WorldWideScience

Sample records for non-mammalian model organisms

  1. Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms.

    Science.gov (United States)

    Cunliffe, Vincent T; Baines, Richard A; Giachello, Carlo N G; Lin, Wei-Hsiang; Morgan, Alan; Reuber, Markus; Russell, Claire; Walker, Matthew C; Williams, Robin S B

    2015-01-01

    This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. We consider recent discoveries made with each model organism and discuss the importance of these advances for the understanding and treatment of epilepsy in humans. The relative ease with which mutations in genes of interest can be produced and studied quickly and cheaply in these organisms, together with their anatomical and physiological simplicity in comparison to mammalian species, are major advantages when researchers are trying to unravel complex disease mechanisms. The short generation times of most of these model organisms also mean that they lend themselves particularly conveniently to the investigation of drug effects or epileptogenic processes across the lifecourse. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. Feathers and fins: non-mammalian models for hair cell regeneration.

    Science.gov (United States)

    Brignull, Heather R; Raible, David W; Stone, Jennifer S

    2009-06-24

    Death of mechanosensory cells in the inner ear results in two profound disabilities: hearing loss and balance disorders. Although mammals lack the capacity to regenerate hair cells, recent studies in mice and other rodents have offered valuable insight into strategies for stimulating hair cell regeneration in mammals. Investigations of model organisms that retain the ability to form new hair cells after embryogenesis, such as fish and birds, are equally important and have provided clues as to the cellular and molecular mechanisms that may block hair cell regeneration in mammals. Here, we summarize studies on hair cell regeneration in the chicken and the zebrafish, discuss specific advantages of each model, and propose future directions for the use of non-mammalian models in understanding hair cell regeneration.

  3. Non-linear leak currents affect mammalian neuron physiology

    Directory of Open Access Journals (Sweden)

    Shiwei eHuang

    2015-11-01

    Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

  4. Mammalian hibernation: lessons for organ preparation?

    Science.gov (United States)

    Green, C

    2000-01-01

    The adaptations to low environmental temperatures exhibited in mammalian hibernation are many and varied, and involve molecular and cellular mechanisms as well as the systematic physiology of the whole organism. Natural torpidity is characterised by a profound reduction in body temperature and other functions lasting from a few hours to several weeks. Controlled reduction of heart rate, respiration and oxygen consumption is followed by the fall in body temperature. However, thermoregulation persists such that a decrease in ambient temperature below dangerous levels typically triggers arousal, and shivering and non-shivering thermogenesis from brown fat provide the heat to restore body temperature to normal levels. Many of the cellular mechanisms for survival are similar to those brought into play during medium-term storage of organs destined for transplantation. For example maintenance of ionic regulation and membrane fluxes is fundamental to cell survival and function at low body temperatures. Differences between hibernating and non-hibernating species are marked by differences in Na+/K+ transport and Ca++pumps. These in turn are probably associated with alterations in the lipoproteins of the plasma membrane and inner mitochondrial membrane. We have accordingly conducted a series of pilot studies in captured Richardson's ground squirrels kept in laboratory conditions as a model for hypothermic organ preservation. Tissue function was compared during the summer (non-hibernating season) with that in the winter when the animals could be: (i) in deep hibernation in a cold chamber at 4 degree C; (ii) maintained in an ambient temperature of 4 degree C but active and awake; or (iii) active at an ambient temperature of 22 degree C. The studies involved: whole animal monitoring of standard physiological parameters; whole organ (kidney) storage and transplantation for viability assessment; storage and functional assessment on an ex vivo test circuit with capacity for

  5. DNA repair in non-mammalian animals

    International Nuclear Information System (INIS)

    Mitani, Hiroshi

    1984-01-01

    Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

  6. Evolutionary patterns of RNA-based duplication in non-mammalian chordates.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young retrocopies in ancient chordate species. Upon comparing these non-mammalian chordate species to the mammalian species, we observed that a larger fraction of the non-mammalian retrocopies was under strong evolutionary constraints than mammalian retrocopies are, as evidenced by signals of purifying selection and expression profiles. For the Western clawed frog, Medaka, and Sea squirt, many retrogenes have evolved gonad and brain expression patterns, similar to what was observed in human. Testing of retrogene movement in the Medaka genome, where the nascent sex chrosomes have been well assembled, did not reveal any significant gene movement. Taken together, our analyses demonstrate that RNA-based duplication generates many functional genes and can make a significant contribution to the evolution of non-mammalian genomes.

  7. Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins.

    Science.gov (United States)

    Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M; Ballard, Grant; Ainley, David G; Varsani, Arvind

    2017-07-01

    The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds ( n  = 5), a fish ( n  = 1), a snake ( n  = 1), and turtles ( n  = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin ( Pygoscelis adeliae ) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota , associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis ), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We

  8. Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins

    Science.gov (United States)

    Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M.; Ballard, Grant; Ainley, David G.; Varsani, Arvind

    2017-01-01

    The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds (n = 5), a fish (n = 1), a snake (n = 1), and turtles (n = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin (Pygoscelis adeliae) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota, associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We estimated the

  9. Modeling Exposure of Mammalian Predatorsto Anticoagulant Rodenticides

    DEFF Research Database (Denmark)

    Topping, Christopher John; Elmeros, Morten

    2016-01-01

    as vectors of AR, and was used to evaluate likely impacts of restrictions imposed on AR use in Denmark banning the use of rodenticides for plant protection in woodlands and tree-crops. The model uses input based on frequencies and timings of baiting for rodent control for urban, rural and woodland locations......Anticoagulant rodenticides (AR) are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is very...... high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice...

  10. Structural and functional organization of ribosomal genes within the mammalian cell nucleolus.

    Science.gov (United States)

    Derenzini, Massimo; Pasquinelli, Gianandrea; O'Donohue, Marie-Françoise; Ploton, Dominique; Thiry, Marc

    2006-02-01

    Data on the in situ structural-functional organization of ribosomal genes in the mammalian cell nucleolus are reviewed here. Major findings on chromatin structure in situ come from investigations carried out using the Feulgen-like osmium ammine reaction as a highly specific electron-opaque DNA tracer. Intranucleolar chromatin shows three different levels of organization: compact clumps, fibers ranging from 11 to 30 nm, and loose agglomerates of extended DNA filaments. Both clumps and fibers of chromatin exhibit a nucleosomal organization that is lacking in the loose agglomerates of extended DNA filaments. In fact, these filaments constantly show a thickness of 2-3 nm, the same as a DNA double-helix molecule. The loose agglomerates of DNA filaments are located in the fibrillar centers, the interphase counterpart of metaphase NORs, therefore being constituted by ribosomal DNA. The extended, non-nucleosomal configuration of this rDNA has been shown to be independent of transcriptional activity and characterizes ribosome genes that are either transcribed or transcriptionally silent. Data reviewed are consistent with a model of control for ribosome gene activity that is not mediated by changes in chromatin structure. The presence of rDNA in mammalian cells always structurally ready for transcription might facilitate a more rapid adjustment of the ribosome production in response to the metabolic needs of the cell.

  11. Investigating ecological speciation in non-model organisms

    DEFF Research Database (Denmark)

    Foote, Andrew David

    2012-01-01

    Background: Studies of ecological speciation tend to focus on a few model biological systems. In contrast, few studies on non-model organisms have been able to infer ecological speciation as the underlying mechanism of evolutionary divergence. Questions: What are the pitfalls in studying ecological...... speciation in non-model organisms that lead to this bias? What alternative approaches might redress the balance? Organism: Genetically differentiated types of the killer whale (Orcinus orca) exhibiting differences in prey preference, habitat use, morphology, and behaviour. Methods: Review of the literature...... on killer whale evolutionary ecology in search of any difficulty in demonstrating causal links between variation in phenotype, ecology, and reproductive isolation in this non-model organism. Results: At present, we do not have enough evidence to conclude that adaptive phenotype traits linked to ecological...

  12. Mottled Mice and Non-Mammalian Models of Menkes Disease

    DEFF Research Database (Denmark)

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critica......-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals....

  13. Enamel formation and growth in non-mammalian cynodonts

    Science.gov (United States)

    Dirks, Wendy; Martinelli, Agustín G.

    2018-01-01

    The early evolution of mammals is associated with the linked evolutionary origin of diphyodont tooth replacement, rapid juvenile growth and determinate adult growth. However, specific relationships among these characters during non-mammalian cynodont evolution require further exploration. Here, polarized light microscopy revealed incremental lines, resembling daily laminations of extant mammals, in histological sections of enamel in eight non-mammalian cynodont species. In the more basal non-probainognathian group, enamel extends extremely rapidly from cusp to cervix. By contrast, the enamel of mammaliamorphs is gradually accreted, with slow rates of crown extension, more typical of the majority of non-hypsodont crown mammals. These results are consistent with the reduction in dental replacement rate across the non-mammalian cynodont lineage, with greater rates of crown extension required in most non-probainognathians, and slower crown extension rates permitted in mammaliamorphs, which have reduced patterns of dental replacement in comparison with many non-probainognathians. The evolution of mammal-like growth patterns, with faster juvenile growth and more abruptly terminating adult growth, is linked with this reduction in dental replacement rates and may provide an additional explanation for the observed pattern in enamel growth rates. It is possible that the reduction in enamel extension rates in mammaliamorphs reflects an underlying reduction in skeletal growth rates at the time of postcanine formation, due to a more abruptly terminating pattern of adult growth in these more mammal-like, crownward species. PMID:29892415

  14. Next-generation mammalian genetics toward organism-level systems biology.

    Science.gov (United States)

    Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

    2017-01-01

    Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

  15. The evolution of gene expression levels in mammalian organs

    DEFF Research Database (Denmark)

    Brawand, David; Soumillon, Magali; Necsulea, Anamaria

    2011-01-01

    and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped......Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across...... ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages...

  16. Organization of left–right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling

    Science.gov (United States)

    Shevtsova, Natalia A; Talpalar, Adolfo E; Markin, Sergey N; Harris-Warrick, Ronald M; Kiehn, Ole; Rybak, Ilya A

    2015-01-01

    Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left–right alternation of neural activity, switching gaits between the left–right alternating walking-like activity and the left–right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits. Key points Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V

  17. Edible Scaffolds Based on Non-Mammalian Biopolymers for Myoblast Growth

    Directory of Open Access Journals (Sweden)

    Javier Enrione

    2017-12-01

    Full Text Available In vitro meat has recently emerged as a new concept in food biotechnology. Methods to produce in vitro meat generally involve the growth of muscle cells that are cultured on scaffolds using bioreactors. Suitable scaffold design and manufacture are critical to downstream culture and meat production. Most current scaffolds are based on mammalian-derived biomaterials, the use of which is counter to the desire to obviate mammal slaughter in artificial meat production. Consequently, most of the knowledge is related to the design and control of scaffold properties based on these mammalian-sourced materials. To address this, four different scaffold materials were formulated using non-mammalian sources, namely, salmon gelatin, alginate, and additives including gelling agents and plasticizers. The scaffolds were produced using a freeze-drying process, and the physical, mechanical, and biological properties of the scaffolds were evaluated. The most promising scaffolds were produced from salmon gelatin, alginate, agarose, and glycerol, which exhibited relatively large pore sizes (~200 μm diameter and biocompatibility, permitting myoblast cell adhesion (~40% and growth (~24 h duplication time. The biodegradation profiles of the scaffolds were followed, and were observed to be less than 25% after 4 weeks. The scaffolds enabled suitable myogenic response, with high cell proliferation, viability, and adequate cell distribution throughout. This system composed of non-mammalian edible scaffold material and muscle-cells is promising for the production of in vitro meat.

  18. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

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    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  19. Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates.

    Science.gov (United States)

    Lee-Liu, Dasfne; Edwards-Faret, Gabriela; Tapia, Víctor S; Larraín, Juan

    2013-08-01

    Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. Copyright © 2013 Wiley Periodicals, Inc.

  20. Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

    Science.gov (United States)

    Unniappan, Suraj

    2010-07-01

    The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

  1. NASCENT: an automatic protein interaction network generation tool for non-model organisms.

    Science.gov (United States)

    Banky, Daniel; Ordog, Rafael; Grolmusz, Vince

    2009-04-24

    Large quantity of reliable protein interaction data are available for model organisms in public depositories (e.g., MINT, DIP, HPRD, INTERACT). Most data correspond to experiments with the proteins of Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Caenorhabditis elegans, Escherichia coli and Mus musculus. For other important organisms the data availability is poor or non-existent. Here we present NASCENT, a completely automatic web-based tool and also a downloadable Java program, capable of modeling and generating protein interaction networks even for non-model organisms. The tool performs protein interaction network modeling through gene-name mapping, and outputs the resulting network in graphical form and also in computer-readable graph-forms, directly applicable by popular network modeling software. http://nascent.pitgroup.org.

  2. Modelling exposure of mammalian predators to anticoagulant rodenticide

    Directory of Open Access Journals (Sweden)

    Christopher John Topping

    2016-12-01

    Full Text Available Anticoagulant rodenticides (AR are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is very high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice as vectors of AR, and was used to evaluate likely impacts of restrictions imposed on AR use in Denmark banning the use of rodenticides for plant protection in woodlands and tree-crops. The model uses input based on frequencies and timings of baiting for rodent control for urban, rural and woodland locations and creates an exposure map based on spatio-temporal modelling of movement of mice-vectored AR (based on Apodemus flavicollis. Simulated predator territories are super-imposed over this exposure map to create an exposure index. Predictions from the model concur with field studies of AR prevalence both before and after the change in AR use. In most cases incidence of exposure to AR is predicted to be greater than 90%, although cessation of use in woodlots and Christmas tree plantations should reduce mean exposure concentrations. Model results suggest that the driver of high AR incidence in non-target small mammal predators is likely to be the pattern of use and not the distance AR is vectored. Reducing baiting frequency by 75% had different effects depending on the landscape simulated, but having a maximum of 12% reduction in exposure incidence, and in one landscape a maximum reduction of <2%. We discuss sources of uncertainty in the model and directions for future development of predictive models for environmental impact assessment of rodenticides. The

  3. Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

    Science.gov (United States)

    Karten, Harvey J.

    2015-01-01

    The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

  4. The role of transposable elements in the evolution of non-mammalian vertebrates and invertebrates

    Science.gov (United States)

    2010-01-01

    Background Transposable elements (TEs) have played an important role in the diversification and enrichment of mammalian transcriptomes through various mechanisms such as exonization and intronization (the birth of new exons/introns from previously intronic/exonic sequences, respectively), and insertion into first and last exons. However, no extensive analysis has compared the effects of TEs on the transcriptomes of mammals, non-mammalian vertebrates and invertebrates. Results We analyzed the influence of TEs on the transcriptomes of five species, three invertebrates and two non-mammalian vertebrates. Compared to previously analyzed mammals, there were lower levels of TE introduction into introns, significantly lower numbers of exonizations originating from TEs and a lower percentage of TE insertion within the first and last exons. Although the transcriptomes of vertebrates exhibit significant levels of exonization of TEs, only anecdotal cases were found in invertebrates. In vertebrates, as in mammals, the exonized TEs are mostly alternatively spliced, indicating that selective pressure maintains the original mRNA product generated from such genes. Conclusions Exonization of TEs is widespread in mammals, less so in non-mammalian vertebrates, and very low in invertebrates. We assume that the exonization process depends on the length of introns. Vertebrates, unlike invertebrates, are characterized by long introns and short internal exons. Our results suggest that there is a direct link between the length of introns and exonization of TEs and that this process became more prevalent following the appearance of mammals. PMID:20525173

  5. Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

    Science.gov (United States)

    Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

    2017-10-12

    The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

  6. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    Science.gov (United States)

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians?

    Science.gov (United States)

    Sarig, Rachel; Tzahor, Eldad

    2017-04-01

    Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells. Interestingly, regenerating amphibian cells are highly resistant to oncogenic transformation. Therapeutic approaches to improve mammalian regeneration mainly include stem-cell transplantations; but, these have proved unsuccessful in non-regenerating organs such as the heart. A recently developed approach is to induce de-differentiation of mature cardiomyocytes using factors that trigger their re-entry into the cell cycle. This novel approach raises numerous questions regarding the balance between transformation and regeneration induced by de-differentiation of mature mammalian somatic cells. Can this balance be controlled artificially? Do de-differentiated cells acquire the protection mechanisms seen in regenerating cells of lower organisms? Is this model unique to the cardiac tissue, which rarely develops tumors? This review describes regeneration processes in both mammals and lower organisms and, particularly, the ability of regenerating cells to avoid transformation. By comparing the characteristics of mammalian embryonic and somatic cells, we discuss therapeutic strategies of using various cell populations for regeneration. Finally, we describe a novel cardiac regeneration approach and its implications for regenerative medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email

  8. Dissection of Mammalian Organs and Opinions about It among Lower and Upper Secondary School Students

    Science.gov (United States)

    Špernjak, Andreja; Šorgo, Andrej

    2017-01-01

    This article describes the results of a study that investigated the use of the dissection of organs in anatomy and physiology classes in Slovenian lower and upper secondary schools. Based on a sample of 485 questionnaires collected from Slovenian lower and upper secondary school students, we can conclude that dissection of mammalian organs during…

  9. Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

    Directory of Open Access Journals (Sweden)

    Katherine Belov

    2006-03-01

    Full Text Available The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum sequence to construct the first map of a marsupial major histocompatibility complex (MHC. The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

  10. Proposal of a model of mammalian neural induction

    Science.gov (United States)

    Levine, Ariel J.; Brivanlou, Ali H.

    2009-01-01

    How does the vertebrate embryo make a nervous system? This complex question has been at the center of developmental biology for many years. The earliest step in this process – the induction of neural tissue – is intimately linked to patterning of the entire early embryo, and the molecular and embryological basis these processes are beginning to emerge. Here, we analyze classic and cutting-edge findings on neural induction in the mouse. We find that data from genetics, tissue explants, tissue grafting, and molecular marker expression support a coherent framework for mammalian neural induction. In this model, the gastrula organizer of the mouse embryo inhibits BMP signaling to allow neural tissue to form as a default fate – in the absence of instructive signals. The first neural tissue induced is anterior and subsequent neural tissue is posteriorized to form the midbrain, hindbrain, and spinal cord. The anterior visceral endoderm protects the pre-specified anterior neural fate from similar posteriorization, allowing formation of forebrain. This model is very similar to the default model of neural induction in the frog, thus bridging the evolutionary gap between amphibians and mammals. PMID:17585896

  11. Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

    Science.gov (United States)

    Scorzoni, Liliana; de Lucas, Maria Pilar; Mesa-Arango, Ana Cecilia; Fusco-Almeida, Ana Marisa; Lozano, Encarnación; Cuenca-Estrella, Manuel; Mendes-Giannini, Maria Jose; Zaragoza, Oscar

    2013-01-01

    The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2–5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei. PMID:23555877

  12. Application of quantum dot nanoparticles for potential non-invasive bio-imaging of mammalian spermatozoa

    Science.gov (United States)

    Various obstacles are encountered by mammalian spermatozoa during their journey through the female genital tract, and only few or none will reach the site of fertilization. Currently, there are limited technical approaches for non-invasive investigation of spermatozoa migration after insemination. A...

  13. Snpdat: Easy and rapid annotation of results from de novo snp discovery projects for model and non-model organisms

    Directory of Open Access Journals (Sweden)

    Doran Anthony G

    2013-02-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most abundant genetic variant found in vertebrates and invertebrates. SNP discovery has become a highly automated, robust and relatively inexpensive process allowing the identification of many thousands of mutations for model and non-model organisms. Annotating large numbers of SNPs can be a difficult and complex process. Many tools available are optimised for use with organisms densely sampled for SNPs, such as humans. There are currently few tools available that are species non-specific or support non-model organism data. Results Here we present SNPdat, a high throughput analysis tool that can provide a comprehensive annotation of both novel and known SNPs for any organism with a draft sequence and annotation. Using a dataset of 4,566 SNPs identified in cattle using high-throughput DNA sequencing we demonstrate the annotations performed and the statistics that can be generated by SNPdat. Conclusions SNPdat provides users with a simple tool for annotation of genomes that are either not supported by other tools or have a small number of annotated SNPs available. SNPdat can also be used to analyse datasets from organisms which are densely sampled for SNPs. As a command line tool it can easily be incorporated into existing SNP discovery pipelines and fills a niche for analyses involving non-model organisms that are not supported by many available SNP annotation tools. SNPdat will be of great interest to scientists involved in SNP discovery and analysis projects, particularly those with limited bioinformatics experience.

  14. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    2013-11-01

    Full Text Available A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  15. Mammalian diversity: gametes, embryos and reproduction.

    Science.gov (United States)

    Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

    2006-01-01

    The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

  16. A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.

    Directory of Open Access Journals (Sweden)

    Melissa J Caimano

    2014-03-01

    Full Text Available Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil's disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of "core" housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host

  17. Improving transcriptome construction in non-model organisms: integrating manual and automated gene definition in Emiliania huxleyi.

    OpenAIRE

    Feldmesser, Ester; Rosenwasser, Shilo; Vardi, Assaf; Ben-Dor, Shifra

    2014-01-01

    Background The advent of Next Generation Sequencing technologies and corresponding bioinformatics tools allows the definition of transcriptomes in non-model organisms. Non-model organisms are of great ecological and biotechnological significance, and consequently the understanding of their unique metabolic pathways is essential. Several methods that integrate de novo assembly with genome-based assembly have been proposed. Yet, there are many open challenges in defining genes, particularly whe...

  18. Gene organization inside replication domains in mammalian genomes

    Science.gov (United States)

    Zaghloul, Lamia; Baker, Antoine; Audit, Benjamin; Arneodo, Alain

    2012-11-01

    We investigate the large-scale organization of human genes with respect to "master" replication origins that were previously identified as bordering nucleotide compositional skew domains. We separate genes in two categories depending on their CpG enrichment at the promoter which can be considered as a marker of germline DNA methylation. Using expression data in mouse, we confirm that CpG-rich genes are highly expressed in germline whereas CpG-poor genes are in a silent state. We further show that, whether tissue-specific or broadly expressed (housekeeping genes), the CpG-rich genes are over-represented close to the replication skew domain borders suggesting some coordination of replication and transcription. We also reveal that the transcription of the longest CpG-rich genes is co-oriented with replication fork progression so that the promoter of these transcriptionally active genes be located into the accessible open chromatin environment surrounding the master replication origins that border the replication skew domains. The observation of a similar gene organization in the mouse genome confirms the interplay of replication, transcription and chromatin structure as the cornerstone of mammalian genome architecture.

  19. Understanding Mammalian Germ Line Development with In Vitro Models.

    Science.gov (United States)

    Martínez-Arroyo, Ana M; Míguez-Forján, Jose M; Remohí, Jose; Pellicer, Antonio; Medrano, Jose V

    2015-09-15

    Germ line development is crucial in organisms with sexual reproduction to complete their life cycle. In mammals, knowledge about germ line development is based mainly on the mouse model, in which genetic and epigenetic events are well described. However, little is known about how germ line development is orchestrated in humans, especially in the earliest stages. New findings derived from human in vitro models to obtain germ cells can shed light on these questions. This comprehensive review summarizes the current knowledge about mammalian germ line development, emphasizing the state of the art obtained from in vitro models for germ cell-like cell derivation. Current knowledge of the pluripotency cycle and germ cell specification has allowed different in vitro strategies to obtain germ cells with proven functionality in mouse models. Several reports during the last 10 years show that in vitro germ cell derivation with proven functionality to generate a healthy offspring is possible in mice. However, differences in the embryo development and pluripotency potential between human and mouse make it difficult to extrapolate these results. Further efforts on both human and mouse in vitro models to obtain germ cells from pluripotent stem cells may help to elucidate how human physiological events take place; therefore, therapeutic strategies can also be considered.

  20. Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE

    OpenAIRE

    Rella, Monika; Elliot, Joann L; Revett, Timothy J; Lanfear, Jerry; Phelan, Anne; Jackson, Richard M; Turner, Anthony J; Hooper, Nigel M

    2007-01-01

    Abstract Background Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple ...

  1. Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Maude Giroud

    2017-11-01

    Full Text Available Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein-coding RNAs (ncRNA, of which the long ncRNAs (lncRNAs constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization. lncRNAs are transcriptional regulators adding an additional regulatory layer in biological processes and pathophysiological conditions. Here, we review lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the substantial number of lncRNA loci in the human genome, the functionally characterized lncRNAs are just the tip of the iceberg. So far, our knowledge concerning lncRNAs in energy homeostasis is still in its infancy, meaning that the rest of the iceberg is a treasure chest yet to be discovered.

  2. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood

    2018-01-01

    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  3. Using energy budgets to combine ecology and toxicology in a mammalian sentinel species

    Science.gov (United States)

    Desforges, Jean-Pierre W.; Sonne, Christian; Dietz, Rune

    2017-04-01

    Process-driven modelling approaches can resolve many of the shortcomings of traditional descriptive and non-mechanistic toxicology. We developed a simple dynamic energy budget (DEB) model for the mink (Mustela vison), a sentinel species in mammalian toxicology, which coupled animal physiology, ecology and toxicology, in order to mechanistically investigate the accumulation and adverse effects of lifelong dietary exposure to persistent environmental toxicants, most notably polychlorinated biphenyls (PCBs). Our novel mammalian DEB model accurately predicted, based on energy allocations to the interconnected metabolic processes of growth, development, maintenance and reproduction, lifelong patterns in mink growth, reproductive performance and dietary accumulation of PCBs as reported in the literature. Our model results were consistent with empirical data from captive and free-ranging studies in mink and other wildlife and suggest that PCB exposure can have significant population-level impacts resulting from targeted effects on fetal toxicity, kit mortality and growth and development. Our approach provides a simple and cross-species framework to explore the mechanistic interactions of physiological processes and ecotoxicology, thus allowing for a deeper understanding and interpretation of stressor-induced adverse effects at all levels of biological organization.

  4. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  5. Optimization of Non-Thermal Plasma Treatment in an In Vivo Model Organism.

    Directory of Open Access Journals (Sweden)

    Amanda Lee

    Full Text Available Non-thermal plasma is increasingly being recognized for a wide range of medical and biological applications. However, the effect of non-thermal plasma on physiological functions is not well characterized in in vivo model systems. Here we use a genetically amenable, widely used model system, Drosophila melanogaster, to develop an in vivo system, and investigate the role of non-thermal plasma in blood cell differentiation. Although the blood system in Drosophila is primitive, it is an efficient system with three types of hemocytes, functioning during different developmental stages and environmental stimuli. Blood cell differentiation in Drosophila plays an essential role in tissue modeling during embryogenesis, morphogenesis and also in innate immunity. In this study, we optimized distance and frequency for a direct non-thermal plasma application, and standardized doses to treat larvae and adult flies so that there is no effect on the viability, fertility or locomotion of the organism. We discovered that at optimal distance, time and frequency, application of plasma induced blood cell differentiation in the Drosophila larval lymph gland. We articulate that the augmented differentiation could be due to an increase in the levels of reactive oxygen species (ROS upon non-thermal plasma application. Our studies open avenues to use Drosophila as a model system in plasma medicine to study various genetic disorders and biological processes where non-thermal plasma has a possible therapeutic application.

  6. A hybrid mammalian cell cycle model

    Directory of Open Access Journals (Sweden)

    Vincent Noël

    2013-08-01

    Full Text Available Hybrid modeling provides an effective solution to cope with multiple time scales dynamics in systems biology. Among the applications of this method, one of the most important is the cell cycle regulation. The machinery of the cell cycle, leading to cell division and proliferation, combines slow growth, spatio-temporal re-organisation of the cell, and rapid changes of regulatory proteins concentrations induced by post-translational modifications. The advancement through the cell cycle comprises a well defined sequence of stages, separated by checkpoint transitions. The combination of continuous and discrete changes justifies hybrid modelling approaches to cell cycle dynamics. We present a piecewise-smooth version of a mammalian cell cycle model, obtained by hybridization from a smooth biochemical model. The approximate hybridization scheme, leading to simplified reaction rates and binary event location functions, is based on learning from a training set of trajectories of the smooth model. We discuss several learning strategies for the parameters of the hybrid model.

  7. Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells.

    Science.gov (United States)

    Autour, Alexis; C Y Jeng, Sunny; D Cawte, Adam; Abdolahzadeh, Amir; Galli, Angela; Panchapakesan, Shanker S S; Rueda, David; Ryckelynck, Michael; Unrau, Peter J

    2018-02-13

    Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.

  8. Feathers and Fins: Non-mammalian models for hair cell regeneration

    OpenAIRE

    Brignull, Heather R.; Raible, David W.; Stone, Jennifer S.

    2009-01-01

    Death of mechanosensory cells in the inner ear results in two profound disabilities: hearing loss and balance disorders. Although mammals lack the capacity to regenerate hair cells, recent studies in mice and other rodents have offered valuable insight into strategies for stimulating hair cell regeneration in mammals. Investigations of model organisms that retain the ability to form new hair cells after embryogenesis, such as fish and chicks, are equally important and have provided clues as t...

  9. A new mammalian circadian oscillator model including the cAMP module

    International Nuclear Information System (INIS)

    Jun-Wei, Wang; Tian-Shou, Zhou

    2009-01-01

    In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops (TTFLs) and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light–dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erbα −/− -mutant mice, and help us make an experimentally-testable prediction: oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erbα −/− mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell. (cross-disciplinary physics and related areas of science and technology)

  10. Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

    Science.gov (United States)

    Guthrie, O'neil W

    2017-10-01

    In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport

    DEFF Research Database (Denmark)

    Larsen, E.H.; Møbjerg, N.; Sørensen, Jens Nørkær

    2006-01-01

    transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane. Conclusion: Our model based on solute-solvent coupling in lateral space......Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule. Methods: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species......: Na+, K+, Cl and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace...

  12. Mathematical model for the contribution of individual organs to non-zero y-intercepts in single and multi-compartment linear models of whole-body energy expenditure.

    Science.gov (United States)

    Kaiyala, Karl J

    2014-01-01

    Mathematical models for the dependence of energy expenditure (EE) on body mass and composition are essential tools in metabolic phenotyping. EE scales over broad ranges of body mass as a non-linear allometric function. When considered within restricted ranges of body mass, however, allometric EE curves exhibit 'local linearity.' Indeed, modern EE analysis makes extensive use of linear models. Such models typically involve one or two body mass compartments (e.g., fat free mass and fat mass). Importantly, linear EE models typically involve a non-zero (usually positive) y-intercept term of uncertain origin, a recurring theme in discussions of EE analysis and a source of confounding in traditional ratio-based EE normalization. Emerging linear model approaches quantify whole-body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys, heart, brain). Proponents of individual organ REE modeling hypothesize that multi-organ linear models may eliminate non-zero y-intercepts. This could have advantages in adjusting REE for body mass and composition. Studies reveal that individual organ REE is an allometric function of total body mass. I exploit first-order Taylor linearization of individual organ REEs to model the manner in which individual organs contribute to whole-body REE and to the non-zero y-intercept in linear REE models. The model predicts that REE analysis at the individual organ-tissue level will not eliminate intercept terms. I demonstrate that the parameters of a linear EE equation can be transformed into the parameters of the underlying 'latent' allometric equation. This permits estimates of the allometric scaling of EE in a diverse variety of physiological states that are not represented in the allometric EE literature but are well represented by published linear EE analyses.

  13. Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.

    Directory of Open Access Journals (Sweden)

    Admane H Shanthanagouda

    Full Text Available BACKGROUND: In human, a reduction in estrogen has been proposed as one of the key contributing factors for postmenopausal osteoporosis. Rodents are conventional models for studying postmenopausal osteoporosis, but the major limitation is that ovariectomy is needed to mimic the estrogen decline after menopause. Interestingly, in medaka fish (Oryzias latipes, we observed a natural drop in plasma estrogen profile in females during aging and abnormal spinal curvature was apparent in old fish, which are similar to postmenopausal women. It is hypothesized that estrogen associated disorders in bone metabolism might be predicted and prevented by estrogen supplement in aging O. latipes, which could be corresponding to postmenopausal osteoporosis in women. PRINCIPAL FINDINGS: In O. latipes, plasma estrogen was peaked at 8 months old and significantly declined after 10, 11 and 22 months in females. Spinal bone mineral density (BMD and micro-architecture by microCT measurement progressively decreased and deteriorated from 8 to 10, 12 and 14 months old, which was more apparent in females than the male counterparts. After 10 months old, O. latipes were supplemented with 17α-ethinylestradiol (EE2, a potent estrogen mimic at 6 and 60 ng/mg fish weight/day for 4 weeks, both reduction in spinal BMD and deterioration in bone micro-architecture were significantly prevented. The estrogenic effect of EE2 in O. latipes was confirmed by significant up-regulation of four key estrogen responsive genes in the liver. In general, bone histomorphometric analyses indicated significantly lowered osteoblasts and osteoclasts numbers and surfaces on vertebrae of EE2-fed medaka. SIGNIFICANCE: We demonstrate osteoporosis development associated with natural drop in estrogen level during aging in female medaka, which could be attenuated by estrogen treatment. This small size fish is a unique alternative non-mammalian vertebrate model for studying estrogen-related molecular

  14. Developmental mechanisms of the tympanic membrane in mammals and non-mammalian amniotes.

    Science.gov (United States)

    Takechi, Masaki; Kitazawa, Taro; Hirasawa, Tatsuya; Hirai, Tamami; Iseki, Sachiko; Kurihara, Hiroki; Kuratani, Shigeru

    2016-01-01

    The tympanic membrane is a thin layer that originates from the ectoderm, endoderm, and mesenchyme. Molecular-genetic investigations have revealed that interaction between epithelial and mesenchymal cells in the pharyngeal arches is essential for development of the tympanic membrane. We have recently reported that developmental mechanisms underlying the tympanic membrane seem to be different between mouse and chicken, suggesting that the tympanic membrane evolved independently in mammals and non-mammalian amniotes. In this review, we summarize previous studies of tympanic membrane formation in the mouse. We also discuss its formation in amniotes from an evolutionary point of view. © 2015 Japanese Teratology Society.

  15. Mammalian Cell Culture Process for Monoclonal Antibody Production: Nonlinear Modelling and Parameter Estimation

    Directory of Open Access Journals (Sweden)

    Dan Selişteanu

    2015-01-01

    Full Text Available Monoclonal antibodies (mAbs are at present one of the fastest growing products of pharmaceutical industry, with widespread applications in biochemistry, biology, and medicine. The operation of mAbs production processes is predominantly based on empirical knowledge, the improvements being achieved by using trial-and-error experiments and precedent practices. The nonlinearity of these processes and the absence of suitable instrumentation require an enhanced modelling effort and modern kinetic parameter estimation strategies. The present work is dedicated to nonlinear dynamic modelling and parameter estimation for a mammalian cell culture process used for mAb production. By using a dynamical model of such kind of processes, an optimization-based technique for estimation of kinetic parameters in the model of mammalian cell culture process is developed. The estimation is achieved as a result of minimizing an error function by a particle swarm optimization (PSO algorithm. The proposed estimation approach is analyzed in this work by using a particular model of mammalian cell culture, as a case study, but is generic for this class of bioprocesses. The presented case study shows that the proposed parameter estimation technique provides a more accurate simulation of the experimentally observed process behaviour than reported in previous studies.

  16. A model for allometric scaling of mammalian metabolism with ambient heat loss

    KAUST Repository

    Kwak, Ho Sang

    2016-02-02

    Background Allometric scaling, which represents the dependence of biological trait or process relates on body size, is a long-standing subject in biological science. However, there has been no study to consider heat loss to the ambient and an insulation layer representing mammalian skin and fur for the derivation of the scaling law of metabolism. Methods A simple heat transfer model is proposed to analyze the allometry of mammalian metabolism. The present model extends existing studies by incorporating various external heat transfer parameters and additional insulation layers. The model equations were solved numerically and by an analytic heat balance approach. Results A general observation is that the present heat transfer model predicted the 2/3 surface scaling law, which is primarily attributed to the dependence of the surface area on the body mass. External heat transfer effects introduced deviations in the scaling law, mainly due to natural convection heat transfer which becomes more prominent at smaller mass. These deviations resulted in a slight modification of the scaling exponent to a value smaller than 2/3. Conclusion The finding that additional radiative heat loss and the consideration of an outer insulation fur layer attenuate these deviation effects and render the scaling law closer to 2/3 provides in silico evidence for a functional impact of heat transfer mode on the allometric scaling law in mammalian metabolism.

  17. Toward a detailed computational model for the mammalian circadian clock

    Science.gov (United States)

    Leloup, Jean-Christophe; Goldbeter, Albert

    2003-06-01

    We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erb and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.

  18. Studying Oogenesis in a Non-model Organism Using Transcriptomics: Assembling, Annotating, and Analyzing Your Data.

    Science.gov (United States)

    Carter, Jean-Michel; Gibbs, Melanie; Breuker, Casper J

    2016-01-01

    This chapter provides a guide to processing and analyzing RNA-Seq data in a non-model organism. This approach was implemented for studying oogenesis in the Speckled Wood Butterfly Pararge aegeria. We focus in particular on how to perform a more informative primary annotation of your non-model organism by implementing our multi-BLAST annotation strategy. We also provide a general guide to other essential steps in the next-generation sequencing analysis workflow. Before undertaking these methods, we recommend you familiarize yourself with command line usage and fundamental concepts of database handling. Most of the operations in the primary annotation pipeline can be performed in Galaxy (or equivalent standalone versions of the tools) and through the use of common database operations (e.g. to remove duplicates) but other equivalent programs and/or custom scripts can be implemented for further automation.

  19. The footprint of metabolism in the organization of mammalian genomes

    Directory of Open Access Journals (Sweden)

    Berná Luisa

    2012-05-01

    Full Text Available Abstract Background At present five evolutionary hypotheses have been proposed to explain the great variability of the genomic GC content among and within genomes: the mutational bias, the biased gene conversion, the DNA breakpoints distribution, the thermal stability and the metabolic rate. Several studies carried out on bacteria and teleostean fish pointed towards the critical role played by the environment on the metabolic rate in shaping the base composition of genomes. In mammals the debate is still open, and evidences have been produced in favor of each evolutionary hypothesis. Human genes were assigned to three large functional categories (as well as to the corresponding functional classes according to the KOG database: (i information storage and processing, (ii cellular processes and signaling, and (iii metabolism. The classification was extended to the organisms so far analyzed performing a reciprocal Blastp and selecting the best reciprocal hit. The base composition was calculated for each sequence of the whole CDS dataset. Results The GC3 level of the above functional categories was increasing from (i to (iii. This specific compositional pattern was found, as footprint, in all mammalian genomes, but not in frog and lizard ones. Comparative analysis of human versus both frog and lizard functional categories showed that genes involved in the metabolic processes underwent the highest GC3 increment. Analyzing the KOG functional classes of genes, again a well defined intra-genomic pattern was found in all mammals. Not only genes of metabolic pathways, but also genes involved in chromatin structure and dynamics, transcription, signal transduction mechanisms and cytoskeleton, showed an average GC3 level higher than that of the whole genome. In the case of the human genome, the genes of the aforementioned functional categories showed a high probability to be associated with the chromosomal bands. Conclusions In the light of different

  20. SEX-DETector: A Probabilistic Approach to Study Sex Chromosomes in Non-Model Organisms

    Science.gov (United States)

    Muyle, Aline; Käfer, Jos; Zemp, Niklaus; Mousset, Sylvain; Picard, Franck; Marais, Gabriel AB

    2016-01-01

    We propose a probabilistic framework to infer autosomal and sex-linked genes from RNA-seq data of a cross for any sex chromosome type (XY, ZW, and UV). Sex chromosomes (especially the non-recombining and repeat-dense Y, W, U, and V) are notoriously difficult to sequence. Strategies have been developed to obtain partially assembled sex chromosome sequences. Most of them remain difficult to apply to numerous non-model organisms, either because they require a reference genome, or because they are designed for evolutionarily old systems. Sequencing a cross (parents and progeny) by RNA-seq to study the segregation of alleles and infer sex-linked genes is a cost-efficient strategy, which also provides expression level estimates. However, the lack of a proper statistical framework has limited a broader application of this approach. Tests on empirical Silene data show that our method identifies 20–35% more sex-linked genes than existing pipelines, while making reliable inferences for downstream analyses. Approximately 12 individuals are needed for optimal results based on simulations. For species with an unknown sex-determination system, the method can assess the presence and type (XY vs. ZW) of sex chromosomes through a model comparison strategy. The method is particularly well optimized for sex chromosomes of young or intermediate age, which are expected in thousands of yet unstudied lineages. Any organisms, including non-model ones for which nothing is known a priori, that can be bred in the lab, are suitable for our method. SEX-DETector and its implementation in a Galaxy workflow are made freely available. PMID:27492231

  1. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  2. Building the mammalian testis

    DEFF Research Database (Denmark)

    Svingen, Terje; Koopman, Peter

    2013-01-01

    Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial...

  3. Generation of induced neurons by direct reprogramming in the mammalian cochlea.

    Science.gov (United States)

    Nishimura, K; Weichert, R M; Liu, W; Davis, R L; Dabdoub, A

    2014-09-05

    Primary auditory neurons (ANs) in the mammalian cochlea play a critical role in hearing as they transmit auditory information in the form of electrical signals from mechanosensory cochlear hair cells in the inner ear to the brainstem. Their progressive degeneration is associated with disease conditions, excessive noise exposure and aging. Replacement of ANs, which lack the ability to regenerate spontaneously, would have a significant impact on research and advancement in cochlear implants in addition to the amelioration of hearing impairment. The aim of this study was to induce a neuronal phenotype in endogenous non-neural cells in the cochlea, which is the essential organ of hearing. Overexpression of a neurogenic basic helix-loop-helix transcription factor, Ascl1, in the cochlear non-sensory epithelial cells induced neurons at high efficiency at embryonic, postnatal and juvenile stages. Moreover, induced neurons showed typical properties of neuron morphology, gene expression and electrophysiology. Our data indicate that Ascl1 alone or Ascl1 and NeuroD1 is sufficient to reprogram cochlear non-sensory epithelial cells into functional neurons. Generation of neurons from non-neural cells in the cochlea is an important step for the regeneration of ANs in the mature mammalian cochlea. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Plasticizer endocrine disruption: Highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species.

    Science.gov (United States)

    Mathieu-Denoncourt, Justine; Wallace, Sarah J; de Solla, Shane R; Langlois, Valerie S

    2015-08-01

    Due to their versatility, robustness, and low production costs, plastics are used in a wide variety of applications. Plasticizers are mixed with polymers to increase flexibility of plastics. However, plasticizers are not covalently bound to plastics, and thus leach from products into the environment. Several studies have reported that two common plasticizers, bisphenol A (BPA) and phthalates, induce adverse health effects in vertebrates; however few studies have addressed their toxicity to non-mammalian species. The aim of this review is to compare the effects of plasticizers in animals, with a focus on aquatic species. In summary, we identified three main chains of events that occur in animals exposed to BPA and phthalates. Firstly, plasticizers affect development by altering both the thyroid hormone and growth hormone axes. Secondly, these chemicals interfere with reproduction by decreasing cholesterol transport through the mitochondrial membrane, leading to reduced steroidogenesis. Lastly, exposure to plasticizers leads to the activation of peroxisome proliferator-activated receptors, the increase of fatty acid oxidation, and the reduction in the ability to cope with the augmented oxidative stress leading to reproductive organ malformations, reproductive defects, and decreased fertility. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

    Directory of Open Access Journals (Sweden)

    Izabella Bajusz

    2018-02-01

    Full Text Available Originally two types of Polycomb Repressive Complexes (PRCs were described, canonical PRC1 (cPRC1 and PRC2. Recently, a versatile set of complexes were identified and brought up several dilemmas in PRC mediated repression. These new class of complexes were named as non-canonical PRC1s (ncPRC1s. Both cPRC1s and ncPRC1s contain Ring finger protein (RING1, RNF2 and Polycomb group ring finger catalytic (PCGF core, but in ncPRCs, RING and YY1 binding protein (RYBP, or YY1 associated factor 2 (YAF2, replaces the Chromobox (CBX and Polyhomeotic (PHC subunits found in cPRC1s. Additionally, ncPRC1 subunits can associate with versatile accessory proteins, which determine their functional specificity. Homozygous null mutations of the ncPRC members in mice are often lethal or cause infertility, which underlines their essential functions in mammalian development. In this review, we summarize the mouse knockout phenotypes of subunits of the six major ncPRCs. We highlight several aspects of their discovery from fly to mice and emerging role in target recognition, embryogenesis and cell-fate decision making. We gathered data from stem cell mediated in vitro differentiation assays and genetically engineered mouse models. Accumulating evidence suggests that ncPRC1s play profound role in mammalian embryogenesis by regulating gene expression during lineage specification of pluripotent stem cells.

  6. Diversity and disparity of sparassodonts (Metatheria) reveal non-analogue nature of ancient South American mammalian carnivore guilds

    Science.gov (United States)

    Dolgushina, Tatiana; Wesley, Gina

    2018-01-01

    This study investigates whether terrestrial mammalian carnivore guilds of ancient South America, which developed in relative isolation, were similar to those of other continents. We do so through analyses of clade diversification, ecomorphology and guild structure in the Sparassodonta, metatherians that were the predominant mammalian carnivores of pre-Pleistocene South America. Body mass and 16 characters of the dentition are used to quantify morphological diversity (disparity) in sparassodonts and to compare them to extant marsupial and placental carnivores and extinct North American carnivoramorphans. We also compare trophic diversity of the Early Miocene terrestrial carnivore guild of Santa Cruz, Argentina to that of 14 modern and fossil guilds from other continents. We find that sparassodonts had comparatively low ecomorphological disparity throughout their history and that South American carnivore palaeoguilds, as represented by that of Santa Cruz, Argentina, were unlike modern or fossil carnivore guilds of other continents in their lack of mesocarnivores and hypocarnivores. Our results add to a growing body of evidence highlighting non-analogue aspects of extinct South American mammals and illustrate the dramatic effects that historical contingency can have on the evolution of mammalian palaeocommunities. PMID:29298933

  7. Quality and Chemical Composition of Organic and Non-Organic Vetiver Oil

    Directory of Open Access Journals (Sweden)

    Asep Kadarohman

    2014-03-01

    Full Text Available Vetiver oil (Vetiveria zizanoides has been used as perfume materials, cosmetics, fragrance soaps, anti-inflammation, repellent, and insecticidal agents. Organic vetiver oil has higher economical value than non-organic vetiver oil and it has been regarded to be able to compete in the global market. Therefore, studies have been carried out using 1 hectare of land and the first generation of organic vetiver oil has produced 0.57% of yield, greater than non-organic (0.50%. The quality of organic and non-organic vetiver oil was analyzed by Indonesian Standard (SNI parameter, pesticide residue test, chemical composition by GC/MS, and the appearance of vetiver root. In general, the result of organic and non-organic vetiver oil has fulfilled the national standard; the quality of organic vetiver oil was better than non-organic one. Physically, the appearance of organic vetiver root was better than non-organic vetiver root; organic vetiver root was denser, more appealing, and did not have any black spots. The pesticide residue of organic vetiver oil was lower than non-organic vetiver oil. Based on SNI test, vetiverol (oxygen compounds in organic vetiver oil was higher than non-organic vetiver oil.

  8. Construction of a new shuttle vector for DNA delivery into mammalian cells using non-invasive Lactococcus lactis.

    Science.gov (United States)

    Yagnik, Bhrugu; Padh, Harish; Desai, Priti

    2016-04-01

    Use of food grade Lactococcus lactis (L. lactis) is fast emerging as a safe alternative for delivery of DNA vaccine. To attain efficient DNA delivery, L. lactis, a non-invasive bacterium is converted to invasive strain either by expressing proteins like Internalin A (InlA) or Fibronectin binding protein A (FnBPA) or through chemical treatments. However the safety status of invasive L. lactis is questionable. In the present report, we have shown that non-invasive L. lactis efficiently delivered the newly constructed reporter plasmid pPERDBY to mammalian cells without any chemical enhancers. The salient features of the vector are; I) Ability to replicate in two different hosts; Escherichia coli (E. coli) and Lactic Acid Bacteria (LAB), II) One of the smallest reporter plasmid for DNA vaccine, III) Enhanced Green Fluorescence Protein (EGFP) linked to Multiple Cloning Site (MCS), IV) Immunostimulatory CpG motifs functioning as an adjuvant. Expression of EGFP in pPERDBY transfected CHO-K1 and Caco-2 cells demonstrates its functionality. Non-invasive r-L. lactis was found efficient in delivering pPERDBY to Caco-2 cells. The in vitro data presented in this article supports the hypothesis that in the absence of invasive proteins or relevant chemical treatment, L. lactis was found efficient in delivering DNA to mammalian cells. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  9. A novel, non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3)

    OpenAIRE

    Fuller, Stephen J; McGuffin, Liam J; Marshall, Andrew K; Giraldo, Alejandro; Pikkarainen, Sampsa; Clerk, Angela; Sugden, Peter

    2012-01-01

    The canonical pathway of regulation of the GCK (germinal centre kinase) III subgroup member, MST3 (mammalian Sterile20-related kinase 3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr178), induction of serine/threonine protein kinase activity and nuclear localization. We identified an alternative ‘non-canonical’ pathway of MST3 activation (regulated primarily thro...

  10. Musculoskeletal networks reveal topological disparity in mammalian neck evolution.

    Science.gov (United States)

    Arnold, Patrick; Esteve-Altava, Borja; Fischer, Martin S

    2017-12-13

    The increase in locomotor and metabolic performance during mammalian evolution was accompanied by the limitation of the number of cervical vertebrae to only seven. In turn, nuchal muscles underwent a reorganization while forelimb muscles expanded into the neck region. As variation in the cervical spine is low, the variation in the arrangement of the neck muscles and their attachment sites (i.e., the variability of the neck's musculoskeletal organization) is thus proposed to be an important source of neck disparity across mammals. Anatomical network analysis provides a novel framework to study the organization of the anatomical arrangement, or connectivity pattern, of the bones and muscles that constitute the mammalian neck in an evolutionary context. Neck organization in mammals is characterized by a combination of conserved and highly variable network properties. We uncovered a conserved regionalization of the musculoskeletal organization of the neck into upper, mid and lower cervical modules. In contrast, there is a varying degree of complexity or specialization and of the integration of the pectoral elements. The musculoskeletal organization of the monotreme neck is distinctively different from that of therian mammals. Our findings reveal that the limited number of vertebrae in the mammalian neck does not result in a low musculoskeletal disparity when examined in an evolutionary context. However, this disparity evolved late in mammalian history in parallel with the radiation of certain lineages (e.g., cetartiodactyls, xenarthrans). Disparity is further facilitated by the enhanced incorporation of forelimb muscles into the neck and their variability in attachment sites.

  11. Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

    Directory of Open Access Journals (Sweden)

    Giuseppe Scapigliati

    2018-05-01

    Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

  12. Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

    OpenAIRE

    Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N.; Lee, Seung-Rock

    2014-01-01

    Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells ...

  13. Divergent evolutionary rates in vertebrate and mammalian specific conserved non-coding elements (CNEs) in echolocating mammals.

    Science.gov (United States)

    Davies, Kalina T J; Tsagkogeorga, Georgia; Rossiter, Stephen J

    2014-12-19

    The majority of DNA contained within vertebrate genomes is non-coding, with a certain proportion of this thought to play regulatory roles during development. Conserved Non-coding Elements (CNEs) are an abundant group of putative regulatory sequences that are highly conserved across divergent groups and thus assumed to be under strong selective constraint. Many CNEs may contain regulatory factor binding sites, and their frequent spatial association with key developmental genes - such as those regulating sensory system development - suggests crucial roles in regulating gene expression and cellular patterning. Yet surprisingly little is known about the molecular evolution of CNEs across diverse mammalian taxa or their role in specific phenotypic adaptations. We examined 3,110 vertebrate-specific and ~82,000 mammalian-specific CNEs across 19 and 9 mammalian orders respectively, and tested for changes in the rate of evolution of CNEs located in the proximity of genes underlying the development or functioning of auditory systems. As we focused on CNEs putatively associated with genes underlying the development/functioning of auditory systems, we incorporated echolocating taxa in our dataset because of their highly specialised and derived auditory systems. Phylogenetic reconstructions of concatenated CNEs broadly recovered accepted mammal relationships despite high levels of sequence conservation. We found that CNE substitution rates were highest in rodents and lowest in primates, consistent with previous findings. Comparisons of CNE substitution rates from several genomic regions containing genes linked to auditory system development and hearing revealed differences between echolocating and non-echolocating taxa. Wider taxonomic sampling of four CNEs associated with the homeobox genes Hmx2 and Hmx3 - which are required for inner ear development - revealed family-wise variation across diverse bat species. Specifically within one family of echolocating bats that utilise

  14. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  15. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

    2014-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  16. Person-Organization Commitment: Bonds of Internal Consumer in the Context of Non-profit Organizations.

    Science.gov (United States)

    Juaneda-Ayensa, Emma; Clavel San Emeterio, Mónica; González-Menorca, Carlos

    2017-01-01

    From an Organizational Behavior perspective, it is important to recognize the links generated between individuals and the organization that encourage a desire for permanence. After more than a half century of research, Organizational Commitment remains one of the open questions in the Psychology of Organizations. It is considered an essential factor for explaining individual behavior in the organization such as satisfaction, turnover intention, or loyalty. In this paper, we analyze different contributions regarding the nature of the bond between the individual and the organization. Taking into account the peculiarities of Non-profit Organizations, we present different interpretation for later validation, comparing results from the Confirmatory Factor Analysis of the four models obtained using exploratory factor analysis, both conducted on a sample of 235 members of Non-profit Organizations.

  17. A general framework for modeling growth and division of mammalian cells.

    Science.gov (United States)

    Gauthier, John H; Pohl, Phillip I

    2011-01-06

    Modeling the cell-division cycle has been practiced for many years. As time has progressed, this work has gone from understanding the basic principles to addressing distinct biological problems, e.g., the nature of the restriction point, how checkpoints operate, the nonlinear dynamics of the cell cycle, the effect of localization, etc. Most models consist of coupled ordinary differential equations developed by the researchers, restricted to deal with the interactions of a limited number of molecules. In the future, cell-cycle modeling--and indeed all modeling of complex biologic processes--will increase in scope and detail. A framework for modeling complex cell-biologic processes is proposed here. The framework is based on two constructs: one describing the entire lifecycle of a molecule and the second describing the basic cellular machinery. Use of these constructs allows complex models to be built in a straightforward manner that fosters rigor and completeness. To demonstrate the framework, an example model of the mammalian cell cycle is presented that consists of several hundred differential equations of simple mass action kinetics. The model calculates energy usage, amino acid and nucleotide usage, membrane transport, RNA synthesis and destruction, and protein synthesis and destruction for 33 proteins to give an in-depth look at the cell cycle. The framework presented here addresses how to develop increasingly descriptive models of complex cell-biologic processes. The example model of cellular growth and division constructed with the framework demonstrates that large structured models can be created with the framework, and these models can generate non-trivial descriptions of cellular processes. Predictions from the example model include those at both the molecular level--e.g., Wee1 spontaneously reactivates--and at the system level--e.g., pathways for timing-critical processes must shut down redundant pathways. A future effort is to automatically estimate

  18. LinkImputeR: user-guided genotype calling and imputation for non-model organisms.

    Science.gov (United States)

    Money, Daniel; Migicovsky, Zoë; Gardner, Kyle; Myles, Sean

    2017-07-10

    Genomic studies such as genome-wide association and genomic selection require genome-wide genotype data. All existing technologies used to create these data result in missing genotypes, which are often then inferred using genotype imputation software. However, existing imputation methods most often make use only of genotypes that are successfully inferred after having passed a certain read depth threshold. Because of this, any read information for genotypes that did not pass the threshold, and were thus set to missing, is ignored. Most genomic studies also choose read depth thresholds and quality filters without investigating their effects on the size and quality of the resulting genotype data. Moreover, almost all genotype imputation methods require ordered markers and are therefore of limited utility in non-model organisms. Here we introduce LinkImputeR, a software program that exploits the read count information that is normally ignored, and makes use of all available DNA sequence information for the purposes of genotype calling and imputation. It is specifically designed for non-model organisms since it requires neither ordered markers nor a reference panel of genotypes. Using next-generation DNA sequence (NGS) data from apple, cannabis and grape, we quantify the effect of varying read count and missingness thresholds on the quantity and quality of genotypes generated from LinkImputeR. We demonstrate that LinkImputeR can increase the number of genotype calls by more than an order of magnitude, can improve genotyping accuracy by several percent and can thus improve the power of downstream analyses. Moreover, we show that the effects of quality and read depth filters can differ substantially between data sets and should therefore be investigated on a per-study basis. By exploiting DNA sequence data that is normally ignored during genotype calling and imputation, LinkImputeR can significantly improve both the quantity and quality of genotype data generated from

  19. Management trends: Internationalization of non-profit organizations

    Directory of Open Access Journals (Sweden)

    Inić Branimir P.

    2015-01-01

    Full Text Available Non-profit organizations are increasingly gaining importance in the modern economy with their development and their numbers increasing day by day. It is very important to note that non-profit organizations are often subject to various benefits that the for-profit companies are not. Thus, for example, preferential tax status of non-profit organizations is manifested primarily in the form of exemption from corporate income tax. In addition, private non-profit organizations enjoy various other state, local and federal taxes exemptions. Under certain conditions, these organizations are exempt from taxes on donations and membership fees. A feature that differentiates various non-profit organizations and profit-oriented companies is their source of income. Profit oriented companies depend on their income, obtained from sales of their goods or services to customers, who usually cover the price and cost of goods and services plus the profit. In contrast, nonprofit organizations are very dependent on membership fees, tax exemptions, members donations or depend on funds of the sponsoring agency which covers most of their costs, for example a federal government agency. Those non-profit organizations that have substantial operating costs beyond national borders and do not identify themselves as purely domestic in their mandate are International non-profit organizations. Most non-profit organizations remain in their national boundaries, on the territory of the country in which they were created, but a large number of non-profit organizations rapidly internationalize, and some larger non-profits have grown into important global actors. The paper includes the following sections: (1 introduction, (2 why is the 'non-profit' important, (3 the internationalization of non-profit organizations, (4 sources of income of non-profit organizations (4.1. causality of impact and of strategic decisions in cases pertaining to universities, (5 the limits of strategic

  20. Actin and myosin contribute to mammalian mitochondrial DNA maintenance

    Science.gov (United States)

    Reyes, A.; He, J.; Mao, C. C.; Bailey, L. J.; Di Re, M.; Sembongi, H.; Kazak, L.; Dzionek, K.; Holmes, J. B.; Cluett, T. J.; Harbour, M. E.; Fearnley, I. M.; Crouch, R. J.; Conti, M. A.; Adelstein, R. S.; Walker, J. E.; Holt, I. J.

    2011-01-01

    Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and β-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of β-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some β-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance. PMID:21398640

  1. A comparative study and a phylogenetic exploration of the compositional architectures of mammalian nuclear genomes.

    Directory of Open Access Journals (Sweden)

    Eran Elhaik

    2014-11-01

    Full Text Available For the past four decades the compositional organization of the mammalian genome posed a formidable challenge to molecular evolutionists attempting to explain it from an evolutionary perspective. Unfortunately, most of the explanations adhered to the "isochore theory," which has long been rebutted. Recently, an alternative compositional domain model was proposed depicting the human and cow genomes as composed mostly of short compositionally homogeneous and nonhomogeneous domains and a few long ones. We test the validity of this model through a rigorous sequence-based analysis of eleven completely sequenced mammalian and avian genomes. Seven attributes of compositional domains are used in the analyses: (1 the number of compositional domains, (2 compositional domain-length distribution, (3 density of compositional domains, (4 genome coverage by the different domain types, (5 degree of fit to a power-law distribution, (6 compositional domain GC content, and (7 the joint distribution of GC content and length of the different domain types. We discuss the evolution of these attributes in light of two competing phylogenetic hypotheses that differ from each other in the validity of clade Euarchontoglires. If valid, the murid genome compositional organization would be a derived state and exhibit a high similarity to that of other mammals. If invalid, the murid genome compositional organization would be closer to an ancestral state. We demonstrate that the compositional organization of the murid genome differs from those of primates and laurasiatherians, a phenomenon previously termed the "murid shift," and in many ways resembles the genome of opossum. We find no support to the "isochore theory." Instead, our findings depict the mammalian genome as a tapestry of mostly short homogeneous and nonhomogeneous domains and few long ones thus providing strong evidence in favor of the compositional domain model and seem to invalidate clade Euarchontoglires.

  2. Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake.

    Directory of Open Access Journals (Sweden)

    Lieming Bao

    Full Text Available Polychlorinated biphenyls (PCBs are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs using the mammalian pregnane X receptor (PXR. In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL-PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants.

  3. Non-linear modeling of active biohybrid materials

    KAUST Repository

    Paetsch, C.

    2013-11-01

    Recent advances in engineered muscle tissue attached to a synthetic substrate motivate the development of appropriate constitutive and numerical models. Applications of active materials can be expanded by using robust, non-mammalian muscle cells, such as those of Manduca sexta. In this study, we propose a model to assist in the analysis of biohybrid constructs by generalizing a recently proposed constitutive law for Manduca muscle tissue. The continuum model accounts (i) for the stimulation of muscle fibers by introducing multiple stress-free reference configurations for the active and passive states and (ii) for the hysteretic response by specifying a pseudo-elastic energy function. A simple example representing uniaxial loading-unloading is used to validate and verify the characteristics of the model. Then, based on experimental data of muscular thin films, a more complex case shows the qualitative potential of Manduca muscle tissue in active biohybrid constructs. © 2013 Elsevier Ltd. All rights reserved.

  4. The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity

    International Nuclear Information System (INIS)

    Cole, Russell D.; Anderson, Gary L.; Williams, Phillip L.

    2004-01-01

    Fifteen organic phosphate pesticides were tested by computer tracking for their acute behavioral toxicity with the nematode Caenorhabditis elegans. Thirteen of these 15 chemicals are used as insecticides and are anticholesterase agents. The other two chemicals are used as herbicides. EC50 values for each chemical were compared to the corresponding LD50 acute lethality value in rats and mice. Order of toxicity was found to be significantly correlated in comparisons of C. elegans to both rats and mice. Mechanistic investigations were conducted by assaying 8 of the 15 chemicals for anticholinesterase activity in C. elegans. Significant cholinesterase inhibition was confirmed for five chemicals that had displayed high behavioral toxicity, while three chemicals of low behavioral toxicity showed no significant decrease in cholinesterase activity. Toxicity for two chemicals that do not inhibit cholinesterase in mammals was linked to pH effects. Detailed comparison of individual chemicals and metabolic issues are discussed. These results have positive implications for the use of C. elegans as a mammalian neurological model and support the use of C. elegans in early rounds of chemical toxicity screening

  5. TRANSPARENCY IN ITALIAN NON PROFIT ORGANIZATIONS

    Directory of Open Access Journals (Sweden)

    Patrizia Gazzola

    2014-07-01

    Full Text Available The aim of the paper is to evaluate the accountability and transparency of Italian non profits organizations. The main goal is to understand if a general accountability or transparency problem, or a systematic publicity deficit, exist in the third sector in Italy. Non profit organizations have an ethical obligation to their stakeholder and to the public to conduct their activities with accountability and transparency. Non profit organizations should regularly and openly convey information to the stakeholder about their vision, mission, objectives, activities, accomplishments, decision-making processes and organizational structure. Information from a non profit organization should be easily accessible to the stakeholder and should create external visibility, public understanding and trust in the organization, conditions necessary to find donors. Non profit organizations work with communities and community donors need to know how their money is used. In the first part the analysis of the definition of transparency and accountability is made and the sustainability report like an important instrument of communication is considered. In the second part an empirical research is presented. The Italian law allows taxpayers to devote 5 per thousand of their income tax to non profit organizations, choosing between charities, social promotion associations, recognized associations, entities dedicated to scientific research and health care, universities, municipal social services and other non profit organizations. The present study present a quantitative research and it’s based on an empirical analysis of non-profit organizations that receive this donation in Italy in the year 2010 and 2011. In the paper we analyze the transparency and the accountability of the top 100 non profit organizations that have received the contribution of 5 per thousand, checking whether they prepare their Sustainability Report or any other kind of report for communicate the use

  6. Stage-structured matrix models for organisms with non-geometric development times

    Science.gov (United States)

    Andrew Birt; Richard M. Feldman; David M. Cairns; Robert N. Coulson; Maria Tchakerian; Weimin Xi; James M. Guldin

    2009-01-01

    Matrix models have been used to model population growth of organisms for many decades. They are popular because of both their conceptual simplicity and their computational efficiency. For some types of organisms they are relatively accurate in predicting population growth; however, for others the matrix approach does not adequately model...

  7. Organic vs. Non-Organic Food Products: Credence and Price Competition

    OpenAIRE

    Yi Wang; Zhanguo Zhu; Feng Chu

    2017-01-01

    We analyze the organic and non-organic production choices of two firms by considering customers’ trust in organic food products. In the context of customers’ possible willingness to pay a premium price and their mistrust in organic food products, two firms first make choices on offering organic and non-organic food products. If offering organic products, a firm can further invest in the credence system to increase customers’ trust in their organic products. At the final stage, two firms deter...

  8. Identification and characterisation of the angiotensin converting enzyme-3 (ACE3 gene: a novel mammalian homologue of ACE

    Directory of Open Access Journals (Sweden)

    Phelan Anne

    2007-06-01

    Full Text Available Abstract Background Mammalian angiotensin converting enzyme (ACE plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. Conclusion In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.

  9. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  10. Organic vs. Non-Organic Food Products: Credence and Price Competition

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2017-04-01

    Full Text Available We analyze the organic and non-organic production choices of two firms by considering customers’ trust in organic food products. In the context of customers’ possible willingness to pay a premium price and their mistrust in organic food products, two firms first make choices on offering organic and non-organic food products. If offering organic products, a firm can further invest in the credence system to increase customers’ trust in their organic products. At the final stage, two firms determine prices. We provide serval insights. First, we characterize the market conditions in which only one firm, both firms or neither firm will choose to offer organic food products. We find that the higher the production costs or credence investment costs for organic food products are, the more likely firms are to choose to produce non-organic food products. Second, if it is expensive enough to invest in organic credence, offering organic food products may still be uncompetitive, even if organic production cost appears to have no disadvantage compared to non-organic food products. Third, we highlight how the prices of organic food products in equilibrium are affected by market parameters. We show that when only one firm offers organic food products, this firm tends to offer a relatively low price if organic credence investment is expensive. Fourth, we highlight how one firm’s credence investment decision in equilibrium can be affected by the product type choice of the other firm. We find that the investment in organic credence is lower when both firms offer organic food products compared with the case when only one firm offers organic food products.

  11. The parental non-equivalence of imprinting control regions during mammalian development and evolution.

    Directory of Open Access Journals (Sweden)

    Reiner Schulz

    2010-11-01

    Full Text Available In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc, using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the

  12. The parental non-equivalence of imprinting control regions during mammalian development and evolution.

    Science.gov (United States)

    Schulz, Reiner; Proudhon, Charlotte; Bestor, Timothy H; Woodfine, Kathryn; Lin, Chyuan-Sheng; Lin, Shau-Ping; Prissette, Marine; Oakey, Rebecca J; Bourc'his, Déborah

    2010-11-18

    In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two

  13. Non-Taylor magnetohydrodynamic self-organization

    International Nuclear Information System (INIS)

    Zhu, Shao-ping; Horiuchi, Ritoku; Sato, Tetsuya.

    1994-10-01

    A self-organization process in a plasma with a finite pressure is investigated by means of a three-dimensional magnetohydrodynamic simulation. It is demonstrated that a non-Taylor finite β self-organized state is realized in which a perpendicular component of the electric current is generated and the force-free(parallel) current decreases until they reach to almost the same level. The self-organized state is described by an MHD force-balance relation, namely, j perpendicular = B x ∇p/B·B and j parallel = μB where μ is not a constant, and the pressure structure resembles the structure of the toroidal magnetic field intensity. Unless an anomalous perpendicular thermal conduction arises, the plasma cannot relax to a Taylor state but to a non-Taylor (non-force-free) self-organized state. This state becomes more prominent for a weaker resistivity condition. The non-Taylor state has a rather universal property, for example, independence of the initial β value. Another remarkable finding is that the Taylor's conjecture of helicity conservation is, in a strict sense, not valid. The helicity dissipation occurs and its rate slows down critically in accordance with the stepwise relaxation of the magnetic energy. It is confirmed that the driven magnetic reconnection caused by the nonlinearly excited plasma kink flows plays the leading role in all of these key features of the non-Taylor self-organization. (author)

  14. Quality by control: Towards model predictive control of mammalian cell culture bioprocesses.

    Science.gov (United States)

    Sommeregger, Wolfgang; Sissolak, Bernhard; Kandra, Kulwant; von Stosch, Moritz; Mayer, Martin; Striedner, Gerald

    2017-07-01

    The industrial production of complex biopharmaceuticals using recombinant mammalian cell lines is still mainly built on a quality by testing approach, which is represented by fixed process conditions and extensive testing of the end-product. In 2004 the FDA launched the process analytical technology initiative, aiming to guide the industry towards advanced process monitoring and better understanding of how critical process parameters affect the critical quality attributes. Implementation of process analytical technology into the bio-production process enables moving from the quality by testing to a more flexible quality by design approach. The application of advanced sensor systems in combination with mathematical modelling techniques offers enhanced process understanding, allows on-line prediction of critical quality attributes and subsequently real-time product quality control. In this review opportunities and unsolved issues on the road to a successful quality by design and dynamic control implementation are discussed. A major focus is directed on the preconditions for the application of model predictive control for mammalian cell culture bioprocesses. Design of experiments providing information about the process dynamics upon parameter change, dynamic process models, on-line process state predictions and powerful software environments seem to be a prerequisite for quality by control realization. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Habituation in non-neural organisms: evidence from slime moulds.

    Science.gov (United States)

    Boisseau, Romain P; Vogel, David; Dussutour, Audrey

    2016-04-27

    Learning, defined as a change in behaviour evoked by experience, has hitherto been investigated almost exclusively in multicellular neural organisms. Evidence for learning in non-neural multicellular organisms is scant, and only a few unequivocal reports of learning have been described in single-celled organisms. Here we demonstrate habituation, an unmistakable form of learning, in the non-neural organism Physarum polycephalum In our experiment, using chemotaxis as the behavioural output and quinine or caffeine as the stimulus, we showed that P. polycephalum learnt to ignore quinine or caffeine when the stimuli were repeated, but responded again when the stimulus was withheld for a certain time. Our results meet the principle criteria that have been used to demonstrate habituation: responsiveness decline and spontaneous recovery. To distinguish habituation from sensory adaptation or motor fatigue, we also show stimulus specificity. Our results point to the diversity of organisms lacking neurons, which likely display a hitherto unrecognized capacity for learning, and suggest that slime moulds may be an ideal model system in which to investigate fundamental mechanisms underlying learning processes. Besides, documenting learning in non-neural organisms such as slime moulds is centrally important to a comprehensive, phylogenetic understanding of when and where in the tree of life the earliest manifestations of learning evolved. © 2016 The Author(s).

  16. [Saccharomyces cerevisiae as a model organism for studying the carcinogenicity of non-ionizing electromagnetic fields and radiation].

    Science.gov (United States)

    Voĭchuk, S I

    2014-01-01

    Medical and biological aspects of the effects of non-ionizing electromagnetic (EM) fields and radiation on human health are the important issues that have arisen as a result of anthropogenic impact on the biosphere. Safe use of man-made sources of non-ionizing electromagnetic fields and radiation in a broad range of frequencies--static, radio-frequency and microwave--is a subject of discussions and speculations. The main problem is the lack of understanding of the mechanism(s) of reception of EMFs by living organisms. In this review we have analyzed the existing literature data regarding the effects of the electromagnetic radiation on the model eukaryotic organism--yeast Saccharomyces cerevisiae. An attempt was made to estimate the probability of induction of carcinogenesis in humans under the influence of magnetic fields and electromagnetic radiation of extremely low frequency, radio frequency and microwave ranges.

  17. Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

    Directory of Open Access Journals (Sweden)

    Velia Siciliano

    2011-06-01

    Full Text Available Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL by generating a clonal population of mammalian cells (CHO carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA, whose expression is regulated by a tTA responsive promoter (CMV-TET, thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP, thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL, by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off, and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

  18. Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

    Science.gov (United States)

    Siciliano, Velia; Menolascina, Filippo; Marucci, Lucia; Fracassi, Chiara; Garzilli, Immacolata; Moretti, Maria Nicoletta; di Bernardo, Diego

    2011-06-01

    Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

  19. Self-illuminating quantum dots for non-invasive bioluminescence imaging of mammalian

    Science.gov (United States)

    Background: The fertility performance of animals is still a mystery and the full comprehension of mammalian gametes maturation and early embryonic development remains to be elucidated. The recent development in nanotechnology offers a new opportunity for real-time study of reproductive cells in thei...

  20. [Mathematical modeling of synergistic interaction of sequential thermoradiation action on mammalian cells].

    Science.gov (United States)

    Belkina, S V; Semkina, M A; Kritskiĭ, R O; Petin, V G

    2010-01-01

    Data obtained by other authors for mammalian cells treated by sequential action of ionizing radiation and hyperthermia were used to estimate the dependence of synergistic enhancement ratio on the ratio of damages induced by these agents. Experimental results were described and interpreted by means of the mathematical model of synergism in accordance with which the synergism is expected to result from the additional lethal damage arising from the interaction of sublesions induced by both agents.

  1. Patient-specific non-linear finite element modelling for predicting soft organ deformation in real-time: application to non-rigid neuroimage registration.

    Science.gov (United States)

    Wittek, Adam; Joldes, Grand; Couton, Mathieu; Warfield, Simon K; Miller, Karol

    2010-12-01

    Long computation times of non-linear (i.e. accounting for geometric and material non-linearity) biomechanical models have been regarded as one of the key factors preventing application of such models in predicting organ deformation for image-guided surgery. This contribution presents real-time patient-specific computation of the deformation field within the brain for six cases of brain shift induced by craniotomy (i.e. surgical opening of the skull) using specialised non-linear finite element procedures implemented on a graphics processing unit (GPU). In contrast to commercial finite element codes that rely on an updated Lagrangian formulation and implicit integration in time domain for steady state solutions, our procedures utilise the total Lagrangian formulation with explicit time stepping and dynamic relaxation. We used patient-specific finite element meshes consisting of hexahedral and non-locking tetrahedral elements, together with realistic material properties for the brain tissue and appropriate contact conditions at the boundaries. The loading was defined by prescribing deformations on the brain surface under the craniotomy. Application of the computed deformation fields to register (i.e. align) the preoperative and intraoperative images indicated that the models very accurately predict the intraoperative deformations within the brain. For each case, computing the brain deformation field took less than 4 s using an NVIDIA Tesla C870 GPU, which is two orders of magnitude reduction in computation time in comparison to our previous study in which the brain deformation was predicted using a commercial finite element solver executed on a personal computer. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. A mathematical model for pressure-based organs behaving as biological pressure vessels.

    Science.gov (United States)

    Casha, Aaron R; Camilleri, Liberato; Gauci, Marilyn; Gatt, Ruben; Sladden, David; Chetcuti, Stanley; Grima, Joseph N

    2018-04-26

    We introduce a mathematical model that describes the allometry of physical characteristics of hollow organs behaving as pressure vessels based on the physics of ideal pressure vessels. The model was validated by studying parameters such as body and organ mass, systolic and diastolic pressures, internal and external dimensions, pressurization energy and organ energy output measurements of pressure-based organs in a wide range of mammals and birds. Seven rules were derived that govern amongst others, lack of size efficiency on scaling to larger organ sizes, matching organ size in the same species, equal relative efficiency in pressurization energy across species and direct size matching between organ mass and mass of contents. The lung, heart and bladder follow these predicted theoretical relationships with a similar relative efficiency across various mammalian and avian species; an exception is cardiac output in mammals with a mass exceeding 10kg. This may limit massive body size in mammals, breaking Cope's rule that populations evolve to increase in body size over time. Such a limit was not found in large flightless birds exceeding 100kg, leading to speculation about unlimited dinosaur size should dinosaurs carry avian-like cardiac characteristics. Copyright © 2018. Published by Elsevier Ltd.

  3. The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium

    Directory of Open Access Journals (Sweden)

    Goetz Thomas

    2004-07-01

    Full Text Available Abstract Background The mammalian retina is a valuable model system to study neuronal biology in health and disease. To obtain insight into intrinsic processes of the retina, great efforts are directed towards the identification and characterization of transcripts with functional relevance to this tissue. Results With the goal to assemble a first genome-wide reference transcriptome of the adult mammalian retina, referred to as the retinome, we have extracted 13,037 non-redundant annotated genes from nearly 500,000 published datasets on redundant retina/retinal pigment epithelium (RPE transcripts. The data were generated from 27 independent studies employing a wide range of molecular and biocomputational approaches. Comparison to known retina-/RPE-specific pathways and established retinal gene networks suggest that the reference retinome may represent up to 90% of the retinal transcripts. We show that the distribution of retinal genes along the chromosomes is not random but exhibits a higher order organization closely following the previously observed clustering of genes with increased expression. Conclusion The genome wide retinome map offers a rational basis for selecting suggestive candidate genes for hereditary as well as complex retinal diseases facilitating elaborate studies into normal and pathological pathways. To make this unique resource freely available we have built a database providing a query interface to the reference retinome 1.

  4. Base Composition Characteristics of Mammalian miRNAs

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

  5. Synchronized mammalian cell culture: part II--population ensemble modeling and analysis for development of reproducible processes.

    Science.gov (United States)

    Jandt, Uwe; Barradas, Oscar Platas; Pörtner, Ralf; Zeng, An-Ping

    2015-01-01

    The consideration of inherent population inhomogeneities of mammalian cell cultures becomes increasingly important for systems biology study and for developing more stable and efficient processes. However, variations of cellular properties belonging to different sub-populations and their potential effects on cellular physiology and kinetics of culture productivity under bioproduction conditions have not yet been much in the focus of research. Culture heterogeneity is strongly determined by the advance of the cell cycle. The assignment of cell-cycle specific cellular variations to large-scale process conditions can be optimally determined based on the combination of (partially) synchronized cultivation under otherwise physiological conditions and subsequent population-resolved model adaptation. The first step has been achieved using the physical selection method of countercurrent flow centrifugal elutriation, recently established in our group for different mammalian cell lines which is presented in Part I of this paper series. In this second part, we demonstrate the successful adaptation and application of a cell-cycle dependent population balance ensemble model to describe and understand synchronized bioreactor cultivations performed with two model mammalian cell lines, AGE1.HNAAT and CHO-K1. Numerical adaptation of the model to experimental data allows for detection of phase-specific parameters and for determination of significant variations between different phases and different cell lines. It shows that special care must be taken with regard to the sampling frequency in such oscillation cultures to minimize phase shift (jitter) artifacts. Based on predictions of long-term oscillation behavior of a culture depending on its start conditions, optimal elutriation setup trade-offs between high cell yields and high synchronization efficiency are proposed. © 2014 American Institute of Chemical Engineers.

  6. Rheotaxis guides mammalian sperm

    Science.gov (United States)

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  7. Non-governmental organizations internal communication in reputation management

    OpenAIRE

    Vaicekauskaitė, Renata

    2010-01-01

    The object of this study is non-governmental organization’s internal communication and its role in reputation management. The aim of this study is to analyse the context of non-governmental organization reputation management and according to it find out the significance of the internal communication factors in non-governmental organization reputation management. The tasks of the study: to analyse the factors which have settled the need of non-governmental organization reputation management; t...

  8. Evaluation of Biogenic Amines in Organic and Non-Organic Wines by HPLC OPA Derivatization

    Directory of Open Access Journals (Sweden)

    Ali Üren

    2007-01-01

    Full Text Available Organic and non-organic wines, selected on the basis of consumers’ preference towards healthy products, were produced from the grapes of Vitis vinifera varieties Semillon, Colombard, Cabernet Sauvignon, Merlot and Carignan and possible effects of different wine making techniques were considered. Concentrations of histamine, tyramine, putrescine, cadaverine, ethylamine, methylamine, tryptamine, agmatine and β-phenylethylamine were quantified by HPLC fluorescence detection of o-phthaldialdehyde (OPA derivatives. The order of analyzed parameters in all wines from the highest to the lowest quantities was determined as follows: putrescine > histamine > ethylamine > methylamine > agmatine > tyramine > cadaverine > tryptamine. One of the analyzed compounds (β-phenylethylamine was not detected. The highest average values for organic and non-organic wines were found as follows (in mg/L: putrescine 5.55, ethylamine 0.825 and histamine 0.628 in organic wines, and putrescine 3.68, histamine 1.14 and agmatine 0.662 in non-organic wines. Considering the wine type (organic/non-organic, an important difference was determined for putrescine. Putrescine content in organic wines was significantly greater than in non-organic ones (p=0.008. Evaluating colour of wines (white/red, a statistically significant difference was obtained for methylamine (p=0.028. Taking into account only grape varieties, statistically significant differences were found for histamine, methylamine, tyramine and cadaverine (p<0.05. The results of principal component analysis demonstrated close relations between the following biogenic amines and wines: agmatine and non-organic Colombard; tryptamine or cadaverine and both organic and non-organic Cabernet Sauvignon wines.

  9. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.

    1981-01-01

    Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

  10. Mammalian Gravity Receptors: Structure and Metabolism

    Science.gov (United States)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  11. Modelling three-dimensional cochlear micromechanics within the guinea pig organ of Corti

    Science.gov (United States)

    Ni, Guangjian; Elliott, Stephen J.

    2018-05-01

    The active amplification process in the mammalian cochlea depends on a complex interaction between cells within the organ of Corti. A three-dimensional (3D) model was developed using the finite element method based on anatomy for the apical end in the guinea pig cochlea, which is comprised of 3D discrete hair cells, 3D continuous membranes and fluid. The basilar membrane, tectorial membrane and the reticular lamina are modelled with orthotropic materials. The Y-shape structures formed by the outer hair cell (OHC), the Deiters' cell and Deiters' cell phalangeal process are also included to account for the structural longitudinal coupling. The motion within the organ of Corti was first simulated in response to a pressure difference loading on the basilar membrane, in order to calculate the passive vibration pattern. Then, the outer hair cells somatic electromotility was implemented by applying a voltage across the OHC walls to investigate its contribution to membranes motion.

  12. Multiobjective Optimization Model for Pricing and Seat Allocation Problem in Non Profit Performing Arts Organization

    DEFF Research Database (Denmark)

    Baldin, Andrea; Bille, Trine; Ellero, Andrea

    The implementation of Revenue Management (RM) techniques in non profit performing arts organizations presents new challenges compared to other sectors, such as transportion or hospitality industries, in which these techniques are more consolidated. Indeed, performing arts organizations are charac......The implementation of Revenue Management (RM) techniques in non profit performing arts organizations presents new challenges compared to other sectors, such as transportion or hospitality industries, in which these techniques are more consolidated. Indeed, performing arts organizations...... are characterized by a multi-objective function that is not solely limited to revenue. On the one hand, theatres aim to increase revenue from box office as a consequence of the systematic reduction of public funds; on the other hand they pursue the objective to increase its attendance. A common practice by theatres...

  13. Epilepsy and non-organic non-affective psychosis. National epidemiologic study

    DEFF Research Database (Denmark)

    Bredkjaer, S R; Mortensen, P B; Parnas, Josef

    1998-01-01

    : The incidences of the spectrum of non-organic non-affective psychosis, non-affective psychosis and schizophrenia were significantly increased both for men and women, even after exclusion of people diagnosed as suffering from a learning disability or substance misuse. CONCLUSION: This study supports the notion...

  14. The shape of mammalian phylogeny

    DEFF Research Database (Denmark)

    Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

    2011-01-01

    an assemblage, ecoregion or larger area always tends to be more unbalanced than expected from the phylogeny of species at the next more inclusive spatial scale. We conclude with a verbal model of mammalian macroevolution, which emphasizes the importance to diversification of accessing new regions...

  15. Mini Screening of Kinase Inhibitors Affecting Period-length of Mammalian Cellular Circadian Clock

    International Nuclear Information System (INIS)

    Yagita, Kazuhiro; Yamanaka, Iori; Koinuma, Satoshi; Shigeyoshi, Yasufumi; Uchiyama, Yasuo

    2009-01-01

    In mammalian circadian rhythms, the transcriptional-translational feedback loop (TTFL) consisting of a set of clock genes is believed to elicit the circadian clock oscillation. The TTFL model explains that the accumulation and degradation of mPER and mCRY proteins control the period-length (tau) of the circadian clock. Although recent studies revealed that the Casein Kinase Iεδ (CKIεδ) regurates the phosphorylation of mPER proteins and the circadian period-length, other kinases are also likely to contribute the phosphorylation of mPER. Here, we performed small scale screening using 84 chemical compounds known as kinase inhibitors to identify candidates possibly affecting the circadian period-length in mammalian cells. Screening by this high-throughput real-time bioluminescence monitoring system revealed that the several chemical compounds apparently lengthened the cellular circadian clock oscillation. These compounds are known as inhibitors against kinases such as Casein Kinase II (CKII), PI3-kinase (PI3K) and c-Jun N-terminal Kinase (JNK) in addition to CKIεδ. Although these kinase inhibitors may have some non-specific effects on other factors, our mini screening identified new candidates contributing to period-length control in mammalian cells

  16. Structural differences between yeast and mammalian microtubules revealed by cryo-EM

    Energy Technology Data Exchange (ETDEWEB)

    Howes, Stuart C. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group; Geyer, Elisabeth A. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; LaFrance, Benjamin [Univ. of California, Berkeley, CA (United States). Molecular and Cell Biology Graduate Program; Zhang, Rui [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Kellogg, Elizabeth H. [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Westermann, Stefan [Univ. of Duisburg-Essen, Essen (Germany). Dept. of Molecular Genetics, Center for Medical Biotechnology; Rice, Luke M. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; Nogales, Eva [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular Biology and California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

    2017-06-26

    Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrations used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.

  17. Structure and function of stem cell pools in mammalian cell renewal systems

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Nothdurft, W.

    1979-01-01

    Stem cells play a key-role in the maintenance of the equilibrium between cell loss and cell production in cell renewal systems as well as in the understanding of the radiation pathophysiology of mammalian organisms. The integrity of mammalian organisms with the need to maintain a constant ''millieu interior'' is depending on the normal functioning of cell renewal systems, especially those of epithelial surfaces and blood cell forming organs. All cell renewal systems of bodies have a very similar functional structure consisting of functional, proliferative - amplifying and stem cell compartments. They differ in transit and cell cycle times and in the number of amplification division - aside from the difference in their functional and biochemical make-up. The stem cell pools are providing the cells capable of differentiation without depleting their own kind. This can be achieved by symmetrical or assymmetrical stem cell division. In normal steady state, 50% of the stem cell division remain in the stem cell pool, while the other 50% leave it to differentiate, proliferate and mature, hemopoietic system is distributed throughout bodies. This is an important factor in the radiation biology of mammalian organisms since the loss of function in one area can be compensated for by more production in other areas, and locally depleted sites can be reseeded with the stem cells migrating in from blood. (Yamashita, S.)

  18. Comparative Corporate Governance of Non-Profit Organizations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2014-01-01

    Based on the impressive work of Hopt and von Hippel (2010), I review the comparative corporate governance of non-profit organizations and propose topics for future research. There is evidence of agency problems in non-profit as well as for-profit organizations, but the governance mechanisms...

  19. Novel method to load multiple genes onto a mammalian artificial chromosome.

    Directory of Open Access Journals (Sweden)

    Anna Tóth

    Full Text Available Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.

  20. Novel method to load multiple genes onto a mammalian artificial chromosome.

    Science.gov (United States)

    Tóth, Anna; Fodor, Katalin; Praznovszky, Tünde; Tubak, Vilmos; Udvardy, Andor; Hadlaczky, Gyula; Katona, Robert L

    2014-01-01

    Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.

  1. Scalable printed electronics: an organic decoder addressing ferroelectric non-volatile memory

    Science.gov (United States)

    Ng, Tse Nga; Schwartz, David E.; Lavery, Leah L.; Whiting, Gregory L.; Russo, Beverly; Krusor, Brent; Veres, Janos; Bröms, Per; Herlogsson, Lars; Alam, Naveed; Hagel, Olle; Nilsson, Jakob; Karlsson, Christer

    2012-01-01

    Scalable circuits of organic logic and memory are realized using all-additive printing processes. A 3-bit organic complementary decoder is fabricated and used to read and write non-volatile, rewritable ferroelectric memory. The decoder-memory array is patterned by inkjet and gravure printing on flexible plastics. Simulation models for the organic transistors are developed, enabling circuit designs tolerant of the variations in printed devices. We explain the key design rules in fabrication of complex printed circuits and elucidate the performance requirements of materials and devices for reliable organic digital logic. PMID:22900143

  2. Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency.

    Directory of Open Access Journals (Sweden)

    Jie Li

    Full Text Available The classical form of α1-antitrypsin deficiency (ATD is associated with hepatic fibrosis and hepatocellular carcinoma. It is caused by the proteotoxic effect of a mutant secretory protein that aberrantly accumulates in the endoplasmic reticulum of liver cells. Recently we developed a model of this deficiency in C. elegans and adapted it for high-content drug screening using an automated, image-based array scanning. Screening of the Library of Pharmacologically Active Compounds identified fluphenazine (Flu among several other compounds as a drug which reduced intracellular accumulation of mutant α1-antitrypsin Z (ATZ. Because it is representative of the phenothiazine drug class that appears to have autophagy enhancer properties in addition to mood stabilizing activity, and can be relatively easily re-purposed, we further investigated its effects on mutant ATZ. The results indicate that Flu reverses the phenotypic effects of ATZ accumulation in the C. elegans model of ATD at doses which increase the number of autophagosomes in vivo. Furthermore, in nanomolar concentrations, Flu enhances the rate of intracellular degradation of ATZ and reduces the cellular ATZ load in mammalian cell line models. In the PiZ mouse model Flu reduces the accumulation of ATZ in the liver and mediates a decrease in hepatic fibrosis. These results show that Flu can reduce the proteotoxicity of ATZ accumulation in vivo and, because it has been used safely in humans, this drug can be moved rapidly into trials for liver disease due to ATD. The results also provide further validation for drug discovery using C. elegans models that can be adapted to high-content drug screening platforms and used together with mammalian cell line and animal models.

  3. Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

    Science.gov (United States)

    Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2016-09-11

    A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. The Degradome database: mammalian proteases and diseases of proteolysis.

    Science.gov (United States)

    Quesada, Víctor; Ordóñez, Gonzalo R; Sánchez, Luis M; Puente, Xose S; López-Otín, Carlos

    2009-01-01

    The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

  5. Small GTPases and formins in mammalian oocyte maturation: cytoskeletal organizers.

    Science.gov (United States)

    Kwon, Sojung; Lim, Hyunjung J

    2011-03-01

    The maturation process of mammalian oocytes accompanies an extensive rearrangement of the cytoskeleton and associated proteins. As this process requires a delicate interplay between the cytoskeleton and its regulators, it is often targeted by various external and internal adversaries that affect the congression and/or segregation of chromosomes. Asymmetric cell division in oocytes also requires specific regulators of the cytoskeleton, including formin-2 and small GTPases. Recent literature providing clues regarding how actin filaments and microtubules interact during spindle migration in mouse oocytes are highlighted in this review.

  6. Modeling the World Health Organization Disability Assessment Schedule II using non-parametric item response models.

    Science.gov (United States)

    Galindo-Garre, Francisca; Hidalgo, María Dolores; Guilera, Georgina; Pino, Oscar; Rojo, J Emilio; Gómez-Benito, Juana

    2015-03-01

    The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a multidimensional instrument developed for measuring disability. It comprises six domains (getting around, self-care, getting along with others, life activities and participation in society). The main purpose of this paper is the evaluation of the psychometric properties for each domain of the WHO-DAS II with parametric and non-parametric Item Response Theory (IRT) models. A secondary objective is to assess whether the WHO-DAS II items within each domain form a hierarchy of invariantly ordered severity indicators of disability. A sample of 352 patients with a schizophrenia spectrum disorder is used in this study. The 36 items WHO-DAS II was administered during the consultation. Partial Credit and Mokken scale models are used to study the psychometric properties of the questionnaire. The psychometric properties of the WHO-DAS II scale are satisfactory for all the domains. However, we identify a few items that do not discriminate satisfactorily between different levels of disability and cannot be invariantly ordered in the scale. In conclusion the WHO-DAS II can be used to assess overall disability in patients with schizophrenia, but some domains are too general to assess functionality in these patients because they contain items that are not applicable to this pathology. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Non-fullerene electron acceptors for organic photovoltaic devices

    Energy Technology Data Exchange (ETDEWEB)

    Jenekhe, Samson A.; Li, Haiyan; Earmme, Taeshik; Ren, Guoqiang

    2017-11-07

    Non-fullerene electron acceptors for highly efficient organic photovoltaic devices are described. The non-fullerene electron acceptors have an extended, rigid, .pi.-conjugated electron-deficient framework that can facilitate exciton and charge derealization. The non-fullerene electron acceptors can physically mix with a donor polymer and facilitate improved electron transport. The non-fullerene electron acceptors can be incorporated into organic electronic devices, such as photovoltaic cells.

  8. Optimization of phenol extraction procedures for preparation of RNA from mammalian lymphoid organs

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Sellin, H.G.; Novelli, G.D.

    1978-07-01

    Methods have been developed to optimize the extraction of RNA from mammalian lymphoid organs (spleen) with respect to both quantity and quality of RNA and with minimal DNA contamination. Nuclease inhibitors, including diethyl pyrocarbonate, polyvinyl sulfate, and bentonite were used in the initial disruption of the tissue, which was accomplished by blender, Dounce homogenizer, or preparation of a cell suspension. Seven buffer systems, varying with respect to pH, detergent, and NaCl concentration, were used in the initial extraction with phenol, and the temperature of extraction was also varied. Protocols involving the selective use of naphthalene 1.5-disulfonic acid and sodium dodecyl sulfate were developed to provide an initial RNA extract with minimal DNA content. Dounce homogenization, followed by separate treatment of nuclear and cytosol fractions, was found to be the most effective technique, both in terms of RNA yield (averaging 76%) and the quality of RNA recovered (as judged by gel electrophoresis). RNA from blender preparations contained larger amounts of DNA and RNA yield was decreased to 54%. RNA extracted from spleen cell suspensions was of poor quality and gave very poor yield (27%).

  9. Evidence for soft bounds in Ubuntu package sizes and mammalian body masses.

    Science.gov (United States)

    Gherardi, Marco; Mandrà, Salvatore; Bassetti, Bruno; Cosentino Lagomarsino, Marco

    2013-12-24

    The development of a complex system depends on the self-coordinated action of a large number of agents, often determining unexpected global behavior. The case of software evolution has great practical importance: knowledge of what is to be considered atypical can guide developers in recognizing and reacting to abnormal behavior. Although the initial framework of a theory of software exists, the current theoretical achievements do not fully capture existing quantitative data or predict future trends. Here we show that two elementary laws describe the evolution of package sizes in a Linux-based operating system: first, relative changes in size follow a random walk with non-Gaussian jumps; second, each size change is bounded by a limit that is dependent on the starting size, an intriguing behavior that we call "soft bound." Our approach is based on data analysis and on a simple theoretical model, which is able to reproduce empirical details without relying on any adjustable parameter and generates definite predictions. The same analysis allows us to formulate and support the hypothesis that a similar mechanism is shaping the distribution of mammalian body sizes, via size-dependent constraints during cladogenesis. Whereas generally accepted approaches struggle to reproduce the large-mass shoulder displayed by the distribution of extant mammalian species, this is a natural consequence of the softly bounded nature of the process. Additionally, the hypothesis that this model is valid has the relevant implication that, contrary to a common assumption, mammalian masses are still evolving, albeit very slowly.

  10. Hairless pigmented guinea pigs: a new model for the study of mammalian pigmentation.

    Science.gov (United States)

    Bolognia, J L; Murray, M S; Pawelek, J M

    1990-09-01

    A stock of hairless pigmented guinea pigs was developed to facilitate studies of mammalian pigmentation. This stock combines the convenience of a hairless animal with a pigmentary system that is similar to human skin. In both human and guinea pig skin, active melanocytes are located in the basal layer of the interfollicular epidermis. Hairless albino guinea pigs on an outbred Hartley background (CrI:IAF/HA(hr/hr)BR; designated hr/hr) were mated with red-haired guinea pigs (designated Hr/Hr). Red-haired heterozygotes from the F1 generation (Hr/hr) were then mated with each other or with hairless albino guinea pigs. The F2 generation included hairless pigmented guinea pigs that retained their interfollicular epidermal melanocytes and whose skin was red-brown in color. Following UV irradiation, there was an increase in cutaneous pigmentation as well as an increase in the number of active epidermal melanocytes. An additional strain of black hairless guinea pigs was developed using black Hr/Hr animals and a similar breeding scheme. These two strains should serve as useful models for studies of the mammalian pigment system.

  11. A carbon dioxide stripping model for mammalian cell culture in manufacturing scale bioreactors.

    Science.gov (United States)

    Xing, Zizhuo; Lewis, Amanda M; Borys, Michael C; Li, Zheng Jian

    2017-06-01

    Control of carbon dioxide within the optimum range is important in mammalian bioprocesses at the manufacturing scale in order to ensure robust cell growth, high protein yields, and consistent quality attributes. The majority of bioprocess development work is done in laboratory bioreactors, in which carbon dioxide levels are more easily controlled. Some challenges in carbon dioxide control can present themselves when cell culture processes are scaled up, because carbon dioxide accumulation is a common feature due to longer gas-residence time of mammalian cell culture in large scale bioreactors. A carbon dioxide stripping model can be used to better understand and optimize parameters that are critical to cell culture processes at the manufacturing scale. The prevailing carbon dioxide stripping models in literature depend on mass transfer coefficients and were applicable to cell culture processes with low cell density or at stationary/cell death phase. However, it was reported that gas bubbles are saturated with carbon dioxide before leaving the culture, which makes carbon dioxide stripping no longer depend on a mass transfer coefficient in the new generation cell culture processes characterized by longer exponential growth phase, higher peak viable cell densities, and higher specific production rate. Here, we present a new carbon dioxide stripping model for manufacturing scale bioreactors, which is independent of carbon dioxide mass transfer coefficient, but takes into account the gas-residence time and gas CO 2 saturation time. The model was verified by CHO cell culture processes with different peak viable cell densities (7 to 12 × 10 6  cells mL -1 ) for two products in 5,000-L and 25,000-L bioreactors. The model was also applied to a next generation cell culture process to optimize cell culture conditions and reduce carbon dioxide levels at manufacturing scale. The model provides a useful tool to understand and better control cell culture carbon dioxide

  12. A QCM-D study of the concentration- and time-dependent interactions of human LL37 with model mammalian lipid bilayers.

    Science.gov (United States)

    Lozeau, Lindsay D; Rolle, Marsha W; Camesano, Terri A

    2018-07-01

    The human antimicrobial peptide LL37 is promising as an alternative to antibiotics due to its biophysical interactions with charged bacterial lipids. However, its clinical potential is limited due to its interactions with zwitterionic mammalian lipids leading to cytotoxicity. Mechanistic insight into the LL37 interactions with mammalian lipids may enable rational design of less toxic LL37-based therapeutics. To this end, we studied concentration- and time-dependent interactions of LL37 with zwitterionic model phosphatidylcholine (PC) bilayers with quartz crystal microbalance with dissipation (QCM-D). LL37 mass adsorption and PC bilayer viscoelasticity changes were monitored by measuring changes in frequency (Δf) and dissipation (ΔD), respectively. The Voigt-Kelvin viscoelastic model was applied to Δf and ΔD to study changes in bilayer thickness and density with LL37 concentration. At low concentrations (0.10-1.00 μM), LL37 adsorbed onto bilayers in a concentration-dependent manner. Further analyses of Δf, ΔD and thickness revealed that peptide saturation on the bilayers was a threshold for interactions observed above 2.00 μM, interactions that were rapid, multi-step, and reached equilibrium in a concentration- and time-dependent manner. Based on these data, we proposed a model of stable transmembrane pore formation at 2.00-10.0 μM, or transition from a primarily lipid to a primarily protein film with a transmembrane pore formation intermediate state at concentrations of LL37 > 10 μM. The concentration-dependent interactions between LL37 and PC bilayers correlated with the observed concentration-dependent biological activities of LL37 (antimicrobial, immunomodulatory and non-cytotoxic at 0.1-1.0 μM, hemolytic and some cytotoxicity at 2.0-13 μM and cytotoxic at >13 μM). Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A practical guide to build de-novo assemblies for single tissues of non-model organisms: the example of a Neotropical frog

    Directory of Open Access Journals (Sweden)

    Santiago Montero-Mendieta

    2017-09-01

    Full Text Available Whole genome sequencing (WGS is a very valuable resource to understand the evolutionary history of poorly known species. However, in organisms with large genomes, as most amphibians, WGS is still excessively challenging and transcriptome sequencing (RNA-seq represents a cost-effective tool to explore genome-wide variability. Non-model organisms do not usually have a reference genome and the transcriptome must be assembled de-novo. We used RNA-seq to obtain the transcriptomic profile for Oreobates cruralis, a poorly known South American direct-developing frog. In total, 550,871 transcripts were assembled, corresponding to 422,999 putative genes. Of those, we identified 23,500, 37,349, 38,120 and 45,885 genes present in the Pfam, EggNOG, KEGG and GO databases, respectively. Interestingly, our results suggested that genes related to immune system and defense mechanisms are abundant in the transcriptome of O. cruralis. We also present a pipeline to assist with pre-processing, assembling, evaluating and functionally annotating a de-novo transcriptome from RNA-seq data of non-model organisms. Our pipeline guides the inexperienced user in an intuitive way through all the necessary steps to build de-novo transcriptome assemblies using readily available software and is freely available at: https://github.com/biomendi/TRANSCRIPTOME-ASSEMBLY-PIPELINE/wiki.

  14. Evolution of circadian organization in vertebrates

    Directory of Open Access Journals (Sweden)

    M. Menaker

    1997-03-01

    Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

  15. The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates.

    Science.gov (United States)

    Zhang, Jiannan; Wan, Yiping; Fang, Chao; Chen, Junan; Ouyang, Wangan; Li, Juan; Wang, Yajun

    2018-06-22

    G protein-coupled receptor 25 (GPR25) is an orphan G protein-coupled receptor in vertebrates, that has been implicated to be associated with autoimmune diseases and regulate blood pressure in humans. However, the endogenous ligand of GPR25 remains unknown in vertebrates. Here, we reported that in non-mammalian vertebrates (zebrafish, spotted gars, and pigeons), GPR25 could be activated by Apelin and Apela peptides, which are also the two endogenous ligands of vertebrate Apelin receptor (APLNR). Using the pGL3-CRE-luciferase reporter assay and confocal microscopy, we first demonstrated that like APLNR, zebrafish GPR25 expressing in HEK293 cells could be effectively activated by zebrafish Apelin and Apela peptides, leading to the inhibition of forskolin-stimulated cAMP production and receptor internalization. Like zebrafish GPR25, pigeon and spotted gar GPR25 could also be activated by Apelin and Apela, and their activation could inhibit forskolin-induced cAMP accumulation. Interestingly, unlike zebrafish (/spotted gar/pigeon) GPR25, human GPR25 could not be activated by Apelin and Apela under the same experimental conditions. RNA-seq analysis further revealed that GPR25 is expressed in a variety of tissues, including the testes and intestine of zebrafish/spotted gars/humans, implying the potential roles of GPR25 signaling in many physiological processes in vertebrates. Taken together, our data not only provides the first proof that the orphan receptor GPR25 possesses two potential ligands 'Apelin and Apela' and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Chemical sporulation and germination: cytoprotective nanocoating of individual mammalian cells with a degradable tannic acid-FeIII complex

    Science.gov (United States)

    Lee, Juno; Cho, Hyeoncheol; Choi, Jinsu; Kim, Doyeon; Hong, Daewha; Park, Ji Hun; Yang, Sung Ho; Choi, Insung S.

    2015-11-01

    Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature.Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature. Electronic supplementary information (ESI) available: Experimental details, LSCM images, and SEM and TEM images. See DOI: 10.1039/c5nr05573c

  17. Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra.

    Science.gov (United States)

    Alexandrova, Olga; Solovei, Irina; Cremer, Thomas; David, Charles N

    2003-12-01

    To investigate the evolutionary conservation of higher order nuclear architecture previously described for mammalian cells we have analyzed the nuclear architecture of the simple polyp Hydra. These diploblastic organisms have large nuclei (8-10 microm) containing about 3x10(9) bp of DNA organized in 15 chromosome pairs. They belong to the earliest metazoan phylum and are separated from mammals by at least 600 million years. Single and double pulse labeling with halogenated nucleotides (bromodeoxyuridine, iododeoxyuridine and chlorodeoxyuridine) revealed striking similarities to the known sequence of replication labeling patterns in mammalian nuclei. These patterns reflect a persistent nuclear arrangement of early, mid-, and late replicating chromatin foci that could be identified during all stages of interphase over at least 5-10 cell generations. Segregation of labeled chromatids led after several cell divisions to nuclei with single or a few labeled chromosome territories. In such nuclei distinct clusters of labeled chromatin foci were separated by extended nuclear areas with non-labeled chromatin, which is typical of a territorial arrangement of interphase chromosomes. Our results indicate the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals and suggest the existence of conserved mechanism(s) controlling this architecture.

  18. Wnt/β-catenin signaling in adult mammalian epithelial stem cells

    NARCIS (Netherlands)

    Kretzschmar, Kai; Clevers, Hans

    2017-01-01

    Adult stem cells self-renew and replenish differentiated cells in various organs and tissues throughout a mammal's life. Over the last 25 years an ever-growing body of knowledge has unraveled the essential regulation of adult mammalian epithelia by the canonical Wnt signaling with its key

  19. Lean management in a non-manufacturing organization

    Directory of Open Access Journals (Sweden)

    Mladen Žvorc

    2013-12-01

    Full Text Available This paper examines the possibilities of a lean approach to non-manufacturing functions, i.e. a market-oriented organization. This refers to purchasing, shipment, storage, sale and delivery of goods; marketing, etc. A lean approach to business operations is discussed and several lean business methods are developed on the basis of which lean management can be used not only in manufacturing, but also in non-manufacturing organizations.

  20. Incorporation of nanoparticles within mammalian spermatozoa using in vitro capacitation

    Science.gov (United States)

    There is still much unknown about the journey of spermatozoa within the female genital tract. Recent studies have investigated mammalian spermatozoa labeling with fluorescent quantum dot nanoparticles (QD) for non-invasive imaging. Furthermore, the incorporation of these QD within the spermatozoa ma...

  1. Development of revolutionizing biomaterials substituting various mammalian organs by means of sintered bioceramics

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, T. [West Saitama National Central Hospital, Tokorozawa (Japan); Hirota, K. [National Inst. for Research in Inorganic Materials Tsukuba, Ibaraki (Japan); Nishihara, K. [Tokyo Univ. (Japan). Dept. of Oral Surgery

    2001-07-01

    Development of biomaterials substituting various mammalian organs can be carried out by means of experimental evolutionary studies using collagen -hydroxyapatite composite, derived from adult cattle. The revolution of the tissue-immune system can be studies by compound-ceramics of collagen-hydroxyapatite composite. Collagen-hydroxyapatite composite was sintered by high-pressure technique using collagen extracted from cattle skin, which had antigenicity. Artificial bone marrow chambers were fabricated with the sintered collagen-hydroxyapatite composite. Experimental evolutionary studies using mammals (dogs) and chondrichthyes (sharks) were carried out implanting the chambers into their muscles. The result showed that around the collagen composed chambers implanted into dorsal muscle of dogs, marked cell differentiation as well as dedifferentiation with atypia could be observed, which resembled a part the digestive tract of intestine histologically. Around the chambers implanted into dorsal muscle of sharks hemopoietic nests could be observed, which were quite similar to those induced by the chambers of conventionally sintered hydroxyapatite. Hemopoiesis and osteoid formation 4 months after surgery were observed around the collagen-apatite chamber implanted in the shark muscle as well as in upper site of vertebral cartilage of the spinal cord. No bone marrow in the cartilaginous tissue in upper site of the spinal cord is evident in control sharks. Xenotransplantation of skin, i.e., skin grafts between sharks of different kinds of species, as well as between sharks and xenopus (amphibian), sharks and mammals (rat) are carried out. All of them are successful and chimera placoids between them are developed. After that, the author successfully carried out xenotransplantation of various organs of chondrichthyes into those of dogs. (orig.)

  2. Modality-Based Organization of Ascending Somatosensory Axons in the Direct Dorsal Column Pathway

    Science.gov (United States)

    Niu, Jingwen; Ding, Long; Li, Jian J.; Kim, Hyukmin; Liu, Jiakun; Li, Haipeng; Moberly, Andrew; Badea, Tudor C.; Duncan, Ian D.; Son, Young-Jin; Scherer, Steven S.

    2013-01-01

    The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the “somatotopic map” model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial–lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough “somatotopic map” was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway. PMID:24198362

  3. A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

    Science.gov (United States)

    Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

    2007-10-01

    Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase.

  4. Engineered Trehalose Permeable to Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Alireza Abazari

    Full Text Available Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre and trehalose tetraacetate (4-O-Ac-Tre. Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies.

  5. Using phylogenetically-informed annotation (PIA) to search for light-interacting genes in transcriptomes from non-model organisms.

    Science.gov (United States)

    Speiser, Daniel I; Pankey, M Sabrina; Zaharoff, Alexander K; Battelle, Barbara A; Bracken-Grissom, Heather D; Breinholt, Jesse W; Bybee, Seth M; Cronin, Thomas W; Garm, Anders; Lindgren, Annie R; Patel, Nipam H; Porter, Megan L; Protas, Meredith E; Rivera, Ajna S; Serb, Jeanne M; Zigler, Kirk S; Crandall, Keith A; Oakley, Todd H

    2014-11-19

    Tools for high throughput sequencing and de novo assembly make the analysis of transcriptomes (i.e. the suite of genes expressed in a tissue) feasible for almost any organism. Yet a challenge for biologists is that it can be difficult to assign identities to gene sequences, especially from non-model organisms. Phylogenetic analyses are one useful method for assigning identities to these sequences, but such methods tend to be time-consuming because of the need to re-calculate trees for every gene of interest and each time a new data set is analyzed. In response, we employed existing tools for phylogenetic analysis to produce a computationally efficient, tree-based approach for annotating transcriptomes or new genomes that we term Phylogenetically-Informed Annotation (PIA), which places uncharacterized genes into pre-calculated phylogenies of gene families. We generated maximum likelihood trees for 109 genes from a Light Interaction Toolkit (LIT), a collection of genes that underlie the function or development of light-interacting structures in metazoans. To do so, we searched protein sequences predicted from 29 fully-sequenced genomes and built trees using tools for phylogenetic analysis in the Osiris package of Galaxy (an open-source workflow management system). Next, to rapidly annotate transcriptomes from organisms that lack sequenced genomes, we repurposed a maximum likelihood-based Evolutionary Placement Algorithm (implemented in RAxML) to place sequences of potential LIT genes on to our pre-calculated gene trees. Finally, we implemented PIA in Galaxy and used it to search for LIT genes in 28 newly-sequenced transcriptomes from the light-interacting tissues of a range of cephalopod mollusks, arthropods, and cubozoan cnidarians. Our new trees for LIT genes are available on the Bitbucket public repository ( http://bitbucket.org/osiris_phylogenetics/pia/ ) and we demonstrate PIA on a publicly-accessible web server ( http://galaxy-dev.cnsi.ucsb.edu/pia/ ). Our new

  6. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system

    Science.gov (United States)

    Kaplan, Bernhard A.; Lansner, Anders

    2014-01-01

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin–Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian–Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian–Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures. PMID

  7. A conceptual model for supporting para-teacher learning in an Indian non-governmental organization.

    NARCIS (Netherlands)

    Raval, Harini; McKenney, Susan; Pieters, Julius Marie

    2010-01-01

    Non-governmental organizations (NGOs) are being recognized globally for their influential role in realizing the UN Millennium Development Goal of education for all in developing countries. NGOs mostly employ untrained para-educators for grassroots activities. The professional development of these

  8. Comparison of amphibian and mammalian thyroperoxidase ...

    Science.gov (United States)

    Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

  9. DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms.

    Science.gov (United States)

    Frías-López, Cristina; Sánchez-Herrero, José F; Guirao-Rico, Sara; Mora, Elisa; Arnedo, Miquel A; Sánchez-Gracia, Alejandro; Rozas, Julio

    2016-12-15

    The development of molecular markers is one of the most important challenges in phylogenetic and genome wide population genetics studies, especially in studies with non-model organisms. A highly promising approach for obtaining suitable markers is the utilization of genomic partitioning strategies for the simultaneous discovery and genotyping of a large number of markers. Unfortunately, not all markers obtained from these strategies provide enough information for solving multiple evolutionary questions at a reasonable taxonomic resolution. We have developed Development Of Molecular markers In Non-model Organisms (DOMINO), a bioinformatics tool for informative marker development from both next generation sequencing (NGS) data and pre-computed sequence alignments. The application implements popular NGS tools with new utilities in a highly versatile pipeline specifically designed to discover or select personalized markers at different levels of taxonomic resolution. These markers can be directly used to study the taxa surveyed for their design, utilized for further downstream PCR amplification in a broader set taxonomic scope, or exploited as suitable templates to bait design for target DNA enrichment techniques. We conducted an exhaustive evaluation of the performance of DOMINO via computer simulations and illustrate its utility to find informative markers in an empirical dataset. DOMINO is freely available from www.ub.edu/softevol/domino CONTACT: elsanchez@ub.edu or jrozas@ub.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Large Mammalian Animal Models of Heart Disease

    Directory of Open Access Journals (Sweden)

    Paula Camacho

    2016-10-01

    Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.

  11. Habituation in non-neural organisms: evidence from slime moulds

    OpenAIRE

    Boisseau, Romain P.; Vogel, David; Dussutour, Audrey

    2016-01-01

    Learning, defined as a change in behaviour evoked by experience, has hitherto been investigated almost exclusively in multicellular neural organisms. Evidence for learning in non-neural multicellular organisms is scant, and only a few unequivocal reports of learning have been described in single-celled organisms. Here we demonstrate habituation, an unmistakable form of learning, in the non-neural organism Physarum polycephalum. In our experiment, using chemotaxis as the behavioural output and...

  12. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  13. Modeling self-organization of novel organic materials

    Science.gov (United States)

    Sayar, Mehmet

    In this thesis, the structural organization of oligomeric multi-block molecules is analyzed by computational analysis of coarse-grained models. These molecules form nanostructures with different dimensionalities, and the nanostructured nature of these materials leads to novel structural properties at different length scales. Previously, a number of oligomeric triblock rodcoil molecules have been shown to self-organize into mushroom shaped noncentrosymmetric nanostructures. Interestingly, thin films of these molecules contain polar domains and a finite macroscopic polarization. However, the fully polarized state is not the equilibrium state. In the first chapter, by solving a model with dipolar and Ising-like short range interactions, we show that polar domains are stable in films composed of aggregates as opposed to isolated molecules. Unlike classical molecular systems, these nanoaggregates have large intralayer spacings (a ≈ 6 nm), leading to a reduction in the repulsive dipolar interactions that oppose polar order within layers. This enables the formation of a striped pattern with polar domains of alternating directions. The energies of the possible structures at zero temperature are computed exactly and results of Monte Carlo simulations are provided at non-zero temperatures. In the second chapter, the macroscopic polarization of such nanostructured films is analyzed in the presence of a short range surface interaction. The surface interaction leads to a periodic domain structure where the balance between the up and down domains is broken, and therefore films of finite thickness have a net macroscopic polarization. The polarization per unit volume is a function of film thickness and strength of the surface interaction. Finally, in chapter three, self-organization of organic molecules into a network of one dimensional objects is analyzed. Multi-block organic dendron rodcoil molecules were found to self-organize into supramolecular nanoribbons (threads) and

  14. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Science.gov (United States)

    Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

    2007-07-27

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  15. Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity

    DEFF Research Database (Denmark)

    Kiehn, O.; Johnson, B. R.; Raastad, M.

    1996-01-01

    We examined the organization of spinal networks controlling locomotion in the isolated spinal cord of the neonatal rat, and in this study we provide the first demonstration of plateau and bursting mechanisms in mammalian interneurons that show locomotor-related activity. Using tight-seal whole...

  16. Leadership in Mammalian Societies: Emergence, Distribution, Power, and Payoff.

    Science.gov (United States)

    Smith, Jennifer E; Gavrilets, Sergey; Mulder, Monique Borgerhoff; Hooper, Paul L; Mouden, Claire El; Nettle, Daniel; Hauert, Christoph; Hill, Kim; Perry, Susan; Pusey, Anne E; van Vugt, Mark; Smith, Eric Alden

    2016-01-01

    Leadership is an active area of research in both the biological and social sciences. This review provides a transdisciplinary synthesis of biological and social-science views of leadership from an evolutionary perspective, and examines patterns of leadership in a set of small-scale human and non-human mammalian societies. We review empirical and theoretical work on leadership in four domains: movement, food acquisition, within-group conflict mediation, and between-group interactions. We categorize patterns of variation in leadership in five dimensions: distribution (across individuals), emergence (achieved versus inherited), power, relative payoff to leadership, and generality (across domains). We find that human leadership exhibits commonalities with and differences from the broader mammalian pattern, raising interesting theoretical and empirical issues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

    Science.gov (United States)

    Cassone, V M; Speh, J C; Card, J P; Moore, R Y

    1988-01-01

    A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

  18. Managing the effects of cultural diversity in HR in a non profit organization, Case organization: Moniheli

    OpenAIRE

    Irfan, Muhammad

    2014-01-01

    Non-profit organizations traditionally operate within limited resources. They cannot spend much of their resources to increase motivation. Especially when the bigger goal of the organization is to promote cultural diversity in society, it is very interesting to observe how a non-profit organization manages the cultural diversity that exists within its own human resources. This report is an attempt to identify the ways through which the case organization Moniheli, a non-profit network of diffe...

  19. Checking the Pulse of Vitamin A Metabolism and Signaling during Mammalian Spermatogenesis

    Directory of Open Access Journals (Sweden)

    Travis Kent

    2014-03-01

    Full Text Available Vitamin A has been shown to be essential for a multitude of biological processes vital for mammalian development and homeostasis. Its active metabolite, retinoic acid (RA, is important for establishing and maintaining proper germ cell development. During spermatogenesis, the germ cells orient themselves in very distinct patterns, which have been organized into stages. There is evidence to show that, in the mouse, RA is needed for many steps during germ cell development. Interestingly, RA has been implicated as playing a role within the same two Stages: VII and VIII, where meiosis is initiated and spermiation occurs. The goal of this review is to outline this evidence, exploring the relevant players in retinoid metabolism, storage, transport, and signaling. Finally, this review will provide a potential model for how RA activity is organized across the murine stages of the spermatogenic cycle.

  20. Improving transcriptome construction in non-model organisms: integrating manual and automated gene definition in Emiliania huxleyi.

    Science.gov (United States)

    Feldmesser, Ester; Rosenwasser, Shilo; Vardi, Assaf; Ben-Dor, Shifra

    2014-02-22

    The advent of Next Generation Sequencing technologies and corresponding bioinformatics tools allows the definition of transcriptomes in non-model organisms. Non-model organisms are of great ecological and biotechnological significance, and consequently the understanding of their unique metabolic pathways is essential. Several methods that integrate de novo assembly with genome-based assembly have been proposed. Yet, there are many open challenges in defining genes, particularly where genomes are not available or incomplete. Despite the large numbers of transcriptome assemblies that have been performed, quality control of the transcript building process, particularly on the protein level, is rarely performed if ever. To test and improve the quality of the automated transcriptome reconstruction, we used manually defined and curated genes, several of them experimentally validated. Several approaches to transcript construction were utilized, based on the available data: a draft genome, high quality RNAseq reads, and ESTs. In order to maximize the contribution of the various data, we integrated methods including de novo and genome based assembly, as well as EST clustering. After each step a set of manually curated genes was used for quality assessment of the transcripts. The interplay between the automated pipeline and the quality control indicated which additional processes were required to improve the transcriptome reconstruction. We discovered that E. huxleyi has a very high percentage of non-canonical splice junctions, and relatively high rates of intron retention, which caused unique issues with the currently available tools. While individual tools missed genes and artificially joined overlapping transcripts, combining the results of several tools improved the completeness and quality considerably. The final collection, created from the integration of several quality control and improvement rounds, was compared to the manually defined set both on the DNA and

  1. Mammalian amyloidogenic proteins promote prion nucleation in yeast.

    Science.gov (United States)

    Chandramowlishwaran, Pavithra; Sun, Meng; Casey, Kristin L; Romanyuk, Andrey V; Grizel, Anastasiya V; Sopova, Julia V; Rubel, Aleksandr A; Nussbaum-Krammer, Carmen; Vorberg, Ina M; Chernoff, Yury O

    2018-03-02

    Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and the expression of a mammalian amyloidogenic protein that is not fused to the Sup35 prion domain failed to promote prion nucleation, further indicating that physical linkage of a mammalian amyloidogenic protein to the prion domain of a yeast protein is required for the nucleation of a yeast prion. Biochemical and cytological approaches confirmed the nucleation of protein aggregates in the yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of human amyloid-β (associated with Alzheimer's disease) and mouse prion protein (associated with prion diseases), respectively, antagonized or enhanced nucleation of a yeast prion by these proteins. The yeast-based prion nucleation assay, developed in our work, can be employed for mutational dissection of amyloidogenic proteins. We anticipate that it will aid in the identification of chemicals that influence initial amyloid nucleation and in searching for new amyloidogenic proteins in a variety of proteomes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Mammalian designer cells: Engineering principles and biomedical applications.

    Science.gov (United States)

    Xie, Mingqi; Fussenegger, Martin

    2015-07-01

    Biotechnology is a widely interdisciplinary field focusing on the use of living cells or organisms to solve established problems in medicine, food production and agriculture. Synthetic biology, the science of engineering complex biological systems that do not exist in nature, continues to provide the biotechnology industry with tools, technologies and intellectual property leading to improved cellular performance. One key aspect of synthetic biology is the engineering of deliberately reprogrammed designer cells whose behavior can be controlled over time and space. This review discusses the most commonly used techniques to engineer mammalian designer cells; while control elements acting on the transcriptional and translational levels of target gene expression determine the kinetic and dynamic profiles, coupling them to a variety of extracellular stimuli permits their remote control with user-defined trigger signals. Designer mammalian cells with novel or improved biological functions not only directly improve the production efficiency during biopharmaceutical manufacturing but also open the door for cell-based treatment strategies in molecular and translational medicine. In the future, the rational combination of multiple sets of designer cells could permit the construction and regulation of higher-order systems with increased complexity, thereby enabling the molecular reprogramming of tissues, organisms or even populations with highest precision. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

    Science.gov (United States)

    Lyu, Zhe; Whitman, William B

    2017-01-01

    Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

  4. Organic non-aqueous cation-based redox flow batteries

    Science.gov (United States)

    Zhang, Lu; Huang, Jinhua; Burrell, Anthony

    2018-05-08

    The present invention provides a non-aqueous redox flow battery comprising a negative electrode immersed in a non-aqueous liquid negative electrolyte, a positive electrode immersed in a non-aqueous liquid positive electrolyte, and a cation-permeable separator (e.g., a porous membrane, film, sheet, or panel) between the negative electrolyte from the positive electrolyte. During charging and discharging, the electrolytes are circulated over their respective electrodes. The electrolytes each comprise an electrolyte salt (e.g., a lithium or sodium salt), a transition-metal free redox reactant, and optionally an electrochemically stable organic solvent. Each redox reactant is selected from an organic compound comprising a conjugated unsaturated moiety, a boron cluster compound, and a combination thereof. The organic redox reactant of the positive electrolyte comprises a tetrafluorohydroquinone ether compound or a tetrafluorocatechol ether compound.

  5. Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

  6. Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

    Science.gov (United States)

    Morawski, M; Brückner, G; Jäger, C; Seeger, G; Künzle, H; Arendt, T

    2010-02-03

    The Madagascan tenrecs (Afrotheria), an ancient mammalian clade, are characterized by unique brain anatomy. Striking features are an expanded paleocortex but a small and poorly differentiated neocortex devoid of a distinct granular layer IV. To investigate the organization of cortical areas we analyzed extracellular matrix components in perineuronal nets (PNs) using antibodies to aggrecan, lectin staining and hyaluronan-binding protein. Selected subcortical regions were studied to correlate the cortical patterns with features in evolutionary conserved systems. In the neocortex, paleocortex and hippocampus PNs were associated with nonpyramidal neurons. Quantitative analysis in the cerebral cortex revealed area-specific proportions and laminar distribution patterns of neurons ensheathed by PNs. Cortical PNs showed divergent structural phenotypes. Diffuse PNs forming a cotton wool-like perisomatic rim were characteristic of the paleocortex. These PNs were associated with a dense pericellular plexus of calretinin-immunoreactive fibres. Clearly contoured PNs were devoid of a calretinin-positive plexus and predominated in the neocortex and hippocampus. The organization of the extracellular matrix in subcortical nuclei followed the widely distributed mammalian type. We conclude that molecular properties of the aggrecan-based extracellular matrix are conserved during evolution of mammals; however, the matrix scaffold is adapted to specific wiring patterns of cortical and subcortical neuronal networks. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Directory of Open Access Journals (Sweden)

    Eleftherios Mylonakis

    2007-07-01

    Full Text Available Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  8. Nanoscale organization of {beta}{sub 2}-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Vobornik, Dusan; Rouleau, Yanouchka; Haley, Jennifer [Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, ON, Canada K1A 0R6 (Canada); Bani-Yaghoub, Mahmud [Institute for Biological Sciences, National Research Council Canada, Ottawa, ON, Canada K1A 0R6 (Canada); Taylor, Rod [Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, ON, Canada K1A 0R6 (Canada); Johnston, Linda J., E-mail: Linda.Johnston@nrc-cnrc.gc.ca [Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, ON, Canada K1A 0R6 (Canada); Pezacki, John Paul, E-mail: John.Pezacki@nrc-cnrc.gc.ca [Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, ON, Canada K1A 0R6 (Canada)

    2009-04-24

    Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize {beta}{sub 2}-adrenergic receptors ({beta}{sub 2}AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the {beta}{sub 2}AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline, the size of domains containing the {beta}{sub 2}AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of {beta}{sub 2}AR are observed in the membrane of the HEK293 cells that stably overexpress {beta}{sub 2}AR-GFP and {beta}{sub 2}AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use {beta}{sub 2}AR-Venus fusion proteins as models for {beta}{sub 2}AR function. These observations are critical for designing future cell models and assays based on {beta}{sub 2}AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.

  9. Organic non-aqueous cation-based redox flow batteries

    Science.gov (United States)

    Jansen, Andrew N.; Vaughey, John T.; Chen, Zonghai; Zhang, Lu; Brushett, Fikile R.

    2016-03-29

    The present invention provides a non-aqueous redox flow battery comprising a negative electrode immersed in a non-aqueous liquid negative electrolyte, a positive electrode immersed in a non-aqueous liquid positive electrolyte, and a cation-permeable separator (e.g., a porous membrane, film, sheet, or panel) between the negative electrolyte from the positive electrolyte. During charging and discharging, the electrolytes are circulated over their respective electrodes. The electrolytes each comprise an electrolyte salt (e.g., a lithium or sodium salt), a transition-metal free redox reactant, and optionally an electrochemically stable organic solvent. Each redox reactant is selected from an organic compound comprising a conjugated unsaturated moiety, a boron cluster compound, and a combination thereof. The organic redox reactant of the positive electrolyte is selected to have a higher redox potential than the redox reactant of the negative electrolyte.

  10. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

    Directory of Open Access Journals (Sweden)

    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

  11. Enhancer evolution across 20 mammalian species

    DEFF Research Database (Denmark)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah

    2015-01-01

    The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

  12. Next-generation phylogeography: a targeted approach for multilocus sequencing of non-model organisms.

    Directory of Open Access Journals (Sweden)

    Jonathan B Puritz

    Full Text Available The field of phylogeography has long since realized the need and utility of incorporating nuclear DNA (nDNA sequences into analyses. However, the use of nDNA sequence data, at the population level, has been hindered by technical laboratory difficulty, sequencing costs, and problematic analytical methods dealing with genotypic sequence data, especially in non-model organisms. Here, we present a method utilizing the 454 GS-FLX Titanium pyrosequencing platform with the capacity to simultaneously sequence two species of sea star (Meridiastra calcar and Parvulastra exigua at five different nDNA loci across 16 different populations of 20 individuals each per species. We compare results from 3 populations with traditional Sanger sequencing based methods, and demonstrate that this next-generation sequencing platform is more time and cost effective and more sensitive to rare variants than Sanger based sequencing. A crucial advantage is that the high coverage of clonally amplified sequences simplifies haplotype determination, even in highly polymorphic species. This targeted next-generation approach can greatly increase the use of nDNA sequence loci in phylogeographic and population genetic studies by mitigating many of the time, cost, and analytical issues associated with highly polymorphic, diploid sequence markers.

  13. On the origins of the universal dynamics of endogenous granules in mammalian cells.

    Science.gov (United States)

    Vanapalli, Siva A; Li, Yixuan; Mugele, Frieder; Duits, Michel H G

    2009-12-01

    Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics--both of which are crucial for the interpretation of the results from MPTM technique--are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms--molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dynamics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.

  14. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  15. Fossilized Mammalian Erythrocytes Associated With a Tick Reveal Ancient Piroplasms.

    Science.gov (United States)

    Poinar, George

    2017-07-01

    Ticks transmit a variety of pathogenic organisms to vertebrates, especially mammals. The fossil record of such associations is extremely rare. An engorged nymphal tick of the genus Ambylomma in Dominican amber was surrounded by erythrocytes from its mammalian host. Some of the exposed erythrocytes contained developmental stages of a hemoprotozoan resembling members of the Order Piroplasmida. The fossil piroplasm is described, its stages compared with those of extant piroplasms, and reasons provided why the mammalian host could have been a primate. The parasites were also found in the gut epithelial cells and body cavity of the fossil tick. Aside from providing the first fossil mammalian red blood cells and the first fossil intraerythrocytic hemoparasites, the present discovery shows that tick-piroplasm associations were already well established in the Tertiary. This discovery provides a timescale that can be used in future studies on the evolution of the Piroplasmida. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com Version of Record, first published online March 20, 2017 with fixed content and layout in compliance with Art. 8.1.3.2 ICZN.

  16. Saccharomyces cerevisiae as a model organism: a comparative study.

    Directory of Open Access Journals (Sweden)

    Hiren Karathia

    Full Text Available BACKGROUND: Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes. CONCLUSIONS/SIGNIFICANCE: The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.

  17. Moving epithelia: Tracking the fate of mammalian limbal epithelial stem cells.

    Science.gov (United States)

    Di Girolamo, Nick

    2015-09-01

    Lineage tracing allows the destiny of a stem cell (SC) and its progeny to be followed through time. In order to track their long-term fate, SC must be permanently marked to discern their distribution, division, displacement and differentiation. This information is essential for unravelling the mysteries that govern their replenishing activity while they remain anchored within their niche microenvironment. Modern-day lineage tracing uses inducible genetic recombination to illuminate cells within embryonic, newborn and adult tissues, and the advent of powerful high-resolution microscopy has enabled the behaviour of labelled cells to be monitored in real-time in a living organism. The simple structural organization of the mammalian cornea, including its accessibility and transparency, renders it the ideal tissue to study SC fate using lineage tracing assisted by non-invasive intravital microscopy. Despite more than a century of research devoted to understanding how this tissue is maintained and repaired, many limitations and controversies continue to plague the field, including uncertainties about the specificity of current SC markers, the number of SC within the cornea, their mode of division, their location, and importantly the signals that dictate cell migration. This communication will highlight historical discoveries as well as recent developments in the corneal SC field; more specifically how the progeny of these cells are mobilised to replenish this dynamic tissue during steady-state, disease and transplantation. Also discussed is how insights gleaned from animal studies can be used to advance our knowledge of the fundamental mechanisms that govern modelling and remodelling of the human cornea in health and disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Mycobacterium bovis infections in domesticated non-bovine mammalian species. Part 1: Review of epidemiology and laboratory submissions in Great Britain 2004-2010.

    Science.gov (United States)

    Broughan, J M; Downs, S H; Crawshaw, T R; Upton, P A; Brewer, J; Clifton-Hadley, R S

    2013-11-01

    Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), can infect a broad range of mammalian species in addition to domestic and feral cattle and badgers. Since legislation introduced in 2006 in Great Britain requires animal keepers, meat inspectors and veterinarians to notify the authorities of suspect bTB lesions or the isolation of M. bovis in any mammal excluding humans, the organism has been increasingly identified in domestic species other than cattle. Although in most cases 'spill-over' hosts, these remain a potential source of infection for cattle, wildlife, and possibly humans. In this first part of a two-part review of M. bovis infections in non-bovine domestic species, current knowledge of the epidemiology of such infections is presented along with novel data relating to diagnostic submissions for mycobacterial culture between 2004 and 2010. Over this period M. bovis infection was identified in 116 cats, 7 dogs, 34 llamas, 133 alpacas, 35 goats, 24 sheep and 85 pigs and wild boar. The risk that such infections pose to the control of bTB, and as zoonoses, is discussed. In part two, the options available to diagnose bTB in these species, as well as the challenges posed to disease detection and control will be discussed in depth. Copyright © 2013. Published by Elsevier Ltd.

  19. A global organism detection and monitoring system for non-native species

    Science.gov (United States)

    Graham, J.; Newman, G.; Jarnevich, C.; Shory, R.; Stohlgren, T.J.

    2007-01-01

    Harmful invasive non-native species are a significant threat to native species and ecosystems, and the costs associated with non-native species in the United States is estimated at over $120 Billion/year. While some local or regional databases exist for some taxonomic groups, there are no effective geographic databases designed to detect and monitor all species of non-native plants, animals, and pathogens. We developed a web-based solution called the Global Organism Detection and Monitoring (GODM) system to provide real-time data from a broad spectrum of users on the distribution and abundance of non-native species, including attributes of their habitats for predictive spatial modeling of current and potential distributions. The four major subsystems of GODM provide dynamic links between the organism data, web pages, spatial data, and modeling capabilities. The core survey database tables for recording invasive species survey data are organized into three categories: "Where, Who & When, and What." Organisms are identified with Taxonomic Serial Numbers from the Integrated Taxonomic Information System. To allow users to immediately see a map of their data combined with other user's data, a custom geographic information system (GIS) Internet solution was required. The GIS solution provides an unprecedented level of flexibility in database access, allowing users to display maps of invasive species distributions or abundances based on various criteria including taxonomic classification (i.e., phylum or division, order, class, family, genus, species, subspecies, and variety), a specific project, a range of dates, and a range of attributes (percent cover, age, height, sex, weight). This is a significant paradigm shift from "map servers" to true Internet-based GIS solutions. The remainder of the system was created with a mix of commercial products, open source software, and custom software. Custom GIS libraries were created where required for processing large datasets

  20. Development Of International Non-Governmental Organizations And Legal Traditions Of Russia

    OpenAIRE

    Alexandra A. Dorskaya

    2015-01-01

    The article examines the role of international non-governmental organizations in the maintenance and creation of a positive attitude to national legal traditions. The basic stages of development of international non-governmental organizations. Analyzed their advantages and disadvantages. Considered as the legal traditions of the Russian society are reflected in the activities of legal entities and individuals - members of international non-governmental organizations.

  1. The Transcriptome Analysis and Comparison Explorer--T-ACE: a platform-independent, graphical tool to process large RNAseq datasets of non-model organisms.

    Science.gov (United States)

    Philipp, E E R; Kraemer, L; Mountfort, D; Schilhabel, M; Schreiber, S; Rosenstiel, P

    2012-03-15

    Next generation sequencing (NGS) technologies allow a rapid and cost-effective compilation of large RNA sequence datasets in model and non-model organisms. However, the storage and analysis of transcriptome information from different NGS platforms is still a significant bottleneck, leading to a delay in data dissemination and subsequent biological understanding. Especially database interfaces with transcriptome analysis modules going beyond mere read counts are missing. Here, we present the Transcriptome Analysis and Comparison Explorer (T-ACE), a tool designed for the organization and analysis of large sequence datasets, and especially suited for transcriptome projects of non-model organisms with little or no a priori sequence information. T-ACE offers a TCL-based interface, which accesses a PostgreSQL database via a php-script. Within T-ACE, information belonging to single sequences or contigs, such as annotation or read coverage, is linked to the respective sequence and immediately accessible. Sequences and assigned information can be searched via keyword- or BLAST-search. Additionally, T-ACE provides within and between transcriptome analysis modules on the level of expression, GO terms, KEGG pathways and protein domains. Results are visualized and can be easily exported for external analysis. We developed T-ACE for laboratory environments, which have only a limited amount of bioinformatics support, and for collaborative projects in which different partners work on the same dataset from different locations or platforms (Windows/Linux/MacOS). For laboratories with some experience in bioinformatics and programming, the low complexity of the database structure and open-source code provides a framework that can be customized according to the different needs of the user and transcriptome project.

  2. Dynamics of radioecological and genetic processes in populations of mammalian model species at contamination of ecosystems

    International Nuclear Information System (INIS)

    Ryabokon', N.I.; Goncharova, R.I.

    2008-01-01

    A short review of data on the time course of radiobiological and genetic processes in natural populations of mammalian model species inhabiting radiocontaminated ecosystems over many generations is presented here. The described time-courses of biological end-points in these populations do not reflect the time course of the whole-body dose rates, but do the outcome of multiple processes, including the direct response to individual irradiation, the transgeneration transmission and accumulation of induced damages and the development of adaptation. (authors)

  3. Development Of International Non-Governmental Organizations And Legal Traditions Of Russia

    Directory of Open Access Journals (Sweden)

    Alexandra A. Dorskaya

    2015-06-01

    Full Text Available The article examines the role of international non-governmental organizations in the maintenance and creation of a positive attitude to national legal traditions. The basic stages of development of international non-governmental organizations. Analyzed their advantages and disadvantages. Considered as the legal traditions of the Russian society are reflected in the activities of legal entities and individuals - members of international non-governmental organizations.

  4. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  5. Computational and Statistical Analyses of Insertional Polymorphic Endogenous Retroviruses in a Non-Model Organism

    Directory of Open Access Journals (Sweden)

    Le Bao

    2014-11-01

    Full Text Available Endogenous retroviruses (ERVs are a class of transposable elements found in all vertebrate genomes that contribute substantially to genomic functional and structural diversity. A host species acquires an ERV when an exogenous retrovirus infects a germ cell of an individual and becomes part of the genome inherited by viable progeny. ERVs that colonized ancestral lineages are fixed in contemporary species. However, in some extant species, ERV colonization is ongoing, which results in variation in ERV frequency in the population. To study the consequences of ERV colonization of a host genome, methods are needed to assign each ERV to a location in a species’ genome and determine which individuals have acquired each ERV by descent. Because well annotated reference genomes are not widely available for all species, de novo clustering approaches provide an alternative to reference mapping that are insensitive to differences between query and reference and that are amenable to mobile element studies in both model and non-model organisms. However, there is substantial uncertainty in both identifying ERV genomic position and assigning each unique ERV integration site to individuals in a population. We present an analysis suitable for detecting ERV integration sites in species without the need for a reference genome. Our approach is based on improved de novo clustering methods and statistical models that take the uncertainty of assignment into account and yield a probability matrix of shared ERV integration sites among individuals. We demonstrate that polymorphic integrations of a recently identified endogenous retrovirus in deer reflect contemporary relationships among individuals and populations.

  6. Non-pharmacological modulation of cerebral white matter organization

    DEFF Research Database (Denmark)

    Kristensen, Tina D; Mandl, Rene C W; Jepsen, Jens R M

    2018-01-01

    OBJECTIVE: Neuroplasticity is a well-described phenomenon, but effects of non-pharmacological interventions on white matter (WM) are unclear. Here we review associations between active non-pharmacological interventions and WM organization in healthy subjects and in psychiatric patients. METHOD...

  7. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.

    2011-01-21

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.

  8. Rapid transcriptome and proteome profiling of a non-model marine invertebrate, Bugula neritina

    KAUST Repository

    Wang, Hao

    2010-06-10

    Non-model organisms represent the majority of life forms in our planet. However, the lack of genetic information hinders us to understand the unique biological phenomena in non-model organisms at the molecular level. In this study, we applied a tandem transcriptome and proteome profiling on a non-model marine fouling organism, Bugula neritina. Using a 454 pyrosequencing platform with the updated titanium reagents, we generated a total of 48M bp transcriptome data consisting of 131 450 high-quality reads. Of these, 122 650 reads (93%) were assembled to produce 6392 contigs with an average length of 538 bases and the remaining 8800 reads were singletons. Of the total 15 192 unigenes, 13 863 ORFs were predicated, of which 6917 were functionally annotated based on gene ontology and eukaryotic orthologous groups. Subsequent proteome analysis identified and quantified 882 proteins from B. neritina. These results would provide fundamental and important information for the subsequent studies of molecular mechanism in larval biology, development, antifouling research. Furthermore, we demonstrated, for the first time, the combined use of two high-throughput technologies as a powerful approach for accelerating the studies of non-model but otherwise important species. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

  9. The food additive vanillic acid controls transgene expression in mammalian cells and mice.

    Science.gov (United States)

    Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

    2012-03-01

    Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

  10. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. Mammalian development in space

    Science.gov (United States)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  12. [Ornithine decarboxylase in mammalian organs and tissues at hibernation and artificial hypobiosis].

    Science.gov (United States)

    Logvinovich, O S; Aksenova, G E

    2013-01-01

    Ornithine decarboxylase (ODC, EC 4.1.1.17.) is a short-lived and dynamically regulated enzyme of polyamines biosynthesis. Regulation of functional, metabolic and proliferative state of organs and tissues involves the modifications of the ODC enzymatic activity. The organ-specific changes in ODC activity were revealed in organs and tissues (liver, spleen, bone marrow, kidney, and intestinal mucosa) of hibernating mammals - squirrels Spermophilus undulates - during the hibernating season. At that, a positive correlation was detected between the decline and recovery of the specialized functions of organs and tissues and the respective modifications of ODC activity during hibernation bouts. Investigation of changes in ODC activity in organs and tissues of non-hibernating mammals under artificial hypobiosis showed that in Wistar rats immediately after exposure to hypothermia-hypoxia-hypercapnia (hypobiosis) the level of ODC activity was low in thymus, spleen, small intestine mucosa, neocortex, and liver. The most marked reduction in enzyme activity was observed in actively proliferating tissues: thymus, spleen, small intestine mucosa. In bone marrow of squirrels, while in a state of torpor, as well as in thymus of rats after exposure to hypothermia-hypoxia-hypercapnia, changes in the ODC activity correlated with changes in the rate of cell proliferation (by the criterion of cells distribution over cell cycle). The results obtained, along with the critical analysis of published data, indicate that the ODC enzyme is involved in biochemical adaptation of mammals to natural and artificial hypobiosis. A decline in the ODC enzymatic activity indicates a decline in proliferative, functional, and metabolic activity of organs and tissues of mammals (bone marrow, mucosa of small intestine, thymus, spleen, neocortex, liver, kidneys) when entering the state of hypobiosis.

  13. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Progress is reported on the following research projects: the effects of N-ethyl-maleimide and hydroxyurea on hamster cells in culture; sensitization of synchronized human cells to x rays by N-ethylmaleimide; sensitization of hypoxic mammalian cells with a sulfhydryl inhibitor; damage interaction due to ionizing and nonionizing radiation in mammalian cells; DNA damage relative to radioinduced cell killing; spurious photolability of DNA labeled with methyl- 14 C-thymidine; radioinduced malignant transformation of cultured mouse cells; a comparison of properties of uv and near uv light relative to cell function and DNA damage; Monte Carlo simulation of DNA damage and repair mechanisms; and radiobiology of fast neutrons

  14. Modeling of the transient mobility in disordered organic semiconductors

    NARCIS (Netherlands)

    Germs, W.C.; Van der Holst, J.M.M.; Van Mensfoort, S.L.M.; Bobbert, P.A.; Coehoorn, R.

    2011-01-01

    In non-steady-state experiments, the electrical response of devicesbased on disordered organic semiconductors often shows a large transient contribution due to relaxation of the out-of-equilibrium charge-carrier distribution. We have developed a model describing this process, based only on the

  15. Mammalian sleep dynamics: how diverse features arise from a common physiological framework.

    Directory of Open Access Journals (Sweden)

    Andrew J K Phillips

    2010-06-01

    Full Text Available Mammalian sleep varies widely, ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans. In humans, rats, mice and cats, sleep patterns are orchestrated by homeostatic and circadian drives to the sleep-wake switch, but it is not known whether this system is ubiquitous among mammals. Here, changes of just two parameters in a recent quantitative model of this switch are shown to reproduce typical sleep patterns for 17 species across 7 orders. Furthermore, the parameter variations are found to be consistent with the assumptions that homeostatic production and clearance scale as brain volume and surface area, respectively. Modeling an additional inhibitory connection between sleep-active neuronal populations on opposite sides of the brain generates unihemispheric sleep, providing a testable hypothetical mechanism for this poorly understood phenomenon. Neuromodulation of this connection alone is shown to account for the ability of fur seals to transition between bihemispheric sleep on land and unihemispheric sleep in water. Determining what aspects of mammalian sleep patterns can be explained within a single framework, and are thus universal, is essential to understanding the evolution and function of mammalian sleep. This is the first demonstration of a single model reproducing sleep patterns for multiple different species. These wide-ranging findings suggest that the core physiological mechanisms controlling sleep are common to many mammalian orders, with slight evolutionary modifications accounting for interspecies differences.

  16. DODAB:monoolein-based lipoplexes as non-viral vectors for transfection of mammalian cells.

    Science.gov (United States)

    Silva, J P Neves; Oliveira, A C N; Casal, M P P A; Gomes, A C; Coutinho, P J G; Coutinho, O P; Oliveira, M E C D Real

    2011-10-01

    DNA/Cationic liposome complexes (lipoplexes) have been widely used as non-viral vectors for transfection. Neutral lipids in liposomal formulation are determinant for transfection efficiency using these vectors. In this work, we studied the potential of monoolein (MO) as helper lipid for cellular transfection. Lipoplexes composed of pDNA and dioctadecyldimethylammonium bromide (DODAB)/1-monooleoyl-rac-glycerol (MO) at different molar ratios (4:1, 2:1 and 1:1) and at different cationic lipid/DNA ratios were investigated. The physicochemical properties of the lipoplexes (size, charge and structure), were studied by Dynamic Light Scattering (DLS), Zeta Potential (ζ) and cryo-transmission electron microscopy (cryo-TEM). The effect of MO on pDNA condensation and the effect of heparin and heparan sulphate on the percentage of pDNA release from the lipoplexes were also studied by Ethidium Bromide (EtBr) exclusion assays and electrophoresis. Cytotoxicity and transfection efficiency of these lipoplexes were evaluated using 293T cells and compared with the golden standard helper lipids 1,2-dioleoyl-sn-glycero-3-hosphoethanolamine (DOPE) and cholesterol (Chol) as well as with a commercial transfection agent (Lipofectamine™ LTX). The internalization of transfected fluorescently-labeled pDNA was also visualized using the same cell line. The results demonstrate that the presence of MO not only increases pDNA compactation efficiency, but also affects the physicochemical properties of the lipoplexes, which can interfere with lipoplex-cell interactions. The DODAB:MO formulations tested showed little toxicity and successfully mediated in vitro cell transfection. These results were supported by fluorescence microscopy studies, which illustrated that lipoplexes were able to access the cytosol and deliver pDNA to the nucleus. DODAB:MO-based lipoplexes were thus validated as non-toxic, efficient lipofection vectors for genetic modification of mammalian cells. Understanding the

  17. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

    Science.gov (United States)

    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  18. Understanding and modeling retention of mammalian cells in fluidized bed centrifuges.

    Science.gov (United States)

    Kelly, William; Rubin, Jonathan; Scully, Jennifer; Kamaraju, Hari; Wnukowski, Piotr; Bhatia, Ravinder

    2016-11-01

    Within the last decade, fully disposable centrifuge technologies, fluidized-bed centrifuges (FBC), have been introduced to the biologics industry. The FBC has found a niche in cell therapy where it is used to collect, concentrate, and then wash mammalian cell product while continuously discarding centrate. The goal of this research was to determine optimum FBC conditions for recovery of live cells, and to develop a mathematical model that can assist with process scaleup. Cell losses can occur during bed formation via flow channels within the bed. Experimental results with the kSep400 centrifuge indicate that, for a given volume processed: the bed height (a bed compactness indicator) is affected by RPM and flowrate, and dead cells are selectively removed during operation. To explain these results, two modeling approaches were used: (i) equating the centrifugal and inertial forces on the cells (i.e., a force balance model or FBM) and (ii) a two-phase computational fluid dynamics (CFD) model to predict liquid flow patterns and cell retention in the bowl. Both models predicted bed height vs. time reasonably well, though the CFD model proved more accurate. The flow patterns predicted by CFD indicate a Coriolis-driven flow that enhances uniformity of cells in the bed and may lead to cell losses in the outflow over time. The CFD-predicted loss of viable cells and selective removal of the dead cells generally agreed with experimental trends, but did over-predict dead cell loss by up to 3-fold for some of the conditions. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1520-1530, 2016. © 2016 American Institute of Chemical Engineers.

  19. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

    Science.gov (United States)

    White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

    2006-06-22

    Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

  20. Golgi structure formation, function, and post-translational modifications in mammalian cells.

    Science.gov (United States)

    Huang, Shijiao; Wang, Yanzhuang

    2017-01-01

    The Golgi apparatus is a central membrane organelle for trafficking and post-translational modifications of proteins and lipids in cells. In mammalian cells, it is organized in the form of stacks of tightly aligned flattened cisternae, and dozens of stacks are often linked laterally into a ribbon-like structure located in the perinuclear region of the cell. Proper Golgi functionality requires an intact architecture, yet Golgi structure is dynamically regulated during the cell cycle and under disease conditions. In this review, we summarize our current understanding of the relationship between Golgi structure formation, function, and regulation, with focus on how post-translational modifications including phosphorylation and ubiquitination regulate Golgi structure and on how Golgi unstacking affects its functions, in particular, protein trafficking, glycosylation, and sorting in mammalian cells.

  1. Report of the NASA Mammalian Developmental Biology Working Group

    Science.gov (United States)

    Keefe, J. R.

    1985-01-01

    Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

  2. Traditions and Management Perspectives of Community and Non-Profit Organizations in Lithuania

    Directory of Open Access Journals (Sweden)

    Andrius Stasiukynas

    2015-02-01

    Full Text Available Purpose – To overview the traditions and management perspectives of community and non-profit organizations in Lithuania.Methodology – For the purpose of this research a literature analysis on community and non-profit organization case studies was conducted. The case studies describing stories of success were singled out and leaders of these organizations were interviewed.Findings – The research has showed the growth of the number of community and nonprofit organizations during the last twenty years and the difficulties of collecting the statistical data. This study presupposes the possibility to identify the tendencies of management in community and non-profit organizations, including the following: increasing use of the social networks for communication; proliferation of strategic planning; greater emphasis on educating and empowering new generation of leaders.Research implications – Prior studies in this area in Lithuania have not exhaustively analyzed the components of human resource management of non-profit organizations. An important follow up on this study would be to analyze the human resource management in community organizations.Practical implications – This study covered the management aspects important for the improvement of how community and non-profit organizations work.Originality/Value – This study expands the knowledge on Lithuanian community and non-profit organization development and management.Research type – literature review, research paper.

  3. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    International Nuclear Information System (INIS)

    Campos-Nebel, Marcelo de; Larripa, Irene; Gonzalez-Cid, Marcela

    2008-01-01

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by γH2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU-induced DSB

  4. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Nebel, Marcelo de [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)], E-mail: mnebel@hematologia.anm.edu.ar; Larripa, Irene; Gonzalez-Cid, Marcela [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)

    2008-11-10

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by {gamma}H2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU

  5. Non-classical structures of organic compounds: unusual stereochemistry and hypercoordination

    International Nuclear Information System (INIS)

    Minkin, Vladimir I; Minyaev, Ruslan M; Hoffmann, Roald

    2002-01-01

    Non-classical structures of organic compounds are defined as molecules containing non-tetrahedral tetracoordinate and/or hypercoordinate carbon atoms. The evolution of the views on this subject is considered and the accumulated theoretical and experimental data on the structures and dynamic transformations of non-classical organic compounds are systematised. It is shown that computational analysis using the methods and the software potential of modern quantum chemistry has now acquired high predictive capacity and is the most important source of data on the structures of non-classical compounds. The bibliography includes 227 references.

  6. Greenhouse gas fluxes from agricultural soils under organic and non-organic management — A global meta-analysis

    International Nuclear Information System (INIS)

    Skinner, Colin; Gattinger, Andreas; Muller, Adrian; Mäder, Paul; Fließbach, Andreas; Stolze, Matthias; Ruser, Reiner; Niggli, Urs

    2014-01-01

    It is anticipated that organic farming systems provide benefits concerning soil conservation and climate protection. A literature search on measured soil-derived greenhouse gas (GHG) (nitrous oxide and methane) fluxes under organic and non-organic management from farming system comparisons was conducted and followed by a meta-analysis. Up to date only 19 studies based on field measurements could be retrieved. Based on 12 studies that cover annual measurements, it appeared with a high significance that area-scaled nitrous oxide emissions from organically managed soils are 492 ± 160 kg CO 2 eq. ha −1 a −1 lower than from non-organically managed soils. For arable soils the difference amounts to 497 ± 162 kg CO 2 eq. ha −1 a −1 . However, yield-scaled nitrous oxide emissions are higher by 41 ± 34 kg CO 2 eq. t −1 DM under organic management (arable and use). To equalize this mean difference in yield-scaled nitrous oxide emissions between both farming systems, the yield gap has to be less than 17%. Emissions from conventionally managed soils seemed to be influenced mainly by total N inputs, whereas for organically managed soils other variables such as soil characteristics seemed to be more important. This can be explained by the higher bioavailability of the synthetic N fertilisers in non-organic farming systems while the necessary mineralisation of the N sources under organic management leads to lower and retarded availability. Furthermore, a higher methane uptake of 3.2 ± 2.5 kg CO 2 eq. ha −1 a −1 for arable soils under organic management can be observed. Only one comparative study on rice paddies has been published up to date. All 19 retrieved studies were conducted in the Northern hemisphere under temperate climate. Further GHG flux measurements in farming system comparisons are required to confirm the results and close the existing knowledge gaps. - Highlights: • Lower area-scaled nitrous oxide emissions from soils managed organically compared

  7. Regeneration of hair cells in the mammalian vestibular system.

    Science.gov (United States)

    Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

    2016-06-01

    Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

  8. Novel snake papillomavirus does not cluster with other non-mammalian papillomaviruses.

    Science.gov (United States)

    Lange, Christian E; Favrot, Claude; Ackermann, Mathias; Gull, Jessica; Vetsch, Elisabeth; Tobler, Kurt

    2011-09-12

    Papillomaviruses (PVs) are associated with the development of neoplasias and have been found in several different species, most of them in humans and other mammals. We identified, cloned and sequenced PV DNA from pigmented papilloma-like lesions of a diamond python (Morelia spilota spilota). This represents the first complete PV genome discovered in a Squamata host (MsPV1). It consists of 7048 nt and contains the characteristic open reading (ORF) frames E6, E7, E1, E2, L1 and L2. The L1 ORF sequence showed the highest percentage of sequence identities to human PV5 (57.9%) and Caribbean manatee (Trichechus manatus) PV1 (55.4%), thus, establishing a new clade. According to phylogenetic analysis, the MsPV1 genome clusters with PVs of mammalian rather than sauropsid hosts.

  9. A Laminar Organization for Selective Cortico-Cortical Communication

    Directory of Open Access Journals (Sweden)

    Rinaldo D. D’Souza

    2017-08-01

    Full Text Available The neocortex is central to mammalian cognitive ability, playing critical roles in sensory perception, motor skills and executive function. This thin, layered structure comprises distinct, functionally specialized areas that communicate with each other through the axons of pyramidal neurons. For the hundreds of such cortico-cortical pathways to underlie diverse functions, their cellular and synaptic architectures must differ so that they result in distinct computations at the target projection neurons. In what ways do these pathways differ? By originating and terminating in different laminae, and by selectively targeting specific populations of excitatory and inhibitory neurons, these “interareal” pathways can differentially control the timing and strength of synaptic inputs onto individual neurons, resulting in layer-specific computations. Due to the rapid development in transgenic techniques, the mouse has emerged as a powerful mammalian model for understanding the rules by which cortical circuits organize and function. Here we review our understanding of how cortical lamination constrains long-range communication in the mammalian brain, with an emphasis on the mouse visual cortical network. We discuss the laminar architecture underlying interareal communication, the role of neocortical layers in organizing the balance of excitatory and inhibitory actions, and highlight the structure and function of layer 1 in mouse visual cortex.

  10. Conceptual hierarchical modeling to describe wetland plant community organization

    Science.gov (United States)

    Little, A.M.; Guntenspergen, G.R.; Allen, T.F.H.

    2010-01-01

    Using multivariate analysis, we created a hierarchical modeling process that describes how differently-scaled environmental factors interact to affect wetland-scale plant community organization in a system of small, isolated wetlands on Mount Desert Island, Maine. We followed the procedure: 1) delineate wetland groups using cluster analysis, 2) identify differently scaled environmental gradients using non-metric multidimensional scaling, 3) order gradient hierarchical levels according to spatiotem-poral scale of fluctuation, and 4) assemble hierarchical model using group relationships with ordination axes and post-hoc tests of environmental differences. Using this process, we determined 1) large wetland size and poor surface water chemistry led to the development of shrub fen wetland vegetation, 2) Sphagnum and water chemistry differences affected fen vs. marsh / sedge meadows status within small wetlands, and 3) small-scale hydrologic differences explained transitions between forested vs. non-forested and marsh vs. sedge meadow vegetation. This hierarchical modeling process can help explain how upper level contextual processes constrain biotic community response to lower-level environmental changes. It creates models with more nuanced spatiotemporal complexity than classification and regression tree procedures. Using this process, wetland scientists will be able to generate more generalizable theories of plant community organization, and useful management models. ?? Society of Wetland Scientists 2009.

  11. Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis.

    Science.gov (United States)

    Sorbara, Matthew T; Philpott, Dana J

    2011-09-01

    Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP-1-4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell-autonomous and whole-organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these diverse contexts. © 2011 John Wiley & Sons A/S.

  12. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    International Nuclear Information System (INIS)

    Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

    1991-02-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

  13. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    Science.gov (United States)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  14. Media Compositions for Three-Dimensional Mammalian Tissue Growth under Microgravity Culture Conditions

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor)

    1998-01-01

    Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue.The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  15. Media Compositions for Three Dimensional Mammalian Tissue Growth Under Microgravity Culture Conditions

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor)

    1998-01-01

    Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  16. Role of non-governmental organizations in formation of non-proliferation culture in new independent countries (NIC)

    International Nuclear Information System (INIS)

    Sevchik, M.

    2000-01-01

    Purpose of the report is demonstrate the non-governmental organizations (NGO) role in formation of non-proliferation culture in former Soviet Union. Activity of Center of Non-proliferation Problems Investigation (CNPI) of Monterey Institute of International Investigations and its collaboration with existing in Commonwealth of Independent States (CIS) non-governmental organizations is considered as example. Brief information about CNPI and reasons for it representatives opening of in Kazakhstan and in other CIS-countries, as well as cooperation of NGO in Belarus, Kazakhstan, Russia and Ukraine for creation on Central Asia zone free from nuclear weapon ia given. Some measures which could promote to formation of non-proliferation culture in region are suggested

  17. pEPito: a significantly improved non-viral episomal expression vector for mammalian cells

    Directory of Open Access Journals (Sweden)

    Ogris Manfred

    2010-03-01

    Full Text Available Abstract Background The episomal replication of the prototype vector pEPI-1 depends on a transcription unit starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP and directed into a 2000 bp long matrix attachment region sequence (MARS derived from the human β-interferon gene. The original pEPI-1 vector contains two mammalian transcription units and a total of 305 CpG islands, which are located predominantly within the vector elements necessary for bacterial propagation and known to be counterproductive for persistent long-term transgene expression. Results Here, we report the development of a novel vector pEPito, which is derived from the pEPI-1 plasmid replicon but has considerably improved efficacy both in vitro and in vivo. The pEPito vector is significantly reduced in size, contains only one transcription unit and 60% less CpG motives in comparison to pEPI-1. It exhibits major advantages compared to the original pEPI-1 plasmid, including higher transgene expression levels and increased colony-forming efficiencies in vitro, as well as more persistent transgene expression profiles in vivo. The performance of pEPito-based vectors was further improved by replacing the CMV-IEP with the human CMV enhancer/human elongation factor 1 alpha promoter (hCMV/EF1P element that is known to be less affected by epigenetic silencing events. Conclusions The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo.

  18. Greenhouse gas fluxes from agricultural soils under organic and non-organic management — A global meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, Colin, E-mail: colin.skinner@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Gattinger, Andreas, E-mail: andreas.gattinger@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Muller, Adrian, E-mail: adrian.mueller@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Mäder, Paul, E-mail: paul.maeder@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Fließbach, Andreas, E-mail: andreas.fliessbach@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Stolze, Matthias, E-mail: matthias.stolze@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland); Ruser, Reiner, E-mail: reiner.ruser@uni-hohenheim.de [Fertilisation and Soil Matter Dynamics (340i), Institute of Crop Science, University of Hohenheim, Fruwirthstraße 20, 70599 Stuttgart (Germany); Niggli, Urs, E-mail: urs.niggli@fibl.org [Research Institute of Organic Agriculture (FiBL), Ackerstrasse 21, 5070 Frick (Switzerland)

    2014-01-01

    It is anticipated that organic farming systems provide benefits concerning soil conservation and climate protection. A literature search on measured soil-derived greenhouse gas (GHG) (nitrous oxide and methane) fluxes under organic and non-organic management from farming system comparisons was conducted and followed by a meta-analysis. Up to date only 19 studies based on field measurements could be retrieved. Based on 12 studies that cover annual measurements, it appeared with a high significance that area-scaled nitrous oxide emissions from organically managed soils are 492 ± 160 kg CO{sub 2} eq. ha{sup −1} a{sup −1} lower than from non-organically managed soils. For arable soils the difference amounts to 497 ± 162 kg CO{sub 2} eq. ha{sup −1} a{sup −1}. However, yield-scaled nitrous oxide emissions are higher by 41 ± 34 kg CO{sub 2} eq. t{sup −1} DM under organic management (arable and use). To equalize this mean difference in yield-scaled nitrous oxide emissions between both farming systems, the yield gap has to be less than 17%. Emissions from conventionally managed soils seemed to be influenced mainly by total N inputs, whereas for organically managed soils other variables such as soil characteristics seemed to be more important. This can be explained by the higher bioavailability of the synthetic N fertilisers in non-organic farming systems while the necessary mineralisation of the N sources under organic management leads to lower and retarded availability. Furthermore, a higher methane uptake of 3.2 ± 2.5 kg CO{sub 2} eq. ha{sup −1} a{sup −1} for arable soils under organic management can be observed. Only one comparative study on rice paddies has been published up to date. All 19 retrieved studies were conducted in the Northern hemisphere under temperate climate. Further GHG flux measurements in farming system comparisons are required to confirm the results and close the existing knowledge gaps. - Highlights: • Lower area-scaled nitrous

  19. Effect of surface organic coatings of cellulose nanocrystals on the viability of mammalian cell lines

    Directory of Open Access Journals (Sweden)

    Jimenez AS

    2017-09-01

    Full Text Available Ambar S Jimenez,1 Francesca Jaramillo,1 Usha D Hemraz,2 Yaman Boluk,3 Karina Ckless,1 Rajesh Sunasee1 1Department of Chemistry, State University of New York at Plattsburgh, Plattsburgh, NY, USA; 2National Research Council, Montreal, QC, Canada, 3Department of Civil & Environmental Engineering, University of Alberta and National Institute for Nanotechnology, National Research Council, Edmonton, AB, Canada Abstract: Cellulose nanocrystals (CNCs have emerged as promising candidates for a number of bio-applications. Surface modification of CNCs continues to gain significant research interest as it imparts new properties to the surface of the nanocrystals for the design of multifunctional CNCs-based materials. A small chemical surface modification can potentially lead to drastic behavioral changes of cell-material interactions thereby affecting the intended bio-application. In this work, unmodified CNCs were covalently decorated with four different organic moieties such as a diaminobutane fragment, a cyclic oligosaccharide (β-cyclodextrin, a thermoresponsive polymer (poly[N-isopropylacrylamide], and a cationic aminomethacrylamide-based polymer using different synthetic covalent methods. The effect of surface coatings of CNCs and the respective dose-response of the above organic moieties on the cell viability were evaluated on mammalian cell cultures (J774A.1 and MFC-7, using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Overall, the results indicated that cells exposed to surface-coated CNCs for 24 h did not display major changes in cell viability, membrane permeability as well as cell morphology. However, with longer exposure, all these parameters were somewhat affected, which appears not to be correlated with either anionic or cationic surface coatings of CNCs used in this study. Keywords: cellulose nanocrystals, surface coating, cell viability, MTT, LDH

  20. Review of the effects of manufactured nanoparticles on mammalian target organs.

    Science.gov (United States)

    Wu, Tianshu; Tang, Meng

    2018-01-01

    Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Non-organ donors' attitudes toward incentives.

    Science.gov (United States)

    Tumin, Makmor; Noh, Abdillah; Chong, Chin-Sieng; Lim, Soo-Kun; Abdullah, Nawi; Ng, Kok-Peng

    2013-01-01

    Malaysians indicating that they did not intend to become organ donors upon their death were surveyed regarding interest in non-fungible financial incentives to be granted to surviving family members. Among the 730 (56% of the total sample of 1311) indicating unwillingness to be donors, 29.6% (216/730) subsequently indicated that they would be willing donors if the government introduced policies that, upon their death, "rewarded your (their) family with incentives for your (their) deeds." Among the 69% (504/730) who insisted that they would not become organ donor even with incentive, nearly 80% (404/501) of them were able to identify relevant incentives they thought should be provided by the state to those who make organ donations upon death. The majority of both groups preferred the state provide medical benefits to a surviving family member, suggesting this may be an attractive policy option for the state to raise the deceased organ donation pool. © 2013 John Wiley & Sons A/S.

  2. Liv. 52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    Saini, M.R.; Saini, N.

    1985-01-01

    Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

  3. Enhancer Evolution across 20 Mammalian Species

    Science.gov (United States)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  4. Spokespersons in media campaigns of non-profit organizations

    Directory of Open Access Journals (Sweden)

    Milovanović Dragana

    2014-01-01

    Full Text Available The subject of this research is how spokespersons can be used in campaigns of non-profit organizations, with a goal to increase their visibility and gain public support. Namely, many companies employ celebrities for their media campaigns as protagonists and promoters of brand values. With their appearance and engagement, celebrities transfer part of their image and credibility to the brand, which widens and enriches the field of associations which brands trigger in consumers' conscience. Non-profit organizations could get similar benefits out of these campaigns. In a society where there is a certain level of fascination with celebrities, i.e. celebrity culture, their influence can be used not only to attract attention to the goods, but also to ideas. The goal of the paper is to show how spokespersons can influence behavior and attitudes of the public by participating in media campaigns, and also the important aspects of choosing a spokesperson. The paper is supposed to be a starting point for practitioners,so they can design creative ideas based on this technique on the non-profit organizations market, especially in Serbia.

  5. Modelling spatio-temporal interactions within the cell

    Indian Academy of Sciences (India)

    Prakash

    Cell signalling pathways make up the regulatory systems of mammalian cells. ... This organization makes it possible to study the signalling networks in a modelling ..... energy transfer (FRET) and fluorescence recovery after photobleaching ...

  6. Accumulation of plutonium in mammalian wildlife tissues: comparison of recent data with the ICRP distribution models

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, M.; Child, D.; Davis, E.; Hotchkis, M.; Payne, T. [Australian Nuclear Science and Technology Org. (Australia); Ikeda-Ohno, A. [University of New South Wales (Australia); Twining, J. [Austral Radioecology (Australia)

    2014-07-01

    We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife to address the paucity of such data under environmental exposure conditions. Pu activity concentrations were measured in Macropus rufus (red kangaroo), Oryctolagus cuniculus (European rabbit), and Pseudomys hermannsburgensis (sandy inland mouse)inhabiting the relatively undisturbed, semi-arid conditions at the former Taranaki weapons test site at Maralinga, Australia. Of the absorbed Pu (distributed via circulatory and lymph systems) accumulation was foremost in bone (83% ±10% SD), followed by muscle (9% ±10%), liver (7% ±7%), kidneys (0.5% ±0.3%), and heart (0.4% ±0.4%). The bone values are higher than those reported in ICRP 19 and 48 (45-50% bone), while the liver values are lower than ICRP values (30-45% liver). The ICRP values were based on data dominated by relatively soluble forms of Pu, including prepared solutions and single-atom ions produced by decay following the volatilisation of uranium during nuclear detonation (fallout Pu, ICRP 1986). In contrast, the Maralinga data relates to low-soluble forms of Pu used in tests designed to simulate accidental release and dispersal. We measured Pu in lung, GI-tract and the skin and fur as distinct from the absorbed Pu in bone, liver, muscle, and kidneys. Compared with the mean absorbed activity concentrations, the results for lung tissues were higher by up to one order of magnitude, and those in the GI tract contents and the washed skin/fur were higher by more than two orders of magnitude. These elevated levels are consistent with the presence of low-soluble Pu, including particulate forms, which pass through, or adhere upon, certain organs, but are not readily absorbed into the bloodstream. This more transitory Pu can provide dose to the lung and GI tract organs, as well as provide potential transfer of contamination when consumed in predator-prey food chains, or during human foodstuff consumption. For example, activity

  7. A model for allometric scaling of mammalian metabolism with ambient heat loss

    KAUST Repository

    Kwak, Ho Sang; Im, Hong G.; Shim, Eun Bo

    2016-01-01

    The finding that additional radiative heat loss and the consideration of an outer insulation fur layer attenuate these deviation effects and render the scaling law closer to 2/3 provides in silico evidence for a functional impact of heat transfer mode on the allometric scaling law in mammalian metabolism.

  8. Mammalian gastrointestinal parasites in rainforest remnants

    Indian Academy of Sciences (India)

    Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

  9. Functional anatomy of the hypoglossal innervated muscles of the rat tongue: a model for elongation and protrusion of the mammalian tongue.

    Science.gov (United States)

    McClung, J R; Goldberg, S J

    2000-12-01

    This anatomical investigation in the rat was designed to illustrate the detailed organization of the tongue's muscles and their innervation in order to elucidate the actions of the muscles of the higher mammalian tongue and thereby clarify the protrusor subdivision of the hypoglossal-tongue complex. The hypoglossal innervated, extrinsic styloglossus, hyoglossus, and genioglossus and the intrinsic transversus, verticalis and longitudinalis linguae muscles were observed by microdissection and analysis of serial transverse-sections of the tongue. Sihler's staining technique was applied to whole rat tongues to demonstrate the hypoglossal nerve branching patterns. Dissections of the tongue demonstrate the angles at which the extrinsic muscles act on the base of the tongue. The Sihler stained hypoglossal nerves demonstrate branches to the styloglossus and hyoglossus emanating from its lateral division while branches to the genioglossus muscle exit from its medial division. The largest portions of both XIIth nerve divisions can be seen to enter the body of the tongue to innervate the intrinsic muscles. Transverse sections of the tongue demonstrate the organization of the intrinsic muscle fibers of the tongue. Longitudinal muscle fibers run along the entire circumference of the tongue. Alternating sheets of transverse lingual and vertical lingual muscles can be observed to insert into the circumference of the tongue. Most importantly in clarifying tongue protrusion, we demonstrate the transversus muscle fibers enveloping the most superior and inferior portions of the longitudinalis muscles. Longitudinal muscle fascicles are completely encircled and thus are likely to be compressed by transverse muscle fascicles resulting in elongation of the tongue. We discuss our findings in relation to biomechanical studies, that describe the tongue as a muscular hydrostat and thereby define the "elongation-protrusion apparatus" of the mammalian tongue. In so doing, we clarify the

  10. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

    Science.gov (United States)

    Nally, Jarlath E; Grassmann, Andre A; Planchon, Sébastien; Sergeant, Kjell; Renaut, Jenny; Seshu, Janakiram; McBride, Alan J; Caimano, Melissa J

    2017-01-01

    Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC) peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE). Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed ( p 1.25 or expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs) are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30 leptospires by 2-D immunoblotting confirmed that modification of proteins with

  11. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals

    Directory of Open Access Journals (Sweden)

    Jarlath E. Nally

    2017-08-01

    Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE. Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed (p < 0.05, fold change >1.25 or < −1.25 across all three conditions. Differentially expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30

  12. Differentiation of organic and non-organic winter wheat cultivars from a controlled field trial by crystallization patterns.

    Science.gov (United States)

    Kahl, Johannes; Busscher, Nicolaas; Mergardt, Gaby; Mäder, Paul; Torp, Torfinn; Ploeger, Angelika

    2015-01-01

    There is a need for authentication tools in order to verify the existing certification system. Recently, markers for analytical authentication of organic products were evaluated. Herein, crystallization with additives was described as an interesting fingerprint approach which needs further evidence, based on a standardized method and well-documented sample origin. The fingerprint of wheat cultivars from a controlled field trial is generated from structure analysis variables of crystal patterns. Method performance was tested on factors such as crystallization chamber, day of experiment and region of interest of the patterns. Two different organic treatments and two different treatments of the non-organic regime can be grouped together in each of three consecutive seasons. When the k-nearest-neighbor classification method was applied, approximately 84% of Runal samples and 95% of Titlis samples were classified correctly into organic and non-organic origin using cross-validation. Crystallization with additive offers an interesting complementary fingerprint method for organic wheat samples. When the method is applied to winter wheat from the DOK trial, organic and non-organic treated samples can be differentiated significantly based on pattern recognition. Therefore crystallization with additives seems to be a promising tool in organic wheat authentication. © 2014 Society of Chemical Industry.

  13. Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

    Science.gov (United States)

    Koppaka, S S; Puchowicz; LaManna, J C; Gatica, J E

    2008-01-01

    Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

  14. On the deduction and analysis of singlet and two-state gating-models from the static structures of mammalian CYP450.

    Science.gov (United States)

    Zawaira, Alexander; Coulson, Lauren; Gallotta, Marco; Karimanzira, Owen; Blackburn, Jonathan

    2011-02-01

    Differential tunnel-opening patterns were established in static structures of mammalian CYP450 isoforms and subsequently applied to identify tunnel-intersecting residues. The identified tunnel-intersecting residues permitted the subsequent construction of gating models via the identification of intra-protein interactions. We define 28 two-state gating models and 37 singlet gating-residue models. Our results reveal the preponderance of aromatic gating residues in CYP3A4 and CYP2A6, whereas we find a preponderance of polar/charged residues in CYP2C5. In CYP2C8 there is balanced presence of polar/charged and hydrophobic aliphatic residues in gating models, whilst in CYP2C9 there is balanced presence of all residue-types. These patterns suggest fast evolutionary dynamics for gating residues and we find that the average rate of evolution of gating residues in CYP2C5, CYP2C8, CYP2C9 and CYP2A6 is significantly faster than the average rate of evolution of the entire sequence. Our study identifies 67% of calculable gating models identified in the literature by molecular dynamics approaches and 92% of residues appearing in literature models appear in our models. However, only 6% of the models identified in this work had been previously-described in the literature. This suggests that our study has defined the most comprehensive list yet of tunnel-gating models in mammalian CYP450 and in doing so have created a benchmark for molecular dynamics approaches to the ligand-tunnelling problem in CYP450. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Localization of two mammalian cyclin dependent kinases during mammalian meiosis

    NARCIS (Netherlands)

    Ashley, T.; Walpita, D.; de rooij, D. G.

    2001-01-01

    Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

  16. Grants Management Guidance for Non-Profit Organizations

    Science.gov (United States)

    This guidance is intended to provide non-profit grant recipients with information to ensure that their organizations remain in compliance with the Code of Federal Regulations (CFR), Office of Management (OMB) cost principles, and the terms and conditions.

  17. Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

    Science.gov (United States)

    Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N; Lee, Seung-Rock

    2014-01-01

    Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

  18. Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

    Directory of Open Access Journals (Sweden)

    Seong-Jeong Han

    Full Text Available Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO, the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

  19. Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis.

    Science.gov (United States)

    Svetlanov, Anton; Cohen, Paula E

    2004-05-15

    Mammalian meiosis differs from that seen in lower eukaryotes in several respects, not least of which is the added complexity of dealing with chromosomal interactions across a much larger genome (12 MB over 16 chromosome pairs in Saccharomyces cerevisiae compared to 2500 MB over 19 autosome pairs in Mus musculus). Thus, the recombination machinery, while being highly conserved through eukaryotes, has evolved to accommodate such issues to preserve genome integrity and to ensure propagation of the species. One group of highly conserved meiotic regulators is the DNA mismatch repair protein family that, as their name implies, were first identified as proteins that act to repair DNA mismatches that arise primarily during DNA replication. Their function in ensuring chromosomal integrity has also translated into a critical role for this family in meiotic recombination in most sexually reproducing organisms. In mice, targeted deletion of certain family members results in severe consequences for meiotic progression and infertility. This review will focus on the studies involving these mutant mouse models, with occasional comparison to the function of these proteins in other organisms.

  20. Publicly available models to predict normal boiling point of organic compounds

    International Nuclear Information System (INIS)

    Oprisiu, Ioana; Marcou, Gilles; Horvath, Dragos; Brunel, Damien Bernard; Rivollet, Fabien; Varnek, Alexandre

    2013-01-01

    Quantitative structure–property models to predict the normal boiling point (T b ) of organic compounds were developed using non-linear ASNNs (associative neural networks) as well as multiple linear regression – ISIDA-MLR and SQS (stochastic QSAR sampler). Models were built on a diverse set of 2098 organic compounds with T b varying in the range of 185–491 K. In ISIDA-MLR and ASNN calculations, fragment descriptors were used, whereas fragment, FPTs (fuzzy pharmacophore triplets), and ChemAxon descriptors were employed in SQS models. Prediction quality of the models has been assessed in 5-fold cross validation. Obtained models were implemented in the on-line ISIDA predictor at (http://infochim.u-strasbg.fr/webserv/VSEngine.html)

  1. Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria

    International Nuclear Information System (INIS)

    Lamhonwah, Anne-Marie; Tein, Ingrid

    2006-01-01

    Carnitine is a zwitterion essential for the β-oxidation of fatty acids. We report novel localization of the organic cation/carnitine transporter, OCTN1, to mitochondria. We made GFP- and RFP-human OCTN1 cDNA constructs and showed expression of hOCTN1 in several transfected mammalian cell lines. Immunostaining of GFP-hOCTN1 transfected cells with different intracellular markers and confocal fluorescent microscopy demonstrated mitochondrial expression of OCTN1. There was striking co-localization of an RFP-hOCTN1 fusion protein and a mitochondrial-GFP marker construct in transfected MEF-3T3 and no co-localization of GFP-hOCTN1 in transfected human skin fibroblasts with other intracellular markers. L-[ 3 H]Carnitine uptake in freshly isolated mitochondria of GFP-hOCTN1 transfected HepG2 demonstrated a K m of 422 μM and Western blot with an anti-GFP antibody identified the expected GFP-hOCTN1 fusion protein (90 kDa). We showed endogenous expression of native OCTN1 in HepG2 mitochondria with anti-GST-hOCTN1 antibody. Further, we definitively confirmed intact L-[ 3 H]carnitine uptake (K m 1324 μM), solely attributable to OCTN1, in isolated mitochondria of mutant human skin fibroblasts having <1% of carnitine acylcarnitine translocase activity (alternate mitochondrial carnitine transporter). This mitochondrial localization was confirmed by TEM of murine heart incubated with highly specific rabbit anti-GST-hOCTN1 antibody and immunogold labeled goat anti-rabbit antibody. This suggests an important yet different role for OCTN1 from other OCTN family members in intracellular carnitine homeostasis

  2. Organ-on-a-Chip: New Platform for Biological Analysis

    Directory of Open Access Journals (Sweden)

    Fan An

    2015-01-01

    Full Text Available Direct detection and analysis of biomolecules and cells in physiological microenvironment is urgently needed for fast evaluation of biology and pharmacy. The past several years have witnessed remarkable development opportunities in vitro organs and tissues models with multiple functions based on microfluidic devices, termed as “organ-on-a-chip”. Briefly speaking, it is a promising technology in rebuilding physiological functions of tissues and organs, featuring mammalian cell co-culture and artificial microenvironment created by microchannel networks. In this review, we summarized the advances in studies of heart-, vessel-, liver-, neuron-, kidney- and Multi-organs-on-a-chip, and discussed some noteworthy potential on-chip detection schemes.

  3. MATRIX-VBS Condensing Organic Aerosols in an Aerosol Microphysics Model

    Science.gov (United States)

    Gao, Chloe Y.; Tsigaridis, Konstas; Bauer, Susanne E.

    2015-01-01

    The condensation of organic aerosols is represented in a newly developed box-model scheme, where its effect on the growth and composition of particles are examined. We implemented the volatility-basis set (VBS) framework into the aerosol mixing state resolving microphysical scheme Multiconfiguration Aerosol TRacker of mIXing state (MATRIX). This new scheme is unique and advances the representation of organic aerosols in models in that, contrary to the traditional treatment of organic aerosols as non-volatile in most climate models and in the original version of MATRIX, this new scheme treats them as semi-volatile. Such treatment is important because low-volatility organics contribute significantly to the growth of particles. The new scheme includes several classes of semi-volatile organic compounds from the VBS framework that can partition among aerosol populations in MATRIX, thus representing the growth of particles via condensation of low volatility organic vapors. Results from test cases representing Mexico City and a Finish forrest condistions show good representation of the time evolutions of concentration for VBS species in the gas phase and in the condensed particulate phase. Emitted semi-volatile primary organic aerosols evaporate almost completely in the high volatile range, and they condense more efficiently in the low volatility range.

  4. Non-Profit Organizations in a Bureaucratic Environment

    OpenAIRE

    Grout, Paul; Schnedler, Wendelin

    2008-01-01

    How does the environment of an organization influence whether workers voluntarily provide effort? We study the power relationship between a non-profit unit (e.g. university department, NGO, health trust), where workers care about the result of their work, and a bu- reaucrat, who supplies some input to the non-profit unit, but has opportunity costs in doing so (e.g. Dean of faculty, corrupt representative, government agency). We find that marginal changes in the balance of power eventually hav...

  5. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

    Directory of Open Access Journals (Sweden)

    Erik A Karlsson

    Full Text Available Astroviruses (AstVs are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific.

  6. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  7. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Science.gov (United States)

    Williams, Tim D; Turan, Nil; Diab, Amer M; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L; Hrydziuszko, Olga; Lyons, Brett P; Stentiford, Grant D; Herbert, John M; Abraham, Joseph K; Katsiadaki, Ioanna; Leaver, Michael J; Taggart, John B; George, Stephen G; Viant, Mark R; Chipman, Kevin J; Falciani, Francesco

    2011-08-01

    The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  8. Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family.

    Science.gov (United States)

    Wilson-O'Brien, Amy L; Patron, Nicola; Rogers, Suzanne

    2010-05-21

    In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

  9. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  10. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    Wu, C-W.; Biggar, K.K.; Storey, K.B.

    2013-01-01

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  11. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  12. Application of several activity coefficient models to water-organic-electrolyte aerosols of atmospheric interest

    Directory of Open Access Journals (Sweden)

    T. Raatikainen

    2005-01-01

    Full Text Available In this work, existing and modified activity coefficient models are examined in order to assess their capabilities to describe the properties of aqueous solution droplets relevant in the atmosphere. Five different water-organic-electrolyte activity coefficient models were first selected from the literature. Only one of these models included organics and electrolytes which are common in atmospheric aerosol particles. In the other models, organic species were solvents such as alcohols, and important atmospheric ions like NH4+ could be missing. The predictions of these models were compared to experimental activity and solubility data in aqueous single electrolyte solutions with 31 different electrolytes. Based on the deviations from experimental data and on the capabilities of the models, four predictive models were selected for fitting of new parameters for binary and ternary solutions of common atmospheric electrolytes and organics. New electrolytes (H+, NH4+, Na+, Cl-, NO3- and SO42- and organics (dicarboxylic and some hydroxy acids were added and some modifications were made to the models if it was found useful. All new and most of the existing parameters were fitted to experimental single electrolyte data as well as data for aqueous organics and aqueous organic-electrolyte solutions. Unfortunately, there are very few data available for organic activities in binary solutions and for organic and electrolyte activities in aqueous organic-electrolyte solutions. This reduces model capabilities in predicting solubilities. After the parameters were fitted, deviations from measurement data were calculated for all fitted models, and for different data types. These deviations and the calculated property values were compared with those from other non-electrolyte and organic-electrolyte models found in the literature. Finally, hygroscopic growth factors were calculated for four 100 nm organic-electrolyte particles and these predictions were compared to

  13. Financial And Non-financial Factors Motivating Individual Donors To Support Public Benefit Organizations

    Directory of Open Access Journals (Sweden)

    WANIAK-MICHALAK HALINA

    2015-03-01

    Full Text Available This study is aimed at determining how the financial data of public benefit organizations (PBOs affects donations received by them and if the donors use financial and non-financial information in order to donate. In order to achieve our aim we used different methods of research: quantitative research (econometric model and survey and qualitative research (laboratory test. The research allowed us to draw the conclusion that Polish donors make very limited use of PBOs’ financial statements in the donation process and that non-financial information plays greater role for donors in making decisions to give charitable donations. The most important information is the organization's goals and descriptions of its projects. At the same time, many donors stated that they donated under the influence of people they knew. This article fits into the scope of world research on PBOs and uses the concept of civil society.

  14. The Developmental Roles of Non-Governmental Organizations: A ...

    African Journals Online (AJOL)

    ... Roles of Non-Governmental Organizations: A Sociological Perspective. ... have a clearly defined constituency and are accountable to that constituency, have ... are self serving but geared towards humanitarian objectives and programmes.

  15. Self-organized criticality revisited: non-local transport by turbulent amplification

    DEFF Research Database (Denmark)

    Milovanov, Alexander V.; Rasmussen, Jens Juul

    2015-01-01

    We revise the applications of self-organized criticality (SOC) as a paradigmatic model for tokamak plasma turbulence. The work, presented here, is built around the idea that some systems do not develop a pure critical state associable with SOC, since their dynamical evolution involves as a compet......We revise the applications of self-organized criticality (SOC) as a paradigmatic model for tokamak plasma turbulence. The work, presented here, is built around the idea that some systems do not develop a pure critical state associable with SOC, since their dynamical evolution involves...... as a competing key factor an inverse cascade of the energy in reciprocal space. Then relaxation of slowly increasing stresses will give rise to intermittent bursts of transport in real space and outstanding transport events beyond the range of applicability of the 'conventional' SOC. Also, we are concerned...... with the causes and origins of non-local transport in magnetized plasma, and show that this type of transport occurs naturally in self-consistent strong turbulence via a complexity coupling to the inverse cascade. We expect these coupling phenomena to occur in the parameter range of strong nonlinearity and time...

  16. Mosaic evolution of the mammalian auditory periphery.

    Science.gov (United States)

    Manley, Geoffrey A

    2013-01-01

    The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

  17. Tree-Structured Digital Organisms Model

    Science.gov (United States)

    Suzuki, Teruhiko; Nobesawa, Shiho; Tahara, Ikuo

    Tierra and Avida are well-known models of digital organisms. They describe a life process as a sequence of computation codes. A linear sequence model may not be the only way to describe a digital organism, though it is very simple for a computer-based model. Thus we propose a new digital organism model based on a tree structure, which is rather similar to the generic programming. With our model, a life process is a combination of various functions, as if life in the real world is. This implies that our model can easily describe the hierarchical structure of life, and it can simulate evolutionary computation through mutual interaction of functions. We verified our model by simulations that our model can be regarded as a digital organism model according to its definitions. Our model even succeeded in creating species such as viruses and parasites.

  18. Non-commutative standard model: model building

    CERN Document Server

    Chaichian, Masud; Presnajder, P

    2003-01-01

    A non-commutative version of the usual electro-weak theory is constructed. We discuss how to overcome the two major problems: (1) although we can have non-commutative U(n) (which we denote by U sub * (n)) gauge theory we cannot have non-commutative SU(n) and (2) the charges in non-commutative QED are quantized to just 0,+-1. We show how the latter problem with charge quantization, as well as with the gauge group, can be resolved by taking the U sub * (3) x U sub * (2) x U sub * (1) gauge group and reducing the extra U(1) factors in an appropriate way. Then we proceed with building the non-commutative version of the standard model by specifying the proper representations for the entire particle content of the theory, the gauge bosons, the fermions and Higgs. We also present the full action for the non-commutative standard model (NCSM). In addition, among several peculiar features of our model, we address the inherentCP violation and new neutrino interactions. (orig.)

  19. A role for carbohydrate recognition in mammalian sperm-egg binding

    International Nuclear Information System (INIS)

    Clark, Gary F.

    2014-01-01

    Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented

  20. A role for carbohydrate recognition in mammalian sperm-egg binding

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Gary F., E-mail: clarkgf@health.missouri.edu

    2014-08-01

    Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented.

  1. The role and importance of Non-Profit Organizations

    Directory of Open Access Journals (Sweden)

    Nicoleta Ciucescu

    2009-12-01

    Full Text Available In a complex and challenging background of the whole country, and the NGO sector also, the non-profit organizations are established with the aim of providing public services to communities where they operate, making them as an intermediary between citizens and authorities. In any democratic society these organizations are meant to serve different types of needs and interests of the community, from both a strategic perspective and ethics, that those which are not covered by other categories of institutions and organizations, mean time providing a framework for civic participation, where citizens may participate to the public life.

  2. Robust expression of a bioactive mammalian protein in chlamydomonas chloroplast

    Science.gov (United States)

    Mayfield, Stephen P.

    2010-03-16

    Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery or proteins/peptides, especially gut active proteins, without purification is disclosed.

  3. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Science.gov (United States)

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  4. Elucidating the Role of Injury-Induced Electric Fields (EFs in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Matthew L Baer

    Full Text Available Injury to the vertebrate central nervous system (CNS induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  5. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Chia-Rui Shen

    2015-11-01

    Full Text Available Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

  6. The organization and administration of community college non-credit workforce education and training cuts

    Science.gov (United States)

    Kozachyn, Karen P.

    Community colleges are struggling financially due to underfunding. Recent state budget cuts coupled with the elimination of federal stimulus money has exacerbated the issue as these funding streams had contributed to operating costs (Moltz, 2011). In response to these budget cuts, community colleges are challenged to improve, increase, and develop revenue producing programs. These factors heighten the need for community colleges to examine their non-credit workforce organizations. The community college units charged with delivering non-credit workforce education and training programs are historically ancillary to the academic divisions that deliver certificate, technical degree, and transfer degree programs. The perceptions of these units are that they are the community college's 'step child' (Grubb, Bradway, and Bell, 2002). This case study examined the organization and administration of community college non-credit workforce education and training units, utilizing observation, interviews, and document analysis. Observational data focused on the physical campus and the unit. Interviews were conducted onsite with decision-making personnel of the division units that deliver non-credit workforce education and training within each community college. Document analysis included college catalogues, program guides, marketing material, and website information. The study was grounded in the review of literature associated with the evolution of the community college, as well as the development of workforce education and training including funding, organizational structure and models, management philosophies, and effectiveness. The findings of the study report that all five units were self-contained and were organized and operated uniquely within the organization. Effectiveness was measured differently by each institution. However, two common benchmarks were revenue and student evaluations. Another outcome of this study is the perceived lack of college-wide alignment between

  7. InXy and SeXy, compact heterologous reporter proteins for mammalian cells.

    Science.gov (United States)

    Fluri, David A; Kelm, Jens M; Lesage, Guillaume; Baba, Marie Daoud-El; Fussenegger, Martin

    2007-10-15

    Mammalian reporter proteins are essential for gene-function analysis, drugscreening initiatives and as model product proteins for biopharmaceutical manufacturing. Bacillus subtilis can maintain its metabolism by secreting Xylanase A (XynA), which converts xylan into shorter xylose oligosaccharides. XynA is a family 11 xylanase monospecific for D-xylose containing substrates. Mammalian cells transgenic for constitutive expression of wild-type xynA showed substantial secretion of this prokaryotic enzyme. Deletion analysis confirmed that a prokaryotic signal sequence encoded within the first 81 nucleotides was compatible with the secretory pathway of mammalian cells. Codon optimization combined with elimination of the prokaryotic signal sequence resulted in an exclusively intracellular mammalian Xylanase A variant (InXy) while replacement by an immunoglobulin-derived secretion signal created an optimal secreted Xylanase A derivative (SeXy). A variety of chromogenic and fluorescence-based assays adapted for use with mammalian cells detected InXy and SeXy with high sensitivity and showed that both reporter proteins resisted repeated freeze/thaw cycles, remained active over wide temperature and pH ranges, were extremely stable in human serum stored at room temperature and could independently be quantified in samples also containing other prominent reporter proteins such as the human placental alkaline phosphatase (SEAP) and the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY). Glycoprofiling revealed that SeXy produced in mammalian cells was N- glycosylated at four different sites, mutation of which resulted in impaired secretion. SeXy was successfully expressed in a variety of mammalian cell lines and primary cells following transient transfection and transduction with adeno-associated virus particles (AAV) engineered for constitutive SeXy expression. Intramuscular injection of transgenic AAVs into mice showed significant SeXy levels in the bloodstream

  8. Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT family

    Directory of Open Access Journals (Sweden)

    Patron Nicola

    2010-05-01

    Full Text Available Abstract Background In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. Results We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. Conclusions The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

  9. Modelling a tethered mammalian sperm cell undergoing hyperactivation

    KAUST Repository

    Curtis, M.P.

    2012-09-01

    The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

  10. Modelling a tethered mammalian sperm cell undergoing hyperactivation

    KAUST Repository

    Curtis, M.P.; Kirkman-Brown, J.C.; Connolly, T.J.; Gaffney, E.A.

    2012-01-01

    The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

  11. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  12. Simulations of organic aerosol concentrations in Mexico City using the WRF-CHEM model during the MCMA-2006/MILAGRO campaign

    Directory of Open Access Journals (Sweden)

    G. Li

    2011-04-01

    Full Text Available Organic aerosol concentrations are simulated using the WRF-CHEM model in Mexico City during the period from 24 to 29 March in association with the MILAGRO-2006 campaign. Two approaches are employed to predict the variation and spatial distribution of the organic aerosol concentrations: (1 a traditional 2-product secondary organic aerosol (SOA model with non-volatile primary organic aerosols (POA; (2 a non-traditional SOA model including the volatility basis-set modeling method in which primary organic components are assumed to be semi-volatile and photochemically reactive and are distributed in logarithmically spaced volatility bins. The MCMA (Mexico City Metropolitan Area 2006 official emission inventory is used in simulations and the POA emissions are modified and distributed by volatility based on dilution experiments for the non-traditional SOA model. The model results are compared to the Aerosol Mass Spectrometry (AMS observations analyzed using the Positive Matrix Factorization (PMF technique at an urban background site (T0 and a suburban background site (T1 in Mexico City. The traditional SOA model frequently underestimates the observed POA concentrations during rush hours and overestimates the observations in the rest of the time in the city. The model also substantially underestimates the observed SOA concentrations, particularly during daytime, and only produces 21% and 25% of the observed SOA mass in the suburban and urban area, respectively. The non-traditional SOA model performs well in simulating the POA variation, but still overestimates during daytime in the urban area. The SOA simulations are significantly improved in the non-traditional SOA model compared to the traditional SOA model and the SOA production is increased by more than 100% in the city. However, the underestimation during daytime is still salient in the urban area and the non-traditional model also fails to reproduce the high level of SOA concentrations in the

  13. New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts.

    Science.gov (United States)

    Weston, David J; Russell, Richard A; Batty, Elizabeth; Jensen, Kirsten; Stephens, David A; Adams, Niall M; Freemont, Paul S

    2015-03-06

    The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate 'aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging.

  14. Introducing Mammalian Cell Culture and Cell Viability Techniques in the Undergraduate Biology Laboratory.

    Science.gov (United States)

    Bowey-Dellinger, Kristen; Dixon, Luke; Ackerman, Kristin; Vigueira, Cynthia; Suh, Yewseok K; Lyda, Todd; Sapp, Kelli; Grider, Michael; Crater, Dinene; Russell, Travis; Elias, Michael; Coffield, V McNeil; Segarra, Verónica A

    2017-01-01

    Undergraduate students learn about mammalian cell culture applications in introductory biology courses. However, laboratory modules are rarely designed to provide hands-on experience with mammalian cells or teach cell culture techniques, such as trypsinization and cell counting. Students are more likely to learn about cell culture using bacteria or yeast, as they are typically easier to grow, culture, and manipulate given the equipment, tools, and environment of most undergraduate biology laboratories. In contrast, the utilization of mammalian cells requires a dedicated biological safety cabinet and rigorous antiseptic techniques. For this reason, we have devised a laboratory module and method herein that familiarizes students with common cell culture procedures, without the use of a sterile hood or large cell culture facility. Students design and perform a time-efficient inquiry-based cell viability experiment using HeLa cells and tools that are readily available in an undergraduate biology laboratory. Students will become familiar with common techniques such as trypsinizing cells, cell counting with a hemocytometer, performing serial dilutions, and determining cell viability using trypan blue dye. Additionally, students will work with graphing software to analyze their data and think critically about the mechanism of death on a cellular level. Two different adaptations of this inquiry-based lab are presented-one for non-biology majors and one for biology majors. Overall, these laboratories aim to expose students to mammalian cell culture and basic techniques and help them to conceptualize their application in scientific research.

  15. Self-organized crystallization mechanism of non-equilibrium 2:1 type phyllosilicate systems

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The crystallization mechanism of 2:1 type regular interstratified minerals is investigated in views of non-equilibrium thermodynamics. The structural chemistry of relative layers and their interstratified combinations is analyzed and six kinds of non-equilibrium chemical systems have been induced. The universal laws of chemical reactions which happened in the interface region of these non-equilibrium systems have been summarized. From these laws, two reaction systems crystallizing out Tosudite and Rectorite respectively have been recovered. The kinetic model of chemical reactions has been developed by means of the mass conservation law. The oscillatory solution showing regular interstratified features has also been obtained numerically. These results indicate that the difference in original chemical composition among systems can affect the chemical connotation of reactants, intermediate products and resultants, and the flow chart of chemical reaction, but cannot change their crystallization behavior of network-forming cations, bigger and smaller network-modifying cations during crystallization. Hence, their kinetic model reflecting the universal crystallization law of these cations is just the same. These systems will crystallize out regular interstratified minerals at suitable parameters, which always exist as domain with nanometer-sized in thickness and can be called the self-organized ordering structure.

  16. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Directory of Open Access Journals (Sweden)

    Tim D Williams

    2011-08-01

    Full Text Available The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  17. Homogenization of Mammalian Cells.

    Science.gov (United States)

    de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

    2015-11-02

    Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

  18. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  19. The effect of non-covalent functionalization on the thermal conductance of graphene/organic interfaces

    International Nuclear Information System (INIS)

    Lin Shangchao; Buehler, Markus J

    2013-01-01

    The intrinsic interfacial thermal resistance at graphene/organic interfaces, as a result of mismatches in the phonon vibrational spectra of the two materials, diminishes the overall heat transfer performance of graphene/organic nanocomposites. In this paper, we use molecular dynamics (MD) simulations to design alkyl-pyrene molecules that can non-covalently functionalize graphene surfaces in contact with a model organic phase composed of octane. The alkyl-pyrene molecules possess phonon-spectra features of both graphene and octane and, therefore, can serve as phonon-spectra linkers to bridge the vibrational mismatch at the graphene/octane interface. In support of this hypothesis, we find that the best linker candidate can enhance the out-of-plane graphene/organic interfacial thermal conductance by ∼22%, attributed to its capability to compensate the low-frequency phonon mode of graphene. We also find that the length of the alkyl chain indirectly affects the interfacial thermal conductance through different orientations of these chains because they dictate the contribution of the out-of-plane high-frequency carbon–hydrogen bond vibrations to the overall phonon transport. This study advances our understanding of the less destructive non-covalent functionalization method and design principles of suitable linker molecules to enhance the thermal performance of graphene/organic nanocomposites while retaining the intrinsic chemical, thermal, and mechanical properties of pristine graphene. (paper)

  20. Pressure of non-professional use of pesticides on operators, aquatic organisms and bees in Belgium.

    Science.gov (United States)

    Fevery, Davina; Houbraken, Michael; Spanoghe, Pieter

    2016-04-15

    Various studies focus on professional pesticide use, whereas pressure of non-professional use on human and the environment is often neglected. In this study, an attempt was made to estimate the pressure of non-professional use of pesticides on operators, aquatic organisms and bees in Belgium based on sales figures and by using three exposure models. A classification in non-professional use was made based on type of pesticide, application method and on intensity of non-professional use. Pressure of non-professional use on operators is highest for intensive operators, caused by the use of insecticides in an aerosol spray can. Pressure of non-professional pesticides on aquatic life is mainly generated by the use of herbicides. The aerosol spray induces the highest pressure whereas the trigger application hardly affects operator and environmental exposure. The ordinary non-professional user generates most pressure on aquatic organisms. Pressure of non-professional pesticides on bees is mainly caused by the use of insecticides, especially the active substance imidacloprid in combination with the aerosol spray can application method applied by an intensive operator. In general, both total usage (kg) and pressure of pesticides decreased for the period 2005 to 2012 due to efforts made by the government and industry. The results of this study suggest to pay special attention to aerosol spray applications and the non-professional use of insecticides. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Social media for non-profit organizations in Vietnam

    OpenAIRE

    Nguyen, Thy

    2016-01-01

    The thesis presents about social media in general and social media for non-profit organizations in Vietnam in particular. The writer wanted to explore the disadvantages that non-profits in Vietnam face when using social media and search for recommendations which helps them to use it more efficiently. In the theoretic part, core concepts related to social media were introduced, namely, definition of social media, its types, the popular platforms, situation of social media in Vietnam, pros...

  2. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  3. Four simple rules that are sufficient to generate the mammalian blastocyst

    DEFF Research Database (Denmark)

    Nissen, Silas Boye; Perera Pérez, Marta; Martin Gonzalez, Javier

    2017-01-01

    requiring any initial transcriptional variation. It also suggests that a fixed time point for the cells’ competence of fibroblast growth factor (FGF)/extracellular signal—regulated kinase (ERK) sets an embryonic clock that enables certain scaling phenomena, a concept that we evaluate quantitatively......Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs...

  4. Aging, neurogenesis, and caloric restriction in different model organisms.

    Science.gov (United States)

    Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

    2013-08-01

    Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

  5. Non-equilibrium and band tailing in organic conductors

    Indian Academy of Sciences (India)

    . Non-equilibrium ... Introduction. Study of organic conductors and semiconductors continues to generate interest with the ... Band tailing reduces band gap or the acti- ..... (9), we can identify Eg(0) with the focal point and is proportional to P2. 1 .

  6. The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.

    Science.gov (United States)

    Richardson, Sandra R; Doucet, Aurélien J; Kopera, Huira C; Moldovan, John B; Garcia-Perez, José Luis; Moran, John V

    2015-04-01

    Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.

  7. Drug repurposing for aging research using model organisms.

    Science.gov (United States)

    Ziehm, Matthias; Kaur, Satwant; Ivanov, Dobril K; Ballester, Pedro J; Marcus, David; Partridge, Linda; Thornton, Janet M

    2017-10-01

    Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila. Our approach combines information on genetic effects on aging, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate aging. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating aging, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

    Science.gov (United States)

    Jenkins, F A; Crompton, A W; Downs, W R

    1983-12-16

    Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

  9. Non-lethal effects of low- and high-LET radiation on cultured mammalian cells

    International Nuclear Information System (INIS)

    Walker, J.T.

    1982-01-01

    In analyzing post-irradiation growth kinetics of cultured mammalian cells, specifically T1-E human cells, this investigation shows that the shift in post-irradiation clone-size distributions toward small colonies is due to both radiation-induced division delay and increased generation times of the irradiated population. Evidence also indicates that the final shape of the final clone-size distribution is influenced by the age density distribution of the parent cells at the time of plating. From computer-generated delay time distributions it was determined that a large percentage of the parent population was found to be in the plateau phase at early growth times and evidence indicates that these cells may contribute heavily to the total population response to radiation

  10. Role Of Governmental And Non-Governmental Organizations In ...

    African Journals Online (AJOL)

    ... non-infected community members, managers of the organizations implementing HIV/AIDS programmes and service providers. In the process 1331 households were interviewed using qualitative and quantitative data collection instruments. Statistical Package for Social Sciences (SPSS) and Nudist 4 packages were used ...

  11. Radioautographic study of two target organs (epididymis and femoral glands) after injection of 3H testosterone in a non-mammalian vertebrate, the viviparous Lizard

    International Nuclear Information System (INIS)

    Dufaure, J.-P.; Chambon, Monique.

    1978-01-01

    After 3 H testosterone injection into castrated males of the Lizard Lacerta vivipara, the radioactive compound is detected by radioautography of epididymis, femoral glands, gut and liver. Between 1 hr. 30 min. to 12 hrs. of retention the 3 H material concentrates progressively into nuclei of the glandular cells of epididymis and femoral organs although no particular concentration occurs in gut and liver cells. This submammalian model is consistent with those previously described for mammals [fr

  12. Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

    International Nuclear Information System (INIS)

    Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

    2014-01-01

    There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

  13. Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models.

    Science.gov (United States)

    Pozo, Carlos; Marín-Sanguino, Alberto; Alves, Rui; Guillén-Gosálbez, Gonzalo; Jiménez, Laureano; Sorribas, Albert

    2011-08-25

    Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

  14. Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

    Directory of Open Access Journals (Sweden)

    Sorribas Albert

    2011-08-01

    Full Text Available Abstract Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

  15. Financing of Romanian Non-governmental Organizations

    Directory of Open Access Journals (Sweden)

    Sebastian Ion CEPTUREANU

    2017-06-01

    Full Text Available Non-governmental organizations (NGOs have become increasingly important in the last decade for the Romanian society. They raise public awareness for human rights, promote development of democracy and seek to improve the well-being of communities by being increasingly engaging in various development, educational, social or health projects. Unfortunately, many NGOs has to cope with significant financing problems since competition for resources amplified and some of the traditional donors cut or reduced support. This paper analyze financing issues in NGOs, based on a quantitative analysis, using a structured questionnaire. Since it is one of the very few studies covering Romania, the scope of the paper was to provide for those involved or interested in NGO sector new data concerning, for instance, sources of revenue or destination of resources, enabling NGOs executives to build financial sustainable organizations.

  16. Financial And Non-financial Factors Motivating Individual Donors To Support Public Benefit Organizations

    OpenAIRE

    WANIAK-MICHALAK HALINA; ZARZYCKA EWELINA

    2015-01-01

    This study is aimed at determining how the financial data of public benefit organizations (PBOs) affects donations received by them and if the donors use financial and non-financial information in order to donate. In order to achieve our aim we used different methods of research: quantitative research (econometric model and survey) and qualitative research (laboratory test). The research allowed us to draw the conclusion that Polish donors make very limited use of PBOs’ financial statements i...

  17. Theoretical modeling of mechanical homeostasis of a mammalian cell under gravity-directed vector.

    Science.gov (United States)

    Zhou, Lüwen; Zhang, Chen; Zhang, Fan; Lü, Shouqin; Sun, Shujin; Lü, Dongyuan; Long, Mian

    2018-02-01

    Translocation of dense nucleus along gravity vector initiates mechanical remodeling of a eukaryotic cell. In our previous experiments, we quantified the impact of gravity vector on cell remodeling by placing an MC3T3-E1 cell onto upward (U)-, downward (D)-, or edge-on (E)- orientated substrate. Our experimental data demonstrate that orientation dependence of nucleus longitudinal translocation is positively correlated with cytoskeletal (CSK) remodeling of their expressions and structures and also is associated with rearrangement of focal adhesion complex (FAC). However, the underlying mechanism how CSK network and FACs are reorganized in a mammalian cell remains unclear. In this paper, we developed a theoretical biomechanical model to integrate the mechanosensing of nucleus translocation with CSK remodeling and FAC reorganization induced by a gravity vector. The cell was simplified as a nucleated tensegrity structure in the model. The cell and CSK filaments were considered to be symmetrical. All elements of CSK filaments and cytomembrane that support the nucleus were simplified as springs. FACs were simplified as an adhesion cluster of parallel bonds with shared force. Our model proposed that gravity vector-directed translocation of the cell nucleus is mechanically balanced by CSK remodeling and FAC reorganization induced by a gravitational force. Under gravity, dense nucleus tends to translocate and exert additional compressive or stretching force on the cytoskeleton. Finally, changes of the tension force acting on talin by microfilament alter the size of FACs. Results from our model are in qualitative agreement with those from experiments.

  18. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V.; Hazen, M.J.

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells

  19. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  20. Pig models on intestinal development and therapeutics.

    Science.gov (United States)

    Yin, Lanmei; Yang, Huansheng; Li, Jianzhong; Li, Yali; Ding, Xueqing; Wu, Guoyao; Yin, Yulong

    2017-12-01

    The gastrointestinal tract plays a vital role in nutrient supply, digestion, and absorption, and has a crucial impact on the entire organism. Much attention is being paid to utilize animal models to study the pathogenesis of gastrointestinal diseases in response to intestinal development and health. The piglet has a body size similar to that of the human and is an omnivorous animal with comparable anatomy, nutritional requirements, and digestive and associated inflammatory processes, and displays similarities to the human intestinal microbial ecosystem, which make piglets more appropriate as an animal model for human than other non-primate animals. Therefore, the objective of this review is to summarize key attributes of the piglet model with which to study human intestinal development and intestinal health through probing into the etiology of several gastrointestinal diseases, thus providing a theoretical and hopefully practical, basis for further studies on mammalian nutrition, health, and disease, and therapeutics. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young piglets and humans, the piglet has been used as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Because of similarities in anatomy and physiology between pigs and mankind, more emphasises are put on how to use the piglet model for human organ transplantation research.

  1. Male germline stem cells in non-human primates

    Directory of Open Access Journals (Sweden)

    S. Sharma

    2017-09-01

    Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

  2. Organization of left-right coordination of neuronal activity in the mammalian spinal cord

    DEFF Research Database (Denmark)

    Shevtsova, Natalia A.; Talpalar, Adolfo E.; Markin, Sergey N.

    2015-01-01

    and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN....... In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified...... inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce...

  3. Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum*

    Science.gov (United States)

    Moxley, Michael A.; Beard, Daniel A.; Bazil, Jason N.

    2016-01-01

    Mammalian E3 is an essential mitochondrial enzyme responsible for catalyzing the terminal reaction in the oxidative catabolism of several metabolites. E3 is a key regulator of metabolic fuel selection as a component of the pyruvate dehydrogenase complex (PDHc). E3 regulates PDHc activity by altering the affinity of pyruvate dehydrogenase kinase, an inhibitor of the enzyme complex, through changes in reduction and acetylation state of lipoamide moieties set by the NAD+/NADH ratio. Thus, an accurate kinetic model of E3 is needed to predict overall mammalian PDHc activity. Here, we have combined numerous literature data sets and new equilibrium spectroscopic experiments with a multitude of independently collected forward and reverse steady-state kinetic assays using pig heart E3. The latter kinetic assays demonstrate a pH-dependent transition of NAD+ activation to inhibition, shown here, to our knowledge, for the first time in a single consistent data set. Experimental data were analyzed to yield a thermodynamically constrained four-redox-state model of E3 that simulates pH-dependent activation/inhibition and active site redox states for various conditions. The developed model was used to determine substrate/product conditions that give maximal E3 rates and show that, due to non-Michaelis-Menten behavior, the maximal flux is different compared with the classically defined kcat. PMID:26644471

  4. Non parametric, self organizing, scalable modeling of spatiotemporal inputs: the sign language paradigm.

    Science.gov (United States)

    Caridakis, G; Karpouzis, K; Drosopoulos, A; Kollias, S

    2012-12-01

    Modeling and recognizing spatiotemporal, as opposed to static input, is a challenging task since it incorporates input dynamics as part of the problem. The vast majority of existing methods tackle the problem as an extension of the static counterpart, using dynamics, such as input derivatives, at feature level and adopting artificial intelligence and machine learning techniques originally designed for solving problems that do not specifically address the temporal aspect. The proposed approach deals with temporal and spatial aspects of the spatiotemporal domain in a discriminative as well as coupling manner. Self Organizing Maps (SOM) model the spatial aspect of the problem and Markov models its temporal counterpart. Incorporation of adjacency, both in training and classification, enhances the overall architecture with robustness and adaptability. The proposed scheme is validated both theoretically, through an error propagation study, and experimentally, on the recognition of individual signs, performed by different, native Greek Sign Language users. Results illustrate the architecture's superiority when compared to Hidden Markov Model techniques and variations both in terms of classification performance and computational cost. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Project-matrix models of marketing organization

    Directory of Open Access Journals (Sweden)

    Gutić Dragutin

    2009-01-01

    Full Text Available Unlike theory and practice of corporation organization, in marketing organization numerous forms and contents at its disposal are not reached until this day. It can be well estimated that marketing organization today in most of our companies and in almost all its parts, noticeably gets behind corporation organization. Marketing managers have always been occupied by basic, narrow marketing activities as: sales growth, market analysis, market growth and market share, marketing research, introduction of new products, modification of products, promotion, distribution etc. They rarely found it necessary to focus a bit more to different aspects of marketing management, for example: marketing planning and marketing control, marketing organization and leading. This paper deals with aspects of project - matrix marketing organization management. Two-dimensional and more-dimensional models are presented. Among two-dimensional, these models are analyzed: Market management/products management model; Products management/management of product lifecycle phases on market model; Customers management/marketing functions management model; Demand management/marketing functions management model; Market positions management/marketing functions management model. .

  6. The ultrastructural basis of steroid production in the Y-organ and the mandibular organ of the crabs Hemigrapsus nudus (Dana) and Carcinus maenas L.

    Science.gov (United States)

    Buchholz, C; Adelung, D

    1980-01-01

    The ultrastructure of the steroid producing Y-organ and the mandibular organ of the crustaceans Hemigrapsus nudus and Carcinus maenas has been studied with reference to the well investigated steroid secreting cells (SSC) of mammals. In accordance with the most important characteristic of mammalian SSC, abundant SER could be shown in the Y-organ, where it is unevenly distributed. The amount of SER seems to vary in correlation with the secretion of moulting hormone during the moult cycle. Most Y-organ cells contain a great number of mitochondria of the tubular type, another important characteristic of mammalian SSC. The ultrastructure of the mandibular organ of C. maenas differs considerably from that of the Y-organ. Some SER was found, mitochondria of unusual shape and size were conspicuous. No definite conclusion as to the function of the mandibular organ is yet to be drawn.

  7. The true meaning of 'exotic species' as a model for genetically engineered organisms.

    Science.gov (United States)

    Regal, P J

    1993-03-15

    The exotic or non-indigenous species model for deliberately introduced genetically engineered organisms (GEOs) has often been misunderstood or misrepresented. Yet proper comparisons of of ecologically competent GEOs to the patterns of adaptation of introduced species have been highly useful among scientists in attempting to determine how to apply biological theory to specific GEO risk issues, and in attempting to define the probabilities and scale of ecological risks with GEOs. In truth, the model predicts that most projects may be environmentally safe, but a significant minority may be very risky. The model includes a history of institutional follies that also should remind workers of the danger of oversimplifying biological issues, and warn against repeating the sorts of professional misjudgements that have too often been made in introducing organisms to new settings. We once expected that the non-indigenous species model would be refined by more analysis of species eruptions, ecological genetics, and the biology of select GEOs themselves, as outlined. But there has been political resistance to the effective regulation of GEOs, and a bureaucratic tendency to focus research agendas on narrow data collection. Thus there has been too little promotion by responsible agencies of studies to provide the broad conceptual base for truly science-based regulation. In its presently unrefined state, the non-indigenous species comparison would overestimate the risks of GEOs if it were (mis)applied to genetically disrupted, ecologically crippled GEOs, but in some cases of wild-type organisms with novel engineered traits, it could greatly underestimate the risks. Further analysis is urgently needed.

  8. An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

    Directory of Open Access Journals (Sweden)

    Young-Geun Lee

    2013-11-01

    Full Text Available BackgroundMammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds.MethodsWe performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course.ResultsAmong the 68 cases of mammalian bite injury, 58 (85% were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap.ConclusionsBased on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds.

  9. Peningkatan Keterampilan Pengambilan Keputusan Dan Penguasaan Konsep IPA Melalui Model Pembelajaran Advance Organizer Di Sekolah Dasar

    OpenAIRE

    Badarudin

    2017-01-01

    Peningkatan Keterampilan Pengambilan Keputusan dan Penguasaan Konsep IPA melalui Model Pembelajaran Advance Organizer di Sekolah Dasar. Penelitian ini bertujuan untuk mengetahui perbedaan peningkatan keterampilan pengambilan keputusan dan pemahaman konsep IPA siswa sebagai dampak dari implementasi model Advance Organizer. Penelitian ini menggunakan metode kuasi eksperimen dengan desain Non equivalent (Pre-Test and Post- Test) Control Groups Design. Subyek penelitian adalah siswa kelas V pada ...

  10. Massive contribution of transposable elements to mammalian regulatory sequences.

    Science.gov (United States)

    Rayan, Nirmala Arul; Del Rosario, Ricardo C H; Prabhakar, Shyam

    2016-09-01

    Barbara McClintock discovered the existence of transposable elements (TEs) in the late 1940s and initially proposed that they contributed to the gene regulatory program of higher organisms. This controversial idea gained acceptance only much later in the 1990s, when the first examples of TE-derived promoter sequences were uncovered. It is now known that half of the human genome is recognizably derived from TEs. It is thus important to understand the scope and nature of their contribution to gene regulation. Here, we provide a timeline of major discoveries in this area and discuss how transposons have revolutionized our understanding of mammalian genomes, with a special emphasis on the massive contribution of TEs to primate evolution. Our analysis of primate-specific functional elements supports a simple model for the rate at which new functional elements arise in unique and TE-derived DNA. Finally, we discuss some of the challenges and unresolved questions in the field, which need to be addressed in order to fully characterize the impact of TEs on gene regulation, evolution and disease processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. A close look at the mammalian blastocyst: epiblast and primitive endoderm formation.

    Science.gov (United States)

    Artus, Jérôme; Chazaud, Claire

    2014-09-01

    During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues--the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time of implantation. The current model proposes that the formation of these lineages results from two consecutive binary cell fate decisions. The first controls the formation of the trophectoderm and the inner cell mass, and the second controls the formation of the primitive endoderm and the epiblast within the inner cell mass. While early mammalian embryos develop with extensive plasticity, the embryonic pattern prior to implantation is remarkably reproducible. Here, we review the molecular mechanisms driving the cell fate decision between primitive endoderm and epiblast in the mouse embryo and integrate data from recent studies into the current model of the molecular network regulating the segregation between these lineages and their subsequent differentiation.

  12. Transgenic Epigenetics: Using Transgenic Organisms to Examine Epigenetic Phenomena

    Directory of Open Access Journals (Sweden)

    Lori A. McEachern

    2012-01-01

    Full Text Available Non-model organisms are generally more difficult and/or time consuming to work with than model organisms. In addition, epigenetic analysis of model organisms is facilitated by well-established protocols, and commercially-available reagents and kits that may not be available for, or previously tested on, non-model organisms. Given the evolutionary conservation and widespread nature of many epigenetic mechanisms, a powerful method to analyze epigenetic phenomena from non-model organisms would be to use transgenic model organisms containing an epigenetic region of interest from the non-model. Interestingly, while transgenic Drosophila and mice have provided significant insight into the molecular mechanisms and evolutionary conservation of the epigenetic processes that target epigenetic control regions in other model organisms, this method has so far been under-exploited for non-model organism epigenetic analysis. This paper details several experiments that have examined the epigenetic processes of genomic imprinting and paramutation, by transferring an epigenetic control region from one model organism to another. These cross-species experiments demonstrate that valuable insight into both the molecular mechanisms and evolutionary conservation of epigenetic processes may be obtained via transgenic experiments, which can then be used to guide further investigations and experiments in the species of interest.

  13. Surgical manipulation of mammalian embryos in vitro.

    Science.gov (United States)

    Naruse, I; Keino, H; Taniguchi, M

    1997-04-01

    Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

  14. The role of BAF (mSWI/SNF) complexes in mammalian neural development.

    Science.gov (United States)

    Son, Esther Y; Crabtree, Gerald R

    2014-09-01

    The BAF (mammalian SWI/SNF) complexes are a family of multi-subunit ATP-dependent chromatin remodelers that use ATP hydrolysis to alter chromatin structure. Distinct BAF complex compositions are possible through combinatorial assembly of homologous subunit families and can serve non-redundant functions. In mammalian neural development, developmental stage-specific BAF assemblies are found in embryonic stem cells, neural progenitors and postmitotic neurons. In particular, the neural progenitor-specific BAF complexes are essential for controlling the kinetics and mode of neural progenitor cell division, while neuronal BAF function is necessary for the maturation of postmitotic neuronal phenotypes as well as long-term memory formation. The microRNA-mediated mechanism for transitioning from npBAF to nBAF complexes is instructive for the neuronal fate and can even convert fibroblasts into neurons. The high frequency of BAF subunit mutations in neurological disorders underscores the rate-determining role of BAF complexes in neural development, homeostasis, and plasticity. © 2014 Wiley Periodicals, Inc.

  15. dDocent: a RADseq, variant-calling pipeline designed for population genomics of non-model organisms.

    Science.gov (United States)

    Puritz, Jonathan B; Hollenbeck, Christopher M; Gold, John R

    2014-01-01

    Restriction-site associated DNA sequencing (RADseq) has become a powerful and useful approach for population genomics. Currently, no software exists that utilizes both paired-end reads from RADseq data to efficiently produce population-informative variant calls, especially for non-model organisms with large effective population sizes and high levels of genetic polymorphism. dDocent is an analysis pipeline with a user-friendly, command-line interface designed to process individually barcoded RADseq data (with double cut sites) into informative SNPs/Indels for population-level analyses. The pipeline, written in BASH, uses data reduction techniques and other stand-alone software packages to perform quality trimming and adapter removal, de novo assembly of RAD loci, read mapping, SNP and Indel calling, and baseline data filtering. Double-digest RAD data from population pairings of three different marine fishes were used to compare dDocent with Stacks, the first generally available, widely used pipeline for analysis of RADseq data. dDocent consistently identified more SNPs shared across greater numbers of individuals and with higher levels of coverage. This is due to the fact that dDocent quality trims instead of filtering, incorporates both forward and reverse reads (including reads with INDEL polymorphisms) in assembly, mapping, and SNP calling. The pipeline and a comprehensive user guide can be found at http://dDocent.wordpress.com.

  16. Impact Of Non-Governmental Organizations\\' Activities In Creating ...

    African Journals Online (AJOL)

    The study examines the impact of Non-Governmental Organizations\\' (NGOs) intervention in creating awareness and changing the mindset of people in typical rural communities in Kaduna State towards victims of HIV/AIDS. Structured questionnaire were used to collect data from adult male and female as well as young ...

  17. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    Science.gov (United States)

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  18. A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

    Science.gov (United States)

    Banks, R W; Hulliger, M; Saed, H H; Stacey, M J

    2009-06-01

    The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend

  19. Radiation activation of transcription factors in mammalian cells

    International Nuclear Information System (INIS)

    Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

    1990-01-01

    In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

  20. Auditory object perception: A neurobiological model and prospective review.

    Science.gov (United States)

    Brefczynski-Lewis, Julie A; Lewis, James W

    2017-10-01

    Interaction with the world is a multisensory experience, but most of what is known about the neural correlates of perception comes from studying vision. Auditory inputs enter cortex with its own set of unique qualities, and leads to use in oral communication, speech, music, and the understanding of emotional and intentional states of others, all of which are central to the human experience. To better understand how the auditory system develops, recovers after injury, and how it may have transitioned in its functions over the course of hominin evolution, advances are needed in models of how the human brain is organized to process real-world natural sounds and "auditory objects". This review presents a simple fundamental neurobiological model of hearing perception at a category level that incorporates principles of bottom-up signal processing together with top-down constraints of grounded cognition theories of knowledge representation. Though mostly derived from human neuroimaging literature, this theoretical framework highlights rudimentary principles of real-world sound processing that may apply to most if not all mammalian species with hearing and acoustic communication abilities. The model encompasses three basic categories of sound-source: (1) action sounds (non-vocalizations) produced by 'living things', with human (conspecific) and non-human animal sources representing two subcategories; (2) action sounds produced by 'non-living things', including environmental sources and human-made machinery; and (3) vocalizations ('living things'), with human versus non-human animals as two subcategories therein. The model is presented in the context of cognitive architectures relating to multisensory, sensory-motor, and spoken language organizations. The models' predictive values are further discussed in the context of anthropological theories of oral communication evolution and the neurodevelopment of spoken language proto-networks in infants/toddlers. These phylogenetic

  1. Non-equilibrium dog-flea model

    Science.gov (United States)

    Ackerson, Bruce J.

    2017-11-01

    We develop the open dog-flea model to serve as a check of proposed non-equilibrium theories of statistical mechanics. The model is developed in detail. Then it is applied to four recent models for non-equilibrium statistical mechanics. Comparison of the dog-flea solution with these different models allows checking claims and giving a concrete example of the theoretical models.

  2. Reactivation of neutron killed mammalian cells by gamma irradiation: The observations, possible mechanism and implication

    International Nuclear Information System (INIS)

    Calkins, J.; Harrison, W.; Einspenner, M.

    1990-01-01

    We have observed that combinations of neutron plus gamma ray exposure can significantly increase the colony forming ability of monkey and human cell cultures over the neutron dose alone. The 'reactivation' of neutron killed mammalian cells by gamma rays is analogous to observations made in lower eukaryotic organisms and fits the pattern termed 'T repair' previously postulated for yeast and protozoans. (orig.)

  3. Model and Algorithm for Substantiating Solutions for Organization of High-Rise Construction Project

    Directory of Open Access Journals (Sweden)

    Anisimov Vladimir

    2018-01-01

    Full Text Available In the paper the models and the algorithm for the optimal plan formation for the organization of the material and logistical processes of the high-rise construction project and their financial support are developed. The model is based on the representation of the optimization procedure in the form of a non-linear problem of discrete programming, which consists in minimizing the execution time of a set of interrelated works by a limited number of partially interchangeable performers while limiting the total cost of performing the work. The proposed model and algorithm are the basis for creating specific organization management methodologies for the high-rise construction project.

  4. Model and Algorithm for Substantiating Solutions for Organization of High-Rise Construction Project

    Science.gov (United States)

    Anisimov, Vladimir; Anisimov, Evgeniy; Chernysh, Anatoliy

    2018-03-01

    In the paper the models and the algorithm for the optimal plan formation for the organization of the material and logistical processes of the high-rise construction project and their financial support are developed. The model is based on the representation of the optimization procedure in the form of a non-linear problem of discrete programming, which consists in minimizing the execution time of a set of interrelated works by a limited number of partially interchangeable performers while limiting the total cost of performing the work. The proposed model and algorithm are the basis for creating specific organization management methodologies for the high-rise construction project.

  5. Color stability and lipid oxidation of broiler breast meat from animals raised on organic versus non-organic production systems.

    Science.gov (United States)

    Viana, F M; Canto, A C V C S; Costa-Lima, B R C; Salim, A P A A; Conte-Junior, C A

    2017-03-01

    The aim of the present research was to evaluate the influence of organic and non-organic production systems on color stability and lipid oxidation of broiler meat Pectoralis major (PM) stored under refrigeration (4°C) for 9 days. PM samples from organic (ORG) and non-organic (NORG) production systems were compared based on physicochemical analyses (instrumental color, myoglobin concentration, metmyoglobin reducing activity (MRA), pH, and lipid oxidation) performed in 4 different trials (n = 4). In general, NORG broilers demonstrated higher (P color stability observed in NORG samples can be partly due to lipid oxidation. Therefore, the production system can affect color and lipid stability of broiler breast meat during storage. © 2016 Poultry Science Association Inc.

  6. Problems of allometric scaling analysis: examples from mammalian reproductive biology.

    Science.gov (United States)

    Martin, Robert D; Genoud, Michel; Hemelrijk, Charlotte K

    2005-05-01

    Biological scaling analyses employing the widely used bivariate allometric model are beset by at least four interacting problems: (1) choice of an appropriate best-fit line with due attention to the influence of outliers; (2) objective recognition of divergent subsets in the data (allometric grades); (3) potential restrictions on statistical independence resulting from phylogenetic inertia; and (4) the need for extreme caution in inferring causation from correlation. A new non-parametric line-fitting technique has been developed that eliminates requirements for normality of distribution, greatly reduces the influence of outliers and permits objective recognition of grade shifts in substantial datasets. This technique is applied in scaling analyses of mammalian gestation periods and of neonatal body mass in primates. These analyses feed into a re-examination, conducted with partial correlation analysis, of the maternal energy hypothesis relating to mammalian brain evolution, which suggests links between body size and brain size in neonates and adults, gestation period and basal metabolic rate. Much has been made of the potential problem of phylogenetic inertia as a confounding factor in scaling analyses. However, this problem may be less severe than suspected earlier because nested analyses of variance conducted on residual variation (rather than on raw values) reveals that there is considerable variance at low taxonomic levels. In fact, limited divergence in body size between closely related species is one of the prime examples of phylogenetic inertia. One common approach to eliminating perceived problems of phylogenetic inertia in allometric analyses has been calculation of 'independent contrast values'. It is demonstrated that the reasoning behind this approach is flawed in several ways. Calculation of contrast values for closely related species of similar body size is, in fact, highly questionable, particularly when there are major deviations from the best

  7. The Role of Non-Governmental Organizations in Rural ...

    African Journals Online (AJOL)

    The main purpose of this study was to investigate the roles of non-governmental organizations in rural transformation in Odukpani Local Government Area of Cross River State, Nigeria. The activities they have engaged in and what result they achieved and how this impacted on rural livelihoods and development. A sample ...

  8. Effects of exposure to electromagnetic fields (microwaves) on mammalian pregnancy

    International Nuclear Information System (INIS)

    Dugauquier, C.

    2006-01-01

    Women soldiers account now for nearly 10 % of the NATO forces. Some studies have alleged that exposure to microwaves may result in pregnancy mishaps. We have tried to assess what was the risk. A lot of studies were conducted on non mammalian species: birds, sea urchins, worms and insects. Extrapolation to the mammals is subject to caution due to the protective effect of intrauterine development. We reviewed the literature dealing only with mammals. Even if some discrepancy persists, it seems that the presence or the absence of thermic effect is essential in order to estimate the risk. Reduced birth weight and increased rate of miscarriage were the most common findings when the exposure reached a thermic effect. In the majority of the studies, non thermic exposure had no impact on pregnancy outcome. (authors)

  9. Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

    Science.gov (United States)

    Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

    2010-10-01

    Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

  10. Enhanced production and isotope enrichment of recombinant glycoproteins produced in cultured mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Skelton, David; Goodyear, Abbey [Florida State University, Department of Chemistry and Biochemistry (United States); Ni, DaQun; Walton, Wendy J.; Rolle, Myron; Hare, Joan T. [Florida State University, Institute of Molecular Biophysics (United States); Logan, Timothy M., E-mail: tlogan@fsu.ed [Florida State University, Department of Chemistry and Biochemistry (United States)

    2010-10-15

    NMR studies of post-translationally modified proteins are complicated by the lack of an efficient method to produce isotope enriched recombinant proteins in cultured mammalian cells. We show that reducing the glucose concentration and substituting glutamate for glutamine in serum-free medium increased cell viability while simultaneously increasing recombinant protein yield and the enrichment of non-essential amino acids compared to culture in unmodified, serum-free medium. Adding dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, further improves cell viability, recombinant protein yield, and isotope enrichment. We demonstrate the method by producing partially enriched recombinant Thy1 glycoprotein from Lec1 Chinese hamster ovary (CHO) cells using U-{sup 13}C-glucose and {sup 15}N-glutamate as labeled precursors. This study suggests that uniformly {sup 15}N,{sup 13}C-labeled recombinant proteins may be produced in cultured mammalian cells starting from a mixture of labeled essential amino acids, glucose, and glutamate.

  11. Enhanced production and isotope enrichment of recombinant glycoproteins produced in cultured mammalian cells

    International Nuclear Information System (INIS)

    Skelton, David; Goodyear, Abbey; Ni, DaQun; Walton, Wendy J.; Rolle, Myron; Hare, Joan T.; Logan, Timothy M.

    2010-01-01

    NMR studies of post-translationally modified proteins are complicated by the lack of an efficient method to produce isotope enriched recombinant proteins in cultured mammalian cells. We show that reducing the glucose concentration and substituting glutamate for glutamine in serum-free medium increased cell viability while simultaneously increasing recombinant protein yield and the enrichment of non-essential amino acids compared to culture in unmodified, serum-free medium. Adding dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, further improves cell viability, recombinant protein yield, and isotope enrichment. We demonstrate the method by producing partially enriched recombinant Thy1 glycoprotein from Lec1 Chinese hamster ovary (CHO) cells using U- 13 C-glucose and 15 N-glutamate as labeled precursors. This study suggests that uniformly 15 N, 13 C-labeled recombinant proteins may be produced in cultured mammalian cells starting from a mixture of labeled essential amino acids, glucose, and glutamate.

  12. The DNA damage response in mammalian oocytes

    Directory of Open Access Journals (Sweden)

    John eCarroll

    2013-06-01

    Full Text Available DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumour formation. In the context of oocytes, the impact of DNA damage is not one of tumour formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.

  13. Organic and Non-Organic Language Disorders after Awake Brain Surgery

    Directory of Open Access Journals (Sweden)

    Elke De Witte

    2014-04-01

    Full Text Available INTRODUCTION: Awake surgery with Direct Electrical Stimulation (DES is considered the ‘gold standard’ to resect brain tumours in the language dominant hemisphere (De Witte & Mariën, 2013. Although transient language impairments are common in the immediate postoperative phase, permanent postoperative language deficits seem to be rare (Duffau, 2007. Milian et al. (2014 stated that most patients tolerate the awake procedure well and would undergo a similar procedure again. However, postoperative psychological symptoms including recurrent distressing dreams and persistent avoidance of stimuli have been recorded following awake surgery (Goebel, Nabavi, Schubert, & Mehdorn, 2010; Milian et al., 2014. To the best of our knowledge, psychogenic language disturbances have never been described after awake surgery. In general, only a handful of non-organic, psychogenic language disorders have been reported in the literature (De Letter et al., 2012. We report three patients with left brain tumours (see table 1 who presented linguistic symptoms after awake surgery that were incompatible with the lesion location, suggesting a psychogenic origin. METHODS: Neurocognitive (language, memory, executive functions investigations were carried out before, during and after awake surgery (6 weeks, 6 months postsurgery on the basis of standardised tests. Pre- and postoperative (fMRI images, DTI results and intraoperative DES findings were analysed. A selection of tasks was used to map language intraoperatively (De Witte et al., 2013. In the postoperative phase spontaneous speech and behavioural phenomena to errors were video-recorded. RESULTS: Preoperative language tests did not reveal any speech or language problems. Intraoperatively, eloquent sites were mapped and preserved enabling good language skills at the end of the awake procedure. However, assessments in the first weeks postsurgery disclosed language and behavioural symptoms that support the hypothesis of a

  14. Prevalence of sexual dimorphism in mammalian phenotypic traits

    Science.gov (United States)

    Karp, Natasha A.; Mason, Jeremy; Beaudet, Arthur L.; Benjamini, Yoav; Bower, Lynette; Braun, Robert E.; Brown, Steve D.M.; Chesler, Elissa J.; Dickinson, Mary E.; Flenniken, Ann M.; Fuchs, Helmut; Angelis, Martin Hrabe de; Gao, Xiang; Guo, Shiying; Greenaway, Simon; Heller, Ruth; Herault, Yann; Justice, Monica J.; Kurbatova, Natalja; Lelliott, Christopher J.; Lloyd, K.C. Kent; Mallon, Ann-Marie; Mank, Judith E.; Masuya, Hiroshi; McKerlie, Colin; Meehan, Terrence F.; Mott, Richard F.; Murray, Stephen A.; Parkinson, Helen; Ramirez-Solis, Ramiro; Santos, Luis; Seavitt, John R.; Smedley, Damian; Sorg, Tania; Speak, Anneliese O.; Steel, Karen P.; Svenson, Karen L.; Obata, Yuichi; Suzuki, Tomohiro; Tamura, Masaru; Kaneda, Hideki; Furuse, Tamio; Kobayashi, Kimio; Miura, Ikuo; Yamada, Ikuko; Tanaka, Nobuhiko; Yoshiki, Atsushi; Ayabe, Shinya; Clary, David A.; Tolentino, Heather A.; Schuchbauer, Michael A.; Tolentino, Todd; Aprile, Joseph Anthony; Pedroia, Sheryl M.; Kelsey, Lois; Vukobradovic, Igor; Berberovic, Zorana; Owen, Celeste; Qu, Dawei; Guo, Ruolin; Newbigging, Susan; Morikawa, Lily; Law, Napoleon; Shang, Xueyuan; Feugas, Patricia; Wang, Yanchun; Eskandarian, Mohammad; Zhu, Yingchun; Nutter, Lauryl M. J.; Penton, Patricia; Laurin, Valerie; Clarke, Shannon; Lan, Qing; Sohel, Khondoker; Miller, David; Clark, Greg; Hunter, Jane; Cabezas, Jorge; Bubshait, Mohammed; Carroll, Tracy; Tondat, Sandra; MacMaster, Suzanne; Pereira, Monica; Gertsenstein, Marina; Danisment, Ozge; Jacob, Elsa; Creighton, Amie; Sleep, Gillian; Clark, James; Teboul, Lydia; Fray, Martin; Caulder, Adam; Loeffler, Jorik; Codner, Gemma; Cleak, James; Johnson, Sara; Szoke-Kovacs, Zsombor; Radage, Adam; Maritati, Marina; Mianne, Joffrey; Gardiner, Wendy; Allen, Susan; Cater, Heather; Stewart, Michelle; Keskivali-Bond, Piia; Sinclair, Caroline; Brown, Ellen; Doe, Brendan; Wardle-Jones, Hannah; Grau, Evelyn; Griggs, Nicola; Woods, Mike; Kundi, Helen; Griffiths, Mark N. D.; Kipp, Christian; Melvin, David G.; Raj, Navis P. S.; Holroyd, Simon A.; Gannon, David J.; Alcantara, Rafael; Galli, Antonella; Hooks, Yvette E.; Tudor, Catherine L.; Green, Angela L.; Kussy, Fiona L.; Tuck, Elizabeth J.; Siragher, Emma J.; Maguire, Simon A.; Lafont, David T.; Vancollie, Valerie E.; Pearson, Selina A.; Gates, Amy S.; Sanderson, Mark; Shannon, Carl; Anthony, Lauren F. E.; Sumowski, Maksymilian T.; McLaren, Robbie S. B.; Swiatkowska, Agnieszka; Isherwood, Christopher M.; Cambridge, Emma L; Wilson, Heather M.; Caetano, Susana S.; Mazzeo, Cecilia Icoresi; Dabrowska, Monika H.; Lillistone, Charlotte; Estabel, Jeanne; Maguire, Anna Karin B.; Roberson, Laura-Anne; Pavlovic, Guillaume; Birling, Marie-Christine; Marie, Wattenhofer-Donze; Jacquot, Sylvie; Ayadi, Abdel; Ali-Hadji, Dalila; Charles, Philippe; André, Philippe; Le Marchand, Elise; El Amri, Amal; Vasseur, Laurent; Aguilar-Pimentel, Antonio; Becker, Lore; Treise, Irina; Moreth, Kristin; Stoeger, Tobias; Amarie, Oana V.; Neff, Frauke; Wurst, Wolfgang; Bekeredjian, Raffi; Ollert, Markus; Klopstock, Thomas; Calzada-Wack, Julia; Marschall, Susan; Brommage, Robert; Steinkamp, Ralph; Lengger, Christoph; Östereicher, Manuela A.; Maier, Holger; Stoeger, Claudia; Leuchtenberger, Stefanie; Yildrim, AliÖ; Garrett, Lillian; Hölter, Sabine M; Zimprich, Annemarie; Seisenberger, Claudia; Bürger, Antje; Graw, Jochen; Eickelberg, Oliver; Zimmer, Andreas; Wolf, Eckhard; Busch, Dirk H; Klingenspor, Martin; Schmidt-Weber, Carsten; Gailus-Durner, Valérie; Beckers, Johannes; Rathkolb, Birgit; Rozman, Jan; Wakana, Shigeharu; West, David; Wells, Sara; Westerberg, Henrik; Yaacoby, Shay; White, Jacqueline K.

    2017-01-01

    The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans. PMID:28650954

  15. Overview of one transistor type of hybrid organic ferroelectric non-volatile memory

    Institute of Scientific and Technical Information of China (English)

    Young; Tea; Chun; Daping; Chu

    2015-01-01

    Organic ferroelectric memory devices based on field effect transistors that can be configured between two stable states of on and off have been widely researched as the next generation data storage media in recent years.This emerging type of memory devices can lead to a new instrument system as a potential alternative to previous non-volatile memory building blocks in future processing units because of their numerous merits such as cost-effective process,simple structure and freedom in substrate choices.This bi-stable non-volatile memory device of information storage has been investigated using several organic or inorganic semiconductors with organic ferroelectric polymer materials.Recent progresses in this ferroelectric memory field,hybrid system have attracted a lot of attention due to their excellent device performance in comparison with that of all organic systems.In this paper,a general review of this type of ferroelectric non-volatile memory is provided,which include the device structure,organic ferroelectric materials,electrical characteristics and working principles.We also present some snapshots of our previous study on hybrid ferroelectric memories including our recent work based on zinc oxide nanowire channels.

  16. Role of Non-Government Organizations in strengthening Kazakstan nuclear export control

    International Nuclear Information System (INIS)

    Tazhibaeva, L.; Prokhodtseva, T.

    2002-01-01

    Non-governmental organizations (NGO) are the structures that were born by the time, the time when deep changes in our society led us to new trends in the all spheres of society development, to new decisions and, as a consequence, to new structural findings that where able to govern, to support and put into reality the new ideas the could not be inserted in the structure assemblies of the former society. All non-governmental organizations in Kazakhstan are younger than ten years old, but they already could be considered highly experienced, for intensity of their activity is rather high. The main advantages of NGOs are flexibility and independent source of ideas, basic data and policy assessment. There are several non-government organizations that are working in the field of non-proliferation and export control. Kazakhstan Nuclear Technology Safety Center (NTSC) is among them. Non-proliferation and export control is only a small part of activity that NTSC is involved in. Non-governmental organizations could be of several types: NGOs that are affiliated with university or institute, independent associations, quasi-governmental structures and various foundations. NTSC complementing efforts of Kazakhstan Atomic Energy Committee (KAEC) in the field of non-proliferation and export control. The activity of NTSC in the field of non-proliferation includes: Holding conferences, seminars and workshops; Creating databases and reports; Develop proposal for legislation; Provide specialized training; Analyze data. NTSC is involved in a number of projects devoted to non-proliferation and export control. The following projects are supported by the US Department of Energy cooperation program on nuclear export controls for Russia and the Newly Independent States: System to review Kazakhstan exports (STROKE); Computerization of historical licensing data; Export control reference materials for Kazakhstan organizations; Additional Protocol. STROKE is a technical analysis database for

  17. Protection capacity against low-density lipoprotein oxidation and antioxidant potential of some organic and non-organic wines.

    Science.gov (United States)

    Kalkan Yildirim, Hatice; Delen Akçay, Yasemin; Güvenç, Ulgar; Yildirim Sözmen, Eser

    2004-08-01

    Current research suggests that phenolics from wine may play a positive role against oxidation of low-density lipoprotein (LDL), which is a key step in the development of atherosclerosis. Considering the effects of different wine-making techniques on phenols and the wine consumption preference influencing the benefical effects of the product, organically and non-organically produced wines were obtained from the grapes of Vitis vinifera origin var: Carignan, Cabernet Sauvignon, Merlot, Grenache, Columbard and Semillon. Levels of total phenols [mg/l gallic acid equivalents (GAE)], antioxidant activity (%) and inhibition of LDL oxidation [%, inhibition of diene and malondialdehyde (MDA) formation] were determined. Some phenolic acids (gallic acid, p-hydroxybenzoic acid, syringic acid, 2,3-dihydroxybenzoic acid, ferulic acid, p-coumaric acid and vanillic acid) were quantified by high-performance liquid chromatography equipped with an electrochemical detection carried at +0.65 V (versus Ag/AgCl, 0.5 microA full scale). The highest concentrations of gallic, syringic and ferulic acids were found in organic Cabernet Sauvignon; 2,3-dihydroxybenzoic acid in organic Carignan and p-coumaric and vanillic acids in non-organic Merlot wine. High levels of antioxidant activity (AOA), inhibition of LDL oxidation and total phenol levels were found in non-organic Merlot (101.950% AOA; 88.570% LDL-diene; 41.000% LDL-MDA; 4700.000 mg/l GAE total phenol) and non-organic Cabernet Sauvignon (92.420% AOA; 91.430% LDL-diene; 67.000% LDL-MDA; 3500.000 mg/l GAE total phenol) grape varieties. Concentrations of some individual phenolic constituents (ferulic, p-coumaric, vanillic) are correlated with high antioxidant activity and inhibition of LDL oxidation. The best r value for all examined characteristics was determined for gallic acid, followed by 2,3-dihydroxybenzoic, syringic, ferulic and p-coumaric acids. Negative correlation of vanillic with MDA and p-hydroxybenzoic acid with LDL were

  18. Environmental non-governmental organizations – The actions of civil society in Curitiba and Metropolitan Area

    Directory of Open Access Journals (Sweden)

    Cleusa Mara WOLSKY CARNEIRO

    2010-04-01

    Full Text Available The present article aims at achieving a diagnosis of the major actions of the environmental non-governmental organizations (NGOs that actuate in Curitiba and Metropolitan Area. It also studies the relations established by these organizations to build a place socially fair and environmental sustainable. In order to do that the main activities of these organizations in the last decades were raised through interviews with their representatives, visitations to the central office and verification of the institutional documents available. The paper explains that the NGOs search to make actions that raise a sustainable model of development, since they understand that the State reduced the participation in this sector and that the people gave them power for it. To achieve so, they need to create a net of relationships between the community, the private and public agents and the NGOs, with the objective of learn the problems, point at the solutions and to develop environmental interventions models to legitimize their actions. That way, the territoriality that these organizations seek to create depend of integrated decisions and of a continuous search of people, information and mobilization, to set up news socials actors and to ensure the development of the activities of these organizations.

  19. Polar and non-polar organic aerosols from large-scale agricultural-waste burning emissions in Northern India: Implications to organic mass-to-organic carbon ratio.

    Science.gov (United States)

    Rajput, Prashant; Sarin, M M

    2014-05-01

    This study focuses on characteristics of organic aerosols (polar and non-polar) and total organic mass-to-organic carbon ratio (OM/OC) from post-harvest agricultural-waste (paddy- and wheat-residue) burning emissions in Northern India. Aerosol samples from an upwind location (Patiala: 30.2°N, 76.3°E) in the Indo-Gangetic Plain were analyzed for non-polar and polar fractions of organic carbon (OC1 and OC2) and their respective mass (OM1 and OM2). On average, polar organic aerosols (OM2) contribute nearly 85% of the total organic mass (OM) from the paddy- and wheat-residue burning emissions. The water-soluble-OC (WSOC) to OC2 ratio, within the analytical uncertainty, is close to 1 from both paddy- and wheat-residue burning emissions. However, temporal variability and relatively low WSOC/OC2 ratio (Av: 0.67±0.06) is attributed to high moisture content and poor combustion efficiency during paddy-residue burning, indicating significant contribution (∼30%) of aromatic carbon to OC2. The OM/OC ratio for non-polar (OM1/OC1∼1.2) and polar organic aerosols (OM2/OC2∼2.2), hitherto unknown for open agricultural-waste burning emissions, is documented in this study. The total OM/OC ratio is nearly identical, 1.9±0.2 and 1.8±0.2, from paddy- and wheat-residue burning emissions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Unipolar resistive switching in metal oxide/organic semiconductor non-volatile memories as a critical phenomenon

    International Nuclear Information System (INIS)

    Bory, Benjamin F.; Meskers, Stefan C. J.; Rocha, Paulo R. F.; Gomes, Henrique L.; Leeuw, Dago M. de

    2015-01-01

    Diodes incorporating a bilayer of an organic semiconductor and a wide bandgap metal oxide can show unipolar, non-volatile memory behavior after electroforming. The prolonged bias voltage stress induces defects in the metal oxide with an areal density exceeding 10 17  m −2 . We explain the electrical bistability by the coexistence of two thermodynamically stable phases at the interface between an organic semiconductor and metal oxide. One phase contains mainly ionized defects and has a low work function, while the other phase has mainly neutral defects and a high work function. In the diodes, domains of the phase with a low work function constitute current filaments. The phase composition and critical temperature are derived from a 2D Ising model as a function of chemical potential. The model predicts filamentary conduction exhibiting a negative differential resistance and nonvolatile memory behavior. The model is expected to be generally applicable to any bilayer system that shows unipolar resistive switching

  1. Non-invasive identification of organic materials in historical stringed musical instruments by reflection infrared spectroscopy: a methodological approach.

    Science.gov (United States)

    Invernizzi, Claudia; Daveri, Alessia; Vagnini, Manuela; Malagodi, Marco

    2017-05-01

    The analysis of historical musical instruments is becoming more relevant and the interest is increasingly moving toward the non-invasive reflection FTIR spectroscopy, especially for the analysis of varnishes. In this work, a specific infrared reflectance spectral library of organic compounds was created with the aim of identifying musical instrument materials in a totally non-invasive way. The analyses were carried out on pure organic compounds, as bulk samples and laboratory wooden models, to evaluate the diagnostic reflection mid-infrared (MIR) bands of proteins, polysaccharides, lipids, and resins by comparing reflection spectra before and after the KK correction. This methodological approach was applied to real case studies represented by four Stradivari violins and a Neapolitan mandolin.

  2. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  3. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)

    OpenAIRE

    Zhou, Yihua; Xu, Bixiong C.; Maheshwari, Hiralal G.; He, Li; Reed, Michael; Lozykowski, Maria; Okada, Shigeru; Cataldo, Lori; Coschigamo, Karen; Wagner, Thomas E.; Baumann, Gerhard; Kopchick, John J.

    1997-01-01

    Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/...

  4. Glomerular Filtration Rate Estimation in Renal and Non-Renal Solid Organ Transplantation

    DEFF Research Database (Denmark)

    Hornum, Mads; Feldt-Rasmussen, Bo

    2017-01-01

    Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like hyperten......Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like...... hypertension, hypotension, drugs and infections may play a causative role as well. Organ-specific causes include hepatorenal syndrome, cirrhosis, low cardiac function, low respiratory function and diabetes developed both before and after TX. It is important to be able to perform precise and valid measurements...... rate methods for use in renal and non-renal TX....

  5. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  6. Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

    Directory of Open Access Journals (Sweden)

    Tarikul Huda Mazumder

    Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

  7. Incorporation of mammalian actin into microfilaments in plant cell nucleus

    Directory of Open Access Journals (Sweden)

    Paves Heiti

    2004-04-01

    Full Text Available Abstract Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area.

  8. Amino acids in the cultivation of mammalian cells.

    Science.gov (United States)

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

  9. Revisiting non-Gaussianity from non-attractor inflation models

    Science.gov (United States)

    Cai, Yi-Fu; Chen, Xingang; Namjoo, Mohammad Hossein; Sasaki, Misao; Wang, Dong-Gang; Wang, Ziwei

    2018-05-01

    Non-attractor inflation is known as the only single field inflationary scenario that can violate non-Gaussianity consistency relation with the Bunch-Davies vacuum state and generate large local non-Gaussianity. However, it is also known that the non-attractor inflation by itself is incomplete and should be followed by a phase of slow-roll attractor. Moreover, there is a transition process between these two phases. In the past literature, this transition was approximated as instant and the evolution of non-Gaussianity in this phase was not fully studied. In this paper, we follow the detailed evolution of the non-Gaussianity through the transition phase into the slow-roll attractor phase, considering different types of transition. We find that the transition process has important effect on the size of the local non-Gaussianity. We first compute the net contribution of the non-Gaussianities at the end of inflation in canonical non-attractor models. If the curvature perturbations keep evolving during the transition—such as in the case of smooth transition or some sharp transition scenarios—the Script O(1) local non-Gaussianity generated in the non-attractor phase can be completely erased by the subsequent evolution, although the consistency relation remains violated. In extremal cases of sharp transition where the super-horizon modes freeze immediately right after the end of the non-attractor phase, the original non-attractor result can be recovered. We also study models with non-canonical kinetic terms, and find that the transition can typically contribute a suppression factor in the squeezed bispectrum, but the final local non-Gaussianity can still be made parametrically large.

  10. [Research progress of mammalian synthetic biology in biomedical field].

    Science.gov (United States)

    Yang, Linfeng; Yin, Jianli; Wang, Meiyan; Ye, Haifeng

    2017-03-25

    Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

  11. Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

    Directory of Open Access Journals (Sweden)

    Xiaoling Lu

    2016-01-01

    Full Text Available Hair cells (HCs are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear.

  12. Plasma treatment of mammalian vascular cells : A quantitative description

    NARCIS (Netherlands)

    Kieft, IE; Darios, D; Roks, AJM; Stoffels, E

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  13. Plasma treatment of mammalian vascular cells: a quantitative description

    NARCIS (Netherlands)

    Kieft, I.E.; Darios, D.; Roks, A.J.M.; Stoffels - Adamowicz, E.

    2005-01-01

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  14. Lysis solution composition and non-linear dose-response to ionizing radiation in the non-denaturing DNA filter elution technique

    International Nuclear Information System (INIS)

    Radford, I.R.

    1990-01-01

    The suggestion by Okayasu and Iliakis (1989) that the non-linear dose-response curve, obtained with the non-denaturing filter elution technique for mammalian cells exposed to low-LET radiation, is the result of a technical artefact, was not confirmed. (author)

  15. Safety culture in the nuclear versus non-nuclear organization

    International Nuclear Information System (INIS)

    Haber, S.B.; Shurberg, D.A.

    1996-01-01

    The importance of safety culture in the safe and reliable operation of nuclear organizations is not a new concept. The greatest barriers to this area of research are twofold: (1) the definition and criteria of safety culture for a nuclear organization and (2) the measurement of those attributes in an objective and systematic fashion. This paper will discuss a proposed resolution of those barriers as demonstrated by the collection of data across nuclear and non-nuclear facilities over a two year period

  16. Highly specialized mammalian skulls from the Late Cretaceous of South America.

    Science.gov (United States)

    Rougier, Guillermo W; Apesteguía, Sebastián; Gaetano, Leandro C

    2011-11-02

    Dryolestoids are an extinct mammalian group belonging to the lineage leading to modern marsupials and placentals. Dryolestoids are known by teeth and jaws from the Jurassic period of North America and Europe, but they thrived in South America up to the end of the Mesozoic era and survived to the beginnings of the Cenozoic. Isolated teeth and jaws from the latest Cretaceous of South America provide mounting evidence that, at least in western Gondwana, dryolestoids developed into strongly endemic groups by the Late Cretaceous. However, the lack of pre-Late Cretaceous dryolestoid remains made study of their origin and early diversification intractable. Here we describe the first mammalian remains from the early Late Cretaceous of South America, including two partial skulls and jaws of a derived dryolestoid showing dental and cranial features unknown among any other group of Mesozoic mammals, such as single-rooted molars preceded by double-rooted premolars, combined with a very long muzzle, exceedingly long canines and evidence of highly specialized masticatory musculature. On one hand, the new mammal shares derived features of dryolestoids with forms from the Jurassic of Laurasia, whereas on the other hand, it is very specialized and highlights the endemic, diverse dryolestoid fauna from the Cretaceous of South America. Our specimens include only the second mammalian skull known for the Cretaceous of Gondwana, bridging a previous 60-million-year gap in the fossil record, and document the whole cranial morphology of a dryolestoid, revealing an unsuspected morphological and ecological diversity for non-tribosphenic mammals.

  17. Insights into inner ear-specific gene regulation: epigenetics and non-coding RNAs in inner ear development and regeneration

    Science.gov (United States)

    Avraham, Karen B.

    2016-01-01

    The vertebrate inner ear houses highly specialized sensory organs, tuned to detect and encode sound, head motion and gravity. Gene expression programs under the control of transcription factors orchestrate the formation and specialization of the non-sensory inner ear labyrinth and its sensory constituents. More recently, epigenetic factors and non-coding RNAs emerged as an additional layer of gene regulation, both in inner ear development and disease. In this review, we provide an overview on how epigenetic modifications and non-coding RNAs, in particular microRNAs (miRNAs), influence gene expression and summarize recent discoveries that highlight their critical role in the proper formation of the inner ear labyrinth and its sensory organs. In contrast to non-mammalian vertebrates, adult mammals lack the ability to regenerate inner ear mechano-sensory hair cells. Finally, we discuss recent insights into how epigenetic factors and miRNAs may facilitate, or in the case of mammals, restrict sensory hair cell regeneration. PMID:27836639

  18. The Role of Relational Reward Benefits for Developing the Non-Financial Value of a Customer to an Organization: Structural Equation Modeling Approach

    Directory of Open Access Journals (Sweden)

    Enny Kristiani

    2014-10-01

    Full Text Available Research on the customer value to an organization has been widely explored, yet most studies only determined on the financial value based on the customer’s purchasing behavior. The value of customers beyond their purchasing behavior –defined as the relational worth - has not been commonly captured yet. This non-financial value is one of the drivers in retaining customers, hence it becomes a crucial factor in preserving the profitability of the organization. For this reason, this paper aims to examine the customer non-financial valuations of a loyalty reward program. The scope of the study covered a reward program involving consumer exertions in the context of a Frequent Flyer Program (FFP offered by an airline in Indonesia. The hypotheses are empirically tested with a sample of FFP members conducted through an online survey (n=475. The data were statistically analyzed using structural equation modeling (SEM as a first order construct. Results indicate that the perceived social rewards lead to an affective and normative commitment as well as consumers’ satisfaction, while the economic reward did not have an effect on developing affective bonds with members for long-term relationships. The relational benefit offered through the FFP creates affectively and normatively committed members who produce relational behaviors, in terms of WOM, immunity, openness and acquiescence of the members to the airline. Furthermore, the FFP members produced social behaviors toward the airline when they felt satisfied with their relational exchanges.

  19. Global patterns of fragmentation and connectivity of mammalian carnivore habitat

    OpenAIRE

    Crooks, Kevin R.; Burdett, Christopher L.; Theobald, David M.; Rondinini, Carlo; Boitani, Luigi

    2011-01-01

    Although mammalian carnivores are vulnerable to habitat fragmentation and require landscape connectivity, their global patterns of fragmentation and connectivity have not been examined. We use recently developed high-resolution habitat suitability models to conduct comparative analyses and to identify global hotspots of fragmentation and connectivity for the world's terrestrial carnivores. Species with less fragmentation (i.e. more interior high-quality habitat) had larger geographical ranges...

  20. Intrinsic non-radiative voltage losses in fullerene-based organic solar cells

    Science.gov (United States)

    Benduhn, Johannes; Tvingstedt, Kristofer; Piersimoni, Fortunato; Ullbrich, Sascha; Fan, Yeli; Tropiano, Manuel; McGarry, Kathryn A.; Zeika, Olaf; Riede, Moritz K.; Douglas, Christopher J.; Barlow, Stephen; Marder, Seth R.; Neher, Dieter; Spoltore, Donato; Vandewal, Koen

    2017-06-01

    Organic solar cells demonstrate external quantum efficiencies and fill factors approaching those of conventional photovoltaic technologies. However, as compared with the optical gap of the absorber materials, their open-circuit voltage is much lower, largely due to the presence of significant non-radiative recombination. Here, we study a large data set of published and new material combinations and find that non-radiative voltage losses decrease with increasing charge-transfer-state energies. This observation is explained by considering non-radiative charge-transfer-state decay as electron transfer in the Marcus inverted regime, being facilitated by a common skeletal molecular vibrational mode. Our results suggest an intrinsic link between non-radiative voltage losses and electron-vibration coupling, indicating that these losses are unavoidable. Accordingly, the theoretical upper limit for the power conversion efficiency of single-junction organic solar cells would be reduced to about 25.5% and the optimal optical gap increases to 1.45-1.65 eV, that is, 0.2-0.3 eV higher than for technologies with minimized non-radiative voltage losses.

  1. Effects of global warming on ancient mammalian communities and their environments.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    2009-06-01

    Full Text Available Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C(3/C(4 transitions and relative seasonality.Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (approximately 1.9 million years ago and Pleistocene (approximately 1.3 million years ago in Florida. Stable isotope data demonstrate increased aridity, increased C(4 grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming.Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees N. Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems.

  2. Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

    LENUS (Irish Health Repository)

    Creagh, Emma M

    2009-01-01

    Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal\\/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal\\/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.

  3. Mutation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Okada, S.

    1982-01-01

    Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

  4. Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eun Joo [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Sowers, Anastasia; Thetford, Angela [Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); McKay-Corkum, Grace; Chung, Su I. [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Citrin, Deborah E., E-mail: citrind@mail.nih.gov [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States)

    2016-11-15

    Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. Methods and Materials: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for β-galactosidase activity. Results: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 μg per lung; irradiation plus rapamycin, 21.4 ± 6.0 μg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1β and transforming growth factor β induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). Conclusions: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes.

  5. Stem Cell Models: A Guide to Understand and Mitigate Aging?

    Science.gov (United States)

    Brunauer, Regina; Alavez, Silvestre; Kennedy, Brian K

    2017-01-01

    Aging is studied either on a systemic level using life span and health span of animal models, or on the cellular level using replicative life span of yeast or mammalian cells. While useful in identifying general and conserved pathways of aging, both approaches provide only limited information about cell-type specific causes and mechanisms of aging. Stem cells are the regenerative units of multicellular life, and stem cell aging might be a major cause for organismal aging. Using the examples of hematopoietic stem cell aging and human pluripotent stem cell models, we propose that stem cell models of aging are valuable for studying tissue-specific causes and mechanisms of aging and can provide unique insights into the mammalian aging process that may be inaccessible in simple model organisms. © 2016 S. Karger AG, Basel.

  6. 3D Bioprinting of Tissue/Organ Models.

    Science.gov (United States)

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-04

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems]: Final report

    International Nuclear Information System (INIS)

    Friedberg, E.C.

    1987-08-01

    This study sought to exploit the use of uv radiation as a source of genomic damage. We explored the molecular mechanism of the repair of DNA damage at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian cells. Not only have observations obtained in one biological system suggested specific experimental approaches in others, but we have also learned that some biochemical pathways for DNA repair are unique to specific organisms. Our studies are summarized in terms of 4 major areas of research activity that span the past 16 years. 86 refs

  8. Recombinant protein production from stable mammalian cell lines and pools.

    Science.gov (United States)

    Hacker, David L; Balasubramanian, Sowmya

    2016-06-01

    We highlight recent developments for the production of recombinant proteins from suspension-adapted mammalian cell lines. We discuss the generation of stable cell lines using transposons and lentivirus vectors (non-targeted transgene integration) and site-specific recombinases (targeted transgene integration). Each of these methods results in the generation of cell lines with protein yields that are generally superior to those achievable through classical plasmid transfection that depends on the integration of the transfected DNA by non-homologous DNA end-joining. This is the main reason why these techniques can also be used for the generation of stable cell pools, heterogenous populations of recombinant cells generated by gene delivery and genetic selection without resorting to single cell cloning. This allows the time line from gene transfer to protein production to be reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. The Role of Non-Governmental Non-Profit Organizations in the Provision of Social Services and the Palliation of Poverty

    Directory of Open Access Journals (Sweden)

    Mihaela Bronić

    2005-01-01

    Full Text Available After introductory considerations, arguments are put forward for non-governmental organisations as exclusive providers of social services. The negative characteristics of the non-governmental organization are subject of the third part of the paper. In the fourth part, the meaning of the social funds is explained (they are a kind of non-governmental organisations, and in Part 5, we explain the importance of the synergy between the government and society in the provision of social services. After the explanation of the situation in Croatia, in the Part 6 of the paper we give our final considerations. In Croatia non-governmental organizations that provide social services are slowly developing. In their further strengthening it is necessary to change the general viewpoints concerning the role and importance of the non-governmental sector in the alleviation of poverty, as well as to achieve better coordination between the state and the sector.

  10. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  11. Integrating chemistry, biophysics and physiology in the evolution of mammalian Myoglobins

    DEFF Research Database (Denmark)

    Dasmeh, Pouria

    a general protein phenotype such as folding stability, that was shown as an example to be positively selected in cetacean Mbs in the iv third part of this thesis, affects the rate of protein evolution. Using a model that combines explicit evolution of Mb sequences, folding stability, and application...... of dN/dS ~ 1.5. Overall, this thesis provides one of the first examples in the study of evolution of function and thermodynamic stability in a mammalian protein with implications for fitness. We quantify and highlight the biological relevance for the selection of a higher concentration of Mb...... in the skeletal muscle of marine mammals and provide an explanation for the increase in folding stability of Mb. Moreover, this thesis provides number of theoretical findings directly testable with future experimental studies regarding the function, physiology and thermodynamic stability of mammalian Mbs....

  12. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  13. Modeling population dynamics of mitochondria in mammalian cells

    Science.gov (United States)

    Kornick, Kellianne; Das, Moumita

    Mitochondria are organelles located inside eukaryotic cells and are essential for several key cellular processes such as energy (ATP) production, cell signaling, differentiation, and apoptosis. All organisms are believed to have low levels of variation in mitochondrial DNA (mtDNA), and alterations in mtDNA are connected to a range of human health conditions, including epilepsy, heart failure, Parkinsons disease, diabetes, and multiple sclerosis. Therefore, understanding how changes in mtDNA accumulate over time and are correlated to changes in mitochondrial function and cell properties can have a profound impact on our understanding of cell physiology and the origins of some diseases. Motivated by this, we develop and study a mathematical model to determine which cellular parameters have the largest impact on mtDNA population dynamics. The model consists of coupled ODEs to describe subpopulations of healthy and dysfunctional mitochondria subject to mitochondrial fission, fusion, autophagy, and mutation. We study the time evolution and stability of each sub-population under specific selection biases and pressures by tuning specific terms in our model. Our results may provide insights into how sub-populations of mitochondria survive and evolve under different selection pressures. This work was supported by a Grant from the Moore Foundation.

  14. A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.

    Directory of Open Access Journals (Sweden)

    Akiko Nakanishi

    Full Text Available Transposable elements, including short interspersed repetitive elements (SINEs, comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs, which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8. Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.

  15. miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells.

    Science.gov (United States)

    Kuhn, Stephanie; Johnson, Stuart L; Furness, David N; Chen, Jing; Ingham, Neil; Hilton, Jennifer M; Steffes, Georg; Lewis, Morag A; Zampini, Valeria; Hackney, Carole M; Masetto, Sergio; Holley, Matthew C; Steel, Karen P; Marcotti, Walter

    2011-02-08

    MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.

  16. Acoustophoretic Synchronization of Mammalian Cells in Microchannels

    DEFF Research Database (Denmark)

    Thévoz, P.; Adams, J.D.; Shea, H.

    2010-01-01

    We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel to selec......We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel...

  17. DNA repair enzyme APE1 from evolutionarily ancient Hydra reveals redox activity exclusively found in mammalian APE1.

    Science.gov (United States)

    Pekhale, Komal; Haval, Gauri; Perween, Nusrat; Antoniali, Giulia; Tell, Gianluca; Ghaskadbi, Surendra; Ghaskadbi, Saroj

    2017-11-01

    Only mammalian apurinic/apyrimidinic endonuclease1 (APE1) has been reported to possess both DNA repair and redox activities. C terminal of the protein is required for base excision repair, while the redox activity resides in the N terminal due to cysteine residues at specific positions. APE1s from other organisms studied so far lack the redox activity in spite of having the N terminal domain. We find that APE1 from the Cnidarian Hydra exhibits both endonuclease and redox activities similar to mammalian APE1. We further show the presence of the three indispensable cysteines in Hydra APE1 for redox activity by site directed mutagenesis. Importance of redox domain but not the repair domain of APE1 in regeneration has been demonstrated by using domain-specific inhibitors. Our findings clearly demonstrate that the redox function of APE1 evolved very early in metazoan evolution and is not a recent acquisition in mammalian APE1 as believed so far. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Modelling organic particles in the atmosphere

    International Nuclear Information System (INIS)

    Couvidat, Florian

    2012-01-01

    Organic aerosol formation in the atmosphere is investigated via the development of a new model named H 2 O (Hydrophilic/Hydrophobic Organics). First, a parameterization is developed to take into account secondary organic aerosol formation from isoprene oxidation. It takes into account the effect of nitrogen oxides on organic aerosol formation and the hydrophilic properties of the aerosols. This parameterization is then implemented in H 2 O along with some other developments and the results of the model are compared to organic carbon measurements over Europe. Model performance is greatly improved by taking into account emissions of primary semi-volatile compounds, which can form secondary organic aerosols after oxidation or can condense when temperature decreases. If those emissions are not taken into account, a significant underestimation of organic aerosol concentrations occurs in winter. The formation of organic aerosols over an urban area was also studied by simulating organic aerosols concentration over the Paris area during the summer campaign of Megapoli (July 2009). H 2 O gives satisfactory results over the Paris area, although a peak of organic aerosol concentrations from traffic, which does not appear in the measurements, appears in the model simulation during rush hours. It could be due to an underestimation of the volatility of organic aerosols. It is also possible that primary and secondary organic compounds do not mix well together and that primary semi volatile compounds do not condense on an organic aerosol that is mostly secondary and highly oxidized. Finally, the impact of aqueous-phase chemistry was studied. The mechanism for the formation of secondary organic aerosol includes in-cloud oxidation of glyoxal, methylglyoxal, methacrolein and methylvinylketone, formation of methyltetrols in the aqueous phase of particles and cloud droplets, and the in-cloud aging of organic aerosols. The impact of wet deposition is also studied to better estimate the

  19. Ionic currents and charge movements in organ-cultured rat skeletal muscle.

    Science.gov (United States)

    Hollingworth, S; Marshall, M W; Robson, E

    1984-12-01

    The middle of the fibre voltage-clamp technique was used to measure ionic currents and non-linear charge movements in intact, organ-cultured (in vitro denervated) mammalian fast-twitch (rat extensor digitorum longus) muscle fibres. Muscle fibres organ cultured for 4 days can be used as electrophysiological and morphological models for muscles in vivo denervated for the same length of time. Sodium currents in organ-cultured muscle fibres are similar to innervated fibres except that in the temperature range 0-20 degrees C (a) in the steady state, the voltage distribution of inactivation in cultured fibres is shifted negatively some 20 mV; (b) at the same temperature and membrane potential, the time constant of inactivation in cultured fibres is about twice that of innervated fibres. Potassium currents in innervated and cultured fibres at 15 degrees C can be fitted with the Hodgkin-Huxley n variable raised to the second power. Despite the large range we would estimate that the maximum value of the steady-state potassium conductance of cultured fibres is about one-half that of innervated fibres. The estimated maximum amount of charge moved in cultured fibre is about one-third that in innervated fibres. Compared to innervated fibres, culturing doubles the kinetics of the decay phase of charge movement. The possibility of a negative shift of the voltage distribution of charge movements in cultured fibres is discussed.

  20. Computational modeling of Metal-Organic Frameworks

    Science.gov (United States)

    Sung, Jeffrey Chuen-Fai

    In this work, the metal-organic frameworks MIL-53(Cr), DMOF-2,3-NH 2Cl, DMOF-2,5-NH2Cl, and HKUST-1 were modeled using molecular mechanics and electronic structure. The effect of electronic polarization on the adsorption of water in MIL-53(Cr) was studied using molecular dynamics simulations of water-loaded MIL-53 systems with both polarizable and non-polarizable force fields. Molecular dynamics simulations of the full systems and DFT calculations on representative framework clusters were utilized to study the difference in nitrogen adsorption between DMOF-2,3-NH2Cl and DMOF-2,5-NH 2Cl. Finally, the control of proton conduction in HKUST-1 by complexation of molecules to the Cu open metal site was investigated using the MS-EVB methodology.

  1. Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells for Lab-On-A-Chip Applications.

    Science.gov (United States)

    Bunge, Frank; Driesche, Sander van den; Vellekoop, Michael J

    2017-07-10

    Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel. The porous membranes are used to separate the culture chamber from two supply channels for gases and nutrients. The cells are fed continuously by diffusion through the membranes without the need of an incubator and low requirements on the supply of medium to the assembly. The diffusion of oxygen is modelled in order to find the optimal dimensions of the chamber. The chip is connected via 3D-printed holders to the macroscopic world. The holders are coated with Parlyene C to ensure that only biocompatible materials are in contact with the culture medium. The experiments with MDCK-cells show the successful seeding inside the chip, culturing and passaging. Consequently, the presented platform is a step towards Lab-on-a-Chip applications that require long-term cultivation of mammalian cells.

  2. Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform

    Directory of Open Access Journals (Sweden)

    Ugo Ripamonti

    2016-09-01

    Full Text Available The soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-β3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-β3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus. In marked contrast, the three mammalian TGF-βs do not initiate the induction of bone formation in rodents and lagomorphs. The induction of bone by hTGF-β3/preloaded bioreactors is orchestrated by inducing fibrin-fibronectin rings that structurally organize tissue patterning and morphogenesis within the macroporous spaces. Induced advancing extracellular matrix rings provide the structural anchorage for hyper chromatic cells, interpreted as differentiating osteoblasts re-programmed by hTGF-β3 from invading myoblastic and/or pericytic differentiated cells. Runx2 and Osteocalcin expression are significantly up-regulated correlating to multiple invading cells differentiating into the osteoblastic phenotype. Bioreactors pre-loaded with recombinant human Noggin (hNoggin, a BMPs antagonist, show down-regulation of BMP-2 and other profiled osteogenic proteins’ genes resulting in minimal bone formation. Coral-derived macroporous constructs preloaded with binary applications of hTGF-β3 and hNoggin also show down-regulation of BMP-2 with the induction of limited bone formation. The induction of bone formation by hTGF-β3 is via the BMPs pathway and it is thus blocked by hNoggin. Our systematic studies in Papio ursinus with translational hTGF-β3 in large cranio-mandibulo-facial defects in humans are now requesting the re-evaluation of Bone

  3. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  4. Radioisotope treatment for benign strictures of non-vascular luminal organs

    International Nuclear Information System (INIS)

    Shin, Ji Hoon

    2006-01-01

    Tissue hyperplasia in one of the most frequently encountered complications when self-expanding stents are placed in benign non-vascular luminal organ strictures, thus causing of the lumen. The investigators postulated that ionizing irradiation could be applied to prevent restenosis caused by tissue hyperplasia in non-vascular luminal organs as it reduced coronary or peripheral arterial narrowing successfully. The authors combined β-irradiation using 188 Re-MAG 3 solution with balloon for animal and clinical studies because this new treatment approach had the advantages such as low penetration depth of β-ray, self-centering irradiation, and mechanical effect of balloon dilation over using γ-irradiation with afterloading devices. In this article, the concept and mechanism of radioisotope balloon dilation, and animal and clinical studies using radioisotope balloon dilation are reviewed

  5. STARTING DETERMINANTS OF STRATEGIC APPROACH TO MARKETING OF NON-PROFIT ORGANIZATIONS: THEORETICAL ELABORATION

    OpenAIRE

    Pavičić, Jurica

    2001-01-01

    Non-profit organizations have remarkably important role in contemporary societies since they participate in solutions of numerous problems which enable or prevent functioning of society in an optimal way. In this, systematic application of marketing influences more efficient activity of non-profit organizations in practice, and by this indirectly contributes to better solution of social problems. If qualitative or systematic application of marketing is observed from the aspect of forming and ...

  6. Tritium ingestion as organically bound tritium (OBT) - incorporation in different organs of pregnant and non-pregnant rats

    International Nuclear Information System (INIS)

    Bhatia, A.L.; Pollaris, K.; Vandecasteele, C.M.; Kowalska, M.

    1998-01-01

    For a better understanding of the hazard of tritium, its bound form in the food constituents (organically bound tritium (OBT)) has not been investigated though study on tritiated water are many. Hence an evaluation of the uptake of tritium incorporated in basic constituents of food viz, proteins, carbohydrates and lipids is warranted. Present study cells with the incorporated three organically bound tritium components separated from tritiated milk powder (casein, butter and lactose). This is further compared in the organs of pregnant (after parturition) and non-pregnant rats

  7. MATRIX-VBS (v1.0): Implementing an Evolving Organic Aerosol Volatility in an Aerosol Microphysics Model

    Science.gov (United States)

    Gao, Chloe Y.; Tsigaridis, Kostas; Bauer, Susanne E.

    2017-01-01

    The gas-particle partitioning and chemical aging of semi-volatile organic aerosol are presented in a newly developed box model scheme, where its effect on the growth, composition, and mixing state of particles is examined. The volatility-basis set (VBS) framework is implemented into the aerosol microphysical scheme MATRIX (Multiconfiguration Aerosol TRacker of mIXing state), which resolves mass and number aerosol concentrations and in multiple mixing-state classes. The new scheme, MATRIX-VBS, has the potential to significantly advance the representation of organic aerosols in Earth system models by improving upon the conventional representation as non-volatile particulate organic matter, often also with an assumed fixed size distribution. We present results from idealized cases representing Beijing, Mexico City, a Finnish forest, and a southeastern US forest, and investigate the evolution of mass concentrations and volatility distributions for organic species across the gas and particle phases, as well as assessing their mixing state among aerosol populations. Emitted semi-volatile primary organic aerosols evaporate almost completely in the intermediate-volatility range, while they remain in the particle phase in the low-volatility range. Their volatility distribution at any point in time depends on the applied emission factors, oxidation by OH radicals, and temperature. We also compare against parallel simulations with the original scheme, which represented only the particulate and non-volatile component of the organic aerosol, examining how differently the condensed-phase organic matter is distributed across the mixing states in the model. The results demonstrate the importance of representing organic aerosol as a semi-volatile aerosol, and explicitly calculating the partitioning of organic species between the gas and particulate phases.

  8. A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

    Science.gov (United States)

    Wu, Jun Jie; Wu, Weiju; Tholozan, Frederique M.; Saunter, Christopher D.; Girkin, John M.; Quinlan, Roy A.

    2015-01-01

    We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses. PMID:26236824

  9. Focusing on RISC assembly in mammalian cells.

    Science.gov (United States)

    Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  10. Focusing on RISC assembly in mammalian cells

    International Nuclear Information System (INIS)

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

    2008-01-01

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

  11. Is ultraviolet enhanced reactivation of mammalian virus mutagenic

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

    1981-01-01

    Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

  12. A mammalianized synthetic nitroreductase gene for high-level expression

    International Nuclear Information System (INIS)

    Grohmann, Maik; Paulmann, Nils; Fleischhauer, Sebastian; Vowinckel, Jakob; Priller, Josef; Walther, Diego J

    2009-01-01

    The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy. We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays. In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect. Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans

  13. Molecular modeling of human acidic mammalian chitinase in complex with the natural-product cyclopentapeptide chitinase inhibitor argifin.

    Science.gov (United States)

    Gouda, Hiroaki; Terashima, Shinichi; Iguchi, Kanami; Sugawara, Akihiro; Saito, Yoshifumi; Yamamoto, Tsuyoshi; Hirose, Tomoyasu; Shiomi, Kazuro; Sunazuka, Toshiaki; Omura, Satoshi; Hirono, Shuichi

    2009-09-01

    Human acidic mammalian chitinase (hAMCase) is an attractive target for developing anti-asthma medications. We used a variety of computational methods to investigate the interaction between hAMCase and the natural-product cyclopentapeptide chitinase inhibitor argifin. The three-dimensional structure of hAMCase was first constructed using homology modeling. The interaction mode and binding free energy between argifin and hAMCase were then examined by the molecular-docking calculation and the molecular mechanics Poisson-Boltzmann surface area method combined with molecular dynamics simulation, respectively. The results suggested that argifin binds to hAMCase in a similar fashion to the interaction mode observed in the crystal structure of argifin-human chitotriosidase complex, and possesses inhibitory activity against hAMCase in the micromolar range. We further designed argifin derivatives expected to be selective for hAMCase.

  14. Distributional congruence of mammalian herbivores in the Trans-Himalayan Mountains

    NARCIS (Netherlands)

    Namgail, T.; Wieren, van S.E.; Prins, H.H.T.

    2013-01-01

    Large-scale distribution and diversity patterns of mammalian herbivores, especially less charismatic species in alpine environments remain little understood. We studied distributional congruence of mammalian herbivores in the Trans-Himalayan region of Ladakh to see if the distributions of less

  15. PENERAPAN MODEL PEMBELAJARAN ADVANCE ORGANIZER BERVISI SETS TERHADAP PENINGKATAN PENGUASAAN KONSEP KIMIA

    Directory of Open Access Journals (Sweden)

    Ilam Pratitis

    2015-11-01

    Full Text Available This study aims to determine the effect of the application of learning model with advance organizer envisions SETS to increase mastery of chemistry concepts in the high school in Semarang on buffer solution material. The design used in this research is the design of the control group non equivalent. Sampling was conducted with a purposive sampling technique, and obtained a XI 6 science grade as experimental class and class XI 5 science grade as control class. Data collection method used is the method of documentation, testing, observation, and questionnaires. The results showed that the average cognitive achievement of experimental class was 84, while the control class was 82. The result of data analysis showed that the effect of the application of learning model with advance organizer envisions SETS was able to increase the mastery of chemical concepts of 4%, with a correlation rate of 0.2. Based on the results, it can be concluded that the learning model with advance organizer envisions SETS had positive effect of increasing mastery of the concept of chemistry on buffer solution material. The advice given is learning model with organizer envisions SETS should also be applied to other chemistry materials. This is of course accompanied by a change in order to suit the needs of its effect on learning outcomes in the form of concept mastery of chemistry to be more increased.Keywords: Advance Organizer, Buffer Solution, Concept Mastery, SETS

  16. DNA damage does not appear to be a trigger for thermotolerance in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, R.L.; Shiu, E.; Fisher, G.A.; Hahn, G.M.

    1988-08-01

    The hypothesis that DNA damage is the trigger for thermotolerance in mammalian cells was tested in Chinese hamster ovary cells by looking for evidence of thermotolerance after ionizing radiation or ultraviolet light exposure. As previous studies have demonstrated that relatively non-toxic radiation exposures do not induce thermotolerance in mammalian cells (Li et al. 1976), higher doses, comparable to those used in yeast to induce thermotolerance (Mitchel and Morison 1984), were tested in this study. Doses of this magnitude are lethal to mammalian cells, thereby precluding the use of clonogenic survival as an endpoint. The authors used three alternative assays as indicators of the subsequent development of thermotolerance: (a) heat-induced inhibition of total protein synthesis, (b) heat-induced uptake of dansyl lysine, and (c) synthesis of heat shock proteins. Only total protein synthesis revealed evidence of a small degree of thermotolerance which occurred immediately after ..gamma..-radiation exposure. By 4 h postirradiation the tolerance, as measured by this assay, was no longer evident. No evidence of thermotolerance was seen following UV exposure. In addition, when a large radiation dose was given either immediately before or after a heat treatment used to induce thermotolerance, there was no alteration in the level of heat-induced tolerance, despite the extensive number of DNA strand breaks caused by the radiation.

  17. DNA damage does not appear to be a trigger for thermotolerance in mammalian cells

    International Nuclear Information System (INIS)

    Anderson, R.L.; Shiu, E.; Fisher, G.A.; Hahn, G.M.

    1988-01-01

    The hypothesis that DNA damage is the trigger for thermotolerance in mammalian cells was tested in Chinese hamster ovary cells by looking for evidence of thermotolerance after ionizing radiation or ultraviolet light exposure. As previous studies have demonstrated that relatively non-toxic radiation exposures do not induce thermotolerance in mammalian cells (Li et al. 1976), higher doses, comparable to those used in yeast to induce thermotolerance (Mitchel and Morison 1984), were tested in this study. Doses of this magnitude are lethal to mammalian cells, thereby precluding the use of clonogenic survival as an endpoint. The authors used three alternative assays as indicators of the subsequent development of thermotolerance: (a) heat-induced inhibition of total protein synthesis, (b) heat-induced uptake of dansyl lysine, and (c) synthesis of heat shock proteins. Only total protein synthesis revealed evidence of a small degree of thermotolerance which occurred immediately after γ-radiation exposure. By 4 h postirradiation the tolerance, as measured by this assay, was no longer evident. No evidence of thermotolerance was seen following UV exposure. In addition, when a large radiation dose was given either immediately before or after a heat treatment used to induce thermotolerance, there was no alteration in the level of heat-induced tolerance, despite the extensive number of DNA strand breaks caused by the radiation. (author)

  18. gEVE: a genome-based endogenous viral element database provides comprehensive viral protein-coding sequences in mammalian genomes.

    Science.gov (United States)

    Nakagawa, So; Takahashi, Mahoko Ueda

    2016-01-01

    In mammals, approximately 10% of genome sequences correspond to endogenous viral elements (EVEs), which are derived from ancient viral infections of germ cells. Although most EVEs have been inactivated, some open reading frames (ORFs) of EVEs obtained functions in the hosts. However, EVE ORFs usually remain unannotated in the genomes, and no databases are available for EVE ORFs. To investigate the function and evolution of EVEs in mammalian genomes, we developed EVE ORF databases for 20 genomes of 19 mammalian species. A total of 736,771 non-overlapping EVE ORFs were identified and archived in a database named gEVE (http://geve.med.u-tokai.ac.jp). The gEVE database provides nucleotide and amino acid sequences, genomic loci and functional annotations of EVE ORFs for all 20 genomes. In analyzing RNA-seq data with the gEVE database, we successfully identified the expressed EVE genes, suggesting that the gEVE database facilitates studies of the genomic analyses of various mammalian species.Database URL: http://geve.med.u-tokai.ac.jp. © The Author(s) 2016. Published by Oxford University Press.

  19. Life in groups: the roles of oxytocin in mammalian sociality

    Directory of Open Access Journals (Sweden)

    Allison eAnacker

    2013-12-01

    Full Text Available In recent decades, scientific understanding of the many roles of oxytocin in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that oxytocin influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of oxytocin to life in mammalian social groups. We provide background on the functions of oxytocin in maternal attachments and the early social environment, and give an overview of the role of oxytocin circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of oxytocin in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in oxytocin receptor levels with seasonal changes in social behavior in female meadow voles, and the effects of oxytocin manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that oxytocin is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. Oxytocin’s effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying friendships, organization of broad social structures, and maintenance of established social relationships with individuals

  20. Shift in the isoelectric-point of milk proteins as a consequence of adaptive divergence between the milks of mammalian species.

    LENUS (Irish Health Repository)

    Khaldi, Nora

    2011-07-29

    Abstract Background Milk proteins are required to proceed through a variety of conditions of radically varying pH, which are not identical across mammalian digestive systems. We wished to investigate if the shifts in these requirements have resulted in marked changes in the isoelectric point and charge of milk proteins during evolution. Results We investigated nine major milk proteins in 13 mammals. In comparison with a group of orthologous non-milk proteins, we found that 3 proteins κ-casein, lactadherin, and muc1 have undergone the highest change in isoelectric point during evolution. The pattern of non-synonymous substitutions indicate that selection has played a role in the isoelectric point shift, since residues that show significant evidence of positive selection are much more likely to be charged (p = 0.03 for κ-casein; p < 10-8 for muc1). However, this selection does not appear to be solely due to adaptation to the diversity of mammalian digestive systems, since striking changes are seen among species that resemble each other in terms of their digestion. Conclusion The changes in charge are most likely due to changes of other protein functions, rather than an adaptation to the different mammalian digestive systems. These functions may include differences in bioactive peptide releases in the gut between different mammals, which are known to be a major contributing factor in the functional and nutritional value of mammalian milk. This raises the question of whether bovine milk is optimal in terms of particular protein functions, for human nutrition and possibly disease resistance. This article was reviewed by Fyodor Kondrashov, David Liberles (nominated by David Ardell), and Christophe Lefevre (nominated by Mark Ragan).

  1. The Proposal of the Changes in the Taxation of Income of the Non-profit Organizations

    Directory of Open Access Journals (Sweden)

    Milena Otavová

    2014-01-01

    Full Text Available The paper is focused on the issue of the taxation of incomes of the non-governmental non-profit organizations, especially the civic associations in the conditions of the Czech Republic and in the selected countries of the European Union (Austria, Slovakia, Germany. The main emphasis is put on the comparison of the corporate income tax of the studied countries. Particularly the tax benefits that are provided to the non-profit organizations in the individual countries are compared here. This paper points to the current situation in the Czech Republic, where there is no clear legislation that would regulate the activities by the studied organizations. Changes in the taxation of the incomes of non-profit organizations are designed to eliminate absences with regard to the simplicity and clarity of the individual provisions, and also to prevent misuse of the benefits and to the speculative behavior of tax entities.

  2. Non-invasive localization of organic matter in soil aggregates using SR-μCT

    Science.gov (United States)

    Peth, Stephan; Mordhorst, Anneka; Chenu, Claire; Uteau Puschmann, Daniel; Garnier, Patricia; Nunan, Naoise; Pot, Valerie; Beckmann, Felix; Ogurreck, Malte

    2014-05-01

    Knowledge of the location of soil organic matter (SOM) and its spatial association to soil structure is an important step in improving modeling approaches for simulating organic matter turnover processes. Advanced models for carbon mineralization are able to account for the 3D distribution of SOM which is assumed to influence mineralisation. However, their application is still limited by the fact that no method exists to non-invasively determine the 3D spatial distribution of SOM in structured soils. SR-based X-ray microtomography (SR-µCT) is an advanced and promising tool in gaining knowledge on the 3-dimensional organization of soil phases (minerals, organic matter, water, air) which on a voxel level could be implemented into spatially explicit models. However, since the contrast of linear attenuation coefficients of soil organic matter on the one hand and mineral components and water on the other hand are relatively low, especially when materials are finely dispersed, organic matter within the soil pore space is often not resolved in ordinary X-ray absorption contrast imaging. To circumvent this problem we have developed a staining procedure for organic matter using Osmium-tetroxide since Osmium is an element with an absorption edge at a higher X-ray energy level. Osmium is known from transmission electron microscopy analysis (TEM) to stain organic matter specifically and irreversibly while having an absorption edge at approximately 74 keV. We report on the application of a novel Osmium vapor staining method to analyze differences in organic matter content and identify small scale spatial distribution of SOM in soil aggregates. To achieve this we have taken soil aggregate samples (6-8 mm across) obtained from arable soils differing in soil management. Aggregate samples were investigated by synchrotron-based X-ray microtomography (SR-µCT) after staining the sample with Osmium-tetroxide (OsO4) vapor. We utilized the monochromatic X-ray beam to locate osmium

  3. A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3).

    Science.gov (United States)

    Fuller, Stephen J; McGuffin, Liam J; Marshall, Andrew K; Giraldo, Alejandro; Pikkarainen, Sampsa; Clerk, Angela; Sugden, Peter H

    2012-03-15

    The canonical pathway of regulation of the GCK (germinal centre kinase) III subgroup member, MST3 (mammalian Sterile20-related kinase 3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr(178)), induction of serine/threonine protein kinase activity and nuclear localization. We identified an alternative 'non-canonical' pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein GOLGA2/gm130 (golgin A2/Golgi matrix protein 130). Activation of MST3 by calyculin A (a protein serine/threonine phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr(178)) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr(328)) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr(178)) phosphorylation increased MST3 kinase activity, but this activity was independent of MST3(Thr(328)) phosphorylation. Interestingly, MST3(Thr(328)) lies immediately C-terminal to a STRAD (Sterile20-related adaptor) pseudokinase-like site identified recently as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr(178)/Thr(328)) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr(328)) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex.

  4. A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants.

    Science.gov (United States)

    Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

    2014-04-01

    Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided.

  5. Pharmacokinetic models relevant to toxicity and metabolism for uranium in humans and animals

    International Nuclear Information System (INIS)

    Wrenn, M.E.

    1989-01-01

    Models to predict short and long term accumulation of uranium in the human kidney are reviewed and summarised. These are generally first order linear compartmental models or pseudo-pharmacokinetic models such as the retention model of the ICRP. Pharmacokinetic models account not only for transfer from blood to organs, but also recirculation from the organ to blood. The most recent information on mammalian and human metabolism of uranium is used to establish a revised model. The model is applied to the short term accumulation of uranium in the human kidney after a single rapid dosage to the blood, such as that obtained by inhaling UF6 or its hydrolysis products. It is shown that the maximum accumulation in the kidney under these conditions is less than the fraction of the material distributed from the blood to kidney if a true pharmacokinetic model is used. The best coefficients applicable to man in the authors' view are summarised in model V. For a half-time of two days in the mammalian kidney, the maximum concentration in kidney is 75% of that predicted by a retention model such as that used by the ICRP following a single acute intake. We conclude that one must use true pharmacokinetic models, which incorporate recirculation from the organs to the blood, in order to realistically predict time dependent uptake in the kidneys and other organs. Information is presented showing that the half-time for urinary excretion of soluble uranium in man after inhalation of UF6 is about one quarter of a day. (author)

  6. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    Science.gov (United States)

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Ester Vázquez-Fernández

    2016-09-01

    Full Text Available 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.

  8. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  9. A hypothesis for the minimal overall structure of the mammalian plasma membrane redox system.

    Science.gov (United States)

    de Grey, Aubrey D N J

    2003-05-01

    After a long period of frustration, many components of the mammalian plasma membrane redox system are now being identified at the molecular level. Some are apparently ubiquitous but are necessary only for a subset of electron donors or acceptors; some are present only in certain cell types; some appear to be associated with proton extrusion; some appear to be capable of superoxide production. The volume and variety of data now available have begun to allow the formulation of tentative models for the overall network of interactions of enzymes and substrates that together make up the plasma membrane redox system. Such a model is presented here. The structure discussed here is of the mammalian system, though parts of it may apply more or less accurately to fungal and plant cells too. Judging from the history of mitochondrial oxidative phosphorylation, it may be hoped that the development of models of the whole system - even if they undergo substantial revision thereafter - will markedly accelerate the pace of research in plasma membrane redox, by providing a coherent basis for the design of future experiments.

  10. AREN - A non-governmental organization acting in public formation and information

    International Nuclear Information System (INIS)

    Mauna, Traian; Anghelescu, Serban Mihnea

    1998-01-01

    The Romanian Association for Nuclear Energy - AREN, founded eight years ago as non-governmental and non-profit organization, is deploying its activity on a voluntary basis. The association comprises 248 fellows, as physical persons, 17 juridical supporting fellows and eight honorary fellows, outstanding personalities with special contributions in promoting Romanian nuclear power development, 'Ionel Purica' - prize winners. AREN co-operates with other domestic NGO's and other sister organizations from abroad, is a collective member of the General Association of Romanian Engineers and is affiliated to European Nuclear Society (ENS). For specialist and public information AREN is publishing and disseminating the following four publications: 1 - 'Energia Nucleara' (Nuclear Energy) journal; 2 - the bulletin 'Nucleus' brought from ENS and translated in Romanian language; 3 - the news 'NUC NET', adopted, worked up and translated in Romanian; 4 - the periodic bulletin 'Nuclear News'. Yearly, AREN organizes the 'Nuclear Energy Days' and the biennial International Symposium of Nuclear Energy (SIEN). (authors)

  11. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  12. Brucella spp. of amphibians comprise genomically diverse motile strains competent for replication in macrophages and survival in mammalian hosts

    Science.gov (United States)

    Al Dahouk, Sascha; Köhler, Stephan; Occhialini, Alessandra; Jiménez de Bagüés, María Pilar; Hammerl, Jens Andre; Eisenberg, Tobias; Vergnaud, Gilles; Cloeckaert, Axel; Zygmunt, Michel S.; Whatmore, Adrian M.; Melzer, Falk; Drees, Kevin P.; Foster, Jeffrey T.; Wattam, Alice R.; Scholz, Holger C.

    2017-01-01

    Twenty-one small Gram-negative motile coccobacilli were isolated from 15 systemically diseased African bullfrogs (Pyxicephalus edulis), and were initially identified as Ochrobactrum anthropi by standard microbiological identification systems. Phylogenetic reconstructions using combined molecular analyses and comparative whole genome analysis of the most diverse of the bullfrog strains verified affiliation with the genus Brucella and placed the isolates in a cluster containing B. inopinata and the other non-classical Brucella species but also revealed significant genetic differences within the group. Four representative but molecularly and phenotypically diverse strains were used for in vitro and in vivo infection experiments. All readily multiplied in macrophage-like murine J774-cells, and their overall intramacrophagic growth rate was comparable to that of B. inopinata BO1 and slightly higher than that of B. microti CCM 4915. In the BALB/c murine model of infection these strains replicated in both spleen and liver, but were less efficient than B. suis 1330. Some strains survived in the mammalian host for up to 12 weeks. The heterogeneity of these novel strains hampers a single species description but their phenotypic and genetic features suggest that they represent an evolutionary link between a soil-associated ancestor and the mammalian host-adapted pathogenic Brucella species. PMID:28300153

  13. Colorimetric determination of alkaline phosphatase as indicator of mammalian feces in corn meal: collaborative study.

    Science.gov (United States)

    Gerber, H

    1986-01-01

    In the official method for rodent filth in corn meal, filth and corn meal are separated in organic solvents, and particles are identified by the presence of hair and a mucous coating. The solvents are toxic, poor separation yields low recoveries, and fecal characteristics are rarely present on all fragments, especially on small particles. The official AOAC alkaline phosphatase test for mammalian feces, 44.181-44.184, has therefore been adapted to determine the presence of mammalian feces in corn meal. The enzyme cleaves phosphate radicals from a test indicator/substrate, phenolphthalein diphosphate. As free phenolphthalein accumulates, a pink-to-red color develops in the gelled test agar medium. In a collaborative study conducted to compare the proposed method with the official method for corn meal, 44.049, the proposed method yielded 45.5% higher recoveries than the official method. Repeatability and reproducibility for the official method were roughly 1.8 times more variable than for the proposed method. The method has been adopted official first action.

  14. Model of Organic Solar Cell Photocurrent Including the Effect of Charge Accumulation at Interfaces and Non-Uniform Carrier Generation

    DEFF Research Database (Denmark)

    Torto, Lorenzo; Cester, Andrea; Rizzo, Antonio

    2017-01-01

    We developed an improved model to fit the photocurrent density versus voltage in organic solar cells. The model has been validated by fitting data from P3HT:PCBM solar cells. Our model quantitatively accounts for the band bending near the electrodes caused by charge accumulation in the active layer...

  15. Modelling non-hydrostatic processes in sill regions

    Science.gov (United States)

    Souza, A.; Xing, J.; Davies, A.; Berntsen, J.

    2007-12-01

    We use a non-hydrostatic model to compute tidally induced flow and mixing in the region of bottom topography representing the sill at the entrance to Loch Etive (Scotland). This site is chosen since detailed measurements were recently made there. With non-hydrostatic dynamics in the model our results showed that the model could reproduce the observed flow characteristics, e.g., hydraulic transition, flow separation and internal waves. However, when calculations were performed using the model in the hydrostatic form, significant artificial convective mixing occurred. This influenced the computed temperature and flow field. We will discuss in detail the effects of non-hydrostatic dynamics on flow over the sill, especially investigate non-linear and non-hydrostatic contributions to modelled internal waves and internal wave energy fluxes.

  16. Metal-organic molecular device for non-volatile memory storage

    International Nuclear Information System (INIS)

    Radha, B.; Sagade, Abhay A.; Kulkarni, G. U.

    2014-01-01

    Non-volatile memory devices have been of immense research interest for their use in active memory storage in powered off-state of electronic chips. In literature, various molecules and metal compounds have been investigated in this regard. Molecular memory devices are particularly attractive as they offer the ease of storing multiple memory states in a unique way and also represent ubiquitous choice for miniaturized devices. However, molecules are fragile and thus the device breakdown at nominal voltages during repeated cycles hinders their practical applicability. Here, in this report, a synergetic combination of an organic molecule and an inorganic metal, i.e., a metal-organic complex, namely, palladium hexadecylthiolate is investigated for memory device characteristics. Palladium hexadecylthiolate following partial thermolysis is converted to a molecular nanocomposite of Pd(II), Pd(0), and long chain hydrocarbons, which is shown to exhibit non-volatile memory characteristics with exceptional stability and retention. The devices are all solution-processed and the memory action stems from filament formation across the pre-formed cracks in the nanocomposite film.

  17. Technology of mammalian cell encapsulation

    NARCIS (Netherlands)

    Uludag, H; De Vos, P; Tresco, PA

    2000-01-01

    Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

  18. Linear non-threshold (LNT) radiation hazards model and its evaluation

    International Nuclear Information System (INIS)

    Min Rui

    2011-01-01

    In order to introduce linear non-threshold (LNT) model used in study on the dose effect of radiation hazards and to evaluate its application, the analysis of comprehensive literatures was made. The results show that LNT model is more suitable to describe the biological effects in accuracy for high dose than that for low dose. Repairable-conditionally repairable model of cell radiation effects can be well taken into account on cell survival curve in the all conditions of high, medium and low absorbed dose range. There are still many uncertainties in assessment model of effective dose of internal radiation based on the LNT assumptions and individual mean organ equivalent, and it is necessary to establish gender-specific voxel human model, taking gender differences into account. From above, the advantages and disadvantages of various models coexist. Before the setting of the new theory and new model, LNT model is still the most scientific attitude. (author)

  19. Distribution of mammalian-like melanopsin in cyclostome retinas exhibiting a different extent of visual functions.

    Directory of Open Access Journals (Sweden)

    Lanfang Sun

    Full Text Available Mammals contain 1 melanopsin (Opn4 gene that is expressed in a subset of retinal ganglion cells to serve as a photopigment involved in non-image-forming vision such as photoentrainment of circadian rhythms. In contrast, most nonmammalian vertebrates possess multiple melanopsins that are distributed in various types of retinal cells; however, their functions remain unclear. We previously found that the lamprey has only 1 type of mammalian-like melanopsin gene, which is similar to that observed in mammals. Here we investigated the molecular properties and localization of melanopsin in the lamprey and other cyclostome hagfish retinas, which contribute to visual functions including image-forming vision and mainly to non-image-forming vision, respectively. We isolated 1 type of mammalian-like melanopsin cDNA from the eyes of each species. We showed that the recombinant lamprey melanopsin was a blue light-sensitive pigment and that both the lamprey and hagfish melanopsins caused light-dependent increases in calcium ion concentration in cultured cells in a manner that was similar to that observed for mammalian melanopsins. We observed that melanopsin was distributed in several types of retinal cells, including horizontal cells and ganglion cells, in the lamprey retina, despite the existence of only 1 melanopsin gene in the lamprey. In contrast, melanopsin was almost specifically distributed to retinal ganglion cells in the hagfish retina. Furthermore, we found that the melanopsin-expressing horizontal cells connected to the rhodopsin-containing short photoreceptor cells in the lamprey. Taken together, our findings suggest that in cyclostomes, the global distribution of melanopsin in retinal cells might not be related to the melanopsin gene number but to the extent of retinal contribution to visual function.

  20. Exciplex fluorescence emission from simple organic intramolecular constructs in non-polar and highly polar media as model systems for DNA-assembled exciplex detectors.

    Science.gov (United States)

    Bichenkova, Elena V; Sardarian, Ali R; Wilton, Amanda N; Bonnet, Pascal; Bryce, Richard A; Douglas, Kenneth T

    2006-01-21

    Organic intramolecular exciplexes, N-(4-dimethylaminobenzyl)-N-(1-pyrenemethyl)amine (1) and N'-4-dimethylaminonaphthyl-N-(1-pyrenemethyl)amine (2), were used as model systems to reveal major factors affecting their exciplex fluorescence, and thus lay the basis for developing emissive target-assembled exciplexes for DNA-mounted systems in solution. These models with an aromatic pyrenyl hydrocarbon moiety as an electron acceptor appropriately connected to an aromatic dimethylamino electron donor component (N,N-dimethylaminophenyl or N,N-dimethylaminonaphthyl) showed strong intramolecular exciplex emission in both non-polar and highly polar solvents. The effect of dielectric constant on the maximum wavelength for exciplex emission was studied, and emission was observed for 1 and 2 over the full range of solvent from non-polar hydrocarbons up to N-methylformamide with a dielectric constant of 182. Quantum yields were determined for these intramolecular exciplexes in a range of solvents relative to that for Hoechst 33,258. Conformational analysis of 1 was performed both computationally and via qualitative 2D NMR using (1)H-NOESY experiments. The results obtained indicated the contribution of pre-folded conformation(s) to the ground state of 1 conducive to exciplex emission. This research provides the initial background for design of self-assembled, DNA-mounted exciplexes and underpins further development of exciplex-based hybridisation bioassays.

  1. Role of H1 linker histones in mammalian development and stem cell differentiation.

    Science.gov (United States)

    Pan, Chenyi; Fan, Yuhong

    2016-03-01

    H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A facile and sensitive method for quantification of cyclic nucleotide monophosphates in mammalian organs: basal levels of eight cNMPs and identification of 2',3'-cIMP.

    Science.gov (United States)

    Jia, Xin; Fontaine, Benjamin M; Strobel, Fred; Weinert, Emily E

    2014-12-12

    A sensitive, versatile and economical method to extract and quantify cyclic nucleotide monophosphates (cNMPs) using LC-MS/MS, including both 3',5'-cNMPs and 2',3'-cNMPs, in mammalian tissues and cellular systems has been developed. Problems, such as matrix effects from complex biological samples, are addressed and have been optimized. This protocol allows for comparison of multiple cNMPs in the same system and was used to examine the relationship between tissue levels of cNMPs in a panel of rat organs. In addition, the study reports the first identification and quantification of 2',3'-cIMP. The developed method will allow for quantification of cNMPs levels in cells and tissues with varying disease states, which will provide insight into the role(s) and interplay of cNMP signalling pathways.

  3. Evaluating analytical ionization quenching correction models for 3D liquid organic scintillator detector

    Science.gov (United States)

    Alsanea, F.; Beddar, S.

    2017-05-01

    Proton therapy offers dosimetric advantage over conventional photon therapy due to the finite range of the proton beam, which improves dose conformity. However, one of the main challenges of proton beam therapy is verification of the complex treatment plans delivered to a patient. Thus, 3D measurements are needed to verify the complex dose distribution. A 3D organic scintillator detector is capable of such measurements. However, organic scintillators exhibit a non-linear relation to the ionization density called ionization quenching. The ionization quenching phenomenon in organic scintillators must be accounted for to obtain accurate dose measurements. We investigated the energy deposition by secondary electrons (EDSE) model to explain ionization quenching in 3D liquid organic scintillator when exposed to proton beams. The EDSE model was applied to volumetric scintillation measurement of proton pencil beam with energies of 85.6, 100.9, 144.9 and 161.9 MeV. The quenching parameter in EDSE model ρq was determined by plotting the total light output vs the initial energy of the ion. The results were compared to the Birks semi-empirical formula of scintillation light emission.

  4. Functional Identification of Dendritic Cells in the Teleost Model, Rainbow Trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Bassity, Elizabeth; Clark, Theodore G.

    2012-01-01

    Dendritic cells are specialized antigen presenting cells that bridge innate and adaptive immunity in mammals. This link between the ancient innate immune system and the more evolutionarily recent adaptive immune system is of particular interest in fish, the oldest vertebrates to have both innate and adaptive immunity. It is unknown whether dendritic cells co-evolved with the adaptive response, or if the connection between innate and adaptive immunity relied on a fundamentally different cell type early in evolution. We approached this question using the teleost model organism, rainbow trout (Oncorhynchus mykiss), with the aim of identifying dendritic cells based on their ability to stimulate naïve T cells. Adapting mammalian protocols for the generation of dendritic cells, we established a method of culturing highly motile, non-adherent cells from trout hematopoietic tissue that had irregular membrane processes and expressed surface MHCII. When side-by-side mixed leukocyte reactions were performed, these cells stimulated greater proliferation than B cells or macrophages, demonstrating their specialized ability to present antigen and therefore their functional homology to mammalian dendritic cells. Trout dendritic cells were then further analyzed to determine if they exhibited other features of mammalian dendritic cells. Trout dendritic cells were found to have many of the hallmarks of mammalian DCs including tree-like morphology, the expression of dendritic cell markers, the ability to phagocytose small particles, activation by toll-like receptor-ligands, and the ability to migrate in vivo. As in mammals, trout dendritic cells could be isolated directly from the spleen, or larger numbers could be derived from hematopoietic tissue and peripheral blood mononuclear cells in vitro. PMID:22427987

  5. Mammalian RNA polymerase II core promoters: insights from genome-wide studies

    DEFF Research Database (Denmark)

    Sandelin, Albin; Carninci, Piero; Lenhard, Boris

    2007-01-01

    The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing...... in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing...

  6. Using non-human primates to benefit humans: research and organ transplantation.

    Science.gov (United States)

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

  7. Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model

    Science.gov (United States)

    Zanin, Mark; Koçer, Zeynep A.; Poulson, Rebecca L.; Gabbard, Jon D.; Howerth, Elizabeth W.; Jones, Cheryl A.; Friedman, Kimberly; Seiler, Jon; Danner, Angela; Kercher, Lisa; McBride, Ryan; Paulson, James C.; Wentworth, David E.; Krauss, Scott; Tompkins, Stephen M.; Stallknecht, David E.

    2016-01-01

    ABSTRACT H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low-pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. Our objective was to assess the disease-causing potential of 30 LP H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. Of these, 17 (56.7%) caused 100% mortality and 24 were of pathogenicity similar to that of A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck origin were more pathogenic than those of shorebird origin, as 13 of 18 (72.2%) duck origin viruses caused 100% mortality while 4 of 12 (33.3%) shorebird origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between the groups. Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids; however, binding to mammalian-type α2,6-linked sialic acids was also detected. These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk. IMPORTANCE Low-pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. To address this, we studied 30 LP avian H7 viruses isolated from wild

  8. A linear solvation energy relationship model of organic chemical partitioning to dissolved organic carbon.

    Science.gov (United States)

    Kipka, Undine; Di Toro, Dominic M

    2011-09-01

    Predicting the association of contaminants with both particulate and dissolved organic matter is critical in determining the fate and bioavailability of chemicals in environmental risk assessment. To date, the association of a contaminant to particulate organic matter is considered in many multimedia transport models, but the effect of dissolved organic matter is typically ignored due to a lack of either reliable models or experimental data. The partition coefficient to dissolved organic carbon (K(DOC)) may be used to estimate the fraction of a contaminant that is associated with dissolved organic matter. Models relating K(DOC) to the octanol-water partition coefficient (K(OW)) have not been successful for many types of dissolved organic carbon in the environment. Instead, linear solvation energy relationships are proposed to model the association of chemicals with dissolved organic matter. However, more chemically diverse K(DOC) data are needed to produce a more robust model. For humic acid dissolved organic carbon, the linear solvation energy relationship predicts log K(DOC) with a root mean square error of 0.43. Copyright © 2011 SETAC.

  9. Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

    Science.gov (United States)

    Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

    2009-10-01

    The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

  10. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  11. Targeted Nanodiamonds for Identification of Subcellular Protein Assemblies in Mammalian Cells

    OpenAIRE

    Lake, Michael P.; Bouchard, Louis-S.

    2017-01-01

    Transmission electron microscopy (TEM) can be used to successfully determine the structures of proteins. However, such studies are typically done ex situ after extraction of the protein from the cellular environment. Here we describe an application for nanodiamonds as targeted intensity contrast labels in biological TEM, using the nuclear pore complex (NPC) as a model macroassembly. We demonstrate that delivery of antibody-conjugated nanodiamonds to live mammalian cells using maltotriose-conj...

  12. Possible involvement of SINEs in mammalian-specific brain formation.

    Science.gov (United States)

    Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

    2008-03-18

    Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

  13. Bioenergetics of mammalian sperm capacitation.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  14. Correlations and Non-Linear Probability Models

    DEFF Research Database (Denmark)

    Breen, Richard; Holm, Anders; Karlson, Kristian Bernt

    2014-01-01

    the dependent variable of the latent variable model and its predictor variables. We show how this correlation can be derived from the parameters of non-linear probability models, develop tests for the statistical significance of the derived correlation, and illustrate its usefulness in two applications. Under......Although the parameters of logit and probit and other non-linear probability models are often explained and interpreted in relation to the regression coefficients of an underlying linear latent variable model, we argue that they may also be usefully interpreted in terms of the correlations between...... certain circumstances, which we explain, the derived correlation provides a way of overcoming the problems inherent in cross-sample comparisons of the parameters of non-linear probability models....

  15. Metaphors of Teacher Candidates' Regarding the Concept of "Non-Governmental Organizations" (NGOs)

    Science.gov (United States)

    Selanik-Ay, Tugba

    2016-01-01

    In this study, a learning area in social studies curriculum called "Groups, institutions and social organizations" was used. It can be seen that an important role for teachers in a social studies programme is to benefit from non-governmental organizations. The aim of this study is to investigate primary school teacher candidates' social…

  16. THE ROLE OF NON-GOVERNMENTAL ORGANIZATIONS AS A CHANGE PROMOTER WITHIN EUROPEAN POLICIES

    Directory of Open Access Journals (Sweden)

    Carmen Claudia ARUSTEI

    2014-10-01

    Full Text Available The importance of the non-governmental organization (NGO in implementing specific activities and priorities of European policies increases continuously because of the new environment requirements. Through a qualitative research, our study aims to highlight the catalysts and the main constraints in operationalizing the European policies involving the civil sector. Our approach is integrative and nontheless sequential and it is based on a multi-player model with the identification of the role and types of actions specific to each party involved. A temporal comparative analysis is also made by highlighting the evolution in time of the strategic pillars, the constraints and problems specific to the NGOs. The conclusions of our study are going towards pro-active measures: a fair placement considering the role of NGOs within implementing European policies considering the fact that they can offer consistent support and can undertake innovative actions that generate benefits for the society, community and the organization itself.

  17. Modelling uptake into roots and subsequent translocation of neutral and ionisable organic compounds

    DEFF Research Database (Denmark)

    Trapp, Stefan

    2000-01-01

    A study on uptake of neutral and dissociating organic compounds from soil solution into roots, and their subsequent translocation, was undertaken using model simulations. The model approach combines the processes of lipophilic sorption, electrochemical interactions, ion trap, advection in xylem...... and dilution by growth. It needs as input data, apart fromplant properties, log KOW, pKa and the valency number of the compound, and pH and chemical concentration in the soil solution. Equilibrium and dynamic (steady-state) models were tested against measured data from several authors, including non...

  18. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

    Science.gov (United States)

    Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

  19. A versatile system for USER cloning-based assembly of expression vectors for mammalian cell engineering.

    Directory of Open Access Journals (Sweden)

    Anne Mathilde Lund

    Full Text Available A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique--USER cloning--to rapidly construct mammalian expression vectors of multiple DNA fragments and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site, cellular localization signals and epitope- and purification tags. Building blocks in the toolbox can be easily combined as they contain defined and tested Flexible Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of gene, promoter or selection marker in existing plasmids and simple construction of vectors encoding proteins, which are fused to fluorescence-, purification-, localization-, or epitope tags. The mammalian expression vector assembly platform currently allows for the assembly of up to seven fragments in a single cloning step with correct directionality and with a cloning efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors.

  20. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model

    Science.gov (United States)

    Martin, François-Pierre J; Dumas, Marc-Emmanuel; Wang, Yulan; Legido-Quigley, Cristina; Yap, Ivan K S; Tang, Huiru; Zirah, Séverine; Murphy, Gerard M; Cloarec, Olivier; Lindon, John C; Sprenger, Norbert; Fay, Laurent B; Kochhar, Sunil; van Bladeren, Peter; Holmes, Elaine; Nicholson, Jeremy K

    2007-01-01

    Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography–mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level. PMID:17515922

  1. Neutrino mass models and the implications of a non-zero reactor angle

    International Nuclear Information System (INIS)

    King, S.F.

    2009-01-01

    In this talk we survey some of the recent promising developments in the search for the theory behind neutrino mass and mixing, and indeed all fermion masses and mixing. The talk is organized in terms of a neutrino mass models decision tree according to which the answers to experimental questions provide sign posts to guide through the maze of theoretical models eventually towards a complete theory of flavour and unification. It is also discussed the theoretical implications of the measurement of non-zero reactor angle, as hinted at by recent experimental measurements.

  2. Influence of Spirulina platensis exudates on the endocrine and nervous systems of a mammalian model

    OpenAIRE

    Samah M.M. Fathy; Ashraf M.M. Essa

    2015-01-01

    Objective: To investigate the effect of intra-peritoneal injection of purified exudates of axenic Spirulina platensis on the mammalian endocrine and nervous systems. Methods: The intra-peritoneal injection of the cyanobacterial exudates in mice was applied. Sex hormonal levels of testosterone and progesterone were measured using radioimmunoassay while the follicular stimulating hormone and luteinizing hormone were evaluated by direct chemiluminescence. In addition, superoxide dismutase, ca...

  3. Secreted factors as synaptic organizers.

    Science.gov (United States)

    Johnson-Venkatesh, Erin M; Umemori, Hisashi

    2010-07-01

    A critical step in synaptic development is the differentiation of presynaptic and postsynaptic compartments. This complex process is regulated by a variety of secreted factors that serve as synaptic organizers. Specifically, fibroblast growth factors, Wnts, neurotrophic factors and various other intercellular signaling molecules are proposed to regulate presynaptic and/or postsynaptic differentiation. Many of these factors appear to function at both the neuromuscular junction and in the central nervous system, although the specific function of the molecules differs between the two. Here we review secreted molecules that organize the synaptic compartments and discuss how these molecules shape synaptic development, focusing on mammalian in vivo systems. Their critical role in shaping a functional neural circuit is underscored by their possible link to a wide range of neurological and psychiatric disorders both in animal models and by mutations identified in human patients. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Voltage-gated sodium (Nav channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions, a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.

  5. Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

    Science.gov (United States)

    Li, Yang; Liu, Huihui; Xia, Mengdie; Gong, Haipeng

    2016-01-01

    Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.

  6. Modeling of Volatility with Non-linear Time Series Model

    OpenAIRE

    Kim Song Yon; Kim Mun Chol

    2013-01-01

    In this paper, non-linear time series models are used to describe volatility in financial time series data. To describe volatility, two of the non-linear time series are combined into form TAR (Threshold Auto-Regressive Model) with AARCH (Asymmetric Auto-Regressive Conditional Heteroskedasticity) error term and its parameter estimation is studied.

  7. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  8. Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction.

    Science.gov (United States)

    Sunagar, Kartik; Johnson, Warren E; O'Brien, Stephen J; Vasconcelos, Vítor; Antunes, Agostinho

    2012-07-01

    Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among others, blockage of cyclic nucleotide-gated and voltage-gated ion channels and inhibition of smooth muscle contraction. We evaluated the molecular evolution of CRISPs in toxicoferan reptiles at both nucleotide and protein levels relative to their nonvenomous mammalian homologs. We show that the evolution of CRISP gene in these reptiles is significantly influenced by positive selection and in snakes (ω = 3.84) more than in lizards (ω = 2.33), whereas mammalian CRISPs were under strong negative selection (CRISP1 = 0.55, CRISP2 = 0.40, and CRISP3 = 0.68). The use of ancestral sequence reconstruction, mapping of mutations on the three-dimensional structure, and detailed evaluation of selection pressures suggests that the toxicoferan CRISPs underwent accelerated evolution aided by strong positive selection and directional mutagenesis, whereas their mammalian homologs are constrained by negative selection. Gene and protein-level selection analyses identified 41 positively selected sites in snakes and 14 sites in lizards. Most of these sites are located on the molecular surface (nearly 76% in snakes and 79% in lizards), whereas the backbone of the protein retains a highly conserved structural scaffold. Nearly 46% of the positively selected sites occur in the cysteine-rich domain of the protein. This directional mutagenesis, where the hotspots of mutations are found on the molecular surface and functional domains of the protein, acts as a diversifying mechanism for the exquisite biological targeting of CRISPs in toxicoferan reptiles. Finally, our analyses suggest that the evolution of toxicoferan-CRISP venoms might have been influenced by the specific predatory

  9. Sarcopenia and piscines: the case for indeterminate-growing fish as unique genetic model organisms in aging and longevity research.

    Directory of Open Access Journals (Sweden)

    Jacob M Froehlich

    2013-08-01

    Full Text Available Sarcopenia and dynapenia pose significant problems for the aged, especially as life expectancy rises in developed countries. Current therapies are marginally efficacious at best, and barriers to breakthroughs in treatment may result from currently employed model organisms. Here, we argue that the use of indeterminate-growing teleost fish in skeletal muscle aging research may lead to therapeutic advancements not possible with current mammalian models. Evidence from a comparative approach utilizing the subfamily Danioninae suggests that the indeterminate growth paradigm of many teleosts arises from adult muscle stem cells with greater proliferative capacity, even in spite of smaller progenitor populations. We hypothesize that paired-box transcription factors, Pax3/7, are involved with this enhanced self-renewal and that prolonged expression of these factors may allow some fish species to escape, or at least forestall, sarcopenia/dynapenia. Future research efforts should focus on the experimental validation of these genes as key factors in indeterminate growth, both in the context of muscle stem cell proliferation and in prevention of skeletal muscle senescence.

  10. The Yersinia pseudotuberculosis and Yersinia pestis toxin complex is active against cultured mammalian cells.

    Science.gov (United States)

    Hares, Michelle C; Hinchliffe, Stewart J; Strong, Philippa C R; Eleftherianos, Ioannis; Dowling, Andrea J; ffrench-Constant, Richard H; Waterfield, Nick

    2008-11-01

    The toxin complex (Tc) genes were first identified in the insect pathogen Photorhabdus luminescens and encode approximately 1 MDa protein complexes which are toxic to insect pests. Subsequent genome sequencing projects have revealed the presence of tc orthologues in a range of bacterial pathogens known to be associated with insects. Interestingly, members of the mammalian-pathogenic yersiniae have also been shown to encode Tc orthologues. Studies in Yersinia enterocolitica have shown that divergent tc loci either encode insect-active toxins or play a role in colonization of the gut in gastroenteritis models of rats. So far little is known about the activity of the Tc proteins in the other mammalian-pathogenic yersiniae. Here we present work to suggest that Tc proteins in Yersinia pseudotuberculosis and Yersinia pestis are not insecticidal toxins but have evolved for mammalian pathogenicity. We show that Tc is secreted by Y. pseudotuberculosis strain IP32953 during growth in media at 28 degrees C and 37 degrees C. We also demonstrate that oral toxicity of strain IP32953 to Manduca sexta larvae is not due to Tc expression and that lysates of Escherichia coli BL21 expressing the Yersinia Tc proteins are not toxic to Sf9 insect cells but are toxic to cultured mammalian cell lines. Cell lysates of E. coli BL21 expressing the Y. pseudotuberculosis Tc proteins caused actin ruffles, vacuoles and multi-nucleation in cultured human gut cells (Caco-2); similar morphology was observed after application of a lysate of E. coli BL21 expressing the Y. pestis Tc proteins to mouse fibroblast NIH3T3 cells, but not Caco-2 cells. Finally, transient expression of the individual Tc proteins in Caco-2 and NIH3T3 cell lines reproduced the actin and nuclear rearrangement observed with the topical applications. Together these results add weight to the growing hypothesis that the Tc proteins in Y. pseudotuberculosis and Y. pestis have been adapted for mammalian pathogenicity. We further

  11. Application of CFD in Bioprocessing: Separation of mammalian cells using disc stack centrifuge during production of biotherapeutics.

    Science.gov (United States)

    Shekhawat, Lalita Kanwar; Sarkar, Jayati; Gupta, Rachit; Hadpe, Sandeep; Rathore, Anurag S

    2018-02-10

    Centrifugation continues to be one of the most commonly used unit operations for achieving efficient harvest of the product from the mammalian cell culture broth during production of therapeutic monoclonal antibodies (mAbs). Since the mammalian cells are known to be shear sensitive, optimal performance of the centrifuge requires a balance between productivity and shear. In this study, Computational Fluid Dynamics (CFD) has been successfully used as a tool to facilitate efficient optimization. Multiphase Eulerian-Eulerian model coupled with Gidaspow drag model along with Eulerian-Eulerian k-ε mixture turbulence model have been used to quantify the complex hydrodynamics of the centrifuge and thus evaluate the turbulent stresses generated by the centrifugal forces. An empirical model has been developed by statistical analysis of experimentally observed cell lysis data as a function of turbulent stresses. An operating window that offers the optimal balance between high productivity, high separation efficiency, and low cell damage has been identified by use of CFD modeling. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Active zones of mammalian neuromuscular junctions: formation, density, and aging.

    Science.gov (United States)

    Nishimune, Hiroshi

    2012-12-01

    Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2 and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. © 2012 New York Academy of Sciences.

  13. Role of cyclins in controlling progression of mammalian spermatogenesis

    OpenAIRE

    WOLGEMUTH, DEBRA J.; MANTEROLA, MARCIA; VASILEVA, ANA

    2013-01-01

    Cyclins are key regulators of the mammalian cell cycle, functioning primarily in concert with their catalytic partners, the cyclin-dependent kinases (Cdks). While their function during mitosis in somatic cells has been extensively documented, their function during both mitosis and meiosis in the germ line is poorly understood. From the perspective of cell cycle regulation there are several aspects of mammalian spermatogenesis that suggest unique modes of regulation and hence, possible unique ...

  14. Self-Organizing Map Models of Language Acquisition

    Directory of Open Access Journals (Sweden)

    Ping eLi

    2013-11-01

    Full Text Available Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic PDP architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development.

  15. A Facile and Sensitive Method for Quantification of Cyclic Nucleotide Monophosphates in Mammalian Organs: Basal Levels of Eight cNMPs and Identification of 2',3'-cIMP

    Directory of Open Access Journals (Sweden)

    Xin Jia

    2014-12-01

    Full Text Available A sensitive, versatile and economical method to extract and quantify cyclic nucleotide monophosphates (cNMPs using LC-MS/MS, including both 3',5'-cNMPs and 2',3'-cNMPs, in mammalian tissues and cellular systems has been developed. Problems, such as matrix effects from complex biological samples, are addressed and have been optimized. This protocol allows for comparison of multiple cNMPs in the same system and was used to examine the relationship between tissue levels of cNMPs in a panel of rat organs. In addition, the study reports the first identification and quantification of 2',3'-cIMP. The developed method will allow for quantification of cNMPs levels in cells and tissues with varying disease states, which will provide insight into the role(s and interplay of cNMP signalling pathways.

  16. Accountability and non-proliferation nuclear regime: a review of the mutual surveillance Brazilian-Argentine model for nuclear safeguards

    International Nuclear Information System (INIS)

    Xavier, Roberto Salles

    2014-01-01

    The regimes of accountability, the organizations of global governance and institutional arrangements of global governance of nuclear non-proliferation and of Mutual Vigilance Brazilian-Argentine of Nuclear Safeguards are the subject of research. The starting point is the importance of the institutional model of global governance for the effective control of non-proliferation of nuclear weapons. In this context, the research investigates how to structure the current arrangements of the international nuclear non-proliferation and what is the performance of model Mutual Vigilance Brazilian-Argentine of Nuclear Safeguards in relation to accountability regimes of global governance. For that, was searched the current literature of three theoretical dimensions: accountability, global governance and global governance organizations. In relation to the research method was used the case study and the treatment technique of data the analysis of content. The results allowed: to establish an evaluation model based on accountability mechanisms; to assess how behaves the model Mutual Vigilance Brazilian-Argentine Nuclear Safeguards front of the proposed accountability regime; and to measure the degree to which regional arrangements that work with systems of global governance can strengthen these international systems. (author)

  17. Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung.

    Directory of Open Access Journals (Sweden)

    Weiling Zheng

    Full Text Available The fish swimbladder is a unique organ in vertebrate evolution and it functions for regulating buoyancy in most teleost species. It has long been postulated as a homolog of the tetrapod lung, but the molecular evidence is scarce. In order to understand the molecular function of swimbladder as well as its relationship with lungs in tetrapods, transcriptomic analyses of zebrafish swimbladder were carried out by RNA-seq. Gene ontology classification showed that genes in cytoskeleton and endoplasmic reticulum were enriched in the swimbladder. Further analyses depicted gene sets and pathways closely related to cytoskeleton constitution and regulation, cell adhesion, and extracellular matrix. Several prominent transcription factor genes in the swimbladder including hoxc4a, hoxc6a, hoxc8a and foxf1 were identified and their expressions in developing swimbladder during embryogenesis were confirmed. By comparison of enriched transcripts in the swimbladder with those in human and mouse lungs, we established the resemblance of transcriptome of the zebrafish swimbladder and mammalian lungs. Based on the transcriptomic data of zebrafish swimbladder, the predominant functions of swimbladder are in its epithelial and muscular tissues. Our comparative analyses also provide molecular evidence of the relatedness of the fish swimbladder and mammalian lung.

  18. Preparation of highly and generally enriched mammalian tissues for solid state NMR

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Veronica Wai Ching; Reid, David G.; Chow, Wing Ying; Rajan, Rakesh [University of Cambridge, Department of Chemistry (United Kingdom); Green, Maggie [University of Cambridge, Central Biomedical Resources, School of Clinical Medicine (United Kingdom); Brooks, Roger A. [University of Cambridge, Department of Trauma and Orthopaedic Surgery, Addenbrooke’s Hospital (United Kingdom); Duer, Melinda J., E-mail: mjd13@cam.ac.uk [University of Cambridge, Department of Chemistry (United Kingdom)

    2015-10-15

    An appreciable level of isotope labelling is essential for future NMR structure elucidation of mammalian biomaterials, which are either poorly expressed, or unexpressable, using micro-organisms. We present a detailed protocol for high level {sup 13}C enrichment even in slow turnover murine biomaterials (fur keratin), using a customized diet supplemented with commercial labelled algal hydrolysate and formulated as a gel to minimize wastage, which female mice consumed during pregnancy and lactation. This procedure produced approximately eightfold higher fur keratin labelling in pups, exposed in utero and throughout life to label, than in adults exposed for the same period, showing both the effectiveness, and necessity, of this approach.

  19. Non-Participatory Intervention in a Traditional Participatory Organization

    DEFF Research Database (Denmark)

    Jønsson, Thomas; Jeppesen, Hans Jeppe

    2009-01-01

    The aim of the present study is to investigate employee attitudes to non-participatory (topdown) changes in an organizational environment that has hitherto been participatory.Until now, research has traditionally investigated the effects of increased organizational influence on employee attitudes...... and behaviour. This study takes the opposite approach by looking at a decrease in influence. The study was undertaken in a production company with 480 employees. The work was organized in production lines and semi-autonomous working groups. Data was compiled via interviews with selected employees from three...... kinds of production areas: Areas that had implemented 1) all of the  planned changes; 2) some of the changes; or 3) only a few of the changes. The results show that the employees’ reactions to the non-participatory change process addressed the decrease of influence and the consequences thereof; i...

  20. Non-adiabatic Excited State Molecule Dynamics Modeling of Photochemistry and Photophysics of Materials

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Tammie Renee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tretiak, Sergei [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-01-06

    Understanding and controlling excited state dynamics lies at the heart of all our efforts to design photoactive materials with desired functionality. This tailor-design approach has become the standard for many technological applications (e.g., solar energy harvesting) including the design of organic conjugated electronic materials with applications in photovoltaic and light-emitting devices. Over the years, our team has developed efficient LANL-based codes to model the relevant photophysical processes following photoexcitation (spatial energy transfer, excitation localization/delocalization, and/or charge separation). The developed approach allows the non-radiative relaxation to be followed on up to ~10 ps timescales for large realistic molecules (hundreds of atoms in size) in the realistic solvent dielectric environment. The Collective Electronic Oscillator (CEO) code is used to compute electronic excited states, and the Non-adiabatic Excited State Molecular Dynamics (NA-ESMD) code is used to follow the non-adiabatic dynamics on multiple coupled Born-Oppenheimer potential energy surfaces. Our preliminary NA-ESMD simulations have revealed key photoinduced mechanisms controlling competing interactions and relaxation pathways in complex materials, including organic conjugated polymer materials, and have provided a detailed understanding of photochemical products and intermediates and the internal conversion process during the initiation of energetic materials. This project will be using LANL-based CEO and NA-ESMD codes to model nonradiative relaxation in organic and energetic materials. The NA-ESMD and CEO codes belong to a class of electronic structure/quantum chemistry codes that require large memory, “long-queue-few-core” distribution of resources in order to make useful progress. The NA-ESMD simulations are trivially parallelizable requiring ~300 processors for up to one week runtime to reach a meaningful restart point.

  1. The Role of environmental non-governmental organizations in citizens participation for environmental conservation in Iran

    International Nuclear Information System (INIS)

    Bahrainy, H.; Amini, F.

    2001-01-01

    This research focuses on the role of the environmental non-governmental organizations in Iran and also the evaluation of their performance in achieving public participation to protect environment. Findings of this research reveal that so far these organizations have lacked the ability to prepare the context for people involvement in environmental conservation, which is due to several major constraints. Political, legal, and judiciary factors have been the major obstacles against the establishment and smooth activities of these organizations. A few organizations which have overcome the difficulties and began their activities, have not been able to make significant impact on protecting the environment. Lack of experience, both in organization and people, were another factor in limiting the success of these organizations in Iran. To be successful, the environmental non-governmental organization in Iran, require proper political, legal, social and economic settings, as well as the knowledge and skill of running these kind of organizations

  2. Electron microscopic comparison of the sequences of single-stranded genomes of mammalian parvoviruses by heteroduplex mapping

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, P.T.; Olson, W.H.; Allison, D.P.; Bates, R.C.; Snyder, C.E.; Mitra, S.

    1983-01-01

    The sequence homologies among the linear single-stranded genomes of several mammalian parvoviruses have been studied by electron microscopic analysis of tthe heteroduplexes produced by reannealing the complementary strands of their DNAs. The genomes of Kilham rat virus, H-1, minute virus of ice and LuIII, which are antigenically distinct non-defective parvoviruses, have considerable homology: about 70% of their sequences are conserved. The homologous regions map at similar locations in the left halves (from the 3' ends) of the genomes. No sequence homology, however, is observed between the DNAs of these nondefective parvoviruses and that of bovine parvovirus, another non-defective virus, or that of defective adenoassociated virus, nor between the genomes of bovine parvovirus and adenoassociated virus. This suggests that only very short, if any, homologous regions are present. From these results, an evolutionary relationship among Kilham rat virus, H-1, minute virus of mice and LuIII is predicted. It is interesting to note that, although LuIII was originally isolated from a human cell line and is specific for human cells in vitro, its genome has sequences in common only with the rodent viruses Kilham rat virus, minute virus of mice and H-1, and not with the other two mammalian parvoviruses tested.

  3. The Time Is Right to Focus on Model Organism Metabolomes

    Directory of Open Access Journals (Sweden)

    Arthur S. Edison

    2016-02-01

    Full Text Available Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  4. Modeling the gas-particle partitioning of secondary organic aerosol: the importance of liquid-liquid phase separation

    Directory of Open Access Journals (Sweden)

    A. Zuend

    2012-05-01

    Full Text Available The partitioning of semivolatile organic compounds between the gas phase and aerosol particles is an important source of secondary organic aerosol (SOA. Gas-particle partitioning of organic and inorganic species is influenced by the physical state and water content of aerosols, and therefore ambient relative humidity (RH, as well as temperature and organic loading levels. We introduce a novel combination of the thermodynamic models AIOMFAC (for liquid mixture non-ideality and EVAPORATION (for pure compound vapor pressures with oxidation product information from the Master Chemical Mechanism (MCM for the computation of gas-particle partitioning of organic compounds and water. The presence and impact of a liquid-liquid phase separation in the condensed phase is calculated as a function of variations in relative humidity, organic loading levels, and associated changes in aerosol composition. We show that a complex system of water, ammonium sulfate, and SOA from the ozonolysis of α-pinene exhibits liquid-liquid phase separation over a wide range of relative humidities (simulated from 30% to 99% RH. Since fully coupled phase separation and gas-particle partitioning calculations are computationally expensive, several simplified model approaches are tested with regard to computational costs and accuracy of predictions compared to the benchmark calculation. It is shown that forcing a liquid one-phase aerosol with or without consideration of non-ideal mixing bears the potential for vastly incorrect partitioning predictions. Assuming an ideal mixture leads to substantial overestimation of the particulate organic mass, by more than 100% at RH values of 80% and by more than 200% at RH values of 95%. Moreover, the simplified one-phase cases stress two key points for accurate gas-particle partitioning calculations: (1 non-ideality in the condensed phase needs to be considered and (2 liquid-liquid phase separation is a consequence of considerable deviations

  5. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.; Gadê lha, H.; Smith, D.J.; Blake, J.R.; Kirkman-Brown, J.C.

    2011-01-01

    the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian

  6. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    International Nuclear Information System (INIS)

    NONE

    1999-01-01

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair

  7. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-02-12

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

  8. Information system for selection of conditions and equipment for the cultivation of mammalian cells

    Directory of Open Access Journals (Sweden)

    D. R. Batyrgazieva

    2017-01-01

    Full Text Available The use of mammals cells and their products wide application, so the actual problem is a creation of an information system in the field of their cultivation for the organizing and structuring of information on process experimental data. This work is devoted the analysis of mammalian cell cultivation. The main technologies of cell cultivation, necessary equipment and matrices are considered. The main stages of database design and information system is described. The justification of software products are provided and the results of the database and information system implementation are done. The detailed description of all modules of the system, as well as a comparative analysis of the results of the search are in the system to verify correct operation of the system. The scientific and practical significance of the work lies in the fact that the effective tool for presenting knowledge and data for search by specific parameters is required. The convenience of the system is that it is not necessary to address in various data sources to get and conditions of cultivation of mammalian cells, it has already been collected and structured according to parameters. With help of the system, it is possible to select conditions for the cultivation of mammalian cells at the stage of scientific researches that will significantly reduce the time and cost of work, also to rank of recommended technological and hardware solutions. The system has a functional completeness, i.e. in a specific subject area, it ensures the fulfillment of user's requirements, and allows to accumulate and process information.

  9. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  10. Non-linear finite element modeling

    DEFF Research Database (Denmark)

    Mikkelsen, Lars Pilgaard

    The note is written for courses in "Non-linear finite element method". The note has been used by the author teaching non-linear finite element modeling at Civil Engineering at Aalborg University, Computational Mechanics at Aalborg University Esbjerg, Structural Engineering at the University...

  11. Determination of the Support Level of Local Organizations in a Model Forest Initiative: Do Local Stakeholders Have Willingness to Be Involved in the Model Forest Development?

    Directory of Open Access Journals (Sweden)

    Ahmet Tolunay

    2014-10-01

    Full Text Available Voluntary cooperation and the support of stakeholders carry a major importance in the development of Model Forests. The identification of the support level of local organizations as stakeholders in the Bucak Model Forest initiative, located in the Mediterranean region of Turkey, constitutes the theme of this study. Within this scope, the views of the stakeholders comprising local government units (LGUs, non-governmental organizations (NGOs, village councils (VCs, professional organizations (POs and forest products enterprises (FPEs located in the district of Bucak were collected by utilizing a survey technique. The data were analysed by using non-parametric statistical analyses due to the absence of a normal distribution. The results show that the information provided about the Model Forest concept to the stakeholders located in the district on the Bucak Model Forest initiative was identified as a factor impacting the support level. Moreover, it was also observed that the stakeholders were more willing to provide advisory support rather than financial support. NGOs and VCs were identified as stakeholders who could not provide financial support due to their restricted budgets. We discuss the benefits for a Model Forest initiative of establishing international cooperation to strengthen the local and regional sustainable development process.

  12. Synthesis of Substituted Thieno[2,3-d]pyrimidin-4-ones and Their Testing for Evaluation of Cytotoxic Activity on Mammalian Cell Models

    Directory of Open Access Journals (Sweden)

    Kh. A. Bozorov

    2013-01-01

    Full Text Available From 2-amino-3-ethoxycarbonyl-4,5-dimethyl-, -polymethylenethiophenes (1-4 were synthesized 2,3-disubstituted thieno[2,3-d]dihydropyrrolo-, tetrahydropyrido-, and tetrahydroazepino[1,2-a]pyrimidin-4-ones (5-16 for pharmacological investigations. The 12 compounds (5-16 were individually evaluated for their antiproliferative activities on mammalian cancer cell models. All tested compounds showed weak affection on human cervix adenocarcinoma cells (HeLa whereas some of the tested compounds exhibited more consistent inhibition of cell growth on murine myeloma cells (P3X. In both cases some compounds enhanced cell proliferation.

  13. Polish and Silesian Non-Profit Organizations Liquidity Strategies

    Directory of Open Access Journals (Sweden)

    Grzegorz Michalski

    2011-12-01

    Full Text Available The kind of realized mission inflows the sensitivity to risk. Among other factors, the risk results from decision about liquid assets investment level and liquid assets financing. The higher the risk exposure, the higher the level of liquid assets. If the specific risk exposure is smaller, the more aggressive could be the net liquid assets strategy. The organization choosing between various solutions in liquid assets needs to decide what level of risk is acceptable for her owners (or donors and / or capital suppliers. The paper shows how, in authors opinion, decisions, about liquid assets management strategy inflow the risk of the organizations and its economicalresults during realization of main mission. Comparison of theoretical model with empirical data for over 450 Silesian nonprofit organization results suggests that nonprofit organization managing teams choose more risky aggressive liquid assets solutions than for-profit firms.

  14. Role of Notch signaling in the mammalian heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

    2013-12-12

    Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

  15. Organic non-volatile memories from ferroelectric phase-separated blends

    Science.gov (United States)

    Asadi, Kamal; de Leeuw, Dago M.; de Boer, Bert; Blom, Paul W. M.

    2008-07-01

    New non-volatile memories are being investigated to keep up with the organic-electronics road map. Ferroelectric polarization is an attractive physical property as the mechanism for non-volatile switching, because the two polarizations can be used as two binary levels. However, in ferroelectric capacitors the read-out of the polarization charge is destructive. The functionality of the targeted memory should be based on resistive switching. In inorganic ferroelectrics conductivity and ferroelectricity cannot be tuned independently. The challenge is to develop a storage medium in which the favourable properties of ferroelectrics such as bistability and non-volatility can be combined with the beneficial properties provided by semiconductors such as conductivity and rectification. Here we present an integrated solution by blending semiconducting and ferroelectric polymers into phase-separated networks. The polarization field of the ferroelectric modulates the injection barrier at the semiconductor-metal contact. The combination of ferroelectric bistability with (semi)conductivity and rectification allows for solution-processed non-volatile memory arrays with a simple cross-bar architecture that can be read out non-destructively. The concept of an electrically tunable injection barrier as presented here is general and can be applied to other electronic devices such as light-emitting diodes with an integrated on/off switch.

  16. Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development

    Directory of Open Access Journals (Sweden)

    Turenne Nicolas

    2012-08-01

    Full Text Available Abstract Background Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries. Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i trophoblast proliferation and differentiation or (ii embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64 that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones. Methods To gain knowledge on molecular-genetic regulations in a non model organism, we offer an

  17. The comet assay in Environmental Risk Assessment of marine pollutants: applications, assets and handicaps of surveying genotoxicity in non-model organisms.

    Science.gov (United States)

    Martins, Marta; Costa, Pedro M

    2015-01-01

    Determining the genotoxic effects of pollutants has long been a priority in Environmental Risk Assessment (ERA) for coastal ecosystems, especially of complex areas such as estuaries and other confined waterbodies. The acknowledged link between DNA damage, mutagenicity and carcinogenicity to the exposure to certain toxicants has been responsible to the growing interest in determining the genotoxic effects of xenobiotics to wildlife as a measure of environmental risk. The comet assay, although widely employed in in vivo and in vitro toxicology, still holds many constraints in ERA, in large part owing to difficulties in obtaining conclusive cause-effect relationships from complex environments. Nevertheless, these challenges do not hinder the attempts to apply the alkaline comet assay on sentinel organisms, wild or subjected to bioassays in or ex situ (from fish to molluscs) as well to standardise protocols and establish general guidelines to the interpretation of findings. Fish have been regarded as an appealing subject due to the ease of performing the comet assay in whole blood. However, the application of the comet assay is becoming increasingly common in invertebrates (e.g. in molluscan haemocytes and solid tissues such as gills). Virtually all sorts of results have been obtained from the application of the comet assay in ERA (null, positive and inconclusive). However, it has become clear that interpreting DNA damage data from wild organisms is particularly challenging due to their ability to adapt to continuous environmental stressors, including toxicants. Also, the comet assay in non-model organisms for the purpose of ERA implies different constraints, assumptions and interpretation of findings, compared with the in vitro procedures from which most guidelines have been derived. This paper critically reviews the application of the comet assay in ERA, focusing on target organisms and tissues; protocol developments, case studies plus data handling and

  18. Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

    Science.gov (United States)

    Beier, Corinne; Palanker, Daniel; Sher, Alexander

    2018-06-04

    Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Facebook Satisfaction and Its Impacts on Fundraising: A Case Study at a Portuguese Non-Profit Organization

    Directory of Open Access Journals (Sweden)

    Raul M. S. Laureano

    2018-01-01

    Full Text Available Non-profit organizations have invested in the development of content for their Facebook pages, believing be an efficient and effective means to publicize its mission and raising resources, whether monetary or human. The purpose of this study is to assess the satisfaction of the participants with the Facebook page, and how that satisfaction influences the dissemination of the organization through the word-of-mouth and the donations practices. In this context, a questionnaire was administered to 204 participants that were aware of the Portuguese non-profit organization “Leigos para o Desenvolvimento” (People for Development. The results show that the participants are satisfied with Facebook page of the organization, and that there is influence of satisfaction on the word-of-mouth and on the frequency and amount of donations. However, satisfaction with the Facebook, itself, does not appear crucial to the realization of donations, either in the present or in future as intended. The study focuses only on one organization and includes a sample that may not represent all the population extracts and so inhibit the generalization of the findings to other populations. The paper includes implications for the development of an effective use of the Facebook as a digital marketing tool that can contribute to the sustainability of non-profit organizations. The study confirms the importance of the Facebook as a digital marketing tool that can contribute to the sustainability of non-profit organizations.

  20. Some important advances in DNA repair study on the mammalian cells

    International Nuclear Information System (INIS)

    Xia Shouxuan.

    1991-01-01

    In the recent years the study of DNA damage and repair in the mammalian cells has gone deeply at gene level and got the following advances: (1) For a long time DNA has been considered to be an uniform unit in case of damage and repair. Now this concept should be replaced by the non-random distribution of damage and heterogenous repair in the genome. These would allow us to study cellular mutagenesis, carcinogenesis, aging and dying processes in great detail, and would be beneficial to the elucidation of mechanisms of radiation sickness and chemical toxicology. (2) The advent of new techniques in molecular biology has made it possible to isolate and clone the human DNA repair genes. Up to now more than ten human DNA repair genes have been cloned and these works would have an important impact on the theoretical and practical study in this field. Because DNA repair system is very complicate, voluminous work should be done in the future. (3) The technique of gene transfer has been efficiently used in the study of DNA repair in mammalian cells and has made great contribution in the cellular engineering. It could modify the genetic behavior of the gene-accepting cells, and enhance the DNA repair ability to physical and chemical damages. Human gene therapy for DNA deficient diseases is now on the day

  1. Viral Cre-LoxP tools aid genome engineering in mammalian cells.

    Science.gov (United States)

    Sengupta, Ranjita; Mendenhall, Amy; Sarkar, Nandita; Mukherjee, Chandreyee; Afshari, Amirali; Huang, Joseph; Lu, Biao

    2017-01-01

    Targeted nucleases have transformed genome editing technology, providing more efficient methods to make targeted changes in mammalian genome. In parallel, there is an increasing demand of Cre-LoxP technology for complex genome manipulation such as large deletion, addition, gene fusion and conditional removal of gene sequences at the target site. However, an efficient and easy-to-use Cre-recombinase delivery system remains lacking. We designed and constructed two sets of expression vectors for Cre-recombinase using two highly efficient viral systems, the integrative lentivirus and non-integrative adeno associated virus. We demonstrate the effectiveness of those methods in Cre-delivery into stably-engineered HEK293 cells harboring LoxP-floxed red fluorescent protein (RFP) and puromycin (Puro) resistant reporters. The delivered Cre recombinase effectively excised the floxed RFP-Puro either directly or conditionally, therefore validating the function of these molecular tools. Given the convenient options of two selections markers, these viral-based systems offer a robust and easy-to-use tool for advanced genome editing, expanding complicated genome engineering to a variety of cell types and conditions. We have developed and functionally validated two viral-based Cre-recombinase delivery systems for efficient genome manipulation in various mammalian cells. The ease of gene delivery with the built-in reporters and inducible element enables live cell monitoring, drug selection and temporal knockout, broadening applications of genome editing.

  2. New models and molecular markers in evaluation of developmental toxicity

    International Nuclear Information System (INIS)

    Huuskonen, Hannele

    2005-01-01

    Mammalian and non-mammalian embryos and embryonic stem cells may be used as models in mechanistic studies and in testing embryotoxicity of compounds. In addition to conventional culture methods, genetic modifications and use of molecular markers offer significant advantages in mechanistic studies as well as in developing new test methods for embryotoxicity. Zebrafish model has been used for a long time and at present several applications are available. It is an easy vertebral non-mammalian model, whose genome is largely known and several genetic modifications are easily constructed to study gene expression or knocked down genes. Fluorescent marker proteins can be used also in zebrafish to indicate gene activation in transgenic models. Chemical genetics approach has been developed using zebrafish model. This is a new approach to screen small molecules that regulate signaling pathways. Embryonic stem cells have been used in mechanistic studies and mouse embryonic stem cell test has been validated to study embryotoxicity in vitro. This method has been improved using quantitative measurements of molecular endpoints by real-time RT-PCR or fluorescent activated cell sorting methods (FACS). Methods facilitating differentiation to several different cell types are available. We have studied preimplantation mouse embryos as a possible model for in vitro testing. In this method, superovulated and in vivo fertilized preimplantation embryos were collected at morula stage and cultured up to blastocysts. The mouse preimplantation culture test was improved by quantitative gene expression measurement using two-step real-time RT-PCR methods. New endpoints improve the tests of in vitro embryotoxicity because subjective assessments are replaced by objective measurements. In addition, automation is possible and less time is needed for analysis. Thus, high throughput screening will come possible to test large numbers of compounds

  3. A non-local model analysis of heat pulse propagation

    International Nuclear Information System (INIS)

    Iwasaki, T.; Itoh, S.I.; Yagi, M.; Stroth, U.

    1998-01-01

    The anomalous transport in high temperature plasma has been studied for a long time, from the beginning of the fusion research. Since the electron channel in stellarators and tokamaks is clearly anomalous, it is of fundamental importance to investigate the electron heat diffusivity coefficient, χ e and to understand the physical mechanism. Recently, the experimental data for the transient transport of the heat pulse propagation in fusion plasma has been accumulated. An observation was reported on W7-AS which the heat flux changes faster than the change of the temperature profile, responding to the switching on off of the central heating power. The observation on the transient response has simulated the transport modeling, e.g., the critical marginality which implies the existence of a finite threshold in ∇T for the excitation of the turbulence, or the model in which the thermal conductivity is assumed to depend on the heating power. Extensive study is made by use of these models, and the critical marginally model seems to be insufficient to explain various transient transport. The rapid change of the plasma state and its hysteresis nature were successfully modeled by a heating-power-dependent model. The foundation of this model, however, is left for future work. The development of the transport modeling remains to be an urgent problem. In this paper, we investigate the role of the non-locality of the plasma transport in the study of the heat pulse propagation. For this purpose, a model equation is proposed, in which the non-local effect is taken into account in the heat flux. The properties of this model are investigated by performing a transport simulation. The organization of this paper is as follows: In Sec. II, the model equation is proposed and the properties of the model are explained. Using the model equation, the switching on off experiment is simulated in Sec. III. Summary and discussion are given in Sec. IV. (author)

  4. Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence.

    Directory of Open Access Journals (Sweden)

    Katja Schäfer

    Full Text Available The soil-borne plant pathogen Fusarium oxysporum causes life-threatening invasive fusariosis in immunocompromised individuals. The mechanism of infection in mammalian hosts is largely unknown. In the present study we show that the symptoms of disseminated fusariosis caused by F. oxysporum in immunosuppressed mice are remarkably similar to those reported in humans. Distinct fungal structures were observed inside the host, depending on the infected organ. Invasive hyphae developed in the heart and kidney, causing massive colonization of the organs. By contrast, chlamydospore-like survival structures were found in lung, spleen and liver. Systemically infected mice also developed skin and eye infections, as well as thrombosis and necrosis in the tail. We further show that F. oxysporum can disseminate and persist in the organs of immunocompetent animals, and that these latent infections can lead to lethal systemic fusariosis if the host is later subjected to immunosuppressive treatment.

  5. Complex Systems and Self-organization Modelling

    CERN Document Server

    Bertelle, Cyrille; Kadri-Dahmani, Hakima

    2009-01-01

    The concern of this book is the use of emergent computing and self-organization modelling within various applications of complex systems. The authors focus their attention both on the innovative concepts and implementations in order to model self-organizations, but also on the relevant applicative domains in which they can be used efficiently. This book is the outcome of a workshop meeting within ESM 2006 (Eurosis), held in Toulouse, France in October 2006.

  6. Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases.

    Science.gov (United States)

    Kauffman, Karlina J; Yu, Shenliang; Jin, Jiaxin; Mugo, Brian; Nguyen, Nathan; O'Brien, Aidan; Nag, Shanta; Lystad, Alf Håkon; Melia, Thomas J

    2018-04-10

    During macroautophagy/autophagy, mammalian Atg8-family proteins undergo 2 proteolytic processing events. The first exposes a COOH-terminal glycine used in the conjugation of these proteins to lipids on the phagophore, the precursor to the autophagosome, whereas the second releases the lipid. The ATG4 family of proteases drives both cleavages, but how ATG4 proteins distinguish between soluble and lipid-anchored Atg8 proteins is not well understood. In a fully reconstituted delipidation assay, we establish that the physical anchoring of mammalian Atg8-family proteins in the membrane dramatically shifts the way ATG4 proteases recognize these substrates. Thus, while ATG4B is orders of magnitude faster at processing a soluble unprimed protein, all 4 ATG4 proteases can be activated to similar enzymatic activities on lipid-attached substrates. The recognition of lipidated but not soluble substrates is sensitive to a COOH-terminal LIR motif both in vitro and in cells. We suggest a model whereby ATG4B drives very fast priming of mammalian Atg8 proteins, whereas delipidation is inherently slow and regulated by all ATG4 homologs.

  7. Non-parametric model selection for subject-specific topological organization of resting-state functional connectivity.

    Science.gov (United States)

    Ferrarini, Luca; Veer, Ilya M; van Lew, Baldur; Oei, Nicole Y L; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, J

    2011-06-01

    In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover, functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however, was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r(2) statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches, based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Action spectra in mammalian cells exposed to ultraviolet radiation

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

  9. Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

    Science.gov (United States)

    Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

    2017-09-15

    Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

  10. The role of non-governmental organizations in the social and the health system.

    Science.gov (United States)

    Piotrowicz, Maria; Cianciara, Dorota

    2013-01-01

    The article presents the definitions, objectives, fields and tasks of non-governmental organizations in social life, health system and health policy. In addition, the article addresses the issue of effectiveness and quality of NGOs' activity. The term "NGOs" (Non-governmental Organizations) includes different categories of entities that operate not to obtain financial gain, and also do not belong to the government sector. Non-governmental Organizations' fields of activity were described in the International Classification of Non-Profit Organizations (ICNPO). NGOs are an integral part of a democratic society. Sociological sciences emphasize their importance in enhancing social integration, implementation of the principle of subsidiarity, building civil society, social dialogue and participatory democracy. The main tasks of NGOs in the health system are providing services and health advocacy. Provision of services includes medical, social and psychological services as well as, integration activities, care and nursing, material and financial support, educational and information services and training. Health advocacy is a combination of individual and social actions designed to gain political commitment, policy support, social acceptance and systems support for a particular health goal or program. An important task carried out by NGOs is participation in the formation of health policy. The increasing role of NGOs in providing social services and the participation in political processes, result in the need to confirm the validity and credibility of their operation. One of the ways could be to introduce the mechanisms to assess quality and efficiency, such as registration as a part of a legal system, self-regulatory activities (card rules, codes of ethics), certification, participation in networks, monitoring and audit.

  11. The Application of the Sfas No.45 on Financial Reporting in the Non-profit Organization Nurul Huda Mosque Kawangkoan

    OpenAIRE

    Walandouw, Stanley Kho; Mangkona, Sri Wardana Saleh

    2015-01-01

    Organization are founded by the public due to the similarity of interests, both in the realization of human nature as well as to meet their needs. Based on the objectives, the organization can be divided into non-profit organizations and commercial organizations. There is a fundamental difference between nonprofit organizations and commercial organizations, the IAI makes SFAS No.45 which regulates the financial statements of non-profit organizations. The purpose of this study is to see whethe...

  12. Evaluation of Mammalian Interspersed Repeats to investigate the goat genome

    Directory of Open Access Journals (Sweden)

    P. Mariani

    2010-01-01

    Full Text Available Among the repeated sequences present in most eukaryotic genomes, SINEs (Short Interspersed Nuclear Elements are widely used to investigate evolution in the mammalian order (Buchanan et al., 1999. One family of these repetitive sequences, the MIR (Mammalian Interspersed Repeats; Jurka et al., 1995, is ubiquitous in all mammals.MIR elements are tRNA-derived SINEs and are identifiable by a conserved core region of about 70 nucleotides.

  13. Factors that May Lead on the Non-renewal of Certified Organic Product According to Organic Producers in Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Rossi Scalco

    Full Text Available Abstract: The regulatory process of the organic sector in Brazil began in 1999 and has gone through several changes, culminating in the Decree-Law of December 2007, which established rules for the production and trading of organic products in Brazil. In such Decree, the certification has become a compulsory requirement for production and trading of such products, whose rules governing their obtaining follow rigorous controls standards. As the certification process of organic products is recent and there is a lack of studies carried on this subject, this study will contribute to fill the existing gap in the international literature, mainly national about this topic, once that aimed to identify factors that influence the possibility of non-renewal of organic production certificate, according to the perception of certified producers in Brazil. Through this effort, this research should contribute to wider adherence and maintenance of the producer in the certified system or, at least, proposals for further works. A total of 200 producers from several Brazilian states participated in this study, and data analysis was performed using descriptive statistics and, later, exploratory factor analysis. The results achieved holds that the determining factors to the non-renewal of the certificate involve variables related to transactions among operators, organization of the supply chain and to the regulations. Furthermore, to overcome the challenges imposed to rural producers, one of the proposals is for greater effective actions from representative industry entities of the sector in aspects that are related to the certification process.

  14. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...

  15. An initial biochemical and cell biological characterization of the mammalian homologue of a central plant developmental switch, COP1

    Directory of Open Access Journals (Sweden)

    Wang Haiyang

    2002-12-01

    Full Text Available Abstract Background Constitutive photomorphogenic 1 (COP1 has been defined as a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. Although COP1 mammalian homologue has been previously reported, its function and distribution in animal kingdom are not known. Results Here we report the characterization of full-length human and mouse COP1 cDNAs and the genomic structures of the COP1 genes from several different species. Mammalian COP1 protein binds to ubiquitinated proteins in vivo and is itself ubiquitinated. Furthermore, mammalian COP1 is predominately nuclear localized and exists primarily as a complex of over 700 kDa. Through mutagenesis studies, we have defined a leucine-rich nuclear export signal (NES within the coiled-coil domain of mammalian COP1 and a nuclear localization signal (NLS, which is composed of two clusters of positive-charged amino acids, bridged by the RING finger. Disruption of the RING finger structure abolishes the nuclear import, while deletion of the entire RING finger restores the nuclear import. Conclusions Our data suggest that mammalian COP1, similar to its plant homologue, may play a role in ubiquitination. Mammalian COP1 contains a classic leucine-rich NES and a novel bipartite NLS bridged by a RING finger domain. We propose a working model in which the COP1 RING finger functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite NLS. Therefore, in addition to its well-characterized role in ubiquitination, the RING finger domain may also play a structural role in nuclear import.

  16. Natural radiation dose of small mammalians in beech forest of Rokkasho, Japan

    International Nuclear Information System (INIS)

    Ohtsuka, Yoshihito; Iyogi, Takashi; Takaku, Yuichi; Hisamatsu, Shun'ichi

    2008-01-01

    Full text: Protection of the environment itself from radiation hazards is recognized as important as that of humans. Actual data on the background natural radiation dose, which is necessary to evaluate the effect of radiation, are very few, especially in the terrestrial environment. Forests around the Japan's first large scale nuclear fuel reprocessing plant in Rokkasho were selected as the research field for evaluating the background natural radiation to the environment. Data observed will be used in future for the comparison with the radiation dose from radionuclides released from the plant. Small mammalians, mouse (Apodeums argentus) and mole (Urotrichus talpoides), were selected as representative animals of the forests in this study, and it was planned to measure their radiation doses from natural sources; environmental γ-rays, Rn and internal radionuclides. The forests around the plant were classified into three types: beech, oak and coniferous. We have been measuring the natural radiation to the mammalians in each of those forests one by one and report the data for the beech forest here. The mammalians caught in traps in the beech forest during June-October, 2006 were analyzed for their natural radionuclides burdens ( 210 Pb, 210 Po, 40 K, 87 Rb, 226 Ra, 238 U and 232 Th) in 11 organs and carcass. Radiation dose rates from environmental γ-rays and atmospheric concentration of Rn in the forest were also measured during August-December, 2006. Mean internal dose rates of mouse and mole caught in June, 2006 were estimated to be 0.036 μGy h -1 and 0.28 μGy h -1 , respectively, from mean concentrations of the nuclides in a total body and internal dose conversion coefficients by FASSET. The difference of the dose between the two mammalian species was attributed to higher contribution of 210 Po in mole, in which dose reached 0.25 μGy h -1 in contrast to that in mouse of 0.016 μGy h -1 . The concentration of 210 Po in kidney of mole (0.37 Bq g -1 wet) was

  17. Non-thermal plasma destruction of allyl alcohol in waste gas: kinetics and modelling

    Science.gov (United States)

    DeVisscher, A.; Dewulf, J.; Van Durme, J.; Leys, C.; Morent, R.; Van Langenhove, H.

    2008-02-01

    Non-thermal plasma treatment is a promising technique for the destruction of volatile organic compounds in waste gas. A relatively unexplored technique is the atmospheric negative dc multi-pin-to-plate glow discharge. This paper reports experimental results of allyl alcohol degradation and ozone production in this type of plasma. A new model was developed to describe these processes quantitatively. The model contains a detailed chemical degradation scheme, and describes the physics of the plasma by assuming that the fraction of electrons that takes part in chemical reactions is an exponential function of the reduced field. The model captured the experimental kinetic data to less than 2 ppm standard deviation.

  18. Non-thermal plasma destruction of allyl alcohol in waste gas: kinetics and modelling

    International Nuclear Information System (INIS)

    Visscher, A de; Dewulf, J; Durme, J van; Leys, C; Morent, R; Langenhove, H Van

    2008-01-01

    Non-thermal plasma treatment is a promising technique for the destruction of volatile organic compounds in waste gas. A relatively unexplored technique is the atmospheric negative dc multi-pin-to-plate glow discharge. This paper reports experimental results of allyl alcohol degradation and ozone production in this type of plasma. A new model was developed to describe these processes quantitatively. The model contains a detailed chemical degradation scheme, and describes the physics of the plasma by assuming that the fraction of electrons that takes part in chemical reactions is an exponential function of the reduced field. The model captured the experimental kinetic data to less than 2 ppm standard deviation

  19. Masticatory loading, function, and plasticity: a microanatomical analysis of mammalian circumorbital soft-tissue structures.

    Science.gov (United States)

    Jasarević, Eldin; Ning, Jie; Daniel, Ashley N; Menegaz, Rachel A; Johnson, Jeffrey J; Stack, M Sharon; Ravosa, Matthew J

    2010-04-01

    In contrast to experimental evidence regarding the postorbital bar, postorbital septum, and browridge, there is exceedingly little evidence regarding the load-bearing nature of soft-tissue structures of the mammalian circumorbital region. This hinders our understanding of pronounced transformations during primate origins, in which euprimates evolved a postorbital bar from an ancestor with the primitive mammalian condition where only soft tissues spanned the lateral orbital margin between frontal bone and zygomatic arch. To address this significant gap, we investigated the postorbital microanatomy of rabbits subjected to long-term variation in diet-induced masticatory stresses. Rabbits exhibit a masticatory complex and feeding behaviors similar to primates, yet retain a more primitive mammalian circumorbital region. Three cohorts were obtained as weanlings and raised on different diets until adult. Following euthanasia, postorbital soft tissues were dissected away, fixed, and decalcified. These soft tissues were divided into inferior, intermediate, and superior units and then dehydrated, embedded, and sectioned. H&E staining was used to characterize overall architecture. Collagen orientation and complexity were evaluated via picrosirius-red staining. Safranin-O identified proteoglycan content with additional immunostaining performed to assess Type-II collagen expression. Surprisingly, the ligament along the lateral orbital wall was composed of elastic fibrocartilage. A more degraded organization of collagen fibers in this postorbital fibrocartilage is correlated with increased masticatory forces due to a more fracture-resistant diet. Furthermore, the lack of marked changes in the extracellular composition of the lateral orbital wall related to tissue viscoelasticity suggests it is unlikely that long-term exposure to elevated masticatory stresses underlies the development of a bony postorbital bar. (c) 2010 Wiley-Liss, Inc.

  20. MOTORCYCLE CRASH PREDICTION MODEL FOR NON-SIGNALIZED INTERSECTIONS

    Directory of Open Access Journals (Sweden)

    S. HARNEN

    2003-01-01

    Full Text Available This paper attempts to develop a prediction model for motorcycle crashes at non-signalized intersections on urban roads in Malaysia. The Generalized Linear Modeling approach was used to develop the model. The final model revealed that an increase in motorcycle and non-motorcycle flows entering an intersection is associated with an increase in motorcycle crashes. Non-motorcycle flow on major road had the greatest effect on the probability of motorcycle crashes. Approach speed, lane width, number of lanes, shoulder width and land use were also found to be significant in explaining motorcycle crashes. The model should assist traffic engineers to decide the need for appropriate intersection treatment that specifically designed for non-exclusive motorcycle lane facilities.