Science.gov

Sample records for age-dependent branching processes

  1. A path integral approach to age dependent branching processes

    NASA Astrophysics Data System (ADS)

    Greenman, Chris D.

    2017-03-01

    Age dependent population dynamics are frequently modeled with generalizations of the classic McKendrick–von Foerster equation. These are deterministic systems, and a stochastic generalization was recently reported in Greenman and Chou (2016 Phys. Rev. E 93 012112, 2016 J. Stat. Phys. 16449). Here we develop a fully stochastic theory for age-structured populations via quantum field theoretical Doi–Peliti techniques. This results in a path integral formulation where birth and death events correspond to cubic and quadratic interaction terms. This formalism allows us to efficiently recapitulate the results in Greenman and Chou (2016 Phys. Rev. E 93 012112, 2016 J. Stat. Phys. 16449), exemplifying the utility of Doi–Peliti methods. Furthermore, we find that the path integral formulation for age-structured moments has an exact perturbative expansion that explicitly relates to the hereditary structure between correlated individuals. These methods are then generalized with a binary fission model of cell division.

  2. An age-dependent branching process model for the analysis of CFSE-labeling experiments

    PubMed Central

    2010-01-01

    Background Over the past decade, flow cytometric CFSE-labeling experiments have gained considerable popularity among experimentalists, especially immunologists and hematologists, for studying the processes of cell proliferation and cell death. Several mathematical models have been presented in the literature to describe cell kinetics during these experiments. Results We propose a multi-type age-dependent branching process to model the temporal development of populations of cells subject to division and death during CFSE-labeling experiments. We discuss practical implementation of the proposed model; we investigate a competing risk version of the process; and we identify the classes of cellular dependencies that may influence the expectation of the process and those that do not. An application is presented where we study the proliferation of human CD8+ T lymphocytes using our model and a competing risk branching process. Conclusions The proposed model offers a widely applicable approach to the analysis of CFSE-labeling experiments. The model fitted very well our experimental data. It provided reasonable estimates of cell kinetics parameters as well as meaningful insights into the processes of cell division and cell death. In contrast, the competing risk branching process could not describe the kinetics of CD8+ T cells. This suggested that the decision of cell division or cell death may be made early in the cell cycle if not in preceding generations. Also, we show that analyses based on the proposed model are robust with respect to cross-sectional dependencies and to dependencies between fates of linearly filiated cells. Reviewers This article was reviewed by Marek Kimmel, Wai-Yuan Tan and Peter Olofsson. PMID:20569476

  3. A composite likelihood approach to the analysis of longitudinal clonal data on multitype cellular systems under an age-dependent branching process

    PubMed Central

    Chen, Rui; Hyrien, Ollivier; Noble, Mark; Mayer-Pröschel, Margot

    2011-01-01

    A recurrent statistical problem in cell biology is to draw inference about cell kinetics from observations collected at discrete time points. We investigate this problem when multiple cell clones are observed longitudinally over time. The theory of age-dependent branching processes provides an appealing framework for the quantitative analysis of such data. Likelihood inference being difficult in this context, we propose an alternative composite likelihood approach, where the estimation function is defined from the marginal or conditional distributions of the number of cells of each observable cell type. These distributions have generally no closed-form expressions but they can be approximated using simulations. We construct a bias-corrected version of the estimating function, which also offers computational advantages. Two algorithms are discussed to compute parameter estimates. Large sample properties of the estimator are presented. The performance of the proposed method in finite samples is investigated in simulation studies. An application to the analysis of the generation of oligodendrocytes from oligodendrocyte type-2 astrocyte progenitor cells cultured in vitro reveals the effect of neurothrophin-3 on these cells. Our work demonstrates also that the proposed approach outperforms the existing ones. PMID:20732974

  4. Anomalous scaling in an age-dependent branching model.

    PubMed

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  5. Optimal Control of Markov Processes with Age-Dependent Transition Rates

    SciTech Connect

    Ghosh, Mrinal K. Saha, Subhamay

    2012-10-15

    We study optimal control of Markov processes with age-dependent transition rates. The control policy is chosen continuously over time based on the state of the process and its age. We study infinite horizon discounted cost and infinite horizon average cost problems. Our approach is via the construction of an equivalent semi-Markov decision process. We characterise the value function and optimal controls for both discounted and average cost cases.

  6. The important role of lipid peroxidation processes in aging and age dependent diseases.

    PubMed

    Spiteller, Gerhard

    2007-09-01

    Any change in the cell membrane structure activates lipoxygenases (LOX). LOX transform polyunsaturated fatty acids (PUFAs) to lipidhydroperoxide molecules (LOOHs). When cells are severely wounded, this physiological process switches to a non-enzymatic lipid peroxidation (LPO) process producing LOO* radicals. These oxidize nearly all-biological molecules such as lipids, sugars, and proteins. The LOO* induced degradations proceed by transfer of the radicals from cell to cell like an infection. The chemical reactions induced by LO* and LOO* radicals seem to be responsible for aging and induction of age dependent diseases.Alternatively, LO* and LOO* radicals are generated by frying of fats and involve cholesterol-PUFA esters and thus induce atherogenesis. Plants and algae are exposed to LOO* radicals generating radiation. In order to remove LOO* radicals, plants and algae transform PUFAs to furan fatty acids, which are incorporated after consumption of vegetables into mammalian tissues where they act as excellent scavengers of LOO* and LO* radicals.

  7. Branching processes in disease epidemics

    NASA Astrophysics Data System (ADS)

    Singh, Sarabjeet

    Branching processes have served as a model for chemical reactions, biological growth processes and contagion (of disease, information or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this thesis, we focus on branching processes as a model for infectious diseases spreading between individuals belonging to different populations. The distinction between populations can arise from species separation (as in the case of diseases which jump across species) or spatial separation (as in the case of disease spreading between farms, cities, urban centers, etc). A prominent example of the former is zoonoses -- infectious diseases that spill from animals to humans -- whose specific examples include Nipah virus, monkeypox, HIV and avian influenza. A prominent example of the latter is infectious diseases of animals such as foot and mouth disease and bovine tuberculosis that spread between farms or cattle herds. Another example of the latter is infectious diseases of humans such as H1N1 that spread from one city to another through migration of infectious hosts. This thesis consists of three main chapters, an introduction and an appendix. The introduction gives a brief history of mathematics in modeling the spread of infectious diseases along with a detailed description of the most commonly used disease model -- the Susceptible-Infectious-Recovered (SIR) model. The introduction also describes how the stochastic formulation of the model reduces to a branching process in the limit of large population which is analyzed in detail. The second chapter describes a two species model of zoonoses with coupled SIR processes and proceeds into the calculation of statistics pertinent to cross species infection using multitype branching processes. The third chapter describes an SIR process driven by a Poisson process of infection spillovers. This is posed as a

  8. Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

    PubMed

    Wild-Wall, Nele; Falkenstein, Michael

    2010-01-01

    By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

  9. Is extinction age dependent?

    USGS Publications Warehouse

    Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.

    2006-01-01

    Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).

  10. Stochastic model for supersymmetric particle branching process

    NASA Astrophysics Data System (ADS)

    Zhang, Yuanyuan; Chan, Aik Hui; Oh, Choo Hiap

    2017-01-01

    We develop a stochastic branching model to describe the jet evolution of supersymmetric (SUSY) particles. This model is a modified two-phase branching process, or more precisely, a two-phase simple birth process plus Poisson process. Both pure SUSY partons initiated jets and SUSY plus ordinary partons initiated jets scenarios are considered. The stochastic branching equations are established and the Multiplicity Distributions (MDs) are derived for these two scenarios. We also fit the distribution of the general case (SUSY plus ordinary partons initiated jets) with experimental data. The fitting shows the SUSY particles have not participated in branching at current collision energy yet.

  11. Residence times of branching diffusion processes

    NASA Astrophysics Data System (ADS)

    Dumonteil, E.; Mazzolo, A.

    2016-07-01

    The residence time of a branching Brownian process is the amount of time that the mother particle and all its descendants spend inside a domain. Using the Feynman-Kac formalism, we derive the residence-time equation as well as the equations for its moments for a branching diffusion process with an arbitrary number of descendants. This general approach is illustrated with simple examples in free space and in confined geometries where explicit formulas for the moments are obtained within the long time limit. In particular, we study in detail the influence of the branching mechanism on those moments. The present approach can also be applied to investigate other additive functionals of branching Brownian process.

  12. Agriculture and Food Processes Branch program summary document

    SciTech Connect

    Not Available

    1981-06-01

    The food industry, its energy consumption, and its energy conservation targets are discussed. Activities of the Agriculture and Food Processes Branch are described. Summaries of research, development, and demonstration programs of the Branch are given. The programs are categorized into the following: energy integrated farm systems; irrigation systems; crop drying systems; fertilizer; dairy and milk processing; meat processing; sugar processing; citrus processing; ethanol production; food processing efficiency systems; and food sterilization. Summaries are presented of 26 completed projects. (MCW)

  13. Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

    PubMed

    Chow, Maggie L; Pramparo, Tiziano; Winn, Mary E; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J; Courchesne, Eric

    2012-01-01

    Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons

  14. Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages

    PubMed Central

    Winn, Mary E.; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J.; Courchesne, Eric

    2012-01-01

    Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons

  15. Finite-size scaling of survival probability in branching processes

    NASA Astrophysics Data System (ADS)

    Garcia-Millan, Rosalba; Font-Clos, Francesc; Corral, Álvaro

    2015-04-01

    Branching processes pervade many models in statistical physics. We investigate the survival probability of a Galton-Watson branching process after a finite number of generations. We derive analytically the existence of finite-size scaling for the survival probability as a function of the control parameter and the maximum number of generations, obtaining the critical exponents as well as the exact scaling function, which is G (y ) =2 y ey /(ey-1 ) , with y the rescaled distance to the critical point. Our findings are valid for any branching process of the Galton-Watson type, independently of the distribution of the number of offspring, provided its variance is finite. This proves the universal behavior of the finite-size effects in branching processes, including the universality of the metric factors. The direct relation to mean-field percolation is also discussed.

  16. The effect of polyglycerol sulfate branching on inflammatory processes.

    PubMed

    Paulus, Florian; Schulze, Ronny; Steinhilber, Dirk; Zieringer, Maximilian; Steinke, Ingo; Welker, Pia; Licha, Kai; Wedepohl, Stefanie; Dernedde, Jens; Haag, Rainer

    2014-05-01

    In this study, the extent to which the scaffold architecture of polyglycerol sulfates affects inflammatory processes and hemocompatibility is investigated. Competitive L-selectin binding assays, cellular uptake studies, and blood compatibility readouts are done to evaluate distinct biological properties. Fully glycerol based hyperbranched polyglycerol architectures are obtained by either homopolymerization of glycidol (60% branching) or a new copolymerization strategy of glycidol with ethoxyethyl glycidyl ether. Two polyglycerols with 24 and 42% degree of branching (DB) are synthesized by using different monomer feed ratios. A perfectly branched polyglycerol dendrimer is synthesized according to an iterative two-step protocol based on allylation of the alcohol and subsequent catalytic dihydroxylation. All the polyglycerol sulfates are synthesized with a comparable molecular weight and degree of sulfation. The DB make the different polymer conjugates perform different ways. The optimal DB is 60% in all biological assays.

  17. Superlinear scaling of offspring at criticality in branching processes

    NASA Astrophysics Data System (ADS)

    Saichev, A.; Sornette, D.

    2014-01-01

    For any branching process, we demonstrate that the typical total number rmp(ντ) of events triggered over all generations within any sufficiently large time window τ exhibits, at criticality, a superlinear dependence rmp(ντ)˜(ντ)γ (with γ >1) on the total number ντ of the immigrants arriving at the Poisson rate ν. In branching processes in which immigrants (or sources) are characterized by fertilities distributed according to an asymptotic power-law tail with tail exponent 1<γ ⩽2, the exponent of the superlinear law for rmp(ντ) is identical to the exponent γ of the distribution of fertilities. For γ >2 and for standard branching processes without power-law distribution of fertilities, rmp(ντ)˜(ντ)2. This scaling law replaces and tames the divergence ντ /(1-n) of the mean total number R¯t(τ) of events, as the branching ratio (defined as the average number of triggered events of first generation per source) tends to 1. The derivation uses the formalism of generating probability functions. The corresponding prediction is confirmed by numerical calculations, and an heuristic derivation enlightens its underlying mechanism. We also show that R¯t(τ) is always linear in ντ even at criticality (n =1). Our results thus illustrate the fundamental difference between the mean total number, which is controlled by a few extremely rare realizations, and the typical behavior represented by rmp(ντ).

  18. Agriculture and Food Processes Branch program summary document

    SciTech Connect

    1980-06-01

    The work of the Agriculture and Food Processes Branch within the US DOE's Office of Industrial Programs is discussed and reviewed. The Branch is responsible for assisting the food and agricultural sectors of the economy in increasing their energy efficiency by cost sharing with industry the development and demonstration of technologies industry by itself would not develop because of a greater than normal risk factor, but have significant energy conservation benefits. This task is made more difficult by the diversity of agriculture and the food industry. The focus of the program is now on the development and demonstration of energy conservation technology in high energy use industry sectors and agricultural functions (e.g., sugar processing, meat processing, irrigation, and crop drying, high energy use functions common to many sectors of the food industry (e.g., refrigeration, drying, and evaporation), and innovative concepts (e.g., energy integrated farm systems. Specific projects within the program are summarized. (LCL)

  19. Random Walks and Branching Processes in Correlated Gaussian Environment

    NASA Astrophysics Data System (ADS)

    Aurzada, Frank; Devulder, Alexis; Guillotin-Plantard, Nadine; Pène, Françoise

    2017-01-01

    We study persistence probabilities for random walks in correlated Gaussian random environment investigated by Oshanin et al. (Phys Rev Lett, 110:100602, 2013). From the persistence results, we can deduce properties of critical branching processes with offspring sizes geometrically distributed with correlated random parameters. More precisely, we obtain estimates on the tail distribution of its total population size, of its maximum population, and of its extinction time.

  20. Interacting Branching Process as a Simple Model of Innovation

    NASA Astrophysics Data System (ADS)

    Sood, Vishal; Mathieu, Myléne; Shreim, Amer; Grassberger, Peter; Paczuski, Maya

    2010-10-01

    We describe innovation in terms of a generalized branching process. Each new invention pairs with any existing one to produce a number of offspring, which is Poisson distributed with mean p. Existing inventions die with probability p/τ at each generation. In contrast with mean field results, no phase transition occurs; the chance for survival is finite for all p>0. For τ=∞, surviving processes exhibit a bottleneck before exploding superexponentially—a growth consistent with a law of accelerating returns. This behavior persists for finite τ. We analyze, in detail, the asymptotic behavior as p→0.

  1. SkQ1 slows development of age-dependent destructive processes in retina and vascular layer of eyes of wistar and OXYS rats.

    PubMed

    Saprunova, V B; Lelekova, M A; Kolosova, N G; Bakeeva, L E

    2012-06-01

    We show the development of clearly pronounced age-related pathological changes in eye tissues of Wistar and OXYS rats. Photoreceptor cells were virtually absent in all OXYS rats in the age of 24 months. Massive accumulations of lipofuscin granules were detected in the pigmented epithelium cells. Flattening, overgrowing, and degradation of endothelial cells of choriocapillaries were also observed. Along with these changes, vessels without signs of degradation were detected in the pigmented epithelium. In 24-month-old Wistar rats these changes were local and were seen in only some of the animals. The mitochondria-targeted antioxidant SkQ1 (the rats were given SkQ1 daily with food at the dose of 250 nmol/kg for 5 months, starting from the age of 19 months) prevented the development of these pathological changes in both Wistar and OXYS rats. The data were subjected to mathematical processing and statistical analysis.

  2. Statistical distributions of earthquake numbers: consequence of branching process

    NASA Astrophysics Data System (ADS)

    Kagan, Yan Y.

    2010-03-01

    We discuss various statistical distributions of earthquake numbers. Previously, we derived several discrete distributions to describe earthquake numbers for the branching model of earthquake occurrence: these distributions are the Poisson, geometric, logarithmic and the negative binomial (NBD). The theoretical model is the `birth and immigration' population process. The first three distributions above can be considered special cases of the NBD. In particular, a point branching process along the magnitude (or log seismic moment) axis with independent events (immigrants) explains the magnitude/moment-frequency relation and the NBD of earthquake counts in large time/space windows, as well as the dependence of the NBD parameters on the magnitude threshold (magnitude of an earthquake catalogue completeness). We discuss applying these distributions, especially the NBD, to approximate event numbers in earthquake catalogues. There are many different representations of the NBD. Most can be traced either to the Pascal distribution or to the mixture of the Poisson distribution with the gamma law. We discuss advantages and drawbacks of both representations for statistical analysis of earthquake catalogues. We also consider applying the NBD to earthquake forecasts and describe the limits of the application for the given equations. In contrast to the one-parameter Poisson distribution so widely used to describe earthquake occurrence, the NBD has two parameters. The second parameter can be used to characterize clustering or overdispersion of a process. We determine the parameter values and their uncertainties for several local and global catalogues, and their subdivisions in various time intervals, magnitude thresholds, spatial windows, and tectonic categories. The theoretical model of how the clustering parameter depends on the corner (maximum) magnitude can be used to predict future earthquake number distribution in regions where very large earthquakes have not yet occurred.

  3. Morphological age-dependent development of the human carotid bifurcation.

    PubMed

    Seong, Jaehoon; Lieber, Baruch B; Wakhloo, Ajay K

    2005-03-01

    The unique morphology of the adult human carotid bifurcation and its sinus has been investigated extensively, but its long-term, age-dependent development has not. It is important fundamentally and clinically to understand the hemodynamics and developmental forces that play a role in remodeling of the carotid bifurcation and maturation of the sinus in association with brain maturation. This understanding can lead to better prognostication and therapy of carotid disease. We analyzed the change of sinus morphology and the angle of the carotid bifurcation in four postnatal developmental stages (Group I: 0-2 years, Group II: 3-9 years, Group III: 10-19 years, and Group IV: 20-36 years, respectively) using multiprojection digital subtraction angiograms and image post-processing techniques. The most significant findings are the substantial growth of the internal carotid artery (ICA) with age and the development of a carotid sinus at the root of the ICA during late adolescence. The bifurcation angle remains virtually unchanged from infancy to adulthood. However, the angle split between the ICA and external carotid artery (ECA) relative to the common carotid artery (CCA) undergoes significant changes. Initially, the ICA appears to emanate as a side branch. Later in life, to reduce hydraulic resistance in response to increased flow demand by the brain, the bifurcation is remodeled to a construct in which both daughter vessels are a skewed continuation of the parent artery. This study provides a new analysis method to examine the development of the human carotid bifurcation over the developmental years, despite the small and sparse database. A larger database will enable in the future a more extensive analysis such as gender or racial differences.

  4. Human serum metabolic profiles are age dependent

    PubMed Central

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-01-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  5. Age-dependent variations of antibody avidity.

    PubMed Central

    Doria, G; D'Agostaro, G; Poretti, A

    1978-01-01

    Age-dependent variations of antibody avidity were studied in the C3HeB/FeJ mouse. Spleen cells from donors of different ages (10--720 days) were transferred and stimulated with TNP-HRBC in lethally irradiated syngenic recipients. The anti-TNP antibody response of the donor cells was estimated from the number of direct PFC per recipient spleen by the Jerne technique with TNP-SRBC. Avidity of the antibodies secreted by PFC was evaluated from the amount of added TNP-BSA that inhibited 50% of the anti-TNP PFC. Under these experimental conditions allowing the exclusion of any influence of the donor milieu during the immune response, age-dependent variations of the antibody response and avidity could be attributed to changes in the donor spleen cell population. Avidity was found to increase with the response and to vary parabolically with age. After appropriate correction of the number of PFC to make it independent from age, avidity values were fitted by a multiple curvilinear regression in which the independent variables playing a significant role were the corrected number of PFC in its linear term and the age in its linear and quadratic terms. From comparison of the standard coefficients of this regression, the observed variations of avidity could be attributed in part (82%) to the response and in part (18%) to the age. For any value of response, avidity increased 15-fold from day 10 to reach a maximum at day 110 and then declined 5-fold at the age of 720 days. Heterogeneity of avidity also changed parabolically with age as high avidity classes were present in adulthood and absent at 10 and 720 days. PMID:361545

  6. Experimental characterization of nonlinear processes of whistler branch waves

    NASA Astrophysics Data System (ADS)

    Tejero, E. M.; Crabtree, C.; Blackwell, D. D.; Amatucci, W. E.; Ganguli, G.; Rudakov, L.

    2016-05-01

    Experiments in the Space Physics Simulation Chamber at the Naval Research Laboratory isolated and characterized important nonlinear wave-wave and wave-particle interactions that can occur in the Earth's Van Allen radiation belts by launching predominantly electrostatic waves in the intermediate frequency range with wave normal angle greater than 85 ° and measuring the nonlinearly generated electromagnetic scattered waves. The scattered waves have a perpendicular wavelength that is nearly an order of magnitude larger than that of the pump wave. Calculations of scattering efficiency from experimental measurements demonstrate that the scattering efficiency is inversely proportional to the damping rate and trends towards unity as the damping rate approaches zero. Signatures of both wave-wave and wave-particle scatterings are also observed in the triggered emission process in which a launched wave resonant with a counter-propagating electron beam generates a large amplitude chirped whistler wave. The possibility of nonlinear scattering or three wave decay as a saturation mechanism for the triggered emission is suggested. The laboratory experiment has inspired the search for scattering signatures in the in situ data of chorus emission in the radiation belts.

  7. SEECAL: Program to calculate age-dependent

    SciTech Connect

    Cristy, M.; Eckerman, K.F.

    1993-12-01

    This report describes the computer program SEECAL, which calculates specific effective energies (SEE) to specified target regions for ages newborn, 1 y, 5 y, 10 y, 15 y, a 70-kg adult male, and a 58-kg adult female. The dosimetric methodology is that of the International Commission on Radiological Protection (ICRP) and is generally consistent with the schema of the Medical Internal Radiation Dose committee of the US Society of Nuclear Medicine. Computation of SEEs is necessary in the computation of equivalent dose rate in a target region, for occupational or public exposure to radionuclides taken into the body. Program SEECAL replaces the program SEE that was previously used by the Dosimetry Research Group at Oak Ridge National Laboratory. The program SEE was used in the dosimetric calculations for occupational exposures for ICRP Publication 30 and is limited to adults. SEECAL was used to generate age-dependent SEEs for ICRP Publication 56, Part 1. SEECAL is also incorporated into DCAL, a radiation dose and risk calculational system being developed for the Environmental Protection Agency. Electronic copies of the program and data files and this report are available from the Radiation Shielding Information Center at Oak Ridge National Laboratory.

  8. Comment on "Finite-size scaling of survival probability in branching processes"

    NASA Astrophysics Data System (ADS)

    Wei, Nanxin; Pruessner, Gunnar

    2016-12-01

    R. Garcia-Millan et al. [Phys. Rev. E 91, 042122 (2015), 10.1103/PhysRevE.91.042122] reported a universal finite-size scaling form of the survival probability in discrete time branching processes. In this comment, we generalize the argument to a wide range of continuous time branching processes. Owing to the continuity, the resulting differential (rather than difference) equations can be solved in closed form, rendering some approximations by R. Garcia-Millan et al. superfluous, although we work along similar lines. In the case of binary branching, our results are in fact exact. Demonstrating that discrete time and continuous time models have their leading order asymptotics in common, raises the question to what extent corrections are identical.

  9. Testing branching process estimators of cascading failure with data from a simulation of transmission line outages.

    PubMed

    Dobson, Ian; Kim, Janghoon; Wierzbicki, Kevin R

    2010-04-01

    We suggest a statistical estimator to quantify the propagation of cascading transmission line failures in large blackouts of electric power systems. We use a Galton-Watson branching process model of cascading failure and the standard Harris estimator of the mean propagation modified to work when the process saturates at a maximum number of components. If the mean number of initial failures and the mean propagation are estimated, then the branching process model predicts the distribution of the total number of failures. We initially test this prediction on failure data generated by a simulation of cascading transmission line outages on two standard test systems. We discuss the effectiveness of the estimator in terms of how many cascades need to be simulated to predict the distribution of the total number of line outages accurately.

  10. Using multitype branching processes to quantify statistics of disease outbreaks in zoonotic epidemics

    NASA Astrophysics Data System (ADS)

    Singh, Sarabjeet; Schneider, David J.; Myers, Christopher R.

    2014-03-01

    Branching processes have served as a model for chemical reactions, biological growth processes, and contagion (of disease, information, or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this work we focus on coupled branching processes as a model of infectious diseases spreading from one population to another. An exceedingly important example of such coupled outbreaks are zoonotic infections that spill over from animal populations to humans. We derive several statistical quantities characterizing the first spillover event from animals to humans, including the probability of spillover, the first passage time distribution for human infection, and disease prevalence in the animal population at spillover. Large stochastic fluctuations in those quantities can make inference of the state of the system at the time of spillover difficult. Focusing on outbreaks in the human population, we then characterize the critical threshold for a large outbreak, the distribution of outbreak sizes, and associated scaling laws. These all show a strong dependence on the basic reproduction number in the animal population and indicate the existence of a novel multicritical point with altered scaling behavior. The coupling of animal and human infection dynamics has crucial implications, most importantly allowing for the possibility of large human outbreaks even when human-to-human transmission is subcritical.

  11. Simple unified view of branching process statistics: Random walks in balanced logarithmic potentials

    NASA Astrophysics Data System (ADS)

    di Santo, Serena; Villegas, Pablo; Burioni, Raffaella; Muñoz, Miguel A.

    2017-03-01

    We revisit the problem of deriving the mean-field values of avalanche exponents in systems with absorbing states. These are well known to coincide with those of unbiased branching processes. Here we show that for at least four different universality classes (directed percolation, dynamical percolation, the voter model or compact directed percolation class, and the Manna class of stochastic sandpiles) this common result can be obtained by mapping the corresponding Langevin equations describing each of them into a random walker confined to the origin by a logarithmic potential. We report on the emergence of nonuniversal continuously varying exponent values stemming from the presence of small external driving - that might induce avalanche merging - that, to the best of our knowledge, has not been noticed in the past. Many of the other results derived here appear in the literature as independently derived for individual universality classes or for the branching process itself. Still, we believe that a simple and unified perspective as the one presented here can help (1) clarify the overall picture, (2) underline the superuniversality of the behavior as well as the dependence on external driving, and (3) avoid the common existing confusion between unbiased branching processes (equivalent to a random walker in a balanced logarithmic potential) and standard (unconfined) random walkers.

  12. Efficient Transition Probability Computation for Continuous-Time Branching Processes via Compressed Sensing

    PubMed Central

    Xu, Jason; Minin, Vladimir N.

    2016-01-01

    Branching processes are a class of continuous-time Markov chains (CTMCs) with ubiquitous applications. A general difficulty in statistical inference under partially observed CTMC models arises in computing transition probabilities when the discrete state space is large or uncountable. Classical methods such as matrix exponentiation are infeasible for large or countably infinite state spaces, and sampling-based alternatives are computationally intensive, requiring integration over all possible hidden events. Recent work has successfully applied generating function techniques to computing transition probabilities for linear multi-type branching processes. While these techniques often require significantly fewer computations than matrix exponentiation, they also become prohibitive in applications with large populations. We propose a compressed sensing framework that significantly accelerates the generating function method, decreasing computational cost up to a logarithmic factor by only assuming the probability mass of transitions is sparse. We demonstrate accurate and efficient transition probability computations in branching process models for blood cell formation and evolution of self-replicating transposable elements in bacterial genomes. PMID:26949377

  13. Process for the conversion of lower alcohols to higher branched oxygenates

    DOEpatents

    Barger, Paul T.

    1996-01-01

    A process is provided for the production of branched C.sub.4+ oxygenates from lower alcohols such as methanol, ethanol, propanol and mixtures thereof. The process comprises contacting the lower alcohols with a solid catalyst comprising a mixed metal oxide support having components selected from the group consisting of oxides of zinc, magnesium, zirconia, titanium, manganese, chromium, and lanthanides, and an activation metal selected from the group consisting of Group VIII metal, Group IB metals, and mixtures thereof. The advantage of the process is improved yields and selectivity to isobutanol which can subsequently be employed in the production of high octane motor gasoline.

  14. Process for the conversion of lower alcohols to higher branched oxygenates

    DOEpatents

    Barger, P.T.

    1996-09-24

    A process is provided for the production of branched C{sub x} oxygenates from lower alcohols such as methanol, ethanol, propanol and mixtures thereof. The process comprises contacting the lower alcohols with a solid catalyst comprising a mixed metal oxide support having components selected from the group consisting of oxides of zinc, magnesium, zirconia, titanium, manganese, chromium, and lanthanides, and an activation metal selected from the group consisting of Group VIII metal, Group IB metals, and mixtures thereof. The advantage of the process is improved yields and selectivity to isobutanol which can subsequently be employed in the production of high octane motor gasoline.

  15. Life spans of a Bellman-Harris branching process with immigration

    SciTech Connect

    Badalbaev, I.S.; Mashrabbaev, A.

    1987-09-10

    One considers two schemes of the Bellman-Harris process with immigration when a) the lifetime of the particles is an integral-valued random variable and the immigration is defined by a sequence of independent random variables; b) the distribution of the lifetime of the particles is nonlattice and the immigration is a process with continuous time. One investigates the properties of the life spans of such processes. The results obtained here are a generalization to the case of Bellman-Harris processes of the results of A.M. Zubkov, obtained for Markov branching processes. For the proof one makes use in an essential manner of the known inequalities of Goldstein, estimating the generating function of the Bellman-Harris process in terms of the generating functions of the imbedded Galton-Watson process.

  16. Age-dependent forest carbon sink: Estimation via inverse modeling

    NASA Astrophysics Data System (ADS)

    Zhou, Tao; Shi, Peijun; Jia, Gensuo; Dai, Yongjiu; Zhao, Xiang; Shangguan, Wei; Du, Ling; Wu, Hao; Luo, Yiqi

    2015-12-01

    Forests have been recognized to sequester a substantial amount of carbon (C) from the atmosphere. However, considerable uncertainty remains regarding the magnitude and time course of the C sink. Revealing the intrinsic relationship between forest age and C sink is crucial for reducing uncertainties in prediction of forest C sink potential. In this study, we developed a stepwise data assimilation approach to combine a process-based Terrestrial ECOsystem Regional model, observations from multiple sources, and stochastic sampling to inversely estimate carbon cycle parameters including carbon sink at different forest ages for evergreen needle-leaved forests in China. The new approach is effective to estimate age-dependent parameter of maximal light-use efficiency (R2 = 0.99) and, accordingly, can quantify a relationship between forest age and the vegetation and soil C sinks. The estimated ecosystem C sink increases rapidly with age, peaks at 0.451 kg C m-2 yr-1 at age 22 years (ranging from 0.421 to 0.465 kg C m-2 yr-1), and gradually decreases thereafter. The dynamic patterns of C sinks in vegetation and soil are significantly different. C sink in vegetation first increases rapidly with age and then decreases. C sink in soil, however, increases continuously with age; it acts as a C source when the age is less than 20 years, after which it acts as a sink. For the evergreen needle-leaved forest, the highest C sink efficiency (i.e., C sink per unit net primary productivity) is approximately 60%, with age between 11 and 43 years. Overall, the inverse estimation of carbon cycle parameters can make reasonable estimates of age-dependent C sequestration in forests.

  17. Study on color identification for monitoring and controlling fermentation process of branched chain amino acid

    NASA Astrophysics Data System (ADS)

    Ma, Lei; Wang, Yizhong; Chen, Ning; Liu, Tiegen; Xu, Qingyang; Kong, Fanzhi

    2008-12-01

    In this paper, a new method for monitoring and controlling fermentation process of branched chain amino acid (BCAA) was proposed based on color identification. The color image of fermentation broth of BCAA was firstly taken by a CCD camera. Then, it was changed from RGB color model to HIS color model. Its histograms of hue H and saturation S were calculated, which were used as the input of a designed BP network. The output of the BP network was the description of the color of fermentation broth of BCAA. After training, the color of fermentation broth was identified by the BP network according to the histograms of H and S of a fermentation broth image. Along with other parameters, the fermentation process of BCAA was monitored and controlled to start the stationary phase of fermentation soon. Experiments were conducted with satisfied results to show the feasibility and usefulness of color identification of fermentation broth in fermentation process control of BCAA.

  18. Oscillatory Critical Amplitudes in Hierarchical Models and the Harris Function of Branching Processes

    NASA Astrophysics Data System (ADS)

    Costin, Ovidiu; Giacomin, Giambattista

    2013-02-01

    Oscillatory critical amplitudes have been repeatedly observed in hierarchical models and, in the cases that have been taken into consideration, these oscillations are so small to be hardly detectable. Hierarchical models are tightly related to iteration of maps and, in fact, very similar phenomena have been repeatedly reported in many fields of mathematics, like combinatorial evaluations and discrete branching processes. It is precisely in the context of branching processes with bounded off-spring that T. Harris, in 1948, first set forth the possibility that the logarithm of the moment generating function of the rescaled population size, in the super-critical regime, does not grow near infinity as a power, but it has an oscillatory prefactor (the Harris function). These oscillations have been observed numerically only much later and, while the origin is clearly tied to the discrete character of the iteration, the amplitude size is not so well understood. The purpose of this note is to reconsider the issue for hierarchical models and in what is arguably the most elementary setting—the pinning model—that actually just boils down to iteration of polynomial maps (and, notably, quadratic maps). In this note we show that the oscillatory critical amplitude for pinning models and the Harris function coincide. Moreover we make explicit the link between these oscillatory functions and the geometry of the Julia set of the map, making thus rigorous and quantitative some ideas set forth in Derrida et al. (Commun. Math. Phys. 94:115-132, 1984).

  19. Paradise Lost: Age-Dependent Mortality of American Communes, 1609-1965

    ERIC Educational Resources Information Center

    Kitts, James A.

    2009-01-01

    Theorists agree that the risk of folding changes as organizations age, but there is little consensus as to the general form or generative processes of age-dependent mortality. This article investigates four such processes (maturation, senescence, legitimation and obsolescence), which have been taken as competing accounts. Using two analytical…

  20. Coherence and Incoherence in QCD Jets Dynamics (QCD Jets and Branching Processes)

    NASA Astrophysics Data System (ADS)

    Giovannini, A.; Ugoccioni, R.

    The interpretation of QCD jets as Markov branching processes obtained by solving Konishi Ukawa Veneziano equations [1] in the leading logarithmic approximation with a fixed cut-off regularization prescription [2] is reviewed, and its impact in multiparticle dynamics critically examined. Independent intermediate gluon sources (clans) are generated through quark bremsstrahlung, each source then decays into final partons according to a cascading mechanism dominated by gluon self-interaction. At the hadron level, approximate universal regularities are expected in the different components (or substructures) of the various classes of high-energy collisions. The general behavior of collective variables of final multiplicity distributions is reproduced in terms of the weighted superposition of the above-mentioned regularities controlling the component behaviors of each collision. Predictions of signals of new physics at LHC [3] are reviewed, and perspective of the 1/N expansion approach [4] indicated.

  1. Quantifying Age-dependent Extinction from Species Phylogenies

    PubMed Central

    Alexander, Helen K.; Lambert, Amaury; Stadler, Tanja

    2016-01-01

    Several ecological factors that could play into species extinction are expected to correlate with species age, i.e., time elapsed since the species arose by speciation. To date, however, statistical tools to incorporate species age into likelihood-based phylogenetic inference have been lacking. We present here a computational framework to quantify age-dependent extinction through maximum likelihood parameter estimation based on phylogenetic trees, assuming species lifetimes are gamma distributed. Testing on simulated trees shows that neglecting age dependence can lead to biased estimates of key macroevolutionary parameters. We then apply this method to two real data sets, namely a complete phylogeny of birds (class Aves) and a clade of self-compatible and -incompatible nightshades (Solanaceae), gaining initial insights into the extent to which age-dependent extinction may help explain macroevolutionary patterns. Our methods have been added to the R package TreePar. PMID:26405218

  2. Quasi- and pseudo-maximum likelihood estimators for discretely observed continuous-time Markov branching processes

    PubMed Central

    Chen, Rui; Hyrien, Ollivier

    2011-01-01

    This article deals with quasi- and pseudo-likelihood estimation in a class of continuous-time multi-type Markov branching processes observed at discrete points in time. “Conventional” and conditional estimation are discussed for both approaches. We compare their properties and identify situations where they lead to asymptotically equivalent estimators. Both approaches possess robustness properties, and coincide with maximum likelihood estimation in some cases. Quasi-likelihood functions involving only linear combinations of the data may be unable to estimate all model parameters. Remedial measures exist, including the resort either to non-linear functions of the data or to conditioning the moments on appropriate sigma-algebras. The method of pseudo-likelihood may also resolve this issue. We investigate the properties of these approaches in three examples: the pure birth process, the linear birth-and-death process, and a two-type process that generalizes the previous two examples. Simulations studies are conducted to evaluate performance in finite samples. PMID:21552356

  3. Growth rate and shape as possible control mechanisms for the selection of mode development in optimal biological branching processes

    NASA Astrophysics Data System (ADS)

    Alarcón, Tomás; Castillo, Jorge; García-Ponce, Berenice; Herrero, Miguel Angel; Padilla, Pablo

    2016-11-01

    Recently three branching modes were characterized during the formation of the lung in mice. These modes are highly stereotyped and correspond to domain formation, planar bifurcation and three dimensional branching respectively. At the same time it is proved that although genetic control mechanisms are presumably related to the selection of any of these modes, other external factors will most probably be involved in the branching process during development. In this paper we propose that the underlying controling factors might be related to the rate at which the tubes that form the lung network grow. We present a mathematical model that allows us to formulate specific experimental predictions on these growth rates. Moreover we show that according to this formulation, there is an optimization criterion which governs the branching process during lung development, namely, efficient local space filling properties of the network. If there is no space limitation the branches are allowed to grow freely and faster, selecting one branching mode, namely, domain formation. As soon as volume constraints appear the growth rate decreases, triggering the selection of planar and orthogonal bifurcation.

  4. Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program.

    PubMed

    Guo, Xin; Bernard, Allister; Orlando, David A; Haase, Steven B; Hartemink, Alexander J

    2013-03-05

    Due to cell-to-cell variability and asymmetric cell division, cells in a synchronized population lose synchrony over time. As a result, time-series measurements from synchronized cell populations do not reflect the underlying dynamics of cell-cycle processes. Here, we present a branching process deconvolution algorithm that learns a more accurate view of dynamic cell-cycle processes, free from the convolution effects associated with imperfect cell synchronization. Through wavelet-basis regularization, our method sharpens signal without sharpening noise and can remarkably increase both the dynamic range and the temporal resolution of time-series data. Although applicable to any such data, we demonstrate the utility of our method by applying it to a recent cell-cycle transcription time course in the eukaryote Saccharomyces cerevisiae. Our method more sensitively detects cell-cycle-regulated transcription and reveals subtle timing differences that are masked in the original population measurements. Our algorithm also explicitly learns distinct transcription programs for mother and daughter cells, enabling us to identify 82 genes transcribed almost entirely in early G1 in a daughter-specific manner.

  5. Living in the branches: population dynamics and ecological processes in dendritic networks

    USGS Publications Warehouse

    Grant, E.H.C.; Lowe, W.H.; Fagan, W.F.

    2007-01-01

    Spatial structure regulates and modifies processes at several levels of ecological organization (e.g. individual/genetic, population and community) and is thus a key component of complex systems, where knowledge at a small scale can be insufficient for understanding system behaviour at a larger scale. Recent syntheses outline potential applications of network theory to ecological systems, but do not address the implications of physical structure for network dynamics. There is a specific need to examine how dendritic habitat structure, such as that found in stream, hedgerow and cave networks, influences ecological processes. Although dendritic networks are one type of ecological network, they are distinguished by two fundamental characteristics: (1) both the branches and the nodes serve as habitat, and (2) the specific spatial arrangement and hierarchical organization of these elements interacts with a species' movement behaviour to alter patterns of population distribution and abundance, and community interactions. Here, we summarize existing theory relating to ecological dynamics in dendritic networks, review empirical studies examining the population- and community-level consequences of these networks, and suggest future research integrating spatial pattern and processes in dendritic systems.

  6. Optimal birth control of age-dependent competitive species

    NASA Astrophysics Data System (ADS)

    He, Ze-Rong

    2005-05-01

    We study optimal birth policies for two age-dependent populations in a competing system, which is controlled by fertilities. New results on problems with free final time and integral phase constraints are presented, and the approximate controllability of system is discussed.

  7. Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...

  8. Age-dependent modulation of the somatosensory network upon eye closure.

    PubMed

    Brodoehl, Stefan; Klingner, Carsten; Witte, Otto W

    2016-02-01

    Eye closure even in complete darkness can improve somatosensory perception by switching the brain to a uni-sensory processing mode. This causes an increased information flow between the thalamus and the somatosensory cortex while decreasing modulation by the visual cortex. Previous work suggests that these modulations are age-dependent and that the benefit in somatosensory performance due to eye closing diminishes with age. The cause of this age-dependency and to what extent somatosensory processing is involved remains unclear. Therefore, we intended to characterize the underlying age-dependent modifications in the interaction and connectivity of different sensory networks caused by eye closure. We performed functional MR-imaging with tactile stimulation of the right hand under the conditions of opened and closed eyes in healthy young and elderly participants. Conditional Granger causality analysis was performed to assess the somatosensory and visual networks, including the thalamus. Independent of age, eye closure improved the information transfer from the thalamus to and within the somatosensory cortex. However, beyond that, we found an age-dependent recruitment strategy. Whereas young participants were characterized by an optimized information flow within the relays of the somatosensory network, elderly participants revealed a stronger modulatory influence of the visual network upon the somatosensory cortex. Our results demonstrate that the modulation of the somatosensory and visual networks by eye closure diminishes with age and that the dominance of the visual system is more pronounced in the aging brain.

  9. Crystal structure and functional implications of Pyrococcus furiosus hef helicase domain involved in branched DNA processing.

    PubMed

    Nishino, Tatsuya; Komori, Kayoko; Tsuchiya, Daisuke; Ishino, Yoshizumi; Morikawa, Kosuke

    2005-01-01

    DNA and RNA frequently form various branched intermediates that are important for the transmission of genetic information. Helicases play pivotal roles in the processing of these transient intermediates during nucleic acid metabolism. The archaeal Hef helicase/ nuclease is a representative protein that processes flap- or fork-DNA structures, and, intriguingly, its C-terminal half belongs to the XPF/Mus81 nuclease family. Here, we report the crystal structure of the helicase domain of the Hef protein from Pyrococcus furiosus. The structure reveals a novel helical insertion between the two conserved helicase core domains. This positively charged extra region, structurally similar to the "thumb" domain of DNA polymerase, plays critical roles in fork recognition. The Hef helicase/nuclease exhibits sequence similarity to the Mph1 helicase from Saccharomyces cerevisiae; XPF/Rad1, involved in DNA repair; and a putative Hef homolog identified in mammals. Hence, our findings provide a structural basis for the functional mechanisms of this helicase/nuclease family.

  10. A branching process, its application in biology: influence of demographic parameters on the social structure in mammal groups.

    PubMed

    Caron-Lormier, G; Masson, J P; Ménard, N; Pierre, J S

    2006-02-07

    Branching processes are widely used in biology. This theoretical tool is used in cell dynamics, epidemics and population dynamics. In population dynamics, branching processes are mainly used to access extinction probabilities of populations, groups or families, with the Galton-Watson branching process. Many mammal species live in socially-structured groups, and the smallest units of these groups are lineages (or families) of kin-related individuals. In many primate species, these lineages are matrilines, as females remain in their natal groups most of the time, whereas males generally disperse. Lineage parameters, such as numbers of matrilines, size of each matriline and average degree of relatedness, could strongly influence the genetic composition of groups. Evidence indicates that division along matrilines could induce substantial differentiation among fission groups. Here, we develop a novel mathematical model based on the branching process theory describing demographic dynamics of groups. The main result of this model is an explicit analytical expression of the joint distribution of numbers of lineages and sizes of socially-structured groups. We investigated the influence of parameters such as natality and mortality on the outcome of the process, including extinction probability. Finally, we discuss this theoretical result with respect to biological significance.

  11. Age-dependent patterns of bovine tuberculosis in cattle

    PubMed Central

    2013-01-01

    Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics. Here, we estimate age-specific reactor rates in Great Britain by combining herd-level testing data with spatial movement data from the Cattle Tracing System (CTS). Using a catalytic model, we find strong age dependencies in infection risk and that the probability of detecting infection increases with age. Between 2004 and 2009, infection incidence in cattle fluctuated around 1%. Age-specific incidence increased monotonically until 24–36 months, with cattle aged between 12 and 36 months experiencing the highest rates of infection. Beef and dairy cattle under 24 months experienced similar infection risks, however major differences occurred in older ages. The average reproductive number in cattle was greater than 1 for the years 2004–2009. These methods reveal a consistent pattern of BTB rates with age, across different population structures and testing patterns. The results provide practical insights into BTB epidemiology and control, suggesting that targeting a mass control programme at cattle between 12 and 36 months could be beneficial. PMID:24131703

  12. Age-dependent patterns of bovine tuberculosis in cattle.

    PubMed

    Brooks-Pollock, Ellen; Conlan, Andrew J K; Mitchell, Andy P; Blackwell, Ruth; McKinley, Trevelyan J; Wood, James L N

    2013-10-16

    Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics. Here, we estimate age-specific reactor rates in Great Britain by combining herd-level testing data with spatial movement data from the Cattle Tracing System (CTS). Using a catalytic model, we find strong age dependencies in infection risk and that the probability of detecting infection increases with age. Between 2004 and 2009, infection incidence in cattle fluctuated around 1%. Age-specific incidence increased monotonically until 24-36 months, with cattle aged between 12 and 36 months experiencing the highest rates of infection. Beef and dairy cattle under 24 months experienced similar infection risks, however major differences occurred in older ages. The average reproductive number in cattle was greater than 1 for the years 2004-2009. These methods reveal a consistent pattern of BTB rates with age, across different population structures and testing patterns. The results provide practical insights into BTB epidemiology and control, suggesting that targeting a mass control programme at cattle between 12 and 36 months could be beneficial.

  13. THE EFFECTS OF ROTATION ON s-PROCESS NUCLEOSYNTHESIS IN ASYMPTOTIC GIANT BRANCH STARS

    SciTech Connect

    Piersanti, L.; Cristallo, S.; Straniero, O.

    2013-09-10

    In this paper, we analyze the effects induced by rotation on low-mass asymptotic giant branch stars. We compute two sets of models, M = 2.0 M{sub Sun} at [Fe/H] = 0 and M = 1.5 M{sub Sun} at [Fe/H] = -1.7, by adopting main-sequence rotation velocities in the range 0-120 km s{sup -1}. At high metallicity, we find that the Goldreich-Schubert-Fricke instability, active at the interface between the convective envelope and the rapid rotating core, contaminates the {sup 13}C-pocket (the major neutron source) with {sup 14}N (the major neutron poison), thus reducing the neutron flux available for the synthesis of heavy elements. As a consequence, the yields of heavy-s elements (Ba, La, Nd, Sm) and, to a lesser extent, those of light-s elements (Sr, Y, Zr) decrease with increasing rotation velocities up to 60 km s{sup -1}. However, for larger initial rotation velocities, the production of light-s and, to a lesser extent, that of heavy-s, begins again to increase, due to mixing induced by meridional circulations. At low metallicity, the effects of meridional circulations are important even at rather low rotation velocity. The combined effect of the Goldreich-Schubert-Fricke instability and meridional circulations determines an increase of light-s and, to a lesser extent, heavy-s elements, while lead is strongly reduced. For both metallicities, the rotation-induced instabilities active during the interpulse phase reduce the neutron-to-seed ratio, so that the spectroscopic indexes [hs/ls] and [Pb/hs] decrease by increasing the initial rotation velocity. Our analysis suggests that rotation could explain the spread in the s-process indexes, as observed in s-process enriched stars at different metallicities.

  14. The Effects of Rotation on s-process Nucleosynthesis in Asymptotic Giant Branch Stars

    NASA Astrophysics Data System (ADS)

    Piersanti, L.; Cristallo, S.; Straniero, O.

    2013-09-01

    In this paper, we analyze the effects induced by rotation on low-mass asymptotic giant branch stars. We compute two sets of models, M = 2.0 M ⊙ at [Fe/H] = 0 and M = 1.5 M ⊙ at [Fe/H] = -1.7, by adopting main-sequence rotation velocities in the range 0-120 km s-1. At high metallicity, we find that the Goldreich-Schubert-Fricke instability, active at the interface between the convective envelope and the rapid rotating core, contaminates the 13C-pocket (the major neutron source) with 14N (the major neutron poison), thus reducing the neutron flux available for the synthesis of heavy elements. As a consequence, the yields of heavy-s elements (Ba, La, Nd, Sm) and, to a lesser extent, those of light-s elements (Sr, Y, Zr) decrease with increasing rotation velocities up to 60 km s-1. However, for larger initial rotation velocities, the production of light-s and, to a lesser extent, that of heavy-s, begins again to increase, due to mixing induced by meridional circulations. At low metallicity, the effects of meridional circulations are important even at rather low rotation velocity. The combined effect of the Goldreich-Schubert-Fricke instability and meridional circulations determines an increase of light-s and, to a lesser extent, heavy-s elements, while lead is strongly reduced. For both metallicities, the rotation-induced instabilities active during the interpulse phase reduce the neutron-to-seed ratio, so that the spectroscopic indexes [hs/ls] and [Pb/hs] decrease by increasing the initial rotation velocity. Our analysis suggests that rotation could explain the spread in the s-process indexes, as observed in s-process enriched stars at different metallicities.

  15. Age-dependent cognitive impairment in a Drosophila Fragile X model and its pharmacological rescue

    PubMed Central

    Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.

    2010-01-01

    Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205

  16. Synthesis of porous carbon nanofiber with bamboo-like carbon nanofiber branches by one-step carbonization process

    NASA Astrophysics Data System (ADS)

    Yoo, Seung Hwa; Joh, Han-Ik; Lee, Sungho

    2017-04-01

    Porous carbon nanofibers (PCNFs) with CNF branches (PCNF/bCNF) were synthesized by a simple heat treatment method. Conventional methods to synthesize this unique structure usually follow a typical route, which consists of CNF preparation, catalyst deposition, and secondary CNF growth. In contrast, our method utilized a one-step carbonization process of polymer nanofibers, which were electrospun from a one-pot solution consisted of polyacrylonitrile, polystyrene (PS), and iron acetylacetonate. Various structures of PCNF/CNF were synthesized by changing the solution composition and molecular weight of PS. It was verified that the content and molecular weight of PS were critical for the growth of catalyst particles and subsequent growth of CNF branches. The morphology, phase of catalyst, and carbon structure of PCNF/bCNF were analyzed at different temperature steps during carbonization. It was found that pores were generated by the evaporation of PS and the catalyst particles were formed on the surface of PCNF at 700 °C. The gases originated from the evaporation of PS acted as a carbon source for the growth of CNF branches that started at 900 °C. Finally, when the carbonization process was finished at 1200 °C, uniform and abundant CNF branches were formed on the surface of PCNF.

  17. Age-dependent magnetosensitivity of heart muscle ouabain receptors.

    PubMed

    Narinyan, Lilia Yu; Ayrapetyan, Gayane S; Ayrapetyan, Sinerik N

    2013-05-01

    In our previous work we have shown that the age-dependent decrease in the magnetosensitivity of heart muscle hydration is accompanied by a dysfunction of the Na(+) /K(+) pump. The reciprocal relation between the Na(+/) K(+) pump and Na(+) /Ca(2+) exchange in development was suggested as a possible pathway for the age-dependent decrease in the magnetosensitivity of heart muscle hydration (water content). Because high and low affinity ouabain receptors in cell membranes are involved in Na(+) /Ca(2+) exchange and Na(+) /K(+) pump functions, respectively, the effect of a 0.2 T static magnetic field (SMF) on dose-dependent, ouabain-induced hydration and [(3) H]-ouabain binding with heart muscle tissues in young, adult and older rats was studied. Three populations of receptors in membranes with high (10(-11) -10(-9)  M), middle (10(-9) -10(-7)  M) and low (10(-7) -10(-4)  M) affinity to [(3) H]-ouabain were distinguished, which had specific dose-dependent [(3) H]-ouabain binding kinetics and effects on muscle hydration. The magnetosensitivity of [(3) H]-ouabain binding kinetics with high affinity receptors was prominent in all the three age groups of animals, while with low affinity receptors it was more expressed only in the young group of animals. All three types of receptors that caused modulations of muscle hydration were age dependent and magnetosensitive. Based on the obtained data we came to the conclusion that heart muscle hydration in young animals is more magnetosensitive due to the intense expression of high affinity ouabain receptors, which declines with aging.

  18. Techno-economic analysis of an improved process for producing saturated branched-chain fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetable oils provide a source of environmentally desirable lubricants, but they are not widely utilized because of their poor oxidative stability. Branched-chain fatty acid isomers are desirable products because they have excellent thermostabilities and lubricities when compared to the parent veg...

  19. Age-dependent changes in mitochondrial morphology and volume are not predictors of lifespan.

    PubMed

    Regmi, Saroj G; Rolland, Stéphane G; Conradt, Barbara

    2014-02-01

    Mitochondrial dysfunction is a hallmark of skeletal muscle degeneration during aging. One mechanism through which mitochondrial dysfunction can be caused is through changes in mitochondrial morphology. To determine the role of mitochondrial morphology changes in age-dependent mitochondrial dysfunction, we studied mitochondrial morphology in body wall muscles of the nematodeC. elegans. We found that in this tissue, animals display a tubular mitochondrial network, which fragments with increasing age. This fragmentation is accompanied by a decrease in mitochondrial volume. Mitochondrial fragmentation and volume loss occur faster under conditions that shorten lifespan and occur slower under conditions that increase lifespan. However, neither mitochondrial morphology nor mitochondrial volume of five- and seven-day old wild-type animals can be used to predict individual lifespan. Our results indicate that while mitochondria in body wall muscles undergo age-dependent fragmentation and a loss in volume, these changes are not the cause of aging but rather a consequence of the aging process.

  20. Exhaled nitric oxide is age-dependent in asthma.

    PubMed

    Avital, Avraham; Uwyyed, Kamal; Berkman, Neville; Bar-Yishay, Ephraim; Godfrey, Simon; Springer, Chaim

    2003-11-01

    We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (age-dependent, with lower values in young children.

  1. Parthanatos Mediates AIMP2 Activated Age Dependent Dopaminergic Neuronal Loss

    PubMed Central

    Lee, Yunjong; Karuppagounder, Senthilkumar S.; Shin, Joo-Ho; Lee, Yun-Il; Ko, Han Seok; Swing, Debbie; Jiang, Haisong; Kang, Sung-Ung; Lee, Byoung Dae; Kang, Ho Chul; Kim, Donghoon; Tessarollo, Lino; Dawson, Valina L.; Dawson, Ted M.

    2013-01-01

    The defining pathogenic feature of Parkinson’s disease is the age dependent loss of dopaminergic neurons. Mutations and inactivation of parkin, an ubiquitin E3 ligase, cause Parkinson’s disease through accumulation of pathogenic substrates. Here we show that transgenic overexpression of the parkin substrate, aminoacyl-tRNA synthetase complex interacting multifunctional protein-2 (AIMP2) leads to a selective, age-dependent progressive loss of dopaminergic neurons via activation of poly(ADP-ribose) polymerase-1 (PARP1). AIMP2 accumulation in vitro and in vivo results in PARP1 overactivation and dopaminergic cell toxicity via direct association of these proteins in the nucleus providing a new path to PARP1 activation other than DNA damage. Inhibition of PARP1 through gene deletion or drug inhibition reverses behavioral deficits and protects in vivo against dopamine neuron death in AIMP2 transgenic mice. These data indicate that brain permeable PARP inhibitors could be effective in delaying or preventing disease progression in Parkinson’s disease. PMID:23974709

  2. Age-dependent social learning in a lizard.

    PubMed

    Noble, Daniel W A; Byrne, Richard W; Whiting, Martin J

    2014-07-01

    Evidence of social learning, whereby the actions of an animal facilitate the acquisition of new information by another, is taxonomically biased towards mammals, especially primates, and birds. However, social learning need not be limited to group-living animals because species with less interaction can still benefit from learning about potential predators, food sources, rivals and mates. We trained male skinks (Eulamprus quoyii), a mostly solitary lizard from eastern Australia, in a two-step foraging task. Lizards belonging to 'young' and 'old' age classes were presented with a novel instrumental task (displacing a lid) and an association task (reward under blue lid). We did not find evidence for age-dependent learning of the instrumental task; however, young males in the presence of a demonstrator learnt the association task faster than young males without a demonstrator, whereas old males in both treatments had similar success rates. We present the first evidence of age-dependent social learning in a lizard and suggest that the use of social information for learning may be more widespread than previously believed.

  3. Role of Mitochondrial Complex IV in Age-Dependent Obesity.

    PubMed

    Soro-Arnaiz, Ines; Li, Qilong Oscar Yang; Torres-Capelli, Mar; Meléndez-Rodríguez, Florinda; Veiga, Sónia; Veys, Koen; Sebastian, David; Elorza, Ainara; Tello, Daniel; Hernansanz-Agustín, Pablo; Cogliati, Sara; Moreno-Navarrete, Jose Maria; Balsa, Eduardo; Fuertes, Esther; Romanos, Eduardo; Martínez-Ruiz, Antonio; Enriquez, Jose Antonio; Fernandez-Real, Jose Manuel; Zorzano, Antonio; De Bock, Katrien; Aragonés, Julián

    2016-09-13

    Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.

  4. Prey behavior, age-dependent vulnerability, and predation rates.

    PubMed

    Lingle, Susan; Feldman, Alex; Boyce, Mark S; Wilson, W Finbarr

    2008-11-01

    Variation in the temporal pattern of vulnerability can provide important insights into predator-prey relationships and the evolution of antipredator behavior. We illustrate these points with a system that has coyotes (Canis latrans) as a predator and two species of congeneric deer (Odocoileus spp.) as prey. The deer employ different antipredator tactics (aggressive defense vs. flight) that result in contrasting patterns of age-dependent vulnerability in their probability of being captured when encountered by coyotes. We use long-term survival data and a simple mathematical model to show that (1) species differences in age-dependent vulnerability are reflected in seasonal predation rates and (2) seasonal variation in prey vulnerability and predator hunt activity, which can be associated with the availability of alternative prey, interact to shape seasonal and annual predation rates for each prey species. Shifting hunt activity from summer to winter, or vice versa, alleviated annual mortality on one species and focused it on the other. Our results indicate that seasonal variation in prey vulnerability and hunt activity interact to influence the impact that a predator has on any particular type of prey. Furthermore, these results indicate that seasonal variation in predation pressure is an important selection pressure shaping prey defenses.

  5. On the inclusion of self regulating branching processes in the working paradigm of evolutionary and population genetics

    PubMed Central

    Mode, Charles J.; Sleeman, Candace K.; Raj, Towfique

    2013-01-01

    The principal goal of this methodological paper is to suggest to a general audience in the genetics community that the consideration of recent developments of self regulating branching processes may lead to the possibility of including this class of stochastic processes as part of working paradigm of evolutionary and population genetics. This class of branching processes is self regulating in the sense that an evolving population will grow only to a total population size that can be sustained by the environment. From the mathematical point of view the class processes under consideration belongs to a subfield of probability and statistics sometimes referred to as computational applied probability and stochastic processes. Computer intensive methods based on Monte Carlo simulation procedures have been used to empirically work out the predictions of a formulation by assigning numerical values to some point in the parameter space and computing replications of realizations of the process over thousands of generations of evolution. Statistical methods are then used on such samples of simulated data to produce informative summarizations of the data that provide insights into the evolutionary implications of computer experiments. Briefly, it is also possible to embed deterministic non-linear difference equations in the stochastic process by using a statistical procedure to estimate the sample functions of the process, which has interesting methodological implications as to whether stochastic or deterministic formulations may be applied separately or in combination in the study of evolution. It is recognized that the literature on population genetics contains a substantial number of papers in which Monte Carlo simulation methods have been used. But, this extensive literature is beyond the scope of this paper, which is focused on potential applications of self regulating branching processes in evolutionary and population genetics. PMID:23424044

  6. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures

    PubMed Central

    Schafer, Marissa J.; Dolgalev, Igor; Alldred, Melissa J.; Heguy, Adriana; Ginsberg, Stephen D.

    2015-01-01

    Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months, 12.5 months of feeding) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector. PMID:26221964

  7. A single carbon fiber microelectrode with branching carbon nanotubes for bioelectrochemical processes.

    PubMed

    Zhao, Xueyan; Lu, Xin; Tze, William T Y; Wang, Ping

    2010-06-15

    Carbon fiber electrodes are greatly promising for microelectronic applications including high performance biosensors, miniaturized transmitters, and energy storage and generation devices. For biosensor applications, one drawback of using carbon fiber microelectrodes, especially single fiber electrodes, is the weak electronic signals, a consequence of low surface area of fibers, which ultimately limit the sensitivity of the sensors. In this paper, we report a novel single fiber microelectrode with branched carbon nanotubes for enhanced sensing performance. The fiber microelectrode was prepared from carbonization of cellulose fibers. Upon introduction of carbon nanotubes, the carbon fibers exhibited a significant increase in the specific surface area from <10 to 36.4 m(2)/g (determined by the BET method). A single fiber electrode with such a hierarchical structure was examined for redox reactions of coenzyme NAD(H) which is useful to mediate the assays and transformations of a broad range of biochemicals. Experimental results showed that carbon nanotubes enhanced the redox reactions on surfaces of the electrode by reducing the oxidation potential of NAD(H) from 0.8 to 0.55 V. The single carbon fiber with branched nanotubes was also examined for the detection of glycerol, and the results showed linear responding signals in a concentration range of 40-250 microM. These results are comparable to the properties of fossil-based carbon materials, and thus our cellulose-based carbon electrodes provide a potentially sustainable alternative in bioelectrochemical applications.

  8. A Game-Theoretic Approach to Branching Time Abstract-Check-Refine Process

    NASA Technical Reports Server (NTRS)

    Wang, Yi; Tamai, Tetsuo

    2009-01-01

    Since the complexity of software systems continues to grow, most engineers face two serious problems: the state space explosion problem and the problem of how to debug systems. In this paper, we propose a game-theoretic approach to full branching time model checking on three-valued semantics. The three-valued models and logics provide successful abstraction that overcomes the state space explosion problem. The game style model checking that generates counter-examples can guide refinement or identify validated formulas, which solves the system debugging problem. Furthermore, output of our game style method will give significant information to engineers in detecting where errors have occurred and what the causes of the errors are.

  9. A comprehensive approach to age-dependent dosimetric modeling

    SciTech Connect

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1986-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks.

  10. Assessing local population vulnerability to wind energy development with branching process models: an application to wind energy development

    USGS Publications Warehouse

    Erickson, Richard A.; Eager, Eric A.; Stanton, Jessica C.; Beston, Julie A.; Diffendorfer, James E.; Thogmartin, Wayne E.

    2015-01-01

    Quantifying the impact of anthropogenic development on local populations is important for conservation biology and wildlife management. However, these local populations are often subject to demographic stochasticity because of their small population size. Traditional modeling efforts such as population projection matrices do not consider this source of variation whereas individual-based models, which include demographic stochasticity, are computationally intense and lack analytical tractability. One compromise between approaches is branching process models because they accommodate demographic stochasticity and are easily calculated. These models are known within some sub-fields of probability and mathematical ecology but are not often applied in conservation biology and applied ecology. We applied branching process models to quantitatively compare and prioritize species locally vulnerable to the development of wind energy facilities. Specifically, we examined species vulnerability using branching process models for four representative species: A cave bat (a long-lived, low fecundity species), a tree bat (short-lived, moderate fecundity species), a grassland songbird (a short-lived, high fecundity species), and an eagle (a long-lived, slow maturation species). Wind turbine-induced mortality has been observed for all of these species types, raising conservation concerns. We simulated different mortality rates from wind farms while calculating local extinction probabilities. The longer-lived species types (e.g., cave bats and eagles) had much more pronounced transitions from low extinction risk to high extinction risk than short-lived species types (e.g., tree bats and grassland songbirds). High-offspring-producing species types had a much greater variability in baseline risk of extinction than the lower-offspring-producing species types. Long-lived species types may appear stable until a critical level of incidental mortality occurs. After this threshold, the risk of

  11. Color identification and fuzzy reasoning based monitoring and controlling of fermentation process of branched chain amino acid

    NASA Astrophysics Data System (ADS)

    Ma, Lei; Wang, Yizhong; Xu, Qingyang; Huang, Huafang; Zhang, Rui; Chen, Ning

    2009-11-01

    The main production method of branched chain amino acid (BCAA) is microbial fermentation. In this paper, to monitor and to control the fermentation process of BCAA, especially its logarithmic phase, parameters such as the color of fermentation broth, culture temperature, pH, revolution, dissolved oxygen, airflow rate, pressure, optical density, and residual glucose, are measured and/or controlled and/or adjusted. The color of fermentation broth is measured using the HIS color model and a BP neural network. The network's input is the histograms of hue H and saturation S, and output is the color description. Fermentation process parameters are adjusted using fuzzy reasoning, which is performed by inference rules. According to the practical situation of BCAA fermentation process, all parameters are divided into four grades, and different fuzzy rules are established.

  12. Age-Dependent Male Mating Investment in Drosophila pseudoobscura

    PubMed Central

    Dhole, Sumit; Pfennig, Karin S.

    2014-01-01

    Male mating investment can strongly influence fitness gained from a mating. Yet, male mating investment often changes with age. Life history theory predicts that mating investment should increase with age, and males should become less discriminatory about their mate as they age. Understanding age-dependent changes in male behavior and their effects on fitness is important for understanding how selection acts in age-structured populations. Although the independent effects of male or female age have been studied in many species, how these interact to influence male mating investment and fitness is less well understood. We mated Drosophila pseudoobscura males of five different age classes (4-, 8-, 11-, 15-, 19-day old) to either young (4-day) or old (11-day) females, and measured copulation duration and early post-mating fecundity. Along with their independent effects, we found a strong interaction between the effects of male and female ages on male mating investment and fitness from individual matings. Male mating investment increased with male age, but this increase was more prominent in matings with young females. Male D. pseudoobscura made smaller investments when mating with old females. The level of such discrimination based on female age, however, also changed with male age. Intermediate aged males were most discriminatory, while the youngest and the oldest males did not discriminate between females of different ages. We also found that larger male mating investments resulted in higher fitness payoffs. Our results show that male and female ages interact to form a complex pattern of age-specific male mating investment and fitness. PMID:24586373

  13. AGE-DEPENDENT ASCENDING AORTA MECHANICS ASSESSED THROUGH MULTIPHASE CT

    PubMed Central

    Martin, Caitlin; Sun, Wei; Primiano, Charles; McKay, Raymond; Elefteriades, John

    2013-01-01

    Quantification of the age- and gender-specific in vivo mechanical characteristics of the ascending aorta (AA) will allow for identification of abnormalities aside from changes brought on by aging alone. Multiphase clinical CT scans of 45 male patients between the ages of 30 and 79 years were analyzed to assess age-dependent in vivo AA characteristics. The three-dimensional AA geometry for each patient was reconstructed from the CT scans for 9–10 phases throughout the cardiac cycle. The AA circumference was measured during each phase and was used to determine the corresponding diameter, circumferential strain, and wall tension at each phase. The pressure-strain modulus was also determined for each patient. The mean diastolic AA diameter was significantly smaller among young (42.6±5.2 years) at 29.9±2.8 mm than old patients (69.0±5.2 years) at 33.2±3.2 mm. The circumferential AA strain from end-diastole to peak-systole decreased from 0.092±0.03 in young to 0.056±0.03 in old patients. The pressure-strain modulus increased two-fold from 68.4±30.5 kPa in young to 162.0±93.5 kPa in old patients, and the systolic AA wall tension increased from 268.5±31.3 kPa in young to 304.9±49.2 kPa in old patients. The AA dilates and stiffens with aging which increases the vessel wall tension, likely predisposing aneurysm and dissection. PMID:23817767

  14. Age-Dependent Cortical Thinning of Peripheral Visual Field Representations in Primary Visual Cortex.

    PubMed

    Griffis, Joseph C; Burge, Wesley K; Visscher, Kristina M

    2016-01-01

    The cerebral cortex changes throughout the lifespan, and the cortical gray matter in many brain regions becomes thinner with advancing age. Effects of aging on cortical thickness (CT) have been observed in many brain regions, including areas involved in basic perceptual functions such as processing visual inputs. An important property of early visual cortices is their topographic organization-the cortical structure of early visual areas forms a topographic map of retinal inputs. Primary visual cortex (V1) is considered to be the most basic cortical area in the visual processing hierarchy, and is topographically organized from posterior (central visual representation) to anterior (peripheral visual representation) along the calcarine sulcus. Some studies have reported strong age-dependent cortical thinning in portions of V1 that likely correspond to peripheral visual representations, while there is less evidence of substantial cortical thinning in central V1. However, the effect of aging on CT in V1 as a function of its topography has not been directly investigated. To address this gap in the literature, we estimated the CT of different eccentricity sectors in V1 using T1-weighted MRI scans acquired from groups of healthy younger and older adults, and then assessed whether between-group differences in V1 CT depended on cortical eccentricity. These analyses revealed age-dependent cortical thinning specific to peripheral visual field representations in anterior portions of V1, but did not provide evidence for age-dependent cortical thinning in other portions of V1. Additional analyses found similar effects when analyses were restricted to the gyral crown, sulcul depth and sulcul wall, indicating that these effects are not likely due to differences in gyral/sulcul contributions to our regions of interest (ROI). Importantly, this finding indicates that age-dependent changes in cortical structure may differ among functionally distinct zones within larger canonical

  15. Age-Dependent Cortical Thinning of Peripheral Visual Field Representations in Primary Visual Cortex

    PubMed Central

    Griffis, Joseph C.; Burge, Wesley K.; Visscher, Kristina M.

    2016-01-01

    The cerebral cortex changes throughout the lifespan, and the cortical gray matter in many brain regions becomes thinner with advancing age. Effects of aging on cortical thickness (CT) have been observed in many brain regions, including areas involved in basic perceptual functions such as processing visual inputs. An important property of early visual cortices is their topographic organization—the cortical structure of early visual areas forms a topographic map of retinal inputs. Primary visual cortex (V1) is considered to be the most basic cortical area in the visual processing hierarchy, and is topographically organized from posterior (central visual representation) to anterior (peripheral visual representation) along the calcarine sulcus. Some studies have reported strong age-dependent cortical thinning in portions of V1 that likely correspond to peripheral visual representations, while there is less evidence of substantial cortical thinning in central V1. However, the effect of aging on CT in V1 as a function of its topography has not been directly investigated. To address this gap in the literature, we estimated the CT of different eccentricity sectors in V1 using T1-weighted MRI scans acquired from groups of healthy younger and older adults, and then assessed whether between-group differences in V1 CT depended on cortical eccentricity. These analyses revealed age-dependent cortical thinning specific to peripheral visual field representations in anterior portions of V1, but did not provide evidence for age-dependent cortical thinning in other portions of V1. Additional analyses found similar effects when analyses were restricted to the gyral crown, sulcul depth and sulcul wall, indicating that these effects are not likely due to differences in gyral/sulcul contributions to our regions of interest (ROI). Importantly, this finding indicates that age-dependent changes in cortical structure may differ among functionally distinct zones within larger canonical

  16. Age-dependent flea (Siphonaptera) parasitism in rodents: a host's life history matters.

    PubMed

    Krasnov, Boris R; Stanko, Michal; Morand, Serge

    2006-04-01

    We studied age-dependent patterns of flea infestation in 7 species of rodents from Slovakia (Apodemus agrarius, A. flavicollis, A. sylvaticus, A. uralensis, Clethrionomys glareolus, Microtus arvalis, and M. subterraneus). We estimated the age of the host from its body mass and expected the host age-dependent pattern of flea abundance, the level of aggregation, and prevalence to be in agreement with theoretical predictions. We expected that the mean abundance and the level of aggregation of fleas would be lowest in hosts of smallest and largest size classes and highest in hosts of medium size classes, whereas pattern of variation of prevalence with host age would be either convex or asymptotic. In general, mean abundance and species richness of fleas increased with an increase in host age, although the pressure of flea parasitism in terms of number of fleas per unit host body surface decreased with host age. We found 2 clear patterns of the change in flea aggregation and prevalence with host age. The first pattern demonstrated a peak of flea aggregation and a trough of flea prevalence in animals of middle age classes (Apodemus species and C. glareolus). The second pattern was an increase of both flea aggregation and flea prevalence with host age (both Microtus species). Consequently, we did not find unequivocal evidence for the main role of either parasite-induced host mortality or acquired resistance in host age-dependent pattern of flea parasitism. Our results suggest that this pattern can be generated by various processes and is strongly affected by natural history parameters of a host species such as dispersal pattern, spatial distribution, and structure of shelters.

  17. {sup 80}Se({gamma},n){sup 79}Se cross section and s-process branching at {sup 79}Se

    SciTech Connect

    Makinaga, A.; Utsunomiya, H.; Kaihori, T.; Yamagata, T.; Akimune, H.; Goriely, S.; Toyokawa, H.; Matsumoto, T.; Harano, H.; Harada, H.; Goko, S.; Kitatani, F.; Hara, K. Y.; Hohara, S.; Lui, Y.-W.

    2008-05-21

    Photoneutron cross sections were measured for {sup 80}Se near the neutron separation energy with laser Compton-backscattered {gamma}-ray beams at AIST. Neutron capture rates are evaluated for {sup 79}Se with the photoreaction data as experimental constraints on the El {gamma}-strength function, a key parameter in the Hauser-Feshbach statistical model calculation. Solving the set of differential equations under a single neutron exposure, we analyzed the solar abundance ratio of the weak components of {sup 80}Kr and {sup 82}Kr in terms of the s-process branching at {sup 79}Se. We discuss the region of temperature and neutron density allowed for the weak s-process nucleosynthesis.

  18. Age-dependent morphological and compositional variations on Ceres

    NASA Astrophysics Data System (ADS)

    Jaumann, Ralf

    2016-04-01

    Extended smooth plains cover the interior of a number of craters on Ceres. Smooth plains appear on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains also ponds in depressions and smaller craters and cover the pre-existing surface creating distinct geological boundaries. Ikapati crater shows smooth plains on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains, ponds in depressions and smaller craters and cover the pre-existing surface creating a distinct geological boundary. The interior of Occator also exhibits extended plains of ponded material, multiple flows originating from the center overwhelming the mass wasting deposits from the rim, dome-like features, vents cracks and fissures. Furthermore, crater densities on Occator's floor are lower than those on the ejecta blanket indicating a post-impact formation age of the flows. The flows to the northeast appear to originate from the central region and move slightly uphill. This indicates either a feeding zone that pushes the flows forward by supplying low-viscosity material or a depression of the crater center, possibly after discharging a subsurface reservoir. The plains and flows as well as some areas surrounding the craters appear spectrally blue. Both plains and flow material are characterized in camera and spectrometer visible spectra by a slightly negative slope with a gradual drop off up to 10% in reflectance from 0.5μm to 1μm. Although the spectral variations in the visible are subtle, they are clearly expressed in the color ratio composite. The crater densities of 20 locations across the surface of Ceres with different spectral behavior were analyzed in order to investigate the age dependence of spectral surface features. The results indicate that bluish material is mainly associated with the youngest impact craters on Ceres (< 0.5 Ga) while

  19. Age Dependent Absolute Plate and Plume Motion Modeling

    NASA Astrophysics Data System (ADS)

    Heaton, D. E.; Koppers, A. A. P.

    2015-12-01

    construct rapidly and represent a time period close to the inception age of the seamount, thus by proxy also the hotspot location. Here we present a new age dependent plate motion model that tests the 'fixed' and 'moving' hotspot hypotheses.

  20. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  1. Development of Processable PMR-Type Polymides with Star-Branched Structures

    NASA Technical Reports Server (NTRS)

    Nguyen, Baochau N.; Eby, R. K.; Meador, Michael A.

    1999-01-01

    In the last two decades, high temperature polyimide matrix composites have found broad applications in aerospace structural components, due to their high specific modulus and high specific strength. As matrix resins, aromatic polyimides exhibit exceptional thermal stability and mechanical properties. However, their rodlike structures often result in poor solubility in most common organic solvents, as well as high melt temperature and melt viscosity, making them difficult to process. To overcome this difficulty, flexible linkages including O, SO2 or CH2 non coplanar biphenyl moieties, bulky lateral substituents, and crankshaft structures are often incorporated into the polymer backbones. Addition-curing of low molecular weight polyimides (resins) is another approach to improve processability. One of the most successfully developed materials has been PMR-15 (Polymerization of Monomer Reactants, molecular weight of 1500 g/mol), because of its good combination of thermal and mechanical properties and ease of processability. However, due to the high melt viscosity of PMR-type resins, use of more economical processing methods, such as resin transfer molding (RTM), is not possible. Recent research has focused on the incorporation of trifunctional monomers into addition-curing polyimides in an attempt to improve the processability of these polymers. The objective of this research is to use an aromatic triamine, 1,3,5 tris (4-aminophenoxy) benzene, to prepare new resin systems with starbranched structures. The glass transition temperatures (Tg's) and thermal oxidative stability TOS) of these polymers are compared to their linear counterparts and PMR-15.

  2. Photodisintegration of {sup 80}Se: Implications for the s-process branching at {sup 79}Se

    SciTech Connect

    Makinaga, A.; Utsunomiya, H.; Kaihori, T.; Akimune, H.; Yamagata, T.; Goriely, S.; Goko, S.; Harada, H.; Kitatani, F.; Hara, Y. K.; Toyokawa, H.; Matsumoto, T.; Harano, H.; Hohara, S.; Lui, Y.-W.

    2009-02-15

    Photoneutron cross sections were measured for {sup 80}Se immediately above the neutron separation energy with quasimonochromatic {gamma}-ray beams to experimentally constrain the E1 {gamma} strength function for {sup 80}Se. Two sets of the {gamma} strength function and the level density that equally meet the experimental constraint predict largely different neutron capture cross sections for {sup 79}Se. Based on the Maxwellian-averaged cross sections of the latest compilation complemented with the predicted cross sections for {sup 79}Se, we calculated {sigma}N values of the main s-process component using a phenomenological model and deduced empirical abundances of the weak s-process component. An attempt is made of considering the implications of the abundance ratios of {sup 80}Kr and {sup 82}Kr within the framework of phenomenological models for the weak s process.

  3. Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein.

    PubMed

    Zheng, Xiao-Feng; Prakash, Rohit; Saro, Dorina; Longerich, Simonne; Niu, Hengyao; Sung, Patrick

    2011-10-10

    The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also offer mechanistic insights as to its ability to efficiently disrupt the D-loop intermediate.

  4. Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

    PubMed Central

    Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

    2016-01-01

    While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209

  5. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs.

  6. A branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts.

    PubMed

    Sakashita, Tetsuya; Hamada, Nobuyuki; Kawaguchi, Isao; Hara, Takamitsu; Kobayashi, Yasuhiko; Saito, Kimiaki

    2014-05-01

    A single cell can form a colony, and ionizing irradiation has long been known to reduce such a cellular clonogenic potential. Analysis of abortive colonies unable to continue to grow should provide important information on the reproductive cell death (RCD) following irradiation. Our previous analysis with a branching process model showed that the RCD in normal human fibroblasts can persist over 16 generations following irradiation with low linear energy transfer (LET) γ-rays. Here we further set out to evaluate the RCD persistency in abortive colonies arising from normal human fibroblasts exposed to high-LET carbon ions (18.3 MeV/u, 108 keV/µm). We found that the abortive colony size distribution determined by biological experiments follows a linear relationship on the log-log plot, and that the Monte Carlo simulation using the RCD probability estimated from such a linear relationship well simulates the experimentally determined surviving fraction and the relative biological effectiveness (RBE). We identified the short-term phase and long-term phase for the persistent RCD following carbon-ion irradiation, which were similar to those previously identified following γ-irradiation. Taken together, our results suggest that subsequent secondary or tertiary colony formation would be invaluable for understanding the long-lasting RCD. All together, our framework for analysis with a branching process model and a colony formation assay is applicable to determination of cellular responses to low- and high-LET radiation, and suggests that the long-lasting RCD is a pivotal determinant of the surviving fraction and the RBE.

  7. Undersampled critical branching processes on small-world and random networks fail to reproduce the statistics of spike avalanches.

    PubMed

    Ribeiro, Tiago L; Ribeiro, Sidarta; Belchior, Hindiael; Caixeta, Fábio; Copelli, Mauro

    2014-01-01

    The power-law size distributions obtained experimentally for neuronal avalanches are an important evidence of criticality in the brain. This evidence is supported by the fact that a critical branching process exhibits the same exponent [Formula: see text]. Models at criticality have been employed to mimic avalanche propagation and explain the statistics observed experimentally. However, a crucial aspect of neuronal recordings has been almost completely neglected in the models: undersampling. While in a typical multielectrode array hundreds of neurons are recorded, in the same area of neuronal tissue tens of thousands of neurons can be found. Here we investigate the consequences of undersampling in models with three different topologies (two-dimensional, small-world and random network) and three different dynamical regimes (subcritical, critical and supercritical). We found that undersampling modifies avalanche size distributions, extinguishing the power laws observed in critical systems. Distributions from subcritical systems are also modified, but the shape of the undersampled distributions is more similar to that of a fully sampled system. Undersampled supercritical systems can recover the general characteristics of the fully sampled version, provided that enough neurons are measured. Undersampling in two-dimensional and small-world networks leads to similar effects, while the random network is insensitive to sampling density due to the lack of a well-defined neighborhood. We conjecture that neuronal avalanches recorded from local field potentials avoid undersampling effects due to the nature of this signal, but the same does not hold for spike avalanches. We conclude that undersampled branching-process-like models in these topologies fail to reproduce the statistics of spike avalanches.

  8. Photodisintegration of 80Se and its implications for s-process branching

    SciTech Connect

    Makinaga, A.; Utsunomiya, H.; Goko, S.; Kaihori, T.; Houhara, S.; Goriely, S.; Toyokawa, H.; Harano, H.; Matsumoto, T.; Harada, H.; Kitatani, F.; Hara, K. Y.; Lui, Y.-W.

    2007-02-26

    Photodisintegration cross sections were measured for 80Se with laser Compton scattering {gamma} beams at E{gamma}=9.98-11.80 MeV near the neutron separation energy. The stellar neutron capture rate for 80Se was evaluated by using the photodisintegration data as constraints on the E1 {gamma} strength function for 80Se within the framework of the Hauser-Feshbach statistical model. It was found that the rate at 30 keV is 0.7-1.1 times that of Bao and Kaeppeler. s-process temperatures deduced from the empirical solar abundances of the s-only nuclei 79Se and 80Kr with this neutron capture rate are 17-25 keV in the neutron density rage of (0.8-1.9)x103/cm3.

  9. Charged lepton flavor violating processes and scalar leptoquark decay branching ratios in the colored Zee-Babu model

    NASA Astrophysics Data System (ADS)

    Chang, We-Fu; Liou, Siao-Cing; Wong, Chi-Fong; Xu, Fanrong

    2016-10-01

    We consider a neutrino mass generating model which employs a scalar leptoquark, Δ, and a scalar diquark, S. The new scalars Δ and S carry the standard model SU(3) c × SU(2) L × U(1) Y quantum numbers (3 , 1 , -1 /3) and (6 , 1 , -2 /3), respectively. The neutrino masses are generated at the two-loop level, as in the Zee-Babu model [1, 2], and Δ /S plays the role of the doubly/singly charged scalar in the Zee-Babu model. With a moderate working assumption that the magnitudes of the six Yukawa couplings between S and the down-type quarks are of the same order, strong connections are found between the neutrino masses and the charged lepton flavor violating processes. In particular, we study Zto overline{l}{l}^' } , and l→ l 'γ and find that some portions of the parameter space of this model are within the reach of the planned charged lepton flavor violating experiments. Interesting lower bounds are predicted that B(Zto overline{l}{l}^')≳ 1{0}^{-16} - 1{0}^{-14}(1{0}^{-14}) × {(1 TeV \\cdotp {m}_S/7{m}{^{Δ}}^2)}^2 and B( l → l' γ) ≳ 10- 17 - 10- 16(10- 18 - 10- 16) × (1 TeV · m S /7 m Δ 2 )2 for neutrino masses being the normal (inverted) hierarchical pattern. The type of neutrino mass hierarchy could also be determined by measuring the charged lepton flavor violating double ratios. Moreover, definite leptoquark decay branching ratios are predicted when there is no Yukawa interaction between the right-handed fermions and Δ (the branching fraction of Δ to a charged lepton and a quark is 50%), which could help refine the collider search limit on the scalar leptoquark mass.

  10. Neutron Capture Cross Sections of the s-Process Branching Points 147Pm, 171Tm, and 204Tl

    NASA Astrophysics Data System (ADS)

    Guerrero, Carlos; Domingo-Pardo, Cesar; Lerendegui-Marco, Jorge; Casanovas, Adria; Cortes-Giraldo, Miguel A.; Dressler, Rugard; Halfon, Shlomi; Heinitz, Stephan; Kivel, Niko; Köster, Ulli; Paul, Michael; Quesada-Molina, Jose Manuel; Schumann, Dorothea; Tarifeño-Saldivia, Ariel; Tessler, Moshe; Weissman, Leo

    The neutron capture cross section of several key unstable isotopes acting as branching points in the s-process are crucial for stellar nucleosynthesis studies, but they are very challenging to measure due to the difficult production of sufficient sample material, the high activity of the resulting samples, and the actual (n, γ) measurement, for which high neutron fluxes and effective background rejection capabilities are required. As part of a new program to measure some of these important branching points, radioactive targets of 147Pm, 171Tm, and 204Tl have been produced by irradiation of stable isotopes (146Nd, 170Er, and 203Tl) at the Institut Laue-Langevin (ILL) high flux reactor. After breeding in the reactor and a certain cooling period, the resulting mixed 204Tl/203Tl sample was used directly while 147Pm and 171Tm were radiochemically separated in non-carrier-added quality at the Paul Scherrer Institut (PSI), then prepared as targets. A set of theses samples has been used for time-of-flight measurements at the CERN n_TOF facility using the 19 and 185 m beam lines, during 2014 and 2015. The capture cascades were detected with a set of four C6D6 scintillators, allowing to observe the associated neutron capture resonances. The results presented in this work are the first ever determination of the resonance capture cross sections of 147Pm, 171Tm, and 204Tl. Activation experiments on the same 147Pm and 171Tm targets with a high-intensity quasi-Maxwellian flux of neutrons have been performed using the SARAF accelerator and the Liquid-Lithium Target (LiLiT) in order to extract the corresponding Maxwellian Average Cross Section (MACS). The experimental setups are here described together with the first, preliminary results of the n_TOF measurement.

  11. Predicting plasticity: acute context-dependent changes to vocal performance predict long-term age-dependent changes

    PubMed Central

    James, Logan S.

    2015-01-01

    Understanding the factors that predict and guide variation in behavioral change can lend insight into mechanisms of motor plasticity and individual differences in behavior. The performance of adult birdsong changes with age in a manner that is similar to rapid context-dependent changes to song. To reveal mechanisms of vocal plasticity, we analyzed the degree to which variation in the direction and magnitude of age-dependent changes to Bengalese finch song could be predicted by variation in context-dependent changes. Using a repeated-measures design, we found that variation in age-dependent changes to the timing, sequencing, and structure of vocal elements (“syllables”) was significantly predicted by variation in context-dependent changes. In particular, the degree to which the duration of intersyllable gaps, syllable sequencing at branch points, and fundamental frequency of syllables within spontaneous [undirected (UD)] songs changed over time was correlated with the degree to which these features changed from UD song to female-directed (FD) song in young-adult finches (FDyoung). As such, the structure of some temporal features of UD songs converged over time onto the structure of FDyoung songs. This convergence suggested that the FDyoung song could serve as a stable target for vocal motor plasticity. Consequently, we analyzed the stability of FD song and found that the temporal structure of FD song changed significantly over time in a manner similar to UD song. Because FD song is considered a state of heightened performance, these data suggest that age-dependent changes could reflect practice-related improvements in vocal motor performance. PMID:26311186

  12. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  13. Age-Dependent Face Detection and Face Categorization Performance

    PubMed Central

    Carbon, Claus-Christian; Grüter, Martina; Grüter, Thomas

    2013-01-01

    Empirical studies on the development of face processing skills with age show inconsistent patterns concerning qualitative vs. quantitative changes over time or the age range for peak cognitive performance. In the present study, we tested the proficiency in face detection and face categorization with a large sample of participants (N = 312; age range: 2-88 yrs). As test objects, we used so-called Mooney faces, two-tone (black and white) images of faces lacking critical information of a local, featural and relational nature, reflecting difficult real world face processing conditions. We found that performance in the assessment of gender and age from Mooney faces increases up to about age 15, and decreases from 65 years on. The implications of these findings are discussed in the light of classic and recent findings from face development literature. PMID:24116236

  14. Oxidative stress is involved in age-dependent spermatogenic damage of Immp2l mutant mice.

    PubMed

    George, Sunil K; Jiao, Yan; Bishop, Colin E; Lu, Baisong

    Mitochondrial reactive oxygen species (ROS) have been implicated in spermatogenic damage, although direct in vivo evidence is lacking. We recently generated a mouse in which the inner mitochondrial membrane peptidase 2-like (Immp2l) gene is mutated. This Immp2l mutation impairs the processing of signal peptide sequences from mitochondrial cytochrome c₁ and glycerol phosphate dehydrogenase 2. The mitochondria from mutant mice generate elevated levels of superoxide ion, which causes age-dependent spermatogenic damage. Here we confirm age-dependent spermatogenic damage in a new cohort of mutants, which started at the age of 10.5 months. Compared with age-matched controls, protein carbonyl content was normal in testes of 2- to 5-month-old mutants, but significantly elevated in testes of 13-month-old mutants, indicating elevated oxidative stress in the testes at the time of impaired spermatogenesis. Testicular expression of superoxide dismutases was not different between control and mutant mice, whereas that of catalase was increased in young and old mutants. The expression of cytosolic glutathione peroxidase 4 (phospholipid hydroperoxidase) in testes was significantly reduced in 13-month-old mutants, concomitant with impaired spermatogenesis. Apoptosis of all testicular populations was increased in mutant mice with spermatogenic damage. The mitochondrial DNA (mtDNA) mutation rate in germ cells of mutant mice with impaired spermatogenesis was unchanged, excluding a major role of mtDNA mutation in ROS-mediated spermatogenic damage. Our data show that increased mitochondrial ROS are one of the driving forces for spermatogenic impairment.

  15. Age-Dependent Changes of Thinking about Verbs

    PubMed Central

    Bonivento, Carolina; Tomasino, Barbara; Garzitto, Marco; Piccin, Sara; Fabbro, Franco; Brambilla, Paolo

    2017-01-01

    We investigated the knowledge of emotional and motor verbs in children and adolescents from three age ranges (8–11, 12–15, 16–19 years). Participants estimated the verbs familiarity, age of acquisition, valence, arousal, imageability, and motor- and emotion-relatedness. Participants were familiar with the verbs in our dataset. The younger (8–11) attributed an emotional character to the verbs less frequently than the middle (12–15) and the older (16–19) groups. In the 8–11 group males rated the verbs as emotion-related less frequently than females. Results indicate that processing verbal concepts as emotion-related develops gradually, and after 12–15 is rather stable. The age of acquisition (AoA) develops late: the older (16–19) had a higher awareness in reporting that they learnt the verbs earlier as compared to the estimations made by the younger (8–11 and 12–15). AoA positively correlated with attribution of emotion relatedness meaning that emotion-related verbs were learned later. Arousal was comparable across ages. Also it increased when attributing motor relatedness to verbs and decreased when attributing emotion relatedness. Reporting the verbs' affective valence (happy vs. unhappy) changes with age: younger (8–11) judged the verbs generally more “happy” than both the older groups. Instead the middle and the older group did not show differences. Happiness increased when processing the verbs as motor related and decreased when processing the verbs as emotion related. Age affected imageability: the younger (8–11) considered the verbs easier to be imagined than the two older groups, suggesting that at this age vividness estimation is still rough, while after 12–15 is stable as the 12–15 and 15–19 group did not differ. Imageability predicted arousal, AoA, emotion- and motor-relatedness indicating that this index influences the way verbs are processed. Imageability was positively correlated to emotion relatedness, indicating

  16. Materials Test Branch

    NASA Technical Reports Server (NTRS)

    Gordon, Gail

    2012-01-01

    The Materials Test Branch resides at Marshall Space Flight Center's Materials and Processing laboratory and has a long history of supporting NASA programs from Mercury to the recently retired Space Shuttle. The Materials Test Branch supports its customers by supplying materials testing expertise in a wide range of applications. The Materials Test Branch is divided into three Teams, The Chemistry Team, The Tribology Team and the Mechanical Test Team. Our mission and goal is to provide world-class engineering excellence in materials testing with a special emphasis on customer service.

  17. Expectation-maximization algorithm for determining natural selection of Y-linked genes through two-sex branching processes.

    PubMed

    González, M; Gutiérrez, C; Martínez, R

    2012-09-01

    A two-dimensional bisexual branching process has recently been presented for the analysis of the generation-to-generation evolution of the number of carriers of a Y-linked gene. In this model, preference of females for males with a specific genetic characteristic is assumed to be determined by an allele of the gene. It has been shown that the behavior of this kind of Y-linked gene is strongly related to the reproduction law of each genotype. In practice, the corresponding offspring distributions are usually unknown, and it is necessary to develop their estimation theory in order to determine the natural selection of the gene. Here we deal with the estimation problem for the offspring distribution of each genotype of a Y-linked gene when the only observable data are each generation's total numbers of males of each genotype and of females. We set out the problem in a non parametric framework and obtain the maximum likelihood estimators of the offspring distributions using an expectation-maximization algorithm. From these estimators, we also derive the estimators for the reproduction mean of each genotype and forecast the distribution of the future population sizes. Finally, we check the accuracy of the algorithm by means of a simulation study.

  18. Size and Age Dependence of Koronis Family Colors

    NASA Astrophysics Data System (ADS)

    Molnar, L. A.

    2011-10-01

    The ancient and massive Koronis family now has four identified subfamilies (asteroid families made by the breakup of fragments of the ancient collision), with ages running from 5.7 to 290 My. This presents unique opportunities to explore space weathering processes, along with dynamical processes such as collisions and binary formation and destruction. Analysis of family members with accurate SDSS measurements shows a correlation of average subfamily color with age that for the first time is highly statistically significant. Yet Thomas et al. (2011) report a size dependence of the colors of the ancient family that demands caution when comparing subfamilies with differing size distributions. Reanalyis of the Thomas et al. data show the reported break near asteroid diameter 5 km is not significant. However, analysis of the much more extensive SDSS data set show a significant break past diameter 2.5 km, with smaller objects systematically bluer. The break is not present in the Karin subfamily (the youngest at 5.7 My), but is already fully developed in the Eriphyla subfamily (only 220 My). The reddening trend with age remains even when comparing only asteroids of similar size, confirming the presence of space weathering phenomena. The meaning of the trend with size is not immediately clear. We consider briefly the strengths and weaknesses of several interpretations of the bluer colors for small objects: 1) those objects receive more jolts from random collisions capable of shaking the regolith and exposing fresh material beneath; 2) those objects receive more jolts from the cycle of fission and recombination driven by YORP; and 3) the lower gravity on those objects retains regolith less well.

  19. Hydrogeochemical processes controlling subsurface transport from an upper subcatchment of Walker Branch watershed during storm events. 1. Hydrologic transport processes

    NASA Astrophysics Data System (ADS)

    Wilson, G. V.; Jardine, P. M.; Luxmoore, R. J.; Zelazny, L. W.; Lietzke, D. A.; Todd, D. E.

    1991-03-01

    Concerns over the effects of acid rain have stimulated numerous hydrometric and geochemical studies on forested watersheds with an emphasis on stream water chemistry. However, integrated studies are seriously lacking, and inferences of soil hydrogeochemical processes from periodic stream water chemistry may be grossly misleading. A small forested subcatchment was intensively instrumented for hydrologic and chemical analyses to improve our understanding of the processes that control subsurface transport of solutes. The timing and volume of subsurface flows were found to be highly dependent upon soil hydromorphologic properties. Development of perched water tables was the predominate mechanism of subsurface flow through the lower layers during moderate to high flow events. Perching of water was insignificant during low flow events and only partially responsible for lateral flow through the upper soil layers during moderate events. The importance of nonequilibrium conditions during even low flow events was illustrated by the occurrence of saturated flow through unsaturated (matric potentials < - 2kPa soil. The initial subsurface flow response of a moderate and high flow event was predominately (> 70%) new water that bypassed the soil matrix. As flows continued the percentage of old water increased. Intermittent rainfall during the high flow event caused multiple peaks in subsurface flow with subtle increases in perching. These hydrograph peaks were associated with decreases in the percentage of old water. This suggests an increase in the portion of infiltrating water that bypasses soil matrix water via macropores causing increases in subsurface flows with limited growth of perched water tables. The persistence of perched water tables as flow decreased was consistently observed. Decreases in solute concentrations causing decreases in conductivity of pores was inferred as one mechanism for this.

  20. Age-dependent change in urine proteome of healthy individuals

    NASA Astrophysics Data System (ADS)

    Dobrokhotov, Igor; Liudmila Pastushkova, MRS.; Larina, Irina; Kononikhin, Alexey

    , proteomic studies of urine samples can detect reliable age differences between groups of subjects, reflecting both age-specific features of processes of protein reabsorption by the kidneys, and the aging process in general.

  1. Age-dependent changes in temperature regulation - a mini review.

    PubMed

    Blatteis, Clark M

    2012-01-01

    It is now well recognized that the body temperature of older men and women is lower than that of younger people and that their tolerance of thermal extremes is more limited. The regulation of body temperature does not depend on a single organ, but rather involves almost all the systems of the body, i.e. systems not exclusively dedicated to thermoregulatory functions such as the cardiovascular and respiratory systems. Since these deteriorate naturally with advancing age, the decrement in their functions resonates throughout all the bodily processes, including those that control body temperature. To the extent that the age-related changes in some of these, e.g. in the musculoskeletal system, can be slowed, or even prevented, by certain measures, e.g. fitness training, so can the decrements in thermoregulatory functions. Some deficits, however, are unavoidable, e.g. structural skin changes and metabolic alterations. These impact directly on the ability of the elderly to maintain thermal homeostasis, particularly when challenged by ambient thermal extremes. Since the maintenance of a relatively stable, optimal core temperature is one of the body's most important activities, its very survival can be threatened by these disorders. The present article describes the principal, age-associated changes in physiological functions that could affect the ability of seniors to maintain their body temperature when exposed to hot or cold environments.

  2. Elastic hysteresis in human eyes is age dependent value.

    PubMed

    Ishii, Kotaro; Saito, Kei; Kameda, Toshihiro; Oshika, Tetsuro

    2012-06-19

    Background:  The elastic hysteresis phenomenon is observed when cyclic loading is applied to a viscoelastic system. The purpose of this study was to quantitatively evaluate elastic hysteresis in living human eyes against an external force. Design:  Prospective case series. Participants:  Twenty-four eyes of 24 normal human subjects (mean age: 41.5 ± 10.6 years) were recruited. Methods:  A non-contact tonometry process was recorded with a high-speed camera. Central corneal thickness (CCT), corneal thickness at 4 mm from the center, corneal curvature, and anterior chamber depth (ACD) were measured. Intraocular pressure (IOP) was also measured using Goldmann applanation tonometry (GAT) and dynamic contour tonometer (DCT). Main Outcome Measures:  Energy loss due to elastic hysteresis was calculated and graphed. Results:  The mean CCT was 552.5 ± 36.1 µm, corneal curvature was 7.84 ± 0.26 mm, and ACD was 2.83 ± 0.29 mm. The mean GAT-IOP was 14.2 ± 2.7 mmHg and DCT-IOP was 16.3 ± 3.5 mmHg. The mean energy loss due to elastic hysteresis was 3.90 × 10(-6) ± 2.49 × 10(-6) Nm. Energy loss due to elastic hysteresis correlated significantly with age (Pearson correlation coefficient = 0.596, p = 0.0016). There were no significant correlations between energy loss due to elastic hysteresis and other measurements. Conclusion:  Energy loss due to elastic hysteresis in the eyes of subjects was found to positively correlate with age, independent of anterior eye structure or IOP. Therefore, it is believed that the viscosity of the eye increases with age. © 2010 The Authors. Clinical and Experimental Ophthalmology © 2010 Royal Australian and New Zealand College of Ophthalmologists.

  3. Age-dependence of malonate-induced striatal toxicity.

    PubMed

    Meldrum, A; Page, K J; Everitt, B J; Dunnett, S B

    2000-10-01

    Malonate is an inhibitor of cellular metabolism, which, following intrastriatal injection, induces a striatal pathology similar to that seen in Huntington's disease. In two parallel studies, we have investigated the suggested relationship between the neuronal vulnerability to metabolic toxicity and the decline in metabolic function with increasing age. The first experiment investigated malonate-induced neuronal loss in animals aged from 6 weeks up to 27 months, and the second assessed the activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase (CYTOX) in animals aged 6 weeks, 3, 8 and 18 months. In the first study, male Lister-Hooded rats received intrastriatal stereotaxic injections of malonate (0.5 or 1.0 M). Animals were killed 10 days after surgery, and the brains were stained with cresyl violet and processed for NADPH-diaphorase activity and glial fibrillary-acidic-protein (GFAP) immunohistochemistry. Animals aged 6 months and older exhibited over 60% striatal neuronal loss. However, the degree of neuronal loss did not show any age-related increase in rats between 6 and 27 months of age, indicating that the extent of malonate-induced toxicity does not increase with age in animals older than 6 months. Infusion of 0.5 M malonate produced smaller lesions, which also demonstrated a consistent extent of neuronal loss from 6 months onwards. Metabolic enzyme activities were decreased in the striatum with increasing age, although this effect was only significant for CYTOX activity. Thus, the pattern of malonate-induced neuronal loss in aged animals partially reflects the changes in metabolic activity during ageing.

  4. Age-Dependent Changes in Pb Concentration in Human Teeth.

    PubMed

    Fischer, Agnieszka; Wiechuła, Danuta

    2016-09-01

    The result of exposure to Pb is its accumulation in mineralized tissues. In human body, they constitute a reservoir of approx. 90 % of the Pb reserve. The conducted research aimed at determining the accumulation of Pb in calcified tissues of permanent teeth. The concentration of Pb in 390 samples of teeth taken from a selected group of Polish people was determined using the AAS method. Average concentration of Pb in teeth amounted to 14.3 ± 8.18 μg/g, range of changes: 2.21-54.8 μgPb/g. Accumulation of Pb in human body was determined based on changes in Pb concentration in teeth of subjects aged 13-84 years. It was found that in calcified tissues of teeth, the increase in concentration of Pb that occurs with age is a statistically significant process (p = 0.02, the ANOVA Kruskal-Wallis test). It was determined that the annual increase in concentration of Pb in tissues of teeth is approx. 0.1 μg/g. Moreover, a different course of changes in Pb concentration in tissues of teeth in people born in different years was observed. The level of Pb concentration in teeth of the oldest subjects (>60 years) decreased for those born in the 1930s compared to those in the 1950s. Teeth from younger persons (<60 years) were characterized by an increasing level of Pb concentration. The analysis of changes of Pb indicates that for low exposure, a relatively greater accumulation of Pb concentration in calcified tissues of teeth can occur.

  5. Barium isotopic composition of mainstream silicon carbides from Murchison: Constraints for s-process nucleosynthesis in asymptotic giant branch stars

    SciTech Connect

    Liu, Nan; Davis, Andrew M.; Pellin, Michael J.; Dauphas, Nicolas; Savina, Michael R.; Gallino, Roberto; Bisterzo, Sara; Straniero, Oscar; Cristallo, Sergio; Gyngard, Frank; Willingham, David G.; Pignatari, Marco; Herwig, Falk

    2014-05-01

    We present barium, carbon, and silicon isotopic compositions of 38 acid-cleaned presolar SiC grains from Murchison. Comparison with previous data shows that acid washing is highly effective in removing barium contamination. Strong depletions in δ({sup 138}Ba/{sup 136}Ba) values are found, down to –400‰, which can only be modeled with a flatter {sup 13}C profile within the {sup 13}C pocket than is normally used. The dependence of δ({sup 138}Ba/{sup 136}Ba) predictions on the distribution of {sup 13}C within the pocket in asymptotic giant branch (AGB) models allows us to probe the {sup 13}C profile within the {sup 13}C pocket and the pocket mass in AGB stars. In addition, we provide constraints on the {sup 22}Ne(α, n){sup 25}Mg rate in the stellar temperature regime relevant to AGB stars, based on δ({sup 134}Ba/{sup 136}Ba) values of mainstream grains. We found two nominally mainstream grains with strongly negative δ({sup 134}Ba/{sup 136}Ba) values that cannot be explained by any of the current AGB model calculations. Instead, such negative values are consistent with the intermediate neutron capture process (i process), which is activated by the very late thermal pulse during the post-AGB phase and characterized by a neutron density much higher than the s process. These two grains may have condensed around post-AGB stars. Finally, we report abundances of two p-process isotopes, {sup 130}Ba and {sup 132}Ba, in single SiC grains. These isotopes are destroyed in the s process in AGB stars. By comparing their abundances with respect to that of {sup 135}Ba, we conclude that there is no measurable decay of {sup 135}Cs (t {sub 1/2} = 2.3 Ma) to {sup 135}Ba in individual SiC grains, indicating condensation of barium, but not cesium into SiC grains before {sup 135}Cs decayed.

  6. Branching Morphogenesis

    PubMed Central

    Horowitz, Arie; Simons, Michael

    2009-01-01

    Tubular structures are a fundamental anatomical theme recurring in a wide range of animal species. In mammals, tubulogenesis underscores the development of several systems and organs, including the vascular system, the lungs, and the kidneys. All tubular systems are hierarchical, branching into segments of gradually diminishing diameter. There are only two cell types that form the lumen of tubular systems – either endothelial cells in the vascular system, or epithelial cells in all other organs. The most important feature in determining the morphology of the tubular systems is the frequency and geometry of branching. Hence, deciphering the molecular mechanisms underlying the sprouting of new branches from pre-existing ones is the key to understanding the formation of tubular systems. The morphological similarity between the various tubular systems is underscored by similarities between the signaling pathways which control their branching. A prominent feature common to these pathways is their duality – an agonist counterbalanced by an inhibitor. The formation of the tracheal system in Drosophila melanogaster is driven by fibroblast growth factor (FGF) and inhibited by Sprouty/Notch. In vertebrates, the analogous pathways are FGF and transforming growth factor β in epithelial tubular systems, or vascular endothelial growth factor and Notch in the vascular system. PMID:19179661

  7. INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Branch Processes of Vortex Filaments and Hopf Invariant Constraint on Scroll Wave

    NASA Astrophysics Data System (ADS)

    Zhu, Tao; Ren, Ji-Rong; Mo, Shu-Fan

    2009-12-01

    In this paper, by making use of Duan's topological current theory, the evolution of the vortex filaments in excitable media is discussed in detail. The vortex filaments are found generating or annihilating at the limit points and encountering, splitting, or merging at the bifurcation points of a complex function Z(vec x, t). It is also shown that the Hopf invariant of knotted scroll wave filaments is preserved in the branch processes (splitting, merging, or encountering) during the evolution of these knotted scroll wave filaments. Furthermore, it also revealed that the “exclusion principle" in some chemical media is just the special case of the Hopf invariant constraint, and during the branch processes the “exclusion principle" is also protected by topology.

  8. Fault Branching

    NASA Astrophysics Data System (ADS)

    Dmowska, R.; Rice, J. R.; Poliakov, A. N.

    2001-12-01

    Theoretical stress analysis for a propagating shear rupture suggests that the propensity of the rupture path to branch is determined by rupture speed and by the preexisting stress state. See Poliakov, Dmowska and Rice (JGR, submitted April 2001, URL below). Deviatoric stresses near a mode II rupture tip are found to be much higher to both sides of the fault plane than directly ahead, when rupture speed becomes close to the Rayleigh speed. However, the actual pattern of predicted Coulomb failure on secondary faults is strongly dependent on the angle between the fault and the direction of maximum compression Smax in the pre-stress field. Steep Smax angles lead to more extensive failure on the extensional side, whereas shallow angles give comparable failure regions on both. Here we test such concepts against natural examples. For crustal thrust faults we may assume that Smax is horizontal. Thus nucleation on a steeply dipping plane, like the 53 ° dip for the 1971 San Fernando earthquake, is consistent with rupture path kinking to the extensional side, as inferred. Nucleation on a shallow dip, like for the 12 ° -18 ° of the 1985 Kettleman Hills event, should activate both sides, as seems consistent with aftershock patterns. Similarly, in a strike slip example, Smax is inferred to be at approximately 60 ° with the Johnson Valley fault where it branched to the extensional side onto the Landers-Kickapoo fault in the 1992 event, and this too is consistent. Further, geological examination of the activation of secondary fault features along the Johnson Valley fault and the Homestead Valley fault consistently shows that most activity occurs on the extensional side. Another strike-slip example is the Imperial Valley 1979 earthquake. The approximate Smax direction is north-south, at around 35 ° with the main fault, where it branched, on the extensional side, onto Brawley fault, again interpretable with the concepts developed.

  9. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival.

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-05-28

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a "standard" model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors.

  10. Sustainable Engineering and Improved Recycling of PET for High-Value Applications: Transforming Linear PET to Lightly Branched PET with a Novel, Scalable Process

    NASA Astrophysics Data System (ADS)

    Pierre, Cynthia; Torkelson, John

    2009-03-01

    A major challenge for the most effective recycling of poly(ethylene terephthalate) concerns the fact that initial melt processing of PET into a product leads to substantial degradation of molecular weight. Thus, recycled PET has insufficient melt viscosity for reuse in high-value applications such as melt-blowing of PET bottles. Academic and industrial research has tried to remedy this situation by synthesis and use of ``chain extenders'' that can lead to branched PET (with higher melt viscosity than the linear recycled PET) via condensation reactions with functional groups on the PET. Here we show that simple processing of PET via solid-state shear pulverization (SSSP) leads to enhanced PET melt viscosity without need for chemical additives. We hypothesize that this branching results from low levels of chain scission accompanying SSSP, leading to formation of polymeric radicals that participate in chain transfer and combination reactions with other PET chains and thereby to in situ branch formation. The pulverized PET exhibits vastly enhanced crystallization kinetics, eliminating the need to employ cold crystallization to achieve maximum PET crystallinity. Results of SSSP processing of PET will be compared to results obtained with poly(butylene terephthalate).

  11. Finding Uncertainties that Cause the Age Dependence of Dose Limits to Be Immature

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    Space radiation permissible exposure limits (PEL) are intended to set acceptable levels of cancer risks, and avoid any clinical significant non-cancer effects. The 1989 recommendation of the National Council of Radiation Protection and Measurements (NCRP) recommended a strong age dependence of dose limits that departed drastically from the then mature 1970 dose limits recommendations from the National Academy of Science, which were independent of age. In 2000, the NCRP recommended revised limits that showed a similar trend of risk with age to the 1989 report. In this model, the cancer risk per Sv varies by more than 2-fold for ages between 30- and 50-yr. Therefore for galactic cosmic rays exposure, astronaut age has a larger influence on risk then radiation shielding mass or material composition, vehicle propulsion method, or position in the solar cycle. For considering the control of mission costs and resources, the possibility of using astronaut age as a trade variable in mission design could be considered. However, the uncertainties in describing the age dependence on risk have not been fully explored. We discuss biological factors that influence the age dependence of radiation risks, including susceptibility, expression and latency, and radiation quality. These factors depend not only on the individual s age, but also their genetic sensitivity and interaction with other environmental factors. Epidemiological data is limited in describing the age dependence on risk. The 2005, BEIR VII report recommends an age dependence for cancer risk attributable solely to the life-table disagreeing strongly with the NCRP model. However, BEIR VII also noted the limited power of human data for concomitantly describing both age and age after exposure dependences of cancer risks. Many experimental studies have shown that high LET radiation (e.g., high charge and energy (HZE) nuclei and neutrons) display reduced latency compared to low LET radiation, suggesting distinct biological

  12. Age-dependent arginine phosphokinase activity changes in male vestigial and wild-type Drosophila melanogaster.

    PubMed

    Baker, G T

    1975-01-01

    The activity of arginine phosphokinase, an important muscle enzyme in insects, was investigated with age in vestigial-winged and wild-type Drosophila melanogaster. Identical patterns of age-dependent activity changes were observed in the vestigial-winged flies as in the wild-type, even though vestigial-winged flies exhibit a 50% mortality approximately two thirds that of the wild-type as well as being incapable of flight. Results indicate that the age-dependent changes in arginine phosphokinase activity are intrinsically regulated within the cells of the flight muscle.

  13. Damage Tolerance Assessment Branch

    NASA Technical Reports Server (NTRS)

    Walker, James L.

    2013-01-01

    The Damage Tolerance Assessment Branch evaluates the ability of a structure to perform reliably throughout its service life in the presence of a defect, crack, or other form of damage. Such assessment is fundamental to the use of structural materials and requires an integral blend of materials engineering, fracture testing and analysis, and nondestructive evaluation. The vision of the Branch is to increase the safety of manned space flight by improving the fracture control and the associated nondestructive evaluation processes through development and application of standards, guidelines, advanced test and analytical methods. The Branch also strives to assist and solve non-aerospace related NDE and damage tolerance problems, providing consultation, prototyping and inspection services.

  14. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences.

    PubMed

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-03-03

    NAD is an essential metabolite that exists in NAD(+) or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD(+)/NADH redox state and modulating cellular signaling processes through the activity of the NAD(+)-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD(+) and NADH contents and the NAD(+)/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.

  15. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

    PubMed Central

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-01-01

    NAD is an essential metabolite that exists in NAD+ or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+ and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ. PMID:25730862

  16. Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences.

    PubMed

    Jintaridth, Pornrutsami; Mutirangura, Apiwat

    2010-04-01

    Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = -0.452, P < 10(-3)) and HERV-K (r = -0.326, P < 10(-3)) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34-68 yr, and loss of methylation of HERV-K occurred during ages 40-63 yr and again during ages 64-83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10(-3)). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

  17. Molecular Correlates of Age-Dependent Seizures in an Inherited Neonatal-Infantile Epilepsy

    ERIC Educational Resources Information Center

    Liao, Yunxiang; Deprez, Liesbet; Maljevic, Snezana; Pitsch, Julika; Claes, Lieve; Hristova, Dimitrina; Jordanova, Albena; Ala-Mello, Sirpa; Bellan-Koch, Astrid; Blazevic, Dragica; Schubert, Simone; Thomas, Evan A.; Petrou, Steven; Becker, Albert J.; De Jonghe, Peter; Lerche, Holger

    2010-01-01

    Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial…

  18. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  19. Ontogenetic changes in genetic variances of age-dependent plasticity along a latitudinal gradient

    PubMed Central

    Nilsson-Örtman, V; Rogell, B; Stoks, R; Johansson, F

    2015-01-01

    The expression of phenotypic plasticity may differ among life stages of the same organism. Age-dependent plasticity can be important for adaptation to heterogeneous environments, but this has only recently been recognized. Whether age-dependent plasticity is a common outcome of local adaptation and whether populations harbor genetic variation in this respect remains largely unknown. To answer these questions, we estimated levels of additive genetic variation in age-dependent plasticity in six species of damselflies sampled from 18 populations along a latitudinal gradient spanning 3600 km. We reared full sib larvae at three temperatures and estimated genetic variances in the height and slope of thermal reaction norms of body size at three points in time during ontogeny using random regression. Our data show that most populations harbor genetic variation in growth rate (reaction norm height) in all ontogenetic stages, but only some populations and ontogenetic stages were found to harbor genetic variation in thermal plasticity (reaction norm slope). Genetic variances in reaction norm height differed among species, while genetic variances in reaction norm slope differed among populations. The slope of the ontogenetic trend in genetic variances of both reaction norm height and slope increased with latitude. We propose that differences in genetic variances reflect temporal and spatial variation in the strength and direction of natural selection on growth trajectories and age-dependent plasticity. Selection on age-dependent plasticity may depend on the interaction between temperature seasonality and time constraints associated with variation in life history traits such as generation length. PMID:25649500

  20. Sex differences in the effects of juvenile and adult diet on age-dependent reproductive effort.

    PubMed

    Houslay, T M; Hunt, J; Tinsley, M C; Bussière, L F

    2015-05-01

    Sexual selection should cause sex differences in patterns of resource allocation. When current and future reproductive effort trade off, variation in resource acquisition might further cause sex differences in age-dependent investment, or in sensitivity to changes in resource availability over time. However, the nature and prevalence of sex differences in age-dependent investment remain unclear. We manipulated resource acquisition at juvenile and adult stages in decorated crickets, Gryllodes sigillatus, and assessed effects on sex-specific allocation to age-dependent reproductive effort (calling in males, fecundity in females) and longevity. We predicted that the resource and time demands of egg production would result in relatively consistent female strategies across treatments, whereas male investment should depend sharply on diet. Contrary to expectations, female age-dependent reproductive effort diverged substantially across treatments, with resource-limited females showing much lower and later investment in reproduction; the highest fecundity was associated with intermediate lifespans. In contrast, long-lived males always signalled more than short-lived males, and male age-dependent reproductive effort did not depend on diet. We found consistently positive covariance between male reproductive effort and lifespan, whereas diet altered this covariance in females, revealing sex differences in the benefits of allocation to longevity. Our results support sex-specific selection on allocation patterns, but also suggest a simpler alternative: males may use social feedback to make allocation decisions and preferentially store resources as energetic reserves in its absence. Increased calling effort with age therefore could be caused by gradual resource accumulation, heightened mortality risk over time, and a lack of feedback from available mates.

  1. Age-dependent increase in the expression of antioxidant-like protein-1 in the gerbil hippocampus

    PubMed Central

    Park, Jin-A; Park, Joon Ha; Ahn, Ji Hyeon; Kim, Jong-Dai; Won, Moo-Ho; Lee, Choong-Hyun

    2016-01-01

    Antioxidant-like protein-1 (AOP-1) reduces the intracellular level of reactive oxygen species. In the present study, the age-related change in AOP-1 expression in the hippocampus among young, adult and aged gerbils was compared using western blot analysis and immunohistochemistry. The results demonstrated that the protein expression of AOP-1 was gradually and significantly increased in the hippocampus during the normal aging process. In addition, the age-dependent increase in AOP-1 immunoreactivity was also observed in pyramidal neurons of the hippocampus proper; however, in the dentate gyrus, AOP-1 immunoreactivity was not altered during the normal aging process. These results indicated that the expression of AOP-1 is significantly increased in the hippocampus proper, but not in the dentate gyrus, during the normal aging process. PMID:27511601

  2. TIEG1-null tenocytes display age-dependent differences in their gene expression, adhesion, spreading and proliferation properties

    SciTech Connect

    Haddad, Oualid; Gumez, Laurie; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Bensamoun, Sabine F.

    2011-07-15

    The remodeling of extracellular matrix is a crucial mechanism in tendon development and the proliferation of fibroblasts is a key factor in this process. The purpose of this study was to further elucidate the role of TIEG1 in mediating important tenocyte properties throughout the aging process. Wildtype and TIEG1 knockout tenocytes adhesion, spreading and proliferation were characterized on different substrates (fibronectin, collagen type I, gelatin and laminin) and the expression levels of various genes known to be involved with tendon development were analyzed by RT-PCR. The experiments revealed age-dependent and substrate-dependent properties for both wildtype and TIEG1 knockout tenocytes. Taken together, our results indicate an important role for TIEG1 in regulating tenocytes adhesion, spreading, and proliferation throughout the aging process. Understanding the basic mechanisms of TIEG1 in tenocytes may provide valuable information for treating multiple tendon disorders.

  3. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    PubMed

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  4. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    PubMed Central

    van der Heijden, Roel A.; Bijzet, Johan; Meijers, Wouter C.; Yakala, Gopala K.; Kleemann, Robert; Nguyen, Tri Q.; de Boer, Rudolf A.; Schalkwijk, Casper G.; Hazenberg, Bouke P. C.; Tietge, Uwe J. F.; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process. PMID:26563579

  5. Age dependence of metals in hair in a selected US population

    SciTech Connect

    Paschal, D.C.; DiPietro, E.S.; Phillips, D.L.; Gunter, E.W. )

    1989-02-01

    Concentrations of 28 metals were determined in hair samples from 199 children (age {le} years) and 322 adults (age 13-73) years. Levels of calcium, barium, magnesium, zinc, and strontium all show a similar age-dependent increase up to about 12-14 years; levels of aluminum show a decrease with age. Relationships of elemental concentrations with age were examined by using correlation, linear regression, t tests, and discriminant analysis. Statistically significant differences in mean concentration values between children and adults were shown for these metals. Discriminant analysis gave about 95% accuracy in classifying a test data set into the categories of children and adults. A hypothesis suggested by the data is that there is an age-dependent excretion in hair of alkali metals during skeletal growth and development. The observed decrease in aluminum is largely unexplained at this time.

  6. MLE and Bayesian inference of age-dependent sensitivity and transition probability in periodic screening.

    PubMed

    Wu, Dongfeng; Rosner, Gary L; Broemeling, Lyle

    2005-12-01

    This article extends previous probability models for periodic breast cancer screening examinations. The specific aim is to provide statistical inference for age dependence of sensitivity and the transition probability from the disease free to the preclinical state. The setting is a periodic screening program in which a cohort of initially asymptomatic women undergo a sequence of breast cancer screening exams. We use age as a covariate in the estimation of screening sensitivity and the transition probability simultaneously, both from a frequentist point of view and within a Bayesian framework. We apply our method to the Health Insurance Plan of Greater New York study of female breast cancer and give age-dependent sensitivity and transition probability density estimates. The inferential methodology we develop is also applicable when analyzing studies of modalities for early detection of other types of progressive chronic diseases.

  7. Age dependence of the concentrations of harmful substances in Baltic herring (Clupea harengus)

    SciTech Connect

    Perttila, M.; Tervo, V.; Parmanne, R.

    1982-01-01

    The age dependence of Zn, Cu, Pb, Cd, Hg, CH/sub 3/-Hg, DDT, DDD, DDE, HCH, HCB and the PCBs have been studied in Baltic herring of 1 to 6 years of age. Lead, cadmium, mercury and the organochlorine concentrations increase significantly with age. In the case of the DDTs and the PCBs, the variations can be attributed almost totally to the combined effect of age and variations in the lipid percentage.

  8. Substrate Specificities and Intracellular Distributions of Three N-glycan Processing Enzymes Functioning at a Key Branch Point in the Insect N-Glycosylation Pathway*

    PubMed Central

    Geisler, Christoph; Jarvis, Donald L.

    2012-01-01

    Man(α1–6)[GlcNAc(β1–2)Man(α1–3)]ManGlcNAc2 is a key branch point intermediate in the insect N-glycosylation pathway because it can be either trimmed by a processing β-N-acetylglucosaminidase (FDL) to produce paucimannosidic N-glycans or elongated by N-acetylglucosaminyltransferase II (GNT-II) to produce complex N-glycans. N-Acetylglucosaminyltransferase I (GNT-I) contributes to branch point intermediate production and can potentially reverse the FDL trimming reaction. However, there has been no concerted effort to evaluate the relationships among these three enzymes in any single insect system. Hence, we extended our previous studies on Spodoptera frugiperda (Sf) FDL to include GNT-I and -II. Sf-GNT-I and -II cDNAs were isolated, the predicted protein sequences were analyzed, and both gene products were expressed and their acceptor substrate specificities and intracellular localizations were determined. Sf-GNT-I transferred N-acetylglucosamine to Man5GlcNAc2, Man3GlcNAc2, and GlcNAc(β1–2)Man(α1–6)[Man(α1–3)]ManGlcNAc2, demonstrating its role in branch point intermediate production and its ability to reverse FDL trimming. Sf-GNT-II only transferred N-acetylglucosamine to Man(α1–6)[GlcNAc(β1–2)Man(α1–3)]ManGlcNAc2, demonstrating that it initiates complex N-glycan production, but cannot use Man3GlcNAc2 to produce hybrid or complex structures. Fluorescently tagged Sf-GNT-I and -II co-localized with an endogenous Sf Golgi marker and Sf-FDL co-localized with Sf-GNT-I and -II, indicating that all three enzymes are Golgi resident proteins. Unexpectedly, fluorescently tagged Drosophila melanogaster FDL also co-localized with Sf-GNT-I and an endogenous Drosophila Golgi marker, indicating that it is a Golgi resident enzyme in insect cells. Thus, the substrate specificities and physical juxtapositioning of GNT-I, GNT-II, and FDL support the idea that these enzymes function at the N-glycan processing branch point and are major factors determining the

  9. Age-dependent tissue-specific exposure of cell phone users

    NASA Astrophysics Data System (ADS)

    Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

    2010-04-01

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  10. Age-dependent effect of static magnetic field on brain tissue hydration.

    PubMed

    Deghoyan, Anush; Nikoghosyan, Anna; Heqimyan, Armenuhi; Ayrapetyan, Sinerik

    2014-01-01

    Age-dependent effect of Static Magnetic Field (SMF) on rats in a condition of active and inactive Na(+)/K(+) pump was studied for comparison of brain tissues hydration state changes and magnetic sensitivity. Influence of 15 min 0, 2 Tesla (T) SMF on brain tissue hydration of three aged groups of male albino rats was studied. Tyrode's physiological solution and 10(-4) M ouabain was used for intraperitoneal injections. For animal immobilization, the liquid nitrogen was used and the definition of tissue water content was performed by tissue drying method. Initial water content in brain tissues of young animals is significantly higher than in those of adult and aged ones. SMF exposure leads to decrease of water content in brain tissues of young animals and increase in brain tissues of adult and aged ones. In case of ouabain-poisoned animals, SMF gives reversal effects on brain tissue's hydration both in young and aged animals, while no significant effect on adults is observed. It is suggested that initial state of tissue hydration could play a crucial role in animal age-dependent magnetic sensitivity and the main reason for this could be age-dependent dysfunction of Na(+)/K(+) pump.

  11. Age-Dependent TLR3 Expression of the Intestinal Epithelium Contributes to Rotavirus Susceptibility

    PubMed Central

    Pott, Johanna; Stockinger, Silvia; Torow, Natalia; Smoczek, Anna; Lindner, Cornelia; McInerney, Gerald; Bäckhed, Fredrik; Baumann, Ulrich; Pabst, Oliver; Bleich, André; Hornef, Mathias W.

    2012-01-01

    Rotavirus is a major cause of diarrhea worldwide and exhibits a pronounced small intestinal epithelial cell (IEC) tropism. Both human infants and neonatal mice are highly susceptible, whereas adult individuals remain asymptomatic and shed only low numbers of viral particles. Here we investigated age-dependent mechanisms of the intestinal epithelial innate immune response to rotavirus infection in an oral mouse infection model. Expression of the innate immune receptor for viral dsRNA, Toll-like receptor (Tlr) 3 was low in the epithelium of suckling mice but strongly increased during the postnatal period inversely correlating with rotavirus susceptibility, viral shedding and histological damage. Adult mice deficient in Tlr3 (Tlr3−/−) or the adaptor molecule Trif (TrifLps2/Lps2) exerted significantly higher viral shedding and decreased epithelial expression of proinflammatory and antiviral genes as compared to wild-type animals. In contrast, neonatal mice deficient in Tlr3 or Trif did not display impaired cell stimulation or enhanced rotavirus susceptibility. Using chimeric mice, a major contribution of the non-hematopoietic cell compartment in the Trif-mediated antiviral host response was detected in adult animals. Finally, a significant age-dependent increase of TLR3 expression was also detected in human small intestinal biopsies. Thus, upregulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection. PMID:22570612

  12. Properties of the 5{sup -} state at 839 keV in {sup 176}Lu and the s-process branching at A=176

    SciTech Connect

    Mohr, P.; Bisterzo, S.; Gallino, R.; Kaeppeler, F.; Kneissl, U.; Winckler, N.

    2009-04-15

    The s-process branching at mass number A=176 depends on the coupling between the high-K ground state and a low-lying low-K isomer in {sup 176}Lu. This coupling is based on electromagnetic transitions via intermediate states at higher energies. The properties of the lowest experimentally confirmed intermediate state at 839 keV are reviewed, and the transition rate between low-K and high-K states under stellar conditions is calculated on the basis of new experimental data for the 839-keV state. Properties of further candidates for intermediate states are briefly analyzed. It is found that the coupling between the high-K ground state and the low-K isomer in {sup 176}Lu is at least one order of magnitude stronger than previously assumed, leading to crucial consequences for the interpretation of the {sup 176}Lu/{sup 176}Hf pair as an s-process thermometer.

  13. Involvement of BDNF in Age-Dependent Alterations in the Hippocampus

    PubMed Central

    Halbach, Oliver von Bohlen und

    2010-01-01

    It is known since a long time that the hippocampus is sensitive to aging. Thus, there is a reduction in the hippocampal volume during aging. This age-related volume reduction is paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks. This age-related volume reduction of the hippocampus is not a consequence of an age-related loss of hippocampal neurons. The morphological changes associated with aging include reductions in the branching pattern of dendrites, as well as reductions in spine densities, reductions in the densities of fibers projecting into the hippocampus as well as declines in the rate of neurogenesis. It is very unlikely that a single factor or a single class of molecules is responsible for all these age-related morphological changes in the hippocampus. Nevertheless, it would be of advantage to identify possible neuromodulators or neuropeptides that may contribute to these age-related changes. In this context, growth factors may play an important role in the maintenance of the postnatal hippocampal architecture. In this review it is hypothesized that brain-derived neurotrophic factor (BDNF) is a factor critically involved in the regulation of age-related processes in the hippocampus. Moreover, evidences suggest that disturbances in the BDNF-system also affect hippocampal dysfunctions, as e.g. seen in major depression or in Alzheimer disease. PMID:20941325

  14. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    PubMed

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.

  15. Disrupting the key circadian regulator CLOCK leads to age-dependent cardiovascular disease.

    PubMed

    Alibhai, Faisal J; LaMarre, Jonathan; Reitz, Cristine J; Tsimakouridze, Elena V; Kroetsch, Jeffrey T; Bolz, Steffen-Sebastian; Shulman, Alex; Steinberg, Samantha; Burris, Thomas P; Oudit, Gavin Y; Martino, Tami A

    2017-04-01

    The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness. Young Clock(Δ19/Δ19) hearts express dysregulated mRNAs and miRNAs in the PTEN-AKT signal pathways important for cardiac hypertrophy. We found a rhythm in the Pten gene and PTEN protein in WT hearts; rhythmic oscillations are lost in Clock(Δ19/Δ19) hearts. Changes in PTEN are associated with reduced AKT activation and changes in downstream mediators GSK-3β, PRAS40, and S6K1. Cardiomyocyte cultures confirm that Clock regulates the AKT signalling pathways crucial for cardiac hypertrophy. In old Clock(Δ19/Δ19) mice cardiac AKT, GSK3β, S6K1 phosphorylation are increased, consistent with the development of age-dependent cardiac hypertrophy. Lastly, we show that pharmacological modulation of the circadian mechanism with the REV-ERB agonist SR9009 reduces AKT activation and heart weight in old WT mice. Furthermore, SR9009 attenuates cardiac hypertrophy in mice subjected to transverse aortic constriction (TAC), supporting that the circadian mechanism plays an important role in regulating cardiac growth. These findings demonstrate a crucial role for Clock in growth and renewal; disrupting Clock leads to age-dependent cardiomyopathy. Pharmacological targeting of the circadian mechanism provides a new opportunity for treating heart disease.

  16. Scheduling Maintenance Operations Which Cause Age-Dependent Failure Rate Changes,

    DTIC Science & Technology

    1983-06-01

    ENGI.. UNCLASSIFIED B EBRAHIMIAN ET AL I JUN 83 F/G 5/1 NLmEEmmEEmmmmEE EEIhEIIhEEIII EEIIIIIIIEIIIE EIIIEIIIIIIIEE IEEIhIhEIhEIhE EIIIEEEEEIhIhE...OPERATIONS WHICH CAUSE AGE-DEPENDENT FAILURE RATE CHANGES BY BEHNAM EBRAHIMIAN AND LEONARD SHAW Prepared for Office of Naval Research Contract N00014-75-C-0858... EBRAHIMIAN AND LEONARD SHAW Prepared for Office of Naval Research Contract N00014-75-C-0858 Report No. POLY EE/CS 83-002 Polytechnic Institute of New York

  17. Age-dependence of hepatic dimethylnitrosamine-demethylase activity in the rat.

    PubMed

    Davies, D L; Bryant, G M; Arcos, J C; Argus, M F

    1976-05-01

    The mixed-function oxidase which activates the carcinogen dimethylnitrosamine (DMN) was determined in the rat liver as a function of animal age. DMN-demethylase activity increased considerably at first to reach a maximum on day 29, and then substantially decreased to day 59; thereafter, enzyme activity remained essentially stable up to at least day 110. Pretreatment with 3-methylcholanthrene, which caused a pronounced decrease in this enzyme activity, did not affect the general shape of the age-dependence curve. The results suggest that rats between weaning and sexual maturity are more susceptible to the carcinogenic effects of pulse doses of DMN than are neonates or adult animals.

  18. Optimal control of an influenza model with seasonal forcing and age-dependent transmission rates.

    PubMed

    Lee, Jeehyun; Kim, Jungeun; Kwon, Hee-Dae

    2013-01-21

    This study considers an optimal intervention strategy for influenza outbreaks. Variations in the SEIAR model are considered to include seasonal forcing and age structure, and control strategies include vaccination, antiviral treatment, and social distancing such as school closures. We formulate an optimal control problem by minimizing the incidence of influenza outbreaks while considering intervention costs. We examine the effects of delays in vaccine production, seasonal forcing, and age-dependent transmission rates on the optimal control and suggest some optimal strategies through numerical simulations.

  19. Suspended-sediment yields and stream-channel processes on Judy's Branch watershed in the St. Louis Metro East region in Illinois

    USGS Publications Warehouse

    Straub, Timothy D.; Johnson, Gary P.; Roseboom, Donald P.; Sierra, Carlos R.

    2006-01-01

    Judy's Branch watershed, a small basin (8.64 square miles) in the St. Louis Metro East region in Illinois, was selected as a pilot site to determine suspended-sediment yields and stream-channel processes in the bluffs and American Bottoms (expansive low-lying valley floor in the region). Suspended-sediment and stream-chan-nel data collected and analyzed for Judy's Branch watershed are presented in this report to establish a baseline of data for water-resource managers to evaluate future stream rehabilitation and manage-ment alternatives. The sediment yield analysis determines the amount of sediment being delivered from the watershed and two subwatersheds: an urban tributary and an undeveloped headwater (pri-marily agricultural). The analysis of the subwater-sheds is used to compare the effects of urbanization on sediment yield to the river. The stream-channel contribution to sediment yield was determined by evaluation of the stream-channel processes operat-ing on the streambed and banks of Judy's Branch watershed. Bank stability was related to hydrologic events, bank stratigraphy, and channel geometry through model development and simulation. The average suspended-sediment yield from two upland subwatersheds (drainage areas of 0.23 and 0.40 sq.mi. was 1,163 tons per square mile per year (tons/sq.mi.-year) between July 2000 and June 2004. The suspended-sediment yield at the Route 157 station was 2,523 tons/sq.mi.-year, near the outlet of Judy's Branch watershed (drainage area = 8.33 sq.mi.). This is approximately 1,360 tons/sq.mi.-year greater than the average at the upland stations for the same time period. This result is unexpected in that, generally, the suspended-sediment yield decreases as the watershed area increases because of sediment stored in the channel and flood plain. The difference indicates a possible increase in yield from a source, such as bank retreat, and supports the concept that land-use changes increase stream-flows that may in turn result in

  20. Light scattering study of the normal human eye lens: Elastic properties and age dependence

    PubMed Central

    Bailey, Sheldon T.; Twa, Michael D.; Gump, Jared C.; Venkiteshwar, Manoj; Bullimore, Mark A.

    2015-01-01

    The human ocular lens is a tissue capable of changing its shape to dynamically adjust the optical power of the eye, a function known as accommodation, which gradually declines with age. This capability is the response of the lens tissue to external forces which, in turn, is modulated by the biomechanical characteristics of lens tissues. In order to investigate the contributions of lens sclerosis to loss of accommodation, we report on in vitro confocal Brillouin light scattering studies of human ocular lenses spanning over a 30-70 year age range. Using this non-destructive measurement method, we determined that the longitudinal bulk modulus (average ± SD) of the lens nucleus (2.79±0.14 GPa) was consistently greater than the bulk modulus of the lens cortex (2.36±0.09 GPa). Moreover, our results showed that these differences were not age dependent over the 40 year age range that we evaluated using healthy lens tissues. Our results are consistent with the hypothesis that an age-dependent change in the bulk modulus of lens tissues does not fully account for the natural decline of accommodation. PMID:20529725

  1. Age-dependent changes in cuticular hydrocarbons of larvae in Aldrichina grahami (Aldrich) (Diptera: Calliphoridae).

    PubMed

    Xu, Hong; Ye, Gong-Yin; Xu, Ying; Hu, Cui; Zhu, Guang-Hui

    2014-09-01

    Necrophagous flies, comprising the first wave of insects present in a cadaver, provide a great potential for more accurate determination of the late postmortem interval (PMI) based on their age. Cuticular hydrocarbons (CHs) are a promising age indicator in some insect species, especially for the larvae of necrophagous flies. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to characterize the age-dependent, quantitative changes in CHs of larval Aldrichina grahami (Aldrich) (Diptera: Calliphoridae) at 24°C. The majority of low-molecular-weight alkanes (≤C25) and almost all of the alkenes decreased in abundance with larval development. By contrast, the abundance of high-molecular-weight alkanes of chain length greater than C25 gradually increased with age. For several peaks, including peak 28 (pentacosene a), peak 31 (n-C25), peak 43 (n-C27) and peak 68 (n-C31), a highly significant correlation was found between peak ratio (n-C29 divided by each chromatographic peak) and chronological age of the larvae. A mathematical model, derived from multivariate linear regression analysis, was developed for determining age of the larvae based on age-dependent changes in CHs. The estimated larval age based on the CHs had a good linear correlation with the chronological age (R(2)>0.9). These results indicate that CHs has a great potential for determining the age of fly larvae, and concomitantly for the PMI in forensic investigation.

  2. Age-dependent responses of glial cells and leptomeninges during systemic inflammation.

    PubMed

    Wu, Zhou; Tokuda, Yukie; Zhang, Xin-Wen; Nakanishi, Hiroshi

    2008-12-01

    Systemic inflammation causes the age-dependent differential glial responses, but little is known about how age influences the barrier function of leptomeninges during systemic inflammation. This study was conducted to elucidate the relationship between the glial responses and the levels of tight junction proteins, occludin and ZO-1, in adjuvant arthritis (AA) rats. In young AA rats, microglia and astrocytes localized to the proximity of the leptomeninges expressed interleukin (IL)-10 and transforming growth factor (TGF)-beta1. The level of occludin significantly increased. In middle-aged AA rats, however, glial cells expressed IL-1beta and prostaglandin E(2) (PGE(2))-synthesizing enzymes. Furthermore, occludin and ZO-1 significantly decreased, resulting in the increased permeability of leptomeninges. In the cultured leptomeningeal cells, IL-1beta and PGE(2) caused a marked loss of occludin and ZO-1, respectively. Pretreatment with IL-10 and TGF-beta1 significantly antagonized their effects. These findings establish that age strongly influences the barrier functions of the leptomeninges through the age-dependent differential glial responses during systemic inflammation.

  3. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function.

  4. Growth of branched actin networks against obstacles.

    PubMed Central

    Carlsson, A E

    2001-01-01

    A method for simulating the growth of branched actin networks against obstacles has been developed. The method is based on simple stochastic events, including addition or removal of monomers at filament ends, capping of filament ends, nucleation of branches from existing filaments, and detachment of branches; the network structure for several different models of the branching process has also been studied. The models differ with regard to their inclusion of effects such as preferred branch orientations, filament uncapping at the obstacle, and preferential branching at filament ends. The actin ultrastructure near the membrane in lamellipodia is reasonably well produced if preferential branching in the direction of the obstacle or barbed-end uncapping effects are included. Uncapping effects cause the structures to have a few very long filaments that are similar to those seen in pathogen-induced "actin tails." The dependence of the growth velocity, branch spacing, and network density on the rate parameters for the various processes is quite different among the branching models. An analytic theory of the growth velocity and branch spacing of the network is described. Experiments are suggested that could distinguish among some of the branching models. PMID:11566765

  5. Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor.

    PubMed Central

    Baylis, C

    1994-01-01

    The glomerulus develops progressive injury with advancing age which is particularly pronounced in males and is not the result of any specific disease process. In the present studies conducted in rats, glomerular function and structure were examined in adult (8 mo), elderly (12 mo), and old (19 mo) Munich Wistar rats. Intact males and females and castrated rats of both sexes were studied to determine the role of the sex hormones in mediating age-dependent glomerular damage. Intact males developed glomerular injury and proteinuria whereas females, both intact and ovariectomized, and castrated males were protected from injury. Glomerular blood pressure did not increase with advancing age in any group and did not correlate with glomerular damage. Glomerular volume did increase with advancing age in all groups but did not correlate with glomerular damage. We found that the presence of the androgens rather than the absence of the estrogens provide the risk factor for development of age-dependent glomerular damage. Neither glomerular hypertension nor glomerular hypertrophy provide the primary mechanism by which age-dependent glomerular injury occurs in the intact male. PMID:7962527

  6. Age-dependent accumulation of (137)Cs by pike Esox lucius in the Yenisei River.

    PubMed

    Zotina, T A; Trofimova, E A; Dementyev, D V; Bolsunovsky, A Ya

    2016-05-01

    Age-dependent accumulation of (137)Cs in the muscles and bodies of the pike Esox lucius (aged two to seven years) inhabiting a section of the Yenisei River polluted with artificial radionuclides has been studied. The content of (137)Cs in muscles varied from 0.5 to 7.0 Bq/kg of fresh weight. The maximum content of the radionuclide has been found in juveniles. The content of (137)Cs in pike muscles and body decreased considerably with age. The high content of (137)Cs in the muscles of juveniles is probably a consequence of their higher intensity of feeding as compared to older individuals, which is due to the intense growth of juveniles.

  7. Age dependent hypergastrinaemia in children with Helicobacter pylori gastritis--evidence of early acquisition of infection.

    PubMed Central

    McCallion, W A; Ardill, J E; Bamford, K B; Potts, S R; Boston, V E

    1995-01-01

    Acute Helicobacter pylori associated gastritis causes achlorhydria, a powerful stimulus to gastrin secretion. If H pylori infection is acquired primarily in early childhood, then the degree of hypergastrinaemia in seropositive children should be age dependent. Anti-Helicobacter antibodies and fasting gastrin concentrations were measured in 439 children aged 4 to 13 years attending hospital for routine day case surgery not connected with any gastrointestinal disorder. Thirty per cent were seropositive for H pylori. There was an inverse relationship between the fasting gastrin concentration and age; the mean fasting gastrin in children aged 4-5 years, 155 ng/l, was significantly higher than that seen in children aged 12-13 years, 90 ng/l. The more noticeable hypergastrinaemia seen in young children with H pylori associated gastritis may reflect achlorhydria associated with acute H pylori infection and suggests that this is primarily acquired in early childhood. PMID:7672676

  8. White LED compared with other light sources: age-dependent photobiological effects and parameters for evaluation.

    PubMed

    Rebec, Katja Malovrh; Klanjšek-Gunde, Marta; Bizjak, Grega; Kobav, Matej B

    2015-01-01

    Ergonomic science at work and living places should appraise human factors concerning the photobiological effects of lighting. Thorough knowledge on this subject has been gained in the past; however, few attempts have been made to propose suitable evaluation parameters. The blue light hazard and its influence on melatonin secretion in age-dependent observers is considered in this paper and parameters for its evaluation are proposed. New parameters were applied to analyse the effects of white light-emitting diode (LED) light sources and to compare them with the currently applied light sources. The photobiological effects of light sources with the same illuminance but different spectral power distribution were determined for healthy 4-76-year-old observers. The suitability of new parameters is discussed. Correlated colour temperature, the only parameter currently used to assess photobiological effects, is evaluated and compared to new parameters.

  9. Distribution of uranium in drinking water and associated age-dependent radiation dose in India.

    PubMed

    Sahoo, S K; Mohapatra, S; Chakrabarty, A; Sumesh, C G; Jha, V N; Tripathi, R M; Puranik, V D

    2009-09-01

    Exposure due to natural radiation is of particular importance because it accounts for the largest contribution (nearly 85 %) to the total collective dose of the world population. An attempt has been made to present the feasibility of uranium occurrence in drinking water samples from different states of India, by laser-induced fluorimetry. The associated age-dependent radiation dose was estimated by taking the prescribed water intake values of different age groups. The concentration of uranium obtained, i.e. 0.1 +/- 0.01 to 19.6 +/- 1.8 microg l(-1), is well below the drinking water guideline value of 30 microg l(-1). The annual ingestion dose due to uranium in drinking water for various age groups is found to vary from 0.14 to 48 microSv y(-1).

  10. Assessment of (226)Ra age-dependent dose from water intake.

    PubMed

    Porntepkasemsan, Boonsom; Srisuksawad, Kanitha

    2008-11-01

    The radioactivity in canal and ground waters collected in a 2-year long observation from the vicinity of the Rare Earth Research and Development Center (RRDC), Phathumthani Province, Thailand, was measured in order to determine the concentration of (226)Ra and to estimate the age-dependent effective dose to humans due to consumption. (226)Ra activities in both canal and ground waters were well below the WHO guidance level for drinking water quality of 1 Bq L(-1). The highest (226)Ra effective doses per year were found for infants and teens. However, the observed levels of calculated (226)Ra effective doses for all age groups in both canal and ground waters show satisfactory low values (less than 15 microSv yr(-1)). These values are acceptable in accordance with the WHO recommended reference dose level of 100 microSv yr(-1) from water intake of 2 Lday(-1).

  11. Transient Elastography-Based Liver Stiffness Age-Dependently Increases in Children

    PubMed Central

    Tokuhara, Daisuke; Cho, Yuki; Shintaku, Haruo

    2016-01-01

    Background and Aims Pediatric use of liver transient elastography (TE) is attractive for its non-invasiveness, but reference values have not been established. We aimed to determine reference values for TE in children. Methods In pediatric patients (1 to 18 years), TE (FibroScan®) with an M probe was used for both liver stiffness measurement (LSM) and measurement of hepatic fat deposition by using a controlled attenuation parameter (CAP). The patients were divided into three relevant age groups: preschoolers (1 to 5 years), elementary school children (6 to 11 years), and adolescents (12 to 18 years). Overweight or obese patients or those with known liver disease, elevated serum liver enzymes, or hepatic echogenic abnormality were excluded from the study. Results Among 139 children, 123 (88.5%; 62 male; median age, 11.7 years; age range, 1.3 to 17.2 years) were successfully subjected to M-probe TE without anesthesia. Median LSM increased with age: it was 3.4 kPa (2.3 to 4.6 kPa, 5th to 95th percentiles) at ages 1 to 5 years; 3.8 (2.5 to 6.1) kPa at ages 6 to 11; and 4.1 (3.3 to 7.9) kPa at ages 12 to 18 (P = 0.001). Median CAP was not age dependent: it was 183 (112 to 242) for ages 1 to 18 years. Conclusions M-probe TE is suitable in a wide age range of children from age 1 year up. In children without evidence of liver disease, LSM has an age-dependent increase, whereas CAP does not differ between ages 1 and 18. PMID:27861607

  12. Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    PubMed Central

    Glushakov, Alexander V.; Arias, Rodrigo A.; Tolosano, Emanuela; Doré, Sylvain

    2016-01-01

    Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wildtype (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp−∕−) in two age cohorts [2–4 mo-old (young adult) and 7–8 mo-old (older adult)]. The data obtained suggest age-dependent significant effects on behavioral and anatomical TBI outcomes and recovery from injury. Moreover, in the adult cohort, neurological deficits in Hp−∕− mice at 24 h were significantly improved compared to WT, whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp−∕− mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp−∕− and WT in selected brain regions of the adult but not the older adult-aged cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes. PMID:27486583

  13. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-11-01

    Long noncoding RNAs (lncRNAs) are ≥200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 weeks) compared to both immature (4 weeks) and old (70 weeks) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  14. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-12-01

    Long noncoding RNAs (lncRNAs) are ≥ 200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 week) compared to both immature (4 week) and old (70 week) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  15. Gestational Age-Dependent Changes in Gene Expression of Metabolic Enzymes and Transporters in Pregnant Mice

    PubMed Central

    Shuster, Diana L.; Bammler, Theo K.; Beyer, Richard P.; MacDonald, James W.; Tsai, Jesse M.; Farin, Frederico M.; Hebert, Mary F.; Thummel, Kenneth E.

    2013-01-01

    Pregnancy-induced changes in drug pharmacokinetics can be explained by changes in expression of drug-metabolizing enzymes and transporters and/or normal physiology. In this study, we determined gestational age-dependent expression profiles for all metabolic enzyme and transporter genes in the maternal liver, kidney, small intestine, and placenta of pregnant mice by microarray analysis. We specifically examined the expression of genes important for xenobiotic, bile acid, and steroid hormone metabolism and disposition, namely, cytochrome P450s (Cyp), UDP-glucuronosyltranserases (Ugt), sulfotransferases (Sult), and ATP-binding cassette (Abc), solute carrier (Slc), and solute carrier organic anion (Slco) transporters. Few Ugt and Sult genes were affected by pregnancy. Cyp17a1 expression in the maternal liver increased 3- to 10-fold during pregnancy, which was the largest observed change in the maternal tissues. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 expression in the liver decreased on gestation days (gd) 15 and 19 compared with nonpregnant controls (gd 0). In contrast, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. In the placenta, Cyp expression on gd 10 and 15 was upregulated compared with gd 19. Notable changes were also observed in Abc and Slc transporters. Abcc3 expression in the liver and Abcb1a, Abcc4, and Slco4c1 expression in the kidney were downregulated on gd 15 and 19. In the placenta, Slc22a3 (Oct3) expression on gd 10 was 90% lower than that on gd 15 and 19. This study demonstrates important gestational age-dependent expression of metabolic enzyme and transporter genes, which may have mechanistic relevance to drug disposition in human pregnancy. PMID:23175668

  16. Age-dependent changes in plasma and brain cholinesterase activities of house wrens and European starlings.

    PubMed

    Mayack, David T; Martin, Tim

    2003-07-01

    We determined age-dependent changes in plasma and brain cholinesterase (ChE) activity for two species of passerines: house wren (Troglodytes aedon) and European starling (Sturnus vulgaris, starling). In plasma from nestlings of both species, total ChE activity increased with age, acetycholinesterase (AChE, EC 3.1.1.7) activity declined rapidly immediately after hatching, and butyrylcholinesterase (BChE, EC 3.1.1.8) activity increased steadily. For both species, total ChE and BChE activities and the BChE:AChE ratio in plasma were significantly greater in adults than nestlings suggesting trends observed in nestlings continue post fledging. In older nestlings and adults, AChE activity in plasma was significantly greater and BChE:AChE ratio less in house wrens than starlings. For house wrens as compared with starlings, ChE activity in brain increased at a significantly greater rate with age in nestlings and was significantly greater in adults. However, ChE activity in brain was similar at fledging for both species suggesting that the increase in ChE in brain is more directly related to ontogeny than chronologic age in nestlings of passerines. For both species, ChE activity increased significantly with brain weight of nestlings but not adults. House wrens hold similar patterns of age-dependent change in ChE activity in common with starlings but also exhibit differences in AChE activity in plasma that should be considered as a factor potentially affecting their relative toxicologic response to ChE inhibitors.

  17. Lung injury after hemorrhage is age-dependent: role of peroxisome proliferator activated receptor γ

    PubMed Central

    Zingarelli, Basilia; Hake, Paul W.; O’Connor, Michael; Burroughs, Timothy J.; Wong, Hector R.; Solomkin, Joseph S.; Lentsch, Alex B.

    2009-01-01

    Objective The incidence of multiple organ failure in pediatric trauma victims is lower than in the adult population. However, the molecular mechanisms are not yet defined. We investigated whether the pathophysiologic characteristics of hemorrhage-induced lung injury may be age-dependent and may be regulated by the peroxisome proliferator activator receptor γ (PPARγ). Design Prospective, laboratory investigation that used an established rodent model of hemorrhagic shock. Setting University hospital laboratory. Subjects Young (n=67; 3–5 months old) and mature (n=66; 11–13 months old) male rats. Interventions Hemorrhagic shock was induced in young and mature rats by withdrawing blood to a mean arterial blood pressure of 50 mmHg. After 3 hrs, rats were rapidly resuscitated by infusing the shed blood and sacrificed 3 hrs thereafter. Measurements and Main Results In young rats, lung injury was characterized by accumulation of red cells and neutrophils at the end of the resuscitation period; at Western blot analysis, lung expression of intercellular adhesion molecule-1 (ICAM-1) was increased. In contrast, the severity of lung injury was more pronounced in mature rats. Lung myeloperoxidase activity and expression of constitutive and inducible ICAM-1 was significantly higher in mature rats when compared to young rats. Mature rats also had higher plasma levels of cytokines and chemokines when compared to young rats. This heightened inflammation was associated with higher degree of activation of nuclear factor-κB and down-regulation of PPARγ and heat shock factor-1 in the lung of mature rats when compared to young rats. Treatment with the PPARγ ligand, the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2, ameliorated lung injury in young, but not in mature animals. Conclusions Lung injury after severe hemorrhage is age-dependent and may be secondary to a diverse regulation of PPARγ. PMID:19384226

  18. Fault branching and rupture directivity

    NASA Astrophysics Data System (ADS)

    Fliss, Sonia; Bhat, Harsha S.; Dmowska, Renata; Rice, James R.

    2005-06-01

    Could the directivity of a complex earthquake be inferred from the ruptured fault branches it created? Typically, branches develop in forward orientation, making acute angles relative to the propagation direction. Direct backward branching of the same style as the main rupture (e.g., both right lateral) is disallowed by the stress field at the rupture front. Here we propose another mechanism of backward branching. In that mechanism, rupture stops along one fault strand, radiates stress to a neighboring strand, nucleates there, and develops bilaterally, generating a backward branch. Such makes diagnosing directivity of a past earthquake difficult without detailed knowledge of the branching process. As a field example, in the Landers 1992 earthquake, rupture stopped at the northern end of the Kickapoo fault, jumped onto the Homestead Valley fault, and developed bilaterally there, NNW to continue the main rupture but also SSE for 4 km forming a backward branch. We develop theoretical principles underlying such rupture transitions, partly from elastostatic stress analysis, and then simulate the Landers example numerically using a two-dimensional elastodynamic boundary integral equation formulation incorporating slip-weakening rupture. This reproduces the proposed backward branching mechanism based on realistic if simplified fault geometries, prestress orientation corresponding to the region, standard lab friction values for peak strength, and fracture energies characteristic of the Landers event. We also show that the seismic S ratio controls the jumpable distance and that curving of a fault toward its compressional side, like locally along the southeastern Homestead Valley fault, induces near-tip increase of compressive normal stress that slows rupture propagation.

  19. Half-lives and branchings for {beta}-delayed neutron emission for neutron-rich Co-Cu isotopes in the r-process

    SciTech Connect

    Hosmer, P.; Estrade, A.; Montes, F.; Ouellette, M.; Pellegrini, E.; Schatz, H.; Aprahamian, A.; Arndt, O.; Pfeiffer, B.; Clement, R. R. C.; Mueller, W. F.; Morton, A. C.; Pereira, J.; Santi, P.; Steiner, M.; Stolz, A.; Farouqi, K.; Kratz, K.-L.; Liddick, S. N.; Mantica, P. F.

    2010-08-15

    The {beta} decays of very neutron-rich nuclides in the Co-Zn region were studied experimentally at the National Superconducting Cyclotron Laboratory using the NSCL {beta}-counting station in conjunction with the neutron detector NERO. We measured the branchings for {beta}-delayed neutron emission (P{sub n} values) for {sup 74}Co (18{+-}15%) and {sup 75-77}Ni (10{+-}2.8%, 14{+-}3.6%, and 30{+-}24%, respectively) for the first time, and remeasured the P{sub n} values of {sup 77-79}Cu, {sup 79,81}Zn, and {sup 82}Ga. For {sup 77-79}Cu and for {sup 81}Zn we obtain significantly larger P{sub n} values compared to previous work. While the new half-lives for the Ni isotopes from this experiment had been reported before, we present here in addition the first half-life measurements of {sup 75}Co (30{+-}11 ms) and {sup 80}Cu (170{sub -50}{sup +110} ms). Our results are compared with theoretical predictions, and their impact on various types of models for the astrophysical rapid neutron-capture process (r-process) is explored. We find that with our new data, the classical r-process model is better able to reproduce the A=78-80 abundance pattern inferred from the solar abundances. The new data also influence r-process models based on the neutrino-driven high-entropy winds in core collapse supernovae.

  20. Evolutionary branching under slow directional evolution.

    PubMed

    Ito, Hiroshi C; Dieckmann, Ulf

    2014-11-07

    Evolutionary branching is the process by which ecological interactions induce evolutionary diversification. In asexual populations with sufficiently rare mutations, evolutionary branching occurs through trait-substitution sequences caused by the sequential invasion of successful mutants. A necessary and sufficient condition for evolutionary branching of univariate traits is the existence of a convergence stable trait value at which selection is locally disruptive. Real populations, however, undergo simultaneous evolution in multiple traits. Here we extend conditions for evolutionary branching to bivariate trait spaces in which the response to disruptive selection on one trait can be suppressed by directional selection on another trait. To obtain analytical results, we study trait-substitution sequences formed by invasions that possess maximum likelihood. By deriving a sufficient condition for evolutionary branching of bivariate traits along such maximum-likelihood-invasion paths (MLIPs), we demonstrate the existence of a threshold ratio specifying how much disruptive selection in one trait direction is needed to overcome the obstruction of evolutionary branching caused by directional selection in the other trait direction. Generalizing this finding, we show that evolutionary branching of bivariate traits can occur along evolutionary-branching lines on which residual directional selection is sufficiently weak. We then present numerical analyses showing that our generalized condition for evolutionary branching is a good indicator of branching likelihood even when trait-substitution sequences do not follow MLIPs and when mutations are not rare. Finally, we extend the derived conditions for evolutionary branching to multivariate trait spaces.

  1. The allele distribution in next-generation sequencing data sets is accurately described as the result of a stochastic branching process.

    PubMed

    Heinrich, Verena; Stange, Jens; Dickhaus, Thorsten; Imkeller, Peter; Krüger, Ulrike; Bauer, Sebastian; Mundlos, Stefan; Robinson, Peter N; Hecht, Jochen; Krawitz, Peter M

    2012-03-01

    With the availability of next-generation sequencing (NGS) technology, it is expected that sequence variants may be called on a genomic scale. Here, we demonstrate that a deeper understanding of the distribution of the variant call frequencies at heterozygous loci in NGS data sets is a prerequisite for sensitive variant detection. We model the crucial steps in an NGS protocol as a stochastic branching process and derive a mathematical framework for the expected distribution of alleles at heterozygous loci before measurement that is sequencing. We confirm our theoretical results by analyzing technical replicates of human exome data and demonstrate that the variance of allele frequencies at heterozygous loci is higher than expected by a simple binomial distribution. Due to this high variance, mutation callers relying on binomial distributed priors are less sensitive for heterozygous variants that deviate strongly from the expected mean frequency. Our results also indicate that error rates can be reduced to a greater degree by technical replicates than by increasing sequencing depth.

  2. Slow age-dependent decline of doublecortin expression and BrdU labeling in the forebrain from lesser hedgehog tenrecs.

    PubMed

    Alpár, Alán; Künzle, Heinz; Gärtner, Ulrich; Popkova, Yulia; Bauer, Ute; Grosche, Jens; Reichenbach, Andreas; Härtig, Wolfgang

    2010-05-12

    In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5-bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi-, and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats.

  3. Age-Dependent Neuroendocrine Signaling from Sensory Neurons Modulates the Effect of Dietary Restriction on Longevity of Caenorhabditis elegans

    PubMed Central

    Fletcher, Marissa

    2017-01-01

    Dietary restriction extends lifespan in evolutionarily diverse animals. A role for the sensory nervous system in dietary restriction has been established in Drosophila and Caenorhabditis elegans, but little is known about how neuroendocrine signals influence the effects of dietary restriction on longevity. Here, we show that DAF-7/TGFβ, which is secreted from the C. elegans amphid, promotes lifespan extension in response to dietary restriction in C. elegans. DAF-7 produced by the ASI pair of sensory neurons acts on DAF-1/TGFβ receptors expressed on interneurons to inhibit the co-SMAD DAF-3. We find that increased activity of DAF-3 in the presence of diminished or deleted DAF-7 activity abrogates lifespan extension conferred by dietary restriction. We also observe that DAF-7 expression is dynamic during the lifespan of C. elegans, with a marked decrease in DAF-7 levels as animals age during adulthood. We show that this age-dependent diminished expression contributes to the reduced sensitivity of aging animals to the effects of dietary restriction. DAF-7 signaling is a pivotal regulator of metabolism and food-dependent behavior, and our studies establish a molecular link between the neuroendocrine physiology of C. elegans and the process by which dietary restriction can extend lifespan. PMID:28107363

  4. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina.

    PubMed

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  5. Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction

    PubMed Central

    Fava, Vinicius M.; Sales-Marques, Carolinne; Alcaïs, Alexandre; Moraes, Milton O.; Schurr, Erwin

    2017-01-01

    A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E−05, pcombined = 1.8E−05, and pcombined = 6.5E−06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54–2.46, pcombined = 2.5E−08 versus OR = 1.46, 95% CI = 1.23–1.73, pcombined = 1.5E−05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span. PMID:28261213

  6. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

    PubMed Central

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  7. Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models.

    PubMed

    Anseloni, Vanessa C Z; Weng, H-R; Terayama, R; Letizia, David; Davis, Barry J; Ren, Ke; Dubner, Ronald; Ennis, Matthew

    2002-05-01

    mechanisms and that an enhanced sucrose effect takes place in hyperalgesic, inflamed animals as compared to naive animals. Taken together, these results indicate that intraoral sucrose alleviates transient pain in response to thermal and mechanical stimuli, and also effectively reduces inflammatory hyperalgesia and allodynia. Sucrose-induced analgesia is age-dependent and limited to the pre-weaning period in rats. The age-dependency of sucrose-induced analgesia and its differential maturation for the fore- and hindpaw may be due to developmental changes in endogenous analgesic mechanisms and developmental modulation of the interaction between gustatory and pain modulatory pathways.

  8. EUROPIUM s-PROCESS SIGNATURE AT CLOSE-TO-SOLAR METALLICITY IN STARDUST SiC GRAINS FROM ASYMPTOTIC GIANT BRANCH STARS

    SciTech Connect

    Avila, Janaina N.; Ireland, Trevor R.; Holden, Peter; Lugaro, Maria; Gyngard, Frank; Zinner, Ernst; Cristallo, Sergio; Rauscher, Thomas

    2013-05-01

    Individual mainstream stardust silicon carbide (SiC) grains and a SiC-enriched bulk sample from the Murchison carbonaceous meteorite have been analyzed by the Sensitive High Resolution Ion Microprobe-Reverse Geometry for Eu isotopes. The mainstream grains are believed to have condensed in the outflows of {approx}1.5-3 M{sub Sun} carbon-rich asymptotic giant branch (AGB) stars with close-to-solar metallicity. The {sup 151}Eu fractions [fr({sup 151}Eu) = {sup 151}Eu/({sup 151}Eu+{sup 153}Eu)] derived from our measurements are compared with previous astronomical observations of carbon-enhanced metal-poor stars enriched in elements made by slow neutron captures (the s-process). Despite the difference in metallicity between the parent stars of the grains and the metal-poor stars, the fr({sup 151}Eu) values derived from our measurements agree well with fr({sup 151}Eu) values derived from astronomical observations. We have also compared the SiC data with theoretical predictions of the evolution of Eu isotopic ratios in the envelope of AGB stars. Because of the low Eu abundances in the SiC grains, the fr({sup 151}Eu) values derived from our measurements show large uncertainties, in most cases being larger than the difference between solar and predicted fr({sup 151}Eu) values. The SiC aggregate yields a fr({sup 151}Eu) value within the range observed in the single grains and provides a more precise result (fr({sup 151}Eu) = 0.54 {+-} 0.03, 95% conf.), but is approximately 12% higher than current s-process predictions. The AGB models can match the SiC data if we use an improved formalism to evaluate the contribution of excited nuclear states in the calculation of the {sup 151}Sm(n, {gamma}) stellar reaction rate.

  9. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  10. Microscale Mechanism of Age Dependent Wetting Properties of Prickly Pear Cacti (Opuntia).

    PubMed

    Rykaczewski, Konrad; Jordan, Jacob S; Linder, Rubin; Woods, Erik T; Sun, Xiaoda; Kemme, Nicholas; Manning, Kenneth C; Cherry, Brian R; Yarger, Jeffery L; Majure, Lucas C

    2016-09-13

    Cacti thrive in xeric environments through specialized water storage and collection tactics such as a shallow, widespread root system that maximizes rainwater absorption and spines adapted for fog droplet collection. However, in many cacti, the epidermis, not the spines, dominates the exterior surface area. Yet, little attention has been dedicated to studying interactions of the cactus epidermis with water drops. Surprisingly, the epidermis of plants in the genus Opuntia, also known as prickly pear cacti, has water-repelling characteristics. In this work, we report that surface properties of cladodes of 25 taxa of Opuntia grown in an arid Sonoran climate switch from water-repelling to superwetting under water impact over the span of a single season. We show that the old cladode surfaces are not superhydrophilic, but have nearly vanishing receding contact angle. We study water drop interactions with, as well as nano/microscale topology and chemistry of, the new and old cladodes of two Opuntia species and use this information to uncover the microscopic mechanism underlying this phenomenon. We demonstrate that composition of extracted wax and its contact angle do not change significantly with time. Instead, we show that the reported age dependent wetting behavior primarily stems from pinning of the receding contact line along multilayer surface microcracks in the epicuticular wax that expose the underlying highly hydrophilic layers.

  11. [Metabolic memory enhances hormesis effect to the copper ions in age-depended manner].

    PubMed

    Bozhkov, A I; Sidorov, V I; Kurguzova, N I; Dlubovskaia, V L

    2014-01-01

    The ability of young and old rats to manifest the hormesis effect to lethal doses of copper sulphate and the ability to save the induced "adaptive" pattern of redistribution of copper ions after the transfer of animals in the standard conditions is the mechanism of metabolic memory. It was found that pretreatment of animals with low-dose (1 mg per 100 g body mass, i.e. 33% of the lethal dose) of copper sulfate induced the formation of their resistance to lethal doses (3 mg per 100 g), so the hormesis effect was manifested. Hormesis effect depended on the number of pre injections of small doses of copper sulphate in an S-shaped manner. The protective effect increased after 1 to 3 of preliminary injections of copper sulfate, and after four or more injections the hormesis effect decreased. It is shown that the cardinal role in intracellular pattern of copper ion redistribution play heat-stable copper binding proteins 12 kDa cytosolic proteins. The formed "adaptive" pattern of intracellular distribution of the copper ions may be reproduced, after at least, one month. The prolonged hormesis effect can be attributed to the forming metabolic memory. The intracellular distribution pattern of the copper ions was age-dependent. Age-related differences were found in hormesis effect induced by copper ions, which results in increased binding capacity of copper binding proteins in old animals, with a higher content of copper ions in the mitochondria and microsomes as compared to young animals.

  12. Age-dependent trajectories differ between within-pair and extra-pair paternity success.

    PubMed

    Hsu, Y-H; Simons, M J P; Schroeder, J; Girndt, A; Winney, I S; Burke, T; Nakagawa, S

    2017-02-24

    Reproductive success is associated with age in many taxa, increasing in early life followed by reproductive senescence. In socially monogamous but genetically polygamous species, this generates the interesting possibility of differential trajectories of within-pair and extra-pair siring success with age in males. We investigate these relationships simultaneously using within-individual analyses with 13 years of data from an insular house sparrow (Passer domesticus) population. As expected, we found that both within- and extra-pair paternity success increased with age, followed by a senescence-like decline. However, the age trajectories of within- and extra-pair paternity successes differed significantly, with the extra-pair paternity success increasing faster, although not significantly, in early life, and showing a delayed decline by 1.5 years on average later in life compared to within-pair paternity success. These different trajectories indicate that the two alternative mating tactics should have age-dependent pay-offs. Males may partition their reproductive effort between within- and extra-pair matings depending on their current age to reap the maximal combined benefit from both strategies. The interplay between these mating strategies and age-specific mortality may explain the variation in rates of extra-pair paternity observed within and between species.

  13. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity

    PubMed Central

    Kinyua, Ann W.; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  14. Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.

    PubMed

    Harten, Ingrid A; Zahr, Rima S; Lemire, Joan M; Machan, Jason T; Moses, Marsha A; Doiron, Robert J; Curatolo, Adam S; Rothman, Frank G; Wight, Thomas N; Toole, Bryan P; Gordon, Leslie B

    2011-11-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive segmental premature aging disease that includes scleroderma-like skin, progressive joint contracture, and atherosclerosis. Affected individuals die prematurely of heart attacks or strokes. Extracellular matrix dysregulation is implicated as a factor in disease progression. We analyzed messenger RNA and protein levels for matrix metalloproteinases (MMPs)-2,-3, and -9 in HGPS primary human dermal fibroblasts using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. MMP-3 messenger RNA and protein levels decreased significantly with increasing donor age in HGPS fibroblasts but not in controls. MMP-2 messenger RNA also showed a donor age-dependent decrease in HGPS fibroblasts, but levels of secreted protein were unchanged. MMP-9 was similar in HGPS and control cultures. The decreased MMP-3 may represent a shift in the inherent extracellular matrix-degrading proteolytic balance in favor of matrix deposition in HGPS. This metalloproteinase has the potential to serve as a biomarker of therapeutic efficacy when assessing treatments for HGPS.

  15. Assessment of age-dependent uranium intake due to drinking water in Hyderabad, India.

    PubMed

    Balbudhe, A Y; Srivastava, S K; Vishwaprasad, K; Srivastava, G K; Tripathi, R M; Puranik, V D

    2012-03-01

    A study has been done to assess the uranium intake through drinking water. The area of study is twin cities of Hyderabad and Secunderabad, India. Uranium concentration in water samples was analysed by laser-induced fluorimetry. The associated age-dependent uranium intake was estimated by taking the prescribed water intake values. The concentration of uranium varies from below detectable level (minimum detectable level = 0.20 ± 0.02 μg l(-1)) to 2.50 ± 0.18 μg l(-1), with the geometric mean (GM) of 0.67 μg l(-1) in tap water, whereas in ground water, the range is 0.60 ± 0.05 to 82 ± 7.1 µg l(-1) with GM of 10.07 µg l(-1). The daily intake of uranium by drinking water pathway through tap water for various age groups is found to vary from 0.14 to 9.50 µg d(-1) with mean of 1.55 µg d(-1).

  16. Large-scale age-dependent skewed sex ratio in a sexually dimorphic avian scavenger.

    PubMed

    Lambertucci, Sergio A; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed.

  17. Large-Scale Age-Dependent Skewed Sex Ratio in a Sexually Dimorphic Avian Scavenger

    PubMed Central

    Lambertucci, Sergio A.; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed. PMID:23029488

  18. Growth impairment shows an age-dependent pattern in boys with chronic kidney disease.

    PubMed

    Zivicnjak, Miroslav; Franke, Doris; Filler, Guido; Haffner, Dieter; Froede, Kerstin; Nissel, Richard; Haase, Sanny; Offner, Gisela; Ehrich, Jochen H H; Querfeld, Uwe

    2007-03-01

    The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3-21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.

  19. Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate.

    PubMed

    Beal, M F; Brouillet, E; Jenkins, B; Henshaw, R; Rosen, B; Hyman, B T

    1993-09-01

    Intrastriatal injection of malonate, a reversible inhibitor of succinate dehydrogenase (SDH), produced age-dependent striatal lesions, which were significantly greater in 4- and 12-month-old animals than in 1-month-old animals. Both histologic and neurochemical studies showed that the lesions were significantly attenuated by administration of the noncompetitive NMDA receptor antagonist MK-801. Water-suppressed chemical shift magnetic resonance imaging showed that malonate produces increased striatal lactate concentrations and striatal lesions on T2-weighted scans that were attenuated by MK-801. Neurochemical characterization of the lesions showed significant decreases in markers of medium-sized spiny neurons (GABA and substance P), whereas a marker of medium-sized aspiny neurons (somatostatin) was not different from control values, consistent with an NMDA receptor-mediated mechanism. The effects of intrastriatal injections of malonate on ATP concentrations were compared with those of the irreversible SDH inhibitor 3-nitropropionic acid (3-NP). The ATP depletions following an equimolar injection of malonate were less marked and more transient than those of 3-NP. These results show that the competitive SDH inhibitor malonate produces more transient and milder bioenergetic defects than 3-NP, which are associated with selective activation of NMDA receptors. The results strengthen the possibility that a subtle impairment of energy metabolism may play a role in the pathogenesis of Huntington's disease.

  20. In vitro age dependent response of macrophages to micro and nano titanium dioxide particles.

    PubMed

    Bruno, Marcos E; Sittner, Maximiliano; Cabrini, Rómulo L; Guglielmotti, María B; Olmedo, Daniel G; Tasat, Deborah R

    2015-02-01

    As a result of corrosion, microparticles (MP) and/or nanoparticles (NP) can be released from the metallic implants surface into the bioenvironment. The biological response to these particles depends not only on the physico-chemical properties of the particles but also on host factors, such as age. Macrophages have attracted wide concern in biomedicine. The aim of this investigation was to study the age related biological response of macrophages to TiO2 -MP and NP in vitro. Alveolar macrophages (AM) obtained from young and senescent rats were cultured and exposed to TiO2 -MP and NP. Cell metabolism, superoxide anion (O2 (-) ) and nitric oxide (NO) generation, and cytokine release (IL-6, TNFα, IL-10) were measured. Cell metabolism was not affected by particle exposure. O2 (-) and NO generation increased in a dose dependent manner. A marked increase on IL-6 release was found in the young-AM subpopulation exposed to TiO2 -MP. Conversely, both particle sizes induced a dose dependent release of TNFα in senescent-AM. Only the highest concentration of TiO2 -particles caused a significant increase in IL-10 release in AM-cultures. These observations lend strong support to the suggestion that cellular response of macrophages to TiO2 -particles is age dependent. The biological effect of the particles would seem to be more deleterious in the senescent age-group.

  1. Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice

    PubMed Central

    Dupont, Aline; Sommer, Felix; Zhang, Kaiyi; Repnik, Urska; Basic, Marijana; Bleich, André; Kühnel, Mark; Bäckhed, Fredrik; Litvak, Yael; Fulde, Marcus; Rosenshine, Ilan; Hornef, Mathias W.

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo. PMID:27159323

  2. Age-dependent effects of carotid endarterectomy or stenting on cognitive performance.

    PubMed

    Wasser, Katrin; Hildebrandt, Helmut; Gröschel, Sonja; Stojanovic, Tomislav; Schmidt, Holger; Gröschel, Klaus; Pilgram-Pastor, Sara M; Knauth, Michael; Kastrup, Andreas

    2012-11-01

    Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.

  3. Age-dependent genetic variance in a life-history trait in the mute swan.

    PubMed

    Charmantier, Anne; Perrins, Christopher; McCleery, Robin H; Sheldon, Ben C

    2006-01-22

    Genetic variance in characters under natural selection in natural populations determines the way those populations respond to that selection. Whether populations show temporal and/or spatial constancy in patterns of genetic variance and covariance is regularly considered, as this will determine whether selection responses are constant over space and time. Much less often considered is whether characters show differing amounts of genetic variance over the life-history of individuals. Such age-specific variation, if present, has important potential consequences for the force of natural selection and for understanding the causes of variation in quantitative characters. Using data from a long-term study of the mute swan Cygnus olor, we report the partitioning of phenotypic variance in timing of breeding (subject to strong natural selection) into component parts over 12 different age classes. We show that the additive genetic variance and heritability of this trait are strongly age-dependent, with higher additive genetic variance present in young and, particularly, old birds, but little evidence of any genetic variance for birds of intermediate ages. These results demonstrate that age can have a very important influence on the components of variation of characters in natural populations, and consequently that separate age classes cannot be assumed to be equivalent, either with respect to their evolutionary potential or response.

  4. Age-dependent modulation of vascular niches for haematopoietic stem cells

    PubMed Central

    Kusumbe, Anjali P.; Ramasamy, Saravana K.; Itkin, Tomer; Andaloussi Mäe, Maarja; Langen, Urs H.; Betsholtz, Christer; Lapidot, Tsvee; Adams, Ralf H.

    2016-01-01

    Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells1–6. The properties of niche-forming vessels and their changes in the ageing organism remain incompletely understood. Here, we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and PDGFRβ-positive perivascular cells, arteriole formation, and elevation of cellular stem cell factor levels. While endothelial hypoxia-inducible factor signalling promotes some of these aspects, it fails to enhance vascular niche function because of lacking arterialization and expansion of PDGFRβ-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings argue that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes. PMID:27074508

  5. Extreme Events and Their Predictability in a Branching Diffusion Model

    NASA Astrophysics Data System (ADS)

    Gabrielov, A.; Zaliapin, I.; Keilis-Borok, V.

    2009-05-01

    Studies in prediction of extreme events, based on real observations and numerical modeling of complex systems, suggest universal patterns of system's behavior signaling approach of an extreme event. These patterns include deviation from self-similarity, increase in background activity, clustering, and long-range correlation. In the absence of a closed theory describing critical transitions in complex systems, and with insufficient and noisy observations, numerical parameters of the patterns have to be data-fitted, creating the risk of self-deception ("With four exponents I can fit the elephant" - J. von Neumann). Here, we introduce a model which provides analytical definition of at least two parameters, intensity and deviation from self-similarity. That drastically reduces non-uniqueness of parametrization, suggesting a simple universal mechanism of premonitory patterns and natural framework for their analytical study. Major conceptual parts of the model - direct cascading or fragmentation, spatial dynamics, and external driving - are combined in a classical age-dependent multi-type branching diffusion process with immigration. A complete analytic description of the size- and space-dependent distributions of particles and their correlations is derived using the generating function approach.

  6. The s-process in low-metallicity stars - II. Interpretation of high-resolution spectroscopic observations with asymptotic giant branch models

    NASA Astrophysics Data System (ADS)

    Bisterzo, S.; Gallino, R.; Straniero, O.; Cristallo, S.; Käppeler, F.

    2011-11-01

    High-resolution spectroscopic observations of 100 metal-poor carbon and s-rich stars (CEMP-s) collected from the literature are compared with the theoretical nucleosynthesis models of the asymptotic giant branch (AGB) presented in Paper I (MAGBini= 1.3, 1.4, 1.5, 2 M⊙, - 3.6 ≲ [ Fe/H ] ≲- 1.5). The s-process enhancement detected in these objects is associated with binary systems: the more massive companion evolved faster through the thermally pulsing AGB phase (TP-AGB), synthesizing s-elements in the inner He intershell, which are partly dredged up to the surface during the third dredge-up (TDU) episode. The secondary observed low-mass companion became CEMP-s by the mass transfer of C- and s-rich material from the primary AGB. We analyse the light elements C, N, O, Na and Mg, as well as the two s-process indicators, [hs/ls] (where ls = is the the light-s peak at N = 50 and hs = the heavy-s peak at N = 82) and [Pb/hs]. We distinguish between CEMP-s with high s-process enhancement, [hs/Fe] >rsim 1.5 (CEMP-sII), and mild s-process enhanced stars, [hs/Fe] < 1.5 (CEMP-sI). To interpret the observations, a range of s-process efficiencies at any given metallicity is necessary. This is confirmed by the high spread observed in [Pb/hs] (˜2 dex). A degeneration of solutions is found with some exceptions: most main-sequence CEMP-sII stars with low [Na/Fe] can only be interpreted with MAGBini= 1.3-1.4 M⊙. Giants having suffered the first dredge-up (FDU) need a dilution >rsim1 dex (dil is defined as the mass of the convective envelope of the observed star, Mobs★, over the material transferred from the AGB to the companion, MtransAGB). Then AGB models with higher AGB initial masses (MAGBini= 1.5-2 M⊙) are adopted to interpret CEMP-sII giants. In general, solutions with AGB models in the mass range MAGBini= 1.3-2 M⊙ and different dilution factors are found for CEMP-sI stars. About half of the CEMP-s stars with europium measurements show a high r-process

  7. Age-dependent uncoupling of mitochondria from Ca2+ release units in skeletal muscle

    PubMed Central

    Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T.; Boncompagni, Simona; Protasi, Feliciano

    2015-01-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling. Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8±0.4 vs. 5.5±0.3 tethers/100μm2) and CRU-mitochondrial pair density (37.4±0.8 vs. 27.0±0.7 pairs/100μm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68±0.08 vs 1.37±0.03) and mitochondrial Ca2+ uptake (9.6±0.050 vs 6.58±0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  8. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.

    PubMed

    Van Dam, Debby; D'Hooge, Rudi; Staufenbiel, Matthias; Van Ginneken, Chris; Van Meir, Frans; De Deyn, Peter P

    2003-01-01

    Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.

  9. [Investigation of the age-dependent development of brachygnathia inferior in the East Friesian milk sheep].

    PubMed

    Pielmeier, Ricarda; Kerkmann, Andrea; Distl, Ottmar

    2012-01-01

    Shortness of the lower jaw (brachygnathia inferior, underbite) is a common anomaly in sheep. In order to study the age-dependent development of brachygnathia inferior, data of 73 East Friesian milk sheep from a breeding experiment over six generations were analysed. Data were recorded in regular intervals of four weeks from birth up to an age of at least 25 weeks. Brachygnathia inferior was determined by the distance between the edge of the central incisor of the lower jaw and the anterior surrounding of the upper jaw (DIFF-UK) using a measuring tape. Four main types of brachygnathia inferior were distinguished using means, standard deviations and maximum values of the individual animals.The thresholds were a maximum and mean DIFF-UK of 0.5 cm and a standard deviation of 0.266 cm. A total of 14 sheep (main types 3 and 4) showed an obvious brachygnathia inferior with mean DIFF-UK larger than 0.5 cm whereof ten animals showed a large variation of DIFF-UK values (standard deviation > 0.226 cm). Mean DIFF-UK values of 59 sheep were smaller than 0.5 cm (main types 1 and 2). One of these 59 animals had during the first four weeks of life DIFF-UK values of 1 cm and than decreasing values reaching zero within the next nine months (main type 2). Five of the 58 animals with main type 1 had a perfect occlusion of jaws, all with DIFF-UK values at zero during the whole recording period. Parents with severe or mild brachygnathia inferior had severely affected progeny. Selection of sheep for breeding with a perfect occlusion of jaws decreases the risk to pass on the hereditary disposition for brachygnathia inferior. An early inspection of potential breeding animals is advisable to detect all cases of brachygnathia inferior even if the underbite decreases in the first year of life.

  10. Age-dependent effects of initial exposure to nicotine on serotonin neurons.

    PubMed

    Bang, S J; Commons, K G

    2011-04-14

    Adolescence is a critical vulnerable period during which exposure to nicotine greatly enhances the possibility to develop drug addiction. Growing evidence suggests that serotonergic (5-HT) neurotransmission may contribute to the initiation and maintenance of addictive behavior. As the dorsal raphe (DR) and median raphe (MnR) nuclei are the primary 5-HT source to the forebrain, the current study tested the hypothesis that there are age-dependent effects of acute nicotine administration on activation of 5-HT neurons within these regions. Both adolescent (Postnatal day 30) and adult (Postnatal day 70) male Sprague-Dawley rats received subcutaneous injection of either saline or nicotine (0.2, 0.4, or 0.8 mg/kg). Subsequently, the number of 5-HT cells that were double-labeled for Fos and tryptophan hydroxylase was counted in seven subregions within the DR and the entire MnR. The results show that acute nicotine injection induces Fos expression in 5-HT neurons in a region-specific manner. In addition, adolescents show broader regional activations at either a lower (0.2 mg/kg) and a higher (0.8 mg/kg) dose of nicotine, displaying a unique U-shape response curve across doses. In contrast, 5-HT cells with activated Fos expression were restricted to fewer regions in adults, and the patterns of expression were more consistent across doses. The results reveal dose-dependent effects of nicotine during adolescence with apparent sensitization at different ends of the dosage spectrum examined compared to adults. These data indicate that initial exposure to nicotine may have unique effects in adolescence on the ascending 5-HT system, with the potential for consequences on the affective-motivational qualities of the drug and the subsequent propensity for repeated use.

  11. Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47.

    PubMed

    Frazier, Elfaridah P; Isenberg, Jeff S; Shiva, Sruti; Zhao, Lei; Schlesinger, Paul; Dimitry, Julie; Abu-Asab, Mones S; Tsokos, Maria; Roberts, David D; Frazier, William A

    2011-03-01

    CD47, a receptor for thrombospondin-1, limits two important regulatory axes: nitric oxide-cGMP signaling and cAMP signaling, both of which can promote mitochondrial biogenesis. Electron microscopy revealed increased mitochondrial densities in skeletal muscle from both CD47 null and thrombospondin-1 null mice. We further assessed the mitochondria status of CD47-null vs WT mice. Quantitative RT-PCR of RNA extracted from tissues of 3 month old mice revealed dramatically elevated expression of mRNAs encoding mitochondrial proteins and PGC-1α in both fast and slow-twitch skeletal muscle from CD47-null mice, but modest to no elevation in other tissues. These observations were confirmed by Western blotting of mitochondrial proteins. Relative amounts of electron transport enzymes and ATP/O(2) ratios of isolated mitochondria were not different between mitochondria from CD47-null and WT cells. Young CD47-null mice displayed enhanced treadmill endurance relative to WTs and CD47-null gastrocnemius had undergone fiber type switching to a slow-twitch pattern of myoglobin and myosin heavy chain expression. In 12 month old mice, both skeletal muscle mitochondrial volume density and endurance had decreased to wild type levels. Expression of myosin heavy chain isoforms and myoglobin also reverted to a fast twitch pattern in gastrocnemius. Both CD47 and TSP1 null mice are leaner than WTs, use less oxygen and produce less heat than WT mice. CD47-null cells produce substantially less reactive oxygen species than WT cells. These data indicate that loss of signaling from the TSP1-CD47 system promotes accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion leading to enhanced physical performance, lower reactive oxygen species production and more efficient metabolism.

  12. Age-Dependent Retinal Iron Accumulation and Degeneration in Hepcidin Knockout Mice

    PubMed Central

    Hadziahmetovic, Majda; Song, Ying; Ponnuru, Padmavathi; Iacovelli, Jared; Hunter, Allan; Haddad, Nadine; Beard, John; Connor, James R.; Vaulont, Sophie

    2011-01-01

    Purpose. Iron dysregulation can cause retinal disease, yet retinal iron regulatory mechanisms are incompletely understood. The peptide hormone hepcidin (Hepc) limits iron uptake from the intestine by triggering degradation of the iron transporter ferroportin (Fpn). Given that Hepc is expressed in the retina and Fpn is expressed in cells constituting the blood-retinal barrier, the authors tested whether the retina may produce Hepc to limit retinal iron import. Methods. Retinas of Hepc−/− mice were analyzed by histology, autofluorescence spectral analysis, atomic absorption spectrophotometry, Perls' iron stain, and immunofluorescence to assess iron-handling proteins. Retinal Hepc mRNA was evaluated through qPCR after intravitreal iron injection. Mechanisms of retinal Hepc upregulation were tested by Western blot analysis. A retinal capillary endothelial cell culture system was used to assess the effect of exogenous Hepc on Fpn. Results. Hepc−/− mice experienced age-dependent increases in retinal iron followed by retinal degeneration with autofluorescent RPE, photoreceptor death, and subretinal neovascularization. Hepc−/− mice had increased Fpn immunoreactivity in vascular endothelial cells. Conversely, in cultured retinal capillary endothelial cells, exogenous Hepc decreased both Fpn levels and iron transport. The retina can sense increased iron levels, upregulating Hepc after phosphorylation of extracellular signal regulated kinases. Conclusions. These findings indicate that Hepc is essential for retinal iron regulation. In the absence of Hepc, retinal degeneration occurs. Increases in Hepc mRNA levels after intravitreal iron injection combined with Hepc-mediated decreases in iron export from cultured retinal capillary endothelial cells suggest that the retina may use Hepc for its tissue-specific iron regulation. PMID:20811044

  13. Characterisation of Age-Dependent Beta Cell Dynamics in the Male db/db Mice

    PubMed Central

    Dalbøge, Louise S.; Almholt, Dorthe L. C.; Neerup, Trine S. R.; Vassiliadis, Efstathios; Vrang, Niels; Pedersen, Lars; Fosgerau, Keld; Jelsing, Jacob

    2013-01-01

    Aim To characterise changes in pancreatic beta cell mass during the development of diabetes in untreated male C57BLKS/J db/db mice. Methods Blood samples were collected from a total of 72 untreated male db/db mice aged 5, 6, 8, 10, 12, 14, 18, 24 and 34 weeks, for measurement of terminal blood glucose, HbA1c, plasma insulin, and C-peptide. Pancreata were removed for quantification of beta cell mass, islet numbers as well as proliferation and apoptosis by immunohistochemistry and stereology. Results Total pancreatic beta cell mass increased significantly from 2.1 ± 0.3 mg in mice aged 5 weeks to a peak value of 4.84 ± 0.26 mg (P < 0.05) in 12-week-old mice, then gradually decreased to 3.27 ± 0.44 mg in mice aged 34 weeks. Analysis of islets in the 5-, 10-, and 24-week age groups showed increased beta cell proliferation in the 10-week-old animals whereas a low proliferation is seen in older animals. The expansion in beta cell mass was driven by an increase in mean islet mass as the total number of islets was unchanged in the three groups. Conclusions/Interpretation The age-dependent beta cell dynamics in male db/db mice has been described from 5-34 weeks of age and at the same time alterations in insulin/glucose homeostasis were assessed. High beta cell proliferation and increased beta cell mass occur in young animals followed by a gradual decline characterised by a low beta cell proliferation in older animals. The expansion of beta cell mass was caused by an increase in mean islet mass and not islet number. PMID:24324833

  14. Age-Dependent Hepatic UDP-Glucuronosyltransferase Gene Expression and Activity in Children

    PubMed Central

    Neumann, Elizabeth; Mehboob, Huma; Ramírez, Jacqueline; Mirkov, Snezana; Zhang, Min; Liu, Wanqing

    2016-01-01

    UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age. We also examined the correlation between age and microsomal activities using 14 known UGT drug substrates in the liver samples (n = 19) of children donors. We found a statistically significant increase (nominal p < 0.05) in the expression of UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT2B7, and UGT2B17, as well as glucuronidation activities of serotonin, testosterone, and vorinostat during the first 25 years of life. Expression of estrogen receptor 1 and pregnane X receptor, two strong UGT transcriptional regulators, were significantly correlated with both age and UGT mRNA expression (p ≤ 0.05). These results suggest that both UGT expression and activity increase during childhood and adolescence, possibly driven in part by hormonal signaling. Our findings may help explain inter-patient variability in response to medications among children. PMID:27899892

  15. The Mass and Age Dependence of Dusty Red Supergiant Winds, and Their Impact on Supernova Progenitors

    NASA Astrophysics Data System (ADS)

    Smith, Nathan

    The dusty winds of red supergiants (RSGs) have a tremendous impact on the evolution of stars of 8-40 M_sun. Wind strength determines whether a star can shed its H envelope or not, thus determining the type of resulting SN, and these dusty winds create the circumstellar medium (CSM) at the end of the stars life. However, RSG mass-loss rates are very uncertain, which hampers the predictive power of stellar evolution models. RSGs are expected to end their lives as Type II-P supernovae. Many RSGs are observed with initial masses well above 20 M_sun, but from Type II-P progenitors directly detected so far it seems that the stars that explode are of relatively low mass, with all progenitor mass estimates below 16-17 M_sun. This is known as the Red Supergiant Problem, prompting suggestions that the massive RSGs collapse to black holes with undetectably faint SNe. Alternatively, it has also been suggested that the more massive RSGs evolve to yield other types of SNe or that dusty CSM could cause the progenitor to faint, underestimating its mass. One expects that the most massive and most evolved RSGs would also have the highest extinction or would be the most likely to evolve to a H-free star -- this is qualitatively what is needed to explain the missing high-mass RSGs. To test this idea, we propose to use FORCAST to obtain mid-IR photometry for RSGs in three coeval star clusters with known ages(and different turnoff masses of 12, 18, and 35 M_sun). By modeling CSM dust emission, we will derive mass and age dependent mass-loss rates and CSM extinction, below and above the derived cutoff mass for Type II-P progenitors, thereby determining whether this effect is large enough to solve the Red Supergiant Problem.

  16. A prognosis method using age-dependent hidden semi-Markov model for equipment health prediction

    NASA Astrophysics Data System (ADS)

    Peng, Ying; Dong, Ming

    2011-01-01

    Health monitoring and prognostics of equipment is a basic requirement for condition-based maintenance (CBM) in many application domains. This paper presents an age-dependent hidden semi-Markov model (HSMM) based prognosis method to predict equipment health. By using hazard function (h.f.), CBM is based on a failure rate which is a function of both the equipment age and the equipment conditions. The state values of the equipment condition considered in CBM, however, are limited to those stochastically increasing over time and those having non-decreasing effect on the hazard rate. The previous HSMM based prognosis algorithm assumed that the transition probabilities are only state-dependent, which means that the probability of making transition to a less healthy state does not increase with the age. In the proposed method, in order to characterize the deterioration of equipment, three types of aging factors that discount the probabilities of staying at current state while increasing the probabilities of transitions to less healthy states are integrated into the HSMM. With an iteration algorithm, the original transition matrix obtained from the HSMM can be renewed with aging factors. To predict the remaining useful life (RUL) of the equipment, hazard rate is introduced to combine with the health-state transition matrix. With the classification information obtained from the HSMM, which provides the current health state of the equipment, the new RUL computation algorithm could be applied for the equipment prognostics. The performances of the HSMMs with aging factors are compared by using historical data colleted from hydraulic pumps through a case study.

  17. Idiopathic scoliosis. Gas exchange and the age dependence of arterial blood gases.

    PubMed Central

    Kafer, E R

    1976-01-01

    The aims were to examine the gas exchange and arterial blood gas abnormalities among patients with scoliosis, and the correlation of these abnormalities with age and severity of deformity. Means among 51 patients were as follows: age 25.4 +/- 17.5 yr, angle of scoliosis 80.2 +/- 29.9 (SD), vital capacity 1.94 +/- 0.91 (SD) (i.e. 60.6 +/- 19.2% of predicted), PaO2 85.8 +/- 12.0 (SD), PaCO2 42.4 +/- 8.0, physiological dead space to tidal volume ratio 0.438 +/- 0.074 (SD), and alveolar-arterial oxygen difference breathing air 14.9 +/- 8.9 (SD). Statistically significant correlations were as follows: the PaCO2 and physiological dead space to tidal volume ratio increased with age, and the PaO2 and alveolar ventilation decreased with age. The PaO2, alveolar ventilation, and tidal volume were inversely related to the angle of scoliosis and directly related to the vital capacity, precent predicted vital capacity, and the compliance of the respiratory system. The physiological dead space to tidal volume ratio and the alveolar-arterial oxygen difference were inversely related to the vital capacity, percent predicted vital capacity, and the compliance of the respiratory system. PaCO2 was directly related to the elastance of the respiratory system. We conclude that ventilation-blood flow maldistribution as a result of deformity of the rib cage was the primary abnormality in gas exchange, and that with age there was progressive deterioration in gas exchange. The age-dependent increase in PaCO2 and decrease in alveolar ventilation were due to the increasing physiological dead space to tidal volume ratio and failure of a compensatory increase in ventilation. PMID:965490

  18. Critical role of alkyl chain branching of organic semiconductors in enabling solution-processed N-channel organic thin-film transistors with mobility of up to 3.50 cm² V(-1) s(-1).

    PubMed

    Zhang, Fengjiao; Hu, Yunbin; Schuettfort, Torben; Di, Chong-an; Gao, Xike; McNeill, Christopher R; Thomsen, Lars; Mannsfeld, Stefan C B; Yuan, Wei; Sirringhaus, Henning; Zhu, Daoben

    2013-02-13

    Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ~0.001 to >3.0 cm(2) V(-1) s(-1). Incorporating a NDI-DTYM2 core with three-branched N-alkyl substituents of C(11,6) results in a dense in-plane molecular packing with an unit cell area of 127 Å(2), larger domain sizes of up to 1000 × 3000 nm(2), and an electron mobility of up to 3.50 cm(2) V(-1) s(-1), which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities.

  19. Cash efficiency for bank branches.

    PubMed

    Cabello, Julia García

    2013-01-01

    Bank liquidity management has become a major issue during the financial crisis as liquidity shortages have intensified and have put pressure on banks to diversity and improve their liquidity sources. While a significant strand of the literature concentrates on wholesale liquidity generation and on the alternative to deposit funding, the management of an inventory of cash holdings within the banks' branches is also a relevant issue as any significant improvement in cash management at the bank distribution channels may have a positive effect in reducing liquidity tensions. In this paper, we propose a simple programme of cash efficiency for the banks' branches, very easy to implement, which conform to a set of instructions to be imposed from the bank to their branches. This model proves to significantly reduce cash holdings at branches thereby providing efficiency improvements in liquidity management. The methodology we propose is based on the definition of some stochastic processes combined with renewal processes, which capture the random elements of the cash flow, before applying suitable optimization programmes to all the costs involved in cash movements. The classical issue of the Transaction Demand for the Cash and some aspects of Inventory Theory are also present. Mathematics Subject Classification (2000) C02, C60, E50.

  20. Lung epithelial branching program antagonizes alveolar differentiation.

    PubMed

    Chang, Daniel R; Martinez Alanis, Denise; Miller, Rachel K; Ji, Hong; Akiyama, Haruhiko; McCrea, Pierre D; Chen, Jichao

    2013-11-05

    Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. Much progress has been made to understand each of the two processes individually; however, it is not clear whether the two processes are coordinated and how they are deployed at the correct time and location. Here we show that an epithelial branching morphogenesis program antagonizes alveolar differentiation in the mouse lung. We find a negative correlation between branching morphogenesis and alveolar differentiation temporally, spatially, and evolutionarily. Gain-of-function experiments show that hyperactive small GTPase Kras expands the branching program and also suppresses molecular and cellular differentiation of alveolar cells. Loss-of-function experiments show that SRY-box containing gene 9 (Sox9) functions downstream of Fibroblast growth factor (Fgf)/Kras to promote branching and also suppresses premature initiation of alveolar differentiation. We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9. The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution.

  1. Age-dependent changes in the functions and compositions of photosynthetic complexes in the thylakoid membranes of Arabidopsis thaliana.

    PubMed

    Nath, Krishna; Phee, Bong-Kwan; Jeong, Suyeong; Lee, Sun Yi; Tateno, Yoshio; Allakhverdiev, Suleyman I; Lee, Choon-Hwan; Nam, Hong Gil

    2013-11-01

    Photosynthetic complexes in the thylakoid membrane of plant leaves primarily function as energy-harvesting machinery during the growth period. However, leaves undergo developmental and functional transitions along aging and, at the senescence stage, these complexes become major sources for nutrients to be remobilized to other organs such as developing seeds. Here, we investigated age-dependent changes in the functions and compositions of photosynthetic complexes during natural leaf senescence in Arabidopsis thaliana. We found that Chl a/b ratios decreased during the natural leaf senescence along with decrease of the total chlorophyll content. The photosynthetic parameters measured by the chlorophyll fluorescence, photochemical efficiency (F v/F m) of photosystem II, non-photochemical quenching, and the electron transfer rate, showed a differential decline in the senescing part of the leaves. The CO2 assimilation rate and the activity of PSI activity measured from whole senescing leaves remained relatively intact until 28 days of leaf age but declined sharply thereafter. Examination of the behaviors of the individual components in the photosynthetic complex showed that the components on the whole are decreased, but again showed differential decline during leaf senescence. Notably, D1, a PSII reaction center protein, was almost not present but PsaA/B, a PSI reaction center protein is still remained at the senescence stage. Taken together, our results indicate that the compositions and structures of the photosynthetic complexes are differentially utilized at different stages of leaf, but the most dramatic change was observed at the senescence stage, possibly to comply with the physiological states of the senescence process.

  2. Melons are Branched Polymers

    NASA Astrophysics Data System (ADS)

    Gurau, Razvan; Ryan, James P.

    2014-11-01

    Melonic graphs constitute the family of graphs arising at leading order in the 1/N expansion of tensor models. They were shown to lead to a continuum phase, reminiscent of branched polymers. We show here that they are in fact precisely branched polymers, that is, they possess Hausdorff dimension 2 and spectral dimension 4/3.

  3. Age-Dependent Effect of Pediatric Cardiac Progenitor Cells After Juvenile Heart Failure

    PubMed Central

    Agarwal, Udit; Smith, Amanda W.; French, Kristin M.; Boopathy, Archana V.; George, Alex; Trac, David; Brown, Milton E.; Shen, Ming; Jiang, Rong; Fernandez, Janet D.; Kogon, Brian E.; Kanter, Kirk R.; Alsoufi, Baahaldin; Wagner, Mary B.; Platt, Manu O.

    2016-01-01

    Children with congenital heart diseases have increased morbidity and mortality, despite various surgical treatments, therefore warranting better treatment strategies. Here we investigate the role of age of human pediatric cardiac progenitor cells (hCPCs) on ventricular remodeling in a model of juvenile heart failure. hCPCs isolated from children undergoing reconstructive surgeries were divided into 3 groups based on age: neonate (1 day to 1 month), infant (1 month to 1 year), and child (1 to 5 years). Adolescent athymic rats were subjected to sham or pulmonary artery banding surgery to generate a model of right ventricular (RV) heart failure. Two weeks after surgery, hCPCs were injected in RV musculature noninvasively. Analysis of cardiac function 4 weeks post-transplantation demonstrated significantly increased tricuspid annular plane systolic excursion and RV ejection fraction and significantly decreased wall thickness and fibrosis in rats transplanted with neonatal hCPCs compared with saline-injected rats. Computational modeling and systems biology analysis were performed on arrays and gave insights into potential mechanisms at the microRNA and gene level. Mechanisms including migration and proliferation assays, as suggested by computational modeling, showed improved chemotactic and proliferative capacity of neonatal hCPCs compared with infant/child hCPCs. In vivo immunostaining further suggested increased recruitment of stem cell antigen 1-positive cells in the right ventricle. This is the first study to assess the role of hCPC age in juvenile RV heart failure. Interestingly, the reparative potential of hCPCs is age-dependent, with neonatal hCPCs exerting the maximum beneficial effect compared with infant and child hCPCs. Significance Stem cell therapy for children with congenital heart defects is moving forward, with several completed and ongoing clinical trials. Although there are studies showing how children differ from adults, few focus on the differences

  4. From CIE 2006 physiological model to improved age-dependent and average colorimetric observers.

    PubMed

    Sarkar, Abhijit; Autrusseau, Florent; Viénot, Françoise; Le Callet, Patrick; Blondé, Laurent

    2011-10-01

    the source of these prediction errors at higher wavelengths. Correcting these errors in the model can lead to an improved age-dependent observer and can also help update the current CIE 10° standard colorimetric observer. Accordingly, it would reduce the discrepancies between color matches with broadband spectral primaries and color matches with narrowband spectral primaries.

  5. Age-dependent changes in diastolic Ca(2+) and Na(+) concentrations in dystrophic cardiomyopathy: Role of Ca(2+) entry and IP3.

    PubMed

    Mijares, Alfredo; Altamirano, Francisco; Kolster, Juan; Adams, José A; López, José R

    2014-10-03

    Duchenne muscular dystrophy (DMD) is a lethal X-inherited disease caused by dystrophin deficiency. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with a dilated cardiomyopathy that leads to progressive heart failure at the end of the second decade. The aim of the present study was to characterize the diastolic Ca(2+) concentration ([Ca(2+)]d) and diastolic Na(+) concentration ([Na(+)]d) abnormalities in cardiomyocytes isolated from 3-, 6-, 9-, and 12-month old mdx mice using ion-selective microelectrodes. In addition, the contributions of gadolinium (Gd(3+))-sensitive Ca(2+) entry and inositol triphosphate (IP3) signaling pathways in abnormal [Ca(2+)]d and [Na(+)]d were investigated. Our results showed an age-dependent increase in both [Ca(2+)]d and [Na(+)]d in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd(3+) treatment significantly reduced both [Ca(2+)]d and [Na(+)]d at all ages. In addition, blockade of the IP3-pathway with either U-73122 or xestospongin C significantly reduced ion concentrations in dystrophic cardiomyocytes. Co-treatment with U-73122 and Gd(3+) normalized both [Ca(2+)]d and [Na(+)]d at all ages in dystrophic cardiomyocytes. These data showed that loss of dystrophin in mdx cardiomyocytes produced an age-dependent intracellular Ca(2+) and Na(+) overload mediated at least in part by enhanced Ca(2+) entry through Gd(3+) sensitive transient receptor potential channels (TRPC), and by IP3 receptors.

  6. On Minkowskian branching structures

    NASA Astrophysics Data System (ADS)

    Wroński, Leszek; Placek, Tomasz

    In Belnap's [Branching space-time. Synthese, 92, 385-434. 'Postprint' archived at http://philsci-archive.pitt.edu/archive/00001003] theory of branching space-times (BST) Our World's possible histories are thought of as space-times, yet the theory has models in which histories do not resemble relativistic space-times or any other physical space-times. The aim of this paper is to define a certain class of BST models, called 'Minkowskian Branching Structures' (MBSs), in which histories are isomorphic to Minkowski space-time. By focusing on these models rather than on general BST models, we hope that one may be able to improve on earlier BST analyses of physical phenomena. Also, introducing MBSs sets the stage for recent discussions about whether or not branching is physically feasible.

  7. The Olive Branch Awards.

    ERIC Educational Resources Information Center

    Harnack, William

    1984-01-01

    The first annual Olive Branch Awards, sponsored by the Writers' and Publishers Alliance and the Editors' Organizing Committee, were given to ten magazines, out of 60 that submitted entries. Winning entries are described briefly. (IM)

  8. An archetypal mechanism for branching organogenesis.

    PubMed

    Clément, Raphaël; Mauroy, Benjamin

    2014-02-01

    Branched structures are ubiquitous in nature, both in living and non-living systems. While the functional benefits of branching organogenesis are straightforward, the developmental mechanisms leading to the repeated branching of epithelia in surrounding mesoderm remain unclear. Both molecular and physical aspects of growth control seem to play a critical role in shape emergence and maintenance. On the molecular side, the existence of a gradient of growth-promoting ligand between epithelial tips and distal mesenchyme seems to be common to branched organs. On the physical side, the branching process seems to require a mechanism of real-time adaptation to local geometry, as suggested by the self-avoiding nature of branching events. In this paper, we investigate the outcomes of a general three-dimensional growth model, in which epithelial growth is implemented as a function of ligand income, while the mesenchyme is considered as a proliferating viscous medium. Our results suggest that the existence of a gradient of growth-promoting ligand between distal and proximal mesenchyme implies a growth instability of the epithelial sheet, resulting in spontaneous self-avoiding branching morphogenesis. While the general nature of the model prevents one from fitting the development of specific organs, it suggests that few ingredients are actually required to achieve branching organogenesis.

  9. 12 CFR 208.6 - Establishment and maintenance of branches.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... processing under § 225.14(c) of Regulation Y (12 CFR 225.14(c)). (2) Expedited procedures. A completed... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Establishment and maintenance of branches. 208... maintenance of national bank branches (12 U.S.C. 36 and 1831u), except that approval of such branches shall...

  10. 12 CFR 208.6 - Establishment and maintenance of branches.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... processing under § 225.14(c) of Regulation Y (12 CFR 225.14(c)). (2) Expedited procedures. A completed... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Establishment and maintenance of branches. 208... maintenance of national bank branches (12 U.S.C. 36 and 1831u), except that approval of such branches shall...

  11. 12 CFR 208.6 - Establishment and maintenance of branches.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... processing under § 225.14(c) of Regulation Y (12 CFR 225.14(c)). (2) Expedited procedures. A completed... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Establishment and maintenance of branches. 208... maintenance of national bank branches (12 U.S.C. 36 and 1831u), except that approval of such branches shall...

  12. 12 CFR 208.6 - Establishment and maintenance of branches.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... processing under § 225.14(c) of Regulation Y (12 CFR 225.14(c)). (2) Expedited procedures. A completed... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Establishment and maintenance of branches. 208... maintenance of national bank branches (12 U.S.C. 36 and 1831u), except that approval of such branches shall...

  13. Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations

    SciTech Connect

    Vetter, U.; Pirsig, W.; Heinze, E.

    1983-02-01

    Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of /sup 35/S-labeled NaSO/sub 4/ into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage.

  14. Age dependent nitro-oxidative load and melatonin receptor expression in the spleen and immunity of goat Capra hircus.

    PubMed

    Singh, Amaresh Kumar; Haldar, Chandana

    2014-12-01

    The decline in the plasma level of melatonin has been associated with increased oxidative stress in the physiological system while aging. The increased levels of oxidants are known to augment the nitro-oxidative stress, which induces the apoptotic factors in lymphoid organs leading to age dependent immunosenescence. There are no reports to date that can suggest how the age dependent nitro-oxidative stress can influence the melatonin membrane MT1/MT2R expression and immune status of any small ruminant. In the present study, we noted the expression of melatonin receptors MT1R and MT2R and inducible nitric oxide synthase (iNOS) along with the apoptotic markers (viz. Bcl-2, Bax and Pro-caspase-3) in the spleen of young, middle-aged and old-aged Indian goat Capra hircus. The lymphocyte proliferation was also recorded along with the total nitrite and nitrate ion concentration (NOx) in the spleen and plasma. An age dependent decline in MT1R and MT2R expressions and lymphocyte proliferation with increased level of reactive nitrogen species (RNS) and iNOS expression was noted. An increased Bax/Bcl-2 ratio and a decreased Pro-caspase-3 expression were observed in the spleen of goat with an age dependent decline in the peripheral melatonin level. This decline in melatonin along with reduced melatonin receptor (MT1/MT2) expression and elevated RNS level in the spleen with aging might have an important role in the regulation of immune function of goats. Our observations suggest that the age-associated immunosenescence observed in goats can be a consequence of declining melatonin and its receptor expression and induction of apoptotic factors influenced by the increased RNS level that deteriorates the proper functioning of the spleen.

  15. Walker Branch Watershed Ecosystems Data

    DOE Data Explorer

    Walker Branch Watershed is located on the U. S. Department of Energy's Oak Ridge Reservation near Oak Ridge, in Anderson County, Tennessee. The Walker Branch Watershed Project began in 1967 under sponsorship of the U. S. Atomic Energy Commission (now the U. S. Department of Energy). Initially, the project centered primarily on the geologic and hydrologic processes that control the amounts and chemistry of water moving through the watershed. Past projects have included: • U. S. Department of Energy funded studies of watershed hydrology and forest nutrient dynamics • National Oceanic and Atmospheric Administration funded studies of forest micrometeorology • Studies of atmospheric deposition under the National Atmospheric Deposition Program • The International Biological Program Eastern Deciduous Forest Biome Project • National Science Foundation sponsored studies of trace element cycling and stream nutrient spiraling • Electric Power Research Institute funded studies of the effects of acidic deposition on canopy processes and soil chemistry. These projects have all contributed to a more complete understanding of how forest watersheds function and have provided insights into the solution of energy-related problems associated with air pollution, contaminant transport, and forest nutrient dynamics. This is one of a few sites in the world characterized by long-term, intensive environmental studies. The Walker Branch Watershed website at http://walkerbranch.ornl.gov/ provides maps, photographs, and data on climate, precipitation, atmospheric deposition, stream discharge and runoff, stream chemistry, and vegetation. [Taken from http://walkerbranch.ornl.gov/ABOUTAAA.HTM

  16. Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

    PubMed

    Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

    2015-12-01

    Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand.

  17. Disassortativity of random critical branching trees.

    PubMed

    Kim, J S; Kahng, B; Kim, D

    2009-06-01

    Random critical branching trees (CBTs) are generated by the multiplicative branching process, where the branching number is determined stochastically, independent of the degree of their ancestor. Here we show analytically that despite this stochastic independence, there exists the degree-degree correlation (DDC) in the CBT and it is disassortative. Moreover, the skeletons of fractal networks, the maximum spanning trees formed by the edge betweenness centrality, behave similarly to the CBT in the DDC. This analytic solution and observation support the argument that the fractal scaling in complex networks originates from the disassortativity in the DDC.

  18. Pen Branch delta expansion

    SciTech Connect

    Nelson, E.A.; Christensen, E.J.; Mackey, H.E.; Sharitz, R.R.; Jensen, J.R.; Hodgson, M.E.

    1984-02-01

    Since 1954, cooling water discharges from K Reactor ({anti X} = 370 cfs {at} 59 C) to Pen Branch have altered vegetation and deposited sediment in the Savannah River Swamp forming the Pen Branch delta. Currently, the delta covers over 300 acres and continues to expand at a rate of about 16 acres/yr. Examination of delta expansion can provide important information on environmental impacts to wetlands exposed to elevated temperature and flow conditions. To assess the current status and predict future expansion of the Pen Branch delta, historic aerial photographs were analyzed using both basic photo interpretation and computer techniques to provide the following information: (1) past and current expansion rates; (2) location and changes of impacted areas; (3) total acreage presently affected. Delta acreage changes were then compared to historic reactor discharge temperature and flow data to see if expansion rate variations could be related to reactor operations.

  19. LETTER TO THE EDITOR: U(1) × U(1) × U(1) symmetry of the Kimura 3ST model and phylogenetic branching processes

    NASA Astrophysics Data System (ADS)

    Bashford, J. D.; Jarvis, P. D.; Sumner, J. G.; Steel, M. A.

    2004-02-01

    An analysis of the Kimura 3ST model of DNA sequence evolution is given on the basis of its continuous Lie symmetries. The rate matrix commutes with a U(1) × U(1) × U(1) phase subgroup of the group GL(4) of 4 × 4 invertible complex matrices acting on a linear space spanned by the four nucleic acid base letters. The diagonal 'branching operator' representing speciation is defined, and shown to intertwine the U(1) × U(1) × U(1) action. Using the intertwining property, a general formula for the probability density on the leaves of a binary tree under the Kimura model is derived, which is shown to be equivalent to established phylogenetic spectral transform methods.

  20. Radioiodinated branched carbohydrates

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1989-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  1. Front Range Branch Officers

    NASA Astrophysics Data System (ADS)

    The Front Range Branch of AGU has installed officers for 1990: Ray Noble, National Center for Atmospheric Research, chair; Sherry Oaks, U.S. Geological Survey, chair-elect; Howard Garcia, NOAA, treasurer; Catharine Skokan, Colorado School of Mines, secretary. JoAnn Joselyn of NOAA is past chair. Members at large are Wallace Campbell, NOAA; William Neff, USGS; and Stephen Schneider, NCAR.

  2. Branching space-times

    NASA Astrophysics Data System (ADS)

    Placek, Tomasz; Müller, Thomas

    The five papers presented below have been selected from among the fourteen read at the European Science Foundation workshop Branching Space-Times (BST), held at the Jagiellonian University in Kraków, Poland, in October 2005. This event gathered for the first time leading researchers working on this subject.

  3. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study.

    PubMed

    Elsner, Viviane Rostirola; Lovatel, Gisele Agustini; Moysés, Felipe; Bertoldi, Karine; Spindler, Christiano; Cechinel, Laura Reck; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-02-01

    Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare. In this preliminary study we investigated the effect of aging and exercise on DNA methyltransferases (DNMT1 and DNMT3b) and H3-K9 methylation levels in hippocampus from 3 and 20-months aged Wistar rats. The animals were submitted to two exercise protocols: single session or chronic treadmill protocol. DNMT1 and H3-K9 methylation levels were decreased in hippocampus from aged rats. The single exercise session decreased both DNMT3b and DNMT1 levels in young adult rats, without any effect in the aged group. Both exercise protocols reduced H3-K9 methylation levels in young adult rats, while the single session reversed the changes on H3-K9 methylation levels induced by aging. Together, these results suggest that an imbalance on DNMTs and H3-K9 methylation levels might be linked to the brain aging process and that the outcome to exercise seems to vary through lifespan.

  4. Age-dependent effects on social interaction of NMDA GluN2A receptor subtype-selective antagonism.

    PubMed

    Green, Torrian L; Burket, Jessica A; Deutsch, Stephen I

    2016-07-01

    NMDA receptor-mediated neurotransmission is implicated in the regulation of normal sociability in mice. The heterotetrameric NMDA receptor is composed of two obligatory GluN1 and either two "modulatory" GluN2A or GluN2B receptor subunits. GluN2A and GluN2B-containing receptors differ in terms of their developmental expression, distribution between synaptic and extrasynaptic locations, and channel kinetic properties, among other differences. Because age-dependent differences in disruptive effects of GluN2A and GluN2B subtype-selective antagonists on sociability and locomotor activity have been reported in rats, the current investigation explored age-dependent effects of PEAQX, a GluN2A subtype-selective antagonist, on sociability, stereotypic behaviors emerging during social interaction, and spatial working memory in 4- and 8-week old male Swiss Webster mice. The data implicate an age-dependent contribution of GluN2A-containing NMDA receptors to the regulation of normal social interaction in mice. Specifically, at a dose of PEAQX devoid of any effect on locomotor activity and mouse rotarod performance, the social interaction of 8-week old mice was disrupted without any effect on the social salience of a stimulus mouse. Moreover, PEAQX attenuated stereotypic behavior emerging during social interaction in 4- and 8-week old mice. However, PEAQX had no effect on spontaneous alternations, a measure of spatial working memory, suggesting that neural circuits mediating sociability and spatial working memory may be discrete and dissociable from each other. Also, the data suggest that the regulation of stereotypic behaviors and sociability may occur independently of each other. Because expression of GluN2A-containing NMDA receptors occurs at a later developmental stage, they may be more involved in mediating the pathogenesis of ASDs in patients with histories of "regression" after a period of normal development than GluN2B receptors.

  5. Leaf age dependent changes in within-canopy variation in leaf functional traits: a meta-analysis.

    PubMed

    Niinemets, Ülo

    2016-05-01

    Within-canopy variation in leaf structural and photosynthetic characteristics is a major means by which whole canopy photosynthesis is maximized at given total canopy nitrogen. As key acclimatory modifications, leaf nitrogen content (N A) and photosynthetic capacity (A A) per unit area increase with increasing light availability in the canopy and these increases are associated with increases in leaf dry mass per unit area (M A) and/or nitrogen content per dry mass and/or allocation. However, leaf functional characteristics change with increasing leaf age during leaf development and aging, but the importance of these alterations for within-canopy trait gradients is unknown. I conducted a meta-analysis based on 71 canopies that were sampled at different time periods or, in evergreens, included measurements for different-aged leaves to understand how within-canopy variations in leaf traits (trait plasticity) depend on leaf age. The analysis demonstrated that in evergreen woody species, M A and N A plasticity decreased with increasing leaf age, but the change in A A plasticity was less suggesting a certain re-acclimation of A A to altered light. In deciduous woody species, M A and N A gradients in flush-type species increased during leaf development and were almost invariable through the rest of the season, while in continuously leaf-forming species, the trait gradients increased constantly with increasing leaf age. In forbs, N A plasticity increased, while in grasses, N A plasticity decreased with increasing leaf age, reflecting life form differences in age-dependent changes in light availability and in nitrogen resorption for growth of generative organs. Although more work is needed to improve the coverage of age-dependent plasticity changes in some plant life forms, I argue that the age-dependent variation in trait plasticity uncovered in this study is large enough to warrant incorporation in simulations of canopy photosynthesis through the growing period.

  6. The age-dependent epigenetic and physiological changes in an Arabidopsis T87 cell suspension culture during long-term cultivation

    SciTech Connect

    Kwiatkowska, Aleksandra; Zebrowski, Jacek; Oklejewicz, Bernadetta; Czarnik, Justyna; Halibart-Puzio, Joanna; Wnuk, Maciej

    2014-05-02

    Highlights: • A decrease in proliferation rate during long-term cultivation of Arabidopsis cells. • Age-dependent increase in senescence-associated gene expression in Arabidopsis cells. • Age-related increase in DNA methylation, H3K9me2, and H3K27me3 in Arabidopsis cells. • High potential of photosynthetic efficiency of long-term cultured Arabidopsis cells. - Abstract: Plant cell suspension cultures represent good model systems applicable for both basic research and biotechnological purposes. Nevertheless, it is widely known that a prolonged in vitro cultivation of plant cells is associated with genetic and epigenetic instabilities, which may limit the usefulness of plant lines. In this study, the age-dependent epigenetic and physiological changes in an asynchronous Arabidopsis T87 cell culture were examined. A prolonged cultivation period was found to be correlated with a decrease in the proliferation rate and a simultaneous increase in the expression of senescence-associated genes, indicating that the aging process started at the late growth phase of the culture. In addition, increases in the heterochromatin-specific epigenetic markers, i.e., global DNA methylation, H3K9 dimethylation, and H3K27 trimethylation, were observed, suggesting the onset of chromatin condensation, a hallmark of the early stages of plant senescence. Although the number of live cells decreased with an increase in the age of the culture, the remaining viable cells retained a high potential to efficiently perform photosynthesis and did not exhibit any symptoms of photosystem II damage.

  7. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers.

    PubMed

    Chera, Simona; Baronnier, Delphine; Ghila, Luiza; Cigliola, Valentina; Jensen, Jan N; Gu, Guoqiang; Furuyama, Kenichiro; Thorel, Fabrizio; Gribble, Fiona M; Reimann, Frank; Herrera, Pedro L

    2014-10-23

    Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display 'somatostatin-to-insulin' δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

  8. IGF-I regulates the age-dependent signaling peptide humanin.

    PubMed

    Lee, Changhan; Wan, Junxiang; Miyazaki, Brian; Fang, Yimin; Guevara-Aguirre, Jaime; Yen, Kelvin; Longo, Valter; Bartke, Andrzej; Cohen, Pinchas

    2014-10-01

    Aging is influenced by endocrine pathways including the growth hormone/insulin-like growth factor-1 (GH/IGF) axis. Mitochondrial function has also been linked to the aging process, but the relevant mitochondrial signals mediating the effects of mitochondria are poorly understood. Humanin is a novel signaling peptide that acts as a potent regulator of cellular stress responses and protects from a variety of in vitro and in vivo toxic and metabolic insults. The circulating levels of humanin decline with age in mice and humans. Here, we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis. Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels. Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects. Our results indicate that GH and IGF are potent regulators of humanin levels and that humanin levels correlate with lifespan in mice. This suggests that humanin represents a circulating mitochondrial signal that participates in modulating the aging process, adding a coordinated mitochondrial element to the endocrine regulation of aging.

  9. Age-dependent distractor suppression across the vision and motor domain.

    PubMed

    Mevorach, Carmel; Spaniol, Mayra Muller; Soden, Matthew; Galea, Joseph M

    2016-09-01

    The ability to inhibit distracting information-distractor suppression-is a fundamental process for the visual and motor systems. Whereas aging is typically linked to a general decline in cognitive processing, a specific impairment in distractor suppression is found during visual attention tasks. Despite this, the effect of aging on a human's capacity to inhibit distracting information during a motor task is currently unknown. Therefore, we tested the ability of young and older adults to inhibit distracting information during a visual attention (global-local) and a motor (reaching) task. When faced with distractors, younger and older adults displayed significant behavioral impairments (accuracy and speed) across both tasks. However, these deficits were substantially enhanced in older adults. Intriguingly, the amount of distractor impairment observed within each participant was correlated across the visual and motor tasks, irrespective of age group. Thus, while all participants' ability to inhibit distractors was correlated across the visual and motor domain, older adults displayed a generalized distractor inhibition deficit. We propose that a shift from proactive to reactive control in older adults could explain such impairment. These results may have important implications regarding the ability of older adults to effectively deal with distractors during complex visuomotor tasks such as driving.

  10. Task- and age-dependent effects of visual stimulus properties on children's explicit numerosity judgments.

    PubMed

    Defever, Emmy; Reynvoet, Bert; Gebuis, Titia

    2013-10-01

    Researchers investigating numerosity processing manipulate the visual stimulus properties (e.g., surface). This is done to control for the confound between numerosity and its visual properties and should allow the examination of pure number processes. Nevertheless, several studies have shown that, despite different visual controls, visual cues remained to exert their influence on numerosity judgments. This study, therefore, investigated whether the impact of the visual stimulus manipulations on numerosity judgments is dependent on the task at hand (comparison task vs. same-different task) and whether this impact changes throughout development. In addition, we examined whether the influence of visual stimulus manipulations on numerosity judgments plays a role in the relation between performance on numerosity tasks and mathematics achievement. Our findings confirmed that the visual stimulus manipulations affect numerosity judgments; more important, we found that these influences changed with increasing age and differed between the comparison and the same-different tasks. Consequently, direct comparisons between numerosity studies using different tasks and age groups are difficult. No meaningful relationship between the performance on the comparison and same-different tasks and mathematics achievement was found in typically developing children, nor did we find consistent differences between children with and without mathematical learning disability (MLD).

  11. Age-dependent expression of osteochondrosis-related genes in equine leukocytes

    PubMed Central

    Mendoza, L.; Piquemal, D.; Lejeune, J. P.; Vander Heyden, L.; Noguier, F.; Bruno, R.; Sandersen, C.; Serteyn, D.

    2015-01-01

    Introduction:  Osteochondrosis (OC) is a developmental disease in horses which has a significant impact on the horse's welfare and performance. The early disturbance in the process of endochondral ossification progresses to inflammatory and repair processes in older horses. Previously, differentially expressed genes in leukocytes of OC-affected horses have been identified. The aim of the present study is to detect age-related changes in these differentially expressed genes. Materials and Methods:  The expression of OC-related genes was analysed by real-time PCR and subsequent statistical analysis (ΔΔCT) in the leukocytes of 135 Belgian Warmblood horses divided into three different age groups: <12 months (n=47), 18–24 months (n=50) >30 months (n=38). Results:  Relative expression of genes of horses less than 12 months of age showed significant induction of the genes MGAT4A, PRKCG, MHCI, ApoB, ApoB3G, B4GALT6 and a significantly lower expression of the genes OAS3. Horses of 18–24 months of age, showed a significantly higher expression of the genes TBC1D9, MGAT4A, IFIH1, MHCIIa and MMP1. Horses of more than 30 months of age showed a significantly higher expression of the genes MGAT4A, HP, SECTM1 compared with their age-matched control groups. Conclusions:  The study demonstrates that OC-related genes are differentially expressed in horses of different ages compared with their age-matched controls. Some of the genes may be implicated in cell signalling and differentiation as well as carbohydrate and lipid metabolism and inflammation. However, the causal relationship between the differentially expressed genes and the development and progression of the OC lesions needs to be determined. PMID:26392886

  12. Interactions between Aβ oligomers and presynaptic cholinergic signaling: age-dependent effects on attentional capacities

    PubMed Central

    Parikh, Vinay; Bernard, Carcha S.; Naughton, Sean X.; Yegla, Brittney

    2014-01-01

    Substantial evidence suggests that cerebral deposition of the neurotoxic fibrillar form of amyloid precursor protein, β-amyloid (Aβ), plays a critical role in the pathogenesis of Alzheimer's disease (AD). Yet, many aspects of AD pathology including the cognitive symptoms and selective vulnerability of cortically-projecting basal forebrain (BF) cholinergic neurons are not well explained by this hypothesis. Specifically, it is not clear why cognitive decline appears early when the loss of BF cholinergic neurons and plaque deposition are manifested late in AD. Soluble oligomeric forms of Aβ are proposed to appear early in the pathology and to be better predictors of synaptic loss and cognitive deficits. The present study was designed to examine the impact of Aβ oligomers on attentional functions and presynaptic cholinergic transmission in young and aged rats. Chronic intracranial infusions of Aβ oligomers produced subtle decrements in the ability of rats to sustain attentional performance with time on task, irrespective of the age of the animals. However, Aβ oligomers produced robust detrimental effects on performance under conditions of enhanced attentional load in aged animals. In vivo electrochemical recordings show reduced depolarization-evoked cholinergic signals in Aβ-infused aged rats. Moreover, soluble Aβ disrupted the capacity of cholinergic synapses to clear exogenous choline from the extracellular space in both young and aged rats, reflecting impairments in the choline transport process that is critical for acetylcholine (ACh) synthesis and release. Although aging per se reduced the cross-sectional area of BF cholinergic neurons and presynaptic cholinergic proteins in the cortex, attentional performance and ACh release remained unaffected in aged rats infused with the control peptide. Taken together, these data suggest that soluble Aβ may marginally influence attentional functions at young ages primarily by interfering with the choline uptake

  13. The role of microglial mtDNA damage in age-dependent prolonged LPS-induced sickness behavior.

    PubMed

    Nakanishi, Hiroshi; Hayashi, Yoshinori; Wu, Zhou

    2011-02-01

    Microglia are the main cellular source of oxidation products and inflammatory molecules in the brain during aging. The accumulation of mitochondrial DNA (mtDNA) oxidative damage in microglia during aging results in the increased production of reactive oxygen species (ROS). The increased intracellular ROS, in turn, activates a redox-sensitive nuclear factor-κB (NF-κB) to provoke excessive neuroinflammation, resulting in memory deficits and the prolonged behavioral consequence of infection. Besides its role in regulating the gene copy number, mitochondrial transcription factor A (TFAM) is closely associated with the stabilization of mtDNA structures. Lipopolysaccharide (LPS) induces the generation of ROS from the actively respirating mitochondria as well as NADPH oxidase, and leads to the subsequent activation of the NF-κB-dependent inflammatory pathway in aging microglia. The overexpression of human TFAM improves the age-dependent prolonged LPS-induced sickness behaviors by ameliorating the mtDNA damage and reducing the resultant redox-regulated inflammatory responses. Therefore, 'microglia-aging' plays important roles in the age-dependent enhanced behavioral consequences of infection.

  14. Age-Dependent Paraoxonase 1 (PON1) Activity and LDL Oxidation in Wistar Rats during Their Entire Lifespan

    PubMed Central

    Kumar, Dileep

    2014-01-01

    Paraoxonase 1 (PON1) is an HDL bound enzyme which plays a key role in the protection of LDL and HDL from oxidation by hydrolyzing activated phospholipids and lipid peroxide products. Oxidative stress plays a crucial role in the development of atherosclerosis by oxidation of LDL. This study was conducted to determine age-dependent changes in plasma PON1 arylesterase activity and LDL oxidation in rats during their entire lifespan. 48 Wistar strain rats were grouped in six different age groups (1, 4, 8, 12, 18, and 24 months). We observe a significant (P < 0.001) age-dependent decrease in plasma PON1 arylesterase activity correlating with increase in susceptibility of LDL oxidation and increase in plasma MDA level concomitantly with a significant (P < 0.001) decrease in plasma radical scavenging activity after 8 months. The reduction of PON1 and free radical scavenging activity with age could have a considerable impact on the increased incidence of atherosclerosis with age. Our observation of a significant decline in PON1 activity which correlates with increased LDL oxidation after 8 months of age is an interesting observation and needs further investigation. PMID:24971380

  15. Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human autosomal-dominant sensory ataxia.

    PubMed

    Kim, Youngsoo; Kim, Seong Hun; Kim, Kook Hwan; Chae, Sujin; Kim, Chanki; Kim, Jeongjin; Shin, Hee-Sup; Lee, Myung-Shik; Kim, Daesoo

    2015-12-20

    Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin ligase known to mediate ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a point mutation of RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), which is characterized by an age-dependent increase of walking abnormalities, a rare genetic disorder reported in only two families. Although this mutant allele is known to be dominant, the functional identity thereof has not been clearly established. Here, we generated mice lacking Rnf170 (Rnf170(-/-)) to evaluate the effect of its loss of function in vivo. Remarkably, Rnf170(-/-) mice began to develop gait abnormalities in old age (12 months) in the form of asynchronous stepping between diagonal limb pairs with a fixed step sequence during locomotion, while age-matched wild-type mice showed stable gait patterns using several step sequence repertoires. As reported in ADSA patients, they also showed a reduced sensitivity for proprioception and thermal nociception. Protein blot analysis revealed that the amount of Itpr1 protein was significantly elevated in the cerebellum and spinal cord but intact in the cerebral cortex in Rnf170(-/-) mice. These results suggest that the loss of Rnf170 gene function mediates ADSA-associated phenotypes and this gives insights on the cure of patients with ADSA and other age-dependent walking abnormalities.

  16. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus.

    PubMed

    Chakraborty, Goutam; Thumpayil, Sherin; Lafontant, David-Erick; Woubneh, Wolde; Toney, Jeffrey H

    2009-11-01

    Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay mice over time and observed a significant (Page-dependent improvement (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age). During the same time period, body weight and food and water consumption were relatively constant. The authors also measured plasma levels of endocrine hormones that are important in diabetes. Levels of insulin were approximately 8 times higher and levels of amylin 3 times higher in 220-d-old KK-Ay mice than in 180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin remained relatively constant. These findings suggest that KK-Ay mice undergo an age-dependent improvement of glucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.

  17. Mitotic epitopes are incorporated into age-dependent neurofibrillary tangles in Niemann-Pick disease type C.

    PubMed

    Zhang, Min; Wang, Xuezhen; Jiang, Feng; Wang, Wei; Vincent, Inez; Bu, Bitao

    2010-03-01

    The mechanism underlying neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) and other neurodegenerative disorders remains elusive. Niemann-Pick disease type C (NPC) is a kind of genetic neurovisceral disorder in which the intracellular sequestration of cholesterol and other lipids in neurons, NFT formation and neuronal degeneration in brain are the neuropathology hallmarks. The age of onset and progression of the disease vary dramatically. We have analyzed the hippocampus from 17 NPC cases, aged from 7 months to 55 years, to depict the temporal characteristics of NFT formation. Unexpectedly, classic NFT was observed in about 4-year-old NPC brain, suggesting that NFT is not aging dependent, and that juvenile brain neurons satisfy the requirements for NFT formation. NFT in the hippocampus of NPC was significantly increased in number with the advance of age. More importantly, multiple mitotic phase markers, which are not usually found in normal mature neurons, were abundant in the affected neurons and incorporated into NFT. The unusual activation of cdc2/cyclin B kinase and downstream mitotic indices are closely associated with the age-dependent NFT formation, signifying the contribution of abortive cell cycle to neurodegeneration. The cdc2 inhibitors may be therapeutically used for early intervention of neurodegeneration and NFT formation in NPC.

  18. Branching structure and strain hardening of branched metallocene polyethylenes

    SciTech Connect

    Torres, Enrique; Li, Si-Wan; Costeux, Stéphane; Dealy, John M.

    2015-09-15

    There have been a number of studies of a series of branched metallocene polyethylenes (BMPs) made in a solution, continuous stirred tank reactor (CSTR) polymerization. The materials studied vary in branching level in a systematic way, and the most highly branched members of the series exhibit mild strain hardening. An outstanding question is which types of branched molecules are responsible for strain hardening in extension. This question is explored here by use of polymerization and rheological models along with new data on the extensional flow behavior of the most highly branched members of the set. After reviewing all that is known about the effects of various branching structures in homogeneous polymers and comparing this with the structures predicted to be present in BMPs, it is concluded that in spite of their very low concentration, treelike molecules with branch-on-branch structure provide a large number of deeply buried inner segments that are essential for strain hardening in these polymers.

  19. Improvement of oxidative stress and immunity by melatonin: an age dependent study in golden hamster.

    PubMed

    Vishwas, Dipanshu Kumar; Mukherjee, Arun; Haldar, Chandana; Dash, Debabrata; Nayak, Manasa K

    2013-02-01

    Reactive oxygen species (ROS) have been proposed to play an important role in balancing the pro- and antioxidant homeostasis during aging. Melatonin has been suggested as an effective free radical scavenger that might have a role during the process of aging. We observed, that melatonin administration (25 μg/100 g body weight for 30 days) significantly augments the activity of anti-oxidative enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the plasma, spleen and bone marrow (BM) of young (6 weeks), adult (30 weeks) and old aged (2.5 years) male golden hamster, Mesocricetus auratus. A sharp decline in generation of ROS was observed in peripheral blood mononuclear cells (PBMC) and splenocytes upon melatonin administration in different age group of hamsters. Reduction in the level of thiobarbituric acid-reactive substances (TBARS) and total nitrite and nitrate concentration as metabolites and indicators of nitric oxide (NO) in plasma, spleen and BM were observed along with night time (22:00 h) melatonin concentration in different age group of hamsters after administration of melatonin and compared to the control group (treated with 0.9% saline). General immune parameters like proliferation of splenocytes, PBMC and colony forming ability of GM-CFU were observed following melatonin treatment in different age group, although it was low only in aged hamsters compared to the young and adult. Our data indicates that the age related increase of oxidative load and simultaneously augments the general immunity in aged hamsters.

  20. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri

    PubMed Central

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-01-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish. PMID:26121607

  1. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri.

    PubMed

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-10-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish.

  2. Age-Dependent Changes in the Inflammatory Nociceptive Behavior of Mice

    PubMed Central

    King-Himmelreich, Tanya S.; Möser, Christine V.; Wolters, Miriam C.; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-01-01

    The processing of pain undergoes several changes in aging that affect sensory nociceptive fibers and the endogenous neuronal inhibitory systems. So far, it is not completely clear whether age-induced modifications are associated with an increase or decrease in pain perception. In this study, we assessed the impact of age on inflammatory nociception in mice and the role of the hormonal inhibitory systems in this context. We investigated the nociceptive behavior of 12-month-old versus 6–8-week-old mice in two behavioral models of inflammatory nociception. Levels of TRP channels, and cortisol as well as cortisol targets, were measured by qPCR, ELISA, and Western blot in the differently aged mice. We observed an age-related reduction in nociceptive behavior during inflammation as well as a higher level of cortisol in the spinal cord of aged mice compared to young mice, while TRP channels were not reduced. Among potential cortisol targets, the NF-κB inhibitor protein alpha (IκBα) was increased, which might contribute to inhibition of NF-κB and a decreased expression and activity of the inducible nitric oxide synthase (iNOS). In conclusion, our results reveal a reduced nociceptive response in aged mice, which might be at least partially mediated by an augmented inflammation-induced increase in the hormonal inhibitory system involving cortisol. PMID:26593904

  3. Age Dependent Switching Role of Cyclin D1 in Breast Cancer

    PubMed Central

    Rinaldi, Carmela; Malara, Natalia Maria; D’Angelo, Rosalia; Sidoti, Antonina; Leotta, Attilio; Lio, Santo; Caparello, Basilio; Ruggeri, Alessia; Mollace, Vincenzo; Amato, Aldo

    2012-01-01

    Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process. Methods: 130 cases of ductal breast cancer in postmenopausal women, aged 52–96 in 3 age classes were selected. Tumoral tissues preserved in formaldehyde solution and subsequently embedded in paraffin were subjected to analysis Fluorescence in situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and immuno-histochemical tests. The molecular variables studied were estimated in relation to the patients’ age. Results: The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we have examined is significantly associated with a lower proliferation rate. Conclusion: Cyclin D1, which characterizes tumor in young women as molecular director involved in strengthening tumoral proliferation mechanisms, may be seen as a potential blocking molecular switch in corresponding tumours in old women. PMID:22231956

  4. Utilization of routinely collected administrative data in monitoring the incidence of aging dependent hip fracture

    PubMed Central

    Sund, Reijo

    2007-01-01

    Societies are facing challenges as the public health burden increases in tandem with population aging. Local information systems are needed that would allow a continuous monitoring of the incidence and effectiveness of treatments. This study investigates the possibilities of routinely collected administrative data as a data source for hip fracture incidence monitoring in Finland. The study demonstrates that a straightforward use of register data results in biased estimates for the numbers of hip fractures. An interpretation of hip fractures from the population aging point of view offers an alternative perspective for hip fracture incidence calculation. This enables development of a generalizable method for probabilistic detection of starting points of hip fracture care episodes. Several risk factor and risk population extraction techniques required in register-based data analyses are also demonstrated. Finally, it is shown that empirical evidence suggests that hip fracture incidence is proportional to population level disability prevalence. In conclusion, Finnish administrative data makes it possible to derive data for rather detailed population level risk factor stratification. Certain limitations of register-based data can be partly avoided by synthesizing data-sensitive methodological solutions during the analysis process. PMID:17555560

  5. Age-dependent and coordinated shift in performance between implicit and explicit skill learning

    PubMed Central

    Nemeth, Dezso; Janacsek, Karolina; Fiser, József

    2013-01-01

    It has been reported recently that while general sequence learning across ages conforms to the typical inverted-U shape pattern, with best performance in early adulthood, surprisingly, the basic ability of picking up in an implicit manner triplets that occur with high vs. low probability in the sequence is best before 12 years of age and it significantly weakens afterwards. Based on these findings, it has been hypothesized that the cognitively controlled processes coming online at around 12 are useful for more targeted explicit learning at the cost of becoming relatively less sensitive to raw probabilities of events. To test this hypothesis, we collected data in a sequence learning task using probabilistic sequences in five age groups from 11 to 39 years of age (N = 288), replicating the original implicit learning paradigm in an explicit task setting where subjects were guided to find repeating sequences. We found that in contrast to the implicit results, performance with the high- vs. low-probability triplets was at the same level in all age groups when subjects sought patterns in the sequence explicitly. Importantly, measurements of explicit knowledge about the identity of the sequences revealed a significant increase in ability to explicitly access the true sequences exactly around the age where the earlier study found the significant drop in ability to learn implicitly raw probabilities. These findings support the conjecture that the gradually increasing involvement of more complex internal models optimizes our skill learning abilities by compensating for the performance loss due to down-weighting the raw probabilities of the sensory input, while expanding our ability to acquire more sophisticated skills. PMID:24155717

  6. Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

    PubMed

    Rogulj, Dinko; El Aklouk, Ismail; Konjevoda, Paško; Ljubić, Spomenka; Pibernik Okanović, Mirjana; Barbir, Ante; Luburić, Marijana; Radman, Maja; Budinski, Ninoslav; Vučić Lovrenčić, Marijana

    2017-03-30

    Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

  7. Age-dependent Wnt gene expression in bone and during the course of osteoblast differentiation

    PubMed Central

    Rauner, Martina; Sipos, Wolfgang

    2008-01-01

    Wnt signaling is vital for osteoblast differentiation and recently has been associated with aging. Because impaired osteoblastogenesis is a cellular characteristic of age-induced bone loss, we investigated whether this process is associated with an altered expression of Wnt signaling-related proteins in bone and osteoblasts. Bone marrow cells were isolated from male C57BL/6 mice, aged 6 weeks, 6 months, and 18 months, respectively. Osteogenic differentiation was induced for 3 weeks and assessed using alizarin red staining. Gene expression of Wnt1, 3a, 4, 5a, 5b, 7b, 9b, 10b, lipoprotein receptor-related protein (LRP)-5/6, as well as dickkopf-1 (Dkk-1), sclerostin, and secreted frizzled related protein-1 (sFRP-1) was determined in bone tissue and osteoblasts on days 7, 14, and 21 by real-time RT-PCR. Osteoblast differentiation was significantly reduced in aged mice compared with young and adult mice. In bone tissue, expression levels of all genes assessed were decreased in adult and old mice, respectively, compared with young mice. Mature osteoblasts of aged compared with those of young mice showed enhanced expression of Wnt9b, LRP-6, and Dkk-1, and decreased expression of Wnt5a and 7b. In early osteoblasts, mRNA levels of Wnt1, 5a, 5b, and 7b were increased significantly in aged mice. The expression of Wnt3a, 4, LRP-5, and sclerostin was not altered in aged osteoblasts. In conclusion, osteoblastic expression of each Wnt-related protein is regulated individually by aging. The overall decreased expression of Wnt-related proteins in bone tissue of aged mice underlines the newly discovered association of Wnt signaling with aging. PMID:19424851

  8. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling.

    PubMed

    González, Oscar C; Krishnan, Giri P; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence; Bazhenov, Maxim

    2015-09-30

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. Significance statement: Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy.

  9. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling

    PubMed Central

    González, Oscar C.; Krishnan, Giri P.; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence

    2015-01-01

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy. PMID:26424890

  10. Age-dependent role of steroids in the regulation of growth of the hen follicular wall

    PubMed Central

    2010-01-01

    , whereas it may inhibit this process in young birds. T and LH are apparently involved in the growth regulation during the pre-ovulatory surge in young hens. PMID:20156346

  11. Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

    PubMed Central

    Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

    2015-01-01

    Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B

  12. Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice.

    PubMed

    Mistry, Akshitkumar M; Thompson, Christopher H; Miller, Alison R; Vanoye, Carlos G; George, Alfred L; Kearney, Jennifer A

    2014-05-01

    Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a(+/-)) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. Scn1a(+/-) mice on strain 129S6/SvEvTac (129.Scn1a(+/-)) have no overt phenotype and normal survival compared with Scn1a(+/-) mice bred to C57BL/6J (F1.Scn1a(+/-)) that have severe epilepsy and premature lethality. We tested the hypothesis that strain differences in sodium current (INa) density in hippocampal neurons contribute to these divergent phenotypes. Whole-cell voltage-clamp recording was performed on acutely-dissociated hippocampal neurons from postnatal days 21-24 (P21-24) 129.Scn1a(+/-) or F1.Scn1a(+/-) mice and wild-type littermates. INa density was lower in GABAergic interneurons from F1.Scn1a(+/-) mice compared to wild-type littermates, while on the 129 strain there was no difference in GABAergic interneuron INa density between 129.Scn1a(+/-) mice and wild-type littermate controls. By contrast, INa density was elevated in pyramidal neurons from both 129.Scn1a(+/-) and F1.Scn1a(+/-) mice, and was correlated with more frequent spontaneous action potential firing in these neurons, as well as more sustained firing in F1.Scn1a(+/-) neurons. We also observed age-dependent differences in pyramidal neuron INa density between wild-type and Scn1a(+/-) animals. We conclude that preserved INa density in GABAergic interneurons contributes to the milder phenotype of 129.Scn1a(+/-) mice. Furthermore, elevated INa density in excitatory pyramidal neurons at P21-24 correlates with age-dependent onset of lethality in F1.Scn1a(+/-) mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution

  13. [ROLE OF NEUTRAL SPHINGOMYELINASE IN AGE-DEPENDENT MUSCLE INSULIN RESISTANCE DEVELOPMENT AND ITS IMPROVEMENT WITH N-ACETYLCYSTEINE].

    PubMed

    Babenko, N A; Timofiĭchuk, O A; Belyĭ, A N

    2015-01-01

    In the present study, we evaluated the role of ceramide in age-dependent and etoposide-induced insulin resistance. A significant increase in the level of ceramide and decrease of gluthatione (GSH) content and tissue sensitivity to insulin has been observed in 24-month-old rats as compared with 3-month-old animals. Etoposide imitates ageing-like changes in muscle tissue of young rats. N-acetylcysteine as well as specific neutral sphingomyelinase (nSMase) inhibitor--GW4869, decreases ceramide content and increases GSH level, and enhances the insulin-induced [3H-D-glucose uptake in the "aged" tissue. These data indicate that nSMase play important role in the age- and drug-induced ceramide-dependent insuline resistance.

  14. Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans.

    PubMed

    Liu, Jie; Zhang, Bi; Lei, Haoyun; Feng, Zhaoyang; Liu, Jianfeng; Hsu, Ao-Lin; Xu, X Z Shawn

    2013-09-03

    Aging is characterized by a progressive decline in multiple physiological functions (i.e., functional aging). As animals age, they exhibit a gradual loss in motor activity, but the underlying mechanisms remain unclear. Here we approach this question in C. elegans by functionally characterizing its aging nervous system and muscles. We find that motor neurons exhibit a progressive functional decline, beginning in early life. Surprisingly, body-wall muscles, which were previously thought to undergo functional aging, do not manifest such a decline until mid-late life. Notably, motor neurons first develop a deficit in synaptic vesicle fusion followed by that in quantal size and vesicle docking/priming, revealing specific functional deteriorations in synaptic transmission. Pharmacological stimulation of synaptic transmission can improve motor activity in aged animals. These results uncover a critical role for the nervous system in age-dependent motor activity decline in C. elegans and provide insights into how functional aging occurs in this organism.

  15. [Age-dependent characteristics of the skin peripheral blood flow oscillations by nonlinear dynamics methods in humans].

    PubMed

    Tankanag, A V; Tikhonova, I V; Chemeris, N K

    2008-03-01

    Study of peripheral microhaemodynamics was carried out with laser Doppler flowmetry in healthy volunteers of different age groups. The ageing changes in the state of the skin peripheral blood flow, in the functioning of separate links and regulatory systems ofmicrovascular bed have been estimated in terms of relative entropy and fractal dimension values. The revealed significant age-dependent decrease of relative entropy values in the respiratory rhythm ranges, the neurogenic and myogenic activities yielded some evidence concerning the reduction of the microcirculation system chaotic changes within these frequency ranges during the ageing. The significant increase of fractal dimension values in the ranges of cardio-rhythm and the endothelial activity in the oldest group with the mean age of 77 years indicated that the structural complexity of the oscillations in these frequency ranges increased during ageing.

  16. Age-dependent potassium iodide effect on the thyroid irradiation by 131I and 133I in the nuclear emergency.

    PubMed

    Jang, M; Kim, H K; Choi, C W; Kang, C S

    2008-01-01

    The initial near-field exposure is primarily through inhalation in a nuclear emergency and the dominant contribution to the effective inhalation dose comes from radioiodine. Thyroid blockade by oral potassium iodide (KI) is efficient and practical for public in the nuclear emergency. Age-dependent radioprotective effect of KI on the thyroid irradiation by (131)I and (133)I has been derived using the simplified compartment model of iodine metabolism and WinSAAM program. Administration of KI within 2 h after (131)I and (133)I intake can block thyroid uptake significantly, yielding protective effect of 78.9% and 74.3%, respectively, for (131)I and (133)I for adults. The mean absorbed doses decrease with age, while protective effects of KI are similar for all age groups.

  17. Age-dependent HLA profiles of the Israeli population: impact on hematopoietic cell donor recruitment and availability.

    PubMed

    Israeli, Moshe; Oudshoorn, Machteld; Haasnoot, Geert W; Klein, Tirza; Zisser, Bracha; Bach, Gideon; Claas, Frans H J

    2014-10-01

    Approximately three million people have immigrated to the state of Israel since it was founded. Consequently, the immunogenetic profile of the younger generation may consist of a genetic mixture of formerly distinct population groups. We aimed to investigate whether HLA profiles in the Israeli population are age dependent and how this influences representation of various age groups in local donor registries. We determined HLA-A*, HLA-B*, and HLA-DRB1* low-resolution phenotypes of three age groups (n = 4,169 in each): (1) cord blood units collected between 2009 and 2013 (BABIES) and adult registry donors (2) aged 18-28 years (YOUNG) and (3) aged 49-60 years (OLD). We compared the results with virtual groups that simulate the offspring of the actual study groups. None of the three actual age groups were in Hardy-Weinberg equilibrium. The YOUNG presented four HLA-B alleles that were absent in the OLD and BABIES. A significantly higher percentage among the OLD and BABIES had a "matched" individual within their group in comparison to the YOUNG. In the YOUNG, the 10 most common haplotypes account for 16.7 % of the population, in comparison to 18.2 % in the OLD or 19.8 % in the BABIES group. The BABIES group was genetically remote from all other groups. Further disparities were found between the actual and the corresponding virtual groups. We conclude that discrete age groups in Israel present distinct immunogenetic profiles, where the younger generation is more heterogeneous. The population dynamics of the age-dependent HLA profile is multifactorial: gradual intersubgroup admixture, nonrandom mating, and entry of new alleles.

  18. Different age-dependent performance in Drosophila wild-type Canton-S and the white mutant w1118 flies.

    PubMed

    Qiu, Shuang; Xiao, Chengfeng; Meldrum Robertson, R

    2017-04-01

    Aging has significant effects on the locomotor performance of insects including Drosophila. Using a protocol for the high-throughput analysis of fly locomotion in a circular arena, we examined age-dependent behavioral characteristics in adult flies. There are widely used wild-type and genetically engineered background lines including the Canton-S strain and the w1118 strain, which has a null mutation of the white gene. Under standard rearing conditions, we found similar survival and median lifespans in Canton-S (50days) and w1118 (54days) strains, however, w1118 flies maintained stable body mass for up to 43days, whereas Canton-S flies gained body mass at young age, followed by a gradual decline. We also tested the behavioral performance of young and old flies. Compared with young w1118 flies (5-10days), old w1118 flies (40-45days) had an increased boundary preference during locomotion in small circular arenas, and increased speed of locomotor recovery from anoxia. Old Canton-S files, however, exhibited unchanged boundary preference and reduced recovery speed from anoxia relative to young flies. In addition, old w1118 flies showed decreased path length per minute and reduced 0.2s path increment compared with young flies, whereas old Canton-S flies displayed the same path length per minute and the same 0.2s path increment compared with young flies. We conclude that age-dependent behavioral and physiological changes differ between Canton-S and w1118 flies. These results illustrate that phenotypic differences between strains can change qualitatively, as well as quantitatively, as the animals age.

  19. Cell cycle age dependence for radiation-induced G/sub 2/ arrest: evidence for time-dependent repair

    SciTech Connect

    Rowley, R.

    1985-09-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G/sub 2/. The sensitivity of Chinese hamster ovary cells to G/sub 2/ arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G/sub 2/. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G/sub 2/ arrest and/or by changes in capability for postirradiation recovery from G/sub 2/ arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G/sub 2/ arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G/sub 2/ arrest, while inhibiting repair of G/sub 2/ arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G/sub 2/ arrest was expressed. The duration of G/sub 2/ arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G/sub 2/ arrest induction is present throughout the cell cycle and that the level of G/sub 2/ arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G/sub 2/ arrest.

  20. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    SciTech Connect

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  1. Fish oil and treadmill exercise have age-dependent effects on episodic memory and oxidative state of the hippocampus.

    PubMed

    Macêdo, Patrícia Fortes Cavalcanti de; de Melo, Janatar Stella Vasconcelos; Costa, Laís Alves Ribeiro; Braz, Glauber Rudá F; de Sousa, Shirley M; Lagranha, Cláudia J; Hornsby, Manuella Batista-de-Oliveira

    2017-01-09

    There is a growing interest to better understand how lifestyle choices can improve memory functions. Treadmill exercise and long-chain n-3 polyunsaturated fatty acids found in fish oil are able to stimulate hippocampal antioxidant defenses and improve memory. The aim was to test whether fish oil and exercise can improve rat's performance on memory tasks and optimize hippocampal antioxidant state in an age-dependent manner. Therefore, young and adult rats were exercised and received fish oil during 4 weeks. The exercise was performed for 30 min/day, with the speed gradually increasing from the first to the last week. Afterwards, episodic memory was measured by the recognition of object identity and spatial location. Hippocampal oxidative state was investigated with the levels of malondialdehyde (MDA), carbonyls content, antioxidant enzymatic activity (superoxide dismutase (SOD), catalase (CAT)), and antioxidant nonenzymatic activity (reduced glutathione, sulfhydryl content). The adult rats treated with fish oil and exercise (FO&EX) were able to recognize object's shape and placement; however, FO&EX young rats had impaired spatial recognition (p < 0.05). The FO&EX young rats did not have reduced MDA or carbonyl content, though either fish oil or exercise reduced MDA (p < 0.05) and carbonyl levels (p < 0.01). Exercise increased SOD (p < 0.001) and CAT activities (p < 0.05), and fish oil enhanced SOD activity (p < 0.05) in young rats. At adulthood, exercise increased MDA levels (p < 0.05), and FO&EX reduced MDA (p < 0.001). Finally, exercise and fish oil improved nonenzymatic antioxidant defense (p < 0.05) only in adult rats. Results support age-dependent effects of fish oil and exercise on memory and oxidative state of the hippocampus during either neurodevelopment or adulthood.

  2. Early restriction of alphavirus replication and dissemination contributes to age-dependent attenuation of systemic hyperinflammatory disease.

    PubMed

    Ryman, Kate D; Gardner, Christina L; Meier, Kathryn C; Biron, Christine A; Johnston, Robert E; Klimstra, William B

    2007-02-01

    Severity of alphavirus infection in humans tends to be strongly age-dependent and several studies using laboratory-adapted Sindbis virus (SB) AR339 strains have indicated that SB-induced disease in mice is similarly contingent upon host developmental status. In the current studies, the consensus wild-type SB, TR339, and in vivo imaging technology have been utilized to examine virus replication and disease manifestations in mice infected subcutaneously at 5 days of age (5D) vs 11D. Initial virulence studies with TR339 indicated that this age range is coincident with rapid transition from fatal to non-fatal outcome. Fatal infection of 5D mice is characterized by high-titre serum viraemia, extensive virus replication in skin, fibroblast connective tissue, muscle and brain, and hyperinflammatory cytokine induction. In contrast, 11D-infected mice experience more limited virus replication and tissue damage and develop mild, immune-mediated pathologies including encephalitis. These results further establish the linkage between hyperinflammatory cytokine induction and fatal outcome of infection. In vivo imaging using luciferase-expressing viruses and non-propagative replicons revealed that host development results in a restriction of virus replication within individual infected cells that is manifested as a delay in reduction of virus replication in the younger mice. Thus, an important contributing factor in age-dependent resistance to alphavirus infection is restriction of replication within first infected cells in peripheral tissues, which may augment other developmentally regulated attenuating effects, such as increasing neuronal resistance to virus infection and apoptotic death.

  3. Thermal Energy Conversion Branch

    NASA Technical Reports Server (NTRS)

    Bielozer, Matthew C.; Schreiber, Jeffrey, G.; Wilson, Scott D.

    2004-01-01

    The Thermal Energy Conversion Branch (5490) leads the way in designing, conducting, and implementing research for the newest thermal systems used in space applications at the NASA Glenn Research Center. Specifically some of the most advanced technologies developed in this branch can be broken down into four main areas: Dynamic Power Systems, Primary Solar Concentrators, Secondary Solar Concentrators, and Thermal Management. Work was performed in the Dynamic Power Systems area, specifically the Stirling Engine subdivision. Today, the main focus of the 5490 branch is free-piston Stirling cycle converters, Brayton cycle nuclear reactors, and heat rejection systems for long duration mission spacecraft. All space exploring devices need electricity to operate. In most space applications, heat energy from radioisotopes is converted to electrical power. The Radioisotope Thermoelectric Generator (RTG) already supplies electricity for missions such as the Cassini Spacecraft. The focus of today's Stirling research at GRC is aimed at creating an engine that can replace the RTG. The primary appeal of the Stirling engine is its high system efficiency. Because it is so efficient, the Stirling engine will significantly reduce the plutonium fuel mission requirements compared to the RTG. Stirling is also being considered for missions such as the lunar/Mars bases and rovers. This project has focused largely on Stirling Engines of all types, particularly the fluidyne liquid piston engine. The fluidyne was developed by Colin D. West. This engine uses the same concepts found in any type of Stirling engine, with the exception of missing mechanical components. All the working components are fluid. One goal was to develop and demonstrate a working Stirling Fluidyne Engine at the 2nd Annual International Energy Conversion Engineering Conference in Providence, Rhode Island.

  4. Combustion Branch Website Development

    NASA Technical Reports Server (NTRS)

    Bishop, Eric

    2004-01-01

    The NASA combustion branch is a leader in developing and applying combustion science to focused aerospace propulsion systems concepts. It is widely recognized for unique facilities, analytical tools, and personnel. In order to better communicate the outstanding research being done in this Branch to the public and other research organization, a more substantial website was desired. The objective of this project was to build an up-to-date site that reflects current research in a usable and attractive manner. In order to accomplish this, information was requested from all researchers in the Combustion branch, on their professional skills and on the current projects. This information was used to fill in the Personnel and Research sections of the website. A digital camera was used to photograph all personnel and these photographs were included in the personnel section as well. The design of the site was implemented using the latest web standards: xhtml and external css stylesheets. This implementation conforms to the guidelines recommended by the w3c. It also helps to ensure that the web site is accessible by disabled users, and complies with Section 508 Federal legislation (which mandates that all Federal websites be accessible). Graphics for the new site were generated using the gimp (www.gimp.org) an open-source graphics program similar to Adobe Photoshop. Also, all graphics on the site were of a reasonable size (less than 20k, most less than 2k) so that the page would load quickly. Technologies such as Macromedia Flash and Javascript were avoided, as these only function on some clients which have the proper software installed or enabled. The website was tested on different platforms with many different browsers to ensure there were no compatibility issues. The website was tested on windows with MS IE 6, MSIE 5 , Netscape 7, Mozilla and Opera. On a Mac, the site was tested with MS IE 5 , Netscape 7 and Safari.

  5. Flight Dynamics Analysis Branch

    NASA Technical Reports Server (NTRS)

    Stengle, Tom; Flores-Amaya, Felipe

    2000-01-01

    This report summarizes the major activities and accomplishments carried out by the Flight Dynamics Analysis Branch (FDAB), Code 572, in support of flight projects and technology development initiatives in fiscal year 2000. The report is intended to serve as a summary of the type of support carried out by the FDAB, as well as a concise reference of key accomplishments and mission experience derived from the various mission support roles. The primary focus of the FDAB is to provide expertise in the disciplines of flight dynamics, spacecraft trajectory, attitude analysis, and attitude determination and control. The FDAB currently provides support for missions and technology development projects involving NASA, government, university, and private industry.

  6. Strigolactone inhibition of shoot branching.

    PubMed

    Gomez-Roldan, Victoria; Fermas, Soraya; Brewer, Philip B; Puech-Pagès, Virginie; Dun, Elizabeth A; Pillot, Jean-Paul; Letisse, Fabien; Matusova, Radoslava; Danoun, Saida; Portais, Jean-Charles; Bouwmeester, Harro; Bécard, Guillaume; Beveridge, Christine A; Rameau, Catherine; Rochange, Soizic F

    2008-09-11

    A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence that carotenoid cleavage dioxygenase 8 shoot branching mutants of pea are strigolactone deficient and that strigolactone application restores the wild-type branching phenotype to ccd8 mutants. Moreover, we show that other branching mutants previously characterized as lacking a response to the branching inhibition signal also lack strigolactone response, and are not deficient in strigolactones. These responses are conserved in Arabidopsis. In agreement with the expected properties of the hormonal signal, exogenous strigolactone can be transported in shoots and act at low concentrations. We suggest that endogenous strigolactones or related compounds inhibit shoot branching in plants. Furthermore, ccd8 mutants demonstrate the diverse effects of strigolactones in shoot branching, mycorrhizal symbiosis and parasitic weed interaction.

  7. Branching toughens fibrous networks.

    PubMed

    Koh, C T; Oyen, M L

    2012-08-01

    Fibrous collagenous networks are not only stiff but also tough, due to their complex microstructures. This stiff yet tough behavior is desirable for both medical and military applications but it is difficult to reproduce in engineering materials. While the nonlinear hyperelastic behavior of fibrous networks has been extensively studied, the understanding of toughness is still incomplete. Here, we identify a microstructure mimicking the branched bundles of a natural type I collagen network, in which partially cross-linked long fibers give rise to novel combinations of stiffness and toughness. Finite element analysis shows that the stiffness of fully cross-linked fibrous networks is amplified by increasing the fibril length and cross-link density. However, a trade-off of such stiff networks is reduced toughness. By having partially cross-linked networks with long fibrils, the networks have comparable stiffness and improved toughness as compared to the fully cross-linked networks. Further, the partially cross-linked networks avoid the formation of kinks, which cause fibril rupture during deformation. As a result, the branching allows the networks to have stiff yet tough behavior.

  8. Pen Branch Fault Program

    SciTech Connect

    Price, V.; Stieve, A.L.; Aadland, R.

    1990-09-28

    Evidence from subsurface mapping and seismic reflection surveys at Savannah River Site (SRS) suggests the presence of a fault which displaces Cretaceous through Tertiary (90--35 million years ago) sediments. This feature has been described and named the Pen Branch fault (PBF) in a recent Savannah River Laboratory (SRL) paper (DP-MS-88-219). Because the fault is located near operating nuclear facilities, public perception and federal regulations require a thorough investigation of the fault to determine whether any seismic hazard exists. A phased program with various elements has been established to investigate the PBF to address the Nuclear Regulatory Commission regulatory guidelines represented in 10 CFR 100 Appendix A. The objective of the PBF program is to fully characterize the nature of the PBF (ESS-SRL-89-395). This report briefly presents current understanding of the Pen Branch fault based on shallow drilling activities completed the fall of 1989 (PBF well series) and subsequent core analyses (SRL-ESS-90-145). The results are preliminary and ongoing: however, investigations indicate that the fault is not capable. In conjunction with the shallow drilling, other activities are planned or in progress. 7 refs., 8 figs., 1 tab.

  9. Cravity modulation of the moss Tortula modica branching

    NASA Astrophysics Data System (ADS)

    Khorkavtsiv, Yaroslava; Kit, Nadja

    45-50 (o) to orthotropic stolon axes, and later it decreased negatively gravitropically. The bending of lateral branches of gravitropic protonemata is carried out in two stages: the light induction makes cells metabolically active, but not sensitive to gravitation, while the wall of daughter cell grows perpendicularly to the axes of mother cell and only after that the branches growth direction acquires dependent on gravitation fixed space orientation. Protonemata on light was branched under the angle 45-50 (o) to the axes of the main stolon, that caused similar phenotype of protonemata turf in many moss species. The growth of lateral branches and the set-point angle from the point of view of growth as physical process, is, perhaps, balanced by the action of gravitation and light, and is controlled endogenously by autotropic growth.

  10. Synthesis of branched polysaccharides with tunable degree of branching.

    PubMed

    Ciric, Jelena; Loos, Katja

    2013-03-01

    An in vitro enzyme-catalyzed tandem reaction using the enzymes phosphorylase b from rabbit muscle and Deinococcus geothermalis glycogen branching enzyme (Dg GBE) to obtain branched polyglucans with tunable degree of branching (2% ÷ 13%) is presented. The tunable degree of branching is obtained by varying the reaction conditions such as pH value, the choice of reducing agent and its concentration and reaction time. Linear amylose is formed by the phosphorylase-catalyzed propagation of glucose-1-phosphate while Dg GBE introduces branching points on the α-(1→6) position by relocating short oligosaccharide chains. Our results show that the best way to obtain different degrees of branching with this set of enzymes is by regulation of the reaction time.

  11. [The mechanism of phenoptosis: I. Age-dependent decrease of the overall rate of protein synthesis is caused by the programmed attenuation of bio-energetics].

    PubMed

    Trubitsyn, A G

    2009-01-01

    The age-dependent degradation of all vital processes of an organism can be result of influences of destructive factors (the stochastic mechanism of aging), or effect of realizations of the genetic program (phenoptosis). The stochastic free-radical theory of aging dominating now contradicts the set of empirical data, and the semicentenial attempts to create the means to slow down aging did not give any practical results. It makes obvious that the stochastic mechanism of aging is incorrect. At the same time, the alternative mechanism of the programmed aging is not developed yet but preconditions for it development have already been created. It is shown that the genes controlling process of aging exist (contrary to the customary opinion) and the increase in the level of damaged macromolecules (basic postulate of the free-radical theory) can be explained by programmed attenuation of bio-energetics. As the bio-energetics is a driving force of all vital processes, decrease of its level is capable to cause degradation of all functions of an organism. However to transform this postulate into a basis of the theory of phenoptosis it is necessary to show, that attenuation of bio-energetics predetermines such fundamental processes accompanying aging as decrease of the overall rate of protein biosynthesis, restriction of cellular proliferations (Hayflick limit), loss of telomeres etc. This article is the first step in this direction: the natural mechanism of interaction of overall rate of protein synthesis with a level of cellular bio-energetics is shown. This is built-in into the translation machine and based on dependence of recirculation rate of eukaryotic initiation factor 2 (elF2) from ATP/ADP value that is created by mitochondrial bio-energetic machine.

  12. Shift from depolarizing to hyperpolarizing glycine action in rat auditory neurones is due to age-dependent Cl− regulation

    PubMed Central

    Ehrlich, Ingrid; Löhrke, Stefan; Friauf, Eckhard

    1999-01-01

    The inhibitory neurotransmitter glycine can elicit depolarizing responses in immature neurones. We investigated the changes in glycine responses and their ionic mechanism in developing neurones of the rat lateral superior olive (LSO), an auditory brainstem nucleus involved in sound localization. Whole-cell and gramicidin perforated-patch recordings were performed from visually identified LSO neurones in brain slices and glycine was pressure applied for 3–100 ms to the soma. Glycine-evoked currents were reversibly blocked by strychnine. They were mostly monophasic, but biphasic responses occurred in ∼30% of P8-11 neurones in perforated-patch recordings. In whole-cell recordings from P2-11 neurones, the reversal potential of glycine-evoked currents (EGly) was determined by the transmembranous Cl− gradient and corresponded closely to the Nernst potential for Cl−, regardless of age. This indicates that Cl− is the principle ion permeating glycine receptors, but is also consistent with a low relative (10–20%) permeability for HCO3−. The Cl− gradient also determined the polarity and amplitude of glycine-evoked membrane potential changes. Leaving the native intracellular [Cl−] undisturbed with gramicidin perforated-patch recordings, we found a highly significant, age-dependent change of EGly from −46.8 ± 1.8 mV (P1-4, n = 28) to −67.6 ± 3.3 mV (P5-8, n = 10) to −82.2 ± 4.1 mV (P9–11, n = 18). The majority of P1–4 neurones were depolarized by glycine (∼80%) and spikes were evoked in ∼30%. In contrast, P9–11 neurones were hyperpolarized. In perforated-patch recordings, EGly was influenced by the voltage protocol and the glycine application interval; it could be shifted in the positive and negative direction. For a given application interval, these shifts were always larger in P1–4 than in P8–11 neurones, pointing to less effective Cl− regulation mechanisms in younger neurones. Furosemide (frusemide), a blocker of cation

  13. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  14. Observing Holliday junction branch migration one step at a time

    NASA Astrophysics Data System (ADS)

    Ha, Taekjip

    2004-03-01

    During genetic recombination, two homologous DNA molecules undergo strand exchange to form a four-way DNA (Holliday) junction and the recognition and processing of this species by branch migration and junction resolving enzymes determine the outcome. We have used single molecule fluorescence techniques to study two intrinsic structural dynamics of the Holliday junction, stacking conformer transitions and spontaneous branch migration. Our studies show that the dynamics of branch migration, resolved with one base pair resolution, is determined by the stability of conformers which in turn depends on the local DNA sequences. Therefore, the energy landscape of Holliday junction branch migation is not uniform, but is rugged.

  15. Absolute measurement of hadronic branching fractions of the Ds+ meson.

    PubMed

    Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; Lopez, A; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Rademacker, J; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L

    2008-04-25

    The branching fractions of D(s)(+/-) meson decays serve to normalize many measurements of processes involving charm quarks. Using 298 pb(-1) of e(+)e(-) collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight D(s)(+/-) decays with a double tag technique. In particular we determine the branching fraction B(D(s)(+)-->K(-)K(+}pi(+))=(5.50+/-0.23+/-0.16)%, where the uncertainties are statistical and systematic, respectively. We also provide partial branching fractions for kinematic subsets of the K(-)K(+)pi(+) decay mode.

  16. Methods and Technologies Branch (MTB)

    Cancer.gov

    The Methods and Technologies Branch focuses on methods to address epidemiologic data collection, study design and analysis, and to modify technological approaches to better understand cancer susceptibility.

  17. Branches in the Everett interpretation

    NASA Astrophysics Data System (ADS)

    Cunningham, Arthur J.

    2014-05-01

    Hugh Everett III describes a quantum measurement as resulting in the "branching" of the quantum state of observer and measured system, with all possible measurement outcomes represented by the ensuing branches of the total quantum state. But Everett does not specify a general rule for decomposing a quantum state into branches, and commentators have long puzzled over how, and even whether, to regard Everett's notion of branching states as physically meaningful. It is common today to appeal to decoherence considerations as a way of giving physical content to the Everettian notion of branches, but these appeals to decoherence are often regarded as considerations foreign to Everett's own approach. This paper contends that this assessment is only half right: though he does not invoke environmental decoherence, Everett does appeal to decoherence considerations, broadly understood, in his treatment of measurement. Careful consideration of his idealized models of measurement, and of the significance he ascribes to the branching of states corresponding to definite measurement outcomes, reveals that his notion of branching refers to a special physical characteristic of elements of a particular decomposition, namely the absence of interference between these component states as a result of the particular dynamics governing the evolution of the system. Characterizations of branching that appeal to the results of modern decoherence theory should therefore be regarded as a natural development of Everett's own physically meaningful conception of branching.

  18. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain.

    PubMed

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-11-07

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain.

  19. Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin

    PubMed Central

    Kinn, Patrick M.; Holdren, Grant O.; Westermeyer, Brittney A.; Abuissa, Mousa; Fischer, Carol L.; Fairley, Janet A.; Brogden, Kim A.; Brogden, Nicole K.

    2015-01-01

    In the skin, aging is associated with overall epidermal thinning, decreased barrier function, and gradual deterioration of the epidermal immune response. However, the presence and role of cytokines, chemokines, and biologic analytes (CCBAs) in immunosenescence are not known. Here we identified age-related changes in skin properties and CCBAs from stratum corneum of healthy human subjects, providing a means to utilize CCBAs as benchmarks for aging skin health. Transepidermal water loss and a(*) (skin redness) decreased in an age-dependent manner, and were significantly lower (p < 0.05) in Groups 2 (56.6 ± 4.6 years) and 3 (72.9 ± 3.0 years) vs. Group 1 (24.3 ± 2.8 years). In skin wash fluid, 48 CCBAs were detected; seven were significantly lower (p < 0.05) in Groups 2 and 3: EGF, FGF-2, IFNα2, IL-1RA, HSA, keratin-6, and involucrin; cortisol was significantly higher (p < 0.05) in Groups 2 and 3. Our results correspond with the pro-inflammatory shift that occurs with immunosenescence and also provides basis for understanding the inflammatory changes in normal aging skin. PMID:26035055

  20. Age-Dependent Expression of Collagen Receptors and Deformation of Type I Collagen Substrates by Rat Cardiac Fibroblasts

    PubMed Central

    Wilson, Christopher G.; Stone, John W.; Fowlkes, Vennece; Morales, Mary O.; Murphy, Catherine J.; Baxter, Sarah C.; Goldsmith, Edie C.

    2014-01-01

    Little is known about how age influences the ways in which cardiac fibroblasts interact with the extracellular matrix. We investigated the deformation of collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer and three-dimensional (3D) cultures, and quantified the expression of three collagen receptors [discoidin domain receptor (DDR) 1, DDR2, and β1 integrin] and the contractile protein alpha smooth muscle actin (α-SMA) in these cells. We report that adult fibroblasts contracted 3D collagen substrates significantly less than their neonate counterparts, whereas no differences were observed in monolayer cultures. Adult cells had lower expression of β1 integrin and α-SMA than neonate cultures, and we detected significant correlations between the expression of α-SMA and each of the collagen receptors in neonate cells but not in adult cells. Consistent with recent work demonstrating age-dependent interactions with myocytes, our results indicate that interactions between cardiac fibroblasts and the extracellular matrix change with age. PMID:21740617

  1. Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

    PubMed Central

    Vannucchi, M G; Goldman-Rakic, P S

    1991-01-01

    In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans. Images PMID:1763062

  2. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-02-27

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

  3. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  4. Dose and age-dependent axonal responses of embryonic trigeminal neurons to localized NGF via p75NTR receptor.

    PubMed

    Ozdinler, P Hande; Ulupinar, Emel; Erzurumlu, Reha S

    2005-02-05

    Nerve growth factor (NGF) and related neurotrophins are target-derived survival factors for sensory neurons. In addition, these peptides modulate neuronal differentiation, axon guidance, and synaptic plasticity. We tested axonal behavior of embryonic trigeminal neurons towards localized sources of NGF in collagen gel assays. Trigeminal axons preferentially grow towards lower doses of localized NGF and grow away from higher concentrations at earlier stages of development, but do not show this response later. Dorsal root ganglion axons also show similar responses to NGF, but NGF-dependent superior cervical ganglion axons do not. Such axonal responses to localized NGF sources were also observed in Bax-/- mice, suggesting that the axonal effects are largely independent of cell survival. Immunocytochemical studies indicated that axons, which grow towards or away from localized NGF are TrkA-positive, and TrkA-/- TG axons do not respond to any dose of NGF. We further show that axonal responses to NGF are absent in TG derived from mice that lack the p75 neurotrophin receptor (p75NTR). Collectively, our results suggest that localized sources of NGF can direct axon outgrowth from trigeminal ganglion in a dose- and age-dependent fashion, mediated by p75NTR signaling through TrkA expressing axons.

  5. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

    SciTech Connect

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-11-07

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain.

  6. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  7. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    PubMed Central

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  8. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    PubMed

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  9. Flat, Branched and Split Electrospun Fibers

    NASA Astrophysics Data System (ADS)

    Koombhongse, Sureeporn; Reneker, Darrell H.

    2001-03-01

    The electrospinning process uses electrical force to overcome the force from surface tension. As the electric field increases, the surface of a droplet becomes nearly conical and a charged jet flows from the vertex. The charged jet moves along a straight line for some distance and then begins a spiraling path, which is triggered by a bending instability.[1] The charged jet solidifies as it dries and electrospun nanofibers are collected. The electrospinning process normally produces cylindrical fibers, but sometimes the fibers are flat, branched or split. Flat fibers were electrospun from polystyrene (PS) and poly(2-hydroxyethyl methacrylate) (HEMA) solution. Flat fibers were formed by the collapse of a tube. Branched fibers of HEMA, PS and poly(vinylidene fluoride) were observed. The thinner branch was usually perpendicular to the axis of the primary jet. Branched fibers are formed by a smaller secondary jet ejected from the surface of the primary jet. The charged jet can split apart into two smaller jets to reduce the charge per unit surface area. Split fibers of HEMA, in which two smaller jets run parallel to the axis of the primary jet were observed. 1. D.H. Reneker, A.L. Yarin, H. Fong, and S. Koombhongse, J. Appl. Phys. 87, 4531 (2000).

  10. Modeling branching in cereals.

    PubMed

    Evers, Jochem B; Vos, Jan

    2013-10-10

    Cereals and grasses adapt their structural development to environmental conditions and the resources available. The primary adaptive response is a variable degree of branching, called tillering in cereals. Especially for heterogeneous plant configurations the degree of tillering varies per plant. Functional-structural plant modeling (FSPM) is a modeling approach allowing simulation of the architectural development of individual plants, culminating in the emergent behavior at the canopy level. This paper introduces the principles of modeling tillering in FSPM, using (I) a probability approach, forcing the dynamics of tillering to correspond to measured probabilities. Such models are particularly suitable to evaluate the effect structural variables on system performance. (II) Dose-response curves, representing a measured or assumed response of tillering to an environmental cue. (III) Mechanistic approaches to tillering including control by carbohydrates, hormones, and nutrients. Tiller senescence is equally important for the structural development of cereals as tiller appearance. Little study has been made of tiller senescence, though similar concepts seem to apply as for tiller appearance.

  11. Changes in NMDA receptor-induced cyclic nucleotide synthesis regulate the age-dependent increase in PDE4A expression in primary cortical cultures

    PubMed Central

    Hajjhussein, Hassan; Suvarna, Neesha U.; Gremillion, Carmen; Judson Chandler, L.; O’Donnell, James M.

    2007-01-01

    NMDA receptor-induced cAMP and cGMP are selectively hydrolyzed by PDE4 and PDE2, respectively, in rat primary cerebral cortical and hippocampal cultures. Because cAMP levels regulate the expression of PDE4 in rat primary cortical cultures, we examined the manner in which NMDA receptor activity regulates the age-dependent increase in the expression of PDE4A observed in vivo and in vitro. Inhibiting the activity of NR2B subunit with ifenprodil blocked NMDA receptor-induced cGMP synthesis and increased NMDA receptor-induced cAMP levels in a manner that reduced PDE4 activity. Therefore, NR1/NR2B receptor-induced cGMP signaling is involved in an acute cross-talk regulation of NR1/NR2A receptor-induced cAMP levels, mediated by PDE4. Chronic inhibition of NMDA receptor activity with MK-801 reduced PDE4A1 and PDE4A5 expression and activity in a time-dependent manner; this effect was reversed by adding the PKA activator dbr-cAMP. Inhibiting GABA receptors with bicuculline increased NMDA receptor-induced cAMP synthesis and PDE4A expression in cultures treated between DIV 16 and DIV 21 but not in cultures treated between DIV 8 and DIV 13. This effect was due to a high tone of NMDA receptor-induced cGMP in younger cultures, which negatively regulated the expression of PDE4A by a PKG-mediated process. The present results are consistent with behavioral data showing that both PDE4 and PDE2 are involved in NMDA receptor-mediated memory processes. PMID:17407767

  12. A Branch Meeting in Avon

    ERIC Educational Resources Information Center

    Vaughan, Kathryn; Coles, Alf

    2011-01-01

    The Association of Teachers of Mathematics (ATM) exists for, and is run by, its members. Branch meetings are so much more than the "grass roots" of the association--it can be a powerhouse of inspiration and creativity. In this article, the authors provide commentaries on a recent branch meeting.

  13. Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

    PubMed Central

    Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

    2015-01-01

    Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

  14. A positive approach to branching.

    PubMed

    Janssen, Bart J; Drummond, Revel S M; Ledger, Susan E; Snowden, Kimberley C

    2010-04-01

    Plants regulate the development of branches in response to environmental and developmental signals in order to maximize reproductive success. A number of hormone signals are involved in the regulation of branching and both their production and transmission affect axillary meristem outgrowth. With the identification of strigolactones as root-derived branch inhibitors it seems likely that a biochemical pathway starting from a carotenoid and resulting in production of a strigolactone hormone is present in most plants. Our observation that loss of CCD7 or CCD8 also results in production of a promoter of branching from roots shows the branching pathway has multiple levels of control which allows a high degree of sensitivity to subtle differences in environmental and developmental signals.

  15. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  16. Age-dependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women.

    PubMed

    Berthold, Heiner K; Unverdorben, Susanne; Zittermann, Armin; Degenhardt, Ralf; Baumeister, Bernhard; Unverdorben, Martin; Krone, Wilhelm; Vetter, Hans; Gouni-Berthold, Ioanna

    2004-06-01

    The use of HMG-CoA-reductase inhibitors (statins) has been associated with decreased risk of bone fractures in epidemiological studies. In vitro evidence suggests that statins may stimulate bone formation, but the data are still preliminary. We assessed the effects of the HMG-CoA-reductase inhibitor atorvastatin on biochemical parameters of bone metabolism in a multicenter, randomized, double-blind, placebo-controlled trial conducted between October 2001 and October 2002 in three hospital-based outpatient metabolism clinics. Forty-nine postmenopausal women, mean age 61 +/- 5 years, mean time postmenopause 12.6 +/- 8.8 years, were treated with atorvastatin, 20 mg per day ( n=24) or matching placebos ( n=25) for 8 weeks. Comparing the differences to baseline between the groups, there were no statistically significant effects of atorvastatin either on the bone formation markers intact osteocalcin and bone-specific alkaline phosphatase or on the bone resorption markers C-telopeptide and intact parathyroid hormone. The marker of bone fractures, undercarboxylated osteocalcin, was also unchanged. When analyzed in dependence of age, atorvastatin increased C-telopeptide and osteocalcin in the younger subjects, while it decreased them in older subjects. Most interestingly, in older subjects, atorvastatin caused a significant decrease in the ratio of C-telopeptide to osteocalcin, an indicator of bone remodeling, while the ratio was increased in younger subjects, suggesting beneficial effects on bone turnover exclusively in older individuals (approx. >63 years). In summary, the present data suggest that short-term treatment with atorvastatin may have age-dependent effects on biochemical markers of bone turnover in postmenopausal women.

  17. Inhibition of medullary raphe serotonergic neurons has age-dependent effects on the CO2 response in newborn piglets.

    PubMed

    Messier, Michelle L; Li, Aihua; Nattie, Eugene E

    2004-05-01

    Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2 response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2 before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2 response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO2 response and piglet age. Younger piglets showed an exaggerated CO2 response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2 response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2 response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

  18. Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats.

    PubMed

    Przybysz, K R; Werner, D F; Diaz, M R

    2017-02-03

    Anxiety disorders are one of the most common and debilitating mental illnesses worldwide. Growing evidence indicates an age-dependent rise in the incidence of anxiety disorders from adolescence through adulthood, suggestive of underlying neurodevelopmental mechanisms. Kappa opioid receptors (KORs) are known to contribute to the development and expression of anxiety; however, the functional role of KORs in the basolateral amygdala (BLA), a brain structure critical in mediating anxiety, particularly across ontogeny, are unknown. Using whole-cell patch-clamp electrophysiology in acute brain slices from adolescent (postnatal day (P) 30-45) and adult (P60+) male Sprague-Dawley rats, we found that the KOR agonist, U69593, increased the frequency of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in the adolescent BLA, without an effect in the adult BLA or on sIPSC amplitude at either age. The KOR effect was blocked by the KOR antagonist, nor-BNI, which alone did not alter GABA transmission at either age, and the effect of the KOR agonist was TTX-sensitive. Additionally, KOR activation did not alter glutamatergic transmission in the BLA at either age. In contrast, U69593 inhibited sIPSC frequency in the central amygdala (CeA) at both ages, without altering sIPSC amplitude. Western blot analysis of KOR expression indicated that KOR levels were not different between the two ages in either the BLA or CeA. This is the first study to provide compelling evidence for a novel and unique neuromodulatory switch in one of the primary brain regions involved in initiating and mediating anxiety that may contribute to the ontogenic rise in anxiety disorders.

  19. Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye

    PubMed Central

    Forward, Krisztina I.; Nguyen, Anthony T.; Bordbari, Matthew H.; Oltjen, Sharon L.; Hjelmeland, Leonard M.

    2014-01-01

    Purpose MicroRNA-34a (miR-34a) has been implicated in neurodegeneration. MiR-34a belongs to a signaling network involving p53 and Sirt-1. This network responds to DNA damage with further downstream signals that induce senescence or apoptosis. Our goal was to measure the expression level of miR-34a in the mouse retina and RPE as a function of age. Methods The age-dependent change in miR-34a expression was quantified using a real-time PCR (RT-PCR) assay on microRNA isolates from eye tissue: the retina and RPE/choroid (4, 18, 24, and 32 months of age). Tissue localization of miR-34a was determined by in situ hybridization (ISH) for a series of time points. Expression of the miR-34a target gene Sirt1 was analyzed using RT-PCR and immunohistochemistry. Results MiR-34a examined with real-time PCR showed a linear increase in expression with age when compared to that of 4-month-old mice. However, the level of expression between the 24 and 32-month-old animals showed mild downregulation. An age-related increase in miR-34a expression was confirmed in the mouse eye using in situ hybridization. An inverse relationship between the levels of expression of miR-34a and its target Sirt1 mRNA was found at 18 and 24 months of age. Conclusions Our data showed that miR-34a expression increased in the retina and RPE with age. The level of DNA damage in mitochondria in the retina and RPE followed a similar time course. This suggests that miR-34a may play a role in the senescence and apoptosis of the retina and RPE cells in the aging eye. PMID:25489229

  20. Neurogenesis upregulation on the healthy hemisphere after stroke enhances compensation for age-dependent decrease of basal neurogenesis.

    PubMed

    Adamczak, Joanna; Aswendt, Markus; Kreutzer, Christina; Rotheneichner, Peter; Riou, Adrien; Selt, Marion; Beyrau, Andreas; Uhlenküken, Ulla; Diedenhofen, Michael; Nelles, Melanie; Aigner, Ludwig; Couillard-Despres, Sebastien; Hoehn, Mathias

    2017-03-01

    Stroke is a leading cause of death and disability worldwide with no treatment for the chronic phase available. Interestingly, an endogenous repair program comprising inflammation and neurogenesis is known to modulate stroke outcome. Several studies have shown that neurogenesis decreases with age but the therapeutic importance of endogenous neurogenesis for recovery from cerebral diseases has been indicated as its ablation leads to stroke aggravation and worsened outcome. A detailed characterization of the neurogenic response after stroke related to ageing would help to develop novel and targeted therapies. In an innovative approach, we used the DCX-Luc mouse, a transgenic model expressing luciferase in doublecortin-positive neuroblasts, to monitor the neurogenic response following middle cerebral artery occlusion over three weeks in three age groups (2, 6, 12months) by optical imaging while the stroke lesion was monitored by quantitative MRI. The individual longitudinal and noninvasive time profiles provided exclusive insight into age-dependent decrease in basal neurogenesis and neurogenic upregulation in response to stroke which are not accessible by conventional BrdU-based measures of cell proliferation. For cortico-striatal strokes the maximal upregulation occurred at 4days post stroke followed by a continuous decrease to basal levels by three weeks post stroke. Older animals effectively compensated for reduced basal neurogenesis by an enhanced sensitivity to the cerebral lesion, resulting in upregulated neurogenesis levels approaching those measured in young mice. In middle aged and older mice, but not in the youngest ones, additional upregulation of neurogenesis was observed in the contralateral healthy hemisphere. This further substantiates the increased propensity of older brains to respond to lesion situation. Our results clearly support the therapeutic relevance of endogenous neurogenesis for stroke recovery and particularly in older brains.

  1. Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.

    PubMed

    Luan, Zhuo; Reddig, Keith; Li, Hong-Sheng

    2014-11-01

    The activity of Na(+)/K(+)-ATPase establishes transmembrane ion gradients and is essential to cell function and survival. Either dysregulation or deficiency of neuronal Na(+)/K(+)-ATPase has been implicated in the pathogenesis of many neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and rapid-onset dystonia Parkinsonism. However, genetic evidence that directly links neuronal Na(+)/K(+)-ATPase deficiency to in vivo neurodegeneration has been lacking. In this study, we use Drosophila photoreceptors to investigate the cell-autonomous effects of neuronal Na(+)/K(+) ATPase. Loss of ATPα, an α subunit of Na(+)/K(+)-ATPase, in photoreceptors through UAS/Gal4-mediated RNAi eliminated the light-triggered depolarization of the photoreceptors, rendering the fly virtually blind in behavioral assays. Intracellular recordings indicated that ATPα knockdown photoreceptors were already depolarized in the dark, which was due to a loss of intracellular K(+). Importantly, ATPα knockdown resulted in the degeneration of photoreceptors in older flies. This degeneration was independent of light and showed characteristics of apoptotic/hybrid cell death as observed via electron microscopy analysis. Loss of Nrv3, a Na(+)/K(+)-ATPase β subunit, partially reproduced the signaling and degenerative defects observed in ATPα knockdown flies. Thus, the loss of Na(+)/K(+)-ATPase not only eradicates visual function but also causes age-dependent degeneration in photoreceptors, confirming the link between neuronal Na(+)/K(+) ATPase deficiency and in vivo neurodegeneration. This work also establishes Drosophila photoreceptors as a genetic model for studying the cell-autonomous mechanisms underlying neuronal Na(+)/K(+) ATPase deficiency-mediated neurodegeneration.

  2. Mössbauer Spectra of Mouse Hearts reveal age-dependent changes in mitochondrial and ferritin iron levels.

    PubMed

    Wofford, Joshua D; Chakrabarti, Mrinmoy; Lindahl, Paul Alan

    2017-02-15

    Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from (57)Fe-enriched mice were evaluated by Mossbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood while the other was due to [Fe4S4](2+) clusters and Fe(II) hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE(-/-) mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE(-/-) livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2(-/-) hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the mothers heart contained low ferritin and normal levels of mitochondrial iron. High-spin Fe(II) ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mossbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets, and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation.

  3. Persistent changes of corticostriatal plasticity in dt(sz) mutant hamsters after age-dependent remission of dystonia.

    PubMed

    Avchalumov, Y; Volkmann, C E; Rückborn, K; Hamann, M; Kirschstein, T; Richter, A; Köhling, R

    2013-10-10

    Abnormal plasticity in the cortico-basal ganglia-thalamocortical loop has been suggested to represent a key factor in the pathophysiology of dystonia. In a model of primary paroxysmal dystonia, the dt(sz) mutant hamster, previous experiments have shown a strongly increased long-term potentiation (LTP) in comparison to non-dystonic control hamsters. These basal changes, i.e. in the absence of dystonia, were found in young animals at an age of 5 weeks, when the age-dependent dystonia in dt(sz) mutant reaches highest severity. In the present study we examined in corticostriatal slices (1) whether the increases in synaptic plasticity can be modulated by stressful stimuli which induce dystonic episodes in young mutant hamsters, and (2) whether increases of LTP persist after spontaneous remission of dystonia in animals older than 10 weeks. The present data show that in slices of young mutant hamsters the extent of LTP was not influenced by the presence of dystonia: In comparison to age-matched control hamsters, LTP was increased in mutant hamsters independent of preceding stressful stimulation. After remission of dystonia, i.e., in older dt(sz) mutant hamsters >10 weeks, only LTP could be elicited, while in preparations from age-matched control hamsters, either LTP or long-term depression developed, depending on previous behavioral challenge. We conclude that in mature brain, corticostriatal connections have the potential for changes in metaplasticity, while in dt(sz) mutant hamsters this metaplasticity is persistently infringed even though stress-inducible dystonic symptoms are lost.

  4. Age-dependent role of pre- and perinatal factors in interaction with genes on ADHD symptoms across adolescence.

    PubMed

    Brinksma, Djûke M; Hoekstra, Pieter J; van den Hoofdakker, Barbara; de Bildt, Annelies; Buitelaar, Jan K; Hartman, Catharina A; Dietrich, Andrea

    2017-02-21

    Little is known about the effects of risk factors on attention-deficit/hyperactivity disorder (ADHD) symptom over time. Here, we longitudinally studied the role of candidate genes, pre- and perinatal factors, and their interactions on ADHD symptoms between ages 10 and 18 years. Subjects were part of the general population or clinic-referred cohort of the TRacking Adolescents' Individual Lives Survey (n = 1667). At mean ages of 11.1 (T1), 13.4 (T2), and 16.2 years (T3), ADHD symptoms were assessed with the Child Behavior Checklist. Linear Mixed Models were used to examine the association of candidate genes (i.e., DRD4, DRD2, 5-HTTLPR, COMT, and MAOA), pre- and perinatal factors (i.e., index measure of various pregnancy and delivery complications, maternal smoking, maternal drinking, and low birth weight), and their interactions with ADHD symptoms across adolescence. Pregnancy and delivery complications were associated with a higher level of ADHD symptoms across all time points, but with a significantly declining influence over time (p = 0.006). We found no main effects of the candidate genes on ADHD symptoms throughout adolescence. The simultaneous presence of the low activity MAOA genotype and low birth weight (p < 0.001) and of the 5-HTTLPR LL-allele and respectively pregnancy and delivery complications (p = 0.04) and maternal smoking (p = 0.04) were associated with more ADHD symptoms particularly during early adolescence, and these influences significantly decreased over time. Findings suggest an age-dependent role of gene-environment interactions on ADHD symptoms across adolescence.

  5. Loss of Na+/K+-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration

    PubMed Central

    Luan, Zhuo; Reddig, Keith; Li, Hong-Sheng

    2014-01-01

    The activity of Na+/K+-ATPase establishes transmembrane ion gradients and is essential to cell function and survival. Either dysregulation or deficiency of neuronal Na+/K+-ATPase has been implicated in the pathogenesis of many neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and rapid-onset dystonia Parkinsonism. However, genetic evidence that directly links neuronal Na+/K+-ATPase deficiency to in vivo neurodegeneration has been lacking. In this study, we use Drosophila photoreceptors to investigate the cell-autonomous effects of neuronal Na+/K+ ATPase. Loss of ATPα, an α subunit of Na+/K+-ATPase, in photoreceptors through UAS/Gal4-mediated RNAi eliminated the light-triggered depolarization of the photoreceptors, rendering the fly virtually blind in behavioral assays. Intracellular recordings indicated that ATPα knockdown photoreceptors were already depolarized in the dark, which was due to a loss of intracellular K+. Importantly, ATPα knockdown resulted in the degeneration of photoreceptors in older flies. This degeneration was independent of light and showed characteristics of apoptotic/hybrid cell death as observed via electron microscopy analysis. Loss of Nrv3, a Na+/K+-ATPase β subunit, partially reproduced the signaling and degenerative defects observed in ATPα knockdown flies. Thus, loss of Na+/K+-ATPase not only eradicates visual function but also causes age-dependent degeneration in photoreceptors, confirming the link between neuronal Na+/K+ ATPase deficiency and in vivo neurodegeneration. This work also establishes Drosophila photoreceptors as a genetic model for studying the cell-autonomous mechanisms underlying neuronal Na+/K+ ATPase deficiency-mediated neurodegeneration. PMID:25205229

  6. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana.

    PubMed

    Saur, Isabel M L; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P

    2016-03-22

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined.

  7. Adult age-dependent differences in resting-state connectivity within and between visual-attention and sensorimotor networks

    PubMed Central

    Roski, Christian; Caspers, Svenja; Langner, Robert; Laird, Angela R.; Fox, Peter T.; Zilles, Karl; Amunts, Katrin; Eickhoff, Simon B.

    2013-01-01

    Healthy aging is accompanied by structural and functional changes in the brain, among which a loss of neural specificity (i.e., dedifferentiation) is one of the most consistent findings. Little is known, however, about changes in interregional integration underlying a dedifferentiation across different functional systems. In a large sample (n = 399) of healthy adults aged from 18 to 85 years, we analyzed age-dependent differences in resting-state (RS) (task-independent) functional connectivity (FC) of a set of brain regions derived from a previous fMRI study. In that study, these regions had shown an age-related loss of activation specificity in visual-attention (superior parietal area 7A and dorsal premotor cortex) or sensorimotor (area OP4 of the parietal operculum) tasks. In addition to these dedifferentiated regions, the FC analysis of the present study included “task-general” regions associated with both attention and sensorimotor systems (rostral supplementary motor area and bilateral anterior insula) as defined via meta-analytical co-activation mapping. Within this network, we observed both selective increases and decreases in RS-FC with age. In line with regional activation changes reported previously, we found diminished anti-correlated FC for inter-system connections (i.e., between sensorimotor-related and visual attention-related regions). Our analysis also revealed reduced FC between system-specific and task-general regions, which might reflect age-related deficits in top-down control possibly leading to dedifferentiation of task-specific brain activity. Together, our results underpin the notion that RS-FC changes concur with regional activity changes in the healthy aging brain, presumably contributing jointly to age-related behavioral changes. PMID:24194718

  8. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana

    PubMed Central

    Saur, Isabel M. L.; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J.; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P.

    2016-01-01

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined. PMID:26944079

  9. Thymic development of autoreactive T cells in NOD mice is regulated in an age-dependent manner.

    PubMed

    He, Qiuming; Morillon, Y Maurice; Spidale, Nicholas A; Kroger, Charles J; Liu, Bo; Sartor, R Balfour; Wang, Bo; Tisch, Roland

    2013-12-15

    Inefficient thymic negative selection of self-specific T cells is associated with several autoimmune diseases, including type 1 diabetes. The factors that influence the efficacy of thymic negative selection, as well as the kinetics of thymic output of autoreactive T cells remain ill-defined. We investigated thymic production of β cell-specific T cells using a thymus-transplantation model. Thymi from different aged NOD mice, representing distinct stages of type 1 diabetes, were implanted into NOD.scid recipients, and the diabetogenicity of the resulting T cell pool was examined. Strikingly, the development of diabetes-inducing β cell-specific CD4(+) and CD8(+) T cells was regulated in an age-dependent manner. NOD.scid recipients of newborn NOD thymi developed diabetes. However, recipients of thymi from 7- and 10-d-old NOD donor mice remained diabetes-free and exhibited a progressive decline in islet infiltration and β cell-specific CD4(+) and CD8(+) T cells. A similar temporal decrease in autoimmune infiltration was detected in some, but not all, tissues of recipient mice implanted with thymi from NOD mice lacking expression of the autoimmune regulator transcription factor, which develop multiorgan T cell-mediated autoimmunity. In contrast, recipients of 10 d or older thymi lacked diabetogenic T cells but developed severe colitis marked by increased effector T cells reactive to intestinal microbiota. These results demonstrate that thymic development of autoreactive T cells is limited to a narrow time window and occurs in a reciprocal manner compared with colonic microbiota-responsive T cells in NOD mice.

  10. Age-dependent survival of island vs. mainland populations of two avian scavengers: delving into migration costs.

    PubMed

    Sanz-Aguilar, Ana; De Pablo, Félix; Donázar, José Antonio

    2015-10-01

    Large terrestrial long-lived birds (including raptors) are typically sedentary on islands, even when they are migratory on the mainland. Density-dependent variation in the age at first breeding has been described as responsible for the long-term persistence of long-lived bird populations on islands. However, sedentary island populations may also benefit from higher survival rates derived from the absence of migration costs, especially for young individuals. Thus, sedentary island populations can mimic a natural experiment to study migration costs. We estimated the age-dependent survival of two sedentary raptors on the island of Menorca (Egyptian vultures Neophron percnopterus and red kites Milvus milvus) and compared these estimates with those reported for other migratory and sedentary populations. In Menorca, Egyptian vultures, but not red kites, showed low levels of human-related mortality resulting in extremely high survival probabilities, probably due to different diet choices and behavioral patterns. Juvenile Egyptian vultures and red kites in the studied population had lower survival probabilities than adults. This difference, however, was smaller than those reported for mainland migrant populations, which showed a lower juvenile survival rate. In fact, between-population comparisons suggested that survival of the young in migrant populations may be triggered by mortality factors in wintering areas. In contrast, adult survival may respond to mortality factors in breeding areas. Our results suggest that raptor species that become sedentary on islands may benefit from higher pre-breeder survival prospects in comparison with their mainland migrant counterparts. This fact, in combination with an earlier age at first reproduction, may facilitate their persistence.

  11. Age-dependent reduction of ghrelin- and motilin-induced contractile activity in the chicken gastrointestinal tract.

    PubMed

    Kitazawa, Takio; Yoshida, Akiko; Tamano, Takuya; Teraoka, Hiroki; Kaiya, Hiroyuki

    2013-05-01

    Ghrelin is an endogenous ligand for growth hormone secretagogue-receptor 1a (GHS-R1a) and stimulates gastrointestinal (GI) motility in the chicken. Since ghrelin stimulates GH release, which regulates growth, it might be interesting to compare ghrelin-induced responses in GI tract of different-aged chickens. Motilin is a ghrelin-related gut peptide that induces strong contraction in the small intestine. Aim of this study was to clarify age-dependent changes in ghrelin- and motilin-induced contractions of the chicken GI tract and expression of their receptor mRNAs. Chicken ghrelin caused contraction of the crop and proventriculus. Ghrelin-induced contraction in the proventriculus decreased gradually up to 100 days after hatching, but the responses to ghrelin in the crop were the same during the growth period. GHS-R1a mRNA expression in the crop tended to increase, but that in the proventriculus decreased depending on the age. Chicken motilin caused contraction of the chicken GI tract. Atropine decreased the responses to motilin in the proventriculus but not in the ileum. Motilin-induced contraction in the proventriculus but not that in the ileum decreased depending on post-hatching days. On the other hand, motilin receptor mRNA expression in every region of the GI tract decreased with age, but the decrease was more marked in the proventriculus than in the ileum. In conclusion, ghrelin- and motilin-induced GI contractions selectively decreased in the chicken proventriculus depending on post-hatching days, probably due to the age-related decrease in respective receptors expression. The results suggest an age-related contribution of ghrelin and motilin to the regulation of chicken GI motility.

  12. Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice

    PubMed Central

    Wang, Sheue-Er; Lin, Ching-Lung; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Background Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington’s disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice. Objective To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients. Methods The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques. Results R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue. Conclusion Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration. PMID:26609226

  13. Regenerative Sampling and Monotonic Branching Processes.

    DTIC Science & Technology

    1986-05-01

    clinical study of a potentially life-saving medical procedure because of its tendency to put more patients on the better treatment (Bartlett et al...Choose s such that s > 1 and r < s < p. Then by Minkowski and Holder inequalities (43) [lT n1 -u-mT nSJi/S zn-i E (E( Zk - 1 J jZk-mZkl sji/s k1 n-i...Zi < kl( 4j jS ZE Zk ’-1 IP]i/p Let q =asp/(p-s). Then by Lemma 1, for some 0 < (x < 1 Zkiq E(E((’ ’-1’LL2)’IF ( Zn~ Z n_2) n-l n-1n-2 (44) E (k) E(( n

  14. A branching process model for sand avalanches

    SciTech Connect

    Garcia-Pelayo, R.; Salazar, I.; Schieve, W.C. )

    1993-07-01

    An analytically solvable model for sand avalanches of noninteracting grains of sand, based on the Chapman-Kolmogorov equations, is presented. For a single avalanche, distributions of lifetimes, sizes of overflows and avalanches, and correlation functions are calculated. Some of these are exponentials, some are power laws. Spatially homogeneous distributions of avalanches are also studied. Computer simulations of avalanches of interacting grains of sand are compared to the solutions to the Chapman-Kolmogorov equations. It is found that within the range of parameters explored in the simulation, the approximation of noninteracting grains of sand is a good one. 20 refs., 4 figs.

  15. Nature of branching in disordered materials

    NASA Astrophysics Data System (ADS)

    Kulkarni, Amit S.

    reflect different features of the global structure, and it is categorically shown that this dimensional analysis results in effective structure characterization of these materials. Small-angle scattering of x-rays and neutrons can be used to quantify branch content and characterize the structure, through application of concepts native to fractal geometry. The application of the scaling model to nano-particulate aggregates yields quantitative information regarding the structure of these materials. In-situ small and ultra small angle x-ray scattering data collected on fumed silica and soot particles is presented in Chapter II. These measurements were performed at Advanced Photon Source, Argonne National Laboratory, UNICAT beam-line and the European Synchrotron Radiation Facility, Grenoble, France, ID2 beam-line. The dimensional analysis is successful in not only giving an average snap-shot of the nano-particulate aggregates, but also yields information regarding the growth processes involved in the complex pyrolysis technique of synthesizing these materials. In case of macromolecular systems, the minimum path dimension, dmin, is shown to reflect the thermodynamics of the system. This is categorically established in Chapter III on hyperbranched polymers, where the scaling model accurately predicts the good-solvent to theta-condition transition in these highly branched polymers with increasing molar mass. The scaling model is applied to the long standing problem of quantifying long chain branching in polyethylene in Chapter IV. Small angle neutron scattering data on dilute solutions of polyethylene were obtained at the Intense Pulsed Neutron Source (SAND beam-line); NIST center for Neutron Scattering (NG3 beam-line); and Los Alamos Neutron Scattering Center (LQD beam-line). This work, for the first time in literature, reports the length of a long chain branch in polyethylene in terms of the average molar mass of the branches, and the average number of carbon atoms in the long

  16. Sex differences in language asymmetry are age-dependent and small: a large-scale, consonant-vowel dichotic listening study with behavioral and fMRI data.

    PubMed

    Hirnstein, Marco; Westerhausen, René; Korsnes, Maria S; Hugdahl, Kenneth

    2013-01-01

    Men are often believed to have a functionally more asymmetrical brain organization than women, but the empirical evidence for sex differences in lateralization is unclear to date. Over the years we have collected data from a vast number of participants using the same consonant-vowel dichotic listening task, a reliable marker for language lateralization. One dataset comprised behavioral data from 1782 participants (885 females, 125 non-right-handers), who were divided in four age groups (children <10 yrs, adolescents = 10-15 yrs, younger adults = 16-49 yrs, and older adults >50 yrs). In addition, we had behavioral and functional imaging (fMRI) data from another 104 younger adults (49 females, aged 18-45 yrs), who completed the same dichotic listening task in a 3T scanner. This database allowed us to comprehensively test whether there is a sex difference in functional language lateralization. Across all participants and in both datasets a right ear advantage (REA) emerged, reflecting left-hemispheric language lateralization. Accordingly, the fMRI data revealed a leftward asymmetry in superior temporal lobe language processing areas. In the N = 1782 dataset no main effect of sex but a significant sex by age interaction emerged: the REA increased with age in both sexes but as a result of an earlier onset in females the REA was stronger in female than male adolescents. In turn, male younger adults showed greater asymmetry than female younger adults (accounting for <1% of variance). There were no sex differences in children and older adults. The males in the fMRI dataset (N = 104) also had a greater REA than females (accounting for 4% of variance), but no sex difference emerged in the neuroimaging data. Handedness did not affect these findings. Taken together, our findings suggest that sex differences in language lateralization as assessed with dichotic listening exist, but they are (a) not necessarily reflected in fMRI data, (b) age-dependent and (c) relatively small.

  17. Age-dependent changes in the sphingolipid composition of CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sphingolipid (SL4) composition can influence the biophysical properties of cell membranes. Additionally, specific SL modulate signaling pathways involved in proliferation, senescence, and apoptosis. We investigated age-dependent changes in the SL composition of CD4+ T cells, and the impact of these ...

  18. Simultaneous age-dependent and age-independent sexual selection in the lekking black grouse (Lyrurus tetrix).

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Soulsbury, Carl D

    2016-05-01

    Individuals' reproductive success is often strongly associated with their age, with typical patterns of early-life reproductive improvement and late-life senescence. These age-related patterns are due to the inherent trade-offs between life-history traits competing for a limited amount of resources available to the organisms. In males, such trade-offs are exacerbated by the resource requirements associated with the expression of costly sexual traits, leading to dynamic changes in trait expression throughout their life span. Due to the age dependency of male phenotypes, the relationship between the expression of male traits and mating success can also vary with male age. Hence, using longitudinal data in a lekking species with strong sexual selection - the black grouse Lyrurus tetrix - we quantified the effects of age, life span and age of first lek attendance (AFL) on male annual mating success (AMS) to separate the effects of within-individual improvement and senescence on AMS from selective (dis)appearance of certain phenotypes. Then, we used male AMS to quantify univariate and multivariate sexual selection gradients on male morphological and behavioural traits with and without accounting for age and age-related effects of other traits. Male AMS increased with age, and there was no significant reproductive senescence. Most males never copulated, and of the ones that did, the majority had only one successful year. Life span was unrelated to AMS, but early AFL tended to lead to higher AMS at ages 1-3. AMS was related to most morphological and behavioural traits when male age was ignored. Accounting for age and age-specific trait effects (i.e. the interaction between a trait and age) reduced the magnitude of the selection gradients and revealed that behavioural traits are under consistent sexual selection, while sexual selection on morphological traits is stronger in old males. Therefore, sexual selection in black grouse operates primarily on male behaviour and

  19. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    PubMed Central

    Bruun, Camilla S; Jørgensen, Claus B; Bay, Lene; Cirera, Susanna; Jensen, Henrik E; Leifsson, Páll S; Nielsen, Jens; Christensen, Knud; Fredholm, Merete

    2008-01-01

    Background A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs. Conclusion A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular

  20. Optimization of forest age-dependent light-use efficiency and its implications on climate-vegetation interactions in china

    NASA Astrophysics Data System (ADS)

    Li, Z.; Zhou, T.

    2015-04-01

    Forest's net primary productivity (NPP) is a key index in studying interactions of climate and vegetation, and accurate prediction of NPP is essential to understand the forests' response to climate change. The magnitude and trends of forest NPP not only depend on climate factors (e.g., temperature and precipitation), but also on the succession stages (i.e., forest stand age). Although forest stand age plays a significant role on NPP, it is usually ignored by remote sensing-based models. In this study, we used remote sensing data and meteorological data to estimate forest NPP in China based on CASA model, and then employed field observations to inversely estimate the parameter of maximum light-use efficiency (ɛmax) of forests in different stand ages. We further developed functions to describe the relationship between maximum light-use efficiency (ɛmax) and forest stand age, and estimated forest age-dependent NPP based on these functions. The results showed that ɛmax has changed according to forest types and the forest stand age. For deciduous broadleaf forest, the average ɛmax of young, middle-aged and mature forest are 0.68, 0.65 and 0.60 gC MJ-1. For evergreen broadleaf forest, the average ɛmax of young, middle-aged and mature forests are 1.05, 1.01 and 0.99 gC MJ-1. For evergreen needleleaf forest, the average ɛmax of young, middle-aged and mature forests are 0.72, 0.57 and 0.52 gC MJ-1.The NPP of young and middle-aged forests were underestimated based on a constant ɛmax. Young forests and middle-aged forests had higher ɛmax, and they were more sensitive to trends and fluctuations of climate change, so they led to greater annual fluctuations of NPP. These findings confirm the importance of considering forest stand age to the estimation of NPP and they are significant to study the response of forests to climate change.

  1. Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

    PubMed Central

    Shimono, Kohei; Fujimoto, Azusa; Tsuyama, Taiichi; Yamamoto-Kochi, Misato; Sato, Motohiko; Hattori, Yukako; Sugimura, Kaoru; Usui, Tadao; Kimura, Ken-ichi; Uemura, Tadashi

    2009-01-01

    Background For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of Drosophila multidendritic sensory neurons - the dendritic arborization (da) neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary. Results We identified multidendritic neurons in the adult Drosophila abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4) of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post-eclosion growth. It exhibited

  2. Cost Reporting at a Navy Branch Clinic

    DTIC Science & Technology

    1993-03-01

    focusing on fundamental cost ingredients . D. EVALUATING ACTIVITIES An activity is a process or workload pattern that can be quantified. Once the...Field [Group ISubgroup Activity Based Costing, James Brimson, Navy Branch Medical Clinic, Full Cost I I - Reporting, Fixed and Variable Costs 19...model, costs are disaggregated into fixed and variable components. Using the Brimson approach, the thesis further explores the application of activity

  3. Asymptotics of Simple Branching Populations

    NASA Astrophysics Data System (ADS)

    Huillet, Thierry; Kłopotowski, Andrzej; Porzio, Anna

    1995-09-01

    In this paper we study a simple deterministic tree structure: an initial individual generates a finite number of offspring, each of which has given integer valued lifetime, iterating the same procedure when dying. Three asymptotic distributions of this asynchronous deterministic branching procedure are considered: the generation distribution, the ability of individuals to generate offspring and the age distribution. Thermodynamic formalism is then developped to reveal the multifractal nature of the mass splitting associated to our process. On considère l'itération d'une structure déterministe arborescente selon laquelle un ancêtre engendre un nombre fini de descendants dont la durée de vie (à valeurs entières) est donnée. Dans un premier temps on s'intéresse aux trois distributions asymptotiques suivantes : répartition des générations, aptitude à engendrer des descendants et répartition selon l'âge. Ensuite nous développons le formalisme thermodynamique pour mettre en évidence le caractère multifractal de la scission d'une masse unitaire associée à cette arborescence.

  4. Electrical communication in branching arterial networks.

    PubMed

    Tran, Cam Ha T; Vigmond, Edward J; Goldman, Daniel; Plane, France; Welsh, Donald G

    2012-09-15

    Electrical communication and its role in blood flow regulation are built on an examination of charge movement in single, isolated vessels. How this process behaves in broader arterial networks remains unclear. This study examined the nature of electrical communication in arterial structures where vessel length and branching were varied. Analysis began with the deployment of an existing computational model expanded to form a variable range of vessel structures. Initial simulations revealed that focal endothelial stimulation generated electrical responses that conducted robustly along short unbranched vessels and to a lesser degree lengthened arteries or branching structures retaining a single branch point. These predictions matched functional observations from hamster mesenteric arteries and support the idea that an increased number of vascular cells attenuate conduction by augmenting electrical load. Expanding the virtual network to 31 branches revealed that electrical responses increasingly ascended from fifth- to first-order arteries when the number of stimulated distal vessels rose. This property enabled the vascular network to grade vasodilation and network perfusion as revealed through blood flow modeling. An elevation in endothelial-endothelial coupling resistance, akin to those in sepsis models, compromised this ascension of vasomotor/perfusion responses. A comparable change was not observed when the endothelium was focally disrupted to mimic disease states including atherosclerosis. In closing, this study highlights that vessel length and branching play a role in setting the conduction of electrical phenomenon along resistance arteries and within networks. It also emphasizes that modest changes in endothelial function can, under certain scenarios, impinge on network responsiveness and blood flow control.

  5. Analysis of the uncertainties associated with the age-dependent thyroid doses and risk of thyroid cancer due to exposure to {sup 131}I

    SciTech Connect

    Hoffman, F.O.; Apostoaei, A.I.; Nair, S.K.

    1996-06-01

    Effects on the thyroid gland due to exposure to {sup 131}I are currently of interest for ongoing retrospective studies of historical releases in Oak Ridge, Tennessee, and Hanford, Washington. Most of the work to date has been limited to dose estimation. This work focuses on estimating both dose and risk of thyroid cancer to an exposed individual. The age-dependent thyroid dose is calculated using a standard metabolic model for iodine. Updated information on thyroid mass from measurements using modem ultrasound techniques was used. The age-dependent risk is calculated using a linear excess relative risk model. An analysis of uncertainties in dose and risk estimates was performed for an individual in a population characterized by the mass of thyroid, by the iodine metabolic parameters, by the background incidence of thyroid cancer and by the excess relative risk per Gy of absorbed dose. The uncertainty analysis was performed using Monte-Carlo simulation, by considering the age-dependent parameters as random functions. The correlation between the metabolic age-dependent parameters was considered explicitly. Special attention is given to a modifying factor that accounts for the effectiveness of {sup 131}I in inducing thyroid cancer as compared to gamma irradiation, for which most of the excess risk factors are derived. This factor is based on review of recent literature and on informal interviews with outside experts, and thus, the expressed uncertainty is subjective in nature. The paper summarizes the age-dependent dose conversion factors (Sv Bq{sup -1}) and slope factors (risk Bq{sup -1}) as well as the uncertainty associated with them. An analysis that identifies the parameters of dominant importance by their contributions to the overall uncertainty is also included.

  6. Novel side branch ostial stent.

    PubMed

    Chen, Shao-Liang; Lv, Shu-Zheng; Kwan, Tak W

    2009-04-01

    Bifurcation lesions are technically challenging and plagued by a high incidence of restenosis, especially at the side branch orifice, which results in a more frequent need for revascularization during the follow-up period. This report discusses two clinical experiences with a novel side branch ostial stent, the BIGUARD stent, designed for the treatment of bifurcation lesions; procedural success with no in-hospital complications was observed in types IVb and Ia lesions.

  7. Structural Mechanics and Dynamics Branch

    NASA Technical Reports Server (NTRS)

    Stefko, George

    2003-01-01

    The 2002 annual report of the Structural Mechanics and Dynamics Branch reflects the majority of the work performed by the branch staff during the 2002 calendar year. Its purpose is to give a brief review of the branch s technical accomplishments. The Structural Mechanics and Dynamics Branch develops innovative computational tools, benchmark experimental data, and solutions to long-term barrier problems in the areas of propulsion aeroelasticity, active and passive damping, engine vibration control, rotor dynamics, magnetic suspension, structural mechanics, probabilistics, smart structures, engine system dynamics, and engine containment. Furthermore, the branch is developing a compact, nonpolluting, bearingless electric machine with electric power supplied by fuel cells for future "more electric" aircraft. An ultra-high-power-density machine that can generate projected power densities of 50 hp/lb or more, in comparison to conventional electric machines, which generate usually 0.2 hp/lb, is under development for application to electric drives for propulsive fans or propellers. In the future, propulsion and power systems will need to be lighter, to operate at higher temperatures, and to be more reliable in order to achieve higher performance and economic viability. The Structural Mechanics and Dynamics Branch is working to achieve these complex, challenging goals.

  8. Quantitative macroinvertebrate survey of Pen Branch and Indian Grave Branch

    SciTech Connect

    Not Available

    1989-02-01

    A total of 80 species were collected at all sites on Pen Branch and Indian Grave Branch during the 28 day period for colonization of the multiplate artificial substrate samplers. The two upstream sites demonstrated the highest species richness. During the sampling interval a release of significant proportion entered Indian Grave Branch, affecting all downstream sites. This effect was most severe at sites 3, 4, and 7, apparently resulting in heavy scouring of the multiplate samplers. Nevertheless, much colonization did occur at sites 3 and 4, with hydropsychid caddisflies, blackflies and midges predominant. At sites 5 and 6 a greater degree of recovery was noted, due to the lessened scouring in the broad floodplain. These downstream sites had significant numbers of mayflies along with the numerous midges. Considered overall, colonization during the period since the K Reactor has ceased releasing thermal effluent into Pen Branch and Indian Grave Branch has been substantial, introducing a substantial proportion of the species known from other nearby streams. 29 tabs.

  9. Fort Collins Science Center Ecosystem Dynamics Branch

    USGS Publications Warehouse

    Wilson, Jim; Melcher, C.; Bowen, Z.

    2009-01-01

    Complex natural resource issues require understanding a web of interactions among ecosystem components that are (1) interdisciplinary, encompassing physical, chemical, and biological processes; (2) spatially complex, involving movements of animals, water, and airborne materials across a range of landscapes and jurisdictions; and (3) temporally complex, occurring over days, weeks, or years, sometimes involving response lags to alteration or exhibiting large natural variation. Scientists in the Ecosystem Dynamics Branch of the U.S. Geological Survey, Fort Collins Science Center, investigate a diversity of these complex natural resource questions at the landscape and systems levels. This Fact Sheet describes the work of the Ecosystems Dynamics Branch, which is focused on energy and land use, climate change and long-term integrated assessments, herbivore-ecosystem interactions, fire and post-fire restoration, and environmental flows and river restoration.

  10. Phenomenological picture of fluctuations in branching random walks.

    PubMed

    Mueller, A H; Munier, S

    2014-10-01

    We propose a picture of the fluctuations in branching random walks, which leads to predictions for the distribution of a random variable that characterizes the position of the bulk of the particles. We also interpret the 1/sqrt[t] correction to the average position of the rightmost particle of a branching random walk for large times t≫1, computed by Ebert and Van Saarloos, as fluctuations on top of the mean-field approximation of this process with a Brunet-Derrida cutoff at the tip that simulates discreteness. Our analytical formulas successfully compare to numerical simulations of a particular model of a branching random walk.

  11. Phenomenological picture of fluctuations in branching random walks

    NASA Astrophysics Data System (ADS)

    Mueller, A. H.; Munier, S.

    2014-10-01

    We propose a picture of the fluctuations in branching random walks, which leads to predictions for the distribution of a random variable that characterizes the position of the bulk of the particles. We also interpret the 1 /√{t } correction to the average position of the rightmost particle of a branching random walk for large times t ≫1 , computed by Ebert and Van Saarloos, as fluctuations on top of the mean-field approximation of this process with a Brunet-Derrida cutoff at the tip that simulates discreteness. Our analytical formulas successfully compare to numerical simulations of a particular model of a branching random walk.

  12. LETTER TO THE EDITOR: Quantum field theory and phylogenetic branching

    NASA Astrophysics Data System (ADS)

    Jarvis, P. D.; Bashford, J. D.

    2001-12-01

    A calculational framework is proposed for phylogenetics, using nonlocal quantum field theories in hypercubic geometry. Quadratic terms in the Hamiltonian give the underlying Markov dynamics, while higher degree terms represent branching events. The spatial dimension L is the number of leaves of the evolutionary tree under consideration. Momentum conservation modulo ←1 scattering corresponds to tree edge labelling using binary L-vectors. The bilocal quadratic term allows for momentum-dependent rate constants - only the tree or trees compatible with selected nonzero edge rates contribute to the branching probability distribution. Applications to models of evolutionary branching processes are discussed.

  13. The need for T₂ correction on MRS-based vertebral bone marrow fat quantification: implications for bone marrow fat fraction age dependence.

    PubMed

    Dieckmeyer, Michael; Ruschke, Stefan; Cordes, Christian; Yap, Samuel P; Kooijman, Hendrik; Hauner, Hans; Rummeny, Ernst J; Bauer, Jan S; Baum, Thomas; Karampinos, Dimitrios C

    2015-04-01

    Vertebral bone marrow fat quantification using single-voxel MRS is confounded by overlapping water-fat peaks and the difference in T2 relaxation time between water and fat components. The purposes of the present study were: (i) to determine the proton density fat fraction (PDFF) of vertebral bone marrow using single-voxel multi-TE MRS, addressing these confounding effects; and (ii) to investigate the implications of these corrections with respect to the age dependence of the PDFF. Single-voxel MRS was performed in the L5 vertebral body of 86 subjects (54 women and 32 men). To reliably extract the water peak from the overlying fat peaks, the mean bone marrow fat spectrum was characterized based on the area of measurable fat peaks and an a priori knowledge of the chemical triglyceride structure. MRS measurements were performed at multiple TEs. The T2 -weighted fat fraction was calculated at each TE. In addition, a T2 correction was performed to obtain the PDFF and the T2 value of water (T2w ) was calculated. The implications of the T2 correction were investigated by studying the age dependence of the T2 -weighted fat fractions and the PDFF. Compared with the PDFF, all T2 -weighted fat fractions significantly overestimated the fat fraction. Compared with the age dependence of the PDFF, the age dependence of the T2 -weighted fat fraction showed an increased slope and intercept as TE increased for women and a strongly increased intercept as TE increased for men. For women, a negative association between the T2 value of bone marrow water and PDFF was found. Single-voxel MRS-based vertebral bone marrow fat quantification should be based on a multi-TE MRS measurement to minimize confounding effects on PDFF determination, and also to allow the simultaneous calculation of T2w , which might be considered as an additional parameter sensitive to the composition of the water compartment.

  14. Fault Branching and Rupture Directivity

    NASA Astrophysics Data System (ADS)

    Dmowska, R.; Rice, J. R.; Kame, N.

    2002-12-01

    Can the rupture directivity of past earthquakes be inferred from fault geometry? Nakata et al. [J. Geogr., 1998] propose to relate the observed surface branching of fault systems with directivity. Their work assumes that all branches are through acute angles in the direction of rupture propagation. However, in some observed cases rupture paths seem to branch through highly obtuse angles, as if to propagate ``backwards". Field examples of that are as follows: (1) Landers 1992. When crossing from the Johnson Valley to the Homestead Valley (HV) fault via the Kickapoo (Kp) fault, the rupture from Kp progressed not just forward onto the northern stretch of the HV fault, but also backwards, i.e., SSE along the HV [Sowers et al., 1994, Spotila and Sieh, 1995, Zachariasen and Sieh, 1995, Rockwell et al., 2000]. Measurements of surface slip along that backward branch, a prominent feature of 4 km length, show right-lateral slip, decreasing towards the SSE. (2) At a similar crossing from the HV to the Emerson (Em) fault, the rupture progressed backwards along different SSE splays of the Em fault [Zachariasen and Sieh, 1995]. (3). In crossing from the Em to Camp Rock (CR) fault, again, rupture went SSE on the CR fault. (4). Hector Mine 1999. The rupture originated on a buried fault without surface trace [Li et al., 2002; Hauksson et al., 2002] and progressed bilaterally south and north. In the south it met the Lavic Lake (LL) fault and progressed south on it, but also progressed backward, i.e. NNW, along the northern stretch of the LL fault. The angle between the buried fault and the northern LL fault is around -160o, and that NNW stretch extends around 15 km. The field examples with highly obtuse branch angles suggest that there may be no simple correlation between fault geometry and rupture directivity. We propose that an important distinction is whether those obtuse branches actually involved a rupture path which directly turned through the obtuse angle (while continuing

  15. Age-Dependent Modifications of AMPA Receptor Subunit Expression Levels and Related Cognitive Effects in 3xTg-AD Mice

    PubMed Central

    Cantanelli, Pamela; Sperduti, Samantha; Ciavardelli, Domenico; Stuppia, Liborio; Gatta, Valentina; Sensi, Stefano Luca

    2014-01-01

    GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca2+-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q–R substitution, a key factor in the regulation of AMPAR Ca2+-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca2+ and Zn2+. The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer’s disease (AD). With quantitative real-time PCR analysis, we assayed hippocampal mRNA expression levels of GluA1–4 subunits occurring in young [3 months of age (m.o.a.)] and old (12 m.o.a) Tg-AD mice and made comparisons with levels found in age-matched wild type (WT) mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for learning short- and long-term spatial memory with the Morris Water Maze (MWM) navigation task. 3xTg-AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg-AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1–4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in

  16. Vaccination against rubella: Analysis of the temporal evolution of the age-dependent force of infection and the effects of different contact patterns

    NASA Astrophysics Data System (ADS)

    Amaku, M.; Coutinho, F. A.; Azevedo, R. S.; Burattini, M. N.; Lopez, L. F.; Massad, E.

    2003-05-01

    In this paper, we analyze the temporal evolution of the age-dependent force of infection and incidence of rubella, after the introduction of a very specific vaccination program in a previously nonvaccinated population where rubella was in endemic steady state. We deduce an integral equation for the age-dependent force of infection, which depends on a number of parameters that can be estimated from the force of infection in a steady state prior to the vaccination program. We present the results of our simulations, which are compared with observed data. We also examine the influence of contact patterns among members of a community on the age-dependent intensity of transmission of rubella and on the results of vaccination strategies. As an example of the theory proposed, we calculate the effects of vaccination strategies for four communities from Caieiras (Brazil), Huixquilucan (Mexico), Finland, and the United Kingdom. The results for each community differ considerably according to the distinct intensity and pattern of transmission in the absence of vaccination. We conclude that this simple vaccination program is not very efficient (very slow) in the goal of eradicating the disease. This gives support to a mixed strategy, proposed by Massad et al., accepted and implemented by the government of the State of São Paulo, Brazil.

  17. 30 CFR 57.6403 - Branch circuits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Branch circuits. 57.6403 Section 57.6403... Blasting-Surface and Underground § 57.6403 Branch circuits. (a) If electric blasting includes the use of branch circuits, each branch shall be equipped with a safety switch or equivalent method to isolate...

  18. 30 CFR 56.6403 - Branch circuits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Branch circuits. 56.6403 Section 56.6403... Blasting § 56.6403 Branch circuits. (a) If electric blasting includes the use of branch circuits, each branch shall be equipped with a safety switch or equivalent method to isolate the circuits to be used....

  19. 17 CFR 166.4 - Branch offices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Branch offices. 166.4 Section... RULES § 166.4 Branch offices. Each branch office of each Commission registrant must use the name of the.... The act, omission or failure of any person acting for the branch office, within the scope of...

  20. Double-branched vortex generator

    NASA Technical Reports Server (NTRS)

    Cantwell, E. R.; Westphal, R. V.; Mehta, R. D.

    1985-01-01

    In order to assess the suitability of using a double branched vortex generator in parametric studies involving vortex interactions, an experimental study of the main vortex and secondary flows produced by a double branched vortex generator was conducted in a 20-by-40 cm indraft wind tunnel. Measurements of the cross flow velocities were made with a five hole pressure probe from which vorticity contours and vortex parameters were derived. The results showed that the optimum configuration consisted of chord extensions with the absence of a centerbody.

  1. The effect of thermal pressurization on dynamic fault branching

    NASA Astrophysics Data System (ADS)

    Urata, Yumi; Hok, Sébastien; Fukuyama, Eiichi; Madariaga, Raúl

    2014-02-01

    We numerically investigate the effect of thermal pressurization (TP) on fault branch behaviour during dynamic rupture propagation, a situation likely to occur during large earthquakes at subduction interfaces. We consider a 2-D mode II (in-plane) rupture in an infinite medium that propagates spontaneously along a planar main fault and encounters an intersection with a pre-existing branching fault. The fault system is subjected to uniform external stresses. We adopt the values used by Kame et al. We use the 2-D boundary integral equation method and the slip-weakening friction law with a Coulomb failure criterion, allowing the effective normal stress to vary as pore pressure changes due to TP. We reveal that TP can alter rupture propagation paths when the dip angle of the main fault is small. The rupture propagation paths depend on the branching angle when TP is not in effect on either of the faults, as described by Kame et al. However, the dynamic rupture processes are controlled more by TP than by the branching angle. When TP is in effect on the main fault only, the rupture propagates along the main fault. It propagates along the branch when TP is in effect on both faults. Finally, we considered the case where there is a free surface above the branch fault system. In this case, the rupture can propagate along both faults because of interaction between the free surface and the branch fault, in addition to TP on the main fault.

  2. Legislative Branch Appropriations Act, 2010

    THOMAS, 111th Congress

    Rep. Wasserman Schultz, Debbie [D-FL-20

    2009-06-17

    10/01/2009 Became Public Law No: 111-68. (PDF) (All Actions) Notes: Division A is the Legislative Branch Appropriations Act, 2010. Division B is the Continuing Appropriations Resolution, 2010. Tracker: This bill has the status Became LawHere are the steps for Status of Legislation:

  3. Legislative Branch Appropriations Act, 2010

    THOMAS, 111th Congress

    Rep. Wasserman Schultz, Debbie [D-FL-20

    2009-06-17

    10/01/2009 Became Public Law No: 111-68. (TXT | PDF) (All Actions) Notes: Division A is the Legislative Branch Appropriations Act, 2010. Division B is the Continuing Appropriations Resolution, 2010. Tracker: This bill has the status Became LawHere are the steps for Status of Legislation:

  4. Branching of keratin intermediate filaments.

    PubMed

    Nafeey, Soufi; Martin, Ines; Felder, Tatiana; Walther, Paul; Felder, Edward

    2016-06-01

    Keratin intermediate filaments (IFs) are crucial to maintain mechanical stability in epithelial cells. Since little is known about the network architecture that provides this stiffness and especially about branching properties of filaments, we addressed this question with different electron microscopic (EM) methods. Using EM tomography of high pressure frozen keratinocytes, we investigated the course of several filaments in a branching of a filament bundle. Moreover we found several putative bifurcations in individual filaments. To verify our observation we also visualized the keratin network in detergent extracted keratinocytes with scanning EM. Here bifurcations of individual filaments could unambiguously be identified additionally to bundle branchings. Interestingly, identical filament bifurcations were also found in purified keratin 8/18 filaments expressed in Escherichia coli which were reassembled in vitro. This excludes that an accessory protein contributes to the branch formation. Measurements of the filament cross sectional areas showed various ratios between the three bifurcation arms. This demonstrates that intermediate filament furcation is very different from actin furcation where an entire new filament is attached to an existing filament. Instead, the architecture of intermediate filament bifurcations is less predetermined and hence consistent with the general concept of IF formation.

  5. NCI: DCTD: Biometric Research Branch

    Cancer.gov

    The Biometric Research Branch (BRB) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  6. NCI: DCTD: Biometric Research Branch

    Cancer.gov

    The Biometric Research Branch (BRP) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  7. Risk Factor Assessment Branch (RFAB)

    Cancer.gov

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  8. 76 FR 13272 - Branch Offices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Office of Thrift Supervision Branch Offices AGENCY: Office of Thrift Supervision (OTS), Treasury. ACTION... 1995, 44 U.S.C. 3507. The Office of Thrift Supervision within the Department of the Treasury...

  9. Multiple pathways regulate shoot branching

    PubMed Central

    Rameau, Catherine; Bertheloot, Jessica; Leduc, Nathalie; Andrieu, Bruno; Foucher, Fabrice; Sakr, Soulaiman

    2015-01-01

    Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TEOSINTE BRANCHED1, CYCLOIDEA, PCF transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply. PMID:25628627

  10. On extreme events for non-spatial and spatial branching Brownian motions

    NASA Astrophysics Data System (ADS)

    Avan, Jean; Grosjean, Nicolas; Huillet, Thierry

    2015-04-01

    We study the impact of having a non-spatial branching mechanism with infinite variance on some parameters (height, width and first hitting time) of an underlying Bienaymé-Galton-Watson branching process. Aiming at providing a comparative study of the spread of an epidemics whose dynamics is given by the modulus of a branching Brownian motion (BBM) we then consider spatial branching processes in dimension d, not necessarily integer. The underlying branching mechanism is either a binary branching model or one presenting infinite variance. In particular we evaluate the chance p(x) of being hit if the epidemics started away at distance x. We compute the large x tail probabilities of this event, both when the branching mechanism is regular and when it exhibits very large fluctuations.

  11. Developmental morphology of branching flowers in Nymphaea prolifera.

    PubMed

    Grob, Valentin; Moline, Philip; Pfeifer, Evelin; Novelo, Alejandro R; Rutishauser, Rolf

    2006-11-01

    Nymphaea and Nuphar (Nymphaeaceae) share an extra-axillary mode of floral inception in the shoot apical meristem (SAM). Some leaf sites along the ontogenetic spiral are occupied by floral primordia lacking a subtending bract. This pattern of flower initiation in leaf sites is repeated inside branching flowers of Nymphaea prolifera (Central and South America). Instead of fertile flowers this species usually produces sterile tuberiferous flowers that act as vegetative propagules. N. prolifera changes the meristem identity from reproductive to vegetative or vice versa repeatedly. Each branching flower first produces some perianth-like leaves, then it switches back to the vegetative meristem identity of the SAM with the formation of foliage leaves and another set of branching flowers. This process is repeated up to three times giving rise to more than 100 vegetative propagules. The developmental morphology of the branching flowers of N. prolifera is described using both microtome sections and scanning electron microscopy.

  12. Age-dependent changes in diastolic Ca{sup 2+} and Na{sup +} concentrations in dystrophic cardiomyopathy: Role of Ca{sup 2+} entry and IP{sub 3}

    SciTech Connect

    Mijares, Alfredo; Altamirano, Francisco; Kolster, Juan; Adams, José A.; López, José R.

    2014-10-03

    Highlights: • Age-dependent increase in [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} in mdx cardiomyocytes. • Gadolinium significantly reduced both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages. • IP{sub 3}-pathway inhibition reduced cations concentrations in dystrophic cardiomyocytes. - Abstract: Duchenne muscular dystrophy (DMD) is a lethal X-inherited disease caused by dystrophin deficiency. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with a dilated cardiomyopathy that leads to progressive heart failure at the end of the second decade. The aim of the present study was to characterize the diastolic Ca{sup 2+} concentration ([Ca{sup 2+}]{sub d}) and diastolic Na{sup +} concentration ([Na{sup +}]{sub d}) abnormalities in cardiomyocytes isolated from 3-, 6-, 9-, and 12-month old mdx mice using ion-selective microelectrodes. In addition, the contributions of gadolinium (Gd{sup 3+})-sensitive Ca{sup 2+} entry and inositol triphosphate (IP{sub 3}) signaling pathways in abnormal [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} were investigated. Our results showed an age-dependent increase in both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd{sup 3+} treatment significantly reduced both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages. In addition, blockade of the IP{sub 3}-pathway with either U-73122 or xestospongin C significantly reduced ion concentrations in dystrophic cardiomyocytes. Co-treatment with U-73122 and Gd{sup 3+} normalized both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages in dystrophic cardiomyocytes. These data showed that loss of dystrophin in mdx cardiomyocytes produced an age-dependent intracellular Ca{sup 2+} and Na{sup +} overload mediated at least in part by enhanced Ca{sup 2+} entry through Gd{sup 3+} sensitive transient receptor potential channels (TRPC), and by IP{sub 3} receptors.

  13. To branch or not to branch: Numerical modeling of dynamically branching faults

    NASA Astrophysics Data System (ADS)

    Dedontney, N. L.; Templeton Barrett, E. L.; Rice, J. R.; Dmowska, R.

    2009-12-01

    Branched fault geometries, and branched rupture paths, occur in strike-slip as well as dip-slip settings [e.g., Poliakov et al., JGR, 2002; Kame et al., JGR, 2003]. The Wenchuan earthquake illustrates such a branched geometry [Hubbard and Shaw, 2009] in a fold and thrust belt, and surface ruptures provide constraints on which faults were activated co-seismically. Additionally, a branched structure, the Central Basin Decollement [Shaw & Suppe, 1996], underlies the Los Angeles Basin. By simulating the dynamic rupture path selection, using explicit finite element methods here, we are able to estimate which faults should be activated under given conditions. Factors that influence coseismic branch activation have been extensively studied [Poliakov et al.; Kame et al.; Oglesby et al., 2003, 2004; Bhat et al., 2004, 2007]. The results show that the rupture velocity, pre-stress orientation and fault geometry influence rupture path selection. We show further that the ratio of σ1/σ3 (equivalently, the seismic S ratio) and the relative frictional fault strength also play a significant role in determining which faults are activated. Our methodology has recently included the use of a regularized friction routine [Ranjith & Rice, 2001; Cochard & Rice, 2000] which reduces the growth of numerical noise throughout the simulations. A difficulty arises in the treatment of surface interactions at the branch junction. When local opening does not occur there, slip on the branch fault must vanish at the junction, a constraint that we impose on the FE model. However, the FE contact routine used demands that slip always be constrained to zero on one or the other fault at such a junction, which is problematic when opening occurs. There is then no fundamental basis for constraining slip at the junction to zero on either fault, and the choice made affects the slip distributions and rupture path selection. Many analyses that we perform are elastic and the same material is used on both sides

  14. Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice.

    PubMed

    Hayashi, Yoshinori; Yoshida, Masayoshi; Yamato, Mayumi; Ide, Tomomi; Wu, Zhou; Ochi-Shindou, Mayumi; Kanki, Tomotake; Kang, Dongchon; Sunagawa, Kenji; Tsutsui, Hiroyuki; Nakanishi, Hiroshi

    2008-08-20

    Mitochondrial DNA (mtDNA) is highly susceptible to injury induced by reactive oxygen species (ROS). During aging, mutations of mtDNA accumulate to induce dysfunction of the respiratory chain, resulting in the enhanced ROS production. Therefore, age-dependent memory impairment may result from oxidative stress derived from the respiratory chain. Mitochondrial transcription factor A (TFAM) is now known to have roles not only in the replication of mtDNA but also its maintenance. We herein report that an overexpression of TFAM in HeLa cells significantly inhibited rotenone-induced mitochondrial ROS generation and the subsequent NF-kappaB (nuclear factor-kappaB) nuclear translocation. Furthermore, TFAM transgenic (TG) mice exhibited a prominent amelioration of an age-dependent accumulation of lipid peroxidation products and a decline in the activities of complexes I and IV in the brain. In the aged TG mice, deficits of the motor learning memory, the working memory, and the hippocampal long-term potentiation (LTP) were also significantly improved. The expression level of interleukin-1beta (IL-1beta) and mtDNA damages, which were predominantly found in microglia, significantly decreased in the aged TG mice. The IL-1beta amount markedly increased in the brain of the TG mice after treatment with lipopolysaccharide (LPS), whereas its mean amount was significantly lower than that of the LPS-treated aged wild-type mice. At the same time, an increased mtDNA damage in microglia and an impaired hippocampal LTP were also observed in the LPS-treated aged TG mice. Together, an overexpression of TFAM is therefore considered to ameliorate age-dependent impairment of the brain functions through the prevention of oxidative stress and mitochondrial dysfunctions in microglia.

  15. Age-dependent alterations of the hippocampal cell composition and proliferative potential in the hAβPPSwInd-J20 mouse.

    PubMed

    Fu, YuHong; Rusznák, Zoltán; Kwok, John B J; Kim, Woojin Scott; Paxinos, George

    2014-01-01

    The J20 mouse expresses human mutant amyloid-β protein precursor (hAβPPSwInd) and is an established transgenic model of Alzheimer's disease (AD). From the age of 5 months, amyloid-β (Aβ) deposits appear in the hippocampus with concomitant increase of AD-associated features. Although changes occurring after the appearance of Aβ deposits have been extensively studied, very little is known about alterations that occur prior to 5 months. The present study aimed to identify changes in the cellular composition and proliferative potential of the J20 hippocampus using 1-18-month-old mice. Neuronal, non-neuronal, Ki-67+, and TUNEL+ cell numbers were counted with the isotropic fractionator method. Age-dependent changes of the expression of microglia-, astrocyte-, and neurogenesis-specific markers were sought in the entire hippocampus. Several transgene-associated changes were revealed before the appearance of Aβ deposits. The number of proliferating cells decreased whereas the number of microglia clusters increased as early as 4 weeks of age. The neurogenesis was also impaired in the dentate gyrus of 7-11-week-old J20 mice. A statistically significant negative correlation was found between the number of proliferating cells and age in both populations, but the time course of the age-dependence was steeper in wild-type than in J20 mice. Negative age-dependence was noted when the number of cells committed to apoptosis was examined. Our results indicate that overexpression of mutant hAβPP initiates a cascade of pathologic events well before the appearance of visible Aβ plaques. Accordingly, early signs of AD include reduced cell proliferation, impaired neurogenesis, and increased activity of microglia in the hippocampus.

  16. BAC Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant Alpha-Synuclein

    PubMed Central

    Lu, Xiao-Hong; Fleming, Sheila M.; Meurers, Bernhard; Ackerson, Larry C.; Mortazavi, Farzad; Lo, Victor; Hernandez, Daniela; Sulzer, David; Jackson, George R.; Maidment, Nigel T.; Chesselet, Marie-Francoise; Yang, X. William

    2009-01-01

    Summary Recessive mutations in parkin are the most common cause of familial early onset Parkinson's disease (PD). Recent studies suggest that certain parkin mutants may exert dominant toxic effects to cultured cells and such dominant toxicity can lead to progressive dopaminergic (DA) neuron degeneration in Drosophila. To explore whether mutant parkin could exert similar pathogenic effects to mammalian DA neurons in vivo, we developed a Bacterial Artificial Chromosome (BAC) transgenic mouse model expressing a C-terminal truncated human mutant parkin (Parkin-Q311X) in DA neurons driven by a dopamine transporter promoter. Parkin-Q311X mice exhibit multiple late-onset and progressive hypokinetic motor deficits. Stereological analyses reveal that the mutant mice develop age-dependent DA neuron degeneration in substantia nigra accompanied by a significant loss of DA neuron terminals in the striatum. Neurochemical analyses reveal a significant reduction of the striatal dopamine level in mutant mice, which is significantly correlated with their hypokinetic motor deficits. Finally, mutant Parkin-Q311X mice, but not wild-type controls, exhibit age-dependent accumulation of proteinase-K resistant endogenous α-synuclein in substantia nigra and co-localized with 3-nitrotyrosine, a marker for oxidative protein damage. Hence, our study provides the first mammalian genetic evidence that dominant toxicity of a parkin mutant is sufficient to elicit age-dependent hypokinetic motor deficits and DA neuron loss in vivo, and uncovers a causal relationship between dominant parkin toxicity and progressive α-synuclein accumulation in DA neurons. Our study underscores the need to further explore the putative link between parkin dominant toxicity and PD. PMID:19228951

  17. New branches of massive gravity

    NASA Astrophysics Data System (ADS)

    Comelli, D.; Crisostomi, M.; Koyama, K.; Pilo, L.; Tasinato, G.

    2015-06-01

    The basic building block for Lorentz-invariant and ghost-free massive gravity is the square root of the combination g-1η , where g-1 is the inverse of the physical metric and η is a reference metric. Since the square root of a matrix is not uniquely defined, it is possible to have physically inequivalent potentials corresponding to different branches. We show that around the Minkowski background, the only perturbatively well-defined branch is the potential proposed by de Rham, Gabadadze and Tolley. On the other hand, if Lorentz symmetry is broken spontaneously, other potentials exist with a standard perturbative expansion. We show this explicitly building new Lorentz-invariant, ghost-free massive gravity potentials for theories that in the background preserve rotational invariance but break Lorentz boosts.

  18. Geodynamics Branch research report, 1982

    NASA Technical Reports Server (NTRS)

    Kahn, W. D. (Editor); Cohen, S. C. (Editor)

    1983-01-01

    The research program of the Geodynamics Branch is summarized. The research activities cover a broad spectrum of geoscience disciplines including space geodesy, geopotential field modeling, tectonophysics, and dynamic oceanography. The NASA programs which are supported by the work described include the Geodynamics and Ocean Programs, the Crustal Dynamics Project, the proposed Ocean Topography Experiment (TOPEX) and Geopotential Research Mission. The individual papers are grouped into chapters on Crustal Movements, Global Earth Dynamics, Gravity Field Model Development, Sea Surface Topography, and Advanced Studies.

  19. Horizontal-branch stellar evolution

    NASA Technical Reports Server (NTRS)

    Sweigart, Allen V.

    1990-01-01

    The results of canonical theory for the evolution of horizontal-branch (HB) stars are examined. Particular attention is given to how an HB star maintains the appropriate composition distribution within the semiconvective zone and how this composition is affected by the finite time-dependence with which convective boundaries actually move. Newly developed models based on time-dependent overshooting are presented for both the core-helium-exhaustion and main HB phases.

  20. Solid State Photovoltaic Research Branch

    SciTech Connect

    Not Available

    1990-09-01

    This report summarizes the progress of the Solid State Photovoltaic Research Branch of the Solar Energy Research Institute (SERI) from October 1, 1988, through September 30,l 1989. Six technical sections of the report cover these main areas of SERIs in-house research: Semiconductor Crystal Growth, Amorphous Silicon Research, Polycrystalline Thin Films, III-V High-Efficiency Photovoltaic Cells, Solid-State Theory, and Laser Raman and Luminescence Spectroscopy. Sections have been indexed separately for inclusion on the data base.

  1. Control of carbohydrate processing: increased beta-1,6 branching in N-linked carbohydrates of Lec9 CHO mutants appears to arise from a defect in oligosaccharide-dolichol biosynthesis.

    PubMed Central

    Rosenwald, A G; Stanley, P; Krag, S S

    1989-01-01

    A correlation between increased beta-1,6 branching of N-linked carbohydrates and the ability of a cell to metastasize or to form a tumor has been observed in several experimental models. Lec9 Chinese hamster ovary (CHO) mutants exhibit a drastic reduction in tumorigenicity in nude mice, and this phenotype directly correlates with their ability to attach an increased proportion of beta-1,6-branched carbohydrates to the G glycoprotein of vesicular stomatitis virus (J. Ripka, S. Shin, and P. Stanley, Mol. Cell. Biol. 6:1268-1275, 1986). In this paper we provide evidence that cellular carbohydrates from Lec9 cells also contain an increased proportion of beta-1,6-branched carbohydrates, although they do not possess significantly increased activity of the beta-1,6 branching enzyme (GlcNAc-transferase V). Biosynthetic labeling experiments show that a substantial degree of underglycosylation occurs in Lec9 cells and that this affects several classes of glycoproteins. Lec9 cells synthesize ca. 40-fold less Glc3Man9GlcNAc2-P-P-lipid and ca. 2-fold less Man5GlcNAc2-P-P-lipid than parental cells do. In addition, Lec9 cells possess ca. fivefold less protein-bound oligosaccharide intermediates, and one major species is resistant to release by endo-beta-N-acetylglucosaminidase H (endo H). Membranes of Lec9 cells exhibit normal mannosylphosphoryldolichol synthase, glucosylphosphoryldolichol synthase, and N-acetylglucosaminylphosphate transferase activities in the presence of exogenous dolichyl phosphate. However, in the absence of exogenous dolichyl phosphate, mannosylphosphoryldolichol synthase and glucosylphosphoryldolichol synthase activities are reduced in membranes of Lec9 cells, indicating that membranes of Lec9 cells are deficient in lipid phosphate. This was confirmed by analysis of lipids labeled by [3H]mevalonate, which showed that Lec9 cells have less lipid phosphate than parental CHO cells. Mechanisms by which a defect in the synthesis of dolichol

  2. Branching dynamics of viral information spreading

    NASA Astrophysics Data System (ADS)

    Iribarren, José Luis; Moro, Esteban

    2011-10-01

    Despite its importance for rumors or innovations propagation, peer-to-peer collaboration, social networking, or marketing, the dynamics of information spreading is not well understood. Since the diffusion depends on the heterogeneous patterns of human behavior and is driven by the participants’ decisions, its propagation dynamics shows surprising properties not explained by traditional epidemic or contagion models. Here we present a detailed analysis of our study of real viral marketing campaigns where tracking the propagation of a controlled message allowed us to analyze the structure and dynamics of a diffusion graph involving over 31 000 individuals. We found that information spreading displays a non-Markovian branching dynamics that can be modeled by a two-step Bellman-Harris branching process that generalizes the static models known in the literature and incorporates the high variability of human behavior. It explains accurately all the features of information propagation under the “tipping point” and can be used for prediction and management of viral information spreading processes.

  3. Branching dynamics of viral information spreading.

    PubMed

    Iribarren, José Luis; Moro, Esteban

    2011-10-01

    Despite its importance for rumors or innovations propagation, peer-to-peer collaboration, social networking, or marketing, the dynamics of information spreading is not well understood. Since the diffusion depends on the heterogeneous patterns of human behavior and is driven by the participants' decisions, its propagation dynamics shows surprising properties not explained by traditional epidemic or contagion models. Here we present a detailed analysis of our study of real viral marketing campaigns where tracking the propagation of a controlled message allowed us to analyze the structure and dynamics of a diffusion graph involving over 31,000 individuals. We found that information spreading displays a non-Markovian branching dynamics that can be modeled by a two-step Bellman-Harris branching process that generalizes the static models known in the literature and incorporates the high variability of human behavior. It explains accurately all the features of information propagation under the "tipping point" and can be used for prediction and management of viral information spreading processes.

  4. Actin filament curvature biases branching direction

    NASA Astrophysics Data System (ADS)

    Wang, Evan; Risca, Viviana; Chaudhuri, Ovijit; Chia, Jia-Jun; Geissler, Phillip; Fletcher, Daniel

    2012-02-01

    Actin filaments are key components of the cellular machinery, vital for a wide range of processes ranging from cell motility to endocytosis. Actin filaments can branch, and essential in this process is a protein complex known as the Arp2/3 complex, which nucleate new ``daughter'' filaments from pre-existing ``mother'' filaments by attaching itself to the mother filament. Though much progress has been made in understanding the Arp2/3-actin junction, some very interesting questions remain. In particular, F-actin is a dynamic polymer that undergoes a wide range of fluctuations. Prior studies of the Arp2/3-actin junction provides a very static notion of Arp2/3 binding. The question we ask is how differently does the Arp2/3 complex interact with a straight filament compared to a bent filament? In this study, we used Monte Carlo simulations of a surface-tethered worm-like chain to explore possible mechanisms underlying the experimental observation that there exists preferential branch formation by the Arp2/3 complex on the convex face of a curved filament. We show that a fluctuation gating model in which Arp2/3 binding to the actin filament is dependent upon a rare high-local-curvature shape fluctuation of the filament is consistent with the experimental data.

  5. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice.

    PubMed

    Gallego, Sandra F; Sprenger, Richard R; Neess, Ditte; Pauling, Josch K; Færgeman, Nils J; Ejsing, Christer S

    2017-02-01

    The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic cholesteryl esters, and that lipids featuring an 18:1 fatty acid moiety are increased in Acbp depleted mice across all tissues investigated. Our results also show that the perturbation of systemic lipid metabolism in Acbp knockout mice is transient and becomes normalized and similar to that of wild type as mice grow older. These findings demonstrate that ACBP serves crucial functions in maintaining lipid metabolic homeostasis in mice during weaning.

  6. Soils of Walker Branch Watershed

    SciTech Connect

    Lietzke, D.A.

    1994-01-01

    The soil survey of Walker Branch Watershed (WBW) utilized the most up-to-date knowledge of soils, geology, and geohydrology in building the soils data base needed to reinterpret past research and to begin new research in the watershed. The soils of WBW were also compared with soils mapped elsewhere along Chestnut Ridge on the Oak Ridge Reservation to (1) establish whether knowledge obtained elsewhere could be used within the watershed, (2) determine whether there were any soils restricted to the watershed, and (3) evaluate geologic formation lateral variability. Soils, surficial geology, and geomorphology were mapped at a scale of 1:1200 using a paper base map having 2-ft contour intervals. Most of the contours seemed to reasonably represent actual landform configurations, except for dense wooded areas. For example, the very large dolines or sinkholes were shown on the contour base map, but numerous smaller ones were not. In addition, small drainageways and gullies were often not shown. These often small but important features were located approximately as soil mapping progressed. WBW is underlain by dolostones of the Knox Group, but only a very small part of the surface area contains outcroppings of rock and most outcrops were located in the lower part. Soil mapping revealed the presence of both ancient alluvium and ancient colluvium deposits, not recognized in previous soil surveys, that have been preserved in high-elevation stable portions of present-day landforms. An erosional geomorphic process of topographic inversion requiring several millions of years within the Pleistocene is necessary to bring about the degree of inversion that is expressed in the watershed. Indeed, some of these ancient alluvial and colluvial remnants may date back into the Tertiary. Also evident in the watershed, and preserved in the broad, nearly level bottoms of dolines, are multiple deposits of silty material either devoid or nearly devoid of coarse fragments. Recent research

  7. Strategy of Irrigation Branch in Russia

    NASA Astrophysics Data System (ADS)

    Zeyliger, A.; Ermolaeva, O.

    2012-04-01

    At this moment, at the starting time of the program on restoration of a large irrigation in Russia till 2020, the scientific and technical community of irrigation branch does not have clear vision on how to promote a development of irrigated agriculture and without repeating of mistakes having a place in the past. In many respects absence of a vision is connected to serious backlog of a scientific and technical and informational and technological level of development of domestic irrigation branch from advanced one. Namely such level of development is necessary for the resolving of new problems in new conditions of managing, and also for adequate answers to new challenges from climate and degradation of ground & water resources, as well as a rigorous requirement from an environment. In such important situation for irrigation branch when it is necessary quickly generate a scientific and technical politics for the current decade for maintenance of translation of irrigated agriculture in the Russian Federation on a new highly effective level of development, in our opinion, it is required to carry out open discussion of needs and requirements as well as a research for a adequate solutions. From political point of view a framework organized in FP6 DESIRE 037046 project is an example of good practice that can serve as methodical approach how to organize and develop such processes. From technical point of view a technology of operational management of irrigation at large scale presents a prospective alternative to the current type of management based on planning. From point of view ICT operational management demands creation of a new platform for the professional environment of activity. This platform should allow to perceive processes in real time, at their partial predictability on signals of a straight line and a feedback, within the framework of variability of decision making scenarious, at high resolution and the big ex-awning of sensor controls and the gauges

  8. Biochemical characterisation of a glycogen branching enzyme from Streptococcus mutans: Enzymatic modification of starch.

    PubMed

    Kim, Eun-Joo; Ryu, Soo-In; Bae, Hyun-Ah; Huong, Nguyen Thi; Lee, Soo-Bok

    2008-10-15

    A gene encoding a putative glycogen branching enzyme (SmGBE) in Streptococcus mutans was expressed in Escherichia coli and purified. The biochemical properties of the purified enzyme were examined relative to its branching specificity for amylose and starch. The activity of the approximately 75kDa enzyme was optimal at pH 5.0, and stable up to 40°C. The enzyme predominantly transferred short maltooligosyl chains with a degree of polymerization (dp) of 6 and 7 throughout the branching process for amylose. When incubated with rice starch, the enzyme modified its optimal branch chain-length from dp 12 to 6 with large reductions in the longer chains, and simultaneously increased its branching points. The results indicate that SmGBE can make a modified starch with much shorter branches and a more branched structure than to native starch. In addition, starch retrogradation due to low temperature storage was significantly retarded along with the enzyme reaction.

  9. Do Vascular Networks Branch Optimally or Randomly across Spatial Scales?

    PubMed Central

    Newberry, Mitchell G.; Savage, Van M.

    2016-01-01

    Modern models that derive allometric relationships between metabolic rate and body mass are based on the architectural design of the cardiovascular system and presume sibling vessels are symmetric in terms of radius, length, flow rate, and pressure. Here, we study the cardiovascular structure of the human head and torso and of a mouse lung based on three-dimensional images processed via our software Angicart. In contrast to modern allometric theories, we find systematic patterns of asymmetry in vascular branching, potentially explaining previously documented mismatches between predictions (power-law or concave curvature) and observed empirical data (convex curvature) for the allometric scaling of metabolic rate. To examine why these systematic asymmetries in vascular branching might arise, we construct a mathematical framework to derive predictions based on local, junction-level optimality principles that have been proposed to be favored in the course of natural selection and development. The two most commonly used principles are material-cost optimizations (construction materials or blood volume) and optimization of efficient flow via minimization of power loss. We show that material-cost optimization solutions match with distributions for asymmetric branching across the whole network but do not match well for individual junctions. Consequently, we also explore random branching that is constrained at scales that range from local (junction-level) to global (whole network). We find that material-cost optimizations are the strongest predictor of vascular branching in the human head and torso, whereas locally or intermediately constrained random branching is comparable to material-cost optimizations for the mouse lung. These differences could be attributable to developmentally-programmed local branching for larger vessels and constrained random branching for smaller vessels. PMID:27902691

  10. Age dependence of the level of the enzymes involved in the protection against active oxygen species in the rat brain

    SciTech Connect

    Scarpa, M.; Rigo, A.; Viglino, P.; Stevanato, R.; Bracco, F.; Battistin, L.

    1987-06-01

    Levels of Cu, Zn superoxide dismutase (CuSOD), Mn superoxide dismutase (MnSOD), catalase, and glutathione peroxidase (GPx) were assessed in the rat brain cortex. The concentrations of Cu- and MnSOD were found to increase linearly with the logarithm of the age of the animal from 3 days before birth to 30 months, both in the whole cortex tissue and in its cytoplasmic fraction. Catalase and GPx levels showed different trends; in particular, GPx, which appears to play a key role in detoxification of hydrogen peroxide, after an initial fall increases steadily with age. The enhancement of the levels of SOD and GPx could be related to protection against an increased production of reactive oxygen species in the aging process.

  11. The ability of lens alpha crystallin to protect against heat-induced aggregation is age-dependent

    NASA Technical Reports Server (NTRS)

    Horwitz, J.; Emmons, T.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Alpha crystallin was prepared from newborn and aged bovine lenses. SDS-PAGE and tryptic peptide mapping demonstrated that both preparations contained only the alpha-A and alpha-B chains, with no significant contamination of other crystallins. Compared with alpha crystallin from the aged lens, alpha crystallin from the newborn lens was much more effective in the inhibition of beta L crystallin denaturation and precipitation induced in vitro by heat. Together, these results demonstrate that during the aging process, the alpha crystallins lose their ability to protect against protein denaturation, consistent with the hypothesis that the alpha crystallins play an important role in the maintenance of protein native structure in the intact lens.

  12. Managing occurrence branching in qualitative simulation

    SciTech Connect

    Tokuda, L.

    1996-12-31

    Qualitative simulators can produce common sense abstractions of complex behaviors given only partial knowledge about a system. One of the problems which limits the applicability of qualitative simulators is the intractable branching of successor states encountered with model of even modest size. Some branches may be unavoidable due to the complex nature of a system. Other branches may be accidental results of the model chosen. A common source of intractability is occurrence branching. Occurrence branching occurs when the state transitions of two variables are unordered with respect to each other. This paper extends the QSIM model to distinguish between interesting occurrence branching and uninteresting occurrence branching. A representation, algorithm, and simulator for efficiently handling uninteresting branching is presented.

  13. Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption.

    PubMed

    Annaert, Pieter; Brouwers, Joachim; Bijnens, Ann; Lammert, Frank; Tack, Jan; Augustijns, Patrick

    2010-01-31

    The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, while the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults.

  14. Protection against age-dependent renal injury in the F344xBrown Norway male rat is associated with maintained nitric oxide synthase.

    PubMed

    Moningka, Natasha C; Sasser, Jennifer M; Croker, Byron; Carter, Christy; Baylis, Chris

    2011-01-01

    Age-dependent renal damage is influenced by genetic background and the Fisher344xBrown Norway (F344xBN) rat is resistant to glomerular injury. In vulnerable strains, a fall in renal nitric oxide synthase (NOS) contributes to age-dependent renal damage. Here, we investigated renal NOS in young (3 months) and old (30 months) male F344xBN to test the hypothesis that renal NOS is maintained in "protected" strains. We also examined if 6 months of renin-angiotensin system (RAS) blockade using angiotensin converting enzyme inhibition (ACEI) and angiotensin receptor blockade (ARB) provides further benefit in these "protected" old rats. Aging increased tubulointerstitial injury but glomerular sclerosis was minimal and NOS and superoxide dismutase abundance increased. There was no change in the NOS inhibitor, ADMA (asymmetric dimethylarginine) or its regulatory enzymes. RAS blockade with ARB protected against tubulointerstitial injury and increased nNOSα, but ACEI, which also increased nNOSα, had no protective effect on the tubulointerstitium. We conclude that the glomerular sclerosis-resistant aged male F344xBN rat maintains renal NOS, thus reinforcing our hypothesis that progressive glomerular injury is related to renal NOS deficiency. The tubulointerstitial injury seen with aging is reversed with 6 months of ARB but not ACEI and is not associated with renal NOS.

  15. Multiple Metazoan Life-span Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration.

    PubMed

    Shen, Jie; Landis, Gary N; Tower, John

    2017-01-01

    The Gompertz equation describes survival in terms of initial mortality rate (parameter a), indicative of health, and age-dependent acceleration in mortality rate (parameter b), indicative of aging. Gompertz parameters were analyzed for several published studies. In Drosophila females, mating increases egg production and decreases median life span, consistent with a trade-off between reproduction and longevity. Mating increased parameter a, causing decreased median life span, whereas time parameter b was decreased. The inverse correlation between parameters indicates the Strehler-Mildvan (S-M) relationship, where loss of low-vitality individuals yields a cohort with slower age-dependent mortality acceleration. The steroid hormone antagonist mifepristone/RU486 reversed these effects. Mating and mifepristone showed robust S-M relationships across genotypes, and dietary restriction showed robust S-M relationship across diets. Because nutrient optima differed between females and males, the same manipulation caused opposite effects on mortality rates in females versus males across a range of nutrient concentrations. Similarly, p53 mutation in Drosophila and mTOR mutation in mice caused increased median life span associated with opposite direction changes in mortality rate parameters in females versus males. The data demonstrate that dietary and genetic interventions have sex-specific and sometimes sexually opposite effects on mortality rates consistent with sexual antagonistic pleiotropy.

  16. Spoken word recognition in young tone language learners: Age-dependent effects of segmental and suprasegmental variation.

    PubMed

    Ma, Weiyi; Zhou, Peng; Singh, Leher; Gao, Liqun

    2017-02-01

    The majority of the world's languages rely on both segmental (vowels, consonants) and suprasegmental (lexical tones) information to contrast the meanings of individual words. However, research on early language development has mostly focused on the acquisition of vowel-consonant languages. Developmental research comparing sensitivity to segmental and suprasegmental features in young tone learners is extremely rare. This study examined 2- and 3-year-old monolingual tone learners' sensitivity to vowels and tones. Experiment 1a tested the influence of vowel and tone variation on novel word learning. Vowel and tone variation hindered word recognition efficiency in both age groups. However, tone variation hindered word recognition accuracy only in 2-year-olds, while 3-year-olds were insensitive to tone variation. Experiment 1b demonstrated that 3-year-olds could use tones to learn new words when additional support was provided, and additionally, that Tone 3 words were exceptionally difficult to learn. Experiment 2 confirmed a similar pattern of results when children were presented with familiar words. This study is the first to show that despite the importance of tones in tone languages, vowels maintain primacy over tones in young children's word recognition and that tone sensitivity in word learning and recognition changes between 2 and 3years of age. The findings suggest that early lexical processes are more tightly constrained by variation in vowels than by tones.

  17. Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array

    PubMed Central

    Baird, Geoffrey S.; Nelson, Sally K.; Keeney, Tracy R.; Stewart, Alex; Williams, Stephen; Kraemer, Stephan; Peskind, Elaine R.; Montine, Thomas J.

    2012-01-01

    An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. PMID:22122984

  18. Age-dependent effects of peripheral inflammation on the electrophysiological properties of neonatal rat dorsal horn neurons.

    PubMed

    Torsney, Carole; Fitzgerald, Maria

    2002-03-01

    The aim of this study was to investigate the postnatal development of spinal cord neurophysiological mechanisms of inflammatory pain. The effect of hindpaw inflammation on the properties of neonatal spinal dorsal horn cells was investigated in urethane-anesthetized newborn rats using in vivo single-unit extracellular recordings. Responses to cutaneous mechanical and electrical A and C fiber stimulation were recorded at postnatal day (P) 3, 10, and 21 in pups that had received a unilateral intraplantar carageenan injection (1%, 1 microl/g body wt) 2-5 h earlier and compared with age-matched controls. At all three ages, carageenan inflammation increased A fiber evoked sensitization, spontaneous activity, and the suprathreshold response magnitude of dorsal horn cells. Receptive field size, which normally decreases with postnatal age, was unaffected by inflammation in P3 and P10 pups but significantly increased at P21 so that the size distribution closely resembled that in control P3 pups. Mechanical thresholds of individual dorsal horn neurons were not altered by carageenan inflammation at any age. The results show that some dorsal horn cell properties that are likely to underlie inflammatory hypersensitivity such as increased spontaneous activity and response magnitude are observed from the earliest postnatal age examined (P3). However inflammation induced expansion of mechanical receptive field size is not observed until at least the second postnatal week. These results have implications for the postnatal processing of inflammatory pain.

  19. Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: a force spectroscopy study on living hippocampal neurons

    PubMed Central

    Ungureanu, Andreea-Alexandra; Benilova, Iryna; Krylychkina, Olga; Braeken, Dries; De Strooper, Bart; Van Haesendonck, Chris; Dotti, Carlos G.; Bartic, Carmen

    2016-01-01

    Small soluble species of amyloid-beta (Aβ) formed during early peptide aggregation stages are responsible for several neurotoxic mechanisms relevant to the pathology of Alzheimer’s disease (AD), although their interaction with the neuronal membrane is not completely understood. This study quantifies the changes in the neuronal membrane elasticity induced by treatment with the two most common Aβ isoforms found in AD brains: Aβ40 and Aβ42. Using quantitative atomic force microscopy (AFM), we measured for the first time the static elastic modulus of living primary hippocampal neurons treated with pre-aggregated Aβ40 and Aβ42 soluble species. Our AFM results demonstrate changes in the elasticity of young, mature and aged neurons treated for a short time with the two Aβ species pre-aggregated for 2 hours. Neurons aging under stress conditions, showing aging hallmarks, are the most susceptible to amyloid binding and show the largest decrease in membrane stiffness upon Aβ treatment. Membrane stiffness defines the way in which cells respond to mechanical forces in their environment and has been shown to be important for processes such as gene expression, ion-channel gating and neurotransmitter vesicle transport. Thus, one can expect that changes in neuronal membrane elasticity might directly induce functional changes related to neurodegeneration. PMID:27173984

  20. Age-dependent changes in neuronal distribution of CacyBP/SIP: comparison to tubulin and the tau protein.

    PubMed

    Filipek, Anna; Schneider, Gabriela; Mietelska, Anna; Figiel, Izabela; Niewiadomska, Grazyna

    2008-09-01

    CacyBP/SIP was originally identified as an S100A6 (calcyclin) target and later on as a Siah-1 interacting protein. Recently, we have shown that CacyBP/SIP interacts with tubulin, which suggests its involvement in the reorganization of microtubules. In this work we examined the localization of CacyBP/SIP in cultured neurons and in brain neurons of young and aged rats, and compared this localization with that of tubulin and the tau protein. We have found that in neurons of young rats CacyBP/SIP, tubulin and tau are present in the cytoplasm and in the neuronal processes, whereas in aged animals CacyBP/SIP and tau are mainly seen in the cytoplasm of the neuronal somata. In aged rats, these changes are also accompanied by a different localization pattern of tubulin. Thus, our results show that localization of CacyBP/SIP in brain neurons is similar to that observed for tau and tubulin, which points to the involvement of CacyBP/SIP in cytoskeletal physiology.

  1. Ultraviolet radiation exposure accelerates the accumulation of the aging-dependent T414G mitochondrial DNA mutation in human skin.

    PubMed

    Birket, Matthew J; Birch-Machin, Mark A

    2007-08-01

    The accumulation of mitochondrial DNA (mtDNA) mutations has been proposed as an underlying cause of the aging process. Such mutations are thought to be generated principally through mechanisms involving oxidative stress. Skin is frequently exposed to a potent mutagen in the form of ultraviolet (UV) radiation and mtDNA deletion mutations have previously been shown to accumulate with photoaging. Here we report that the age-related T414G point mutation originally identified in skin fibroblasts from donors over 65 years also accumulates with age in skin tissue. Moreover, there is a significantly greater incidence of this mutation in skin from sun-exposed sites (chi(2)= 6.8, P < 0.01). Identification and quantification of the T414G mutation in dermal skin tissue from 108 donors ranging from 8 to 97 years demonstrated both increased occurrence with photoaging as well as an increase in the proportion of molecules affected. In addition, we have discovered frequent genetic linkage between a common photoaging-associated mtDNA deletion and the T414G mutation. This linkage indicates that mtDNA mutations such as these are unlikely to be distributed equally across the mtDNA population within the skin tissue, increasing their likelihood of exerting focal effects at the cellular level. Taken together, these data significantly contribute to our understanding of the DNA damaging effects of UV exposure and how resultant mutations may ultimately contribute towards premature aging.

  2. Guide to the Seattle Archives Branch.

    ERIC Educational Resources Information Center

    Hobbs, Richard, Comp.

    The guide presents an overview of the textual and microfilmed records located at the Seattle Branch of the National Archives of the United States. Established in 1969, the Seattle Archives Branch is one of 11 branches which preserve and make available for research those U.S. Government records of permanent value created and maintained by Federal…

  3. Introduction of Branching Degrees of Octane Isomers.

    PubMed

    Perdih, Anton

    2016-01-01

    The concept of branching degrees is introduced. In the case of octane isomers it is derived from the values of a set of their physicochemical properties, calculating for each isomer the average of the normalized values and these averages are defined as branching degrees of octane isomers. The sequence of these branching degrees of octane isomers does not differ much from the »regular« one defined earlier. 2,2-Dimethylhexane appears to be less branched than 3,4-dimethylhexane and 3-ethyl, 2-methylpentane, whereas 2,3,4-trimethylpentane appears to be less branched than 3-ethyl, 3-methylpentane. While the increasing number of branches gives rise to increasing branching degrees, the peripheral position of branches and the separation between branches decreases the value of the branching degree. The central position of branches increases it. A bigger branch increases it more than a smaller one. The quantification of these structural features and their correlations with few indices is given as well.

  4. Structural dynamics branch research and accomplishments

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Summaries are presented of fiscal year 1989 research highlights from the Structural Dynamics Branch at NASA Lewis Research Center. Highlights from the branch's major work areas include aeroelasticity, vibration control, dynamic systems, and computation structural methods. A listing of the fiscal year 1989 branch publications is given.

  5. Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration

    PubMed Central

    Izquierdo, Iván; Bevilaqua, Lia R.; Rossato, Janine I.; Lima, Ramón H.; Medina, Jorge H.; Cammarota, Martín

    2008-01-01

    Healthy human volunteers 16–82 years of age with at least 10 years of schooling were exposed to two different memory tasks. The first task involved incidental memory. The subjects were asked, as casually as possible: “Did you watch any movie on TV 2 days ago? And 7 days ago? If so, do you remember the title of the movie(s) and the name of the first two actors (actresses)?” Retention scores (maximum = 3: title, actor 1, and actor 2) were equally high (overall mean = 2.6, n = 61) in all age groups (16–20, 21–30, 31–40, 41–60, and 61–82 years) for the day 2 scores. Scores for the movie seen 7 days before decreased significantly and progressively in the three older groups in relation to age, which indicates reduced persistence of this type of memory beginning at the age of 41–50 years and becoming more extensive over the years. The other task was a formal memory procedure. Subjects were asked to study a brief text with factual information on the 1954 World Soccer Cup for 10 min. They were then exposed to 10 questions on the text 2 days and, again, 7 days later. Retention scores declined between the two tests, but in this task, the decline of persistence occurred to a similar extent in all age groups, and thus was not dependent on age. Methylphenidate (10 mg p.o.) given 12 hours after acquisition markedly enhanced persistence of the two memory types. This suggests an involvement of dopaminergic processes in persistence in the late posttraining period. PMID:19050076

  6. Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration.

    PubMed

    Izquierdo, Iván; Bevilaqua, Lia R; Rossato, Janine I; Lima, Ramón H; Medina, Jorge H; Cammarota, Martín

    2008-12-09

    Healthy human volunteers 16-82 years of age with at least 10 years of schooling were exposed to two different memory tasks. The first task involved incidental memory. The subjects were asked, as casually as possible: "Did you watch any movie on TV 2 days ago? And 7 days ago? If so, do you remember the title of the movie(s) and the name of the first two actors (actresses)?" Retention scores (maximum = 3: title, actor 1, and actor 2) were equally high (overall mean = 2.6, n = 61) in all age groups (16-20, 21-30, 31-40, 41-60, and 61-82 years) for the day 2 scores. Scores for the movie seen 7 days before decreased significantly and progressively in the three older groups in relation to age, which indicates reduced persistence of this type of memory beginning at the age of 41-50 years and becoming more extensive over the years. The other task was a formal memory procedure. Subjects were asked to study a brief text with factual information on the 1954 World Soccer Cup for 10 min. They were then exposed to 10 questions on the text 2 days and, again, 7 days later. Retention scores declined between the two tests, but in this task, the decline of persistence occurred to a similar extent in all age groups, and thus was not dependent on age. Methylphenidate (10 mg p.o.) given 12 hours after acquisition markedly enhanced persistence of the two memory types. This suggests an involvement of dopaminergic processes in persistence in the late posttraining period.

  7. Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations

    PubMed Central

    Beltran, William A.; Acland, Gregory M.; Aguirre, Gustavo D.

    2009-01-01

    Purpose To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 & XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. Methods Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. Results A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches an increased density of cones was found to persist over time. Patches of disease gradually disappeared such that by 39 weeks of age the overall retinal morphology, albeit thinner, had improved lamination. In older XLPRA2 carriers (≥8.8 years), extended regions of severe degeneration occurred in the peripheral/mid-peripheral retina. In XLPRA1 carriers, opsin mislocalization and rare events of rod death were detected by TUNEL assay at 20 weeks of age, however patchy degeneration was only seen by 1.4 years, and was still apparent at 7.8 years. Conclusion The time of onset and the progression of the disease differed between the two models. In the early onset form (XLPRA2) the morphologic appearance of the retinal mosaic changed as a function of age, suggesting that structural plasticity persists in the early postnatal canine retina as mutant photoreceptors die. In the late onset form (XLPRA1), patches of disease persisted until later ages. PMID:19255154

  8. Stability of earthquake clustering models: criticality and branching ratios.

    PubMed

    Zhuang, Jiancang; Werner, Maximilian J; Harte, David S

    2013-12-01

    We study the stability conditions of a class of branching processes prominent in the analysis and modeling of seismicity. This class includes the epidemic-type aftershock sequence (ETAS) model as a special case, but more generally comprises models in which the magnitude distribution of direct offspring depends on the magnitude of the progenitor, such as the branching aftershock sequence (BASS) model and another recently proposed branching model based on a dynamic scaling hypothesis. These stability conditions are closely related to the concepts of the criticality parameter and the branching ratio. The criticality parameter summarizes the asymptotic behavior of the population after sufficiently many generations, determined by the maximum eigenvalue of the transition equations. The branching ratio is defined by the proportion of triggered events in all the events. Based on the results for the generalized case, we show that the branching ratio of the ETAS model is identical to its criticality parameter because its magnitude density is separable from the full intensity. More generally, however, these two values differ and thus place separate conditions on model stability. As an illustration of the difference and of the importance of the stability conditions, we employ a version of the BASS model, reformulated to ensure the possibility of stationarity. In addition, we analyze the magnitude distributions of successive generations of the BASS model via analytical and numerical methods, and find that the compound density differs substantially from a Gutenberg-Richter distribution, unless the process is essentially subcritical (branching ratio less than 1) or the magnitude dependence between the parent event and the direct offspring is weak.

  9. Stability of earthquake clustering models: Criticality and branching ratios

    NASA Astrophysics Data System (ADS)

    Zhuang, Jiancang; Werner, Maximilian J.; Harte, David S.

    2013-12-01

    We study the stability conditions of a class of branching processes prominent in the analysis and modeling of seismicity. This class includes the epidemic-type aftershock sequence (ETAS) model as a special case, but more generally comprises models in which the magnitude distribution of direct offspring depends on the magnitude of the progenitor, such as the branching aftershock sequence (BASS) model and another recently proposed branching model based on a dynamic scaling hypothesis. These stability conditions are closely related to the concepts of the criticality parameter and the branching ratio. The criticality parameter summarizes the asymptotic behavior of the population after sufficiently many generations, determined by the maximum eigenvalue of the transition equations. The branching ratio is defined by the proportion of triggered events in all the events. Based on the results for the generalized case, we show that the branching ratio of the ETAS model is identical to its criticality parameter because its magnitude density is separable from the full intensity. More generally, however, these two values differ and thus place separate conditions on model stability. As an illustration of the difference and of the importance of the stability conditions, we employ a version of the BASS model, reformulated to ensure the possibility of stationarity. In addition, we analyze the magnitude distributions of successive generations of the BASS model via analytical and numerical methods, and find that the compound density differs substantially from a Gutenberg-Richter distribution, unless the process is essentially subcritical (branching ratio less than 1) or the magnitude dependence between the parent event and the direct offspring is weak.

  10. Age-dependent neuroplasticity mechanisms in Alzheimer Tg2576 mice following modulation of brain amyloid-β levels.

    PubMed

    Lilja, Anna M; Röjdner, Jennie; Mustafiz, Tamanna; Thomé, Carina M; Storelli, Elisa; Gonzalez, Daniel; Unger-Lithner, Christina; Greig, Nigel H; Nordberg, Agneta; Marutle, Amelia

    2013-01-01

    The objective of this study was to investigate the effects of modulating brain amyloid-β (Aβ) levels at different stages of amyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes perturbed in Alzheimer's disease (AD). Young (4- to 6-month-old) and older (15- to 18-month-old) APP(SWE) transgenic (Tg2576) mice were treated with the AD candidate drug (+)-phenserine for 16 consecutive days. We found significant reductions in insoluble Aβ1-42 levels in the cortices of both young and older transgenic mice, while significant reductions in soluble Aβ1-42 levels and insoluble Aβ1-40 levels were only found in animals aged 15-18 months. Autoradiography binding with the amyloid ligand Pittsburgh Compound B ((3)H-PIB) revealed a trend for reduced fibrillar Aβ deposition in the brains of older phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, while decreased interleukin-1β and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels were detected in the cortices of older mice. The reduction in Aβ1-42 levels was associated with an increased number of bromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determine whether the increased cell proliferation was accompanied by increased neuronal production, the endogenous early neuronal marker doublecortin (DCX) was examined in the dentate gyrus (DG) using immunohistochemical detection. Although no changes in the total number of DCX(+)-expressing neurons were detected in the DG in Tg2576 mice at either age following (+)-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576 mice. Collectively, these findings indicate that reducing Aβ1-42 levels in Tg2576 mice at an early pathological stage affects synaptic function by modulating the maturation and plasticity of newborn neurons in the brain

  11. A Novel Genetic Screen Identifies Modifiers of Age-Dependent Amyloid β Toxicity in the Drosophila Brain

    PubMed Central

    Belfiori-Carrasco, Lautaro F.; Marcora, María S.; Bocai, Nadia I.; Ceriani, M. Fernanda; Morelli, Laura; Castaño, Eduardo M.

    2017-01-01

    The accumulation of amyloid β peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients begins many years before clinical onset. Such process has been proposed to be pathogenic through the toxicity of Aβ soluble oligomers leading to synaptic dysfunction, phospho-tau aggregation and neuronal loss. Yet, a massive accumulation of Aβ can be found in approximately 30% of aged individuals with preserved cognitive function. Therefore, within the frame of the “amyloid hypothesis”, compensatory mechanisms and/or additional neurotoxic or protective factors need to be considered and investigated. Here we describe a modifier genetic screen in Drosophila designed to identify genes that modulate toxicity of Aβ42 in the CNS. The expression of Aβ42 led to its accumulation in the brain and a moderate impairment of negative geotaxis at 18 days post-eclosion (d.p.e) as compared with genetic or parental controls. These flies were mated with a collection of lines carrying chromosomal deletions and negative geotaxis was assessed at 5 and 18 d.p.e. Our screen is the first to take into account all of the following features, relevant to sporadic AD: (1) pan-neuronal expression of wild-type Aβ42; (2) a quantifiable complex behavior; (3) Aβ neurotoxicity associated with progressive accumulation of the peptide; and (4) improvement or worsening of climbing ability only evident in aged animals. One hundred and ninety-nine deficiency (Df) lines accounting for ~6300 genes were analyzed. Six lines, including the deletion of 52 Drosophila genes with human orthologs, significantly modified Aβ42 neurotoxicity in 18-day-old flies. So far, we have validated CG11796 and identified CG17249 as a strong candidate (whose human orthologs are HPD and PRCC, respectively) by using RNAi or mutant hemizygous lines. PRCC encodes proline-rich protein PRCC (ppPRCC) of unknown function associated with papillary renal cell carcinoma. HPD encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key

  12. Functional Redundancy of Septin Homologs in Dendritic Branching

    PubMed Central

    Kaplan, Charlotte; Steinmann, Mayra; Zapiorkowska, Natalia A.; Ewers, Helge

    2017-01-01

    Septins are cytoskeletal GTPases present in nonpolar heteromeric complexes that assemble in a palindromic fashion from two to eight subunits. Mammalian septins function in several fundamental cellular processes at the membrane-cytoskeleton interface including dendritic branching in neurons. Sequence homology divides the 13 mammalian septin genes into four homology groups. Experimental findings suggest that septin function is redundant among septins from one homology group. This is best understood for the isoforms of the SEPT2 group, which form a homodimer at the center of septin complexes. In vitro, all SEPT2-group septins form recombinant hexameric complexes with two copies of SEPT6 and SEPT7. However, it remains unclear to what extent homologs septins can substitute for each other in specific cellular processes. Here, we use the experimental paradigm of dendritic branching in hippocampal rat neurons to ask, to what extent septins of the SEPT2-group are functionally redundant. Dendritic branching is significantly reduced when SEPT5 is downregulated. In neurons expressing SEPT5-shRNA, simultaneously expressed SEPT2-GFP, and SEPT4-GFP colocalize with SEPT7 at dendritic spine necks and rescue dendritic branching. In contrast, SEPT1-GFP is diffusely distributed in the cytoplasm in SEPT5 downregulated neurons and cannot rescue dendritic branching. Our findings provide a basis for the study of septin-specific functions in cells. PMID:28265560

  13. Decibel: The Relational Dataset Branching System

    PubMed Central

    Maddox, Michael; Goehring, David; Elmore, Aaron J.; Madden, Samuel; Parameswaran, Aditya; Deshpande, Amol

    2017-01-01

    As scientific endeavors and data analysis become increasingly collaborative, there is a need for data management systems that natively support the versioning or branching of datasets to enable concurrent analysis, cleaning, integration, manipulation, or curation of data across teams of individuals. Common practice for sharing and collaborating on datasets involves creating or storing multiple copies of the dataset, one for each stage of analysis, with no provenance information tracking the relationships between these datasets. This results not only in wasted storage, but also makes it challenging to track and integrate modifications made by different users to the same dataset. In this paper, we introduce the Relational Dataset Branching System, Decibel, a new relational storage system with built-in version control designed to address these shortcomings. We present our initial design for Decibel and provide a thorough evaluation of three versioned storage engine designs that focus on efficient query processing with minimal storage overhead. We also develop an exhaustive benchmark to enable the rigorous testing of these and future versioned storage engine designs. PMID:28149668

  14. Large branched self-assembled DNA complexes

    NASA Astrophysics Data System (ADS)

    Tosch, Paul; Wälti, Christoph; Middelberg, Anton P. J.; Davies, A. Giles

    2007-04-01

    Many biological molecules have been demonstrated to self-assemble into complex structures and networks by using their very efficient and selective molecular recognition processes. The use of biological molecules as scaffolds for the construction of functional devices by self-assembling nanoscale complexes onto the scaffolds has recently attracted significant attention and many different applications in this field have emerged. In particular DNA, owing to its inherent sophisticated self-organization and molecular recognition properties, has served widely as a scaffold for various nanotechnological self-assembly applications, with metallic and semiconducting nanoparticles, proteins, macromolecular complexes, inter alia, being assembled onto designed DNA scaffolds. Such scaffolds may typically contain multiple branch-points and comprise a number of DNA molecules selfassembled into the desired configuration. Previously, several studies have used synthetic methods to produce the constituent DNA of the scaffolds, but this typically constrains the size of the complexes. For applications that require larger self-assembling DNA complexes, several tens of nanometers or more, other techniques need to be employed. In this article, we discuss a generic technique to generate large branched DNA macromolecular complexes.

  15. Fertilization Affects Branching Pattern in Norway Spruce

    NASA Astrophysics Data System (ADS)

    Palmroth, S.; Stenberg, P.; Smolander, H.

    2001-12-01

    The increase in stand productivity from fertilization can be attributed to an increase in photosynthetic capacity, and a faster accumulation of leaf area index (LAI). Differences in the steady-state LAI are likely to reflect differences in PAR interception and/or conversion efficiency at shoot and leaf level. Furthermore, shoots ability to export carbohydrates to developing buds could be the mechanism responsible for light dependent branching. Within-canopy distribution of PAR and leaf area form the core in process-based models that are used to assess impacts of changes in the environment on production and resource use efficiency of forest stands. However, feedback between structure and radiation environment is not often incorporated in the models. We studied the relationships between light availability, shoot structure and branching pattern in Norway spruce (Picea abies (L.) Karst.) at a long-term fertilization experiment at Flakaliden research area in northern Sweden. Sampling of shoots was designed to cover the variation in canopy exposure within the live crown zone, where current shoots were still found. Canopy openness was used as a measure of the light availability at the shoot?s position. Our data showed that, at similar canopy openness, shoots of fertilized trees were longer and the number and total length of daughters were higher than in control trees. Fertilization increased the steady-state LAI and resulted in a deeper canopy, i.e. foliage is produced and survive at much lower light levels.

  16. S-branch CARS applicability to thermometry

    SciTech Connect

    Akihama, K.; Asai, T. )

    1990-07-20

    The pressure and temperature dependence of background-free {ital S}-branch CARS spectra of N{sub 2} are investigated in the temperature range of 300--700 K for pressures of 1--20 atm. Collisional narrowing for {ital S}-branch CARS spectra is proved to be negligible. Individual {ital S}-branch lines are clearly resolved in the entire range, enabling unequivocal determination of temperatures by their peak ratios. Advantages and disadvantages of {ital S}-branch CARS thermometry are discussed on the basis of experimental results. The dual narrowband Stokes CARS technique is also discussed as a practical method of {ital S}-branch CARS thermometry.

  17. S-branch CARS applicability to thermometry.

    PubMed

    Akihama, K; Asai, T

    1990-07-20

    The pressure and temperature dependence of background-free S-branch CARS spectra of N(2) are investigated in the temperature range of 300-700 K for pressures of 1-20 atm. Collisional narrowing for S-branch CARS spectra is proved to be negligible. Individual S-branch lines are clearly resolved in the entire range, enabling unequivocal determination of temperatures by their peak ratios. Advantages and disadvantages of S-branch CARS thermometry are discussed on the basis of experimental results. The dual narrowband Stokes CARS technique is also discussed as a practical method of S-branch CARS thermometry.

  18. Improved Li(+) Storage through Homogeneous N-Doping within Highly Branched Tubular Graphitic Foam.

    PubMed

    Dong, Jinyang; Xue, Yanming; Zhang, Chao; Weng, Qunhong; Dai, Pengcheng; Yang, Yijun; Zhou, Min; Li, Cuiling; Cui, Qiuhong; Kang, Xiaohong; Tang, Chengchun; Bando, Yoshio; Golberg, Dmitri; Wang, Xi

    2017-02-01

    A novel carbon structure, highly branched homogeneous-N-doped graphitic (BNG) tubular foam, is designed via a novel N, N-dimethylformamide (DMF)-mediated chemical vapor deposition method. More structural defects are found at the branched portions as compared with the flat tube domains providing abundant active sites and spacious reservoirs for Li(+) storage. An individual BNG branch nanobattery is constructed and tested using in situ transmission electron microscopy and the lithiation process is directly visualized in real time.

  19. Chiral methyl-branched pheromones.

    PubMed

    Ando, Tetsu; Yamakawa, Rei

    2015-07-01

    Insect pheromones are some of the most interesting natural products because they are utilized for interspecific communication between various insects, such as beetles, moths, ants, and cockroaches. A large number of compounds of many kinds have been identified as pheromone components, reflecting the diversity of insect species. While this review deals only with chiral methyl-branched pheromones, the chemical structures of more than one hundred non-terpene compounds have been determined by applying excellent analytical techniques. Furthermore, their stereoselective syntheses have been achieved by employing trustworthy chiral sources and ingenious enantioselective reactions. The information has been reviewed here not only to make them available for new research but also to understand the characteristic chemical structures of the chiral pheromones. Since biosynthetic studies are still limited, it might be meaningful to examine whether the structures, particularly the positions and configurations of the branched methyl groups, are correlated with the taxonomy of the pheromone producers and also with the function of the pheromones in communication systems.

  20. Sustained overexpression of IGF-1 prevents age-dependent decrease in charge movement and intracellular Ca(2+) in mouse skeletal muscle.

    PubMed

    Wang, Zhong-Min; Messi, María Laura; Delbono, Osvaldo

    2002-03-01

    In this work we tested the hypothesis that transgenic sustained overexpression of IGF-1 prevents age-dependent decreases in charge movement and intracellular Ca(2+) in skeletal muscle fibers. To this end, short flexor digitorum brevis (FDB) muscle fibers from 5-7- and 21-24-month-old FVB (wild-type) and S1S2 (IGF-1 transgenic) mice were studied. Fibers were voltage-clamped in the whole-cell configuration of the patch-clamp technique according to described procedures (Wang, Z. M., M. L. Messi, and O. Delbono. 1999. Biophys. J. 77:2709-2716). Charge movement and intracellular Ca(2+) concentration were recorded simultaneously. The maximum charge movement (Q(max)) recorded in young wild-type and transgenic mice was (mean +/- SEM, in nC microF(-1)): 52 +/- 2.1 (n = 46) and 54 +/- 1.9 (n = 38) (non-significant, ns), respectively, whereas in old wild-type and old transgenic mice the values were 36 +/- 2.1 (n = 32) and 49 +/- 2.3 (n = 35), respectively (p < 0.01). The peak intracellular calcium [Ca(2+)](i) recorded in young wild-type and transgenic mice was (in muM): 14.5 +/- 0.9 and 16 +/- 2.1 (ns), whereas in old wild-type and transgenic mice the values were 9.9 +/- 0.1 and 14 +/- 1.1 (p < 0.01), respectively. No significant changes in the voltage distribution or steepness of the Q-V or [Ca(2+)]-V relationship were found. These data support the concept that overexpression of IGF-1 in skeletal muscle prevents age-dependent reduction in charge movement and peak [Ca(2+)](i).

  1. Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages.

    PubMed

    Song, Gina; Sun, Xueying; Hines, Ronald N; McCarver, D Gail; Lake, Brian G; Osimitz, Thomas G; Creek, Moire R; Clewell, Harvey J; Yoon, Miyoung

    2017-02-22

    Predicting age-specific metabolism is important for evaluating age-related drug and chemical sensitivity. Multiple cytochrome P450s (CYP) and carboxylesterase (CES) enzymes are responsible for human pyrethroid metabolism. Complete ontogeny data for each enzyme is needed to support in vitro to in vivo extrapolation (IVIVE). This study was designed to determine age-dependent human hepatic CYP2C8 expression, for which only limited ontogeny data are available, and to further define CYP1A2 ontogeny. CYP2C8 and 1A2 protein levels were measured by quantitative Western blotting using liver microsomal samples prepared from 222 subjects with ages ranging from 8 weeks gestation to 18 years after birth. The median CYP2C8 expression was significantly greater among samples from subjects older than 35 postnatal days (n=122) compared to fetal samples and those from very young infants (fetal to 35 days postnatal, n=100) (0.00 vs. 13.38 pmol/mg microsomal protein; p<0.0001). In contrast, the median CYP1A2 expression was significantly greater after 15 months postnatal age (n=55) than in fetal and younger postnatal samples (fetal to 15 months postnatal, n=167) (0.0167 vs. 2.354 pmol/mg microsomal protein; p<0.0001). CYP2C8, but not CYP1A2, protein levels, significantly correlated with those of CYP2C9, CYP2C19, and CYP3A4 (p<0.001) consistent with CYP2C8 and CYP1A2 ontogeny being probably controlled by different mechanisms. This study provides key data for physiologically based pharmacokinetic model-based prediction of age-dependent pyrethroid metabolism, which will be used for IVIVE to support pyrethroid risk assessment for early life stages.

  2. Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

    SciTech Connect

    Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

    1988-07-12

    The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.

  3. Nucleosynthesis in asymptotic giant branch stars

    SciTech Connect

    El Eid, Mounib F.

    2014-05-09

    The nucleosynthesis in asymptotic giant branch stars (briefly: AGB)is a challenging and fascinating subject in the theory of stellar evolution and important for observations as well. This is because about of half the heavy elements beyond iron are synthesized during thermal pulsation phases of these stars. Furthermore, the understanding of the production of the heavy elements and some light elements like carbon and fluorine represent a powerful tool to get more insight into the internal structure of these stars. The diversity of nuclear processing during the AGB phases may also motivate experimental activities in measuring important nuclear reactions. In this contribution, we emphasize several interesting feature of the nucleosynthesis in AGB stars which still needs further elaboration especially from theoretical point of view.

  4. Decay branching ratios of excited 24Mg

    NASA Astrophysics Data System (ADS)

    Munson, J. M.; Norman, E. B.; Burke, J. T.; Casperson, R. J.; Phair, L. W.; McCleskey, E.; McCleskey, M.; Lee, D.; Hughes, R. O.; Ota, S.; Czeszumska, A.; Chodash, P. A.; Saastamoinen, A. J.; Austin, R. A. E.; Spiridon, A. E.; Dag, M.; Chyzh, R.; Basunia, M. S.; Ressler, J. J.; Ross, T. J.

    2017-01-01

    The nuclear reactions 12C(12C,α )20Ne , 12C(12C,p )23Na , and 12C(12C,n )23Mg are the primary reactions in carbon burning, which occurs as part of several stellar processes. The Gamow window, which describes the energy range where most of these reactions take place, is typically around 1.5 MeV in the center-of-mass frame. Direct measurements of the cross sections at this energy are difficult due to the large Coulomb barrier present between the carbon nuclei; however, a successful surrogate measurement can provide the branching ratios between these reactions while avoiding the 12C+12C Coulomb barrier. An experiment was performed using inelastic scattering of 40 MeV α particles on 24Mg as a possible surrogate for the 12C+12C compound nucleus.

  5. Nucleosynthesis in asymptotic giant branch stars

    NASA Astrophysics Data System (ADS)

    El Eid, Mounib F.

    2014-05-01

    The nucleosynthesis in asymptotic giant branch stars (briefly: AGB)is a challenging and fascinating subject in the theory of stellar evolution and important for observations as well. This is because about of half the heavy elements beyond iron are synthesized during thermal pulsation phases of these stars. Furthermore, the understanding of the production of the heavy elements and some light elements like carbon and fluorine represent a powerful tool to get more insight into the internal structure of these stars. The diversity of nuclear processing during the AGB phases may also motivate experimental activities in measuring important nuclear reactions. In this contribution, we emphasize several interesting feature of the nucleosynthesis in AGB stars which still needs further elaboration especially from theoretical point of view.

  6. Branching pattern of gluco-oligosaccharides and 1.5kDa dextran grafted by the α-1,2 branching sucrase GBD-CD2.

    PubMed

    Brison, Yoann; Laguerre, Sandrine; Lefoulon, François; Morel, Sandrine; Monties, Nelly; Potocki-Véronèse, Gabrielle; Monsan, Pierre; Remaud-Simeon, Magali

    2013-04-15

    GBD-CD2, an engineered sucrose-acting enzyme of glycoside hydrolase family 70, transfers D-glucopyranosyl (D-Glcp) units from sucrose onto dextrans or gluco-oligosaccharides (GOS) through the formation of α-(1→2) linkages leading to branched products of interest for health, food and cosmetic applications. Structural characterization of the branched products obtained from sucrose and pure GOS of degree of polymerization (DP) 4 or DP 5 revealed that highly α-(1→2) branched and new molecular structures can be synthesized by GBD-CD2. The formation of α-(1→2) branching is kinetically controlled and can occur onto vicinal α-(1→6)-linked D-Glcp residues. To investigate the mode of branching of 1.5 kDa dextran, simulations of various branching scenarios and resistance to glucoamylase degradation were performed. Analysis of the simulation results suggests that the branching process is stochastic and indicates that the enzyme acceptor site can accommodate both linear and poly-branched acceptors. This opens the way to the design of novel enzyme-based processes yielding carbohydrate structures varying in size and resistance to hydrolytic enzymes.

  7. Recursive Branching Simulated Annealing Algorithm

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew; Smith, J. Scott; Aronstein, David

    2012-01-01

    This innovation is a variation of a simulated-annealing optimization algorithm that uses a recursive-branching structure to parallelize the search of a parameter space for the globally optimal solution to an objective. The algorithm has been demonstrated to be more effective at searching a parameter space than traditional simulated-annealing methods for a particular problem of interest, and it can readily be applied to a wide variety of optimization problems, including those with a parameter space having both discrete-value parameters (combinatorial) and continuous-variable parameters. It can take the place of a conventional simulated- annealing, Monte-Carlo, or random- walk algorithm. In a conventional simulated-annealing (SA) algorithm, a starting configuration is randomly selected within the parameter space. The algorithm randomly selects another configuration from the parameter space and evaluates the objective function for that configuration. If the objective function value is better than the previous value, the new configuration is adopted as the new point of interest in the parameter space. If the objective function value is worse than the previous value, the new configuration may be adopted, with a probability determined by a temperature parameter, used in analogy to annealing in metals. As the optimization continues, the region of the parameter space from which new configurations can be selected shrinks, and in conjunction with lowering the annealing temperature (and thus lowering the probability for adopting configurations in parameter space with worse objective functions), the algorithm can converge on the globally optimal configuration. The Recursive Branching Simulated Annealing (RBSA) algorithm shares some features with the SA algorithm, notably including the basic principles that a starting configuration is randomly selected from within the parameter space, the algorithm tests other configurations with the goal of finding the globally optimal

  8. Vere-Jones' self-similar branching model.

    PubMed

    Saichev, A; Sornette, D

    2005-11-01

    Motivated by its potential application to earthquake statistics as well as for its intrinsic interest in the theory of branching processes, we study the exactly self-similar branching process introduced recently by Vere-Jones. This model extends the ETAS class of conditional self-excited branching point-processes of triggered seismicity by removing the problematic need for a minimum (as well as maximum) earthquake size. To make the theory convergent without the need for the usual ultraviolet and infrared cutoffs, the distribution of magnitudes m' of daughters of first-generation of a mother of magnitude m has two branches m < m' with exponent beta - d and m' > m with exponent beta + d, where beta and d are two positive parameters. We investigate the condition and nature of the subcritical, critical, and supercritical regime in this and in an extended version interpolating smoothly between several models. We predict that the distribution of magnitudes of events triggered by a mother of magnitude m over all generations has also two branches m' < m with exponent and with exponent beta - h, with h=d squareroot of (1-s), where s is the fraction of triggered events. This corresponds to a renormalization of the exponent d into h by the hierarchy of successive generations of triggered events. For a significant part of the parameter space, the distribution of magnitudes over a full catalog summed over an average steady flow of spontaneous sources (immigrants) reproduces the distribution of the spontaneous sources with a single branch and is blind to the exponents beta, d of the distribution of triggered events. Since the distribution of earthquake magnitudes is usually obtained with catalogs including many sequences, we conclude that the two branches of the distribution of aftershocks are not directly observable and the model is compatible with real seismic catalogs. In summary, the exactly self-similar Vere-Jones model provides an attractive new approach to model triggered

  9. Vere-Jones' self-similar branching model

    NASA Astrophysics Data System (ADS)

    Saichev, A.; Sornette, D.

    2005-11-01

    Motivated by its potential application to earthquake statistics as well as for its intrinsic interest in the theory of branching processes, we study the exactly self-similar branching process introduced recently by Vere-Jones. This model extends the ETAS class of conditional self-excited branching point-processes of triggered seismicity by removing the problematic need for a minimum (as well as maximum) earthquake size. To make the theory convergent without the need for the usual ultraviolet and infrared cutoffs, the distribution of magnitudes m' of daughters of first-generation of a mother of magnitude m has two branches m'm with exponent β+d , where β and d are two positive parameters. We investigate the condition and nature of the subcritical, critical, and supercritical regime in this and in an extended version interpolating smoothly between several models. We predict that the distribution of magnitudes of events triggered by a mother of magnitude m over all generations has also two branches m'm with exponent β+h , with h=d1-s , where s is the fraction of triggered events. This corresponds to a renormalization of the exponent d into h by the hierarchy of successive generations of triggered events. For a significant part of the parameter space, the distribution of magnitudes over a full catalog summed over an average steady flow of spontaneous sources (immigrants) reproduces the distribution of the spontaneous sources with a single branch and is blind to the exponents β,d of the distribution of triggered events. Since the distribution of earthquake magnitudes is usually obtained with catalogs including many sequences, we conclude that the two branches of the distribution of aftershocks are not directly observable and the model is compatible with real seismic catalogs. In summary, the exactly self-similar Vere-Jones model provides an attractive new approach to model triggered seismicity, which

  10. Vere-Jones' self-similar branching model

    SciTech Connect

    Saichev, A.; Sornette, D.

    2005-11-01

    Motivated by its potential application to earthquake statistics as well as for its intrinsic interest in the theory of branching processes, we study the exactly self-similar branching process introduced recently by Vere-Jones. This model extends the ETAS class of conditional self-excited branching point-processes of triggered seismicity by removing the problematic need for a minimum (as well as maximum) earthquake size. To make the theory convergent without the need for the usual ultraviolet and infrared cutoffs, the distribution of magnitudes m{sup '} of daughters of first-generation of a mother of magnitude m has two branches m{sup '}m with exponent {beta}+d, where {beta} and d are two positive parameters. We investigate the condition and nature of the subcritical, critical, and supercritical regime in this and in an extended version interpolating smoothly between several models. We predict that the distribution of magnitudes of events triggered by a mother of magnitude m over all generations has also two branches m{sup '}m with exponent {beta}+h, with h=d{radical}(1-s), where s is the fraction of triggered events. This corresponds to a renormalization of the exponent d into h by the hierarchy of successive generations of triggered events. For a significant part of the parameter space, the distribution of magnitudes over a full catalog summed over an average steady flow of spontaneous sources (immigrants) reproduces the distribution of the spontaneous sources with a single branch and is blind to the exponents {beta},d of the distribution of triggered events. Since the distribution of earthquake magnitudes is usually obtained with catalogs including many sequences, we conclude that the two branches of the distribution of aftershocks are not directly observable and the model is compatible with real seismic catalogs. In summary, the exactly self-similar Vere-Jones model provides an

  11. Vegetation survey of PEN Branch wetlands

    SciTech Connect

    Not Available

    1991-01-01

    A survey was conducted of vegetation along Pen Branch Creek at Savannah River Site (SRS) in support of K-Reactor restart. Plants were identified to species by overstory, understory, shrub, and groundcover strata. Abundance was also characterized and richness and diversity calculated. Based on woody species basal area, the Pen Branch delta was the most impacted, followed by the sections between the reactor and the delta. Species richness for shrub and groundcover strata were also lowest in the delta. No endangered plant species were found. Three upland pine areas were also sampled. In support of K Reactor restart, this report summarizes a study of the wetland vegetation along Pen Branch. Reactor effluent enters Indian Grove Branch and then flows into Pen Branch and the Pen Branch Delta.

  12. Research program of the Geodynamics Branch

    NASA Technical Reports Server (NTRS)

    Kahn, W. D. (Editor); Cohen, S. C. (Editor); Boccucci, B. S. (Editor)

    1986-01-01

    This report is the Fourth Annual Summary of the Research Program of the Geodynamics Branch. The branch is located within the Laboratory for Terrestrial Physics of the Space and Earth Sciences Directorate of the Goddard Space Flight Center. The research activities of the branch staff cover a broad spectrum of geoscience disciplines including: tectonophysics, space geodesy, geopotential field modeling, and dynamic oceanography. The NASA programs which are supported by the work described in this document include the Geodynamics and Ocean Programs, the Crustal Dynamics Project and the proposed Ocean Topography Experiment (TOPEX). The reports highlight the investigations conducted by the Geodynamics Branch staff during calendar year 1985. The individual papers are grouped into chapters on Crustal Movements and Solid Earth Dynamics, Gravity Field Modeling and Sensing Techniques, and Sea Surface Topography. Further information on the activities of the branch or the particular research efforts described herein can be obtained through the branch office or from individual staff members.

  13. Quantitative Analysis of Axonal Branch Dynamics in the Developing Nervous System

    PubMed Central

    Scott, Ethan K.; Goodhill, Geoffrey J.

    2016-01-01

    Branching is an important mechanism by which axons navigate to their targets during neural development. For instance, in the developing zebrafish retinotectal system, selective branching plays a critical role during both initial pathfinding and subsequent arborisation once the target zone has been reached. Here we show how quantitative methods can help extract new information from time-lapse imaging about the nature of the underlying branch dynamics. First, we introduce Dynamic Time Warping to this domain as a method for automatically matching branches between frames, replacing the effort required for manual matching. Second, we model branch dynamics as a birth-death process, i.e. a special case of a continuous-time Markov process. This reveals that the birth rate for branches from zebrafish retinotectal axons, as they navigate across the tectum, increased over time. We observed no significant change in the death rate for branches over this time period. However, blocking neuronal activity with TTX slightly increased the death rate, without a detectable change in the birth rate. Third, we show how the extraction of these rates allows computational simulations of branch dynamics whose statistics closely match the data. Together these results reveal new aspects of the biology of retinotectal pathfinding, and introduce computational techniques which are applicable to the study of axon branching more generally. PMID:26998842

  14. Combining living anionic polymerization with branching reactions in an iterative fashion to design branched polymers.

    PubMed

    Higashihara, Tomoya; Sugiyama, Kenji; Yoo, Hee-Soo; Hayashi, Mayumi; Hirao, Akira

    2010-06-16

    This paper reviews the precise synthesis of many-armed and multi-compositional star-branched polymers, exact graft (co)polymers, and structurally well-defined dendrimer-like star-branched polymers, which are synthetically difficult, by a commonly-featured iterative methodology combining living anionic polymerization with branched reactions to design branched polymers. The methodology basically involves only two synthetic steps; (a) preparation of a polymeric building block corresponding to each branched polymer and (b) connection of the resulting building unit to another unit. The synthetic steps were repeated in a stepwise fashion several times to successively synthesize a series of well-defined target branched polymers.

  15. Mechanical Components Branch Test Facilities and Capabilities

    NASA Technical Reports Server (NTRS)

    Oswald, Fred B.

    2004-01-01

    The Mechanical Components Branch at NASA Glenn Research Center formulates, conducts, and manages research focused on propulsion systems for both present and advanced aeronautical and space vehicles. The branch is comprised of research teams that perform basic research in three areas: mechanical drives, aerospace seals, and space mechanisms. Each team has unique facilities for testing aerospace hardware and concepts. This report presents an overview of the Mechanical Components Branch test facilities.

  16. 31 CFR 100.2 - Scope of regulations; transactions effected through Federal Reserve banks and branches...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... effected through Federal Reserve banks and branches; distribution of coin and currencies. 100.2 Section 100... effected through Federal Reserve banks and branches; distribution of coin and currencies. The regulations... national bank notes and Federal Reserve bank notes in process of retirement and Federal Reserve...

  17. 31 CFR 100.2 - Scope of regulations; transactions effected through Federal Reserve banks and branches...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... effected through Federal Reserve banks and branches; distribution of coin and currencies. 100.2 Section 100... effected through Federal Reserve banks and branches; distribution of coin and currencies. The regulations... national bank notes and Federal Reserve bank notes in process of retirement and Federal Reserve...

  18. 31 CFR 100.2 - Scope of regulations; transactions effected through Federal Reserve banks and branches...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... effected through Federal Reserve banks and branches; distribution of coin and currencies. 100.2 Section 100... effected through Federal Reserve banks and branches; distribution of coin and currencies. The regulations... national bank notes and Federal Reserve bank notes in process of retirement and Federal Reserve...

  19. 31 CFR 100.2 - Scope of regulations; transactions effected through Federal Reserve banks and branches...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... effected through Federal Reserve banks and branches; distribution of coin and currencies. 100.2 Section 100... effected through Federal Reserve banks and branches; distribution of coin and currencies. The regulations... national bank notes and Federal Reserve bank notes in process of retirement and Federal Reserve...

  20. Toward improved branch prediction through data mining.

    SciTech Connect

    Hemmert, K. Scott; Johnson, D. Eric

    2009-09-01

    Data mining and machine learning techniques can be applied to computer system design to aid in optimizing design decisions, improving system runtime performance. Data mining techniques have been investigated in the context of branch prediction. Specifically, a comparison of traditional branch predictor performance has been made to data mining algorithms. Additionally, the possiblity of whether additional features available within the architectural state might serve to further improve branch prediction has been evaluated. Results show that data mining techniques indicate potential for improved branch prediction, especially when register file contents are included as a feature set.

  1. Branched silver nanowires as controllable plasmon routers.

    PubMed

    Fang, Yurui; Li, Zhipeng; Huang, Yingzhou; Zhang, Shunping; Nordlander, Peter; Halas, Naomi J; Xu, Hongxing

    2010-05-12

    Using polarization dependent scattering spectroscopy, we investigate plasmon propagation on branched silver nanowires. By controlling the polarization of the incident laser light, the wire plasmons can be routed into different wire branches and result in light emission from the corresponding wire ends. This routing behavior is found to be strongly dependent on the wavelength of light. Thus for certain incident polarizations, light of different wavelength will be routed into different branches. The branched nanowire can thus serve as a controllable router and multiplexer in integrated plasmonic circuits.

  2. Clinical and Translational Epidemiology Branch (CTEB)

    Cancer.gov

    The Clinical and Translational Epidemiology Branch focuses on factors that influence cancer progression, recurrence, survival, and other treatment outcomes, and factors associated with cancer development.

  3. Ventricular fiber optimization utilizing the branching structure.

    PubMed

    Washio, Takumi; Yoneda, Kazunori; Okada, Jun-Ichi; Kariya, Taro; Sugiura, Seiryo; Hisada, Toshiaki

    2016-07-01

    In this paper, we propose an algorithm that optimizes the ventricular fiber structure of the human heart. A number of histological studies and diffusion tensor magnetic resonance imaging analyses have revealed that the myocardial fiber forms a right-handed helix at the endocardium. However, the fiber formation changes its orientation as a function of transmural depth, becoming a left-handed helix at the epicardium. To determine how nature can construct such a structure, which obtains surprising pumping performance, we introduce macroscopic modeling of the branching structure of cardiac myocytes in our finite element ventricular model and utilize this in an optimization process. We put a set of multidirectional fibers around a central fiber orientation at each point of the ventricle walls and simulate heartbeats by generating contraction forces along each of these directions. We examine two optimization processes using the workloads or impulses measured in these directions to update the central fiber orientation. Both processes improve the pumping performance towards an optimal value within several tens of heartbeats, starting from an almost-flat fiber orientation. However, compared with the workload optimization, the impulse optimization produces better agreement with experimental studies on transmural changes of fiber helix angle, streamline patterns of characteristic helical structures, and temporal changes in strain. Furthermore, the impulse optimization is robust under geometrical changes of the heart and tends to homogenize various mechanical factors such as the stretch and stretch rate along the fiber orientation, the contraction force, and energy consumption. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Age-dependent changes in the functional expression of two nicotinic receptor subtypes in CA1 stratum radiatum interneurons in the rat hippocampus.

    PubMed

    Alkondon, Manickavasagom; Pereira, Edna F R; Albuquerque, Edson X

    2007-10-15

    Protein density measurements and mRNA analysis have provided valuable information on age-dependent changes in the distribution of different nicotinic receptor (nAChR) subtypes in various areas of the rat brain, including the hippocampus. However, very little is known regarding the functional expression of nAChRs in individual neuron types at various ages. Likewise, there is paucity of information regarding the functional and pharmacological profile of nAChRs in the mature rat hippocampus. To address these issues, we used the whole-cell patch-clamp technique to record nicotinic responses from CA1 stratum radiatum (SR) interneurons in hippocampal slices from rat pups (5-19 days old) and adult rats (2-5 months old). As previously observed in the hippocampus of rat pups, CA1 SR interneurons in the hippocampus of adult rats responded to choline (10mM, 12s) with whole-cell currents that decayed to the baseline within the agonist pulse, were sensitive to inhibition by methyllycaconitine (10nM) or alpha-bungarotoxin (50 nM), and were, therefore, mediated by alpha7*(1)[1] nAChRs. Likewise, as previously observed in the hippocampus of young rats, in the adult rat hippocampus excitatory postsynaptic currents (EPSCs) were recorded from SR interneurons in response to a pulse of ACh (0.1 mM, 12s) applied in the presence of the GABA(A) receptor antagonist bicuculline. ACh-triggered EPSCs were inhibited by mecamylamine (1 microM) or choline (1 mM) and were, therefore, likely to have resulted from activation of alpha3beta4beta2* nAChR. The magnitude of alpha7* nAChR-mediated responses increased with the age of the animals. In contrast, the magnitude of alpha3beta4beta2* nAChR-mediated responses was highest at the second postnatal week. The distinct age dependency of functional expression of alpha7* and alpha3beta4beta2* nAChRs strongly suggests that the excitability of CA1 SR interneurons is differentially regulated by the nicotinic cholinergic system in the hippocampus of rat pups

  5. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Schrantee, Anouk; Tamminga, Hyke G. H.; Bouziane, Cheima; Bottelier, Marco A.; Bron, Esther E.; Mutsaerts, Henk-Jan M. M.; Zwinderman, Aeilko H.; Groote, Inge R.; Rombouts, Serge A. R. B.; Lindauer, Ramon J. L.; Klein, Stefan; Niessen, Wiro J.; Opmeer, Brent C.; Boer, Frits; Lucassen, Paul J.; Andersen, Susan L.; Geurts, Hilde M.; Reneman, Liesbeth

    2017-01-01

    IMPORTANCE Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain–Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment–naive status. INTERVENTIONS Treatment with either methylphenidate or a matched placebo for 16 weeks. MAIN OUTCOMES AND MEASURES Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses. RESULTS Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4–12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7–14.8; P = .03). CONCLUSIONS AND RELEVANCE We

  6. Derivation of a Provisional, Age-dependent, AIS2+ Thoracic Risk Curve for the THOR50 Test Dummy via Integration of NASS Cases, PMHS Tests, and Simulation Data.

    PubMed

    Laituri, Tony R; Henry, Scott; El-Jawahri, Raed; Muralidharan, Nirmal; Li, Guosong; Nutt, Marvin

    2015-11-01

    A provisional, age-dependent thoracic risk equation (or, "risk curve") was derived to estimate moderate-to-fatal injury potential (AIS2+), pertaining to men with responses gaged by the advanced mid-sized male test dummy (THOR50). The derivation involved two distinct data sources: cases from real-world crashes (e.g., the National Automotive Sampling System, NASS) and cases involving post-mortem human subjects (PMHS). The derivation was therefore more comprehensive, as NASS datasets generally skew towards younger occupants, and PMHS datasets generally skew towards older occupants. However, known deficiencies had to be addressed (e.g., the NASS cases had unknown stimuli, and the PMHS tests required transformation of known stimuli into THOR50 stimuli). For the NASS portion of the analysis, chest-injury outcomes for adult male drivers about the size of the THOR50 were collected from real-world, 11-1 o'clock, full-engagement frontal crashes (NASS, 1995-2012 calendar years, 1985-2012 model-year light passenger vehicles). The screening for THOR50-sized men involved application of a set of newly-derived "correction" equations for self-reported height and weight data in NASS. Finally, THOR50 stimuli were estimated via field simulations involving attendant representative restraint systems, and those stimuli were then assigned to corresponding NASS cases (n=508). For the PMHS portion of the analysis, simulation-based closure equations were developed to convert PMHS stimuli into THOR50 stimuli. Specifically, closure equations were derived for the four measurement locations on the THOR50 chest by cross-correlating the results of matched-loading simulations between the test dummy and the age-dependent, Ford Human Body Model. The resulting closure equations demonstrated acceptable fidelity (n=75 matched simulations, R2≥0.99). These equations were applied to the THOR50-sized men in the PMHS dataset (n=20). The NASS and PMHS datasets were combined and subjected to survival

  7. Pacific Coastal Ecology Branch: Research Overview

    EPA Science Inventory

    The Pacific Coastal Ecology Branch, Newport, Oregon is part of the Western Ecology Division of the National Health and Environmental Effects Research Laboratory of the U.S. EPA. The Branch conducts research and provides scientific technical support to Headquarters and Regional O...

  8. On an Integral with Two Branch Points

    ERIC Educational Resources Information Center

    de Oliveira, E. Capelas; Chiacchio, Ary O.

    2006-01-01

    The paper considers a class of real integrals performed by using a convenient integral in the complex plane. A complex integral containing a multi-valued function with two branch points is transformed into another integral containing a pole and a unique branch point. As a by-product we obtain a new class of integrals which can be calculated in a…

  9. Anaphora and Branching Direction in Japanese.

    ERIC Educational Resources Information Center

    O'Grady, William; And Others

    1994-01-01

    This paper constitutes a response to Lust and Mazuka's (1989) defense of the Principal Branching parameter and their critique of O'Grady, Suzuki-Wei, and Cho's (1986) experiment, which purported to show that even children learning left-branching languages exhibit a preference for forward patterns of anaphora. (Contains 16 references.) (JL)

  10. Suppression of branches in Eucalyptus trees.

    PubMed

    Senthalir, P; Sharanya, S; Paramathma, M

    2004-06-01

    The effect of neem oil, which acts as a suckericide in tobacco, on branch suppression in Eucalyptus tereticornis was assessed to help maximize stem biomass. Lateral branches of selected trees were pruned, and neem oil solutions at concentrations of either 80%, 40%, 20%, 10%, or 0% (untreated control) were applied to leaf axils of the pruned branches. Regeneration of branches was suppressed, and the magnitude of suppression was proportional to the concentration of neem oil. Compared to the control, the percentage reduction in branching at 80% neem oil was 41.6%. When regenerated branches were repruned and neem oil applied at either 100%, 80%, or 0% (control), the regenerating ability of these branches was severely repressed by 78% at 100% neem oil relative to the control. Apical shoots were also topped and treated at either 100% or 0% (control) neem oil to identify the principal suppressive component in neem oil. The principal component azadirachtin was tested at 375, 750, 1500, 3125, 6250, 12 500, 25 000, 50 000, and 100 000 ppm and 0 ppm as the control. Reduction in the coppicing shoot was as high as 85%. Azadirachtin was responsible for the suppression. By pruning the lateral branches with neem oil, wasteful consumption of photosynthates can be precluded and the stem biomass maximized.

  11. Branching out Has So Much to Offer

    ERIC Educational Resources Information Center

    Murray, Joe

    2012-01-01

    In 1989 there were thirty ATM branches nationally. In January 2012 there were just twelve ATM branches with another three "proposed". How can that happen? How did it happen? Maybe the most pertinent question is: Why did it happen? There is no single answer to the last question, but perhaps it was something to do with the changes that…

  12. Polyphyly of true branching cyanobacteria (Stigonematales).

    PubMed

    Gugger, Muriel F; Hoffmann, Lucien

    2004-03-01

    Cyanobacteria with true branching are classified in Subsection V (formerly order Stigonematales) in the phylum CYANOBACTERIA: They exhibit a high degree of morphological complexity and are known from particular biotopes. Only a few stigonematalean morphotypes have been cultured, and therefore the high variability of morphotypes found in nature is under-represented in culture. Axenic cultures of Chlorogloeopsis and Fischerella sensu Rippka et al. were, to date, the only representatives of this Subsection in phylogenetic studies. The 16S rDNA sequence analysis data in this report confirm that heterocyst-forming cyanobacteria are a monophyletic group. However, unlike previous studies have suggested, these 16S rDNA data on new Stigonematales strains show that the true branching cyanobacteria are polyphyletic and can be separated into at least two major groups defined by their branching type, the first group being characterized by T-branching and the second group by Y-branching. Cyanobacteria with intercalary heterocysts and either no branching or false-branching also formed separate clusters. In consequence, our phylogenetic data do not correlate with the bacteriological and traditional classifications, which distinguish filamentous heterocystous cyanobacteria with or without true branching (Nostocales/Stigonematales).

  13. Phytochrome regulation of branching in Arabidopsis.

    PubMed

    Finlayson, Scott A; Krishnareddy, Srirama R; Kebrom, Tesfamichael H; Casal, Jorge J

    2010-04-01

    The red light:far-red light ratio perceived by phytochromes controls plastic traits of plant architecture, including branching. Despite the significance of branching for plant fitness and productivity, there is little quantitative and mechanistic information concerning phytochrome control of branching responses in Arabidopsis (Arabidopsis thaliana). Here, we show that in Arabidopsis, the negative effects of the phytochrome B mutation and of low red light:far-red light ratio on branching were largely due to reduced bud outgrowth capacity and an increased degree of correlative inhibition acting on the buds rather than due to a reduced number of leaves and buds available for branching. Phytochrome effects on the degree of correlative inhibition required functional BRANCHED1 (BRC1), BRC2, AXR1, MORE AXILLARY GROWTH2 (MAX2), and MAX4. The analysis of gene expression in selected buds indicated that BRC1 and BRC2 are part of different gene networks. The BRC1 network is linked to the growth capacity of specific buds, while the BRC2 network is associated with coordination of growth among branches. We conclude that the branching integrators BRC1 and BRC2 are necessary for responses to phytochrome, but they contribute differentially to these responses, likely acting through divergent pathways.

  14. Command and Data Handling Branch Internship

    NASA Technical Reports Server (NTRS)

    Billings, Rachel Mae

    2016-01-01

    Modular Integrated Stackable Layers (MISL) is a computer system designed for simple, fast, and cost effective flexible reconfiguration in space environments such as the ISS and Orion projects for various uses. Existing applications include wireless and wired communications, data acquisition and instrumentation, and camera systems, and potential applications include bus protocol converters and subsystem control. MISL is based on Texas Instruments (TI)' MSP430 16-bit ultra-low-power microcontroller device. The purpose of my project was to integrate the MISL system with a liquid crystal display (LCD) touchscreen. The LCD, manufactured by Crystalfontz and part number CFAF320240F-035T-TS, is a 320 by 240 RGB resistive color screen including an optional carrier board. The vast majority of the project was done with Altium Designer, a tool for printed circuit board (PCB) schematic capture, 3D design, and FPGA (Field Programmable Gate Array) development. The new PCB was to allow the LCD to directly stack to the rest of MISL. Research was done with datasheets for the TI microcontroller and touchscreen display in order to meet desired hardware specifications. Documentation on prior MISL projects was also utilized. The initial step was to create a schematic for the LCD, power bus, and data bus connections between components. A layout was then designed with the required physical dimensions, routed traces and vias, power and ground planes, layer stacks, and other specified design rules such as plane clearance and hole size. Multiple consultation sessions were held with Hester Yim, the technical discipline lead for the Command and Data Handling Branch, and Christy Herring, the lead PCB layout designer in the Electronic Design and Manufacturing Branch in order to ensure proper configuration. At the moment, the PCB is awaiting revision by the latter-mentioned branch. Afterwards, the board will begin to undergo the manufacturing and testing process. Throughout the internship at

  15. Quantitative Proteomics Analysis of Herbaceous Peony in Response to Paclobutrazol Inhibition of Lateral Branching

    PubMed Central

    Zhao, Daqiu; Gong, Saijie; Hao, Zhaojun; Meng, Jiasong; Tao, Jun

    2015-01-01

    Herbaceous peony (Paeonia lactiflora Pall.) is an emerging high-grade cut flower worldwide, which is usually used in wedding bouquets and known as the “wedding flower”. However, abundant lateral branches appear frequently in some excellent cultivars, and a lack of a method to remove Paeonia lactiflora lateral branches other than inefficient artificial methods is an obstacle for improving the quality of its cut flowers. In this study, paclobutrazol (PBZ) application was found to inhibit the growth of lateral branches in Paeonia lactiflora for the first time, including 96.82% decreased lateral bud number per branch, 77.79% and 42.31% decreased length and diameter of lateral branches, respectively, declined cell wall materials and changed microstructures. Subsequently, isobaric tag for relative and absolute quantitation (iTRAQ) technology was used for quantitative proteomics analysis of lateral branches under PBZ application and control. The results indicated that 178 differentially expressed proteins (DEPs) successfully obtained, 98 DEPs were up-regulated and 80 DEPs were down-regulated. Thereafter, 34 candidate DEPs associated with the inhibited growth of lateral branches were screened according to their function and classification. These PBZ-stress responsive candidate DEPs were involved in eight biological processes, which played a very important role in the growth and development of lateral branches together with the response to PBZ stress. These results provide a better understanding of the molecular theoretical basis for removing Paeonia lactiflora lateral branches using PBZ application. PMID:26473855

  16. A TrkB/EphrinA interaction controls retinal axon branching and synaptogenesis.

    PubMed

    Marler, Katharine J M; Becker-Barroso, Elena; Martínez, Albert; Llovera, Marta; Wentzel, Corinna; Poopalasundaram, Subathra; Hindges, Robert; Soriano, Eduardo; Comella, Joan; Drescher, Uwe

    2008-11-26

    Toward understanding topographically specific branching of retinal axons in their target area, we have studied the interaction between neurotrophin receptors and members of the Eph family. TrkB and its ligand BDNF are uniformly expressed in the retina and tectum, respectively, and exert a branch-promoting activity, whereas EphAs and ephrinAs are expressed in gradients in retina and tectum and can mediate a suppression of axonal branching. We have identified a novel cis interaction between ephrinA5 and TrkB on retinal ganglion cell axons. TrkB interacts with ephrinA5 via its second cysteine-rich domain (CC2), which is necessary and sufficient for binding to ephrinA5. Their functional interaction is twofold: ephrinA5 augments BDNF-promoted retinal axon branching in the absence of its activator EphA7-Fc, whereas EphA7-Fc application abolishes branching in a local and concentration-dependent manner. The importance of TrkB in this process is shown by the fact that overexpression of an isolated TrkB-CC2 domain interfering with the ephrinA/TrkB interaction abolishes this regulatory interplay, whereas knockdown of TrkB via RNA interference diminishes the ephrinA5-evoked increase in branching. The ephrinA/Trk interaction is neurotrophin induced and specifically augments the PI-3 kinase/Akt pathway generally known to be involved in the promotion of branching. In addition, ephrinAs/TrkB modulate axon branching and also synapse formation of hippocampal neurons. Our findings uncover molecular mechanisms of how spatially restricted axon branching can be achieved by linking globally expressed branch-promoting with differentially expressed branch-suppressing activities. In addition, our data suggest that growth factors and the EphA-ephrinA system interact in a way that affects axon branching and synapse development.

  17. Source, settling and degradation of branched glycerol dialkyl glycerol tetraethers in the marine water column

    NASA Astrophysics Data System (ADS)

    Yamamoto, Masanobu; Shimamoto, Akifumi; Fukuhara, Tatsuo; Tanaka, Yuichiro

    2016-10-01

    Branched glycerol dialkyl glycerol tetraethers (branched GDGTs) are commonly found in distal marine sediments. However, their presence in the water column, source and delivery process are not fully understood. In this study, we examined seasonal and depth variation in the flux of branched GDGTs in sinking particles and underlying sediment at 39°N, 147°E in the mid-latitude NW Pacific from November 1997 to August 1999. Branched GDGTs showed synchronous variation in their sinking flux at different depths, and the variation was similar to that of lithogenic material of eolian dust origin. Their degrees of cyclization and methylation were nearly constant and bear some resemblance to those of alkaline soils. This suggests that westerly winds transport branched GDGTs to the study site via the atmosphere from continental Asia. The sinking flux of branched GDGTs was higher in 1999 than in 1998, presumably reflecting changes in the migration path of Asian dust in response to the El Niño-Southern Oscillation. Synchronous variation in branched GDGT concentrations at different depths implies rapid vertical transport of branched GDGTs to deep water with a sinking velocity exceeding 260 m d-1. The sinking flux of the branched GDGTs decreased with increasing depth, but the rate of decrease was much smaller than those of other compounds. The preservation efficiency of branched GDGTs was 3.5-6.4% of surface inputs at the water-sediment interface, which is much higher than those of isoprenoid GDGTs (1.0-1.3%) and other compounds. The branched and isoprenoid tetraether (BIT) index values were extremely low (i.e. <0.0015) in comparison with any other studies so far. The BIT values in the surface sediment were five times higher than those in sinking particles, which is attributed to the preferential preservation of branched GDGTs in oxic environments.

  18. Processing-structure-property studies of: (I) submicron polymeric fibers produced by electrospinning and (II) films of linear low density polyethylenes as influenced by the short chain branch length in copolymers of ethylene/1-butene, ethylene/1-hexene and ethylene/1-octene synthesized by a single site metallocene catalyst

    NASA Astrophysics Data System (ADS)

    Gupta, Pankaj

    The overall theme of the research discussed in this dissertation has been to explore processing-structure-property relationships for submicron polymeric fibers produced by electrospinning (Part I) and to ascertain whether or not the length of the short chain branch has any effect on the physical properties of films of linear low-density polyethylenes (LLDPEs) (Part II). The research efforts discussed in Part I of this dissertation relate to some fundamental as well as more applied investigations involving electrospinning. These include investigating the effects of solution rheology on fiber formation and developing novel methodologies to fabricate polymeric mats comprising of high specific surface submicron fibers of more than one polymer, high chemical resistant substrates produced by in situ photo crosslinking during electrospinning, superparamagnetic flexible substrates by electrospinning a solution of an elastomeric polymer containing ferrite nanoparticles of Mn-Zn-Ni and substrates for filtration applications. Bicomponent electrospinning of poly(vinyl chloride)-polyurethane and poly(vinylidiene fluoride)-polyurethane was successfully performed. In addition, filtration properties of single and bicomponent electrospun mats of polyacrylonitrile and polystyrene were investigated. Results indicated lower aerosol penetration or higher filtration efficiencies of the filters based on submicron electrospun fibers in comparison to the conventional filter materials. In addition, Part II of this dissertation explores whether or not the length of the short chain branch affects the physical properties of blown and compression molded films of LLDPEs that were synthesized by a single site metallocene catalyst. Here, three resins based on copolymers of ethylene/1-butene, ethylene/1-hexene, and ethylene/1-octene were utilized that were very similar in terms of their molecular weight and distribution, melt rheology, density, crystallinity and short chain branching content and

  19. Floral bud damage compensation by branching and biomass allocation in genotypes of Brassica napus with different architecture and branching potential

    PubMed Central

    Pinet, Amélie; Mathieu, Amélie; Jullien, Alexandra

    2015-01-01

    Plant branching is a key process in the yield elaboration of winter oilseed rape (WOSR). It is also involved in plant tolerance to flower damage because it allows the setting of new fertile inflorescences. Here we characterize the changes in the branching and distribution of the number of pods between primary and secondary inflorescences in response to floral bud clippings. Then we investigate the impacts of the modifications in branching on the biomass allocation and its consequence on the crop productivity (harvest index). These issues were addressed on plants with contrasted architecture and branching potential, using three genotypes (Exocet, Pollen, and Gamin) grown under two levels of nitrogen fertilization. Clipping treatments of increasing intensities were applied to either inflorescences or flower buds. We were able to show that restoration of the number of pods after clipping is the main lever for the compensation. Genotypes presented different behaviors in branching and biomass allocation as a function of clipping treatments. The number of fertile ramifications increased for the high intensities of clipping. In particular, the growth of secondary ramifications carried by branches developed before clipping has been observed. The proportions of yield and of number of pods carried by these secondary axes increased and became almost equivalent to the proportion carried by primary inflorescences. In terms of biomass allocation, variations have also been evidenced in the relationship between pod dry mass on a given axis and the number of pods set, while the shoot/root ratio was not modified. The harvest index presented different responses: it decreased after flower buds clipping, while it was maintained after the clipping of the whole inflorescences. The results are discussed relative to their implications regarding the identification of interesting traits to be target in breeding programs in order to improve WOSR tolerance. PMID:25759703

  20. DIFFERENTIAL AND AGE-DEPENDENT EXPRESSION OF HYPERPOLARIZATION-ACTIVATED, CYCLIC NUCLEOTIDE-GATED CATION CHANNEL ISOFORMS 1–4 SUGGESTS EVOLVING ROLES IN THE DEVELOPING RAT HIPPOCAMPUS

    PubMed Central

    BENDER, R. A.; BREWSTER, A.; SANTORO, B.; LUDWIG, A.; HOFMANN, F.; BIEL, M.; BARAM, T. Z.

    2011-01-01

    Hyperpolarization-activated cation currents (Ih) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. Ih currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of Ih-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level. The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus. Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity. PMID:11682156

  1. APP Deletion Accounts for Age-Dependent Changes in the Bioenergetic Metabolism and in Hyperphosphorylated CaMKII at Stimulated Hippocampal Presynaptic Active Zones

    PubMed Central

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Neupärtl, Moritz; Array, Tabiwang N.; Harde, Eva; Beckert, Benedikt; Golghalyani, Vahid; Ackermann, Jörg; Koch, Ina; Müller, Ulrike C.; Karas, Michael; Acker-Palmer, Amparo; Volknandt, Walter

    2017-01-01

    Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice. PMID:28163681

  2. Age-dependent cyclic locomotor activity in the cricket, Gryllus bimaculatus, and the effect of adipokinetic hormone on locomotion and excitability.

    PubMed

    Fassold, Katharina; El-Damanhouri, Hassan I H; Lorenz, Matthias W

    2010-04-01

    Excitability and locomotor activity of male and female last instar larvae and adults of the two-spotted cricket are measured under crowded conditions, allowing the animals to interact with conspecifics during observations. Male and female last instar larvae display age-dependent cyclic patterns of activity with maxima during early to mid scotophase and minima during early photophase. A period of low locomotor activity without time of day-dependent cyclic changes starts 1 day before the final moult and lasts until 1 day after the moult. Then, both excitability and locomotor activity increase and become cyclic again within 2 or 3 days. The cyclic changes gradually dampen in adult females older than 6 days and finally cease. When injected into photophase larvae and adults, adipokinetic hormone (AKH) increases excitability and locomotor activity in a dose-dependent manner, whereas it has no such effect when injected into scotophase animals. Other behaviours (jumping, hind wing trembling) that mostly occur in scotophase crickets are also increased by injecting AKH into photophase crickets. We argue that AKH could be responsible for linking the endogenous clock output with the cyclic changes in locomotor activity. Furthermore, AKH may serve to synchronise metabolism and behaviour to optimise larval development and reproduction.

  3. The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus.

    PubMed

    Kim, Su-Jeong; Guerrero, Noel; Wassef, Gabriella; Xiao, Jialin; Mehta, Hemal H; Cohen, Pinchas; Yen, Kelvin

    2016-07-26

    Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age-specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner.

  4. Oogenesis-flight syndrome in crickets: age-dependent egg production, flight performance, and biochemical composition of the flight muscles in adult female Gryllus bimaculatus.

    PubMed

    Lorenz, Matthias W

    2007-08-01

    Age-dependent changes in flight performance, biochemical composition of flight muscles, and fresh mass of the flight muscles and ovaries were analysed in adult female two-spotted crickets, Gryllus bimaculatus. After the final moult the flight muscle mass increased significantly to a maximum at days 2 and 3. On day 2 the highest flight activity was also observed. Between days 2 and 3 the ovary weight started to rapidly increase due to vitellogenic egg growth, which continued at a high rate until day 10. With the onset of ovarial growth, flight performance decreased and the flight muscles started to histolyse. A high correlation between flight muscle mass and the content of protein, lipid, glycogen, and free carbohydrate in the flight muscle indicated that energy-rich substrates from the degrading flight muscles were used to fuel oogenesis, although flight muscle histolysis can provide only a small fraction of the substrates needed for egg production. In general, there was a clear trade-off between egg production and flight ability. Surprisingly, however, some females possessed well-developed ovaries but displayed no signs of flight muscle histolysis. This observation was corroborated by flight experiments which revealed that, although most flying females had small ovaries, some of them carried an appreciable amount of mature eggs, and thus, somehow managed to evade the oogenesis-flight syndrome.

  5. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    PubMed Central

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  6. Age dependence of dielectric properties of bovine brain and ocular tissues in the frequency range of 400 MHz to 18 GHz

    NASA Astrophysics Data System (ADS)

    Schmid, Gernot; Überbacher, Richard

    2005-10-01

    In order to identify possible age-dependent dielectric properties of brain and eye tissues in the frequency range of 400 MHz to 18 GHz, measurements on bovine grey and white matter as well as on cornea, lens (cortical) and the vitreous body were performed using a commercially available open-ended coaxial probe and a computer-controlled vector network analyser. Freshly excised tissues of 52 animals of two age groups (42 adult animals, i.e. 16-24 month old and 10 young animals, i.e. 4-6 month old calves) were examined within 8 min (brain tissue) and 15 min (eye tissue), respectively, of the animals' death. Tissue temperatures for the measurements were 32 ± 1 °C and 25 ± 1 °C for brain and eye tissues, respectively. Statistical analysis of the measured data revealed significant differences in the dielectric properties of white matter and cortical lens tissue between the adult and the young group. In the case of white matter the mean values of conductivity and permittivity of young tissue were 15%-22% and 12%-15%, respectively, higher compared to the adult tissue in the considered frequency range. Similarly, young cortical lens tissue was 25%-76% higher in conductivity and 27%-39% higher in permittivity than adult cortical lens tissue.

  7. Neural activity and neurotransmission regulate the maturation of the innervation field of cortical GABAergic interneurons in an age-dependent manner.

    PubMed

    Baho, Elie; Di Cristo, Graziella

    2012-01-18

    Neural activity guides the patterning of neuron synaptic territory in the developing nervous system. Evidence supporting this hypothesis comes from numerous studies on projection neurons in neuromuscular and visual systems. It is unknown whether the innervation field of GABAergic interneurons, which forms local dense innervations, follows similar rules. Cortical basket cells innervate hundreds of pyramidal cell somata and proximal dendrites. Thanks to this connectivity pattern, they can tightly control neural excitability and synchronization. Here we show that reducing excitation, and thus neurotransmitter release, in mouse cortical single basket cells in slice cultures decreases the number of innervated cells without changing the pattern of perisomatic innervation, both at the peak and after the proliferation phase of perisomatic synapse formation. Conversely, suppressing neurotransmitter release in single basket cells can have completely opposite effects depending on the developmental stage. Our results reveal a remarkably specific and age-dependent role of neural activity and neurotransmission levels in the establishment of the synaptic territory of cortical GABAergic cells.

  8. Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the Fmr1 Knockout Mouse Model of Fragile X Syndrome.

    PubMed

    Martin, Henry G S; Lassalle, Olivier; Brown, Jonathan T; Manzoni, Olivier J

    2016-05-01

    The most common inherited monogenetic cause of intellectual disability is Fragile X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood; however, neurophysiological data exploring this phenomenon are limited. The Fmr1 knockout (Fmr1KO) mouse models FXS, but studies in these mice of prefrontal cortex (PFC) function are underrepresented, and aging linked data are absent. We studied synaptic physiology and activity-dependent synaptic plasticity in the medial PFC of Fmr1KO mice from 2 to 12 months. In young adult Fmr1KO mice, NMDA receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12-month-old mice this LTP is impaired. In parallel, there was an increase in the AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12-month-old Fmr1KO mice. We found that acute pharmacological blockade of mGlu5 receptor in 12-month-old Fmr1KO mice restored a normal AMPAR/NMDAR ratio and LTP. Taken together, the data reveal an age-dependent deficit in LTP in Fmr1KO mice, which may correlate to some of the complex age-related deficits in FXS.

  9. APP Deletion Accounts for Age-Dependent Changes in the Bioenergetic Metabolism and in Hyperphosphorylated CaMKII at Stimulated Hippocampal Presynaptic Active Zones.

    PubMed

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Neupärtl, Moritz; Array, Tabiwang N; Harde, Eva; Beckert, Benedikt; Golghalyani, Vahid; Ackermann, Jörg; Koch, Ina; Müller, Ulrike C; Karas, Michael; Acker-Palmer, Amparo; Volknandt, Walter

    2017-01-01

    Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.

  10. The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus

    PubMed Central

    Kim, Su-Jeong; Guerrero, Noel; Wassef, Gabriella; Xiao, Jialin; Mehta, Hemal H.; Cohen, Pinchas; Yen, Kelvin

    2016-01-01

    Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age-specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner. PMID:27384491

  11. Study of Age-Dependent Structural and Functional Changes of Mitochondria in Skeletal Muscles and Heart of Naked Mole Rats (Heterocephalus glaber).

    PubMed

    Holtze, S; Eldarov, C M; Vays, V B; Vangeli, I M; Vysokikh, M Yu; Bakeeva, L E; Skulachev, V P; Hildebrandt, T B

    2016-12-01

    Morphometric analysis of mitochondria in skeletal muscles and heart of 6- and 60-month-old naked mole rats (Heterocephalus glaber) revealed a significant age-dependent increase in the total area of mitochondrial cross-sections in studied muscle fibers. For 6- and 60-month-old animals, these values were 4.8 ± 0.4 and 12.7 ± 1.8%, respectively. This effect is mainly based on an increase in the number of mitochondria. In 6-month-old naked mole rats, there were 0.23 ± 0.02 mitochondrial cross-sections per µm(2) of muscle fiber, while in 60-month-old animals this value was 0.47 ± 0.03. The average area of a single mitochondrial cross-section also increased with age in skeletal muscles - from 0.21 ± 0.01 to 0.29 ± 0.03 µm(2). Thus, naked mole rats show a drastic enlargement of the mitochondrial apparatus in skeletal muscles with age due to an increase in the number of mitochondria and their size. They possess a neotenic type of chondriome accompanied by specific features of mitochondrial functioning in the state of oxidative phosphorylation and a significant decrease in the level of matrix adenine nucleotides.

  12. Age-Dependent Loss of Tolerance to an Immunodominant Epitope of Glutamic Acid Decarboxylase in Diabetic prone RIP-B7/DR4 Mice

    PubMed Central

    Gebe, John A.; Unrath, Kellee A; Falk, Ben A.; Ito, Kouichi; Wen, Li; Daniels, Terri L.; Lernmark, Åke; Nepom, Gerald T.

    2007-01-01

    We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice, and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4+/FoxP3+ cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice. PMID:16979383

  13. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

    PubMed

    Gebe, John A; Unrath, Kellee A; Falk, Ben A; Ito, Kouichi; Wen, Li; Daniels, Terri L; Lernmark, Ake; Nepom, Gerald T

    2006-12-01

    We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice.

  14. Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts

    PubMed Central

    Park, Jinny; Song, Hwa-Ryung; Lee, Minok; Hong, On-Yu; Whang, Pyoung H.; Han, Myung-Kwan; Kwon, Kang-Beom

    2016-01-01

    Reactive oxygen species (ROS) play a major role in both chronological aging and photoaging. ROS induce skin aging through their damaging effect on cellular constituents. However, the origins of ROS have not been fully elucidated. We investigated that ROS generation of replicative senescent fibroblasts is generated by the modulation of phosphatidylinositol 3,4,5-triphosphate (PIP3) metabolism. Reduction of the PTEN protein, which dephosphorylates PIP3, was responsible for maintaining a high level of PIP3 in replicative cells and consequently mediated the activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway. Increased ROS production was blocked by inhibition of PI3K or protein kinase C (PKC) or by NADPH oxidase activating in replicative senescent cells. These data indicate that the signal pathway to ROS generation in replicative aged skin cells can be stimulated by reduced PTEN level. Our results provide new insights into skin aging-associated modification of the PI3K/NADPH oxidase signaling pathway and its relationship with a skin aging-dependent increase of ROS in human dermal fibroblasts. PMID:28003865

  15. Analysis of Capillary Rise in Asymmetric Branch-Like Capillary

    NASA Astrophysics Data System (ADS)

    Li, Caoxiong; Shen, Yinghao; Ge, Hongkui; Yang, Zhihui; Su, Shuai; Ren, Kai; Huang, Heyu

    2016-05-01

    Transport in porous media is common in nature, attracting many attentions for a long time. Tree-like network model is often used as a simplification for porous space, expressing the complexity of pore spaces instead of capillary bundle. To investigate spontaneous imbibition characteristics in this network, a dynamic asymmetric branch-like capillary model is used to represent basic network structure, using fractal method to represent tortuosity. This work investigates the influence of parameters on imbibition process in the branch-like capillary model. An analytical equation for the imbibition mass versus time is derived. Parameters from capillary structures to liquid properties are taken into account and analyzed based on the numerical solution of the equation. It is found that the imbibition process in asymmetric branch-like capillary model can be recognized by four sections and brunching tubes are positive for imbibition process. Concomitantly, meniscus arrest event is simulated and discussed. Moreover, the influence of parameters on imbibition process is discussed. These parameters can be classified as static and dynamic. Static parameters mainly change the capillary force, which are related to the ultimate imbibition mass or imbibition ability, while dynamic parameters mainly have influence on resistance of flowing fluid, which are related to the imbibition speed in the imbibition process.

  16. Toward an understanding of fibrin branching structure

    NASA Astrophysics Data System (ADS)

    Fogelson, Aaron L.; Keener, James P.

    2010-05-01

    The blood clotting enzyme thrombin converts fibrinogen molecules into fibrin monomers which polymerize to form a fibrous three-dimensional gel. The concentration of thrombin affects the architecture of the resulting gel, in particular, a higher concentration of thrombin produces a gel with more branch points per unit volume and with shorter fiber segments between branch points. We propose a mechanism by which fibrin branching can occur and show that this mechanism can lead to dependence of the gel’s structure (at the time of gelation) on the rate at which monomer is supplied. A higher rate of monomer supply leads to a gel with a higher branch concentration and with shorter fiber segments between branch points. The origin of this dependence is explained.

  17. Using branching simulations in treatment fidelity plans.

    PubMed

    Kovach, Christine R; Rababa, Mohammad

    2014-01-01

    The purpose of this article is to present a new approach to treatment fidelity using branching simulations. Branching simulations are case scenarios that require the user to generate a series of step-by-step decisions and actions. The user is given immediate feedback on the consequences of his or her decisions and actions. Branching simulations may be a particularly useful fidelity strategy for interventions that require clinical decision making represented in terms of a flow of critical thinking and action steps. Results of fidelity testing in the current study using branching simulations revealed that 15 (22%) of 67 interventionists scored below the study's a priori 80% criterion for full retraining and retesting. Thirty (45%) interventionists needed partial retraining in using specific components of the intervention. Potential threats to internal validity posed by inadequate or erroneous adherence to multicomponent intervention protocols can be decreased through treatment fidelity using branching simulations.

  18. Root branching: mechanisms, robustness, and plasticity.

    PubMed

    Dastidar, Mouli Ghosh; Jouannet, Virginie; Maizel, Alexis

    2012-01-01

    Plants are sessile organisms that must efficiently exploit their habitat for water and nutrients. The degree of root branching impacts the efficiency of water uptake, acquisition of nutrients, and anchorage. The root system of plants is a dynamic structure whose architecture is determined by modulation of primary root growth and root branching. This plasticity relies on the continuous integration of environmental inputs and endogenous developmental programs controlling root branching. This review focuses on the cellular and molecular mechanisms involved in the regulation of lateral root distribution, initiation, and organogenesis with the main focus on the root system of Arabidopsis thaliana. We also examine the mechanisms linking environmental changes to the developmental pathways controlling root branching. Recent progress that emphasizes the parallels to the formation of root branches in other species is discussed.

  19. Specialization and evolutionary branching within migratory populations.

    PubMed

    Torney, Colin J; Levin, Simon A; Couzin, Iain D

    2010-11-23

    Understanding the mechanisms that drive specialization and speciation within initially homogeneous populations is a fundamental challenge for evolutionary theory. It is an issue of relevance for significant open questions in biology concerning the generation and maintenance of biodiversity, the origins of reciprocal cooperation, and the efficient division of labor in social or colonial organisms. Several mathematical frameworks have been developed to address this question and models based on evolutionary game theory or the adaptive dynamics of phenotypic mutation have demonstrated the emergence of polymorphic, specialized populations. Here we focus on a ubiquitous biological phenomenon, migration. Individuals in our model may evolve the capacity to detect and follow an environmental cue that indicates a preferred migration route. The strategy space is defined by the level of investment in acquiring personal information about this route or the alternative tendency to follow the direction choice of others. The result is a relation between the migratory process and a game theoretic dynamic that is generally applicable to situations where information may be considered a public good. Through the use of an approximation of social interactions, we demonstrate the emergence of a stable, polymorphic population consisting of an uninformed subpopulation that is dependent upon a specialized group of leaders. The branching process is classified using the techniques of adaptive dynamics.

  20. Characterization of the branching patterns of glycogen branching enzyme truncated on the N-terminus.

    PubMed

    Devillers, Claire H; Piper, Mary E; Ballicora, Miguel A; Preiss, Jack

    2003-10-01

    Truncation of 112 amino acids at the N-terminus (Nd(1-112)) changes the chain transfer pattern of the Escherichia coli glycogen branching enzyme (GBE) [Arch. Biochem. Biophys. 397 (2002) 279]. We investigated further the role of the N-terminus by engineering other truncated GBEs and analyzing the branching pattern by high-performance anion-exchange chromatography. The wild type GBE transfers mainly chains with a degree of polymerization (d.p.) of 8-14, the Nd(1-112) enzyme transfers a greater proportion of chains with higher d.p. 15-20, whereas the 63- and 83-amino acid deleted enzymes had an intermediate pattern of transferred chains (d.p. 10-20). These data showed that a progressive shortening of the N-terminus leads to a gradual increase in the length of the transferred chains, suggesting that the N-terminus provides a support for the glucan substrate during the processes of cleavage and transfer of the alpha-(1-4) glucan chains.

  1. Pen Branch Delta and Savannah River Swamp Hydraulic Model

    SciTech Connect

    Chen, K.F.

    1999-05-13

    The proposed Savannah River Site (SRS) Wetlands Restoration Project area is located in Barnwell County, South Carolina on the southwestern boundary of the SRS Reservation. The swamp covers about 40.5 km2 and is bounded to the west and south by the Savannah River and to the north and east by low bluffs at the edge of the Savannah River floodplain. Water levels within the swamp are determined by stage along the Savannah River, local drainage, groundwater seepage, and inflows from four tributaries, Beaver Dam Creek, Fourmile Branch, Pen Branch, and Steel Creek. Historic discharges of heated process water into these tributaries scoured the streambed, created deltas in the adjacent wetland, and killed native vegetation in the vicinity of the delta deposits. Future releases from these tributaries will be substantially smaller and closer to ambient temperatures. One component of the proposed restoration project will be to reestablish indigenous wetland vegetation on the Pen Branch delta that covers about 1.0 km2. Long-term predictions of water levels within the swamp are required to determine the characteristics of suitable plants. The objective of the study was to predict water levels at various locations within the proposed SRS Wetlands Restoration Project area for a range of Savannah River flows and regulated releases from Pen Branch. TABS-MD, a United States Army Corps of Engineer developed two-dimensional finite element open channel hydraulic computer code, was used to model the SRS swamp area for various flow conditions.

  2. Branch architecture, light interception and crown development in saplings of a plagiotropically branching tropical tree, Polyalthia jenkinsii (Annonaceae).

    PubMed

    Osada, Noriyuki; Takeda, Hiroshi

    2003-01-01

    To investigate crown development patterns, branch architecture, branch-level light interception, and leaf and branch dynamics were studied in saplings of a plagiotropically branching tree species, Polyalthia jenkinsii Hk. f. & Thoms. (Annonaceae) in a Malaysian rain forest. Lengths of branches and parts of the branches lacking leaves ('bare' branches) were smaller in upper branches than in lower branches within crowns, whereas lengths of 'leafy' parts and the number of leaves per branch were larger in intermediate than in upper and lower branches. Maximum diffuse light absorption (DLA) of individual leaves was not related to sapling height or branch position within crowns, whereas minimum DLA was lower in tall saplings. Accordingly, branch-level light interception was higher in intermediate than in upper and lower branches. The leaf production rate was higher and leaf loss rate was smaller in upper than in intermediate and lower branches. Moreover, the branch production rate of new first-order branches was larger in the upper crowns. Thus, leaf and branch dynamics do not correspond to branch-level light interception in the different canopy zones. As a result of architectural constraints, branches at different vertical positions experience predictable light microenvironments in plagiotropic species. Accordingly, this pattern of carbon allocation among branches might be particularly important for growth and crown development in plagiotropic species.

  3. A tool for simulating parallel branch-and-bound methods

    NASA Astrophysics Data System (ADS)

    Golubeva, Yana; Orlov, Yury; Posypkin, Mikhail

    2016-01-01

    The Branch-and-Bound method is known as one of the most powerful but very resource consuming global optimization methods. Parallel and distributed computing can efficiently cope with this issue. The major difficulty in parallel B&B method is the need for dynamic load redistribution. Therefore design and study of load balancing algorithms is a separate and very important research topic. This paper presents a tool for simulating parallel Branchand-Bound method. The simulator allows one to run load balancing algorithms with various numbers of processors, sizes of the search tree, the characteristics of the supercomputer's interconnect thereby fostering deep study of load distribution strategies. The process of resolution of the optimization problem by B&B method is replaced by a stochastic branching process. Data exchanges are modeled using the concept of logical time. The user friendly graphical interface to the simulator provides efficient visualization and convenient performance analysis.

  4. Universal properties of branching random walks in confined geometries

    NASA Astrophysics Data System (ADS)

    de Mulatier, C.; Mazzolo, A.; Zoia, A.

    2014-08-01

    Characterizing the occupation statistics of random walks through confined geometries amounts to assessing the distribution of the travelled length ℓ and the number of collisions n performed by the stochastic process in a given region, for which remarkably simple Cauchy-like formulas were established in the case of branching Pearson random walks with exponentially distributed jumps. In this letter, we derive two key results: first, we show that such formulas strikingly carry over to the much broader class of branching processes with arbitrary jumps, and have thus a universal character; second, we obtain a stronger version of these formulas relating the travelled length density and the collision density at any point of the phase space. Our results are key to such technological issues as the analysis of radiation flow for nuclear reactor design and medical diagnosis and apply more broadly to physical and biological systems with diffusion, reproduction and death.

  5. Tillering and panicle branching genes in rice.

    PubMed

    Liang, Wei-hong; Shang, Fei; Lin, Qun-ting; Lou, Chen; Zhang, Jing

    2014-03-01

    Rice (Oryza sativa L.) is one of the most important staple food crops in the world, and rice tillering and panicle branching are important traits determining grain yield. Since the gene MONOCULM 1 (MOC 1) was first characterized as a key regulator in controlling rice tillering and branching, great progress has been achieved in identifying important genes associated with grain yield, elucidating the genetic basis of yield-related traits. Some of these important genes were shown to be applicable for molecular breeding of high-yielding rice. This review focuses on recent advances, with emphasis on rice tillering and panicle branching genes, and their regulatory networks.

  6. UNILATERAL WHISKER CLIPPING EXACERBATES ETHANOL-INDUCED SOCIAL AND SOMATOSENSORY BEHAVIORAL DEFICITS IN A SEX-AND AGE-DEPENDENT MANNER

    PubMed Central

    Wellmann, Kristen A.; Mooney, Sandra M.

    2015-01-01

    Prenatal exposure to ethanol results in sensory deficits and altered social interactions in animal and clinical populations. Sensory stimuli serve as important cues and shape sensory development; developmental exposure to ethanol or sensory impoverishment can impair somatosensory development, but their combined effects on behavioral outcomes are unknown. We hypothesized that 1) chronic prenatal ethanol exposure would disrupt social interaction and somatosensory performance during adolescence, 2) that a mild sensory impoverishment (neonatal unilateral whisker clipping; WC) would have a mildly impairing to sub-threshold effect on these behavioral outcomes, and 3) that the effect of ethanol would be exacerbated by WC. Long-Evans dams were fed a liquid diet containing ethanol or pair-fed with non-ethanol diet on gestational day (G) 6-G21. Chow-fed control animals were also included. One male and female pup per litter underwent WC on postnatal day (P)1, P3, and P5. Controls were unclipped. Offspring underwent social interaction on P28 or P42, and gap-crossing (GC) on P31 or P42. Ethanol-exposed pups played less and crossed shorter gaps than control pups regardless of age or sex. WC further exacerbated ethanol-induced play fighting and GC deficits in all males but only in 28-day-old females. WC alone reduced sniffing in all males and in younger females. Thus, prenatal ethanol exposure induced deficits in social interaction and somatosensory performance during adolescence. Sensory impoverishment exacerbates ethanol's effect in 28-day-old male and female animals and in 42-day-old males, suggesting sex-and age-dependent changes in outcomes in ethanol-exposed offspring. PMID:25283794

  7. IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor.

    PubMed

    Deane, Rashid; Sagare, Abhay; Hamm, Katie; Parisi, Margaret; LaRue, Barbra; Guo, Huang; Wu, Zhenhua; Holtzman, David M; Zlokovic, Berislav V

    2005-12-14

    The role of blood-brain barrier (BBB) transport in clearance of amyloid beta-peptide (Abeta) by Abeta immunotherapy is not fully understood. To address this issue, we studied the effects of peripherally and centrally administered Abeta-specific IgG on BBB influx of circulating Abeta and efflux of brain-derived Abeta in APPsw(+/-) mice, a model that develops Alzheimer's disease-like amyloid pathology, and wild-type mice. Our data show that anti-Abeta IgG blocks the BBB influx of circulating Abeta in APPsw(+/-) mice and penetrates into the brain to sequester brain Abeta. In young mice, Abeta-anti-Abeta complexes were cleared from brain to blood by transcytosis across the BBB via the neonatal Fc receptor (FcRn) and the low-density lipoprotein receptor-related protein (LRP), whereas in older mice, there was an age-dependent increase in FcRn-mediated IgG-assisted Abeta BBB efflux and a decrease in LRP-mediated clearance of Abeta-anti-Abeta complexes. Inhibition of the FcRn pathway in older APPsw(+/-) mice blocked clearance of endogenous Abeta40/42 by centrally administered Abeta immunotherapy. Moreover, deletion of the FcRn gene in wild-type mice inhibited clearance of endogenous mouse Abeta40/42 by systemically administered anti-Abeta. Our data suggest that the FcRn pathway at the BBB plays a crucial role in IgG-assisted Abeta removal from the aging brain.

  8. A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction.

    PubMed

    Weiss, Robert B; Baker, Timothy B; Cannon, Dale S; von Niederhausern, Andrew; Dunn, Diane M; Matsunami, Nori; Singh, Nanda A; Baird, Lisa; Coon, Hilary; McMahon, William M; Piper, Megan E; Fiore, Michael C; Scholand, Mary Beth; Connett, John E; Kanner, Richard E; Gahring, Lorise C; Rogers, Scott W; Hoidal, John R; Leppert, Mark F

    2008-07-11

    People who begin daily smoking at an early age are at greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic variants and nicotine dependence assessed in adulthood will be stronger among smokers who began daily nicotine exposure during adolescence. We compared nicotine addiction-measured by the Fagerstrom Test of Nicotine Dependence-in three cohorts of long-term smokers recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene approach with the neuronal nAChR subunit genes. This SNP panel included common coding variants and haplotypes detected in eight alpha and three beta nAChR subunit genes found in European American populations. In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity (p = 2.0x10(-5); odds ratio = 1.82; 95% confidence interval 1.39-2.39) in subjects who began daily smoking at or before the age of 16, an exposure period that results in a more severe form of adult nicotine dependence. A substantial shift in susceptibility versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%) was observed in the group that began smoking by age 16. This genetic effect was not observed in subjects who began daily nicotine use after the age of 16. These results establish a strong mechanistic link among early nicotine exposure, common CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent populations of European origins. The identification of an age-dependent susceptibility haplotype reinforces the importance of preventing early exposure to tobacco through public health policies.

  9. Age-Dependent Switch of the Role of Serotonergic 5-HT1A Receptors in Gating Long-Term Potentiation in Rat Visual Cortex In Vivo

    PubMed Central

    Gagolewicz, Peter J.; Dringenberg, Hans C.

    2016-01-01

    The rodent primary visual cortex (V1) is densely innervated by serotonergic axons and previous in vitro work has shown that serotonin (5-HT) can modulate plasticity (e.g., long-term potentiation (LTP)) at V1 synapses. However, little work has examined the effects of 5-HT on LTP under in vivo conditions. We examined the role of 5-HT on LTP in V1 elicited by theta burst stimulation (TBS) of the lateral geniculate nucleus in urethane-anesthetized (adult and juvenile) rats. Thalamic TBS consistently induced potentiation of field postsynaptic potentials (fPSPs) recorded in V1. While 5-HT application (0.1–10 mM) itself did not alter LTP levels, the broad-acting 5-HT receptor antagonists methiothepin (1 mM) resulted in a clear facilitation of LTP in adult animals, an effect that was mimicked by the selective 5-HT1A receptor antagonist WAY 100635 (1 mM). Interestingly, in juvenile rats, WAY 100635 application inhibited LTP, indicative of an age-dependent switch in the role of 5-HT1A receptors in gating V1 plasticity. Analyses of spontaneous electrocorticographic (ECoG) activity in V1 indicated that the antagonist-induced LTP enhancement was not related to systematic changes in oscillatory activity in V1. Together, these data suggest a facilitating role of 5-HT1A receptor activation on LTP in the juvenile V1, which switches to a tonic, inhibitory influence in adulthood. PMID:27247804

  10. Stress Marker Signatures in Lesion Mimic Single and Double Mutants Identify a Crucial Leaf Age-Dependent Salicylic Acid Related Defense Signal.

    PubMed

    Kaurilind, Eve; Brosché, Mikael

    2017-01-01

    Plants are exposed to abiotic and biotic stress conditions throughout their lifespans that activates various defense programs. Programmed cell death (PCD) is an extreme defense strategy the plant uses to manage unfavorable environments as well as during developmentally induced senescence. Here we investigated the role of leaf age on the regulation of defense gene expression in Arabidopsis thaliana. Two lesion mimic mutants with misregulated cell death, catalase2 (cat2) and defense no death1 (dnd1) were used together with several double mutants to dissect signaling pathways regulating defense gene expression associated with cell death and leaf age. PCD marker genes showed leaf age dependent expression, with the highest expression in old leaves. The salicylic acid (SA) biosynthesis mutant salicylic acid induction deficient2 (sid2) had reduced expression of PCD marker genes in the cat2 sid2 double mutant demonstrating the importance of SA biosynthesis in regulation of defense gene expression. While the auxin- and jasmonic acid (JA)- insensitive auxin resistant1 (axr1) double mutant cat2 axr1 also led to decreased expression of PCD markers; the expression of several marker genes for SA signaling (ISOCHORISMATE SYNTHASE 1, PR1 and PR2) were additionally decreased in cat2 axr1 compared to cat2. The reduced expression of these SA markers genes in cat2 axr1 implicates AXR1 as a regulator of SA signaling in addition to its known role in auxin and JA signaling. Overall, the current study reinforces the important role of SA signaling in regulation of leaf age-related transcript signatures.

  11. Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study.

    PubMed

    Nakajima, Shinichiro; Caravaggio, Fernando; Boileau, Isabelle; Chung, Jun K; Plitman, Eric; Gerretsen, Philip; Wilson, Alan A; Houle, Sylvain; Mamo, David C; Graff-Guerrero, Ariel

    2015-11-01

    Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D2/3 receptor (D2/3R) availability decreases with age. However, no study has specifically assessed whether D2/3R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D3R availability changes with age in healthy humans. Thus, we explored the relationship between age and D2/3R availability in healthy humans using the D3 receptor (D3R)-preferential agonist radiotracer [(11)C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [(11)C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D3R to the [(11)C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D3R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D2/3R-mixed regions, and the caudate and putamen represent D2 receptor (D2R)-specific regions. With [(11)C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BPND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [(11)C]-Raclopride, negative correlations were observed between age and BPND in the caudate (r(68)=-0.50, P<0.001), putamen (r(68)=-0.41, P<0.001), and ventral striatum (r(68)=-0.43, P<0.001). In conclusion, in contrast with the age-dependent decrease in D2R availability, these findings suggest that D3R availability does not change with age.

  12. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

    PubMed Central

    Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

    2016-01-01

    Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo—in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29–38, evident as higher rates of induced action potential firing at low current injections (100–200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26–28) and older animals (PD40–62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits. PMID:27065812

  13. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

    PubMed

    Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

    2016-01-01

    Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  14. Age-Dependent Decrease and Alternative Splicing of Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism

    PubMed Central

    Muratore, Christina R.; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Persico, Antonio M.; Lintas, Carla; De La Monte, Suzanne; Deth, Richard C.

    2013-01-01

    The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin) from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression. PMID:23437274

  15. Age-dependent effects of microglial inhibition in vivo on Alzheimer’s disease neuropathology using bioactive-conjugated iron oxide nanoparticles

    PubMed Central

    2013-01-01

    Background Tau dysfunction is believed to be the primary cause of neurodegenerative disorders referred to as tauopathies, including Alzheimer’s disease, Pick’s disease, frontotemporal dementia and Parkinsonism. The role of microglial cells in the pathogenesis of tauopathies is still unclear. The activation of microglial cells has been correlated with neuroprotective effects through the release of neurotrophic factors and through clearance of cell debris and phagocytosis of cells with intracellular inclusions. In contrast, microglial activation has also been linked with chronic neuroinflammation contributing to the development of neurodegenerative diseases such as tauopathies. Microglial activation has been recently reported to precede tangle formation and the attenuation of tau pathology occurs after immunosuppression of transgenic mice. Methods Here we report the specific inhibition of microglial cells in rTg4510 tau-mutant mice by using fibrin γ377-395 peptide conjugated to iron oxide (γ-Fe2O3) nanoparticles of 21 ± 3.5 nm diameter. Results Stabilization of the peptide by its covalent conjugation to the γ-Fe2O3 nanoparticles significantly decreased the number of the microglial cells compared to the same concentration of the free peptide. The specific microglial inhibition induces different effects on tau pathology in an age dependent manner. The reduction of activation of microglial cells at an early age increases the number of neurons with hyperphosphorylated tau in transgenic mice. In contrast, reduction of activation of microglial cells reduced the severity of the tau pathology in older mice. The number of neurons with hyperphosphorylated tau and the number of neurons with tangles are reduced than those in animals not receiving the fibrin γ377-395 peptide-nanoparticle conjugate. Conclusions These results demonstrate a differential effect of microglial activity on tau pathology using the fibrin γ377-395 peptide-nanoparticle conjugate, depending on

  16. Evidence that a single gene with gender- and age-dependent effects influences systolic blood pressure determination in a population-based sample.

    PubMed Central

    Pérusse, L; Moll, P P; Sing, C F

    1991-01-01

    A biometrical study was carried out to evaluate the role of genetic variation in determining interindividual differences in systolic blood pressure (SBP) in the population at large. SBP was measured in 1,266 Caucasian individuals in 278 pedigrees ascertained through children enrolled in the Rochester, MN, school system. The sample included 646 males and 620 females 550 years of age and not taking antihypertensive medication or oral contraceptives. Complex segregation analysis was first applied to these data by using a regression model for age, in which the intercept was gender and ousiotype specific but in which the slope was only gender specific. When the slope was independent of ousiotype, neither variation at a single gene combined with polygenic effects (mixed genetic model) nor variation in a single environmental factor combined with polygenetic effects (mixed environmental model) explained the distribution of SBP in this sample. However, when the regression model for age allowed both the intercept and slope to be gender and ousiotype specific, the mixed environmental model was rejected whereas the mixed genetic model was not. These results suggest that variability in SBP may be influenced by major effects of allelic variation at a single gene that are both gender and age dependent. This study (1) suggests that particular genotypes determined by a single gene are associated with a steeper increase of SBP with age among males and females 550 years of age in the general population and (2) illustrates the need to consider models that more realistically represent the relationship between genotypic variability and phenotypic variability, to understand the genetics of human quantitative traits. PMID:2063879

  17. NRFL-1, the C. elegans NHERF orthologue, interacts with amino acid transporter 6 (AAT-6) for age-dependent maintenance of AAT-6 on the membrane.

    PubMed

    Hagiwara, Kohei; Nagamori, Shushi; Umemura, Yasuhiro M; Ohgaki, Ryuichi; Tanaka, Hidekazu; Murata, Daisuke; Nakagomi, Saya; Nomura, Kazuko H; Kage-Nakadai, Eriko; Mitani, Shohei; Nomura, Kazuya; Kanai, Yoshikatsu

    2012-01-01

    The NHERF (Na(+)/H(+) exchanger regulatory factor) family has been proposed to play a key role in regulating transmembrane protein localization and retention at the plasma membrane. Due to the high homology between the family members, potential functional compensations have been a concern in sorting out the function of individual NHERF numbers. Here, we studied C. elegans NRFL-1 (C01F6.6) (nherf-like protein 1), the sole C. elegans orthologue of the NHERF family, which makes worm a model with low genetic redundancy of NHERF homologues. Integrating bioinformatic knowledge of C. elegans proteins into yeast two-hybrid scheme, we identified NRFL-1 as an interactor of AAT-6, a member of the C. elegans AAT (amino acid transporter) family. A combination of GST pull-down assay, localization study, and co-immunoprecipitation confirmed the binding and characterized the PDZ interaction. AAT-6 localizes to the luminal membrane even in the absence of NRFL-1 when the worm is up to four-day old. A fluorescence recovery after photobleaching (FRAP) analysis suggested that NRFL-1 immobilizes AAT-6 at the luminal membrane. When the nrfl-1 deficient worm is six-day or older, in contrast, the membranous localization of AAT-6 is not observed, whereas AAT-6 tightly localizes to the membrane in worms with NRFL-1. Sorting out the in vivo functions of the C. elegans NHERF protein, we found that NRFL-1, a PDZ-interactor of AAT-6, is responsible for the immobilization and the age-dependent maintenance of AAT-6 on the intestinal luminal membrane.

  18. Age-dependent decline in density of human nerve and spinal ganglia neurons expressing the α3 isoform of Na/K-ATPase

    PubMed Central

    Romanovsky, Dmitry; Mrak, Robert E.; Dobretsov, Maxim

    2015-01-01

    Ambulatory instability and falls are a major source of morbidity in the elderly. Age-related loss of tendon reflexes is a major contributing factor to this morbidity, and deterioration of the afferent limb of the stretch reflex is a potential contributing factor to such age-dependent loss of tendon reflexes. To evaluate this, we assessed the number and distribution of muscle spindle afferent fibers in human sacral spinal ganglia (S1) and tibial nerve samples obtained at autopsy, using immunohistochemical staining for the α3 isoform of Na+,K+-ATPase (α3NKA), a marker of muscle spindle afferents. Across all age groups, an average of 26±4% of myelinated fibers of tibial nerve and 17±2% of ganglion neuronal profiles were α3NKA-positive (n=8 per group). Subject age explained 85% of the variability in these counts. The relative frequency of α3NKA-labeled fibers/neurons starts to decline during the 5th decade of life, approaching half that of young adult values in 65-year-old subjects. At all ages, α3NKA-positive neurons were among the largest of spinal ganglia neurons. However, as compared to younger subjects, the population of α3NKA-positive neurons from advanced-age subjects showed diminished numbers of large (both moderately and strongly labeled), and medium-sized (strongly labeled) profiles. Considering the critical significance of ion transport by NKA for neuronal activity, our data suggest that functional impairment and, also, most likely atrophy and/or degeneration of muscle spindle afferents, are mechanisms underlying loss of tendon reflexes with age. The larger and more strongly α3NKA-expressing spindle afferents appear to be proportionally more vulnerable. PMID:26386295

  19. Vascular and extravascular immunoreactivity for Intercellular Adhesion Molecule 1 in the orbitofrontal cortex of subjects with major depression: age-dependent changes

    PubMed Central

    Miguel-Hidalgo, Jose Javier; Overholser, James C.; Jurjus, George J.; Meltzer, Herbert Y.; Dieter, Lesa; Konick, Lisa; Stockmeier, Craig A.; Rajkowska, Grazyna

    2011-01-01

    Background Vascular and immune alterations in the prefrontal cortex may contribute to major depression in elderly subjects. Intercellular adhesion molecule-1 (ICAM-1), major inflammatory mediator in vessels and astrocytes, could be altered in geriatric depression, but little is known about its age-dependent expression in subjects with depression and its relationship to astrocytes identified by the marker glial fibrillary acidic protein (GFAP), found to be reduced in depression. Methods We measured the percentage of gray matter area fraction covered by ICAM-1 immunoreactivity in blood vessels and in extravascular accumulations of ICAM-1 immunoreactivity in 19 non-psychiatric comparison subjects and 18 subjects with major depression, all characterized by postmortem psychological diagnosis. Association of extravascular ICAM-1 to GFAP-positive astrocytes was investigated by double-labeling immunofluorescence. Results Vascular and extravascular fractions of ICAM-1 immunoreactivity were lower in subjects with MDD than in non-psychiatric comparison subjects. Non-psychiatric comparison subjects older than 60 experienced dramatic increase in extravascular ICAM-1 immunoreactivity, but this increase was attenuated in elderly subjects with MDD, particularly in those dying by suicide. Most extracellular ICAM-1 immunoreactivity was coextensive with GFAP-immunoreactive astrocytes in both groups. Limitations Heterogeneity in type and dosage of antidepressant medication. Difficulty in determining the exact onset of depression in subjects older than 60 at the time of death. Routine cerebrovascular pathological screening may miss subtle subcellular and molecular changes. Conclusions There is significant attenuation of extravascular and vascular ICAM-1 immunoreactivity in elderly subjects with major depression suggesting an astrocyte-associated alteration in immune function in the aging orbitofrontal cortex of subjects with MDD. PMID:21536333

  20. Stress Marker Signatures in Lesion Mimic Single and Double Mutants Identify a Crucial Leaf Age-Dependent Salicylic Acid Related Defense Signal

    PubMed Central

    2017-01-01

    Plants are exposed to abiotic and biotic stress conditions throughout their lifespans that activates various defense programs. Programmed cell death (PCD) is an extreme defense strategy the plant uses to manage unfavorable environments as well as during developmentally induced senescence. Here we investigated the role of leaf age on the regulation of defense gene expression in Arabidopsis thaliana. Two lesion mimic mutants with misregulated cell death, catalase2 (cat2) and defense no death1 (dnd1) were used together with several double mutants to dissect signaling pathways regulating defense gene expression associated with cell death and leaf age. PCD marker genes showed leaf age dependent expression, with the highest expression in old leaves. The salicylic acid (SA) biosynthesis mutant salicylic acid induction deficient2 (sid2) had reduced expression of PCD marker genes in the cat2 sid2 double mutant demonstrating the importance of SA biosynthesis in regulation of defense gene expression. While the auxin- and jasmonic acid (JA)- insensitive auxin resistant1 (axr1) double mutant cat2 axr1 also led to decreased expression of PCD markers; the expression of several marker genes for SA signaling (ISOCHORISMATE SYNTHASE 1, PR1 and PR2) were additionally decreased in cat2 axr1 compared to cat2. The reduced expression of these SA markers genes in cat2 axr1 implicates AXR1 as a regulator of SA signaling in addition to its known role in auxin and JA signaling. Overall, the current study reinforces the important role of SA signaling in regulation of leaf age-related transcript signatures. PMID:28107453

  1. A critical role for NF2 and the Hippo pathway in branching morphogenesis.

    PubMed

    Reginensi, Antoine; Enderle, Leonie; Gregorieff, Alex; Johnson, Randy L; Wrana, Jeffrey L; McNeill, Helen

    2016-08-02

    Branching morphogenesis is a complex biological process common to the development of most epithelial organs. Here we demonstrate that NF2, LATS1/2 and YAP play a critical role in branching morphogenesis in the mouse kidney. Removal of Nf2 or Lats1/2 from the ureteric bud (UB) lineage cause