only calibration were included. Since the overall water balance is usually a crucial goal in hydrologic modelling, spatial-pattern-oriented optimisation should always be accompanied by traditional discharge measurements. In such a multi-objective framework, the current study promotes the use of a novel bias-insensitive spatial pattern metric, which exploits the key information contained in the observed patterns while allowing the water balance to be informed by discharge observations.

Metals in obex and retropharyngeal lymph nodes of Illinois white-tailed deer and their variations associated with CWD status.

PubMed

Rivera, Nelda A; Novakofski, Jan; Weng, Hsin-Yi; Kelly, Amy; Satterthwaite-Phillips, Damian; Ruiz, Marilyn O; Mateus-Pinilla, Nohra

2015-01-01

Prion proteins (PrP(C)) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP(C)'s participation in metal transport and cellular protection against stress in the central nervous system (CNS). On the other hand PrP(Sc), the misfolded isoform of PrP(C) and the pathogenic agent in transmissible spongiform encephalopathies (TSE), has been associated with brain metal dyshomeostasis in prion diseases. Thus, changes in metal concentration associated with protein misfolding and aggregation have been reported for human and animal prion diseases, as well as for other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. The use of metal concentrations in tissues as surrogate markers for early detection of TSEs has been suggested. Studies on the accumulation of metals in free-ranging white-tailed deer have not been conducted. This study established concentrations of copper, iron, manganese, and magnesium in 2 diagnostic tissues used for CWD testing (obex and retropharyngeal lymph nodes (RLN)). We compared these concentrations between tissues and in relation to CWD status. We established reference intervals (RIs) for these metals and explored their ability to discriminate between CWD-positive and CWD-negative animals. Our results indicate that independent of CWD status, white-tailed deer accumulate higher concentrations of Fe, Mn and Mg in RLN than in obex. White-tailed deer infected with CWD accumulated significantly lower concentrations of Mn and Fe than CWD-negative deer. These patterns differed from other species infected with prion diseases. Overlapping values between CWD positive and negative groups indicate that evaluation of these metals in obex and RLN may not be appropriate as a diagnostic tool for CWD infection in white-tailed deer. Because the CWD-negative deer were included in constructing the RIs, high specificities were expected and should be interpreted with caution. Due to the low sensitivity derived from the RIs, we do not recommend using metal concentrations for disease discrimination.

Scattering apodizer for laser beams

DOEpatents

Summers, Mark A.; Hagen, Wilhelm F.; Boyd, Robert D.

1985-01-01

A method is disclosed for apodizing a laser beam to smooth out the production of diffraction peaks due to optical discontinuities in the path of the laser beam, such method comprising introduction of a pattern of scattering elements for reducing the peak intensity in the region of such optical discontinuities, such pattern having smoothly tapering boundaries in which the distribution density of the scattering elements is tapered gradually to produce small gradients in the distribution density, such pattern of scattering elements being effective to reduce and smooth out the diffraction effects which would otherwise be produced. The apodizer pattern may be produced by selectively blasting a surface of a transparent member with fine abrasive particles to produce a multitude of minute pits. In one embodiment, a scattering apodizer pattern is employed to overcome diffraction patterns in a multiple element crystal array for harmonic conversion of a laser beam. The interstices and the supporting grid between the crystal elements are obscured by the gradually tapered apodizer pattern of scattering elements.

Scattering apodizer for laser beams

DOEpatents

Summers, M.A.; Hagen, W.F.; Boyd, R.D.

1984-01-01

A method is disclosed for apodizing a laser beam to smooth out the production of diffraction peaks due to optical discontinuities in the path of the laser beam, such method comprising introduction of a pattern of scattering elements for reducing the peak intensity in the region of such optical discontinuities, such pattern having smoothly tapering boundaries in which the distribution density of the scattering elements is tapered gradually to produce small gradients in the distribution density, such pattern of scattering elements being effective to reduce and smooth out the diffraction effects which would otherwise be produced. The apodizer pattern may be produced by selectively blasting a surface of a transparent member with fine abrasive particles to produce a multitude of minute pits. In one embodiment, a scattering apodizer pattern is employed to overcome diffraction patterns in a multiple element crystal array for harmonic conversion of a laser beam. The interstices and the supporting grid between the crystal elements are obscured by the gradually tapered apodizer pattern of scattering elements.

Synthesis of Seafood Catch, Distribution, and Consumption Patterns in the Gulf of Mexico Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steimle and Associates, Inc.

The purpose of this task was to gather and assemble information that will provide a synthesis of seafood catch, distribution and consumption patterns for the Gulf of Mexico (GOM) region. This task was part of a U.S. Department of Energy (DOE)-sponsored project entitled ''Environmental and Economic Assessment of Discharges from Gulf of Mexico Region Oil and Gas Operations.'' Personal interviews were conducted with a total of 905 recreational fishermen and 218 commercial fishermen (inclusive of shrimpers, crabbers, oystermen and finfishermen) in Louisiana and Texas using survey questionnaires developed for the study. Results of these interviews detail the species and quantitiesmore » caught, location of catch, mode of fishing, distribution of catch, family consumption patterns and demographics of the fishermen.« less

Demographic expansion of two Tamarix species along the Yellow River caused by geological events and climate change in the Pleistocene.

PubMed

Liang, Hong-Yan; Feng, Zhi-Pei; Pei, Bing; Li, Yong; Yang, Xi-Tian

2018-01-08

The geological events and climatic fluctuations during the Pleistocene played important roles in shaping patterns of species distribution. However, few studies have evaluated the patterns of species distribution that were influenced by the Yellow River. The present work analyzed the demography of two endemic tree species that are widely distributed along the Yellow River, Tamarix austromongolica and Tamarix chinensis, to understand the role of the Yellow River and Pleistocene climate in shaping their distribution patterns. The most common chlorotype, chlorotype 1, was found in all populations, and its divergence time could be dated back to 0.19 million years ago (Ma). This dating coincides well with the formation of the modern Yellow River and the timing of Marine Isotope Stages 5e-6 (MIS 5e-6). Bayesian reconstructions along with models of paleodistribution revealed that these two species experienced a demographic expansion in population size during the Quaternary period. Approximate Bayesian computation analyses supported a scenario of expansion approximately from the upper to lower reaches of the Yellow River. Our results provide support for the roles of the Yellow River and the Pleistocene climate in driving demographic expansion of the populations of T. austromongolica and T. chinensis. These findings are useful for understanding the effects of geological events and past climatic fluctuations on species distribution patterns.

Examining the relationship between comprehension and production processes in code-switched language

PubMed Central

Guzzardo Tamargo, Rosa E.; Valdés Kroff, Jorge R.; Dussias, Paola E.

2016-01-01

We employ code-switching (the alternation of two languages in bilingual communication) to test the hypothesis, derived from experience-based models of processing (e.g., Boland, Tanenhaus, Carlson, & Garnsey, 1989; Gennari & MacDonald, 2009), that bilinguals are sensitive to the combinatorial distributional patterns derived from production and that they use this information to guide processing during the comprehension of code-switched sentences. An analysis of spontaneous bilingual speech confirmed the existence of production asymmetries involving two auxiliary + participle phrases in Spanish–English code-switches. A subsequent eye-tracking study with two groups of bilingual code-switchers examined the consequences of the differences in distributional patterns found in the corpus study for comprehension. Participants’ comprehension costs mirrored the production patterns found in the corpus study. Findings are discussed in terms of the constraints that may be responsible for the distributional patterns in code-switching production and are situated within recent proposals of the links between production and comprehension. PMID:28670049

Examining the relationship between comprehension and production processes in code-switched language.

PubMed

Guzzardo Tamargo, Rosa E; Valdés Kroff, Jorge R; Dussias, Paola E

2016-08-01

We employ code-switching (the alternation of two languages in bilingual communication) to test the hypothesis, derived from experience-based models of processing (e.g., Boland, Tanenhaus, Carlson, & Garnsey, 1989; Gennari & MacDonald, 2009), that bilinguals are sensitive to the combinatorial distributional patterns derived from production and that they use this information to guide processing during the comprehension of code-switched sentences. An analysis of spontaneous bilingual speech confirmed the existence of production asymmetries involving two auxiliary + participle phrases in Spanish-English code-switches. A subsequent eye-tracking study with two groups of bilingual code-switchers examined the consequences of the differences in distributional patterns found in the corpus study for comprehension. Participants' comprehension costs mirrored the production patterns found in the corpus study. Findings are discussed in terms of the constraints that may be responsible for the distributional patterns in code-switching production and are situated within recent proposals of the links between production and comprehension.

The influence of body fat distribution patterns and body mass index on MENQOL in women living in an urban area.

PubMed

Kutheerawong, L; Vichinsartvichai, P

2016-01-01

To investigate the influence of patterns of body fat distribution and body mass index (BMI) on menopause-specific quality of life in peri- and postmenopausal women living in an urban area. A total of 214 peri- and postmenopausal women, mean age 55 years, with intact uterus and no history of hormonal treatment were recruited. Anthropometric measurements were conducted as standard techniques. The Menopause-specific Quality of Life (MENQOL) questionnaire was used to evaluate menopause-specific quality of life. The Mann-Whitney U test and Kruskal-Wallis test were used to compare MENQOL between body fat patterns or BMI. According to the body fat distribution patterns, 53.3% were women of the android type and 46.7% were of the gynoid type. The android body pattern was associated with worsening of vasomotor and psychosocial domains (p < 0.05). However, overweight and obese women had slightly better scores in the sexual domain of the MENQOL. Peri- and postmenopausal women with the android body pattern have lower quality of life in the vasomotor and psychosocial domains while women with normal BMI have the slightly lower quality of life in the sexual domain. The maintenance of premenopausal body proportion might mitigate the menopause-specific quality of life.

Spatial emission distribution of InGaN/GaN light-emitting diodes depending on the pattern structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kwanjae; Lee, Hyunjung; Lee, Cheul-Ro

2014-10-15

Highlights: • We study carrier lifetimes of InGaN/GaN LEDs fabricated on different PSS. • Spatial EL distribution was investigated depending on the pattern structure. • The carrier lifetime of the LEDs was compared with the spatial EL distribution. - Abstract: We investigated the emission characteristics of InGaN/GaN light-emitting diodes (LEDs) fabricated on lens-shaped (LS) patterned-sapphire substrates (PSS) by using time-resolved photoluminescence (TRPL) and confocal-scanning-electroluminescence microscopy (CSEM). The carrier lifetimes evaluated from the TRPL spectra for the LEDs on the LS-PSS (LS-LEDs) at 10 K were relatively shorter than those of the LEDs on a conventional planar substrate (C-LED). However, themore » carrier lifetimes for the LS-LEDs were relatively long compared to that of the C-LED at room temperature. In the CSEM images of the LS-LEDs, the emission beam around the center region of the LS pattern was relatively weaker than that of the edge region. In addition, the beam profile for the LS-LEDs showed different shapes according to the pattern structures. The emission beam around the boundary region of the LS pattern showed periodic fluctuation with the peak-to-peak distance of 814 nm.« less

Distribution of IS900 restriction fragment length polymorphism types among animal Mycobacterium avium subsp. paratuberculosis isolates from Argentina and Europe.

PubMed

Moreira, A R; Paolicchi, F; Morsella, C; Zumarraga, M; Cataldi, A; Fabiana, B; Alicia, A; Piet, O; van Soolingen, D; Isabel, R M

1999-12-01

Sixty-one Mycobacterium avium subsp. paratuberculosis isolates from cattle and deer from the Buenos Aires province, an important livestock region in Argentina, were typed by restriction fragment length polymorphisms (RFLP) analysis based on IS900. Four different RFLP patterns (designated 'A', 'B', 'C' and 'E') were identified in BstEII digests of genomic DNA. The most frequently observed type, pattern 'A', was found in 46 isolates (75%). The second, pattern 'E', included 8 isolates (13%), while the third, pattern 'B', included 6 isolates (10%). Pattern 'C' was found for only one isolate. All of the deer isolates were classified as pattern 'A', while cattle isolates represented all four RFLP patterns. Twenty-one isolates representing the four different BstEII-RFLP patterns were digested with PstI. Twenty isolates showed identical PstI-RFLP pattern. BstEII-RFLP patterns from Argentine cattle and deer were compared with patterns found in cattle, goat, deer, rabbit, and human isolates from Europe. The most common pattern in Argentina, pattern 'A', was identical to a less frequently occurring pattern R9 (C17) from Europe. The other Argentine patterns 'B', 'C' and 'E', were not found in the Europe. These results indicate that the distribution of M. avium subsp. paratuberculosis genotypes in the Buenos Aires province of Argentina is different from that found in Europe.

Potential effects of climate change on the distribution range of the main silicate sinker of the Southern Ocean.

PubMed

Pinkernell, Stefan; Beszteri, Bánk

2014-08-01

Fragilariopsis kerguelensis, a dominant diatom species throughout the Antarctic Circumpolar Current, is coined to be one of the main drivers of the biological silicate pump. Here, we study the distribution of this important species and expected consequences of climate change upon it, using correlative species distribution modeling and publicly available presence-only data. As experience with SDM is scarce for marine phytoplankton, this also serves as a pilot study for this organism group. We used the maximum entropy method to calculate distribution models for the diatom F. kerguelensis based on yearly and monthly environmental data (sea surface temperature, salinity, nitrate and silicate concentrations). Observation data were harvested from GBIF and the Global Diatom Database, and for further analyses also from the Hustedt Diatom Collection (BRM). The models were projected on current yearly and seasonal environmental data to study current distribution and its seasonality. Furthermore, we projected the seasonal model on future environmental data obtained from climate models for the year 2100. Projected on current yearly averaged environmental data, all models showed similar distribution patterns for F. kerguelensis. The monthly model showed seasonality, for example, a shift of the southern distribution boundary toward the north in the winter. Projections on future scenarios resulted in a moderately to negligibly shrinking distribution area and a change in seasonality. We found a substantial bias in the publicly available observation datasets, which could be reduced by additional observation records we obtained from the Hustedt Diatom Collection. Present-day distribution patterns inferred from the models coincided well with background knowledge and previous reports about F. kerguelensis distribution, showing that maximum entropy-based distribution models are suitable to map distribution patterns for oceanic planktonic organisms. Our scenario projections indicate moderate effects of climate change upon the biogeography of F. kerguelensis.

The causes of spatial patterning of mounds of a fungus-cultivating termite: results from nearest-neighbour analysis and ecological studies.

PubMed

Korb, Judith; Linsenmair, Karl Eduard

2001-05-01

Little is known about processes regulating population dynamics in termites. We investigated the distribution of mound-colonies of the fungus-cultivating termite Macrotermes bellicosus (Smeathman) in two habitats in the Comoé National Park (Côte d'Ivoire) with nearest-neighbour analysis differentiating between different age classes. These results were compared with ecological data on processes influencing population dynamics. High mound densities were recorded in shrub savannah while only a few mounds were found in gallery forest. Mounds were distributed randomly in both habitats when all mounds were considered together, and when inhabited and uninhabited mounds were treated separately. However, distinctive non-random patterns were revealed in the savannah when we distinguished between different age classes. Small, young colonies were aggregated when they coexisted with larger, older colonies, which were more regularly distributed. This indicates that the distribution of older colonies is influenced by intraspecific competition whereas that of younger colonies is influenced by opposing factors that lead to aggregation. This is in accordance with ecological data. Food is a limiting resource for large colonies, while patchily distributed appropriate microclimatic conditions seem to be more important for young colonies. Colonies that had formerly coexisted (i.e. living colonies and recently dead colonies) showed aggregated, random and regular distribution patterns, suggesting several causes of mortality. Colonies that had never had contact with each other were randomly distributed and no specific regulation mechanism was implicated. These results show that different age classes seem to be regulated by different processes and that separation between age classes is necessary to reveal indicative spatial patterns in nearest-neighbour analysis.

[Effects of sub-watershed landscape patterns at the upper reaches of Minjiang River on soil erosion].

PubMed

Yang, Meng; Li, Xiu-zhen; Yang, Zhao-ping; Hu, Yuan-man; Wen, Qing-chun

2007-11-01

Based on GIS, the spatial distribution of soil loss and sediment yield in Heishui and Zhenjiangguan sub-watersheds at the upper reaches of Minjiang River was simulated by using sediment delivery-distribution (SEDD) model, and the effects of land use/cover types on soil erosion and sediment yield were discussed, based on the simulated results and related land use maps. A landscape index named location-weighted landscape contrast index (LCI) was calculated to evaluate the effects of landscape components' spatial distribution, weight, and structure of land use/cover on soil erosion. The results showed the soil erosion modulus varied with land use pattern, and decreased in the order of bare rock > urban/village > rangeland > farmland > shrub > forest. There were no significant differences in sediment yield modules among different land use/covers. In the two sub-watersheds, the spatial distribution of land use/covers on slope tended to decrease the final sediment load at watershed outlet, hut as related to relative elevation, relative distance, and flow length, the spatial distribution tended to increase sediment yield. The two sub-watersheds had different advantages as related to landscape components' spatial distribution, but, when the land use/cover weight was considered, the advantages of Zhenjiangguan sub-watershed increased. If the land use/cover structure was considered in addition, the landscape pattern of Zhenjiangguan subwatershed was better. Therefore, only the three elements, i.e., landscape components' spatial distribution, land use/cover weight, and land use/cover structure, were considered comprehensively, can we get an overall evaluation on the effects of landscape pattern on soil erosion. The calculation of LCI related to slope suggested that this index couldn' t accurately reflect the effects of land use/cover weight and structure on soil erosion, and thus, needed to be modified.

Investigating distribution pattern of species in a warm-temperate conifer-broadleaved-mixed forest in China for sustainably utilizing forest and soils.

PubMed

Song, Houjuan; Xu, Yudan; Hao, Jing; Zhao, Bingqing; Guo, Donggang; Shao, Hongbo

2017-02-01

The maintaining mechanisms and potential ecological processes of species diversity in warm temperate- conifer-broadleaved-mixed forest are far from clear understanding. In this paper, the relative neighborhood density Ω was used to analyze the spatial distribution patterns of 34 species with ≥11 individuals in a warm- temperate-conifer-broadleaved-mixed forest, northern China. Then we used canonical correspondence analysis (CCA) and Torus-translation test (TTT) to explain the distribution of observed species. Our results show that aggregated distribution is the dominant pattern in warm-temperate natural forest and four species regular distribution at the spatial scale >30m. The aggregated percentage and intensity decline with spatial scale, abundance and size classes increasing. Rare species are aggregated more than intermediate and abundant species. These results prove sufficiently the effects existence of scale separation, self-thinning and Janzen-Connell hypothesis. In addition, functional traits (dispersal modes and shade tolerance) also have a significant influence on distribution of species. The results of CCA confirm that slope and convexity are the most important factors affecting the distribution of tree species distribution, elevation and slope of shrub species though the combination of topographic variables only explained 1% of distribution of tree species and 2% of shrub species. Most species don't have habitat preference; however 47.1% (16/34) species including absolutely dominant tree (Pinus tabulaeformis and Quercus wutaishanica) and shrub species (Rosa xanthina) and most other species with important value in the front, are strongly positively or negatively associated with at least one habitat. The valley and ridge are most distinct habitat with association of 12 species in the plot. However, high elevation slope with 257 quadrats is the most extensive habitat with only four species. Therefore, there is obvious evidence that habitat heterogeneity play an important role on shaping spatial distribution of species in warm temperate forest. Our research results provide significant evidence that dispersal limitation and habitat heterogeneity have a contribution jointly to regulating the spatial distribution pattern of species in warm-temperate-forest in China. Copyright © 2016 Elsevier B.V. All rights reserved.

Normal and compound poisson approximations for pattern occurrences in NGS reads.

PubMed

Zhai, Zhiyuan; Reinert, Gesine; Song, Kai; Waterman, Michael S; Luan, Yihui; Sun, Fengzhu

2012-06-01

Next generation sequencing (NGS) technologies are now widely used in many biological studies. In NGS, sequence reads are randomly sampled from the genome sequence of interest. Most computational approaches for NGS data first map the reads to the genome and then analyze the data based on the mapped reads. Since many organisms have unknown genome sequences and many reads cannot be uniquely mapped to the genomes even if the genome sequences are known, alternative analytical methods are needed for the study of NGS data. Here we suggest using word patterns to analyze NGS data. Word pattern counting (the study of the probabilistic distribution of the number of occurrences of word patterns in one or multiple long sequences) has played an important role in molecular sequence analysis. However, no studies are available on the distribution of the number of occurrences of word patterns in NGS reads. In this article, we build probabilistic models for the background sequence and the sampling process of the sequence reads from the genome. Based on the models, we provide normal and compound Poisson approximations for the number of occurrences of word patterns from the sequence reads, with bounds on the approximation error. The main challenge is to consider the randomness in generating the long background sequence, as well as in the sampling of the reads using NGS. We show the accuracy of these approximations under a variety of conditions for different patterns with various characteristics. Under realistic assumptions, the compound Poisson approximation seems to outperform the normal approximation in most situations. These approximate distributions can be used to evaluate the statistical significance of the occurrence of patterns from NGS data. The theory and the computational algorithm for calculating the approximate distributions are then used to analyze ChIP-Seq data using transcription factor GABP. Software is available online (www-rcf.usc.edu/∼fsun/Programs/NGS_motif_power/NGS_motif_power.html). In addition, Supplementary Material can be found online (www.liebertonline.com/cmb).

The Biogeography of Putative Microbial Antibiotic Production

PubMed Central

Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

2015-01-01

Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

Submicron Surface-Patterned Fibers and Textiles

DTIC Science & Technology

2016-11-04

These authors contributed equally Keywords: grating, fiber, polymer , patterning, textile Distribution A: approved for public release...requirements. Second, textile materials are primarily polymer -based, while most surface-patterning techniques have been developed for silicon...Alternative substrates, especially flexible polymers , remain challenging to pattern [25,26] due to the highly specific surface chemistry of different

Infectious particles, stress, and induced prion amyloids

PubMed Central

2013-01-01

Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrPSc) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging. PMID:23633671

β-sheet-like formation during the mechanical unfolding of prion protein

NASA Astrophysics Data System (ADS)

Tao, Weiwei; Yoon, Gwonchan; Cao, Penghui; Eom, Kilho; Park, Harold S.

2015-09-01

Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrPC, whose misfolded form PrPSc can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

Alteration of the endocannabinoid system in mouse brain during prion disease.

PubMed

Petrosino, S; Ménard, B; Zsürger, N; Di Marzo, V; Chabry, J

2011-03-17

Prion diseases are neurodegenerative disorders characterized by deposition of the pathological prion protein (PrPsc) within the brain of affected humans and animals. Microglial cell activation is a common feature of prion diseases; alterations of various neurotransmitter systems and neurotransmission have been also reported. Owing to its ability to modulate both neuroimmune responses and neurotransmission, it was of interest to study the brain endocannabinoid system in a prion-infected mouse model. The production of the endocannabinoid, 2-arachidonoyglycerol (2-AG), was enhanced 10 weeks post-infection, without alteration of the other endocannabinoid, anandamide. The CB2 receptor expression was up-regulated in brains of prion-infected mice as early as 10 weeks and up to 32 weeks post-infection whereas the mRNAs of other cannabinoid receptors (CBRs) remain unchanged. The observed alterations of the endocannabinoid system were specific for prion infection since no significant changes were observed in the brain of prion-resistant mice, that is, mice devoid of the Prnp gene. Our study highlights important alterations of the endocannabinoid system during early stages of the disease long before the clinical signs of the disease. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Spatial distribution of 12 class B notifiable infectious diseases in China: A retrospective study.

PubMed

Zhu, Bin; Fu, Yang; Liu, Jinlin; Mao, Ying

2018-01-01

China is the largest developing country with a relatively developed public health system. To further prevent and eliminate the spread of infectious diseases, China has listed 39 notifiable infectious diseases characterized by wide prevalence or great harm, and classified them into classes A, B, and C, with severity decreasing across classes. Class A diseases have been almost eradicated in China, thus making class B diseases a priority in infectious disease prevention and control. In this retrospective study, we analyze the spatial distribution patterns of 12 class B notifiable infectious diseases that remain active all over China. Global and local Moran's I and corresponding graphic tools are adopted to explore and visualize the global and local spatial distribution of the incidence of the selected epidemics, respectively. Inter-correlations of clustering patterns of each pair of diseases and a cumulative summary of the high/low cluster frequency of the provincial units are also provided by means of figures and maps. Of the 12 most commonly notifiable class B infectious diseases, viral hepatitis and tuberculosis show high incidence rates and account for more than half of the reported cases. Almost all the diseases, except pertussis, exhibit positive spatial autocorrelation at the provincial level. All diseases feature varying spatial concentrations. Nevertheless, associations exist between spatial distribution patterns, with some provincial units displaying the same type of cluster features for two or more infectious diseases. Overall, high-low (unit with high incidence surrounded by units with high incidence, the same below) and high-high spatial cluster areas tend to be prevalent in the provincial units located in western and southwest China, whereas low-low and low-high spatial cluster areas abound in provincial units in north and east China. Despite the various distribution patterns of 12 class B notifiable infectious diseases, certain similarities between their spatial distributions are present. Substantial evidence is available to support disease-specific, location-specific, and disease-combined interventions. Regarding provinces that show high-high/high-low patterns of multiple diseases, comprehensive interventions targeting different diseases should be established. As to the adjacent provincial units revealing similar patterns, coordinated actions need to be taken across borders.

Co-occurrence patterns of trees along macro-climatic gradients and their potential influence on the present and future distribution of Fagus sylvatica L.

USGS Publications Warehouse

Meier, E.S.; Edwards, T.C.; Kienast, Felix; Dobbertin, M.; Zimmermann, N.E.

2011-01-01

Aim During recent and future climate change, shifts in large-scale species ranges are expected due to the hypothesized major role of climatic factors in regulating species distributions. The stress-gradient hypothesis suggests that biotic interactions may act as major constraints on species distributions under more favourable growing conditions, while climatic constraints may dominate under unfavourable conditions. We tested this hypothesis for one focal tree species having three major competitors using broad-scale environmental data. We evaluated the variation of species co-occurrence patterns in climate space and estimated the influence of these patterns on the distribution of the focal species for current and projected future climates.Location Europe.Methods We used ICP Forest Level 1 data as well as climatic, topographic and edaphic variables. First, correlations between the relative abundance of European beech (Fagus sylvatica) and three major competitor species (Picea abies, Pinus sylvestris and Quercus robur) were analysed in environmental space, and then projected to geographic space. Second, a sensitivity analysis was performed using generalized additive models (GAM) to evaluate where and how much the predicted F. sylvatica distribution varied under current and future climates if potential competitor species were included or excluded. We evaluated if these areas coincide with current species co-occurrence patterns.Results Correlation analyses supported the stress-gradient hypothesis: towards favourable growing conditions of F. sylvatica, its abundance was strongly linked to the abundance of its competitors, while this link weakened towards unfavourable growing conditions, with stronger correlations in the south and at low elevations than in the north and at high elevations. The sensitivity analysis showed a potential spatial segregation of species with changing climate and a pronounced shift of zones where co-occurrence patterns may play a major role.Main conclusions Our results demonstrate the importance of species co-occurrence patterns for calibrating improved species distribution models for use in projections of climate effects. The correlation approach is able to localize European areas where inclusion of biotic predictors is effective. The climate-induced spatial segregation of the major tree species could have ecological and economic consequences. ?? 2010 Blackwell Publishing Ltd.

Rooting depth distribution and nitrogen acquisition using 15N tracer, Barrow, Alaska, 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colleen Iversen

Permafrost thaw and degradation may lead to altered thickness of the active soil layer and a changing distribution of plant-available nutrients throughout the soil, but little is known about the nutrient acquisition strategies of dominant tundra plant species. We conducted an 15N isotope tracer experiment to assess the vertical distribution of nutrient acquisition among three dominant species representing important plant functional types (PFTs) on the Barrow Environmental Observatory (BEO) in Barrow, Alaska. We found that vertical patterns of root distribution and nutrient acquisition varied among plant species, and that root density may not entirely explain patterns of nutrient acquisition formore » all species.« less

A Theoretical Approach to Analyze the Parametric Influence on Spatial Patterns of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) Populations.

PubMed

Garcia, A G; Godoy, W A C

2017-06-01

Studies of the influence of biological parameters on the spatial distribution of lepidopteran insects can provide useful information for managing agricultural pests, since the larvae of many species cause serious impacts on crops. Computational models to simulate the spatial dynamics of insect populations are increasingly used, because of their efficiency in representing insect movement. In this study, we used a cellular automata model to explore different patterns of population distribution of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), when the values of two biological parameters that are able to influence the spatial pattern (larval viability and adult longevity) are varied. We mapped the spatial patterns observed as the parameters varied. Additionally, by using population data for S. frugiperda obtained in different hosts under laboratory conditions, we were able to describe the expected spatial patterns occurring in corn, cotton, millet, and soybean crops based on the parameters varied. The results are discussed from the perspective of insect ecology and pest management. We concluded that computational approaches can be important tools to study the relationship between the biological parameters and spatial distributions of lepidopteran insect pests.

Low reflection and field localization over surface plasmon device with subwavelength patterned aluminum film

NASA Astrophysics Data System (ADS)

Yuan, Ying; Peng, Sha; Long, Huabao; Liu, Runhan; Wei, Dong; Zhang, Xinyu; Wang, Haiwei; Xie, Changsheng

2018-02-01

In this paper, we propose a new device composed of patterned sub-wavelength arrays to investigate surface plasmons (SPs) over sub-wavelength metal nano-structures. The device consists of silicon substrate and sub-wavelength patterns fabricated on a layer of aluminum film with nanometer thickness. Each sub-wavelength pattern formed in aluminum film is composed of a basic nano-square and twelve triangles for shaping single nano-pattern, which are uniformly distributed on the four sides of each square. Reflectance spectra and electric field distribution in infrared region are simulated. Numerical simulation results demonstrate that the device can efficiently lower its reflectance in infrared spectrum, and the response frequency can be controlled by only changing the device parameters such as square side length and then triangle vertex angle. Besides, the simulated electric field distribution of the device shows obviously field localization effect at the edges of aluminum film nano-structure. The electric filed around the tips of aluminum triangles is localized into sub-wavelength scale, so as to be beyond the common diffraction limitation. Our work will help to reveal the interesting properties of SPs device, and also bring new prospect of photonic device.

Are there general spatial patterns of mangrove structure and composition along estuarine salinity gradients in Todos os Santos Bay?

NASA Astrophysics Data System (ADS)

Costa, Patrícia; Dórea, Antônio; Mariano-Neto, Eduardo; Barros, Francisco

2015-12-01

Species distribution and structural patterns of mangrove fringe forests along three tropical estuaries were evaluated in northeast of Brazil. Interstitial water salinity, percentage of fine sediments and organic matter content were investigated as explanatory variables. In all estuaries (Jaguaripe, Paraguaçu and Subaé estuaries), it was observed similar distribution patterns of four mangrove species and these patterns were mostly related with interstitial water salinity. Rhizophora mangle and Avicennia schaueriana tended to dominate sites under greater marine influence (lower estuary), while Avicennia germinans and Laguncularia racemosa dominated areas under greater freshwater influence (upper estuary), although the latter showed a wider distribution over these tropical estuarine gradients. Organic matter best explained canopy height and mean height. At higher salinities, there was practically no correlation between organic matter and density, but at lower salinity, organic matter was related to decreases in abundances. The described patterns can be related to interspecific differences in salt tolerance and competitive abilities and they are likely to be found at other tropical Atlantic estuaries. Future studies should investigate anthropic influences and causal processes in order to further improve the design of monitoring and restoration projects.

Seasonal changes in spatial patterns of two annual plants in the Chihuahuan Desert, USA

USGS Publications Warehouse

Yin, Z.-Y.; Guo, Q.; Ren, H.; Peng, S.-L.

2005-01-01

Spatial pattern of a biotic population may change over time as its component individuals grow or die out, but whether this is the case for desert annual plants is largely unknown. Here we examined seasonal changes in spatial patterns of two annuals, Eriogonum abertianum and Haplopappus gracilis, in initial (winter) and final (summer) densities. The density was measured as the number of individuals from 384 permanent quadrats (each 0.5 m × 0.5 m) in the Chihuahuan Desert near Portal, Arizona, USA. We used three probability distributions (binomial, Poisson, and negative binomial or NB) that represent three basic spatial patterns (regular, random, and clumped) to fit the observed frequency distributions of densities of the two annuals. Both species showed clear clumped patterns as characterized by the NB and had similar inverse J-shaped frequency distribution curves in two density categories. Also, both species displayed a reduced degree of aggregation from winter to summer after the spring drought (massive die-off), as indicated by the increased k-parameter of the NB and decreased values of another NB parameter p, variance/mean ratio, Lloyd’s Index of Patchiness, and David and Moore’s Index of Clumping. Further, we hypothesized that while the NB (i.e., Poisson-logarithmic) well fits the distribution of individuals per quadrat, its components, the Poisson and logarithmic, may describe the distributions of clumps per quadrat and of individuals per clump, respectively. We thus obtained the means and variances for (1) individuals per quadrat, (2) clumps per quadrat, and (3) individuals per clump. The results showed that the decrease of the density from winter to summer for each plant resulted from the decrease of individuals per clump, rather than from the decrease of clumps per quadrat. The great similarities between the two annuals indicate that our observed temporal changes in spatial patterns may be common among desert annual plants.

The multiscale nature of magnetic pattern on the solar surface

NASA Astrophysics Data System (ADS)

Scardigli, S.; Del Moro, D.; Berrilli, F.

Multiscale magnetic underdense regions (voids) appear in high resolution magnetograms of quiet solar surface. These regions may be considered a signature of the underlying convective structure. The study of the associated pattern paves the way for the study of turbulent convective scales from granular to global. In order to address the question of magnetic pattern driven by turbulent convection we used a novel automatic void detection method to calculate void distributions. The absence of preferred scales of organization in the calculated distributions supports the multiscale nature of flows on the solar surface and the absence of preferred convective scales.

Quantifying Shark Distribution Patterns and Species-Habitat Associations: Implications of Marine Park Zoning

PubMed Central

Espinoza, Mario; Cappo, Mike; Heupel, Michelle R.; Tobin, Andrew J.; Simpfendorfer, Colin A.

2014-01-01

Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches. PMID:25207545

Movements of wintering surf scoters: Predator responses to different prey landscapes

USGS Publications Warehouse

Kirk, M.; Esler, Daniel N.; Iverson, S.A.; Boyd, W.S.

2008-01-01

The distribution of predators is widely recognized to be intimately linked to the distribution of their prey. Foraging theory suggests that predators will modify their behaviors, including movements, to optimize net energy intake when faced with variation in prey attributes or abundance. While many studies have documented changes in movement patterns of animals in response to temporal changes in food, very few have contrasted movements of a single predator species naturally occurring in dramatically different prey landscapes. We documented variation in the winter movements, foraging range size, site fidelity, and distribution patterns of a molluscivorous sea duck, the surf scoter (Melanitta perspicillata), in two areas of coastal British Columbia with very different shellfish prey features. Baynes Sound has extensive tidal flats with abundant clams, which are high-quality and temporally stable prey for scoters. Malaspina Inlet is a rocky fjord-like inlet where scoters consume mussels that are superabundant and easily accessible in some patches but are heavily depleted over the course of winter. We used radio telemetry to track surf scoter movements in both areas and found that in the clam habitats of Baynes Sound, surf scoters exhibited limited movement, small winter ranges, strong foraging site fidelity, and very consistent distribution patterns. By contrast, in mussel habitats in the Malaspina Inlet, surf scoters displayed more movement, larger ranges, little fidelity to specific foraging sites, and more variable distribution patterns. We conclude that features associated with the different prey types, particularly the higher depletion rates of mussels, strongly influenced seasonal space use patterns. These findings are consistent with foraging theory and confirm that predator behavior, specifically movements, is environmentally mediated. ?? 2008 Springer-Verlag.

No difference in mitochondrial distribution is observed in human oocytes after cryopreservation.

PubMed

Stimpfel, Martin; Vrtacnik-Bokal, Eda; Virant-Klun, Irma

2017-08-01

The primary aim of this study was to determine if any difference in mitochondrial distribution can be observed between fresh and cryopreserved (slow-frozen/thawed and vitrified/warmed) oocytes when oocytes are stained with Mitotracker Red CMXRos and observed under a conventional fluorescent microscope. Additionally, the influence of cryopreservation procedure on the viable rates of oocytes at different maturation stages was evaluated. The germinal vesicle (GV) and MII oocytes were cryopreserved with slow-freezing and vitrification. After thawing/warming, oocytes were stained using Mitotracker Red CMXRos and observed under a conventional fluorescent microscope. Mitotracker staining revealed that in GV oocytes the pattern of mitochondrial distribution appeared as aggregated clusters around the whole oocyte. In mature MII oocytes, three different patterns of mitochondrial distribution were observed; a smooth pattern around the polar body with aggregated clusters at the opposite side of the polar body, a smooth pattern throughout the whole cell, and aggregated clusters as can be seen in GV oocytes. There were no significant differences in the observed patterns between fresh, vitrified/warmed and frozen/thawed oocytes. When comparing the viable rates of oocytes after two different cryopreservation procedures, the results showed no significant differences, although the trend of viable MII oocytes tends to be higher after vitrification/warming and for viable GV oocytes it tends to be higher after slow-freezing/thawing. Mitotracker Red CMXRos staining of mitochondria in oocytes did not reveal differences in mitochondrial distribution between fresh and cryopreserved oocytes at different maturity stages. Additionally, no difference was observed in the viable rates of GV and MII oocytes after slow-freezing/thawing and vitrification/warming.

Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

PubMed

Espinoza, Mario; Cappo, Mike; Heupel, Michelle R; Tobin, Andrew J; Simpfendorfer, Colin A

2014-01-01

Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches.

Capacity for patterns and sequences in Kanerva's SDM as compared to other associative memory models. [Sparse, Distributed Memory

NASA Technical Reports Server (NTRS)

Keeler, James D.

1988-01-01

The information capacity of Kanerva's Sparse Distributed Memory (SDM) and Hopfield-type neural networks is investigated. Under the approximations used here, it is shown that the total information stored in these systems is proportional to the number connections in the network. The proportionality constant is the same for the SDM and Hopfield-type models independent of the particular model, or the order of the model. The approximations are checked numerically. This same analysis can be used to show that the SDM can store sequences of spatiotemporal patterns, and the addition of time-delayed connections allows the retrieval of context dependent temporal patterns. A minor modification of the SDM can be used to store correlated patterns.

Elevational Gradients in Fish Diversity in the Himalaya: Water Discharge Is the Key Driver of Distribution Patterns

PubMed Central

Bhatt, Jay P.; Manish, Kumar; Pandit, Maharaj K.

2012-01-01

Background Studying diversity and distribution patterns of species along elevational gradients and understanding drivers behind these patterns is central to macroecology and conservation biology. A number of studies on biogeographic gradients are available for terrestrial ecosystems, but freshwater ecosystems remain largely neglected. In particular, we know very little about the species richness gradients and their drivers in the Himalaya, a global biodiversity hotspot. Methodology/Principal Findings We collated taxonomic and distribution data of fish species from 16 freshwater Himalayan rivers and carried out empirical studies on environmental drivers and fish diversity and distribution in the Teesta river (Eastern Himalaya). We examined patterns of fish species richness along the Himalayan elevational gradients (50–3800 m) and sought to understand the drivers behind the emerging patterns. We used generalized linear models (GLM) and generalized additive models (GAM) to examine the richness patterns; GLM was used to investigate relationship between fish species richness and various environmental variables. Regression modelling involved stepwise procedures, including elimination of collinear variables, best model selection, based on the least Akaike’s information criterion (AIC) and the highest percentage of deviance explained (D2). This maiden study on the Himalayan fishes revealed that total and non-endemic fish species richness monotonously decrease with increasing elevation, while endemics peaked around mid elevations (700–1500 m). The best explanatory model (synthetic model) indicated that water discharge is the best predictor of fish species richness patterns in the Himalayan rivers. Conclusions/Significance This study, carried out along one of the longest bioclimatic elevation gradients of the world, lends support to Rapoport’s elevational rule as opposed to mid domain effect hypothesis. We propose a species-discharge model and contradict species-area model in predicting fish species richness. We suggest that drivers of richness gradients in terrestrial and aquatic ecosystems are likely to be different. These studies are crucial in context of the impacts of unprecedented on-going river regulation on fish diversity and distribution in the Himalaya. PMID:23029444

An Intelligent System for Document Retrieval in Distributed Office Environments.

ERIC Educational Resources Information Center

Mukhopadhyay, Uttam; And Others

1986-01-01

MINDS (Multiple Intelligent Node Document Servers) is a distributed system of knowledge-based query engines for efficiently retrieving multimedia documents in an office environment of distributed workstations. By learning document distribution patterns and user interests and preferences during system usage, it customizes document retrievals for…

Dynamic Pattern Formation for Wings of Pterygota in an Eclosion ---Pattern Analysis for Wings with the Imago---

NASA Astrophysics Data System (ADS)

Seino, M.; Kakazu, Y.

The vein and cell patterns for the fore and hind wing of Lepidoptera, Hemiptera, Orthoptera and Odonata are analyzed and discussed. For vein patterns of them, the fractal properties are shown and the inequality between four orders is obtained. The nature of wings observed by mass distributions for fractal dimensions of the vein pattern is presented.

Flight Investigation of the Cooling Characteristics of a Two-row Radial Engine Installation III : Engine Temperature Distribution

NASA Technical Reports Server (NTRS)

Rennak, Robert M; Messing, Wesley E; Morgan, James E

1946-01-01

The temperature distribution of a two-row radial engine in a twin-engine airplane has been investigated in a series of flight tests. The test engine was operated over a wide range of conditions at density altitudes of 5000 and 20,000 feet; quantitative results are presented showing the effects of flight and engine variables upon average engine temperature and over-all temperature spread. Discussions of the effect of the variables on the shape of the temperature patterns and on the temperature distribution of individual cylinders are also included. The results indicate that, for the tests conducted, the temperature distribution patterns were chiefly determined by the fuel-air ratio and cooling-air distributions. It was possible to calculate individual cylinder temperature, on the assumption of equal power distribution among cylinders, to within an average of plus or minus 14 degrees F. of the actual temperature. A considerable change occurred in either the spread or the thrust axis, the average engine fuel-air ratio, the engine speed, the power, or the blower ratio. Smaller effects on the temperature pattern were noticed with a change in cowl-flap opening and altitude. In most of the tests, a change in conditions affected the temperature of the barrels less than that of the heads. The variation of flight and engine variables had a negligible effect on the temperature distributions of the individual cylinders. (author)

Laser induced Erasable Patterns in a N* Liquid Crystal on an Iron Doped Lithium Niobate (Postprint)

DTIC Science & Technology

2017-10-12

be applied selectively to erase these patterns. Thus, a promising method is reported to generate reconfigurable patterns, photonic motives , and...erase these patterns. Thus, a promising method is reported to generate reconfigurable patterns, photonic motives , and touch sensitive devices in a...release (PA): distribution unlimited. loss of the patterns inscribed. Possible motives are not limited to graphics. It should be also possible to write

The distribution pattern of ERα expression, ESR1 genetic variation and expression of growth factor receptors: association with breast cancer prognosis in Russian patients treated with adjuvant tamoxifen.

PubMed

Babyshkina, Nataliya; Vtorushin, Sergey; Zavyalova, Marina; Patalyak, Stanislav; Dronova, Tatyana; Litviakov, Nikolay; Slonimskaya, Elena; Kzhyshkowska, Julia; Cherdyntseva, Nadejda; Choynzonov, Evgeny

2017-08-01

Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group-TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group-TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.

Modelling both dominance and species distribution provides a more complete picture of changes to mangrove ecosystems under climate change.

PubMed

Crase, Beth; Vesk, Peter A; Liedloff, Adam; Wintle, Brendan A

2015-08-01

Dominant species influence the composition and abundance of other species present in ecosystems. However, forecasts of distributional change under future climates have predominantly focused on changes in species distribution and ignored possible changes in spatial and temporal patterns of dominance. We develop forecasts of spatial changes for the distribution of species dominance, defined in terms of basal area, and for species occurrence, in response to sea level rise for three tree taxa within an extensive mangrove ecosystem in northern Australia. Three new metrics are provided, indicating the area expected to be suitable under future conditions (Eoccupied ), the instability of suitable area (Einstability ) and the overlap between the current and future spatial distribution (Eoverlap ). The current dominance and occurrence were modelled in relation to a set of environmental variables using boosted regression tree (BRT) models, under two scenarios of seedling establishment: unrestricted and highly restricted. While forecasts of spatial change were qualitatively similar for species occurrence and dominance, the models of species dominance exhibited higher metrics of model fit and predictive performance, and the spatial pattern of future dominance was less similar to the current pattern than was the case for the distributions of species occurrence. This highlights the possibility of greater changes in the spatial patterning of mangrove tree species dominance under future sea level rise. Under the restricted seedling establishment scenario, the area occupied by or dominated by a species declined between 42.1% and 93.8%, while for unrestricted seedling establishment, the area suitable for dominance or occurrence of each species varied from a decline of 68.4% to an expansion of 99.5%. As changes in the spatial patterning of dominance are likely to cause a cascade of effects throughout the ecosystem, forecasting spatial changes in dominance provides new and complementary information in addition to that provided by forecasts of species occurrence. © 2015 John Wiley & Sons Ltd.

Spatial distribution of soil organic carbon stock in Moso bamboo forests in subtropical China.

PubMed

Tang, Xiaolu; Xia, Mingpeng; Pérez-Cruzado, César; Guan, Fengying; Fan, Shaohui

2017-02-14

Moso bamboo (Phyllostachys heterocycla (Carr.) Mitford cv. Pubescens) is an important timber substitute in China. Site specific stand management requires an accurate estimate of soil organic carbon (SOC) stock for maintaining stand productivity and understanding global carbon cycling. This study compared ordinary kriging (OK) and inverse distance weighting (IDW) approaches to study the spatial distribution of SOC stock within 0-60 cm using 111 soil samples in Moso bamboo forests in subtropical China. Similar spatial patterns but different spatial distribution ranges of SOC stock from OK and IDW highlighted the necessity to apply different approaches to obtain accurate and consistent results of SOC stock distribution. Different spatial patterns of SOC stock suggested the use of different fertilization treatments in Moso bamboo forests across the study area. SOC pool within 0-60 cm was 6.46 and 6.22 Tg for OK and IDW; results which were lower than that of conventional approach (CA, 7.41 Tg). CA is not recommended unless coordinates of the sampling locations are missing and the spatial patterns of SOC stock are not required. OK is recommended for the uneven distribution of sampling locations. Our results can improve methodology selection for investigating spatial distribution of SOC stock in Moso bamboo forests.

Spatial distribution of soil organic carbon stock in Moso bamboo forests in subtropical China

PubMed Central

Tang, Xiaolu; Xia, Mingpeng; Pérez-Cruzado, César; Guan, Fengying; Fan, Shaohui

2017-01-01

Moso bamboo (Phyllostachys heterocycla (Carr.) Mitford cv. Pubescens) is an important timber substitute in China. Site specific stand management requires an accurate estimate of soil organic carbon (SOC) stock for maintaining stand productivity and understanding global carbon cycling. This study compared ordinary kriging (OK) and inverse distance weighting (IDW) approaches to study the spatial distribution of SOC stock within 0–60 cm using 111 soil samples in Moso bamboo forests in subtropical China. Similar spatial patterns but different spatial distribution ranges of SOC stock from OK and IDW highlighted the necessity to apply different approaches to obtain accurate and consistent results of SOC stock distribution. Different spatial patterns of SOC stock suggested the use of different fertilization treatments in Moso bamboo forests across the study area. SOC pool within 0–60 cm was 6.46 and 6.22 Tg for OK and IDW; results which were lower than that of conventional approach (CA, 7.41 Tg). CA is not recommended unless coordinates of the sampling locations are missing and the spatial patterns of SOC stock are not required. OK is recommended for the uneven distribution of sampling locations. Our results can improve methodology selection for investigating spatial distribution of SOC stock in Moso bamboo forests. PMID:28195207

Delayed-enhanced cardiac MRI for differentiation of Fabry's disease from symmetric hypertrophic cardiomyopathy.

PubMed

De Cobelli, Francesco; Esposito, Antonio; Belloni, Elena; Pieroni, Maurizio; Perseghin, Gianluca; Chimenti, Cristina; Frustaci, Andrea; Del Maschio, Alessandro

2009-03-01

Fabry's disease may be difficult to differentiate from symmetric hypertrophic cardiomyopathy. Our aim was to compare the myocardial location and distribution patterns of delayed enhancement between patients with Fabry's disease who are affected by symmetric myocardial hypertrophy and patients with symmetric hypertrophic cardiomyopathy in order to identify a specific sign to best differentiate the two diseases. Patients with Fabry's disease-related hypertrophy showed left ventricular (LV) delayed enhancement with a typical and consistently found pattern characterized by the involvement of the inferolateral basal or mid basal segments and a mesocardial distribution that spared the subendocardium. This pattern seems to be specific to Fabry's disease; in fact, patients with symmetric hypertrophic cardiomyopathy had variable locations and distributions of delayed enhancement. These observations may contribute to identifying Fabry's disease as a specific cause of symmetric hypertrophy.

Frontal and Parietal Cortical Interactions with Distributed Visual Representations during Selective Attention and Action Selection

PubMed Central

Stokes, Mark; Nobre, Anna C.; Rushworth, Matthew F. S.

2013-01-01

Using multivoxel pattern analysis (MVPA), we studied how distributed visual representations in human occipitotemporal cortex are modulated by attention and link their modulation to concurrent activity in frontal and parietal cortex. We detected similar occipitotemporal patterns during a simple visuoperceptual task and an attention-to-working-memory task in which one or two stimuli were cued before being presented among other pictures. Pattern strength varied from highest to lowest when the stimulus was the exclusive focus of attention, a conjoint focus, and when it was potentially distracting. Although qualitatively similar effects were seen inside regions relatively specialized for the stimulus category and outside, the former were quantitatively stronger. By regressing occipitotemporal pattern strength against activity elsewhere in the brain, we identified frontal and parietal areas exerting top-down control over, or reading information out from, distributed patterns in occipitotemporal cortex. Their interactions with patterns inside regions relatively specialized for that stimulus category were higher than those with patterns outside those regions and varied in strength as a function of the attentional condition. One area, the frontal operculum, was distinguished by selectively interacting with occipitotemporal patterns only when they were the focus of attention. There was no evidence that any frontal or parietal area actively inhibited occipitotemporal representations even when they should be ignored and were suppressed. Using MVPA to decode information within these frontal and parietal areas showed that they contained information about attentional context and/or readout information from occipitotemporal cortex to guide behavior but that frontal regions lacked information about category identity. PMID:24133250

Frontal and parietal cortical interactions with distributed visual representations during selective attention and action selection.

PubMed

Nelissen, Natalie; Stokes, Mark; Nobre, Anna C; Rushworth, Matthew F S

2013-10-16

Using multivoxel pattern analysis (MVPA), we studied how distributed visual representations in human occipitotemporal cortex are modulated by attention and link their modulation to concurrent activity in frontal and parietal cortex. We detected similar occipitotemporal patterns during a simple visuoperceptual task and an attention-to-working-memory task in which one or two stimuli were cued before being presented among other pictures. Pattern strength varied from highest to lowest when the stimulus was the exclusive focus of attention, a conjoint focus, and when it was potentially distracting. Although qualitatively similar effects were seen inside regions relatively specialized for the stimulus category and outside, the former were quantitatively stronger. By regressing occipitotemporal pattern strength against activity elsewhere in the brain, we identified frontal and parietal areas exerting top-down control over, or reading information out from, distributed patterns in occipitotemporal cortex. Their interactions with patterns inside regions relatively specialized for that stimulus category were higher than those with patterns outside those regions and varied in strength as a function of the attentional condition. One area, the frontal operculum, was distinguished by selectively interacting with occipitotemporal patterns only when they were the focus of attention. There was no evidence that any frontal or parietal area actively inhibited occipitotemporal representations even when they should be ignored and were suppressed. Using MVPA to decode information within these frontal and parietal areas showed that they contained information about attentional context and/or readout information from occipitotemporal cortex to guide behavior but that frontal regions lacked information about category identity.

Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei.

PubMed

Bass, Hank W; Hoffman, Gregg G; Lee, Tae-Jin; Wear, Emily E; Joseph, Stacey R; Allen, George C; Hanley-Bowdoin, Linda; Thompson, William F

2015-11-01

Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. Here we report findings from 3D quantitative analysis of DNA replication and endoreduplication in nuclei from pulse-labeled developing maize root tips. In both early and middle S phase nuclei, flow-sorted on the basis of DNA content, replicative labeling was widely distributed across euchromatic regions of the nucleoplasm. We did not observe the perinuclear or perinucleolar replicative labeling patterns characteristic of middle S phase in mammals. Instead, the early versus middle S phase patterns in maize could be distinguished cytologically by correlating two quantitative, continuous variables, replicative labeling and DAPI staining. Early S nuclei exhibited widely distributed euchromatic labeling preferentially localized to regions with weak DAPI signals. Middle S nuclei also exhibited widely distributed euchromatic labeling, but the label was preferentially localized to regions with strong DAPI signals. Highly condensed heterochromatin, including knobs, replicated during late S phase as previously reported. Similar spatiotemporal replication patterns were observed for both mitotic and endocycling maize nuclei. These results revealed that maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with "gene islands" mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.

Evidence of territoriality and species interactions from spatial point-pattern analyses of subarctic-nesting geese

USGS Publications Warehouse

Reiter, Matthew E.; Andersen, David E.

2013-01-01

Quantifying spatial patterns of bird nests and nest fate provides insights into processes influencing a species’ distribution. At Cape Churchill, Manitoba, Canada, recent declines in breeding Eastern Prairie Population Canada geese (Branta canadensis interior) has coincided with increasing populations of nesting lesser snow geese (Chen caerulescens caerulescens) and Ross’s geese (Chen rossii). We conducted a spatial analysis of point patterns using Canada goose nest locations and nest fate, and lesser snow goose nest locations at two study areas in northern Manitoba with different densities and temporal durations of sympatric nesting Canada and lesser snow geese. Specifically, we assessed (1) whether Canada geese exhibited territoriality and at what scale and nest density; and (2) whether spatial patterns of Canada goose nest fate were associated with the density of nesting lesser snow geese as predicted by the protective-association hypothesis. Between 2001 and 2007, our data suggest that Canada geese were territorial at the scale of nearest neighbors, but were aggregated when considering overall density of conspecifics at slightly broader spatial scales. The spatial distribution of nest fates indicated that lesser snow goose nest proximity and density likely influence Canada goose nest fate. Our analyses of spatial point patterns suggested that continued changes in the distribution and abundance of breeding lesser snow geese on the Hudson Bay Lowlands may have impacts on the reproductive performance of Canada geese, and subsequently the spatial distribution of Canada goose nests.

Spatial patterns of cutaneous vibration during whole-hand haptic interactions

PubMed Central

Hayward, Vincent; Visell, Yon

2016-01-01

We investigated the propagation patterns of cutaneous vibration in the hand during interactions with touched objects. Prior research has highlighted the importance of vibrotactile signals during haptic interactions, but little is known of how vibrations propagate throughout the hand. Furthermore, the extent to which the patterns of vibrations reflect the nature of the objects that are touched, and how they are touched, is unknown. Using an apparatus comprised of an array of accelerometers, we mapped and analyzed spatial distributions of vibrations propagating in the skin of the dorsal region of the hand during active touch, grasping, and manipulation tasks. We found these spatial patterns of vibration to vary systematically with touch interactions and determined that it is possible to use these data to decode the modes of interaction with touched objects. The observed vibration patterns evolved rapidly in time, peaking in intensity within a few milliseconds, fading within 20–30 ms, and yielding interaction-dependent distributions of energy in frequency bands that span the range of vibrotactile sensitivity. These results are consistent with findings in perception research that indicate that vibrotactile information distributed throughout the hand can transmit information regarding explored and manipulated objects. The results may further clarify the role of distributed sensory resources in the perceptual recovery of object attributes during active touch, may guide the development of approaches to robotic sensing, and could have implications for the rehabilitation of the upper extremity. PMID:27035957

Spatial distribution and implications to sources of halogenated flame retardants in riverine sediments of Taizhou, an intense e-waste recycling area in eastern China.

PubMed

Zhou, Shanshan; Fu, Jie; He, Huan; Fu, Jianjie; Tang, Qiaozhi; Dong, Minfeng; Pan, Yongqiang; Li, An; Liu, Weiping; Zhang, Limin

2017-10-01

Concentrations and spatial distribution pattern of organohalogen flame retardants were investigated in the riverine surface sediments from Taizhou, an intensive e-waste recycling region in China. The analytes were syn- and anti- Dechlorane Plus (DP), Dechloranes 602, 603, and 604, a DP monoadduct, two dechlorinated DPs and 8 congeners of polybrominated diphenyl ethers (PBDEs). The concentrations of Σ 8 PBDEs, ΣDP, ΣDec600s, and ΣDP-degradates ranged from <100 to 172,000, 100 to 55,000, not detectable (nd) to 1600, and nd to 2800 pg/g dry weight, respectively. BDE-209 and DP, both have been manufactured in China, had similar spatial distribution patterns in the study area, featured by distinctly recognizable hotspots some of which are in proximity to known e-waste dumping or metal recycling facilities. Such patterns were largely shared by Dec602 and dechlorinated DP, although their concentration levels were much lower. These major flame retardants significantly correlate with each other, and cluster together in the loading plot of principle component analysis. In contrast, most non-deca PBDE congeners do not correlate with DPs. Dec604 stood out having distinctly different spatial distribution pattern, which could be linked to historical use of mirex. Organic matter content of the sediment was not the dominant factor in determining the spatial pattern of pollution by halogenated flame retardants in the rivers of this study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatial and Temporal Variation of Japanese encephalitis Disease and Detection of Disease Hotspots: a Case Study of Gorakhpur District, Uttar Pradesh, India

NASA Astrophysics Data System (ADS)

Verma, S.; Gupta, R. D.

2014-11-01

In recent times, Japanese Encephalitis (JE) has emerged as a serious public health problem. In India, JE outbreaks were recently reported in Uttar Pradesh, Gorakhpur. The present study presents an approach to use GIS for analyzing the reported cases of JE in the Gorakhpur district based on spatial analysis to bring out the spatial and temporal dynamics of the JE epidemic. The study investigates spatiotemporal pattern of the occurrence of disease and detection of the JE hotspot. Spatial patterns of the JE disease can provide an understanding of geographical changes. Geospatial distribution of the JE disease outbreak is being investigated since 2005 in this study. The JE incidence data for the years 2005 to 2010 is used. The data is then geo-coded at block level. Spatial analysis is used to evaluate autocorrelation in JE distribution and to test the cases that are clustered or dispersed in space. The Inverse Distance Weighting interpolation technique is used to predict the pattern of JE incidence distribution prevalent across the study area. Moran's I Index (Moran's I) statistics is used to evaluate autocorrelation in spatial distribution. The Getis-Ord Gi*(d) is used to identify the disease areas. The results represent spatial disease patterns from 2005 to 2010, depicting spatially clustered patterns with significant differences between the blocks. It is observed that the blocks on the built up areas reported higher incidences.

A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain.

PubMed

Dutkiewicz, Anne-Sophie; Ezzedine, Khaled; Mazereeuw-Hautier, Juliette; Lacour, Jean-Philippe; Barbarot, Sébastien; Vabres, Pierre; Miquel, Juliette; Balguerie, Xavier; Martin, Ludovic; Boralevi, Franck; Bessou, Pierre; Chateil, Jean-François; Léauté-Labrèze, Christine

2015-03-01

Upper facial port-wine stain (PWS) is a feature of Sturge-Weber syndrome (SWS). Recent studies suggest that the distribution of the PWS corresponds to genetic mosaicism rather than to trigeminal nerve impairment. We sought to refine the cutaneous distribution of upper facial PWS at risk for SWS. This was a prospective multicenter study of consecutive cases of upper facial PWS larger than 1 cm² located in the ophthalmic division of trigeminal nerve distribution in infants aged less than 1 year, seen in 8 French pediatric dermatology departments between 2006 and 2012. Clinical data, magnetic resonance imaging, and photographs were systematically collected and studied. PWS were classified into 6 distinct patterns. In all, 66 patients were included. Eleven presented with SWS (magnetic resonance imaging signs and seizure). Four additional infants had suspected SWS without neurologic manifestations. Hemifacial (odds ratio 7.7, P = .003) and median (odds ratio 17.08, P = .008) PWS patterns were found to be at high risk for SWS. A nonmedian linear pattern was not associated with SWS. Small number of patients translated to limited power of the study. Specific PWS distribution patterns are associated with an increased risk of SWS. These PWS patterns conform to areas of somatic mosaicism. Terminology stipulating ophthalmic division of trigeminal nerve territory involvement in SWS should be abandoned. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data

PubMed Central

2010-01-01

Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well as biological patterns of interest, even when the latter display a high complexity (PROSITE signatures for example). In addition, these exact algorithms allow us to avoid the edge effect observed under the single sequence approximation, which leads to erroneous results, especially when the marginal distribution of the model displays a slow convergence toward the stationary distribution. We end up with a discussion on our method and on its potential improvements. PMID:20205909

Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data.

PubMed

Nuel, Gregory; Regad, Leslie; Martin, Juliette; Camproux, Anne-Claude

2010-01-26

In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well as biological patterns of interest, even when the latter display a high complexity (PROSITE signatures for example). In addition, these exact algorithms allow us to avoid the edge effect observed under the single sequence approximation, which leads to erroneous results, especially when the marginal distribution of the model displays a slow convergence toward the stationary distribution. We end up with a discussion on our method and on its potential improvements.

Implications of recurrent disturbance for genetic diversity.

PubMed

Davies, Ian D; Cary, Geoffrey J; Landguth, Erin L; Lindenmayer, David B; Banks, Sam C

2016-02-01

Exploring interactions between ecological disturbance, species' abundances and community composition provides critical insights for ecological dynamics. While disturbance is also potentially an important driver of landscape genetic patterns, the mechanisms by which these patterns may arise by selective and neutral processes are not well-understood. We used simulation to evaluate the relative importance of disturbance regime components, and their interaction with demographic and dispersal processes, on the distribution of genetic diversity across landscapes. We investigated genetic impacts of variation in key components of disturbance regimes and spatial patterns that are likely to respond to climate change and land management, including disturbance size, frequency, and severity. The influence of disturbance was mediated by dispersal distance and, to a limited extent, by birth rate. Nevertheless, all three disturbance regime components strongly influenced spatial and temporal patterns of genetic diversity within subpopulations, and were associated with changes in genetic structure. Furthermore, disturbance-induced changes in temporal population dynamics and the spatial distribution of populations across the landscape resulted in disrupted isolation by distance patterns among populations. Our results show that forecast changes in disturbance regimes have the potential to cause major changes to the distribution of genetic diversity within and among populations. We highlight likely scenarios under which future changes to disturbance size, severity, or frequency will have the strongest impacts on population genetic patterns. In addition, our results have implications for the inference of biological processes from genetic data, because the effects of dispersal on genetic patterns were strongly mediated by disturbance regimes.

Line-edge roughness performance targets for EUV lithography

NASA Astrophysics Data System (ADS)

Brunner, Timothy A.; Chen, Xuemei; Gabor, Allen; Higgins, Craig; Sun, Lei; Mack, Chris A.

2017-03-01

Our paper will use stochastic simulations to explore how EUV pattern roughness can cause device failure through rare events, so-called "black swans". We examine the impact of stochastic noise on the yield of simple wiring patterns with 36nm pitch, corresponding to 7nm node logic, using a local Critical Dimension (CD)-based fail criteria Contact hole failures are examined in a similar way. For our nominal EUV process, local CD uniformity variation and local Pattern Placement Error variation was observed, but no pattern failures were seen in the modest (few thousand) number of features simulated. We degraded the image quality by incorporating Moving Standard Deviation (MSD) blurring to degrade the Image Log-Slope (ILS), and were able to find conditions where pattern failures were observed. We determined the Line Width Roughness (LWR) value as a function of the ILS. By use of an artificial "step function" image degraded by various MSD blur, we were able to extend the LWR vs ILS curve into regimes that might be available for future EUV imagery. As we decreased the image quality, we observed LWR grow and also began to see pattern failures. For high image quality, we saw CD distributions that were symmetrical and close to Gaussian in shape. Lower image quality caused CD distributions that were asymmetric, with "fat tails" on the low CD side (under-exposed) which were associated with pattern failures. Similar non-Gaussian CD distributions were associated with image conditions that caused missing contact holes, i.e. CD=0.