Chk1 promotes replication fork progression by controlling replication initiation
Petermann, Eva; Woodcock, Mick; Helleday, Thomas
2010-01-01
DNA replication starts at initiation sites termed replication origins. Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the cyclin-dependent kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1 activity display reduced rates of replication fork progression. Here we investigate the causal relationship between increased origin firing and reduced replication fork progression. We use the Cdk inhibitor roscovitine or RNAi depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow replication fork speeds in Chk1-deficient cells. Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity. PMID:20805465
The dynamics of genome replication using deep sequencing
Müller, Carolin A.; Hawkins, Michelle; Retkute, Renata; Malla, Sunir; Wilson, Ray; Blythe, Martin J.; Nakato, Ryuichiro; Komata, Makiko; Shirahige, Katsuhiko; de Moura, Alessandro P.S.; Nieduszynski, Conrad A.
2014-01-01
Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number during a synchronous S-phase allowed the precise determination of genome replication. To map origin locations, replication forks were stalled close to their initiation sites; therefore, copy number enrichment was limited to origins. Replication timing profiles were generated from asynchronous cultures using fluorescence-activated cell sorting. Applying this technique we show that the replication profiles of haploid and diploid cells are indistinguishable, indicating that both cell types use the same cohort of origins with the same activities. Finally, increasing sequencing depth allowed the direct measure of replication dynamics from an exponentially growing culture. This is the first time this approach, called marker frequency analysis, has been successfully applied to a eukaryote. These data provide a high-resolution resource and methodological framework for studying genome biology. PMID:24089142
Kwan, Elizabeth X.; Foss, Eric J.; Tsuchiyama, Scott; Alvino, Gina M.; Kruglyak, Leonid; Kaeberlein, Matt; Raghuraman, M. K.; Brewer, Bonita J.; Kennedy, Brian K.; Bedalov, Antonio
2013-01-01
Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics. PMID:23505383
Kwan, Elizabeth X; Foss, Eric J; Tsuchiyama, Scott; Alvino, Gina M; Kruglyak, Leonid; Kaeberlein, Matt; Raghuraman, M K; Brewer, Bonita J; Kennedy, Brian K; Bedalov, Antonio
2013-01-01
Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics.
Universal Temporal Profile of Replication Origin Activation in Eukaryotes
NASA Astrophysics Data System (ADS)
Goldar, Arach
2011-03-01
The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.
Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.
2012-01-01
Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023
The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency
Patel, Prasanta K.; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John
2008-01-01
Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency. PMID:18799612
Li, Shuyan; Li, Jijin; Yuan, Jing; Li, Guoxue; Zang, Bing; Li, Yangyang
2017-07-01
The aim of this study was to investigate the influence of inoculants on compost stability, maturity and enzyme activities during composting of chicken manure and cornstalk. Two microbial inoculants (originated from aerobic municipal sludge and municipal solid waste, respectively) were used in composting at the rate of 0.3% of initial raw materials (wet weight). No microbial inoculums were added to the control. The experiment was conducted under aerobic conditions for 53 days. The results show that enzyme activity is an important index to comprehensively evaluate the composting stability and maturity. Microbes originated from sludge works best in terms of composting stability and maturity (C:N ratio decreased from 15.5 to 10, and germination index increased to 109%). Microbial inoculums originated from sludge and municipal solid waste extended the time of thermophilic phase for 11 and 7 days, respectively. Microbial inoculums originated from sludge and MSW significantly increased the average of catalase activity (by 15.0% and 12.1%, respectively), urease activity (by 21.5% and 12.2%, respectively) and cellulase activity (by 32.1% and 26.1%, respectively) during composting.
Female infertility, active component service women, U.S. Armed Forces, 2000-2012.
2013-09-01
Infertility is the inability to become pregnant after one year of regular, unprotected sexual intercourse. Among active component service women, 16,807 received a diagnosis of female infertility during the 13-year surveillance period. The incidence rate of infertility diagnoses increased during the period, mainly due to increasing rates of infertility of unspecified origin. Infertility of tubal origin and anovulation were the most common specified types of infertility. Incidence rates of infertility were highest among women in their thirties; however, rates increased the most in women in their forties. Black, non-Hispanic women had the highest rates of infertility overall and in infertility of tubal and uterine origin. The higher rates among women in their thirties and forties may reflect high and increasing rates of clinical care seeking for infertility among women who elect to delay pregnancy until older ages and an increase in treatment options for women who have been unable to become pregnant.
Nonchronological video synopsis and indexing.
Pritch, Yael; Rav-Acha, Alex; Peleg, Shmuel
2008-11-01
The amount of captured video is growing with the increased numbers of video cameras, especially the increase of millions of surveillance cameras that operate 24 hours a day. Since video browsing and retrieval is time consuming, most captured video is never watched or examined. Video synopsis is an effective tool for browsing and indexing of such a video. It provides a short video representation, while preserving the essential activities of the original video. The activity in the video is condensed into a shorter period by simultaneously showing multiple activities, even when they originally occurred at different times. The synopsis video is also an index into the original video by pointing to the original time of each activity. Video Synopsis can be applied to create a synopsis of an endless video streams, as generated by webcams and by surveillance cameras. It can address queries like "Show in one minute the synopsis of this camera broadcast during the past day''. This process includes two major phases: (i) An online conversion of the endless video stream into a database of objects and activities (rather than frames). (ii) A response phase, generating the video synopsis as a response to the user's query.
Soriano, Ignacio; Morafraile, Esther C; Vázquez, Enrique; Antequera, Francisco; Segurado, Mónica
2014-09-13
Eukaryotic genomes are replicated during S phase according to a temporal program. Several determinants control the timing of origin firing, including the chromatin environment and epigenetic modifications. However, how chromatin structure influences the timing of the activation of specific origins is still poorly understood. By performing high-resolution analysis of genome-wide nucleosome positioning we have identified different chromatin architectures at early and late replication origins. These different patterns are already established in G1 and are tightly correlated with the organization of adjacent transcription units. Moreover, specific early and late nucleosomal patterns are fixed robustly, even in rpd3 mutants in which histone acetylation and origin timing have been significantly altered. Nevertheless, higher histone acetylation levels correlate with the local modulation of chromatin structure, leading to increased origin accessibility. In addition, we conducted parallel analyses of replication and nucleosome dynamics that revealed that chromatin structure at origins is modulated during origin activation. Our results show that early and late replication origins present distinctive nucleosomal configurations, which are preferentially associated to different genomic regions. Our data also reveal that origin structure is dynamic and can be locally modulated by histone deacetylation, as well as by origin activation. These data offer novel insight into the contribution of chromatin structure to origin selection and firing in budding yeast.
Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier
2011-01-01
Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics. PMID:22219720
Kalashnikova, S P; Solovyov, V G
2016-01-01
In experimental studies on 448 rats treated with bear fat diet (0.08 ml/100 g body weight), the nature and mechanisms of influence of this additive on the process of blood coagulation in experimental thromboplastinemia of different origin has been studied. As a result of intravenous injection in the jugular vein of a suspension of thrombin (exogenous thrombinemia) all clothingsee tests lengthened in the control animals (p<0.05): prothrombin time by 11.1%, activated partial thromboplastin time - by 13.4%, thrombin time by 16.8%. Fibrinogen fell by 1.9 fold, that was accompanied by increase of the level of soluble fibrin monomer complexes and reduce of activity of antithrombin III by 20.2%. At the same time severe thrombocytopenia developed with a relative increase in the number of activated forms (by 73.1%). Consumption coagulopathy was also observed in rats treated with bear fat, but the potential of hemostatic cascade and anticoagulation system remained high (judging by the tests PTV, thrombin time and content of antithrombin III). Under endogenous thromboplastinemia caused by combined stress (hypothermia + physical activity) in animals of the control group on the background of the shortening of the APTT (by 24.9%) and PTV (16.8%), RCMP concentration increased by 52% and activity of antithrombin III increased compensatory. There was an increase of platelet count, due to the activated forms. To 3 h signs of hypocoagulation aggravated even more. In animals treated with bear fat, the results of clothing tests did not differ from the original figures, and by 3 h, the majority of the indicators have reached their original values. The increase in platelet count has not been observed.
Gastrointestinal effects of water reuse for public park irrigation.
Durand, R; Schwebach, G
1989-01-01
To investigate the gastrointestinal effects of employing recycled water as an irrigation source for urban public parks, we studied subjects active in parks irrigated with potable water, nonpotable water of wastewater origin, and nonpotable water of runoff origin. Wet grass conditions during activity and elevated densities of common indicator bacteria, but not exposure to nonpotable irrigation water per se, were found associated with an increased rate of gastrointestinal illness. PMID:2817197
Qureshi, T M; Vegarud, G E; Abrahamsen, R K; Skeie, S
2013-02-01
The angiotensin I-converting enzyme (ACE) inhibitory activity of Gamalost cheese, its pH 4.6-soluble fraction, and Norvegia cheese was monitored before and after digestion with human gastric and duodenal juices. Both Gamalost and Norvegia cheeses showed an increased ACE-inhibitory activity during gastrointestinal digestion. However, only Norvegia showed pronounced increased activity after duodenal digestion. More peptides were detected in digested Gamalost compared with digested Norvegia. Most of the peptides in Gamalost were derived from β-casein (CN), some originated from α(s1)-CN, and only a very few originated from α(s2)-CN and κ-CN. In general, the number of peptides increased during gastrointestinal digestion, whereas some peptides were further degraded and disappeared; however, surprisingly, a few peptides remained stable. The aromatic amino acids, such as Tyr, Phe, and Trp; the positively charged amino acids (Arg and Lys); and Leu increased after simulated gastrointestinal digestion of Gamalost and Norvegia. After in vitro gastrointestinal digestion, both Gamalost and Norvegia showed high ACE-inhibitory activity, which may contribute in lowering of mild hypertension. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Differential Chromatin Structure Encompassing Replication Origins in Transformed and Normal Cells
Di Paola, Domenic; Rampakakis, Emmanouil; Chan, Man Kid
2012-01-01
This study examines the chromatin structure encompassing replication origins in transformed and normal cells. Analysis of the global levels of histone H3 acetylated at K9&14 (open chromatin) and histone H3 trimethylated at K9 (closed chromatin) revealed a higher ratio of open to closed chromatin in the transformed cells. Also, the trithorax and polycomb group proteins, Brg-1 and Bmi-1, respectively, were overexpressed and more abundantly bound to chromatin in the transformed cells. Quantitative comparative analyses of episomal and in situ chromosomal replication origin activity as well as chromatin immunoprecipitation (ChIP) assays, using specific antibodies targeting members of the pre-replication complex (pre-RC) as well as open/closed chromatin markers encompassing both episomal and chromosomal origins, revealed that episomal origins had similar levels of in vivo activity, nascent DNA abundance, pre-RC protein association, and elevated open chromatin structure at the origin in both cell types. In contrast, the chromosomal origins corresponding to 20mer1, 20mer2, and c-myc displayed a 2- to 3-fold higher activity and pre-RC protein abundance as well as higher ratios of open to closed chromatin and of Brg-1 to Bmi-1 in the transformed cells, whereas the origin associated with the housekeeping lamin B2 gene exhibited similar levels of activity, pre-RC protein abundance, and higher ratios of open to closed chromatin and of Brg-1 to Bmi-1 in both cell types. Nucleosomal positioning analysis, using an MNase-Southern blot assay, showed that all the origin regions examined were situated within regions of inconsistently positioned nucleosomes, with the nucleosomes being spaced farther apart from each other prior to the onset of S phase in both cell types. Overall, the results indicate that cellular transformation is associated with differential epigenetic regulation, whereby chromatin structure is more open, rendering replication origins more accessible to initiator proteins, thus allowing increased origin activity. PMID:23050047
Kaltenbach, Miriam; Emond, Stephane; Hollfelder, Florian; Tokuriki, Nobuhiko
2016-10-01
The extent to which an emerging new function trades off with the original function is a key characteristic of the dynamics of enzyme evolution. Various cases of laboratory evolution have unveiled a characteristic trend; a large increase in a new, promiscuous activity is often accompanied by only a mild reduction of the native, original activity. A model that associates weak trade-offs with "evolvability" was put forward, which proposed that enzymes possess mutational robustness in the native activity and plasticity in promiscuous activities. This would enable the acquisition of a new function without compromising the original one, reducing the benefit of early gene duplication and therefore the selection pressure thereon. Yet, to date, no experimental study has examined this hypothesis directly. Here, we investigate the causes of weak trade-offs by systematically characterizing adaptive mutations that occurred in two cases of evolutionary transitions in enzyme function: (1) from phosphotriesterase to arylesterase, and (2) from atrazine chlorohydrolase to melamine deaminase. Mutational analyses in various genetic backgrounds revealed that, in contrast to the prevailing model, the native activity is less robust to mutations than the promiscuous activity. For example, in phosphotriesterase, the deleterious effect of individual mutations on the native phosphotriesterase activity is much larger than their positive effect on the promiscuous arylesterase activity. Our observations suggest a revision of the established model: weak trade-offs are not caused by an intrinsic robustness of the native activity and plasticity of the promiscuous activity. We propose that upon strong adaptive pressure for the new activity without selection against the original one, selected mutations will lead to the largest possible increases in the new function, but whether and to what extent they decrease the old function is irrelevant, creating a bias towards initially weak trade-offs and the emergence of generalist enzymes.
Hanley, Gregory P; Tiger, Jeffrey H; Ingvarsson, Einar T; Cammilleri, Anthony P
2009-01-01
The present study evaluated the effects of classwide satiation and embedded reinforcement procedures on preschoolers' activity preferences during scheduled free-play periods. The goal of the study was to increase time allocation to originally nonpreferred, but important, activities (instructional zone, library, and science) while continuing to provide access to all free-play activities. The satiation intervention applied to preferred activities resulted in increased time allocation to the instructional and science activities, the customized embedded reinforcement interventions resulted in increased time allocation to all three target activities, and high levels of attendance to the instructional and library activities were maintained during follow-up observations. Implications for the design of preschool free-play periods are discussed.
ERIC Educational Resources Information Center
Hanley, Gregory P.; Tiger, Jeffrey H.; Ingvarsson, Einar T.; Cammilleri, Anthony P.
2009-01-01
The present study evaluated the effects of classwide satiation and embedded reinforcement procedures on preschoolers' activity preferences during scheduled free-play periods. The goal of the study was to increase time allocation to originally nonpreferred, but important, activities (instructional zone, library, and science) while continuing to…
Rivera, Desirée; Mejías, Violeta; Jáuregui, Berta M; Costa-Tenorio, Marga; López-Archilla, Ana Isabel; Peco, Begoña
2014-01-01
The construction of linear transport infrastructure has severe effects on ecosystem functions and properties, and the restoration of the associated roadslopes contributes to reduce its impact. This restoration is usually approached from the perspective of plant cover regeneration, ignoring plant-soil interactions and the consequences for plant growth. The addition of a 30 cm layer of topsoil is a common practice in roadslope restoration projects to increase vegetation recovery. However topsoil is a scarce resource. This study assesses the effects of topsoil spreading and its depth (10 to 30 cm) on two surrogates of microbial activity (β-glucosidase and phosphatase enzymes activity and soil respiration), and on plant cover, plant species richness and floristic composition of embankment vegetation. The study also evaluates the differences in selected physic-chemical properties related to soil fertility between topsoil and the original embankment substrate. Topsoil was found to have higher values of organic matter (11%), nitrogen (44%), assimilable phosphorous (50%) and silt content (54%) than the original embankment substrate. The topsoil spreading treatment increased microbial activity, and its application increased β-glucosidase activity (45%), phosphatase activity (57%) and soil respiration (60%). Depth seemed to affect soil respiration, β-glucosidase and phosphatase activity. Topsoil application also enhanced the species richness of restored embankments in relation to controls. Nevertheless, the depth of the spread topsoil did not significantly affect the resulting plant cover, species richness or floristic composition, suggesting that both depths could have similar effects on short-term recovery of the vegetation cover. A significant implication of these results is that it permits the application of thinner topsoil layers, with major savings in this scarce resource during the subsequent slope restoration work, but the quality of topsoil relative to the original substrate should be previously assessed on a site by site basis.
Physical activity patterns among Latinos in the United States: putting the pieces together.
Ham, Sandra A; Yore, Michelle M; Kruger, Judy; Heath, Gregory W; Moeti, Refilwe
2007-10-01
Estimates of participation in physical activity among Latinos are inconsistent across studies. To obtain better estimates and examine possible reasons for inconsistencies, we assessed 1) patterns of participation in various categories of physical activity among Latino adults, 2) changes in their activity patterns with acculturation, and 3) variations in their activity patterns by region of origin. Using data from four national surveillance systems (the National Health and Nutrition Examination Survey, 1999-2002; the Behavioral Risk Factor Surveillance System, 2003; the National Household Travel Survey, 2001; and the National Health Interview Survey Cancer Supplement, 2000), we estimated the percentage of Latinos who participated at least once per week in leisure-time, household, occupational, or transportation-related physical activity, as well as in an active pattern of usual daily activity. We reported prevalences by acculturation measures and region of origin. The percentage of Latinos who participated in the various types of physical activity ranged from 28.7% for having an active level of usual daily activity (usually walking most of the day and usually carrying or lifting objects) to 42.8% for participating in leisure-time physical activity at least once per week. The percentage who participated in leisure-time and household activities increased with acculturation, whereas the percentage who participated in occupational and transportation-related activities decreased with acculturation. Participation in an active level of usual daily activity did not change significantly. The prevalence of participation in transportation-related physical activity and of an active level of usual daily activity among Latino immigrants varied by region of origin. Physical activity patterns among Latinos vary with acculturation and region of origin. To assess physical activity levels in Latino communities, researchers should measure all types of physical activity and the effects of acculturation on each type of activity.
Source analysis of electrophysiological correlates of beat induction as sensory-guided action
Todd, Neil P. M.; Lee, Christopher S.
2015-01-01
In this paper we present a reanalysis of electrophysiological data originally collected to test a sensory-motor theory of beat induction (Todd et al., 2002; Todd and Seiss, 2004; Todd and Lee, 2015). The reanalysis is conducted in the light of more recent findings and in particular the demonstration that auditory evoked potentials contain a vestibular dependency. At the core of the analysis is a model which predicts brain dipole source current activity over time in temporal and frontal lobe areas during passive listening to a rhythm, or active synchronization, where it dissociates the frontal activity into distinct sources which can be identified as respectively pre-motor and motor in origin. The model successfully captures the main features of the rhythm in showing that the metrical structure is manifest in an increase in source current activity during strong compared to weak beats. In addition the outcomes of modeling suggest that: (1) activity in both temporal and frontal areas contribute to the metrical percept and that this activity is distributed over time; (2) transient, time-locked activity associated with anticipated beats is increased when a temporal expectation is confirmed following a previous violation, such as a syncopation; (3) two distinct processes are involved in auditory cortex, corresponding to tangential and radial (possibly vestibular dependent) current sources. We discuss the implications of these outcomes for the insights they give into the origin of metrical structure and the power of syncopation to induce movement and create a sense of groove. PMID:26321991
Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats
NASA Technical Reports Server (NTRS)
Golin, Raffaello M. A.; Gotoh, Eiji; Keil, Lanny C.; Shackelford, Roy L.; Ganong, William F.
1989-01-01
The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.
Duncan, Dustin T; Méline, Julie; Kestens, Yan; Day, Kristen; Elbel, Brian; Trasande, Leonardo; Chaix, Basile
2016-06-20
Few studies have used GPS data to analyze the relationship between Walk Score, transportation choice and walking. Additionally, the influence of Walk Score is understudied using trips rather than individuals as statistical units. The purpose of this study is to examine associations at the trip level between Walk Score, transportation mode choice, and walking among Paris adults who were tracked with GPS receivers and accelerometers in the RECORD GPS Study. In the RECORD GPS Study, 227 participants were tracked during seven days with GPS receivers and accelerometers. Participants were also surveyed with a GPS-based web mapping application on their activities and transportation modes for all trips (6969 trips). Walk Score, which calculates neighborhood walkability, was assessed for each origin and destination of every trip. Multilevel logistic and linear regression analyses were conducted to estimate associations between Walk Score and walking in the trip or accelerometry-assessed number of steps for each trip, after adjustment for individual/neighborhood characteristics. The mean overall Walk Scores for trip origins were 87.1 (SD = 14.4) and for trip destinations 87.1 (SD = 14.5). In adjusted trip-level associations between Walk Score and walking only in the trip, we found that a walkable neighborhood in the trip origin and trip destination was associated with increased odds of walking in the trip assessed in the survey. The odds of only walking in the trip were 3.48 (95% CI: 2.73 to 4.44) times higher when the Walk Score for the trip origin was "Walker's Paradise" compared to less walkable neighborhoods (Very/Car-Dependent or Somewhat Walkable), with an identical independent effect of trip destination Walk Score on walking. The number of steps per 10 min (as assessed with accelerometry) was cumulatively higher for trips both originating and ending in walkable neighborhoods (i.e., "Very Walkable"). Walkable neighborhoods were associated with increases in walking among adults in Paris, as documented at the trip level. Creating walkable neighborhoods (through neighborhood design increased commercial activity) may increase walking trips and, therefore, could be a relevant health promotion strategy to increase physical activity.
Duncan, Dustin T.; Méline, Julie; Kestens, Yan; Day, Kristen; Elbel, Brian; Trasande, Leonardo; Chaix, Basile
2016-01-01
Background: Few studies have used GPS data to analyze the relationship between Walk Score, transportation choice and walking. Additionally, the influence of Walk Score is understudied using trips rather than individuals as statistical units. The purpose of this study is to examine associations at the trip level between Walk Score, transportation mode choice, and walking among Paris adults who were tracked with GPS receivers and accelerometers in the RECORD GPS Study. Methods: In the RECORD GPS Study, 227 participants were tracked during seven days with GPS receivers and accelerometers. Participants were also surveyed with a GPS-based web mapping application on their activities and transportation modes for all trips (6969 trips). Walk Score, which calculates neighborhood walkability, was assessed for each origin and destination of every trip. Multilevel logistic and linear regression analyses were conducted to estimate associations between Walk Score and walking in the trip or accelerometry-assessed number of steps for each trip, after adjustment for individual/neighborhood characteristics. Results: The mean overall Walk Scores for trip origins were 87.1 (SD = 14.4) and for trip destinations 87.1 (SD = 14.5). In adjusted trip-level associations between Walk Score and walking only in the trip, we found that a walkable neighborhood in the trip origin and trip destination was associated with increased odds of walking in the trip assessed in the survey. The odds of only walking in the trip were 3.48 (95% CI: 2.73 to 4.44) times higher when the Walk Score for the trip origin was “Walker’s Paradise” compared to less walkable neighborhoods (Very/Car-Dependent or Somewhat Walkable), with an identical independent effect of trip destination Walk Score on walking. The number of steps per 10 min (as assessed with accelerometry) was cumulatively higher for trips both originating and ending in walkable neighborhoods (i.e., “Very Walkable”). Conclusions: Walkable neighborhoods were associated with increases in walking among adults in Paris, as documented at the trip level. Creating walkable neighborhoods (through neighborhood design increased commercial activity) may increase walking trips and, therefore, could be a relevant health promotion strategy to increase physical activity. PMID:27331818
Hanley, Gregory P; Tiger, Jeffrey H; Ingvarsson, Einar T; Cammilleri, Anthony P
2009-01-01
The present study evaluated the effects of classwide satiation and embedded reinforcement procedures on preschoolers' activity preferences during scheduled free-play periods. The goal of the study was to increase time allocation to originally nonpreferred, but important, activities (instructional zone, library, and science) while continuing to provide access to all free-play activities. The satiation intervention applied to preferred activities resulted in increased time allocation to the instructional and science activities, the customized embedded reinforcement interventions resulted in increased time allocation to all three target activities, and high levels of attendance to the instructional and library activities were maintained during follow-up observations. Implications for the design of preschool free-play periods are discussed. PMID:19721728
Araújo, Jucilene Silva; Chambó, Emerson Dechechi; Costa, Maria Angélica Pereira de Carvalho; Cavalcante da Silva, Samira Maria Peixoto; Lopes de Carvalho, Carlos Alfredo; M. Estevinho, Leticia
2017-01-01
Recent research shows variations in pollen chemical constituents and, consequently, in their therapeutic properties. Mono and multifloral bee pollen extracts were investigated for antioxidant and enzyme inhibitory activity properties, phenolic compounds and fatty acid composition. Generally, Eucalyptus spp. and multifloral extracts exhibited potent inhibitory activity against α-amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic activity. Cocos nucifera and Miconia spp. extracts exhibited important antioxidant properties in the different assays (ABTS, DPPH, β-carotene/linoleic acid and reducing power). Moreover, these extracts had greater amounts of total phenols and flavonoids in comparison to others. The increase in antioxidant activity (decrease in EC50 values) was accompanied by an increase in the amount of total phenols in the extracts. The pollen extracts contained linoleic acid and α-linolenic acid as major fatty acids, followed by palmitic acid, and oleic acid. In this study, differences were observed in both chemical constituents and biological activities of the samples related to the geographical and botanical origin of bee pollen. PMID:28448467
Abdelbaqi, Khalil; Di Paola, Domenic; Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria
2013-01-01
Human origins of DNA replication are specific sequences within the genome whereby DNA replication is initiated. A select group of proteins, known as the pre-replication (pre-RC) complex, in whose formation the Ku protein (Ku70/Ku86) was shown to play a role, bind to replication origins to initiate DNA replication. In this study, we have examined the involvement of Ku in breast tumorigenesis and tumor progression and found that the Ku protein expression levels in human breast metastatic (MCF10AC1a) cells were higher in the chromatin fraction compared to hyperplastic (MCF10AT) and normal (MCF10A) human breast cells, but remained constant in both the nuclear and cytoplasmic fractions. In contrast, in human intestinal cells, the Ku expression level was relatively constant for all cell fractions. Nascent DNA abundance and chromatin association of Ku70/86 revealed that the c-myc origin activity in MCF10AC1a is 2.5 to 5-fold higher than in MCF10AT and MCF10A, respectively, and Ku was bound to the c-myc origin more abundantly in MCF10AC1a, by approximately 1.5 to 4.2-fold higher than in MCF10AT and MCF10A, respectively. In contrast, similar nascent DNA abundance and chromatin association was found for all cell lines for the lamin B2 origin, associated with the constitutively active housekeeping lamin B2 gene. Electrophoretic mobility shift assays (EMSAs) performed on the nuclear extracts (NEs) of the three cell types revealed the presence of protein-DNA replication complexes on both the c-myc and lamin B2 origins, but an increase in binding activity was observed from normal, to transformed, to cancer cells for the c-myc origin, whereas no such difference was seen for the lamin B2 origin. Overall, the results suggest that increased Ku chromatin association, beyond wild type levels, alters cellular processes, which have been implicated in tumorigenesis. PMID:23781282
Origin recognition is the predominant role for DnaA-ATP in initiation of chromosome replication.
Grimwade, Julia E; Rozgaja, Tania A; Gupta, Rajat; Dyson, Kyle; Rao, Prassanna; Leonard, Alan C
2018-05-25
In all cells, initiation of chromosome replication depends on the activity of AAA+ initiator proteins that form complexes with replication origin DNA. In bacteria, the conserved, adenosine triphosphate (ATP)-regulated initiator protein, DnaA, forms a complex with the origin, oriC, that mediates DNA strand separation and recruitment of replication machinery. Complex assembly and origin activation requires DnaA-ATP, which differs from DnaA-ADP in its ability to cooperatively bind specific low affinity sites and also to oligomerize into helical filaments. The degree to which each of these activities contributes to the DnaA-ATP requirement for initiation is not known. In this study, we compared the DnaA-ATP dependence of initiation from wild-type Escherichia coli oriC and a synthetic origin (oriCallADP), whose multiple low affinity DnaA sites bind DnaA-ATP and DnaA-ADP similarly. OriCallADP was fully occupied and unwound by DnaA-ADP in vitro, and, in vivo, oriCallADP suppressed lethality of DnaA mutants defective in ATP binding and ATP-specific oligomerization. However, loss of preferential DnaA-ATP binding caused over-initiation and increased sensitivity to replicative stress. The findings indicate both DnaA-ATP and DnaA-ADP can perform most of the mechanical functions needed for origin activation, and suggest that a key reason for ATP-regulation of DnaA is to control replication initiation frequency.
Tooth, David; Garsed, Klara; Singh, Gulzar; Marciani, Luca; Lam, Ching; Fordham, Imogen; Fields, Annie; Banwait, Rawinder; Lingaya, Melanie; Layfield, Robert; Hastings, Maggie; Whorwell, Peter; Spiller, Robin
2014-05-01
Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=-0.32, p=0.005) and HV (r=-0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140-426) to 1031 (435-2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. NCT00745004.
Relationships between solar activity and climate change. [sunspot cycle effects on lower atmosphere
NASA Technical Reports Server (NTRS)
Roberts, W. O.
1974-01-01
Recurrent droughts are related to the double sunspot cycle. It is suggested that high solar activity generally increases meridional circulations and blocking patterns at high and intermediate latitudes, especially in winter. This effect is related to the sudden formation of cirrus clouds during strong geomagnetic activity that originates in the solar corpuscular emission.
Response in thermal neutrons intensity on the activation of seismic processes
NASA Astrophysics Data System (ADS)
Antonova, Valentina; Chubenko, Alexandr; Kryukov, Sergey; Lutsenko, Vadim
2017-04-01
Results of study of thermal and high-energy neutrons intensity during the activation of seismic activity are presented. Installations are located close to the fault of the earth's crust at the high-altitude station of cosmic rays (3340 m above sea level, 20 km from Almaty) in the mountains of Northern Tien-Shan. High correlation and similarity of responses to changes of space and geophysical conditions in the absence of seismic activity are obtained between data of thermal neutron detectors and data of the standard neutron monitor, recording the intensity of high-energy particles. These results confirm the genetic connection of thermal neutrons at the Earth's surface with high-energy neutrons of the galactic origin and suggest same sources of disturbances of their flux. However, observations and analysis of experimental data during the activation of seismic activity showed the frequent breakdown of the correlation between the intensity of thermal and high-energy neutrons and the absence of similarity between variations during these periods. We suppose that the cause of this phenomenon is the additional thermal neutron flux of the lithospheric origin, which appears under these conditions. Method of separating of thermal neutron intensity variations of the lithospheric origin from neutrons variations generated in the atmosphere is proposed. We used this method for analysis of variations of thermal neutrons intensity during earthquakes (with intensity ≥ 3b) in the vicinity of Almaty which took place in 2006-2015. The increase of thermal neutrons flux of the lithospheric origin during of seismic processes activation was observed for 60% of events. However, before the earthquake the increase of thermal neutron flux is only observed for 25-30% of events. It is shown that the amplitude of the additional thermal neutron flux from the Earth's crust is equal to 5-7% of the background level.
CDK activity provides temporal and quantitative cues for organizing genome duplication
Perrot, Anthony; Millington, Christopher Lee; Gómez-Escoda, Blanca; Schausi-Tiffoche, Diane
2018-01-01
In eukaryotes, the spatial and temporal organization of genome duplication gives rise to distinctive profiles of replication origin usage along the chromosomes. While it has become increasingly clear that these programs are important for cellular physiology, the mechanisms by which they are determined and modulated remain elusive. Replication initiation requires the function of cyclin-dependent kinases (CDKs), which associate with various cyclin partners to drive cell proliferation. Surprisingly, although we possess detailed knowledge of the CDK regulators and targets that are crucial for origin activation, little is known about whether CDKs play a critical role in establishing the genome-wide pattern of origin selection. We have addressed this question in the fission yeast, taking advantage of a simplified cell cycle network in which cell proliferation is driven by a single cyclin-CDK module. This system allows us to precisely control CDK activity in vivo using chemical genetics. First, in contrast to previous reports, our results clearly show that distinct cyclin-CDK pairs are not essential for regulating specific subsets of origins and for establishing a normal replication program. Importantly, we then demonstrate that the timing at which CDK activity reaches the S phase threshold is critical for the organization of replication in distinct efficiency domains, while the level of CDK activity at the onset of S phase is a dose-dependent modulator of overall origin efficiencies. Our study therefore implicates these different aspects of CDK regulation as versatile mechanisms for shaping the architecture of DNA replication across the genome. PMID:29466359
Guerrero, Cecilia; Vera, Carlos; Conejeros, Raúl; Illanes, Andrés
2015-03-01
β-Galactosidases exhibit both hydrolytic and transgalactosylation activities; the former has been used traditionally for the production of delactosed milk and dairies, while the latter is being increasingly used for the synthesis of lactose-derived oligosaccharides: balance between both activities was highly dependent on the enzyme origin: β-galactosidases from Aspegillus oryzae and Bacillus circulans exhibited high transgalactosylation activity, while those from one from Kluyveromyces exhibited high hydrolytic activity but quite low transgalactosylation activity. Also the affinity for the donors (lactose or lactulose) and the acceptors (lactose, lactulose or fructose) of transgalactosylated galactose was dependent on the enzyme origin, as reflected by the Michaelis constants obtained in the synthesis of galacto-oligosaccharides, fructosyl-galacto-oligosaccharides and lactulose. Finally, the balance between transgalactosylation and hydrolytic activities of β-galactosidases could be tuned by changing the concentration of galactose donor. Copyright © 2014 Elsevier Inc. All rights reserved.
Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans
Skurnik, David; Clermont, Olivier; Guillard, Thomas; Launay, Adrien; Danilchanka, Olga; Pons, Stéphanie; Diancourt, Laure; Lebreton, François; Kadlec, Kristina; Roux, Damien; Jiang, Deming; Dion, Sara; Aschard, Hugues; Denamur, Maurice; Cywes-Bentley, Colette; Schwarz, Stefan; Tenaillon, Olivier; Andremont, Antoine; Picard, Bertrand; Mekalanos, John; Brisse, Sylvain; Denamur, Erick
2016-01-01
In the context of the great concern about the impact of human activities on the environment, we studied 403 commensal Escherichia coli/Escherichia clade strains isolated from several animal and human populations that have variable contacts to one another. Multilocus sequence typing (MLST) showed a decrease of diversity 1) in strains isolated from animals that had an increasing contact with humans and 2) in all strains that had increased antimicrobial resistance. A specific B1 phylogroup clonal complex (CC87, Institut Pasteur schema nomenclature) of animal origin was identified and characterized as being responsible for the increased antimicrobial resistance prevalence observed in strains from the environments with a high human-mediated antimicrobial pressure. CC87 strains have a high capacity of acquiring and disseminating resistance genes with specific metabolic and genetic determinants as demonstrated by high-throughput sequencing and phenotyping. They are good mouse gut colonizers but are not virulent. Our data confirm the predominant role of human activities in the emergence of antimicrobial resistance in the environmental bacterial strains and unveil a particular E. coli clonal complex of animal origin capable of spreading antimicrobial resistance to other members of microbial communities. PMID:26613786
Diversity dynamics of Miocene mammals in relation to the history of tectonism and climate
Finarelli, John A.; Badgley, Catherine
2010-01-01
Continental biodiversity gradients result not only from ecological processes, but also from evolutionary and geohistorical processes involving biotic turnover in landscape and climatic history over millions of years. Here, we investigate the evolutionary and historical contributions to the gradient of increasing species richness with topographic complexity. We analysed a dataset of 418 fossil rodent species from western North America spanning 25 to 5 Ma. We compared diversification histories between tectonically active (Intermontane West) and quiescent (Great Plains) regions. Although diversification histories differed between the two regions, species richness, origination rate and extinction rate per million years were not systematically different over the 20 Myr interval. In the tectonically active region, the greatest increase in originations coincided with a Middle Miocene episode of intensified tectonic activity and global warming. During subsequent global cooling, species richness declined in the montane region and increased on the Great Plains. These results suggest that interactions between tectonic activity and climate change stimulate diversification in mammals. The elevational diversity gradient characteristic of modern mammalian faunas was not a persistent feature over geologic time. Rather, the Miocene rodent record suggests that the elevational diversity gradient is a transient feature arising during particular episodes of Earth's history. PMID:20427339
Engineering an Affinity-Enhanced Peptide through Optimization of Cyclization Chemistry.
Ngambenjawong, Chayanon; Pineda, Julio Marco B; Pun, Suzie H
2016-12-21
Peptide cyclization is a strategy used to improve stability and activity of peptides. The most commonly used cyclization method is disulfide bridge formation of cysteine-containing peptides, as is typically found in nature. Over the years, an increasing number of alternative chemistries for peptide cyclization with improved efficiency, kinetics, orthogonality, and stability have been reported. However, there has been less appreciation for the opportunity to fine-tune peptide activity via the diverse chemical entities introduced at the site of linkage by different cyclization strategies. Here, we demonstrate how cyclization optimization of an M2 "anti-inflammatory" macrophage-binding peptide (M2pep) resulted in a significant increase in binding affinity of the optimized analog to M2 macrophages while maintaining binding selectivity compared to M1 "pro-inflammatory" macrophages. In this study, we report synthesis and evaluation of four cyclic M2pep(RY) analogs with diverse cyclization strategies: (1) Asp-[amide]-Lys, (2) azido-Lys-[triazole(copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC))]-propargyl-Gly, (3) Cys-[decafluorobiphenyl (DFBP)]-Cys, and (4) Cys-[decafluorobiphenyl sulfone (DFS)]-Cys, whereby the chemical entity or linker at the linkage site is shown in the square bracket and is between the residues involved in cyclization. These peptides are compared to a disulfide-cyclized M2pep(RY) that we previously reported as a serum-stable, affinity-enhanced analog to the original linear M2pep. DFBP-cyclized M2pep(RY) exhibits the highest binding activity to M2 macrophages with apparent dissociation constant (K D ) about 2.03 μM compared to 36.3 μM for the original disulfide-cyclized M2pep(RY) and 220 μM for the original linear peptide. DFS-cyclized M2pep(RY) also binds more strongly than the original cyclized analog, whereas amide- and triazole-cyclized M2pep(RY) analogs bind less strongly. We verified that DFBP alone has negligible binding to M2 macrophages and the incorporation of diphenylalanine to the original sequence improves binding activity at the expense of solubility and increased toxicity. In conclusion, we report development of cyclic M2pep(RY) analogs with diverse cyclization strategies leading to the discovery of DFBP-cyclized M2pep(RY) with enhanced M2 macrophage-binding activity.
Sitnikova, Tatiana; Rosen, Bruce R.; Lord, Louis-David; West, W. Caroline
2014-01-01
Adaptive, original actions, which can succeed in multiple contextual situations, require understanding of what is relevant to a goal. Recognizing what is relevant may also help in predicting kinematics of observed, original actions. During action observation, comparisons between sensory input and expected action kinematics have been argued critical to accurate goal inference. Experimental studies with laboratory tasks, both in humans and nonhuman primates, demonstrated that the lateral prefrontal cortex (LPFC) can learn, hierarchically organize, and use goal-relevant information. To determine whether this LPFC capacity is generalizable to real-world cognition, we recorded functional magnetic resonance imaging (fMRI) data in the human brain during comprehension of original and usual object-directed actions embedded in video-depictions of real-life behaviors. We hypothesized that LPFC will contribute to forming goal-relevant representations necessary for kinematic predictions of original actions. Additionally, resting-state fMRI was employed to examine functional connectivity between the brain regions delineated in the video fMRI experiment. According to behavioral data, original videos could be understood by identifying elements relevant to real-life goals at different levels of abstraction. Patterns of enhanced activity in four regions in the left LPFC, evoked by original, relative to usual, video scenes, were consistent with previous neuroimaging findings on representing abstract and concrete stimuli dimensions relevant to laboratory goals. In the anterior left LPFC, the activity increased selectively when representations of broad classes of objects and actions, which could achieve the perceived overall behavioral goal, were likely to bias kinematic predictions of original actions. In contrast, in the more posterior regions, the activity increased even when concrete properties of the target object were more likely to bias the kinematic prediction. Functional connectivity was observed between contiguous regions along the rostro-caudal LPFC axis, but not between the regions that were not immediately adjacent. These findings generalize the representational hierarchy account of LPFC function to diverse core principles that can govern both production and comprehension of flexible real-life behavior. PMID:25224997
Rivera, Desirée; Mejías, Violeta; Jáuregui, Berta M.; López-Archilla, Ana Isabel; Peco, Begoña
2014-01-01
The construction of linear transport infrastructure has severe effects on ecosystem functions and properties, and the restoration of the associated roadslopes contributes to reduce its impact. This restoration is usually approached from the perspective of plant cover regeneration, ignoring plant-soil interactions and the consequences for plant growth. The addition of a 30 cm layer of topsoil is a common practice in roadslope restoration projects to increase vegetation recovery. However topsoil is a scarce resource. This study assesses the effects of topsoil spreading and its depth (10 to 30 cm) on two surrogates of microbial activity (β-glucosidase and phosphatase enzymes activity and soil respiration), and on plant cover, plant species richness and floristic composition of embankment vegetation. The study also evaluates the differences in selected physic-chemical properties related to soil fertility between topsoil and the original embankment substrate. Topsoil was found to have higher values of organic matter (11%), nitrogen (44%), assimilable phosphorous (50%) and silt content (54%) than the original embankment substrate. The topsoil spreading treatment increased microbial activity, and its application increased β-glucosidase activity (45%), phosphatase activity (57%) and soil respiration (60%). Depth seemed to affect soil respiration, β-glucosidase and phosphatase activity. Topsoil application also enhanced the species richness of restored embankments in relation to controls. Nevertheless, the depth of the spread topsoil did not significantly affect the resulting plant cover, species richness or floristic composition, suggesting that both depths could have similar effects on short-term recovery of the vegetation cover. A significant implication of these results is that it permits the application of thinner topsoil layers, with major savings in this scarce resource during the subsequent slope restoration work, but the quality of topsoil relative to the original substrate should be previously assessed on a site by site basis. PMID:24984137
Soares, Sonia; Pinto, Diana; Rodrigues, Francisca; Alves, Rita C; Oliveira, M Beatriz P P
2017-08-11
Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L*, a*, b*) and antioxidant profile (total phenolics content, total flavonoids content, DPPH• scavenging activity, and ferric reducing power). The samples were analysed fresh and after 4-years of storage (at 25 °C and protected from light). The hydroxymethylfurfural content and diastase activity of the fresh samples were in accordance with the recommended values described in the legislation. In general, the antioxidant activity of the samples correlated more with the bioactive compounds content than with colour. The storage affected differently each individual sample, especially regarding the antioxidant profile. Nevertheless, although in general the lightness of the samples decreased (and the redness increased), after 4 years, 11 samples still presented acceptable diastase activity and hydroxymethylfurfural values.
Evolutionary relationships between miRNA genes and their activity.
Zhu, Yan; Skogerbø, Geir; Ning, Qianqian; Wang, Zhen; Li, Biqing; Yang, Shuang; Sun, Hong; Li, Yixue
2012-12-22
The emergence of vertebrates is characterized by a strong increase in miRNA families. MicroRNAs interact broadly with many transcripts, and the evolution of such a system is intriguing. However, evolutionary questions concerning the origin of miRNA genes and their subsequent evolution remain unexplained. In order to systematically understand the evolutionary relationship between miRNAs gene and their function, we classified human known miRNAs into eight groups based on their evolutionary ages estimated by maximum parsimony method. New miRNA genes with new functional sequences accumulated more dynamically in vertebrates than that observed in Drosophila. Different levels of evolutionary selection were observed over miRNA gene sequences with different time of origin. Most genic miRNAs differ from their host genes in time of origin, there is no particular relationship between the age of a miRNA and the age of its host genes, genic miRNAs are mostly younger than the corresponding host genes. MicroRNAs originated over different time-scales are often predicted/verified to target the same or overlapping sets of genes, opening the possibility of substantial functional redundancy among miRNAs of different ages. Higher degree of tissue specificity and lower expression level was found in young miRNAs. Our data showed that compared with protein coding genes, miRNA genes are more dynamic in terms of emergence and decay. Evolution patterns are quite different between miRNAs of different ages. MicroRNAs activity is under tight control with well-regulated expression increased and targeting decreased over time. Our work calls attention to the study of miRNA activity with a consideration of their origin time.
Vorobyeva, Nadezhda E.; Mazina, Marina U.; Golovnin, Anton K.; Kopytova, Daria V.; Gurskiy, Dmitriy Y.; Nabirochkina, Elena N.; Georgieva, Sofia G.; Georgiev, Pavel G.; Krasnov, Aleksey N.
2013-01-01
Despite increasing data on the properties of replication origins, molecular mechanisms underlying origin recognition complex (ORC) positioning in the genome are still poorly understood. The Su(Hw) protein accounts for the activity of best-studied Drosophila insulators. Here, we show that Su(Hw) recruits the histone acetyltransferase complex SAGA and chromatin remodeler Brahma to Su(Hw)-dependent insulators, which gives rise to regions with low nucleosome density and creates conditions for ORC binding. Depletion in Su(Hw) leads to a dramatic drop in the levels of SAGA, Brahma and ORC subunits and a significant increase in nucleosome density on Su(Hw)-dependent insulators, whereas artificial Su(Hw) recruitment itself is sufficient for subsequent SAGA, Brahma and ORC binding. In contrast to the majority of replication origins that associate with promoters of active genes, Su(Hw)-binding sites constitute a small proportion (6%) of ORC-binding sites that are localized preferentially in transcriptionally inactive chromatin regions termed BLACK and BLUE chromatin. We suggest that the key determinants of ORC positioning in the genome are DNA-binding proteins that constitute different DNA regulatory elements, including insulators, promoters and enhancers. Su(Hw) is the first example of such a protein. PMID:23609538
Insights into the increasing virulence of the swine-origin pandemic H1N1/2009 influenza virus
Zou, Wei; Chen, Dijun; Xiong, Min; Zhu, Jiping; Lin, Xian; Wang, Lun; Zhang, Jun; Chen, Lingling; Zhang, Hongyu; Chen, Huanchun; Chen, Ming; Jin, Meilin
2013-01-01
Pandemic H1N1/2009 viruses have been stabilized in swine herds, and some strains display higher pathogenicity than the human-origin isolates. In this study, high-throughput RNA sequencing (RNA-seq) is applied to explore the systemic transcriptome responses of the mouse lungs infected by swine (Jia6/10) and human (LN/09) H1N1/2009 viruses. The transcriptome data show that Jia6/10 activates stronger virus-sensing signals, such as the toll-like receptor, RIG-I like receptor and NOD-like receptor signalings, as well as a stronger NF-κB and JAK-STAT singals, which play significant roles in inducing innate immunity. Most cytokines and interferon-stimulated genes show higher expression lever in Jia/06 infected groups. Meanwhile, virus Jia6/10 activates stronger production of reactive oxygen species, which might further promote higher mutation rate of the virus genome. Collectively, our data reveal that the swine-origin pandemic H1N1/2009 virus elicits a stronger innate immune reaction and pro-oxidation stimulation, which might relate closely to the increasing pathogenicity. PMID:23549303
Culturable yeasts in meltwaters draining from two glaciers in the Italian Alps
NASA Astrophysics Data System (ADS)
Buzzini, Pietro; Turchetti, Benedetta; Diolaiuti, Guglielmina; D'Agata, Carlo; Martini, Alessandro; Smiraglia, Claudio
The meltwaters draining from two glaciers in the Italian Alps contain metabolically active yeasts isolable by culture-based laboratory procedures. The average number of culturable yeast cells in the meltwaters was 10 20 colony-forming units (CFU) L-1, whereas supraglacial stream waters originating from overlying glacier ice contained <1 CFU L-1. Yeast cell number increased as the suspended-sediment content of the water samples increased. Basidiomycetous yeasts represent >80% of isolated strains (Cryptococcus spp. and Rhodotorula spp. were 33.3% and 17.8% of total strains, respectively). Culturable yeasts were psychrotolerant, predominantly obligate aerobes and able to degrade organic macromolecules (e.g. starch, esters, lipids, proteins). To the authors' knowledge, this is the first study to report the presence of culturable yeasts in meltwaters originating from glaciers. On the basis of these results, it is reasonable to suppose that the viable yeasts observed in meltwaters derived predominantly from the subglacial zone and that they originated from the subglacial microbial community. Their metabolic abilities could contribute to the microbial activity occurring in subglacial environments.
Marine algal toxins: origins, health effects, and their increased occurrence.
Van Dolah, F M
2000-01-01
Certain marine algae produce potent toxins that impact human health through the consumption of contaminated shellfish and finfish and through water or aerosol exposure. Over the past three decades, the frequency and global distribution of toxic algal incidents appear to have increased, and human intoxications from novel algal sources have occurred. This increase is of particular concern, since it parallels recent evidence of large-scale ecologic disturbances that coincide with trends in global warming. The extent to which human activities have contributed to their increase therefore comes into question. This review summarizes the origins and health effects of marine algal toxins, as well as changes in their current global distribution, and examines possible causes for the recent increase in their occurrence. Images Figure 2 Figure 3 PMID:10698729
NASA Astrophysics Data System (ADS)
Fernández-Reiriz, M. J.; Navarro, J. M.; Cisternas, B. A.; Babarro, J. M. F.; Labarta, U.
2013-12-01
We analyzed absorption efficiency (AE) and digestive enzyme activity (amylase, cellulase complex, and laminarinase) of the infaunal bivalve Tagelus dombeii originating from two geographic sites, Corral-Valdivia and Melinka-Aysén, which have different long-term paralytic shellfish poisoning (PSP) exposure rates. We report the effects of past feeding history (origin) on T. dombeii exposed to a mixed diet containing the toxic dinoflagellate Alexandrium catenella and another dinoflagellate-free control diet over a 12-day period in the laboratory. Absorption efficiency values of T. dombeii individuals that experienced PSP exposure in their habitat (Melinka-Aysén) remained unchanged during exposure to toxic food in the laboratory. In contrast, T. dombeii from a non-PSP exposure field site (Corral-Valdivia) showed a significant reduction in AE with toxic exposure time. This study established that the amylase and cellulase complexes were the most important enzymes in the digestive glands of Tagelus from both sites. The temporal evolution of enzymatic activity under toxic diet was fitted to exponential (amylase and cellulase) and to a logarithmic (laminarinase) models. In all fits, we found significant effect of origin in the model parameters. At the beginning of the experiment, higher enzymatic activity was observed for clams from Corral-Valdivia. The amylase activity decreased with time exposure for individuals from Corral and increased for individuals from Melinka. Cellulase activity did not vary over time for clams from Corral, but increased for individuals from Melinka and laminarinase activity decreased over time for individuals from Corral and remained unchanged over time for Melinka. A feeding history of exposure to the dinoflagellate A. catenella was reflected in the digestive responses of both T. dombeii populations.
Jepson, Ruth; Harris, Fiona M; Bowes, Alison; Robertson, Roma; Avan, Ghizala; Sheikh, Aziz
2012-01-01
People of South Asian backgrounds living in the UK have a five-fold increased risk of diabetes and a two-fold increased risk of heart disease when compared to the general population. Physical activity can reduce the risk of premature death from a range of conditions. The aim of the study was to explore the motivating and facilitating factors likely to increase physical activity for South Asian adults and their families, in order to develop successful interventions and services. This was a qualitative study using focus groups and in-depth interviews. Participants were 59 purposively selected Bangladeshi-, Indian- and Pakistani-origin men and women with an additional 10 key informants. The setting was three urban areas of Scotland: Aberdeen, Glasgow and Edinburgh. We undertook a theoretically informed thematic analysis of data. Study participants described engaging in a range of physical activities, particularly football and the gym for men, and walking and swimming for women. The main motivators for taking part in physical activity were external motivators--i.e. undertaking physical activity as a means to an end, which included the opportunities that physical activity provided for social activity and enjoyment. The goals of weight reduction and improving mental and physical health and were also mentioned. Role models were seen as important to inspire and motivate people to undertake activities that they may otherwise lack confidence in. Few people undertook physical activity for its own sake (intrinsic motivation). Attempts at promoting physical activity in people of South Asian origin need to take account of the social context of people's lives and the external motivators that encourage them to engage in physical activity. Undertaking group based physical activity is important and can be facilitated through religious, community, friendship or family networks. Role models may also prove particularly helpful.
Rojas Montero, G M; Alvarez López, M R; López Bermejo, A; Moya Quiles, M R; Muro Amador, M
2006-11-01
To perform a descriptive study of the activity of the Bank of marrow donors from Murcia Region. All donors in the Bank of bone marrow from 1994 until 2004 (n=3137). This study analysed the number of donors, their origin and, performed donor searches activity. Donors were typed by serological microlymphocytotoxicity and molecular PCR-SSO and PCR-SSP techniques. The Bank of bone marrow has 3,137 voluntary donors typed in low- and high-resolution. A total of 680 donor searches have been realized. The origin of the donors according to several Areas of Health in which the Autonomous Community of Murcia is divided, is the following one: Area I (28%), Area II (18 %), Area III (23 %), Area IV (6 %), Area VI (10 %) and other provinces (12%). An increase is observed in the number of annual donors as well as an increase very marked of donor searches that are realized every year, especially in 2004.
Ashida, Sato; Wilkinson, Anna V.; Koehly, Laura M.
2011-01-01
Purpose To evaluate whether influence from social network members is associated with motivation to change dietary and physical activity behaviors. Design Baseline assessment followed by mailing of family health history-based personalized messages (2 weeks) and follow-up assessment (3 months). Setting Families from an ongoing population-based cohort in Houston, TX. Subjects 475 adults from 161 Mexican origin families. Out of 347 households contacted, 162 (47%) participated. Measures Family health history, social networks, and motivation to change behaviors. Analysis Two-level logistic regression modeling. Results Having at least one network member who encourages one to eat more fruits and vegetables (p=.010) and to engage in regular physical activity (p=.046) was associated with motivation to change the relevant behavior. About 40% of the participants did not have encouragers for these behaviors. Conclusions Identification of new encouragers within networks and targeting natural encouragers (e.g., children, spouses) may increase the efficacy of interventions to motivate behavioral changes among Mexican origin adults. PMID:22208416
Ashida, Sato; Wilkinson, Anna V; Koehly, Laura M
2012-01-01
To evaluate whether influence from social network members is associated with motivation to change dietary and physical activity behaviors. Baseline assessment followed by mailing of family health history-based personalized messages (2 weeks) and follow-up assessment (3 months). Families from an ongoing population-based cohort in Houston, Texas. 475 adults from 161 Mexican-origin families. Out of 347 households contacted, 162 (47%) participated. Family health history, social networks, and motivation to change behaviors. Two-level logistic regression modeling. Having at least one network member who encourages one to eat more fruits and vegetables (p = .010) and to engage in regular physical activity (p = .046) was associated with motivation to change the relevant behavior. About 40% of the participants did not have encouragers for these behaviors. Identification of new encouragers within networks and targeting natural encouragers (e.g., children, spouses) may increase the efficacy of interventions to motivate behavioral changes among Mexican-origin adults.
Biologically Enhanced Energy and Carbon Cycling on Titan?
NASA Astrophysics Data System (ADS)
Schulze-Makuch, Dirk; Grinspoon, David H.
2005-08-01
With the Cassini-Huygens Mission in orbit around Saturn, the large moon Titan, with its reducing atmosphere, rich organic chemistry, and heterogeneous surface, moves into the astrobiological spotlight. Environmental conditions on Titan and Earth were similar in many respects 4 billion years ago, the approximate time when life originated on Earth. Life may have originated on Titan during its warmer early history and then developed adaptation strategies to cope with the increasingly cold conditions. If organisms originated and persisted, metabolic strategies could exist that would provide sufficient energy for life to persist, even today. Metabolic reactions might include the catalytic hydrogenation of photochemically produced acetylene, or involve the recombination of radicals created in the atmosphere by ultraviolet radiation. Metabolic activity may even contribute to the apparent youth, smoothness, and high activity of Titan's surface via biothermal energy.
Biologically enhanced energy and carbon cycling on Titan?
Schulze-Makuch, Dirk; Grinspoon, David H
2005-08-01
With the Cassini-Huygens Mission in orbit around Saturn, the large moon Titan, with its reducing atmosphere, rich organic chemistry, and heterogeneous surface, moves into the astrobiological spotlight. Environmental conditions on Titan and Earth were similar in many respects 4 billion years ago, the approximate time when life originated on Earth. Life may have originated on Titan during its warmer early history and then developed adaptation strategies to cope with the increasingly cold conditions. If organisms originated and persisted, metabolic strategies could exist that would provide sufficient energy for life to persist, even today. Metabolic reactions might include the catalytic hydrogenation of photochemically produced acetylene, or involve the recombination of radicals created in the atmosphere by ultraviolet radiation. Metabolic activity may even contribute to the apparent youth, smoothness, and high activity of Titan's surface via biothermal energy.
Effects of Resource Chemistry on the Composition and Function of Stream Hyporheic Biofilms
Hall, E. K.; Besemer, K.; Kohl, L.; Preiler, C.; Riedel, K.; Schneider, T.; Wanek, W.; Battin, T. J.
2012-01-01
Fluvial ecosystems process large quantities of dissolved organic matter as it moves from the headwater streams to the sea. In particular, hyporheic sediments are centers of high biogeochemical reactivity due to their elevated residence time and high microbial biomass and activity. However, the interaction between organic matter and microbial dynamics in the hyporheic zone remains poorly understood. We evaluated how variance in resource chemistry affected the microbial community and its associated activity in experimentally grown hyporheic biofilms. To do this we fed beech leaf leachates that differed in chemical composition to a series of bioreactors filled with sediment from a sub-alpine stream. Differences in resource chemistry resulted in differences in diversity and phylogenetic origin of microbial proteins, enzyme activity, and microbial biomass stoichiometry. Specifically, increased lignin, phenolics, and manganese in a single leachate resulted in increased phenoloxidase and peroxidase activity, elevated microbial biomass carbon:nitrogen ratio, and a greater proportion of proteins of Betaproteobacteria origin. We used this model system to attempt to link microbial form (community composition and metaproteome) with function (enzyme activity) in order to better understand the mechanisms that link resource heterogeneity to ecosystem function in stream ecosystems. PMID:22347877
Effects of resource chemistry on the composition and function of stream hyporheic biofilms.
Hall, E.K.; Besemer, K.; Kohl, L.; Preiler, C.; Reidel, K.; Schneider, T.; Wanek, W.; Battin, T.J.
2012-01-01
Fluvial ecosystems process large quantities of dissolved organic matter as it moves from the headwater streams to the sea. In particular, hyporheic sediments are centers of high biogeochemical reactivity due to their elevated residence time and high microbial biomass and activity. However, the interaction between organic matter and microbial dynamics in the hyporheic zone remains poorly understood. We evaluated how variance in resource chemistry affected the microbial community and its associated activity in experimentally grown hyporheic biofilms. To do this we fed beech leaf leachates that differed in chemical composition to a series of bioreactors filled with sediment from a sub-alpine stream. Differences in resource chemistry resulted in differences in diversity and phylogenetic origin of microbial proteins, enzyme activity, and microbial biomass stoichiometry. Specifically, increased lignin, phenolics, and manganese in a single leachate resulted in increased phenoloxidase and peroxidase activity, elevated microbial biomass carbon:nitrogen ratio, and a greater proportion of proteins of Betaproteobacteria origin. We used this model system to attempt to link microbial form (community composition and metaproteome) with function (enzyme activity) in order to better understand the mechanisms that link resource heterogeneity to ecosystem function in stream ecosystems.
Cdc7 is required throughout the yeast S phase to activate replication origins.
Donaldson, A D; Fangman, W L; Brewer, B J
1998-02-15
The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.
The activities of eukaryotic replication origins in chromatin.
Weinreich, Michael; Palacios DeBeer, Madeleine A; Fox, Catherine A
2004-03-15
DNA replication initiates at chromosomal positions called replication origins. This review will focus on the activity, regulation and roles of replication origins in Saccharomyces cerevisiae. All eukaryotic cells, including S. cerevisiae, depend on the initiation (activity) of hundreds of replication origins during a single cell cycle for the duplication of their genomes. However, not all origins are identical. For example, there is a temporal order to origin activation with some origins firing early during the S-phase and some origins firing later. Recent studies provide evidence that posttranslational chromatin modifications, heterochromatin-binding proteins and nucleosome positioning can control the efficiency and/or timing of chromosomal origin activity in yeast. Many more origins exist than are necessary for efficient replication. The availability of excess replication origins leaves individual origins free to evolve distinct forms of regulation and/or roles in chromosomes beyond their fundamental role in DNA synthesis. We propose that some origins have acquired roles in controlling chromatin structure and/or gene expression. These roles are not linked obligatorily to replication origin activity per se, but instead exploit multi-subunit replication proteins with the potential to form context-dependent protein-protein interactions.
NASA Astrophysics Data System (ADS)
Parshina, S. S.; Tokaeva, L. K.; Dolgova, E. M.; Afanas'yeva, T. N.; Strelnikova, O. A.
The origin of hemorheologic and endothelial defects in patients with unstable angina (comparing with healthy persons) is determined by a solar activity period: the blood viscosity increases in a period of high solar activity in the vessels of small, medium and macro diameters, a local decompensate dysfunction of small vessels endothelium had been fixed (microcirculation area). In the period of a low solar activity there is an increase of a blood viscosity in vessels of all diameters, generalized subcompensated endothelial dysfunction is developed (on the background of the III phase blood clotting activating). In the period of a high solar activity a higher blood viscosity had been fixed, comparing with the period of a low solar activity.
Cerebral gigantism of hypothalamic origin.
Ranke, M B; Bierich, J R
1983-04-01
In five cases of Sotos Syndrome serum somatomedin activities were measured. In two of these cases elevated levels and an increased secretion of growth hormone was observed. In one case (index case) a suspected hypothalamic tumor mass could be excluded, but hydrocephalus with increased intracranial pressure was present. The pathogenesis of gigantism in this syndrome is discussed.
Endothelial- and Platelet-Derived Microparticles Are Generated During Liver Resection in Humans.
Banz, Yara; Item, Gian-Marco; Vogt, Andreas; Rieben, Robert; Candinas, Daniel; Beldi, Guido
2016-01-01
Cell-derived plasma microparticles (<1.5 μm) originating from various cell types have the potential to regulate thrombogenesis and inflammatory responses. The aim of this study was to test the hypothesis that microparticles generated during hepatic surgery co-regulate postoperative procoagulant and proinflammatory events. In 30 patients undergoing liver resection, plasma microparticles were isolated, quantitated, and characterized as endothelial (CD31+, CD41-), platelet (CD41+), or leukocyte (CD11b+) origin by flow cytometry and their procoagulant and proinflammatory activity was measured by immunoassays. During liver resection, the total numbers of microparticles increased with significantly more Annexin V-positive, endothelial and platelet-derived microparticles following extended hepatectomy compared to standard and minor liver resections. After liver resection, microparticle tissue factor and procoagulant activity increased along with overall coagulation as assessed by thrombelastography. Levels of leukocyte-derived microparticles specifically increased in patients with systemic inflammation as assessed by C-reactive protein but are independent of the extent of liver resection. Endothelial and platelet-derived microparticles are specifically elevated during liver resection, accompanied by increased procoagulant activity. Leukocyte-derived microparticles are a potential marker for systemic inflammation. Plasma microparticles may represent a specific response to surgical stress and may be an important mediator of postoperative coagulation and inflammation.
Butts, I A E; Litvak, M K; Trippel, E A
2010-04-15
The objective was to investigate changes, throughout the spawning season, in body size attributes and quantitative semen characteristics of wild-caught and cultivated Atlantic cod, Gadus morhua L. Sperm velocity increased significantly throughout the spawning season of cod from both origins. Curvilinear velocity (VCL; 30 sec post-activation) increased from 78.9+/-6.5 to 128.2+/-6.5 microm/sec (mean+/-SEM) between the beginning and end of the spawning season, respectively, for wild-caught cod, whereas for cultivated fish, it increased from 26.6+/-2.4 to 48.9+/-3.1 microm/sec between January and March. Spermatocrit did not undergo a significant seasonal change in wild-caught cod but did thicken for cultivated cod (24.6+/-4.2% in January to 40.5+/-4.4% in April; P<0.01). Sperm head area, perimeter, length, and width declined significantly at the end of the spawning season of cod from both origins (all P values<0.01). Seminal plasma osmolality and Na(+) ion concentration followed a dome-shaped function through the spawning season for both wild-caught and cultivated cod (P<0.05). For cultivated cod, seminal plasma pH was significantly lower at the start of the spawning season (P<0.001), whereas Ca(2+) increased then decreased (P<0.05). Body size attributes, spermatocrit, and seminal plasma constituents had significant relationships with sperm activity variables. These relationships varied as a function of time post-activation, month, and fish origin. Our findings may be used to (i) assess spermiation stage without killing males; (ii) optimize semen collection for hatchery production; (iii) characterize the potential impact of farming on sperm quality; and (iv) improve success of sperm cryopreservation and short-term storage. Copyright 2010 Elsevier Inc. All rights reserved.
Relationships between solar activity and climate change
NASA Technical Reports Server (NTRS)
Roberts, W. O.
1975-01-01
The relationship between recurrent droughts in the High Plains of the United States and the double sunspot cycle is discussed in detail. It is suggested that high solar activity is generally related to an increase in meridional circulation and blocking patterns at high and intermediate latitudes, especially in winter, and the effect is related to the sudden formation of cirrus clouds during strong geomagnetic activity that originates in the solar corpuscular emission.
CLB5-dependent activation of late replication origins in S. cerevisiae.
Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L
1998-08-01
Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.
Yang, Ji; Cao, Limei; Guo, Rui; Jia, Jinping
2010-12-15
Granular activated carbon was modified with dimethyl dichlorosilane to improve its surface hydrophobicity, and therefore to improve the performance of permeable reactive barrier constructed with the modified granular activated carbon and elemental iron. X-ray photoelectron spectroscopy shows that the surface silicon concentration of the modified granular activated carbon is higher than that of the original one, leading to the increased surface hydrophobicity. Although the specific surface area decreased from 895 to 835 m(2)g(-1), the modified granular activated carbon could adsorb 20% more 2,4-dichlorophenol than the original one did in water. It is also proven that the permeable reactive barrier with the modified granular activated carbon is more efficient at 2,4-dichlorophenol dechlorination, in which process 2,4-dichlorophenol is transformed to 2-chlorophenol or 4-chlorophenol then to phenol, or to phenol directly. Copyright © 2010 Elsevier B.V. All rights reserved.
Origins of correlated activity in an olfactory circuit.
Kazama, Hokto; Wilson, Rachel I
2009-09-01
Multineuronal recordings often reveal synchronized spikes in different neurons. The manner in which correlated spike timing affects neural codes depends on the statistics of correlations, which in turn reflects the connectivity that gives rise to correlations. However, determining the connectivity of neurons recorded in vivo can be difficult. We investigated the origins of correlated activity in genetically labeled neurons of the Drosophila antennal lobe. Dual recordings showed synchronized spontaneous spikes in projection neurons (PNs) postsynaptic to the same type of olfactory receptor neuron (ORN). Odors increased these correlations. The primary origin of correlations lies in the divergence of each ORN onto every PN in its glomerulus. Reciprocal PN-PN connections make a smaller contribution to correlations and PN spike trains in different glomeruli were only weakly correlated. PN axons from the same glomerulus reconverge in the lateral horn, where pooling redundant signals may allow lateral horn neurons to average out noise that arises independently in these PNs.
Nucleosomes influence multiple steps during replication initiation
Azmi, Ishara F; Watanabe, Shinya; Maloney, Michael F; Kang, Sukhyun; Belsky, Jason A; MacAlpine, David M; Peterson, Craig L; Bell, Stephen P
2017-01-01
Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation. Origin licensing assays showed that local nucleosome positioning enhanced origin specificity and modulated helicase loading by influencing ORC DNA binding. Interestingly, SWI/SNF- and RSC-remodeled nucleosomes were permissive for origin licensing but showed reduced helicase activation. Specific CREs rescued replication of these templates if added prior to helicase activation, indicating a permissive chromatin state must be established during origin licensing to allow efficient origin activation. Our studies show nucleosomes directly modulate origin licensing and activation through distinct mechanisms and provide insights into the regulation of replication initiation by chromatin. DOI: http://dx.doi.org/10.7554/eLife.22512.001 PMID:28322723
Wilson, Michael B; Pawlus, Alison D; Brinkman, Doug; Gardner, Gary; Hegeman, Adrian D; Spivak, Marla; Cohen, Jerry D
2017-06-01
Honey bees, Apis mellifera, collect antimicrobial plant resins from the environment and deposit them in their nests as propolis. This behavior is of practical concern to beekeepers since the presence of propolis in the hive has a variety of benefits, including the suppression of disease symptoms. To connect the benefits that bees derive from propolis with particular resinous plants, we determined the identity and botanical origin of propolis compounds active against bee pathogens using bioassay-guided fractionation against the bacterium Paenibacillus larvae, the causative agent of American foulbrood. Eleven dihydroflavonols were isolated from propolis collected in Fallon, NV, including pinobanksin-3-octanoate. This hitherto unknown derivative and five other 3-acyl-dihydroflavonols showed inhibitory activity against both P. larvae (IC 50 = 17-68 μM) and Ascosphaera apis (IC 50 = 8-23 μM), the fungal agent of chalkbrood. A structure-activity relationship between acyl group size and antimicrobial activity was found, with longer acyl groups increasing activity against P. larvae and shorter acyl groups increasing activity against A. apis. Finally, it was determined that the isolated 3-acyl-dihydroflavonols originated from Populus fremontii, and further analysis showed these compounds can also be found in other North American Populus spp. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ancient climate change, antifreeze, and the evolutionary diversification of Antarctic fishes
Near, Thomas J.; Dornburg, Alex; Kuhn, Kristen L.; Eastman, Joseph T.; Pennington, Jillian N.; Patarnello, Tomaso; Zane, Lorenzo; Fernández, Daniel A.; Jones, Christopher D.
2012-01-01
The Southern Ocean around Antarctica is among the most rapidly warming regions on Earth, but has experienced episodic climate change during the past 40 million years. It remains unclear how ancient periods of climate change have shaped Antarctic biodiversity. The origin of antifreeze glycoproteins (AFGPs) in Antarctic notothenioid fishes has become a classic example of how the evolution of a key innovation in response to climate change can drive adaptive radiation. By using a time-calibrated molecular phylogeny of notothenioids and reconstructed paleoclimate, we demonstrate that the origin of AFGP occurred between 42 and 22 Ma, which includes a period of global cooling approximately 35 Ma. However, the most species-rich lineages diversified and evolved significant ecological differences at least 10 million years after the origin of AFGPs, during a second cooling event in the Late Miocene (11.6–5.3 Ma). This pattern indicates that AFGP was not the sole trigger of the notothenioid adaptive radiation. Instead, the bulk of the species richness and ecological diversity originated during the Late Miocene and into the Early Pliocene, a time coincident with the origin of polar conditions and increased ice activity in the Southern Ocean. Our results challenge the current understanding of the evolution of Antarctic notothenioids suggesting that the ecological opportunity that underlies this adaptive radiation is not linked to a single trait, but rather to a combination of freeze avoidance offered by AFGPs and subsequent exploitation of new habitats and open niches created by increased glacial and ice sheet activity. PMID:22331888
Ozawa, Rika; Endo, Hiroki; Iijima, Mei; Sugimoto, Koichi; Takabayashi, Junji; Gotoh, Tetsuo; Arimura, Gen-Ichiro
2017-02-27
Two genotypes coexist among Kanzawa spider mites, one of which causes red scars and the other of which causes white scars on leaves, and they elicit different defense responses in host plants. Based on RNA-Seq analysis, we revealed here that the expression levels of genes involved in the detoxification system were higher in Red strains than White strains. The corresponding enzyme activities as well as performances for acaricide resistance and host adaptation toward Laminaceae were also higher in Red strains than White strains, indicating that Red strains were superior in trait(s) of the detox system. In subsequent generations of strains that had survived exposure to fenpyroximate, both strains showed similar resistance to this acaricide, as well as similar detoxification activities. The endogenous levels of salicylic acid and jasmonic acid were increased similarly in bean leaves damaged by original Red strains and their subsequent generations that inherited high detox activity. Jasmonic acid levels were increased in leaves damaged by original White strains, but not by their subsequent generations that inherited high detox activity. Together, these data suggest the existence of intraspecific variation - at least within White strains - with respect to their capacity to withstand acaricides and host plant defenses.
Relationship Between Human Physiological Parameters And Geomagnetic Variations Of Solar Origin
NASA Astrophysics Data System (ADS)
Dimitrova, S.
This study attempts to assess the influence of increased geomagnetic activity on some human physiological parameters. The blood pressure, heart rate and general well-being of 86 volunteers were measured (the latter by means of a standardized questionnaire) on work days in autumn 2001 (01/10 to 09/11) and in spring 2002 (08/04 to 28/05). These periods were chosen because of maximal expected geomagnetic activity. Altogether, 2799 recordings were obtained and analysed. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The three factors were the following: 1) planetary geomagnetic activity level estimated by Ap-index and divided into five levels; 2) gender - males and females; 3) blood pressure degree - persons in the group examined were divided into hypotensive, normotensive and hypertensive. Post hoc analysis was performed to elicit the significance of differences in the factors' levels. The average arterial blood pressure of the group was found to increase significantly with the increase of geomagnetic activity level. The average increment of systolic and diastolic blood pressure reached 9%, which deserves attention from a medical point of view. This effect was present irrespectively of gender. Results obtained suppose that hypertensive persons have the highest sensitivity and the hypotensive persons have the lowest sensitivity of the arterial blood pressure to increase of geomagnetic activity. The results did not show significant changes in the heart rate. The percentage of the persons who reported subjective psycho-physiological complaints was also found to increase significantly with the geomagnetic activity increase. During severe geomagnetic storms 30% of the persons examined reported subjective complaints and the highest sensitivity was revealed for the hypertensive females. The results obtained add further evidence that blood pressure seems to be affected by geomagnetic variations of solar origin. The examinations and analyses performed show that space weather prediction may be utilized for the purpose of pharmacological and regime measures to limit the adverse physiological reactions to geomagnetic storms.
A DNA sequence element that advances replication origin activation time in Saccharomyces cerevisiae.
Pohl, Thomas J; Kolor, Katherine; Fangman, Walton L; Brewer, Bonita J; Raghuraman, M K
2013-11-06
Eukaryotic origins of DNA replication undergo activation at various times in S-phase, allowing the genome to be duplicated in a temporally staggered fashion. In the budding yeast Saccharomyces cerevisiae, the activation times of individual origins are not intrinsic to those origins but are instead governed by surrounding sequences. Currently, there are two examples of DNA sequences that are known to advance origin activation time, centromeres and forkhead transcription factor binding sites. By combining deletion and linker scanning mutational analysis with two-dimensional gel electrophoresis to measure fork direction in the context of a two-origin plasmid, we have identified and characterized a 19- to 23-bp and a larger 584-bp DNA sequence that are capable of advancing origin activation time.
Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans.
Skurnik, David; Clermont, Olivier; Guillard, Thomas; Launay, Adrien; Danilchanka, Olga; Pons, Stéphanie; Diancourt, Laure; Lebreton, François; Kadlec, Kristina; Roux, Damien; Jiang, Deming; Dion, Sara; Aschard, Hugues; Denamur, Maurice; Cywes-Bentley, Colette; Schwarz, Stefan; Tenaillon, Olivier; Andremont, Antoine; Picard, Bertrand; Mekalanos, John; Brisse, Sylvain; Denamur, Erick
2016-04-01
In the context of the great concern about the impact of human activities on the environment, we studied 403 commensal Escherichia coli/Escherichia clade strains isolated from several animal and human populations that have variable contacts to one another. Multilocus sequence typing (MLST) showed a decrease of diversity 1) in strains isolated from animals that had an increasing contact with humans and 2) in all strains that had increased antimicrobial resistance. A specific B1 phylogroup clonal complex (CC87, Institut Pasteur schema nomenclature) of animal origin was identified and characterized as being responsible for the increased antimicrobial resistance prevalence observed in strains from the environments with a high human-mediated antimicrobial pressure. CC87 strains have a high capacity of acquiring and disseminating resistance genes with specific metabolic and genetic determinants as demonstrated by high-throughput sequencing and phenotyping. They are good mouse gut colonizers but are not virulent. Our data confirm the predominant role of human activities in the emergence of antimicrobial resistance in the environmental bacterial strains and unveil a particular E. coli clonal complex of animal origin capable of spreading antimicrobial resistance to other members of microbial communities. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Alday, Erick A Perez; Colman, Michael A; Langley, Philip; Zhang, Henggui
2017-03-01
Atrial tachy-arrhytmias, such as atrial fibrillation (AF), are characterised by irregular electrical activity in the atria, generally associated with erratic excitation underlain by re-entrant scroll waves, fibrillatory conduction of multiple wavelets or rapid focal activity. Epidemiological studies have shown an increase in AF prevalence in the developed world associated with an ageing society, highlighting the need for effective treatment options. Catheter ablation therapy, commonly used in the treatment of AF, requires spatial information on atrial electrical excitation. The standard 12-lead electrocardiogram (ECG) provides a method for non-invasive identification of the presence of arrhythmia, due to irregularity in the ECG signal associated with atrial activation compared to sinus rhythm, but has limitations in providing specific spatial information. There is therefore a pressing need to develop novel methods to identify and locate the origin of arrhythmic excitation. Invasive methods provide direct information on atrial activity, but may induce clinical complications. Non-invasive methods avoid such complications, but their development presents a greater challenge due to the non-direct nature of monitoring. Algorithms based on the ECG signals in multiple leads (e.g. a 64-lead vest) may provide a viable approach. In this study, we used a biophysically detailed model of the human atria and torso to investigate the correlation between the morphology of the ECG signals from a 64-lead vest and the location of the origin of rapid atrial excitation arising from rapid focal activity and/or re-entrant scroll waves. A focus-location algorithm was then constructed from this correlation. The algorithm had success rates of 93% and 76% for correctly identifying the origin of focal and re-entrant excitation with a spatial resolution of 40 mm, respectively. The general approach allows its application to any multi-lead ECG system. This represents a significant extension to our previously developed algorithms to predict the AF origins in association with focal activities.
MetILs 3: A Strategy for High Density Energy Storage Using Redox-Active Ionic Liquids
Small, Leo J.; Pratt, Harry D.; Staiger, Chad L.; ...
2017-07-26
We present a systematic approach for increasing the concentration of redox-active species in electrolytes for nonaqueous redox flow batteries (RFBs). Starting with an ionic liquid consisting of a metal coordination cation (MetIL), ferrocene-containing ligands and iodide anions are substituted incrementally into the structure. While chemical structures can be drawn for molecules with 10 m redox-active electrons (RAE), practical limitations such as melting point and phase stability constrain the structures to 4.2 m RAE, a 2.3× improvement over the original MetIL. Dubbed “MetILs 3,” these ionic liquids possess redox activity in the cation core, ligands, and anions. Throughout all compositions, infraredmore » spectroscopy shows the ethanolamine-based ligands primarily coordinate to the Fe 2+ core via hydroxyl groups. Calorimetry conveys a profound change in thermophysical properties, not only in melting temperature but also in suppression of a cold crystallization only observed in the original MetIL. Square wave voltammetry reveals redox processes characteristic of each molecular location. Testing a laboratory-scale RFB demonstrates Coulombic efficiencies >95% and increased voltage efficiencies due to more facile redox kinetics, effectively increasing capacity 4×. Application of this strategy to other chemistries, optimizing melting point and conductivity, can yield >10 m RAE, making nonaqueous RFB a viable technology for grid scale storage.« less
Pisciotta, Marzia; Morgavi, Giovanna; Jahnsen, Henrik
2010-10-28
Dynamic aspects of the propagation of epileptiform activity have so far received little attention. With the aim of providing new insights about the spatial features of the propagation of epileptic seizures in the nervous system, we studied in vitro the initiation and propagation of traveling epileptiform waves of electrophysiological activity in the hippocampus by means of substrate three-dimensional microelectrode arrays (MEAs) for extracellular measurements. Pharmacologically disinhibited hippocampal slices spontaneously generate epileptiform bursts mostly originating in CA3 and propagating to CA1. Our study specifically addressed the activity-dependent changes of the propagation of traveling electrophysiological waves in organotypic hippocampal slices during epileptiform discharge and in particular our question is: what happens to the epileptic signals during their propagation through the slice? Multichannel data analysis enabled us to quantify an activity-dependent increase in the propagation velocity of spontaneous bursts. Moreover, through the evaluation of the coherence of the signals, it was possible to point out that only the lower-frequency components (<95Hz) of the electrical activity are completely coherent with respect to the activity originating in the CA3, while components at higher frequencies lose the coherence, possibly suggesting that the cellular mechanism mediating propagation of electrophysiological activity becomes ineffective for those firing rates exceeding an upper bound or that some noise of neuronal origin was added to the signal during propagation. Copyright © 2010 Elsevier B.V. All rights reserved.
Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2.
Zallocchi, Marisa Laura; Matkovic, Laura; Calvo, Juan Carlos; Damasco, María Cristina
2004-06-01
Renal 11beta-hydroxysteroid dehydrogenase 2 (HSD2) catalyzes the conversion of active glucocorticoids to inert 11beta-keto compounds, thereby preventing the illicit binding of these hormones to mineralocorticoid receptors (MRs) and, thus, conferring aldosterone specificity. Absence or inhibition of HSD2 activity, originates a hypertensive syndrome with sodium retention and increased potassium elimination. Recent studies from our laboratory reported an increment of HSD2 activity in intact-stressed rats. To evaluate the adrenal involvement in this increase, we analyzed HSD2 activity and protein abundance in Intact, Sham-operated, and adrenalectomized rats under stress situations (gavage with an overload of 200 mM HCl (10 ml) and simulated gavage) or with corticosterone replacement. HSD2 activity was assessed in renal microsomal preparations obtained from different groups of animals. HSD2 protein abundance was measured by Western-blot. Circulating corticosterone was determined by radioimmunoassay. Sham-operated animals showed an increase in HSD2 activity and abundance compared to Intact and adrenalectomized rats suggesting the involvement of stress-related adrenal factors in HSD2 regulation. In the case of acidotic adrenalectomized animals, there was an increase in renal HSD2 activity when, along with the HCl overload, the rats were injected with corticosterone. This increment occurred without an increase in enzyme abundance. These results suggest the importance of circulating levels of glucocorticoids to respond to a metabolic acidosis, through regulation of HSD2 stimulation. The group subjected to a simulated gavage showed an increase in enzyme activity and protein abundance, thus demonstrating the need for both adrenal and extra-factors in the modulation of renal HSD2. The adrenalectomized animals injected with different doses of corticosterone, produced a progressive increase in enzyme activity and abundance, being significant for the dose of 68 microg corticosterone/100 g body weight. The highest dose (308 microg/100 g body weight) did not show any variation in activity and abundance compared to the control group. This biphasic effect of glucocorticoids could be explained taking into account their permissive and suppressive actions, depending on their blood levels. Knowing that stress induces multifactorial responses, it should not be surprising to observe a differential regulation in renal HSD2, confirming that different stressors act through different factors of both, adrenal and extra-adrenal origin. Copyright 2004 Wiley-Liss, Inc.
"Project Psychology": A Classroom Competition
ERIC Educational Resources Information Center
Fleck, Bethany K. B.; Hussey, Heather D.
2009-01-01
The authors describe an original and unique series of classroom group-work activities organized as a competitive game called "Project Psychology," which was implemented in an Introduction to Psychology course. The project goals included increasing student participation, interest, content comprehension, and motivation. Fostering…
Dawes, Nickki Pearce; Modecki, Kathryn L; Gonzales, Nancy; Dumka, Larry; Millsap, Roger
2015-11-01
The potential benefits of participation in extracurricular activities may be especially important for youth who are at risk for academic underachievement, such as low income Mexican-origin youth in the U.S. To advance understanding of factors that drive participation for this population, this study examined Mexican-origin youth's trajectories of participation in extracurricular activities across Grades 7-12 and tested theoretically-derived predictors of these trajectories. Participants were 178 adolescents (53.9 % Female, Mage = 12.28) and their mothers who separately completed in-home interviews. Youth reported the frequency of their participation across a range of extracurricular activities. Latent growth curve models of overall extracurricular activities participation, sports participation, and fine arts participation were individually estimated via structural equation modeling. The findings demonstrated developmental declines in overall participation and in sports participation. For fine arts, declines in participation in middle school were followed by subsequent increases during high school (a curvilinear pattern). Motivationally-salient predictors of participation trajectories included youth's traditional cultural values orientation (sports), the mothers' educational aspirations for the youth (sports, fine arts, overall activity), and youth gender (sports, fine arts). Overall, the results suggest variability in participation trajectories based on program type, and highlight the need for additional research to enhance our understanding of the impact of culturally-relevant predictors on participation over time.
Rudolf, Emil; Cervinka, Miroslav
2009-08-10
In this study we examined interactions between human dermal fibroblasts and chromium acetate hydroxide originating from environmental waste sediments. We show that initially exposure of fibroblasts to Cr (III) induced membrane-dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal-regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3. At later treatment intervals (48-96 h), caspase-3 activity became suppressed and markedly increased lactate dehydrogenase (LDH) release was observed. Further experiments demonstrated that LDH release occurred in the presence of increased oxidative stress, extensive DNA damage, overactivation of poly(ADP-ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it was demonstrated that oxidative stress along with PARP-1 activity are responsible for cell death mode switch and upon their inhibition caspase-3 activity could be restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage and resulting PARP-1 activity.
A DNA Sequence Element That Advances Replication Origin Activation Time in Saccharomyces cerevisiae
Pohl, Thomas J.; Kolor, Katherine; Fangman, Walton L.; Brewer, Bonita J.; Raghuraman, M. K.
2013-01-01
Eukaryotic origins of DNA replication undergo activation at various times in S-phase, allowing the genome to be duplicated in a temporally staggered fashion. In the budding yeast Saccharomyces cerevisiae, the activation times of individual origins are not intrinsic to those origins but are instead governed by surrounding sequences. Currently, there are two examples of DNA sequences that are known to advance origin activation time, centromeres and forkhead transcription factor binding sites. By combining deletion and linker scanning mutational analysis with two-dimensional gel electrophoresis to measure fork direction in the context of a two-origin plasmid, we have identified and characterized a 19- to 23-bp and a larger 584-bp DNA sequence that are capable of advancing origin activation time. PMID:24022751
Efficient adsorption of Hg (II) ions in water by activated carbon modified with melamine
NASA Astrophysics Data System (ADS)
Qin, Hangdao; Meng, Jingling; Chen, Jing
2018-04-01
Removal of Hg (II) ions from industrial wastewater is important for the water treatment, and adsorption is an efficient treatment process. Activated carbon (AC) was modified with melamine, which introduced nitrogen-containing functional groups onto AC surface. Original AC and melamine modified activated carbon (ACM) were characterized by elemental analysis, N2 adsorption-desorption, determination of the pH of the point of zero charge (pHpzc) and X-ray photoelectron spectroscopy (XPS) and their performance in the adsorption of Hg(II) ions was investigated. Langmuir model fitted the experimental data of equilibrium isotherms well. ACM showed the higher Hg (II) ions adsorption capacity, increasing more than more than 1.8 times compared to the original one. Moreover, ACM showed a wider pH range for the maximum adsorption than the parent AC.
Muscle Co-activation: Definitions, Mechanisms, and Functions.
Latash, Mark L
2018-03-28
The phenomenon of agonist-antagonist muscle co-activation is discussed with respect to its consequences for movement mechanics (such as increasing joint apparent stiffness, facilitating faster movements, and effects on action stability), implication for movement optimization, and involvement of different neurophysiological structures. Effects of co-activation on movement stability are ambiguous and depend on the effector representing a kinematic chain with a fixed origin or free origin. Further, co-activation is discussed within the framework of the equilibrium-point hypothesis and the idea of hierarchical control with spatial referent coordinates. Relations of muscle co-activation to changes in one of the basic commands, the c-command, are discussed and illustrated. A hypothesis is suggested that agonist-antagonist co-activation reflects a deliberate neural control strategy to preserve effector-level control and avoid making it degenerate and facing the necessity to control at the level of signals to individual muscles. This strategy, in particular, allows stabilizing motor actions by co-varied adjustments in spaces of control variables. This hypothesis is able to account for higher levels of co-activation in young healthy persons performing challenging tasks and across various populations with movement impairments.
Kozaki, Ikko; Shimizu, Kazunori; Honda, Hiroyuki
2017-08-01
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention as regulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; it combined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can be delivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of the present study was to demonstrate that the proposed screening system can be used for assessing the intracellular activity of peptides. The cell death-inducing peptide (LNLISKLF) identified in a mitochondria-targeting domain (MTD) of the Noxa protein served as an original peptide sequence for screening of peptides with higher activity via modification of the peptide sequence. We obtained 4 peptides with higher activity, in which we substituted serine (S) at the fifth position with phenylalanine (F), valine (V), tryptophan (W), or tyrosine (Y). During analysis of the mechanism of action, the modified peptides induced an increase in intracellular calcium concentration, which was caused by the treatment with the original peptide. Higher capacity for cell death induction by the modified peptides may be caused by increased hydrophobicity or an increased number of aromatic residues. Thus, the present work suggests that the intracellular activity of peptides can be assessed using the proposed screening system. It could be used for identifying intracellular functional peptides with higher activity through comprehensive screening. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Multiple determinants controlling activation of yeast replication origins late in S phase.
Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L
1996-07-01
Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.
Laallam, Hadda; Boughediri, Larbi; Bissati, Samia; Menasria, Taha; Mouzaoui, Mohamed S.; Hadjadj, Soumia; Hammoudi, Rokia; Chenchouni, Haroun
2015-01-01
Background: Honey has multiple therapeutic properties due to its composition with diverse components. Objectives: This study aims to investigate the antimicrobial efficacy of Saharan honeys against bacterial pathogens, the variation of honey floral origins, and its physicochemical characteristics. Materials and Methods: The antimicrobial activity of 32 samples of honey collected from the Algerian Sahara Desert was tested on four bacteria; Bacillus subtilis, Clostridium perfringens, Escherichia coli, and Staphylococcus aureus. The botanical origin of honeys and their physicochemical properties were determined and their combined antibacterial effects were modeled using a generalized linear mixed model (GLMM). Results: Out of the 32 study samples, 14 were monofloral and 18 were multifloral. The pollen density was on average 7.86 × 106 grains/10 g of honey, water content was 14.6%, electrical conductivity (EC) was 0.5 μS/cm, pH was 4.38 ± 0 50, hydroxymethylfurfural (HMF) content was 82 mg/kg of honey, total sugars = 83%, reducing sugars = 71%, and the concentration of proline = 525.5 ± 550.2 mg/kg of honey. GLMM revealed that the antibacterial effect of honey varied significantly between bacteria and floral origins. This effect increased with increasing of water content and reducing sugars in honey, but it significantly decreased with increase of honey EC. E. coli was the most sensitive species with an inhibition zone of 10.1 ± 4.7 mm, while C. perfringens was the less sensitive. Honeys dominated by pollen of Fabaceae sp. were most effective with an overall antimicrobial activity equals to 13.5 ± 4.7 mm. Conclusion: Saharan honeys, of certain botanical origins, have physicochemical and pollinic characteristics with relevant potential for antibacterial purposes. This encourages a more comprehensive characterization of honeys with in vivo and in vitro investigations. PMID:26594206
ERIC Educational Resources Information Center
Clements, John D.; Connell, Nancy D.; Dirks, Clarissa; El-Faham, Mohamed; Hay, Alastair; Heitman, Elizabeth; Stith, James H.; Bond, Enriqueta C.; Colwell, Rita R.; Anestidou, Lida; Husbands, Jo L.; Labov, Jay B.
2013-01-01
Numerous studies are demonstrating that engaging undergraduate students in original research can improve their achievement in the science, technology, engineering, and mathematics (STEM) fields and increase the likelihood that some of them will decide to pursue careers in these disciplines. Associated with this increased prominence of research in…
Cloning and establishment of a line of rats for high levels of voluntary wheel running.
Morishima-Yamato, Masaki; Hisaoka, Fumiko; Shinomiya, Sachiko; Harada, Nagakatsu; Matoba, Hideki; Takahashi, Akira; Nakaya, Yutaka
2005-06-17
We generated an original Wistar line of rats that displayed increased levels of wheel running, which we named SPORTS (Spontaneously-Running-Tokushima-Shikoku). Male SPORTS rats ran voluntarily in a running wheel almost six times longer than male control Wistar rats, established without selection for their running activity. The running phenotype of female SPORTS rats was the same as female control Wistar rats. However, male offspring from the cross-mating between a female SPORTS rat and a male control rat also showed a similar level of hyper-running activity as the original SPORTS line. Compared to control rats, male SPORTS rats had lower levels of mean body weight, abdominal fat and plasma insulin after 4 weeks of running. It is likely that all these beneficial changes observed in the SPORTS rats reflected the increases in glucose disposal we observed in oral glucose tolerance tests carried out on the animals. We also found hyper-running caused a significant increase in skeletal muscle oxidative capacity, measured as the ratio of malate dehydrogenase to phosphofructokinase activity, an index of aerobic metabolism. These results indicate that the SPORTS rat may be a good animal model for determining the mechanisms responsible for up-regulation of running motivation, in addition to investigating changes in nutrient metabolism induced by high intensity exercise.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Small, Leo J.; Pratt, Harry D.; Staiger, Chad L.
We present a systematic approach for increasing the concentration of redox-active species in electrolytes for nonaqueous redox flow batteries (RFBs). Starting with an ionic liquid consisting of a metal coordination cation (MetIL), ferrocene-containing ligands and iodide anions are substituted incrementally into the structure. While chemical structures can be drawn for molecules with 10 m redox-active electrons (RAE), practical limitations such as melting point and phase stability constrain the structures to 4.2 m RAE, a 2.3× improvement over the original MetIL. Dubbed “MetILs 3,” these ionic liquids possess redox activity in the cation core, ligands, and anions. Throughout all compositions, infraredmore » spectroscopy shows the ethanolamine-based ligands primarily coordinate to the Fe 2+ core via hydroxyl groups. Calorimetry conveys a profound change in thermophysical properties, not only in melting temperature but also in suppression of a cold crystallization only observed in the original MetIL. Square wave voltammetry reveals redox processes characteristic of each molecular location. Testing a laboratory-scale RFB demonstrates Coulombic efficiencies >95% and increased voltage efficiencies due to more facile redox kinetics, effectively increasing capacity 4×. Application of this strategy to other chemistries, optimizing melting point and conductivity, can yield >10 m RAE, making nonaqueous RFB a viable technology for grid scale storage.« less
Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel
2017-11-27
Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.
Masschelein, J; Jenner, M; Challis, G L
2017-07-01
Covering: up to 2017The overwhelming majority of antibiotics in clinical use originate from Gram-positive Actinobacteria. In recent years, however, Gram-negative bacteria have become increasingly recognised as a rich yet underexplored source of novel antimicrobials, with the potential to combat the looming health threat posed by antibiotic resistance. In this article, we have compiled a comprehensive list of natural products with antimicrobial activity from Gram-negative bacteria, including information on their biosynthetic origin(s) and molecular target(s), where known. We also provide a detailed discussion of several unusual pathways for antibiotic biosynthesis in Gram-negative bacteria, serving to highlight the exceptional biocatalytic repertoire of this group of microorganisms.
Nagai, T; Kai, N; Tanoue, Y; Suzuki, N
2018-02-01
The chemical parameters and the functionalities of six monofloral honeys of different botanical and geographical origins were investigated. Vitamins B 1 , B 2 , and C and the protein content of majority of honeys were distinguishable from general honey. Honeys not only were rich in a variety of functional components like flavonoids but also had strong anti-oxidant activities, scavenging activities against ROS, and anti-hypertensive and anti-allergic activities. Honeys were heated at 100 °C for 24 h and their browning intensity during heating process was observed to vary with botanical origin. The functional properties of caramelization and maillard reaction (MR) products derived from honeys during heating were evaluated. The browning of honeys progressed regardless of honey species. Anti-oxidant activities and scavenging activities against superoxide and DPPH radicals of products drastically increased, but ACE and hyaluronidase activities gradually decreased with passage of heating time. It concluded that the products, mainly melanoidins, produced simultaneously to browning process in caramelization and MR contributed to the expression of its useful function.
Tousch, Didier; Bidel, Luc P R; Cazals, Guillaume; Ferrare, Karine; Leroy, Jeremy; Faucanié, Marie; Chevassus, Hugues; Tournier, Michel; Lajoix, Anne-Dominique; Azay-Milhau, Jacqueline
2014-08-06
In the present study, we obtained a dried burdock root extract (DBRE) rich in caffeoylquinic acids derivatives. We performed the chemical characterization of DBRE and explored its antihyperglycemic potential in both in vitro and in vivo experiments. Chemical analysis of DBRE using LC-MS and GC-MS revealed the presence of a great majority of dicaffeoylquinic acid derivatives (75.4%) of which 1,5-di-O-caffeoyl-4-O-maloylquinic acid represents 44% of the extract. In the in vitro experiments, DBRE is able to increase glucose uptake in cultured L6 myocytes and to decrease glucagon-induced glucose output from rat isolated hepatocytes together with a reduction of hepatic glucose 6-phosphatase activity. DBRE did not increase insulin secretion in the INS-1 pancreatic β-cell line. In vivo, DBRE improves glucose tolerance both after intraperitoneal and oral subchronic administration. In conclusion, our data demonstrate that DBRE constitutes an original set of caffeoylquinic acid derivatives displaying antihyperglycemic properties.
Fu, Haiqing; Martin, Melvenia M.; Regairaz, Marie; Huang, Liang; You, Yang; Lin, Chi-Mei; Ryan, Michael; Kim, RyangGuk; Shimura, Tsutomu; Pommier, Yves; Aladjem, Mirit I.
2015-01-01
The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81 deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81 deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins. PMID:25879486
Percolation Model of Sensory Transmission and Loss of Consciousness Under General Anesthesia
NASA Astrophysics Data System (ADS)
Zhou, David W.; Mowrey, David D.; Tang, Pei; Xu, Yan
2015-09-01
Neurons communicate with each other dynamically; how such communications lead to consciousness remains unclear. Here, we present a theoretical model to understand the dynamic nature of sensory activity and information integration in a hierarchical network, in which edges are stochastically defined by a single parameter p representing the percolation probability of information transmission. We validate the model by comparing the transmitted and original signal distributions, and we show that a basic version of this model can reproduce key spectral features clinically observed in electroencephalographic recordings of transitions from conscious to unconscious brain activities during general anesthesia. As p decreases, a steep divergence of the transmitted signal from the original was observed, along with a loss of signal synchrony and a sharp increase in information entropy in a critical manner; this resembles the precipitous loss of consciousness during anesthesia. The model offers mechanistic insights into the emergence of information integration from a stochastic process, laying the foundation for understanding the origin of cognition.
He, Xiao-Song; Xi, Bei-Dou; Gao, Ru-Tai; Wang, Lei; Ma, Yan; Cui, Dong-Yu; Tan, Wen-Bing
2015-06-01
Groundwater was collected in 2011 and 2012, and fluorescence spectroscopy coupled with chemometric analysis was employed to investigate the composition, origin, and dynamics of dissolved organic matter (DOM) in the groundwater. The results showed that the groundwater DOM comprised protein-, fulvic-, and humic-like substances, and the protein-like component originated predominantly from microbial production. The groundwater pollution by landfill leachate enhanced microbial activity and thereby increased microbial by-product-like material such as protein-like component in the groundwater. Excitation-emission matrix fluorescence spectra combined with parallel factor analysis showed that the protein-like matter content increased from 2011 to 2012 in the groundwater, whereas the fulvic- and humic-like matter concentration exhibited no significant changes. In addition, synchronous-scan fluorescence spectra coupled with two-dimensional correlation analysis showed that the change of the fulvic- and humic-like matter was faster than that of the protein-like substances, as the groundwater flowed from upstream to downstream in 2011, but slower than that of the protein-like substance in 2012 due to the enhancement of microbial activity. Fluorescence spectroscopy combined with chemometric analysis can investigate groundwater pollution characteristics and monitor DOM dynamics in groundwater.
Intraspecific variation among Tetranychid mites for ability to detoxify and to induce plant defenses
Ozawa, Rika; Endo, Hiroki; Iijima, Mei; Sugimoto, Koichi; Takabayashi, Junji; Gotoh, Tetsuo; Arimura, Gen-ichiro
2017-01-01
Two genotypes coexist among Kanzawa spider mites, one of which causes red scars and the other of which causes white scars on leaves, and they elicit different defense responses in host plants. Based on RNA-Seq analysis, we revealed here that the expression levels of genes involved in the detoxification system were higher in Red strains than White strains. The corresponding enzyme activities as well as performances for acaricide resistance and host adaptation toward Laminaceae were also higher in Red strains than White strains, indicating that Red strains were superior in trait(s) of the detox system. In subsequent generations of strains that had survived exposure to fenpyroximate, both strains showed similar resistance to this acaricide, as well as similar detoxification activities. The endogenous levels of salicylic acid and jasmonic acid were increased similarly in bean leaves damaged by original Red strains and their subsequent generations that inherited high detox activity. Jasmonic acid levels were increased in leaves damaged by original White strains, but not by their subsequent generations that inherited high detox activity. Together, these data suggest the existence of intraspecific variation - at least within White strains - with respect to their capacity to withstand acaricides and host plant defenses. PMID:28240222
2010-01-01
Background Mandatory generic substitution (GS) was introduced in Finland on 1 April 2003. The aim of this study was to explore and compare the impacts of GS on the activities of pharmaceutical companies representing mainly original or generic pharmaceutical products in Finland. The self-reported impact of GS from pharmaceutical companies' perspective was explored with a focus on the number of employees, the range of sales packages on the market, the marketing activities, the research and development of new pharmaceutical products and storage of pharmaceuticals. Methods A cross-sectional postal survey was conducted among pharmaceutical companies with an office in Finland and substitutable medicines in the Finnish pharmaceutical market one year (2004) and five years (2008) after the introduction of GS. Completed questionnaires were returned by 16 original and 7 generic product companies in 2004 (response rate 56%, n = 41) and by 16 original and 6 generic product companies in 2008 (response rate 56%, n = 39). Descriptive statistical analyses were performed. Results The number of employees (2004: n = 6/16, 2008: n = 7/16) and the amount of prescription medicine marketing (2004: n = 7/16, 2008: n = 8/16) decreased in many of the original product companies after the introduction of GS. GS resulted in problems related to the storage of pharmaceuticals in the original product companies shortly after GS was introduced (p = 0.032 between 2004 and 2008). In the generic product companies, the prescription medicine representatives' visits to pharmacies increased at the beginning of GS (p = 0.021 between 2004 and 2008). In addition, GS caused problems with the storage of pharmaceuticals one year and five years after the reform (2004: n = 4/7, 2008: n = 3/6). The differences between original and generic product companies regarding the impacts of GS were not, however, statistically significant. GS did not affect on the range of sales packages on the market or the research activities of the majority of companies. Conclusions The study suggests that GS has had impacts on the activities of pharmaceutical companies in Finland. There were also some differences, although not statistically significant, between the surveyed original and generic product companies regarding the self-reported impacts of GS. More investigations are needed in this field. PMID:20964869
Timonen, Johanna; Bengtström, Marina; Karttunen, Pekka; Ahonen, Riitta
2010-10-22
Mandatory generic substitution (GS) was introduced in Finland on 1 April 2003. The aim of this study was to explore and compare the impacts of GS on the activities of pharmaceutical companies representing mainly original or generic pharmaceutical products in Finland. The self-reported impact of GS from pharmaceutical companies' perspective was explored with a focus on the number of employees, the range of sales packages on the market, the marketing activities, the research and development of new pharmaceutical products and storage of pharmaceuticals. A cross-sectional postal survey was conducted among pharmaceutical companies with an office in Finland and substitutable medicines in the Finnish pharmaceutical market one year (2004) and five years (2008) after the introduction of GS. Completed questionnaires were returned by 16 original and 7 generic product companies in 2004 (response rate 56%, n = 41) and by 16 original and 6 generic product companies in 2008 (response rate 56%, n = 39). Descriptive statistical analyses were performed. The number of employees (2004: n = 6/16, 2008: n = 7/16) and the amount of prescription medicine marketing (2004: n = 7/16, 2008: n = 8/16) decreased in many of the original product companies after the introduction of GS. GS resulted in problems related to the storage of pharmaceuticals in the original product companies shortly after GS was introduced (p = 0.032 between 2004 and 2008). In the generic product companies, the prescription medicine representatives' visits to pharmacies increased at the beginning of GS (p = 0.021 between 2004 and 2008). In addition, GS caused problems with the storage of pharmaceuticals one year and five years after the reform (2004: n = 4/7, 2008: n = 3/6). The differences between original and generic product companies regarding the impacts of GS were not, however, statistically significant. GS did not affect on the range of sales packages on the market or the research activities of the majority of companies. The study suggests that GS has had impacts on the activities of pharmaceutical companies in Finland. There were also some differences, although not statistically significant, between the surveyed original and generic product companies regarding the self-reported impacts of GS. More investigations are needed in this field.
Nucleosome occupancy as a novel chromatin parameter for replication origin functions
Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio
2017-01-01
Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110
Ongoing modification of Mediterranean Pleistocene sapropels mediated by prokaryotes.
Coolen, Marco J L; Cypionka, Heribert; Sass, Andrea M; Sass, Henrik; Overmann, Jörg
2002-06-28
Late Pleistocene organic-rich sediments (sapropels) from the eastern Mediterranean Sea harbor unknown, metabolically active chemoorganotrophic prokaryotes. As compared to the carbon-lean intermediate layers, sapropels exhibit elevated cell numbers, increased activities of hydrolytic exoenzymes, and increased anaerobic glucose degradation rates, suggesting that microbial carbon substrates originate from sapropel layers up to 217,000 years old. 16S ribosomal RNA gene analyses revealed that as-yet-uncultured green nonsulfur bacteria constitute up to 70% of the total microbial biomass. Crenarchaeota constitute a smaller fraction (on average, 16%). A slow but significant turnover of glucose could be detected. Apparently, sapropels are still altered by the metabolic activity of green nonsulfur bacteria and crenarchaeota.
Concentration and variability of ice nuclei in the subtropical maritime boundary layer
NASA Astrophysics Data System (ADS)
Welti, André; Müller, Konrad; Fleming, Zoë L.; Stratmann, Frank
2018-04-01
Measurements of the concentration and variability of ice nucleating particles in the subtropical maritime boundary layer are reported. Filter samples collected in Cabo Verde over the period 2009-2013 are analyzed with a drop freezing experiment with sensitivity to detect the few rare ice nuclei active at low supercooling. The data set is augmented with continuous flow diffusion chamber measurements at temperatures below -24 °C from a 2-month field campaign in Cabo Verde in 2016. The data set is used to address the following questions: what are typical concentrations of ice nucleating particles active at a certain temperature? What affects their concentration and where are their sources? Concentration of ice nucleating particles is found to increase exponentially by 7 orders of magnitude from -5 to -38 °C. Sample-to-sample variation in the steepness of the increase indicates that particles of different origin, with different ice nucleation properties (size, composition), contribute to the ice nuclei concentration at different temperatures. The concentration of ice nuclei active at a specific temperature varies over a range of up to 4 orders of magnitude. The frequency with which a certain ice nuclei concentration is measured within this range is found to follow a lognormal distribution, which can be explained by random dilution during transport. To investigate the geographic origin of ice nuclei, source attribution of air masses from dispersion modeling is used to classify the data into seven typical conditions. While no source could be attributed to the ice nuclei active at temperatures higher than -12 °C, concentrations at lower temperatures tend to be elevated in air masses originating from the Sahara.
Mechanisms of nickel uptake, and hyperaccumulation by plants and implications to soil remediation
USDA-ARS?s Scientific Manuscript database
Soil contamination by heavy metals like Ni was originally restricted to metalliferous soils but in recent years it has become a general problem due to the increasingly frequent anthropogenic activities. Because of the characteristics of cost-effectiveness, environmental friendliness, and fewer side...
Cross-Bardell, Laura; George, Tracey; Bhoday, Mandeep; Tuomainen, Helena; Qureshi, Nadeem; Kai, Joe
2015-01-01
Objectives To explore perspectives on enhancing physical activity and diet among South Asians in urban deprived communities at high risk of chronic disease and to inform development of culturally appropriate health promotion intervention. Design Qualitative study using semistructured one-to-one and family group interviews with thematic analysis of data. Setting Urban disadvantaged communities in the East Midlands of the UK. Participants 45 respondents, including 34 people of South Asian origin (16 at-risk individuals, six family groups involving 18 relatives), of mainly Pakistani and Indian origin, including 16 non-English speakers; and 11 health professionals working locally with communities of concern. Results South Asian participants underlined the challenges of requiring family members across generations to engage in modifying dietary behaviours, and the central role of communal eating of traditional ‘Asian’ food in their cultural lives. Barriers to increasing physical activity included cost, personal safety and lack of time outside of long working hours and carer commitments. However, increasing walking activity was regarded as feasible by both community and health professional participants. Respondents emphasised using a social approach for potential interventions, undertaking activity with family or friends and with bilingual community peers to facilitate engagement, motivation and support. Spoken content and delivery of interventions was favoured, including personal stories and multilingual audio–visual information; within local informal rather than provider settings, including the home; and aided by pedometers for self-monitoring. Conclusions Focusing on physical activity by increasing walking may hold promise as health promotion in this deprived South Asian community context. Further intervention development, with exploration of feasibility and acceptability of the social approach and elements suggested, is merited. PMID:25724983
Nucleosomes in the neighborhood
Dorn, Elizabeth Suzanne
2011-01-01
The importance of local chromatin structure in regulating replication initiation has become increasingly apparent. Most recently, histone methylation and nucleosome positioning have been added to the list of modifications demonstrated to regulate origins. In particular, the methylation states of H3K4, H3K36 and H4K20 have been associated with establishing active, repressed or poised origins depending on the timing and extent of methylation. The stability and precise positioning of nucleosomes has also been demonstrated to affect replication efficiency. Although it is not yet clear how these modifications alter the behavior of specific replication factors, ample evidence establishes their role in maintaining coordinated replication. This review will summarize recent advances in understanding these aspects of chromatin structure in DNA replication origin control. PMID:21364325
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-04
... transactions. Transactions that originate from unrelated algorithms or separate and distinct trading strategies... transactions were undertaken for manipulative or other fraudulent purposes. Algorithms or trading strategies... activity and the use of algorithms by firms to make trading decisions, FINRA has observed an increase in...
The forestry industry in the southeastern United States relies upon soils that are highly eroded and depleted of their original organic matter and nutrient content. Pro-active land management can ensure continued and possibly increased production and revenue through the managemen...
Replacement-ready? Succession planning tops health care administrators' priorities.
Husting, P M; Alderman, M
2001-09-01
Nurses' increasing age coupled with health care's rapidly changing environment moves succession planning, originally only a business sector tool, to a top administrative priority. Through active support of your facility's executive leadership and a clear linkage to long range organization objectives, you can implement this progressive procedure.
Increased urinary excretion of platelet activating factor in mice with lupus nephritis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Macconi, D.; Noris, M.; Benfenati, E.
1991-01-01
Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that:more » (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.« less
Smallman, Bettina; Dexter, Franklin; Masursky, Danielle; Li, Fenghua; Gorji, Reza; George, Dave; Epstein, Richard H
2013-04-01
Theoretically, communication systems have the potential to increase the productivity of anesthesiologists supervising anesthesia providers. We evaluated the maximal potential of communication systems to increase the productivity of anesthesia care by enhancing anesthesiologists' coordination of care (activities) among operating rooms (ORs). At hospital A, data for 13,368 pages were obtained from files recorded in the internal alphanumeric text paging system. Pages from the postanesthesia care unit were processed through a numeric paging system and thus not included. At hospital B, in a different US state, 3 of the authors categorized each of 898 calls received using the internal wireless audio system (Vocera(®)). Lower and upper 95% confidence limits for percentages are the values reported. At least 45% of pages originated from outside the ORs (e.g., 20% from holding area) at hospital A and at least 56% of calls (e.g., 30% administrative) at hospital B. In contrast, requests from ORs for urgent presence of the anesthesiologist were at most 0.2% of pages at hospital A and 1.8% of calls at hospital B. Approximately half of messages to supervising anesthesiologists are for activity originating outside the ORs being supervised. To use communication tools to increase anesthesia productivity on the day of surgery, their use should include a focus on care coordination outside ORs (e.g., holding area) and among ORs (e.g., at the control desk).
Hebets, Eileen A.; Welch-Lazoritz, Melissa; Tisdale, Pawl; Wonch Hill, Trish
2018-01-01
Increased integration and synergy between formal and informal learning environments is proposed to provide multiple benefits to science learners. In an effort to better bridge these two learning contexts, we developed an educational model that employs the charismatic nature of arachnids to engage the public of all ages in science learning; learning that aligns with the Next Generation Science Standards (NGSS Disciplinary Core Ideas associated with Biodiversity and Evolution). We created, implemented, and evaluated a family-focused, interactive science event—Eight-Legged Encounters (ELE)—which encompasses more than twenty modular activities. Volunteers facilitated participant involvement at each activity station and original artwork scattered throughout the event was intended to attract visitors. Initial ELE goals were to increase interest in arachnids and science more generally, among ELE participants. In this study, we tested the efficacy of ELE in terms of (i) activity-specific visitation rates and self-reported interest levels, (ii) the self-reported efficacy of our use of volunteers and original artwork on visitor engagement, and (iii) self-reported increases in interest in both spiders and science more generally. We collected survey data across five ELE events at four museum and zoo sites throughout the Midwest. We found that all activities were successful at attracting visitors and capturing their interest. Both volunteers and artwork were reported to be effective at engaging visitors, though likely in different ways. Additionally, most participants reported increased interest in learning about arachnids and science. In summary, ELE appears effective at engaging the public and piquing their interest. Future work is now required to assess learning outcomes directly, as well as the ability for participants to transfer knowledge gain across learning environments. PMID:29495395
Hebets, Eileen A; Welch-Lazoritz, Melissa; Tisdale, Pawl; Wonch Hill, Trish
2018-02-26
Increased integration and synergy between formal and informal learning environments is proposed to provide multiple benefits to science learners. In an effort to better bridge these two learning contexts, we developed an educational model that employs the charismatic nature of arachnids to engage the public of all ages in science learning; learning that aligns with the Next Generation Science Standards (NGSS Disciplinary Core Ideas associated with Biodiversity and Evolution). We created, implemented, and evaluated a family-focused, interactive science event- Eight-Legged Encounters (ELE )-which encompasses more than twenty modular activities. Volunteers facilitated participant involvement at each activity station and original artwork scattered throughout the event was intended to attract visitors. Initial ELE goals were to increase interest in arachnids and science more generally, among ELE participants. In this study, we tested the efficacy of ELE in terms of (i) activity-specific visitation rates and self-reported interest levels, (ii) the self-reported efficacy of our use of volunteers and original artwork on visitor engagement, and (iii) self-reported increases in interest in both spiders and science more generally. We collected survey data across five ELE events at four museum and zoo sites throughout the Midwest. We found that all activities were successful at attracting visitors and capturing their interest. Both volunteers and artwork were reported to be effective at engaging visitors, though likely in different ways. Additionally, most participants reported increased interest in learning about arachnids and science. In summary, ELE appears effective at engaging the public and piquing their interest. Future work is now required to assess learning outcomes directly, as well as the ability for participants to transfer knowledge gain across learning environments.
Wu, Peng; Zhao, Xihong; Pan, Siyi
2014-09-03
Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L -1 , which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable.
Wu, Peng; Zhao, Xihong; Pan, Siyi
2014-01-01
Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L−1, which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable. PMID:26019572
NASA Astrophysics Data System (ADS)
Delmas, Daniel; Labry, Claire; Youenou, Agnes; Quere, Julien; Auguet, Jean Christophe; Montanie, Helene
2014-05-01
The non-conservative behavior of phosphate within the estuarine salinity gradient is essentially assigned to physico-chemical processes, such as desorption at low salinity and to benthic exchanges. Microbial phosphatase activity (APA), generally related to phosphate deficiency, is seldom studied in phosphate rich estuarine waters. In order to address the impact of microbial activity (bacterial abundance, production BSP, APA) on phosphate behavior, we studied these activities on a seasonal basis within the salinity gradient of two macrotidal estuaries presenting different levels of suspended solids. Whatever the season the Charente estuary is characterized by high levels of Suspended Particulate Matter (SPM > 1g.L-1), particularly in the Maximum Turbidity Zone (MTZ) located at the 5-10 psu. In this area characterized by high BSP and APA there is a significant increase of PO4 levels especially during summer. In the Aulne estuary the particle load is significantly lower (1/10) but high BSP and APA are equally recorded. In the highly turbid waters of the Charente estuary, active phytoplankton is virtually absent as pheopigments constitute up to 80% of the total pigments, particularly in the MTZ, therefore APA may essentially have a bacterial origin. In the Aulne estuary attached bacteria are dominant, both in numbers and production, and their distribution along the haline gradient perfectly follows those of APA and phosphate levels. These observations, associated with the very close relationships observed between APA, SPM and BSP, suggest that APA derive mainly from bacterial (attached) origin and operate at the expense of particulate phosphorus and hence contribute to PO4 regeneration, especially in spring and summer. Finally, as APA increased as PO4, whereas the reverse is observed in both fresh and marine waters, an original scheme for APA regulation, related to the large dominance of attached bacteria can be described for the estuarine waters.
Light-Induced Nuclear Synthesis of Spinach Chloroplast Fructose-1,6-bisphosphatase 1
Chueca, Ana; Lázaro, Juan José; Gorgé, Julio López
1984-01-01
Etiolated spinach (Spinacia oleracea L. var Winter Giant) seedlings show a residual photosynthetic fructose-1,6-bisphosphatase activity, which sharply rises under illumination. This increase in activity is due to a light-induced de novo synthesis, as it has been demonstrated by enzyme labeling experiments with 2H2O and [35S]methionine. The rise of bisphosphatase activity under illumination is strongly inhibited by cycloheximide, but not by the 70S ribosome inhibitor lincocin, which shows the nuclear origin of this chloroplastic enzyme. Images Fig. 3 PMID:16663662
Paraoxonase activity and dementia.
Wehr, Hanna; Bednarska-Makaruk, Małgorzata; Graban, Ałła; Lipczyńska-Łojkowska, Wanda; Rodo, Maria; Bochyńska, Anna; Ryglewicz, Danuta
2009-08-15
Paraoxonase activity, homocysteine level and lipids were determined in 120 patients with dementia (51 with Alzheimer disease, 28 with dementia of vascular origin, 41 with mixed dementia), 45 with mild cognitive impairment and in 61 age and sex matched controls without dementia. Paraoxonase activity was decreased in Alzheimer disease and in mixed dementia as compared with control group. In the same forms of dementia homocysteine levels were increased. In Alzheimer disease paraoxonase activity was negatively correlated with homocysteine levels. Minimental State Examination results showed positive correlation with paraoxonase activity. The results suggest an important role of oxidative stress in the development of the forms of dementia with prevailing neurodegeneration.
Can physical activity improve peak bone mass?
Specker, Bonny; Minett, Maggie
2013-09-01
The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.
Novozyme 435-catalyzed efficient acylation of 3-n-butylphthalide in organic medium.
He, Laping; Sun, Jiong; Xu, Yan; Sun, Zhihao; Zheng, Changge
2008-01-01
Novozyme 435 could catalyze efficient acylation of 3-n-butylphthalide in organic medium. The conversion of 3-n-butylphthalide increased with the increase of hydrophobicity of solvent below that of hexane. The more available solvent was hexane. Salt hydride could control fixed water activity. The optimum water activity was 0.62. And the optimum of reaction time, velocity of agitation, dosage of Novozyme 435 and acetic anhydride to 3-n-butylphtrhalide molar ratio were 48 hours, 150 rpm, 8 mg/mL and 8:1, respectively. The conversion of 48.9% could be obtained at a water activity of 0.62 in hexane. Furthermore, Novozyme 435 had an enantioselective acylation of racemic 3-n-butylphthalide by original analysis.
Enhancing creative cognition with a rapid right-parietal neurofeedback procedure.
Agnoli, Sergio; Zanon, Marco; Mastria, Serena; Avenanti, Alessio; Corazza, Giovanni Emanuele
2018-02-14
The present article describes an innovative neurofeedback training (NFT) procedure aimed at increasing creative cognition through the enhancement of specific brain activities previously associated with divergent thinking. We designed and tested two NFT protocols based on training alpha and beta EEG oscillations selectively measured over the right parietal region. A total of 80 participants were involved, 40 in the alpha NFT protocol and 40 in the beta NFT protocol. The NFT loop was closed on a video stream that would advance only when oscillation power exceeded a normalized threshold. The total duration of the protocol was two hours in a single day, hence its classification as rapid. Changes in ideational fluency and originality, measured with a divergent thinking task, were compared between participants receiving real video feedback and participants receiving sham feedback. We controlled for individual differences in creative achievement level. Results showed that the protocols were effective at enhancing alpha and beta activities in the targeted area. Differences between the two protocols emerged in their effectiveness at promoting divergent thinking. While no significant changes in originality resulted from the rapid alpha NFT, increases in both originality and fluency emerged as a consequence of the rapid beta NFT. These results were particularly evident in participants starting with a low creative achievement level. Possible interpretations and future directions are proposed and discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.
2012-09-01
Maintenance activities, as this will allow new methods and Operational changes to be made if necessary (i.e., more downtime than originally planned or...increased complexity of military hardware, both new systems and their integration with legacy systems, requires a correspondingly increased expertise in...available Little of that added weight involves weapons or armor that actually is becoming lighter as new technologies and composites are utilized (Task
Tay, Wee Tek; Walsh, Thomas K.; Downes, Sharon; Anderson, Craig; Jermiin, Lars S.; Wong, Thomas K. F.; Piper, Melissa C.; Chang, Ester Silva; Macedo, Isabella Barony; Czepak, Cecilia; Behere, Gajanan T.; Silvie, Pierre; Soria, Miguel F.; Frayssinet, Marie; Gordon, Karl H. J.
2017-01-01
The Old World bollworm Helicoverpa armigera is now established in Brazil but efforts to identify incursion origin(s) and pathway(s) have met with limited success due to the patchiness of available data. Using international agricultural/horticultural commodity trade data and mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) gene markers, we inferred the origins and incursion pathways into Brazil. We detected 20 mtDNA haplotypes from six Brazilian states, eight of which were new to our 97 global COI-Cyt b haplotype database. Direct sequence matches indicated five Brazilian haplotypes had Asian, African, and European origins. We identified 45 parsimoniously informative sites and multiple substitutions per site within the concatenated (945 bp) nucleotide dataset, implying that probabilistic phylogenetic analysis methods are needed. High diversity and signatures of uniquely shared haplotypes with diverse localities combined with the trade data suggested multiple incursions and introduction origins in Brazil. Increasing agricultural/horticultural trade activities between the Old and New Worlds represents a significant biosecurity risk factor. Identifying pest origins will enable resistance profiling that reflects countries of origin to be included when developing a resistance management strategy, while identifying incursion pathways will improve biosecurity protocols and risk analysis at biosecurity hotspots including national ports. PMID:28350004
Tay, Wee Tek; Walsh, Thomas K; Downes, Sharon; Anderson, Craig; Jermiin, Lars S; Wong, Thomas K F; Piper, Melissa C; Chang, Ester Silva; Macedo, Isabella Barony; Czepak, Cecilia; Behere, Gajanan T; Silvie, Pierre; Soria, Miguel F; Frayssinet, Marie; Gordon, Karl H J
2017-03-28
The Old World bollworm Helicoverpa armigera is now established in Brazil but efforts to identify incursion origin(s) and pathway(s) have met with limited success due to the patchiness of available data. Using international agricultural/horticultural commodity trade data and mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) gene markers, we inferred the origins and incursion pathways into Brazil. We detected 20 mtDNA haplotypes from six Brazilian states, eight of which were new to our 97 global COI-Cyt b haplotype database. Direct sequence matches indicated five Brazilian haplotypes had Asian, African, and European origins. We identified 45 parsimoniously informative sites and multiple substitutions per site within the concatenated (945 bp) nucleotide dataset, implying that probabilistic phylogenetic analysis methods are needed. High diversity and signatures of uniquely shared haplotypes with diverse localities combined with the trade data suggested multiple incursions and introduction origins in Brazil. Increasing agricultural/horticultural trade activities between the Old and New Worlds represents a significant biosecurity risk factor. Identifying pest origins will enable resistance profiling that reflects countries of origin to be included when developing a resistance management strategy, while identifying incursion pathways will improve biosecurity protocols and risk analysis at biosecurity hotspots including national ports.
NASA Astrophysics Data System (ADS)
Tay, Wee Tek; Walsh, Thomas K.; Downes, Sharon; Anderson, Craig; Jermiin, Lars S.; Wong, Thomas K. F.; Piper, Melissa C.; Chang, Ester Silva; Macedo, Isabella Barony; Czepak, Cecilia; Behere, Gajanan T.; Silvie, Pierre; Soria, Miguel F.; Frayssinet, Marie; Gordon, Karl H. J.
2017-03-01
The Old World bollworm Helicoverpa armigera is now established in Brazil but efforts to identify incursion origin(s) and pathway(s) have met with limited success due to the patchiness of available data. Using international agricultural/horticultural commodity trade data and mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) and cytochrome b (Cyt b) gene markers, we inferred the origins and incursion pathways into Brazil. We detected 20 mtDNA haplotypes from six Brazilian states, eight of which were new to our 97 global COI-Cyt b haplotype database. Direct sequence matches indicated five Brazilian haplotypes had Asian, African, and European origins. We identified 45 parsimoniously informative sites and multiple substitutions per site within the concatenated (945 bp) nucleotide dataset, implying that probabilistic phylogenetic analysis methods are needed. High diversity and signatures of uniquely shared haplotypes with diverse localities combined with the trade data suggested multiple incursions and introduction origins in Brazil. Increasing agricultural/horticultural trade activities between the Old and New Worlds represents a significant biosecurity risk factor. Identifying pest origins will enable resistance profiling that reflects countries of origin to be included when developing a resistance management strategy, while identifying incursion pathways will improve biosecurity protocols and risk analysis at biosecurity hotspots including national ports.
Assessing worldwide research activity on probiotics in pediatrics using Scopus database: 1994-2014.
Sweileh, Waleed M; Shraim, Naser Y; Al-Jabi, Samah W; Sawalha, Ansam F; Rahhal, Belal; Khayyat, Rasha A; Zyoud, Sa'ed H
2016-01-01
A wide variety of probiotic products has been introduced into the market in the past decade. Research trends and activity on probiotics help understand how these products were evolved and their potential future role in medicine. The objective of this study was to assess the research activity on probiotics in pediatrics using bibliometric indicators and network visualization. Original and review articles on probiotics in pediatrics published worldwide were retrieved from SciVerse, Scopus (1994-2014) and analyzed. VOSviewer was used for network visualization. The total number of documents published on probiotics in pediatrics was 2817. Research activity on probiotics in pediatrics showed approximately 90- fold increase during the study period. Approximately 22 % of published articles originated from USA and has the greatest share, however, Finland ranked first when data were stratified by population or income. The most productive institution in this field was Turku University in Finland with 82 (2.91 %) articles. Half of the prolific authors were also from Finland. Most of the published research activity appeared in Journal of Pediatric Gastroenterology and Nutrition. Most frequently encountered title terms include nutrition, infant formula, necrotizing enetrocolitis, allergy, and diarrhea. The total number of citations for the retreived documents documents was 70991, and the average citation per article was 25.20. Interest in probiotic research and its potential benefits in pediatric ailments is relatively recent but significantly increasing. Bibliometric analysis can be used as an indicator of the importance and growth of probiotic use in pediatrics.
Reptile thermogenesis and the origins of endothermy.
Tattersall, Glenn J
2016-10-01
Extant endotherms have high rates of metabolism, elevated body temperatures, usually tight control over body temperature, and a reasonable scope for further increases in metabolism through locomotor activity. Vertebrate ectotherms, on the other hand, rely on behavioural thermoregulation and cardiovascular adjustments to facilitate warming, and generally lack specific biochemical and cellular mechanisms for sustained, elevated metabolism. Nevertheless, the ancestral condition to endothermy is thought to resemble that of many extant reptiles, which raises the question of the origins and selection pressures relevant to the transitional state. Numerous hypotheses have emerged to explain the multiple origins of endothermy in vertebrates, including thermoregulatory, locomotory, and reproductive activity as possible drivers for these sustained and elevated metabolic rates. In this article, I discuss recent evidence for facultative endothermy in an extant lepidosaur, the tegu lizard. Since lepidosaurs are a sister group to the archosaurs, understanding how a novel form of endothermy evolved will open up opportunities to test the compatibility or incompatibility of the various endothermy hypotheses, with potential to elucidate and resolve long contentious ideas in evolutionary physiology. Copyright © 2016 Elsevier GmbH. All rights reserved.
The Reach up Early Childhood Parenting Program: Origins, Content, and Implementation
ERIC Educational Resources Information Center
Walker, Susan P.; Chang, Susan M.; Smith, Joanne A.; Baker-Henningham, Helen
2018-01-01
Nurturing care in early childhood requires responsive interactions and opportunities to learn; however, there are few large-scale programs in low- and middle-income countries that support parents' ability to provide responsive care and activities that help children learn. The Reach Up training program was developed to increase capacity of…
Origins of intracellular calcium mobilization evoked by infrared laser stimulation
NASA Astrophysics Data System (ADS)
Olsovsky, Cory A.; Tolstykh, Gleb P.; Ibey, Bennett L.; Beier, Hope T.
2015-03-01
Cellular delivery of pulsed IR laser energy has been shown to stimulate action potentials in neurons. The mechanism for this stimulation is not completely understood. Certain hypotheses suggest the rise in temperature from IR exposure could activate temperature- or pressure-sensitive channels, or create pores in the cellular outer membrane. Studies using intensity-based Ca2+-responsive dyes show changes in Ca2+ levels after various IR stimulation parameters; however, determination of the origin of this signal proved difficult. An influx of larger, typically plasma-membrane-impermeant ions has been demonstrated, which suggests that Ca2+ may originate from the external solution. However, activation of intracellular signaling pathways, possibly indicating a more complex role of increasing Ca2+ concentration, has also been shown. By usingCa2+ sensitive dye Fura-2 and a high-speed ratiometric imaging system that rapidly alternates the excitation wavelengths, we have quantified the Ca2+ mobilization in terms of influx from the external solution and efflux from intracellular organelles. CHO-K1 cells, which lack voltage-gated Ca2+ channels, and NG-108 neuroblastoma cells, which do not produce action potentials in an early undifferentiated state, are used to determine the origin of the Ca2+ signals and investigate the role these mechanisms may play in IR neural stimulation.
Hameury, Sebastien; Borderie, Laurent; Monneuse, Jean-Marc; Skorski, Gilbert; Pradines, Dominique
2018-05-23
The application of ingredients from marine and maritime origins is increasingly common in skin care products, driven by consumer expectations for natural ingredients. However, these ingredients are typically studied for a few isolated in vitro activities. The purpose of this study was to carry out a comprehensive evaluation of the activity on the skin of an association of ingredients from marine and maritime origins using label-free quantitative proteomic analysis, in order to predict the clinical benefits if used in a skin care product. An aqueous gel containing 6.1% of ingredients from marine and maritime origins (amino acid-enriched giant kelp extract, trace element-enriched seawater, dedifferentiated sea fennel cells) was topically applied on human skin explants. The skin explants' proteome was analyzed in a label-free manner by high-performance liquid nano-chromatography coupled with tandem mass spectrometry. A specific data processing pipeline (CORAVALID) providing an objective and comprehensive interpretation of the statistically relevant biological activities processed the results. Compared to untreated skin explants, 64 proteins were significantly regulated by the gel treatment (q-value ≤ 0.05). Computer data processing revealed an activity of the ingredients on the epidermis and the dermis. These significantly regulated proteins are involved in gene expression, cell survival and metabolism, inflammatory processes, dermal extracellular matrix synthesis, melanogenesis and keratinocyte proliferation, migration, and differentiation. These results suggest that the tested ingredients could help to preserve a healthy epidermis and dermis, and possibly to prevent the visible signs of skin aging. © 2018 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-30
...-0100] Agency Information Collection Activities: Request for the Return of Original Documents, Form... Collection. (2) Title of the Form/Collection: Request for the Return of Original Documents. (3) Agency form... obtain original document(s) contained in an alien file. (5) An estimate of the total number of...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-08
...-0100] Agency Information Collection Activities: Request for the Return of Original Documents, Form.... (2) Title of the Form/Collection: Request for the Return of Original Documents. (3) Agency form... obtain original document(s) contained in an alien file. (5) An estimate of the total number of...
Oreščanin-Dušić, Zorana; Tatalović, Nikola; Vidonja-Uzelac, Teodora; Nestorov, Jelena; Nikolić-Kokić, Aleksandra; Mijušković, Ana; Spasić, Mihajlo; Paškulin, Roman; Bresjanac, Mara; Blagojević, Duško
2018-01-01
Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga . It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H 2 O 2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H 2 O 2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.
Paškulin, Roman
2018-01-01
Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis. PMID:29599898
Zhao, Zhi-Gang; Gao, Shu-Rui; Hou, Jun-Ling; Wang, Wen-Quan; Xu, Zhen-Guang; Song, Yan; Zhang, Xian-Ming; Li, Jun
2014-04-01
In this paper the contents of rosmarinic acid, salvianolic acid B, crytotanshinone, tanshinone II(A) in samples of different original processed Salvia Miltiorrhizae Radix et Rhizoma were determined by HPLC. Different processing methods have varied influences on four active ingredients in Salvia Miltiorrhizae Radix et Rhizoma. Sun-drying reduced the content of crytotanshinone, tanshi-none II(A) and rosmarinic acid, integralsamples were better than those cut into segments. Oven dry method had great influence on water--soluble ingredients, high temperature (80-100 degrees C) could easily cause big loss of rosmarinic acid and salvianolic acid B. The role of traditional processing method "fahan: was complicated, the content of rosmarinic acid decreased, crytotanshinone and tanshinone II(A) increased, and salvianolic acid B showed no difference after "fahan". Drying in the shade and oven dry under low temperatrure (40-60 degrees C) were all effective to keep active ingredients of Salvia Miltiorrhizae Radix et Rhizoma, and, there was no difference between integral samples and samples cut into segments. Therefore, considering comprehensively the content of active ingredients in Salvia Miltiorrhizae Radix et Rhizoma, and processing costing etc., shade-drying or oven dry underlow temperature (40-60 degrees C) should be the most suitable original processing method.
Reinik, Janek; Heinmaa, Ivo; Kirso, Uuve; Kallaste, Toivo; Ritamäki, Johannes; Boström, Dan; Pongrácz, Eva; Huuhtanen, Mika; Larsson, William; Keiski, Riitta; Kordás, Krisztián; Mikkola, Jyri-Pekka
2011-11-30
Environmentally friendly product, calcium-silica-aluminum hydrate, was synthesized from oil shale fly ash, which is rendered so far partly as an industrial waste. Reaction conditions were: temperature 130 and 160°C, NaOH concentrations 1, 3, 5 and 8M and synthesis time 24h. Optimal conditions were found to be 5M at 130°C at given parameter range. Original and activated ash samples were characterized by XRD, XRF, SEM, EFTEM, (29)Si MAS-NMR, BET and TGA. Semi-quantitative XRD and MAS-NMR showed that mainly tobermorites and katoite are formed during alkaline hydrothermal treatment. Physical adsorption of CO(2) on the surface of the original and activated ash samples was measured with thermo-gravimetric analysis. TGA showed that the physical adsorption of CO(2) on the oil shale fly ash sample increases from 0.06 to 3-4 mass% after alkaline hydrothermal activation with NaOH. The activated product has a potential to be used in industrial processes for physical adsorption of CO(2) emissions. Copyright © 2011 Elsevier B.V. All rights reserved.
Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.
2012-01-01
Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735
Tain, You-Lin; Hsu, Chien-Ning
2018-06-12
Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.
Magnani, Maria Beatrice; Blanpied, Michael L; DeShon, Heather R; Hornbach, Matthew J
2017-11-01
To assess whether recent seismicity is induced by human activity or is of natural origin, we analyze fault displacements on high-resolution seismic reflection profiles for two regions in the central United States (CUS): the Fort Worth Basin (FWB) of Texas and the northern Mississippi embayment (NME). Since 2009, earthquake activity in the CUS has increased markedly, and numerous publications suggest that this increase is primarily due to induced earthquakes caused by deep-well injection of wastewater, both flowback water from hydrofracturing operations and produced water accompanying hydrocarbon production. Alternatively, some argue that these earthquakes are natural and that the seismicity increase is a normal variation that occurs over millions of years. Our analysis shows that within the NME, faults deform both Quaternary alluvium and underlying sediments dating from Paleozoic through Tertiary, with displacement increasing with geologic unit age, documenting a long history of natural activity. In the FWB, a region of ongoing wastewater injection, basement faults show deformation of the Proterozoic and Paleozoic units, but little or no deformation of younger strata. Specifically, vertical displacements in the post-Pennsylvanian formations, if any, are below the resolution (~15 m) of the seismic data, far less than expected had these faults accumulated deformation over millions of years. Our results support the assertion that recent FWB earthquakes are of induced origin; this conclusion is entirely independent of analyses correlating seismicity and wastewater injection practices. To our knowledge, this is the first study to discriminate natural and induced seismicity using classical structural geology analysis techniques.
Magnani, Maria Beatrice; Blanpied, Michael L.; DeShon, Heather R.; Hornbach, Matthew J.
2017-01-01
To assess whether recent seismicity is induced by human activity or is of natural origin, we analyze fault displacements on high-resolution seismic reflection profiles for two regions in the central United States (CUS): the Fort Worth Basin (FWB) of Texas and the northern Mississippi embayment (NME). Since 2009, earthquake activity in the CUS has increased markedly, and numerous publications suggest that this increase is primarily due to induced earthquakes caused by deep-well injection of wastewater, both flowback water from hydrofracturing operations and produced water accompanying hydrocarbon production. Alternatively, some argue that these earthquakes are natural and that the seismicity increase is a normal variation that occurs over millions of years. Our analysis shows that within the NME, faults deform both Quaternary alluvium and underlying sediments dating from Paleozoic through Tertiary, with displacement increasing with geologic unit age, documenting a long history of natural activity. In the FWB, a region of ongoing wastewater injection, basement faults show deformation of the Proterozoic and Paleozoic units, but little or no deformation of younger strata. Specifically, vertical displacements in the post-Pennsylvanian formations, if any, are below the resolution (~15 m) of the seismic data, far less than expected had these faults accumulated deformation over millions of years. Our results support the assertion that recent FWB earthquakes are of induced origin; this conclusion is entirely independent of analyses correlating seismicity and wastewater injection practices. To our knowledge, this is the first study to discriminate natural and induced seismicity using classical structural geology analysis techniques. PMID:29202029
Nogueira, Lygia Sega; Bianchini, Adalto; Smith, Scott; Jorge, Marianna Basso; Diamond, Rachael L; Wood, Chris M
2017-01-01
Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis-one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of these five NOMS alone (at 8 mg/L), of three metals alone (copper, lead and zinc at 6 µg Cu/L, 20 µg Pb/L, and 25 µg Zn/L respectively), and of each metal in combination with each NOM, were evaluated in 48-h exposures of mussel larvae. Endpoints were whole body Ca 2+ +Mg 2+ -ATPase activity, carbonic anhydrase activity and lipid peroxidation. By themselves, NOMs increased lipid peroxidation, Ca 2+ +Mg 2+ -ATPase, and/or carbonic anhydrase activities (significant in seven of 15 NOM-endpoint combinations), whereas metals by themselves did not affect the first two endpoints, but Cu and Pb increased carbonic anhydrase activities. In combination, the effects of NOMs predominated, with the metal exerting no additional effect in 33 out of 45 combinations. While NOM effects varied amongst different isolates, there was no clear pattern with respect to optical or chemical properties. When NOMs were treated as a single source by data averaging, NOM had no effect on Ca 2+ +Mg 2+ -ATPase activity but markedly stimulated carbonic anhydrase activity and lipid peroxidation, and there were no additional effects of any metal. Our results indicate that marine NOMs may have direct effects on this model marine organism, as well as protective effects against metal toxicity, and the quality of marine NOMs may be an important factor in these actions.
Bianchini, Adalto; Smith, Scott; Jorge, Marianna Basso; Diamond, Rachael L.; Wood, Chris M.
2017-01-01
Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of these five NOMS alone (at 8 mg/L), of three metals alone (copper, lead and zinc at 6 µg Cu/L, 20 µg Pb/L, and 25 µg Zn/L respectively), and of each metal in combination with each NOM, were evaluated in 48-h exposures of mussel larvae. Endpoints were whole body Ca2++Mg2+-ATPase activity, carbonic anhydrase activity and lipid peroxidation. By themselves, NOMs increased lipid peroxidation, Ca2++Mg2+-ATPase, and/or carbonic anhydrase activities (significant in seven of 15 NOM-endpoint combinations), whereas metals by themselves did not affect the first two endpoints, but Cu and Pb increased carbonic anhydrase activities. In combination, the effects of NOMs predominated, with the metal exerting no additional effect in 33 out of 45 combinations. While NOM effects varied amongst different isolates, there was no clear pattern with respect to optical or chemical properties. When NOMs were treated as a single source by data averaging, NOM had no effect on Ca2++Mg2+-ATPase activity but markedly stimulated carbonic anhydrase activity and lipid peroxidation, and there were no additional effects of any metal. Our results indicate that marine NOMs may have direct effects on this model marine organism, as well as protective effects against metal toxicity, and the quality of marine NOMs may be an important factor in these actions. PMID:28413723
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kwon, Hyeok-Ran; Lee, Ki Won; Dong, Zigang
2010-01-01
T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells.more » Ablation of TOPK negatively regulated TRAIL-mediated NF-{kappa}B activity. Furthermore, expression of NF-{kappa}B-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-{kappa}B activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.« less
A Link between ORC-Origin Binding Mechanisms and Origin Activation Time Revealed in Budding Yeast
Hoggard, Timothy; Shor, Erika; Müller, Carolin A.; Nieduszynski, Conrad A.; Fox, Catherine A.
2013-01-01
Eukaryotic DNA replication origins are selected in G1-phase when the origin recognition complex (ORC) binds chromosomal positions and triggers molecular events culminating in the initiation of DNA replication (a.k.a. origin firing) during S-phase. Each chromosome uses multiple origins for its duplication, and each origin fires at a characteristic time during S-phase, creating a cell-type specific genome replication pattern relevant to differentiation and genome stability. It is unclear whether ORC-origin interactions are relevant to origin activation time. We applied a novel genome-wide strategy to classify origins in the model eukaryote Saccharomyces cerevisiae based on the types of molecular interactions used for ORC-origin binding. Specifically, origins were classified as DNA-dependent when the strength of ORC-origin binding in vivo could be explained by the affinity of ORC for origin DNA in vitro, and, conversely, as ‘chromatin-dependent’ when the ORC-DNA interaction in vitro was insufficient to explain the strength of ORC-origin binding in vivo. These two origin classes differed in terms of nucleosome architecture and dependence on origin-flanking sequences in plasmid replication assays, consistent with local features of chromatin promoting ORC binding at ‘chromatin-dependent’ origins. Finally, the ‘chromatin-dependent’ class was enriched for origins that fire early in S-phase, while the DNA-dependent class was enriched for later firing origins. Conversely, the latest firing origins showed a positive association with the ORC-origin DNA paradigm for normal levels of ORC binding, whereas the earliest firing origins did not. These data reveal a novel association between ORC-origin binding mechanisms and the regulation of origin activation time. PMID:24068963
Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H
2016-12-01
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.
Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.
2016-01-01
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055
Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase.
Warren, Christopher M; van den Brink, Ruud L; Nieuwenhuis, Sander; Bosch, Jos A
2017-04-01
It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy adult participants in a double-blind, placebo-controlled cross-over design. Atomoxetine administration significantly increased SAA secretion and concentrations at 75-180min after treatment (more than doubling baseline levels). Consistent with evidence that elevation in central NE is a co-determinant of hypothalamic-pituitary-adrenal axis activity, salivary cortisol also approximately doubled at the same time points. Moreover, changes in salivary cortisol positively correlated with SAA (0.44
NASA Astrophysics Data System (ADS)
Wang, Feng; Wang, Riyuan; Wang, Yuancheng; Zhao, Ping; Xia, Qingyou
2015-11-01
With an increasing clinical demand for functional therapeutic proteins every year, there is an increasing requirement for the massive production of bioactive recombinant human acidic fibroblast growth factor (r-haFGF). In this present study, we delicately explore a strategy for the mass production of r-haFGF protein with biological activity in the transgenic silkworm cocoons. The sequence-optimized haFGF was inserted into an enhanced sericin-1 expression system to generate the original transgenic silkworm strain, which was then further crossed with a PIG jumpstarter strain to achieve the remobilization of the expression cassette to a “safe harbor” locus in the genome for the efficient expression of r-haFGF. In consequence, the expression of r-haFGF protein in the mutant line achieved a 5.6-fold increase compared to the original strain. The high content of r-haFGF facilitated its purification and large-scald yields. Furthermore, the r-haFGF protein bioactively promoted the growth, proliferation and migration of NIH/3T3 cells, suggesting the r-haFGF protein possessed native mitogenic activity and the potential for wound healing. These results show that the silk gland of silkworm could be an efficient bioreactor strategy for recombinant production of bioactive haFGF in silkworm cocoons.
Razumnikova, O M; Vol'f, N V
2012-01-01
Sex differences in creativity related global-local hemispheric selective processing were examined by hierarchical letter presenting in conditions of their perception and comparison. Fifty-six right-handed males and 68 females (aged 17-22 years) participated in the experiments. Originality-imagery was assessed by a computer-based Torrance 'Incomplete Figures' test software. Verbal creativity was valued by original sentence using of three nouns from remote semantic categories. The results show that irrespectively of the sex factor and the type of creative thinking, its originality is provided by high speed of right-hemispheric processes of information selection on the global level and delay in the interhemispheric communication. Relationships between originality of ideas and hemispheric attentional characteristics are presented mostly in men while verbal creative problem solving, and in women while figurative original thinking. Originality of verbal activity in men is more associated with success of selective processes in the left hemisphere, but in women--with selective functions of both hemispheres. Figurative thinking in men is less related to hemispheric characteristics of attention compared with women. Increase of figurative originality in women is accompanied acceleration of processes of selection of the information in the right hemisphere, and also higher efficiency of local attention as well as speeds ofglobal processing in the left hemisphere.
Ferrar, Katia Elizabeth; Smith, Ashleigh E; Davison, Kade
2017-08-01
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious illness of biological origin characterized by profound physical and cognitive exhaustion and postexertion malaise. Pacing is a common strategy used to manage available energy and complete activities of daily living; yet little research has investigated this as a strategy to increase physical activity levels. Typically, people living with ME/CFS are faced by unique barriers to physical activity participation and are less physically active than healthy peers. As such they are at increased risk of physical inactivity-related health consequences. Active video games may be a feasible and acceptable avenue to deliver physical activity intervention by overcoming many of the reported barriers to participation. The primary objective of this pilot study is to determine the feasibility and acceptability of active video games to increase physical activity levels of people with ME/CFS. The secondary aims are to explore the preliminary effectiveness of pacing and active video gaming to pacing alone and pacing plus conventional physical activity to increase the physical activity levels of adults with ME/CFS and explore the relationship between physical activity and cumulative inflammatory load (allostatic load). This study will use a mixed method design, with a 3-arm pilot randomized controlled trial, exit interviews, and collection of feasibility and process data. A total of 30 adults with ME/CFS will be randomized to receive either (1) pacing, (2) pacing and conventional physical activity, or (3) pacing and active video gaming. The intervention duration will be 6 months, and participants will be followed up for 6 months postintervention completion. The intervention will be conducted in the participant's home, and activity intensity will be determined by continuously monitored heart rate and ratings of perceived exertion. Feasibility and acceptability and process data will be collected during and at the end of the intervention. Health-related outcomes (eg, physical activity, blood samples, quality of life, and functioning) will be collected at baseline, end of intervention, and 6 months after intervention completion. This protocol was developed after 6 months of extensive stakeholder and community consultation. Enrollment began in January 2017; as of publication, 12 participants were enrolled. Baseline testing is scheduled to commence in mid-2017. This pilot study will provide essential feasibility and acceptability data which will guide the use of active video games for people with ME/CFS to increase their physical activity levels. Physical activity promotion in this clinical population has been poorly and under-researched, and any exploration of alternative physical activity options for this population is much needed. Australia New Zealand Clinical Trials Registry: ACTRN12616000285459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370224 (Archived by WebCite at http://www.webcitation.org/6qgOLhWWf). ©Katia Elizabeth Ferrar, Ashleigh E Smith, Kade Davison. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.08.2017.
Depositional environment of near-surface sediments, King George Basin, Bransfield Strait, Antarctica
NASA Astrophysics Data System (ADS)
Yoon, H. I.; Park, B. K.; Chang, S. K.; Han, M. W.; Oh, J. K.
1994-03-01
Four sediment cores were collected to determine the depositional environments of the King George Basin northeast of Bransfield Strait, Antarctica. The cored section revealed three distinct lithofacies: laminated siliceous ooze derived from an increased paleoproductivity near the receding sea-ice edges, massive muds that resulted from hemipelagic sedimentation in open water, and graded sediments that originated from nearby local seamounts by turbidity currents. Clay mineral data of the cores indicate a decreasing importance of volcanic activity through time. Active volcanism and hydrothermal activity appear to be responsible for the enrichment of smectite near the Penguin and Bridgeman Islands.
A second mechanism of increase of cerebellar hypermetria in humans
Manto, Mario-Ubaldo; Bosse, Pierre
2003-01-01
So far, there is only one procedure known to increase hypermetria in cerebellar patients. Facing an increased inertia of the moving limb, patients presenting a lesion of the lateral cerebellum are able to increase appropriately the intensity of the agonist electromyographic (EMG) activity (the launching force), but are unable to adapt the intensity of the antagonist activity (the braking force). As a result, hypermetria is larger when the inertial load is artificially increased. Recent studies have demonstrated that hyperventilation increases hypermetria in patients presenting a spinocerebellar ataxia type 6 (SCA 6), a disorder associated with polyglutamine expansions in the α1A-voltage-dependent calcium channel. The mechanism of this increase of hypermetria has not been identified so far. In the present work, we combined kinematic, EMG and transcranial Doppler studies to understand the effects of hyperventilation on fast goal-directed movements in patients presenting a SCA 6. Both in the normal mechanical state and after increasing the inertial load of the moving hand, hyperventilation induced an increase of hypermetria. Hyperventilation increased the delay of the onset latency of the antagonist EMG activity and decreased the rate of rise of both the agonist and the antagonist EMG activities. Hyperventilation induced a marked decrease in cerebral blood flow velocities. The mechanism of this provocative test is original and is distinct from the mechanism of the load-induced increase of hypermetria. PMID:12588903
Liu, Yan; He, Zhangxiu; Zhang, Yan; Dong, Zengxiang; Bi, Yayan; Kou, Junjie; Zhou, Jin; Shi, Jialan
2016-08-01
We evaluated cellular origin, numbers, and procoagulant activity of phosphatidylserine-positive microparticles (MPs) among subgroups in acute coronary syndromes (ACS). Parameters were measured on admission, days 1 (within 24 h of admission), 2, 3, and 7. All ST-elevated myocardial infarction (STEMI) patients presented more than 3 h from symptom onset and received fibrinolysis treatment; controls included unstable angina and non-STEMI patients as well as healthy controls. Phosphatidylserine-positive MPs were detected by flow cytometry, whereas procoagulant activity was assessed by coagulation time, purified coagulation complex assays, and fibrin formation. MP-induced fibrins were visualized by confocal microscopy. On admission, the total MP count was ∼2.5-fold higher in the ACS groups compared with the healthy controls (P<0.05), primarily originating from platelets and endothelial cells, and there were no significant differences among ACS subgroups. Specifically, leukocyte-derived and erythrocyte-derived MPs were higher in the STEMI group compared with unstable angina and non-STEMI groups (both P<0.05). Further, MPs from the ACS groups reduced coagulation time by 27.5% and induced intrinsic and extrinsic FXase, prothrombinase, and fibrin formation by 2.8-, 2.3-, 2.5-, and 1.7-fold, respectively (P<0.05 for all), whereas blocking phosphatidylserine with lactadherin inhibited ∼70% of procoagulant activity. MP number and concomitant coagulation decreased significantly by day 2 and continued to decrease gradually during the recovery period. This study shows that MP characteristics from circulating blood may be used as prognostic indicators to reflect the origin cell of activation and thrombophilic states found in ACS subgroups.
van ’t Ent, D.; van Beijsterveldt, C.E.M.; Derks, E.M.; Hudziak, J.J.; Veltman, D.J.; Todd, R.D.; Boomsma, D.I.; De Geus, E.J.C.
2009-01-01
Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced by genetic factors, but environmental influences are considered important as well. To distinguish between functional brain changes underlying primarily genetically and environmentally mediated ADHD, we used functional MRI to compare response interference in monozygotic twins highly concordant or discordant for attention problems (AP). AP scores were assessed longitudinally with the Child Behavior Check List attention problem scale (CBCL-AP). Response interference was measured during two executive function paradigms; a color-word Stroop and a flanker task. The neuroimaging results indicated that, across the entire sample, children with high CBCL-AP scores, relative to children with low CBCL-AP scores, showed decreased activation to response interference in dorsolateral prefrontal, parietal and temporal brain regions. Increased activation was noted in the premotor cortex and regions associated with visual selective attention processing, possibly reflecting compensatory mechanisms to maintain task performance. Specific comparisons of high and low scoring concordant twin pairs suggest that AP of genetic origin was characterized by decreased activation of the left dorsolateral prefrontal cortex during the Stroop task and right parietal lobe during the flanker task. In contrast, comparison of twins from discordant monozygotic pairs, suggest that AP of environmental origin was characterized by decreased activation in left and right temporal lobe areas, but only during Stroop interference. The finding of distinct brain activation changes to response interference in inattention/hyperactivity of ‘genetic’ versus ‘environmental’ origin, indicate that genetic and environmental risk factors for attention/hyperactivity problems affect the brain in different ways. PMID:19409224
ERIC Educational Resources Information Center
Olivos, Edward M.; Mendoza, Marcela
2009-01-01
Immigration enforcement efforts have become increasingly intrusive and arbitrary in Latino-origin communities in the U.S. As a result, there are very real possibilities that schools which serve large Latino populations may be affected by immigration enforcement activities (also known as "raids") in their communities. This article offers…
12 CFR 225.137 - Acquisitions of shares pursuant to section 4(c)(6) of the Bank Holding Company Act.
Code of Federal Regulations, 2010 CFR
2010-01-01
... would be maintained for each stockholder consisting of the original capital contribution increased or... group of holding companies, through concerted action, to engage in an activity as entrepreneurs. Section... that of an entrepreneur rather than that of an investor. (g) Accordingly, on the basis of the factual...
Computer-Based Education: The Best of ERIC, June 1976-1982. Revised and Updated.
ERIC Educational Resources Information Center
Hall, Keith A.
This revision of the annotated bibliography, "Computer-Based Education: The Best of ERIC, June 1976-August 1980," includes 224 new entries as well as most of the 156 ERIC documents and journal articles originally cited. The new materials reflect the increased activity in the field with contributions about new technology (artificial…
Geographical patterns of the standing and active human gut microbiome in health and IBD.
Rehman, Ateequr; Rausch, Philipp; Wang, Jun; Skieceviciene, Jurgita; Kiudelis, Gediminas; Bhagalia, Ketan; Amarapurkar, Deepak; Kupcinskas, Limas; Schreiber, Stefan; Rosenstiel, Philip; Baines, John F; Ott, Stephan
2016-02-01
A global increase of IBD has been reported, especially in countries that previously had low incidence rates. Also, the knowledge of the human gut microbiome is steadily increasing, however, limited information regarding its variation on a global scale is available. In the light of the microbial involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated mucosal microbiota patterns from different geographical regions including Europe (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling based on 16S rRNA transcripts provides additional resolution, both of which may hold important clinical relevance. In this study, we analyse a set of 89 mucosal biopsies sampled from individuals of German, Lithuanian and Indian origins, using bacterial community profiling of a roughly equal number of healthy controls, patients with Crohn's disease and UC from each location, and analyse 16S rDNA and rRNA as proxies for standing and active microbial community structure, respectively. We find pronounced population-specific as well as general disease patterns in the major phyla and patterns of diversity, which differ between the standing and active communities. The geographical origin of samples dominates the patterns of β diversity with locally restricted disease clusters and more pronounced effects in the active microbial communities. However, two genera belonging to the Clostridium leptum subgroup, Faecalibacteria and Papillibacter, display consistent patterns with respect to disease status and may thus serve as reliable 'microbiomarkers'. These analyses reveal important interactions of patients' geographical origin and disease in the interpretation of disease-associated changes in microbial communities and highlight the added value of analysing communities on both the 16S rRNA gene (DNA) and transcript (RNA) level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Cross-Bardell, Laura; George, Tracey; Bhoday, Mandeep; Tuomainen, Helena; Qureshi, Nadeem; Kai, Joe
2015-02-27
To explore perspectives on enhancing physical activity and diet among South Asians in urban deprived communities at high risk of chronic disease and to inform development of culturally appropriate health promotion intervention. Qualitative study using semistructured one-to-one and family group interviews with thematic analysis of data. Urban disadvantaged communities in the East Midlands of the UK. 45 respondents, including 34 people of South Asian origin (16 at-risk individuals, six family groups involving 18 relatives), of mainly Pakistani and Indian origin, including 16 non-English speakers; and 11 health professionals working locally with communities of concern. South Asian participants underlined the challenges of requiring family members across generations to engage in modifying dietary behaviours, and the central role of communal eating of traditional 'Asian' food in their cultural lives. Barriers to increasing physical activity included cost, personal safety and lack of time outside of long working hours and carer commitments. However, increasing walking activity was regarded as feasible by both community and health professional participants. Respondents emphasised using a social approach for potential interventions, undertaking activity with family or friends and with bilingual community peers to facilitate engagement, motivation and support. Spoken content and delivery of interventions was favoured, including personal stories and multilingual audio-visual information; within local informal rather than provider settings, including the home; and aided by pedometers for self-monitoring. Focusing on physical activity by increasing walking may hold promise as health promotion in this deprived South Asian community context. Further intervention development, with exploration of feasibility and acceptability of the social approach and elements suggested, is merited. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
On the Origin of the 1,000 Hz Peak in the Spectrum of the Human Tympanic Electrical Noise
Pardo-Jadue, Javiera; Dragicevic, Constantino D.; Bowen, Macarena; Delano, Paul H.
2017-01-01
The spectral analysis of the spontaneous activity recorded with an electrode positioned near the round window of the guinea pig cochlea shows a broad energy peak between 800 and 1,000 Hz. This spontaneous electric activity is called round window noise or ensemble background activity. In guinea pigs, the proposed origin of this peak is the random sum of the extracellular field potentials generated by action potentials of auditory nerve neurons. In this study, we used a non-invasive method to record the tympanic electric noise (TEN) in humans by means of a tympanic wick electrode. We recorded a total of 24 volunteers, under silent conditions or in response to stimuli of different modalities, including auditory, vestibular, and motor activity. Our results show a reliable peak of spontaneous activity at ~1,000 Hz in all studied subjects. In addition, we found stimulus-driven responses with broad-band noise that in most subjects produced an increase in the magnitude of the energy band around 1,000 Hz (between 650 and 1,200 Hz). Our results with the vestibular stimulation were not conclusive, as we found responses with all caloric stimuli, including 37°C. No responses were observed with motor tasks, like eye movements or blinking. We demonstrate the feasibility of recording neural activity from the electric noise of the tympanic membrane with a non-invasive method. From our results, we suggest that the 1,000 Hz component of the TEN has a mixed origin including peripheral and central auditory pathways. This research opens up the possibility of future clinical non-invasive techniques for the functional study of auditory and vestibular nerves in humans. PMID:28744193
On the Origin of the 1,000 Hz Peak in the Spectrum of the Human Tympanic Electrical Noise.
Pardo-Jadue, Javiera; Dragicevic, Constantino D; Bowen, Macarena; Delano, Paul H
2017-01-01
The spectral analysis of the spontaneous activity recorded with an electrode positioned near the round window of the guinea pig cochlea shows a broad energy peak between 800 and 1,000 Hz. This spontaneous electric activity is called round window noise or ensemble background activity. In guinea pigs, the proposed origin of this peak is the random sum of the extracellular field potentials generated by action potentials of auditory nerve neurons. In this study, we used a non-invasive method to record the tympanic electric noise (TEN) in humans by means of a tympanic wick electrode. We recorded a total of 24 volunteers, under silent conditions or in response to stimuli of different modalities, including auditory, vestibular, and motor activity. Our results show a reliable peak of spontaneous activity at ~1,000 Hz in all studied subjects. In addition, we found stimulus-driven responses with broad-band noise that in most subjects produced an increase in the magnitude of the energy band around 1,000 Hz (between 650 and 1,200 Hz). Our results with the vestibular stimulation were not conclusive, as we found responses with all caloric stimuli, including 37°C. No responses were observed with motor tasks, like eye movements or blinking. We demonstrate the feasibility of recording neural activity from the electric noise of the tympanic membrane with a non-invasive method. From our results, we suggest that the 1,000 Hz component of the TEN has a mixed origin including peripheral and central auditory pathways. This research opens up the possibility of future clinical non-invasive techniques for the functional study of auditory and vestibular nerves in humans.
Traffic safety for the cell: influence of cyclin-dependent kinase activity on genomic stability.
Enders, Greg H; Maude, Shannon L
2006-04-12
Genomic instability has long been considered a key factor in tumorigenesis. Recent evidence suggests that DNA damage may be widespread in early pre-neoplastic states, with deregulation of cyclin-dependent kinase (Cdk) activity a driving force. Increased Cdk activity may critically reduce licensing of origins of DNA replication, drive re-replication, or mediate overexpression of checkpoint proteins, inducing deleterious cell cycle delay. Conversely, inhibition of Cdk activity may compromise replication efficiency, expression of checkpoint proteins, or activation of DNA repair proteins. These vital functions point to the impact of Cdk activity on the stability of the genome. Insight into these pathways may improve our understanding of tumorigenesis and lead to more rational cancer therapies.
Isolated muscular sarcoidosis causing fever of unknown origin: The value of gallium-67 imaging
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patel, N.; Krasnow, A.; Sebastian, J.L.
1991-02-01
An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 ({sup 67}Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using {sup 67}Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis.
Berry, Tanya R; McCarville, Ron E; Rhodes, Ryan E
2008-03-01
The purpose of this research was to conduct a content analysis of physical activity advertisements in an effort to determine which advertisements were more likely to include features that may attract and maintain attention levels. Fifty-seven advertisements were collected from top circulation Canadian magazines. The advertisements ranged from publicly funded health promotion pieces to corporate sponsored advertisements using physical activity to sell a product. Advertisements were examined for textual and pictorial factors thought to increase attention allocated to advertising of this nature. Only two public health advertisements were found, and the majority of advertisements (57.9%) were from commercial advertisers using physical activity images to sell products or to encourage brand recognition. The advertisements originating with the private sector tended to possess most of the characteristics thought to attract the attention of readers. Once this attention was gained, however, most of these advertisements failed to highlight the benefits of physical activity. As a result, the positive effect of these advertisements may have been compromised. Public health advertisements were so infrequent that we could not compare their characteristics with those originating with the private sector. The characteristics with those we did find were inconsistent with those thought to attract and maintain attention levels. Results are discussed in terms of potential implications for promoting physical activity.
Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.
Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho
2012-12-06
Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.
Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation
Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.
2016-01-01
Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658
Vargas, Alexander O; Ruiz-Flores, Macarena; Soto-Acuña, Sergio; Haidr, Nadia; Acosta-Hospitaleche, Carolina; Ossa-Fuentes, Luis; Muñoz-Walther, Vicente
2017-12-01
Embryonic muscular activity (EMA) is involved in the development of several distinctive traits of birds. Modern avian diversity and the fossil record of the dinosaur-bird transition allow special insight into their evolution. Traits shaped by EMA result from mechanical forces acting at post-morphogenetic stages, such that genes often play a very indirect role. Their origin seldom suggests direct selection for the trait, but a side-effect of other changes such as musculo-skeletal rearrangements, heterochrony in skeletal maturation, or increased incubation temperature (which increases EMA). EMA-shaped traits like sesamoids may be inconstant, highly conserved, or even disappear and then reappear in evolution. Some sesamoids may become increasingly influenced in evolution by genetic-molecular mechanisms (genetic assimilation). There is also ample evidence of evolutionary transitions from sesamoids to bony eminences at tendon insertion sites, and vice-versa. This can be explained by newfound similarities in the earliest development of both kinds of structures, which suggest these transitions are likely triggered by EMA. Other traits that require EMA for their formation will not necessarily undergo genetic assimilation, but still be conserved over tens and hundreds of millions of years, allowing evolutionary reduction and loss of other skeletal elements. Upon their origin, EMA-shaped traits may not be directly genetic, nor immediately adaptive. Nevertheless, EMA can play a key role in evolutionary innovation, and have consequences for the subsequent direction of evolutionary change. Its role may be more important and ubiquitous than currently suspected. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.
RADIOACTIVE NUCLIDES PRODUCED BY COSMIC RAYS IN SPUTNIK 4
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shedlovsky, J.P.; Kaye, J.H.
1963-09-01
The Sputnik 4 satellite re-entered the earth's atmosphere on September 5, 1962, after 843 days in orbit. From a portion of the recovered iron mass, a number of radioactive nuclides were measured after wet chemical separations. These activities are compared with those found in the Aroos iron meteorite. The ratio of saturation activities Sputnik 4/ Aroos increases, with increasing A, from 0.20 for Ar/sup 37/ to 0.68 for Fe/sup 55/. It appears that this increase is caused by low-energy solar-flare particles. The Co sup 56+57+58/ ratio is 0.098, which reflects the different nickel contents of the two objects. The samplemore » contains 40 dpm/kg Co/sup 60/, which is of noncosmogenic origin. (auth)« less
Tsai, Hung-Ji; Baller, Joshua A.; Liachko, Ivan; Koren, Amnon; Burrack, Laura S.; Hickman, Meleah A.; Thevandavakkam, Mathuravani A.; Rusche, Laura N.
2014-01-01
ABSTRACT Origins of DNA replication are key genetic elements, yet their identification remains elusive in most organisms. In previous work, we found that centromeres contain origins of replication (ORIs) that are determined epigenetically in the pathogenic yeast Candida albicans. In this study, we used origin recognition complex (ORC) binding and nucleosome occupancy patterns in Saccharomyces cerevisiae and Kluyveromyces lactis to train a machine learning algorithm to predict the position of active arm (noncentromeric) origins in the C. albicans genome. The model identified bona fide active origins as determined by the presence of replication intermediates on nondenaturing two-dimensional (2D) gels. Importantly, these origins function at their native chromosomal loci and also as autonomously replicating sequences (ARSs) on a linear plasmid. A “mini-ARS screen” identified at least one and often two ARS regions of ≥100 bp within each bona fide origin. Furthermore, a 15-bp AC-rich consensus motif was associated with the predicted origins and conferred autonomous replicating activity to the mini-ARSs. Thus, while centromeres and the origins associated with them are epigenetic, arm origins are dependent upon critical DNA features, such as a binding site for ORC and a propensity for nucleosome exclusion. PMID:25182328
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Influence of plant-originated gastroproteciive and antiulcer substances on gastric mucosal repair.
Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Brzozowski, T; Gzhegotsky, M R
2004-01-01
Fundamental basis of cellular and molecular mechanisms involved in mucosal injury and repair in gastrointestinal tract helps to develop new therapeutic approaches to various gut mucosal injury- related diseases. The study was aimed to assess the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulceric activities and to deteminate if these effects are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically. The following plant-originated substances were considered: Solon, capsaicin, grapefruit-seed extract and amaranth. The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). male Wistar rats, weighing 180-220 g fasted for 24 h before the study, 100% ethanol was applied ig to induced gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by an increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment-with L-NNA. Plant-originated substances are highly gastroprotective probably due to enhancement of the expression of NOS I, NO release and an increase in gastric microcirculation.
Development, fabrication and test of a high purity silica heat shield
NASA Technical Reports Server (NTRS)
Rusert, E. L.; Drennan, D. N.; Biggs, M. S.
1978-01-01
A highly reflective hyperpure ( 25 ppm ion impurities) slip cast fused silica heat shield material developed for planetary entry probes was successfully scaled up. Process development activities for slip casting large parts included green strength improvements, casting slip preparation, aggregate casting, strength, reflectance, and subscale fabrication. Successful fabrication of a one-half scale Saturn probe (shape and size) heat shield was accomplished while maintaining the silica high purity and reflectance through the scale-up process. However, stress analysis of this original aggregate slip cast material indicated a small margin of safety (MS. = +4%) using a factor of safety of 1.25. An alternate hyperpure material formulation to increase the strength and toughness for a greater safety margin was evaluated. The alternate material incorporates short hyperpure silica fibers into the casting slip. The best formulation evaluated has a 50% by weight fiber addition resulting in an 80% increase in flexural strength and a 170% increase in toughness over the original aggregate slip cast materials with comparable reflectance.
Goldsmith, B A; Abrams, T W
1992-12-01
Enhancement of the defensive withdrawal reflex of Aplysia involves a prolongation of the action potentials of mechanosensory neurons, which contributes to facilitation of transmitter release from these cells. Recent reports have suggested that whereas cAMP-dependent modulation of K+ current increases sensory neuron excitability, a cAMP-independent decrease in K+ current may increase the action potential duration and, thus, facilitate transmitter release. We have tested this proposal using Walsh cAMP-dependent protein kinase inhibitor or activators of the cAMP cascade and found that cAMP plays a major role in the spike-broadening effects of facilitatory transmitter; however, broadening requires higher levels of activation of the cAMP-dependent kinase than does increasing excitability. A steeply voltage-dependent transient K+ current, termed IKV,early, and the slowly activating S-type K+ (S-K+) current are both reduced by activation of the cAMP cascade, although with different sensitivities to the second messenger, enabling excitability and spike duration to be regulated independently. Differences in cAMP sensitivity also suggested that the originally described S-K+ current actually consists of two independent components, a slowly activating component and a time-independent, "steady-state" current that is activated at rest.
75 FR 28276 - Agency Information Collection Activities: NAFTA Regulations and Certificate of Origin
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2010-05-20
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Active role of a human genomic insert in replication of a yeast artificial chromosome.
van Brabant, A J; Fangman, W L; Brewer, B J
1999-06-01
Yeast artificial chromosomes (YACs) are a common tool for cloning eukaryotic DNA. The manner by which large pieces of foreign DNA are assimilated by yeast cells into a functional chromosome is poorly understood, as is the reason why some of them are stably maintained and some are not. We examined the replication of a stable YAC containing a 240-kb insert of DNA from the human T-cell receptor beta locus. The human insert contains multiple sites that serve as origins of replication. The activity of these origins appears to require the yeast ARS consensus sequence and, as with yeast origins, additional flanking sequences. In addition, the origins in the human insert exhibit a spacing, a range of activation efficiencies, and a variation in times of activation during S phase similar to those found for normal yeast chromosomes. We propose that an appropriate combination of replication origin density, activation times, and initiation efficiencies is necessary for the successful maintenance of YAC inserts.
Effects of alprazolam on cortical activity and tremors in patients with essential tremor.
Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A; Romero, Juan P; Saíz-Díaz, Rosana A; Benito-León, Julián; Rocon, Eduardo
2014-01-01
Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4-12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Alprazolam significantly attenuated tremors (EMG: 76.2 ± 22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor.
Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene
2008-10-01
Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.
DNA sequence templates adjacent nucleosome and ORC sites at gene amplification origins in Drosophila
Liu, Jun; Zimmer, Kurt; Rusch, Douglas B.; Paranjape, Neha; Podicheti, Ram; Tang, Haixu; Calvi, Brian R.
2015-01-01
Eukaryotic origins of DNA replication are bound by the origin recognition complex (ORC), which scaffolds assembly of a pre-replicative complex (pre-RC) that is then activated to initiate replication. Both pre-RC assembly and activation are strongly influenced by developmental changes to the epigenome, but molecular mechanisms remain incompletely defined. We have been examining the activation of origins responsible for developmental gene amplification in Drosophila. At a specific time in oogenesis, somatic follicle cells transition from genomic replication to a locus-specific replication from six amplicon origins. Previous evidence indicated that these amplicon origins are activated by nucleosome acetylation, but how this affects origin chromatin is unknown. Here, we examine nucleosome position in follicle cells using micrococcal nuclease digestion with Ilumina sequencing. The results indicate that ORC binding sites and other essential origin sequences are nucleosome-depleted regions (NDRs). Nucleosome position at the amplicons was highly similar among developmental stages during which ORC is or is not bound, indicating that being an NDR is not sufficient to specify ORC binding. Importantly, the data suggest that nucleosomes and ORC have opposite preferences for DNA sequence and structure. We propose that nucleosome hyperacetylation promotes pre-RC assembly onto adjacent DNA sequences that are disfavored by nucleosomes but favored by ORC. PMID:26227968
Signaling cascades modulate the speed of signal propagation through space.
Govern, Christopher C; Chakraborty, Arup K
2009-01-01
Cells are not mixed bags of signaling molecules. As a consequence, signals must travel from their origin to distal locations. Much is understood about the purely diffusive propagation of signals through space. Many signals, however, propagate via signaling cascades. Here, we show that, depending on their kinetics, cascades speed up or slow down the propagation of signals through space, relative to pure diffusion. We modeled simple cascades operating under different limits of Michaelis-Menten kinetics using deterministic reaction-diffusion equations. Cascades operating far from enzyme saturation speed up signal propagation; the second mobile species moves more quickly than the first through space, on average. The enhanced speed is due to more efficient serial activation of a downstream signaling module (by the signaling molecule immediately upstream in the cascade) at points distal from the signaling origin, compared to locations closer to the source. Conversely, cascades operating under saturated kinetics, which exhibit zero-order ultrasensitivity, can slow down signals, ultimately localizing them to regions around the origin. Signal speed modulation may be a fundamental function of cascades, affecting the ability of signals to penetrate within a cell, to cross-react with other signals, and to activate distant targets. In particular, enhanced speeds provide a way to increase signal penetration into a cell without needing to flood the cell with large numbers of active signaling molecules; conversely, diminished speeds in zero-order ultrasensitive cascades facilitate strong, but localized, signaling.
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Joakim Larsson, D G; Fick, Jerker
2009-04-01
Recent findings have shown that wastewater from bulk drug production can be a source of very high environmental concentrations of drugs in certain locations. The release of active ingredients is often not specifically regulated, and thus rapid initiatives from the industries themselves are warranted. Possible ways to stimulate action include changes in local and international regulations, including the implementation of appropriate environmental standards within existing industry guidelines as well as demands from prescribers and consumers of medicines. The lack of readily available information regarding the origin of drugs and the environmental impact of the production, however, prevents consumers from making informed decisions. Here, we investigated the origin of active pharmaceutical ingredients (APIs) in 242 selected products on the Swedish market. By comparing registers from Sweden and India we found that the APIs in 71 products (31%) originated from Indian manufacturers sending their waste to a treatment plant where unprecedented amount of environmental pollution with broad-spectrum antibiotics and other drugs recently has been documented. We propose that increased transparency throughout the production chain would be one of several important steps to reducing pollution from the manufacturing of drugs.
Long-term changes of the glacial seismicity: case study from Spitsbergen
NASA Astrophysics Data System (ADS)
Gajek, Wojciech; Trojanowski, Jacek; Malinowski, Michał
2016-04-01
Changes in global temperature balance have proved to have a major impact on the cryosphere, and therefore withdrawing glaciers are the symbol of the warming climate. Our study focuses on year-to-year changes in glacier-generated seismicity. We have processed 7-year long continuous seismological data recorded by the HSP broadband station located in the proximity of Hansbreen glacier (Hornsund, southern Spitsbergen), obtaining seismic activity distribution between 2008 and 2014. We developed a new fuzzy logic algorithm to distinguish between glacier- and non-glacier-origin events. The algorithm takes into account the frequency of seismic signal and the energy flow in certain time interval. Our research has revealed that the number of detected glacier-origin events over last two years has doubled. Annual events distribution correlates well with temperature and precipitation curves, illustrating characteristic yearlong behaviour of glacier seismic activity. To further support our observations, we have analysed 5-year long distribution of glacier-origin tremors detected in the vicinity of the Kronebreen glacier using KBS broadband station located in Ny-Ålesund (western Spitsbergen). We observe a steady increase in the number of detected events. detected each year, however not as significant as for Hornsund dataset.
ERIC Educational Resources Information Center
Organisation for Economic Cooperation and Development, Paris (France).
Conclusions are presented indicating the role which public bodies, employers, trade unions, and other private groups can play in improving the employment opportunities of special groups, such as older workers, workers with family responsibilities, and workers of rural origin engaged in non-agricultural employment. Because of the increasing number…
Unveiling the high-activity origin of single-atom iron catalysts for oxygen reduction reaction.
Yang, Liu; Cheng, Daojian; Xu, Haoxiang; Zeng, Xiaofei; Wan, Xin; Shui, Jianglan; Xiang, Zhonghua; Cao, Dapeng
2018-06-26
It is still a grand challenge to develop a highly efficient nonprecious-metal electrocatalyst to replace the Pt-based catalysts for oxygen reduction reaction (ORR). Here, we propose a surfactant-assisted method to synthesize single-atom iron catalysts (SA-Fe/NG). The half-wave potential of SA-Fe/NG is only 30 mV less than 20% Pt/C in acidic medium, while it is 30 mV superior to 20% Pt/C in alkaline medium. Moreover, SA-Fe/NG shows extremely high stability with only 12 mV and 15 mV negative shifts after 5,000 cycles in acidic and alkaline media, respectively. Impressively, the SA-Fe/NG-based acidic proton exchange membrane fuel cell (PEMFC) exhibits a high power density of 823 mW cm -2 Combining experimental results and density-functional theory (DFT) calculations, we further reveal that the origin of high-ORR activity of SA-Fe/NG is from the Fe-pyrrolic-N species, because such molecular incorporation is the key, leading to the active site increase in an order of magnitude which successfully clarifies the bottleneck puzzle of why a small amount of iron in the SA-Fe catalysts can exhibit extremely superior ORR activity.
Capannesi, Geraldo; Lopez, Francesco
2013-01-01
Human activities introduce compounds increasing levels of many dangerous species for environment and population. In this way, trace elements in airborne particulate have a preeminent position due to toxic element presence affecting the biological systems. The main problem is the analytical determination of such species at ultratrace levels: a very specific methodology is necessary with regard to the accuracy and precision and contamination problems. Instrumental Neutron Activation Analysis and Instrumental Photon Activation Analysis assure these requirements. A retrospective element analysis in airborne particulate collected in the last 4 decades has been carried out for studying their trend. The samples were collected in urban location in order to determine only effects due to global aerosol circulation; semiannual samples have been used to characterize the summer/winter behavior of natural and artificial origin. The levels of natural origin element are higher than those in other countries owing to geological and meteorological factors peculiar to Central Italy. The levels of artificial elements are sometimes less than those in other countries, suggesting a less polluted general situation for Central Italy. However, for a few elements (e.g., Pb) the levels measured are only slight lower than those proposed as air ambient standard. PMID:23878525
Enhanced oxidation resistance of active nanostructures via dynamic size effect
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Yun; Yang, Fan; Zhang, Yi
A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O 2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeOmore » NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O 2. We find this dynamic size effect to govern the chemical properties of active NSs.« less
Enhanced oxidation resistance of active nanostructures via dynamic size effect
Liu, Yun; Yang, Fan; Zhang, Yi; ...
2017-02-22
A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O 2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeOmore » NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O 2. We find this dynamic size effect to govern the chemical properties of active NSs.« less
The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb
Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.
2013-01-01
SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. PMID:23827682
Earthquake effects in thermal neutron variations at the high-altitude station of Northern
NASA Astrophysics Data System (ADS)
Antonova, Valentina; Chubenko, Alexandr; Kryukov, Sergey; Lutsenko, Vadim
2016-04-01
Results of study of thermal neutron variations under various space and geophysical conditions on the basis of measurements on stationary installations with high statistical accuracy are presented. Installations are located close to the fault of the earth's crust at the high-altitude station of cosmic rays (3340 m above sea level, 43.02 N, 76.56 E, 20 km from Almaty) in the mountains of Northern Tien-Shan. Responses of the most effective gelio- and geophysical events (variations of atmospheric pressure, coronal mass ejections, earthquakes) has consistently considered in the variations of the thermal neutron flux and compared with variations of high-energy neutrons (standard monitor 18NM64) of galactic origin during these periods. Coefficients of correlation were calculated between data of thermal neutron detectors and data of the neutron monitor, recording the intensity of high-energy particles. High correlation coefficients and similarity of responses to changes of space and geophysical conditions are obtained, that confirms the conclusion of the genetic connection of thermal neutrons with high-energy neutrons of galactic origin and suggests same sources of disturbances in the absence of seismic activity. Observations and analysis of experimental data during the activation of seismic activity in the vicinity of Almaty showed the frequent breakdown of the correlation between the intensity of thermal and high-energy neutrons and the absence of similarity between variations during these periods. We suppose that the additional thermal neutron flux of the lithospheric origin appears under these conditions. Method of separating of thermal neutron flux variations of the lithospheric origin from neutrons variations generated in the atmosphere by subtracting the normalized data is proposed, taking into account the conclusion that variations caused with the atmospheric and interplanetary origins in thermal neutron detectors are similar to variations of high-energy neutrons, and the probability of detecting by 18NM64 monitor of thermal neutrons is extremely low (less than 0, 01). We used it for analysis variations of thermal neutrons during earthquakes 2006-2015. The catalog of earthquakes in the vicinity of Almaty with intensity ≥ 3b, including 25 events, is composed on the basis of observations of the Kazakhstan National Data center. Experimental data of registration of thermal and high-energy neutrons (≥ 200 MeV) with duration not less than 14 days are prepared for an each event. The main statistical characteristics of experimental data are calculated and the normalization is carried out. The increase of thermal neutrons flux of the lithospheric origin during of seismic processes activation is observed for ~ 60% of events. However, before the earthquake the increase of thermal neutron flux is observed only for ~ 30-35% of events. It is shown that the amplitude of the additional thermal neutron flux from the Earth's crust is equal to 5-7% of the background level. Sometimes it reaches values of 10-12%. We propose to employ method of allocating the thermal neutron flux of the lithospheric origin for short-term prediction of earthquakes in seismoactive regions.
Bigman, Galya; Rajesh, Vandita; Koehly, Laura M; Strong, Larkin L; Oluyomi, Abiodun O; Strom, Sara S; Wilkinson, Anna V
2015-07-01
Existing racial/ethnic disparities in physical activity during childhood increase Hispanics' risk of developing chronic diseases, which serves to increase health disparities. This study examined associations of family cohesion and conflict with self-reported moderate-to-vigorous physical activity (MVPA), controlling for psychosocial covariates such as subjective social status, anxiety, and sensation-seeking. 1000 Mexican origin adolescents reported their MVPA levels approximately 2 years apart. Psychosocial covariates, family cohesion and conflict were measured at the first assessment. Generalized Linear Models were used to prospectively examine the relationship between family cohesion and conflict and subsequent MVPA based on 711 participants who had low levels of baseline MVPA. 35% of boys and 24% of girls reported adequate MVPA levels at follow-up; girls were less likely to report adequate MVPA (RR = 0.76; 95% CI: 0.61-0.93) than boys. Overall, family cohesion was associated with MVPA (P = .01), but family cohesion was not (P = .41). Gender-based analyses revealed that adequate MVPA was associated with family cohesion (RR = 1.40; 95% CI: 1.03-1.88), sensation seeking (RR = 1.05; 95% CI: 1.00-1.10), and age (RR = 0.85; 95% CI: 0.74-0.98) among girls and with subjective social status (RR = 1.20; 95% CI: 1.08-1.33) among boys. The family social environment and gender differences should be addressed in health promotion programs targeting MVPA.
Verluyten, Jurgen; Messens, Winy; De Vuyst, Luc
2004-01-01
Lactobacillus curvatus LTH 1174, a strain originating in fermented sausage, produces the antilisterial bacteriocin curvacin A. Its biokinetics of cell growth and bacteriocin production as a function of various concentrations of salt (sodium chloride) were investigated in vitro during laboratory fermentations using modified MRS medium. A model was set up to describe the effects of different NaCl concentrations on microbial behavior. Both cell growth and bacteriocin activity were affected by changes in the salt concentration. Sodium chloride clearly slowed down the growth of L. curvatus LTH 1174, but more importantly, it had a detrimental effect on specific curvacin A production (kB) and hence on overall bacteriocin activity. Even a low salt concentration (2%, wt/vol) decreased bacteriocin production, while growth was unaffected at this concentration. The inhibitory effect of NaCl was mainly due to its role as an aw-lowering agent. Further, it was clear that salt interfered with bacteriocin induction. Additionally, when 6% (wt/vol) sodium chloride was added, the minimum biomass concentration necessary to start the production of curvacin A (XB) was 0.90 g (cell dry mass) per liter. Addition of the cell-free culture supernatant or a protein solution as a source of induction factor resulted in a decrease in XB, an increase in kB, and hence an increase in the maximum attainable bacteriocin activity. PMID:15066822
DOE Office of Scientific and Technical Information (OSTI.GOV)
Crozat, G.; Domergue, J.L.; Bogui, V.
Atmospheric aerosols were sampled on filters to the air near ground level over the Ivory Coast and the Gulf of Guinea. Several elements were measured of filters by neutron activation and gamma spectrometry. Correlation thats applied to these elements allow them to be classified in groups of common origin. Study of the sampling collected over the Ivory Coast, along a''North- South'' axis, showed an increase of the concentrations of the terrestrial elements, as one passes from the coast to the north of the country. However, no particular increase of the concentrations was observed, to ground level air, when passing frommore » one side of the intertropical front to the other. In the air above the land, concentrations of marine aerosols decrease from the coast forth, especially near it. Daily variations may be noticed for all the elements The experiments performed in marthe atmosphere, over the Guif of Guinea, show that a high number of the elements measured are of terrestrial origin. (UK)« less
Soper, Colin; Wicker, Evan; Kulick, Catherine V.; N’Gouemo, Prosper; Forcelli, Patrick A.
2016-01-01
Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. PMID:26721319
Soper, Colin; Wicker, Evan; Kulick, Catherine V; N'Gouemo, Prosper; Forcelli, Patrick A
2016-03-01
Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.
Thorn, Stephanie R.; Brown, Laura D.; Rozance, Paul J.; Hay, William W.; Friedman, Jacob E.
2013-01-01
Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH2-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator–activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR. PMID:22933111
Shang, Yang; Sun, Du; Shao, Yiming; Zhang, Dongfeng; Guo, Lin; Yang, Shihe
2012-11-05
Cutting edge: A Cu(2)O jagged polyhedron, with numerous {110} edges and {111} corners, has been developed through a top-down selective oxidative etching process at the expense of the original {111} facet (see figure). The as-prepared nanocrystals exhibited higher photocatalytic activities for the degradation of methylene orange, which may be primarily ascribed to the increased edges and corners. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Temperate mountain grasslands: a climate-herbivore hypothesis for origins and persistence
Weigl, Peter D; Knowles, Travis W
2014-01-01
Temperate montane grasslands and their unique biotas are declining worldwide as they are increasingly being invaded by forests. The origin and persistence of these landscapes have been the focus of such controversy that in many areas their conservation is in doubt. In the USA some biologists have largely dismissed the grass balds of the Southern Appalachians as human artifacts or anomalous and transitory elements of regional geography, worthy of only limited preservation efforts. On the basis of information from biogeography, community ecology, regional history and palaeontology and from consideration of two other montane grassland ecosystems—East Carpathian poloninas and Oregon Coast Range grass balds—we hypothesize that these landscapes are more widespread than was formerly recognized; they are, in many cases, natural and ancient and largely owe their origin and persistence to past climatic extremes and the activities of large mammalian herbivores. PMID:24118866
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Marino-Merlo, Francesca; Papaianni, Emanuela; Maugeri, Teresa L; Zammuto, Vincenzo; Spanò, Antonio; Nicolaus, Barbara; Poli, Annarita; Di Donato, Paola; Mosca, Claudia; Mastino, Antonio; Gugliandolo, Concetta
2017-10-01
Herpes simplex virus type 1 (HSV-1) is responsible of common and widespread viral infections in humans through the world, and of rare, but extremely severe, clinical syndromes in the central nervous system. The emergence of resistant strains to drugs actually in use encourages the searching for novel antiviral compounds, including those of natural origin. In this study, the recently described poly-γ-glutamic acid (γ-PGA-APA), produced by the marine thermotolerant Bacillus horneckiae strain APA, and previously shown to possess biological and antiviral activity, was evaluated for its anti-HSV-1 and immunomodulatory properties. The biopolymer hindered the HSV-1 infection in the very early phase of virus replication. In addition, the γ-PGA-APA was shown to exert low cytotoxicity and noticeable immunomodulatory activities towards TNF-α and IL-1β gene expression. Moreover, the capacity to positively modulate the transcriptional activity of the cytokine genes was paired with increased level of activation of the transcription factor NF-kB by γ-PGA-APA. Overall, as non-cytotoxic biopolymer able to contribute in the antiviral defense against HSV-1, γ-PGA-APA could lead to the development of novel natural drugs for alternative therapies.
Brownian Motion with Active Fluctuations
NASA Astrophysics Data System (ADS)
Romanczuk, Pawel; Schimansky-Geier, Lutz
2011-06-01
We study the effect of different types of fluctuation on the motion of self-propelled particles in two spatial dimensions. We distinguish between passive and active fluctuations. Passive fluctuations (e.g., thermal fluctuations) are independent of the orientation of the particle. In contrast, active ones point parallel or perpendicular to the time dependent orientation of the particle. We derive analytical expressions for the speed and velocity probability density for a generic model of active Brownian particles, which yields an increased probability of low speeds in the presence of active fluctuations in comparison to the case of purely passive fluctuations. As a consequence, we predict sharply peaked Cartesian velocity probability densities at the origin. Finally, we show that such a behavior may also occur in non-Gaussian active fluctuations and discuss briefly correlations of the fluctuating stochastic forces.
Antioxidative activity and growth regulation of Brassicaceae induced by oxygen radical irradiation
NASA Astrophysics Data System (ADS)
Hayashi, Nobuya; Ono, Reoto; Shiratani, Masaharu; Yonesu, Akira
2015-06-01
The growth regulation characteristics of plants are investigated when plant seeds are irradiated with atmospheric discharge plasma. Enhancement of the germination and lengths of the stem and root of plants are observed after seeding. The total length of the stem and root increases approximately 1.6 times after a cultivation period of 72 h. The growth regulation effect is found to be maintained for 80 h of cultivation after seeding. The growth regulation originates from the change in the antioxidative activity of plant cells induced by active oxygen species generated in the oxygen plasma, which leads to the production of growth factor in plants.
NASA Astrophysics Data System (ADS)
Tielmann, Patrick; Kierkels, Hans; Zonta, Albin; Ilie, Adriana; Reetz, Manfred T.
2014-05-01
The entrapment of lipases in hydrophobic silicate matrices formed by sol-gel mediated hydrolysis of RSi(OCH3)3/Si(OCH3)4 as originally reported in 1996 has been improved over the years by a number of modifications. In the production of second-generation sol-gel lipase immobilizates, a variety of additives during the sol-gel process leads to increased activity and enhanced stereoselectivity in esterifying kinetic resolution. Recent advances in this type of lipase immobilization are reviewed here, in addition to new results regarding the sol-gel entrapment of the lipase from Burkholderia cepacia. It constitutes an excellent heterogeneous biocatalyst in the acylating kinetic resolution of two synthetically and industrially important chiral alcohols, rac-sulcatol and rac-trans-2-methoxycyclohexanol. The observation that the catalyst can be used 10 times in recycling experiments without losing its significant activity or enantioselectivity demonstrates the practical viability of the sol-gel approach.The entrapment of lipases in hydrophobic silicate matrices formed by sol-gel mediated hydrolysis of RSi(OCH3)3/Si(OCH3)4 as originally reported in 1996 has been improved over the years by a number of modifications. In the production of second-generation sol-gel lipase immobilizates, a variety of additives during the sol-gel process leads to increased activity and enhanced stereoselectivity in esterifying kinetic resolution. Recent advances in this type of lipase immobilization are reviewed here, in addition to new results regarding the sol-gel entrapment of the lipase from Burkholderia cepacia. It constitutes an excellent heterogeneous biocatalyst in the acylating kinetic resolution of two synthetically and industrially important chiral alcohols, rac-sulcatol and rac-trans-2-methoxycyclohexanol. The observation that the catalyst can be used 10 times in recycling experiments without losing its significant activity or enantioselectivity demonstrates the practical viability of the sol-gel approach. Dedicated to the pioneer of sol-gel enzyme immobilization, Professor David Avnir, on the occasion of his 65th birthday.
NASA Astrophysics Data System (ADS)
Kim, T.; Kwon, E.; Kim, G.
2011-12-01
In order to determine the origin of dissolved organic matter (DOM) in the subterranean estuary (STE), the mixing zone of fresh terrestrial groundwater and recirculating seawater in a coastal permeable aquifer, we conducted water sampling from two STEs with different geological settings: (1) Jeju Island beaches (Hwasun and Samyang), which are composed of volcanic rocks and sandy sediments, and (2) Hampyeong beach, which is located in a large intertidal, sandy flat zone. The distributions of salinity, total hydrolysable amino acids (THAA), dissolved organic carbon (DOC), and colored DOM (CDOM) were measured for groundwater samples in these STEs. In the Hwasun STE, the humic-like peak decreases with increasing salinity, whereas the protein-like peak does not show a clear relationship with salinity. In contrast, in the Samyang STE, both humic-like peak and protein-like peak increase with increasing salinity. These contrasting results indicate that DOM in the Hwasun STE originates mainly from terrestrial inputs, while that in the Samyang STE originates mainly from biological and/or microbial activities. In the Hampyeong STE, we observed good correlations among the biodegradation index, alanine D/L ratios, THAA concentrations, DOC, and CDOM index (both humic-like and protein-like). Together with their geographical distribution patterns, these correlations indicate that DOM in the Hampyeong STE is mainly derived from marine sediments in the course of seawater recirculation. Our study shows that CDOM and amino acids are excellent tracers of DOM in the STE where DOM is derived from diverse sources.
Tassi, E; Giorgetti, L; Morelli, E; Peralta-Videa, J R; Gardea-Torresdey, J L; Barbafieri, M
2017-01-01
Little is known about the interaction of nanoparticles (NPs) with soil constituents and their effects in plants. Boron (B), an essential micronutrient that reduces crop production at both deficiency and excess, has not been investigated with respect to its interaction with cerium oxide NPs (nano-CeO 2 ). Considering conflicting results on the nano-CeO 2 toxicity and protective role as antioxidant, their possible modulation on B toxicity in sunflower (Helianthus annuus L.) was investigated. Sunflower was cultivated for 30 days in garden pots containing original or B-spiked soil amended with nano-CeO 2 at 0-800 mg kg -1 . At harvest, Ce and B concentrations in tissues, biomass, and activities of stress enzymes in leaves were determined. Results showed that in the original soil, Ce accumulated mainly in roots, with little translocation to stems and leaves, while reduced root Ce was observed in plants from B-spiked soil. In the original soil, higher levels of nano-CeO 2 reduced plant B concentration. Although morphological effects were not visible, changes in biomass and oxidative stress response were observed. Sunflower leaves from B-spiked soil showed visible symptoms of B toxicity, such as necrosis and chlorosis in old leaves, as well as an increase of superoxide dismutase (SOD) activity. However, at high nano-CeO 2 level, SOD activity decreased reaching values similar to that of the control. This study has shown that nano-CeO 2 reduced both the B nutritional status of sunflower in original soil and the B phytotoxicity in B-spiked soil. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Activation of immobilized enzymes by acoustic wave resonance oscillation.
Nishiyama, Hiroshi; Watanabe, Tomoya; Inoue, Yasunobu
2014-12-01
Acoustic wave resonance oscillation has been used successfully in the development of methods to activate immobilized enzyme catalysts. In this study, resonance oscillation effects were demonstrated for enzyme reactions on galactose oxidase (GAD), D-amino acid oxidase (DAAO), and L-amino acid oxidase (LAAO), all of which were immobilized covalently on a ferroelectric lead zirconate titanate (PZT) device that could generate thickness-extensional resonance oscillations (TERO) of acoustic waves. For galactose oxidation on immobilized GAD in a microreactor, TERO generation immediately increased enzyme activity 2- to 3-fold. Eliminating TERO caused a slight decrease in the activity, with ∼90% of the enhanced activity retained while the reaction proceeded. Contact of the enhanced enzyme with a galactose-free solution caused almost complete reversion of the activity to the original low level before TERO generation, indicating that, not only TERO-induced GAD activation, but also preservation of the increased activity, required a galactose substrate. Similar activity changes with TERO were observed for enzyme reactions on DAAO and LAAO. Kinetic analysis demonstrated that TERO helped strengthen the interactions of the immobilized enzyme with the reactant substrate and promoted formation of an activation complex. Copyright © 2014 Elsevier Inc. All rights reserved.
Replication Origins and Timing of Temporal Replication in Budding Yeast: How to Solve the Conundrum?
Barberis, Matteo; Spiesser, Thomas W.; Klipp, Edda
2010-01-01
Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicates its genome with a defined timing. In this organism, well-defined, site-specific origins, are efficient and fire in almost every round of DNA replication. However, this strategy is neither conserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophila embryos, nor in higher eukaryotes, in which DNA replication initiates asynchronously throughout S phase at random sites. Temporal and spatial controls can contribute to the timing of replication such as Cdk activity, origin localization, epigenetic status or gene expression. However, a debate is going on to answer the question how individual origins are selected to fire in budding yeast. Two opposing theories were proposed: the “replicon paradigm” or “temporal program” vs. the “stochastic firing”. Recent data support the temporal regulation of origin activation, clustering origins into temporal blocks of early and late replication. Contrarily, strong evidences suggest that stochastic processes acting on origins can generate the observed kinetics of replication without requiring a temporal order. In mammalian cells, a spatiotemporal model that accounts for a partially deterministic and partially stochastic order of DNA replication has been proposed. Is this strategy the solution to reconcile the conundrum of having both organized replication timing and stochastic origin firing also for budding yeast? In this review we discuss this possibility in the light of our recent study on the origin activation, suggesting that there might be a stochastic component in the temporal activation of the replication origins, especially under perturbed conditions. PMID:21037857
A role for intestinal TLR4-driven inflammatory response during activity-based anorexia
Belmonte, Liliana; Achamrah, Najate; Nobis, Séverine; Guérin, Charlène; Riou, Gaëtan; Bôle-Feysot, Christine; Boyer, Olivier; Richard, Vincent; Rego, Jean Claude Do; Déchelotte, Pierre; Goichon, Alexis; Coëffier, Moïse
2016-01-01
Anorexia nervosa (AN) is associated with low-grade systemic inflammation and altered gut microbiota. However, the molecular origin of the inflammation remains unknown. Toll-like receptors are key regulators of innate immune response and their activation seems also to be involved in the control of food intake. We used activity-based anorexia (ABA) model to investigate the role of TLR4 and its contribution in anorexia-associated low-grade inflammation. Here, we found that ABA affected early the intestinal inflammatory status and the hypothalamic response. Indeed, TLR4 was upregulated both on colonic epithelial cells and intestinal macrophages, leading to elevated downstream mucosal cytokine production. These mucosal changes occurred earlier than hypothalamic changes driving to increased levels of IL-1β and IL-1R1 as well as increased levels of plasma corticosterone. Paradoxically, TLR4-deficient mice exhibited greater vulnerability to ABA with increased mortality rate, suggesting a major contribution of TLR4-mediated responses during ABA-induced weight loss. PMID:27779218
A role for intestinal TLR4-driven inflammatory response during activity-based anorexia.
Belmonte, Liliana; Achamrah, Najate; Nobis, Séverine; Guérin, Charlène; Riou, Gaëtan; Bôle-Feysot, Christine; Boyer, Olivier; Richard, Vincent; Rego, Jean Claude Do; Déchelotte, Pierre; Goichon, Alexis; Coëffier, Moïse
2016-10-25
Anorexia nervosa (AN) is associated with low-grade systemic inflammation and altered gut microbiota. However, the molecular origin of the inflammation remains unknown. Toll-like receptors are key regulators of innate immune response and their activation seems also to be involved in the control of food intake. We used activity-based anorexia (ABA) model to investigate the role of TLR4 and its contribution in anorexia-associated low-grade inflammation. Here, we found that ABA affected early the intestinal inflammatory status and the hypothalamic response. Indeed, TLR4 was upregulated both on colonic epithelial cells and intestinal macrophages, leading to elevated downstream mucosal cytokine production. These mucosal changes occurred earlier than hypothalamic changes driving to increased levels of IL-1β and IL-1R1 as well as increased levels of plasma corticosterone. Paradoxically, TLR4-deficient mice exhibited greater vulnerability to ABA with increased mortality rate, suggesting a major contribution of TLR4-mediated responses during ABA-induced weight loss.
On the origin of the electron blocking effect by an n-type AlGaN electron blocking layer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Zi-Hui; Ji, Yun; Liu, Wei
2014-02-17
In this work, the origin of electron blocking effect of n-type Al{sub 0.25}Ga{sub 0.75}N electron blocking layer (EBL) for c+ InGaN/GaN light-emitting diodes has been investigated through dual-wavelength emission method. It is found that the strong polarization induced electric field within the n-EBL reduces the thermal velocity and correspondingly the mean free path of the hot electrons. As a result, the electron capture efficiency of the multiple quantum wells is enhanced, which significantly reduces the electron overflow from the active region and increases the radiative recombination rate with holes.
Synchronous Papillary Carcinoma and Hemangiopericytoma with Lung Metastases
Malagutti, Nicola; Iannini, Valeria; Rocchi, Andrea; Stomeo, Francesco; Frassoldati, Antonio; Borin, Michela; Pelucchi, Stefano
2013-01-01
Hemangiopericytomas (HPC) are uncommon tumors that originate from perivascular cells of capillary vessels. HPC are about 1% of all vascular tumors and can be found in the head-neck region with an incidence between 16% and 33%. HPC is a neoplasm of uncertain malignant potential; it can behave as an aggressive tumor with metastases and increased mitotic activity or as a relatively benign neoplasm with only local development. In this paper we describe a case of hemangiopericytoma with uncertain malignant potential with cervical location associated with a concomitant papillary thyroid carcinoma and lung metastasis of unknown origin; this case led us to follow a specific and uncommon diagnostic and therapeutic strategy. PMID:24368958
NASA Astrophysics Data System (ADS)
Chen, Congjin; Li, Xin; Tong, Zhangfa; Li, Yue; Li, Mingfei
2014-10-01
Granular fir-based activated carbon (GFAC) was modified with H2O2, and orthogonal array experimental design method was used to optimize the process. The properties of the original and modified GFAC were characterized by N2 adsorption-desorption isotherms, Brunauer-Emmett-Teller (BET) equation, Barett-Joyner-Halenda (BJH) equation, field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectroscopy (FT-IR) analysis, etc. When 10.00 g of GFAC with particle size of 0.25-0.85 mm was modified by 150.0 ml of aqueous H2O2 solution, the optimized conditions were found to be as follows: aqueous H2O2 solution concentration 1.0 mol·l-1, modification temperature 30.0 °C, modification time 4.0 h. Modified under the optimized conditions, decolonization of caramel, methylene blue adsorption, phenol adsorption and iodine number of the modified GFAC increased by 500.0%, 59.7%, 32.5%, and 15.1%, respectively. The original and optimally modified GFAC exhibited adsorption isotherms of hybrid Type I-IV isotherms with H4 hysteresis. BET surface area, micropore area, total pore volume, micropore volume, and microporosity of the modified GFAC increased by 7.33%, 11.25%, 3.89%, 14.23%, 9.91%, respectively. Whereas the average pore width decreased by 3.16%. In addition, the amount of surface oxygen groups (such as carbonyl or carboxyl) increased in the modified GFAC.
Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans
NASA Technical Reports Server (NTRS)
Kaufmann, H.; Biaggioni, I.; Voustianiouk, A.; Diedrich, A.; Costa, F.; Clarke, R.; Gizzi, M.; Raphan, T.; Cohen, B.
2002-01-01
It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.
Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans.
Kaufmann, H; Biaggioni, I; Voustianiouk, A; Diedrich, A; Costa, F; Clarke, R; Gizzi, M; Raphan, T; Cohen, B
2002-04-01
It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.
Salinas, Jennifer J; Hilfinger Messias, DeAnne K; Morales-Campos, Daisy; Parra-Medina, Deborah
2014-02-01
To examine the relationship between English language proficiency (ELP), physical activity, and physical activity-related psychosocial measures (i.e., exercise self-efficacy, exercise social support, perceptions of environmental supports) among Mexican-origin women in South Carolina and Texas. Adjusted robust regression and interaction modeling to evaluate baseline questionnaire data on self-reported ELP with CHAMPS leisure-time moderate-to-vigorous physical activity (MVPA), accelerometry data, Physical Activity Self-Efficacy, Physical Activity Social Support, and Environmental Support for Physical Activity in 118 Mexican-origin women. The adjusted regression revealed a significant association between ELP and perceived physical activity self-efficacy (β = 234.2, p = .004), but not with physical activity social support. In South Carolina, CHAMPS leisure-time MVPA (411.4 versus 114.3 minutes, p < .05) was significantly different between women in the high ELP quartile and those in the very low quartile. Among high ELP Mexican-origin women, participants in Texas reported significantly higher MVPA measured by accelerometry (p = .042) than those in South Carolina. Our findings indicate that ELP was associated with physical activity and that contextual factors may also play a role.
Roles of cyclic AMP and Ca in epithelial ion transport across corneal epithelium: a review.
Reinach, P S
1985-04-01
The messenger roles of cyclic AMP and the calcium ion in stimulus-secretion coupling are considered in the frog and bovine corneal epithelium, respectively. In the frog cornea, epinephrine stimulates net C1 transport by increasing cyclic AMP content. This stimulation is associated with a larger apical membrane C1 conductance and basolateral membrane ionic conductance. The response of the apical membrane conductance is thought to result from an increase in cyclic AMP content whereas the basolateral membrane ionic conductance increase is unrelated based on measurements of the effects of the calcium channel antagonist, diltiazem, and the beta agonist, isoproterenol, on the electrical parameters and cyclic AMP content. The basolateral membrane is essentially K permselective since the K channel blocker, Ba, depolarized the intracellular potential difference and increased the basolateral membrane resistance. Diltiazem had even larger effects on these parameters suggesting that this compound is a more effective inhibitor of K channel activity than barium. In broken cell preparations of bovine corneal epithelium, a high affinity form of Ca + Mg activated ATPase is present (Km = .06 microM for Ca) and is essentially of plasma membrane origin. This ATPase activation is at a Ca activity similar to the expected intracellular value and suggests that this activity is the enzymatic basis for net Ca transport.
Břendová, Kateřina; Zemanová, Veronika; Pavlíková, Daniela; Tlustoš, Pavel
2016-10-01
In the present study, the content of risk elements and content of free amino acids were studied in spinach (Spinacia oleracea L.) and mustard (Sinapis alba L.) subsequently grown on uncontaminated and contaminated soils (5 mg Cd/kg, 1000 mg Pb/kg and 400 mg Zn/kg) with the addition of activated carbon (from coconut shells) or biochar (derived from local wood residues planted for phytoextaction) in different seasons (spring, summer and autumn). The results showed that activated carbon and biochar increased biomass production on contaminated site. Application of amendments decreased Cd and Zn uptake by spinach plants. Mustard significantly increased Pb accumulation in the biomass as well in subsequently grown autumn spinach. Glutamic acid and glutamine were major free amino acids in leaves of all plants (15-34% and 3-45%) from total content. Application of activated carbon and biochar increased content of glutamic acid in all plants on uncontaminated and contaminated soils. Activated carbon and biochar treatments also induced an increase of aspartic acid in spinach plants. Biochar produced from biomass originated from phytoextraction technologies promoted higher spinach biomass yield comparing unamended control and showed a tendency to reduce accumulation of cadmium and zinc and thus it is promising soil amendment. Copyright © 2016. Published by Elsevier Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Segel, G.B.; Lichtman, M.A.
Human blood T-lymphocytes increase their potassium (K/sup +/) permeability and active K/sup +/ transport following lectin or antigen stimulation. We have studied the permeability and active transport of K/sup +/ by lymphocytes in chronic lymphocytic leukemia (CLL) to determine if their membrane K/sup +/ transport was similar to resting or lectin-stimulated normal blood lymphocytes. K/sup +/ transport was assessed both by the rate of isotopic /sup 42/K/sup +/ uptake and by the rate of change in cell K/sup +/ concentration after inhibition of the K/sup +/ transport system with ouabain. CLL lymphocytes had a marked decrease in membrane K/sup +/more » permeability and active transport of K/sup +/ when compared to blood T lymphocytes. K/sup +/ transport in five subjects with CLL (10 mmol . 1 cell water/sup -1/ . h/sup -1/) was half that in normal blood T-lymphocytes (20 mmol . 1 cell water/sup -1/ h/sup -1/). Phytohemagglutinin (PHA) treatment of CLL lymphocytes did not increase significantly their active K/sup +/ transport, whereas K/sup +/ transport by normal T-lymphocytes increased by 100%. Since there were 73% T-lymphocytes in normal blood and 14% in CLL blood, the difference in membrane K/sup +/ turnover could be related either to neoplasia or to the proposed B-lymphocyte origin of CLL. We studied human tonsillar lymphocytes which contained a mean of 34% T-cells. In five studies of tonsils, K/sup +/ transport was 14 mmol . 1 cell water/sup -1/ . h/sup -1/ and treatment with PHA increased K/sup +/ transport only 30%. The intermediate values for basal K/sup +/ transport and K/sup +/ transport in response to PHA in tonsillar lymphocytes were consistent with the proportion of T-lymphocytes present. These data sugges t that B-lymphocytes have reduced membrane permeability and active transport of K/sup +/. Thus the marked decrease in CLL lymphocyte membrane K/sup +/ permeability and transport may be a reflection of its presumed B-cell origin, rather than a membrane alteration related to malignant transformation.« less
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2010-06-04
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Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders
Peiker, Ina; Schneider, Till R.; Milne, Elizabeth; Schöttle, Daniel; Vogeley, Kai; Münchau, Alexander; Schunke, Odette; Siegel, Markus; Engel, Andreas K.; David, Nicole
2015-01-01
Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatory-inhibitory balance underlies enhanced neural responses to coherent motion in ASD. PMID:26147342
Farooq, Faraz; Abadía-Molina, Francisco; MacKenzie, Duncan; Hadwen, Jeremiah; Shamim, Fahad; O'Reilly, Sean; Holcik, Martin; MacKenzie, Alex
2013-09-01
The loss of functional Survival Motor Neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes autosomal recessive neurodegenerative spinal muscle atrophy (SMA). A potential treatment strategy for SMA is to upregulate the amount of SMN protein originating from the highly homologous SMN2 gene, compensating in part for the absence of the functional SMN1 gene. We have previously shown that in vitro activation of the p38 pathway stabilizes and increases SMN mRNA levels leading to increased SMN protein levels. In this report, we explore the impact of the p38 activating, FDA-approved, blood brain barrier permeating compound celecoxib on SMN levels in vitro and in a mouse model of SMA. We demonstrate a significant induction of SMN protein levels in human and mouse neuronal cells upon treatment with celecoxib. We show that activation of the p38 pathway by low doses celecoxib increases SMN protein in a HuR protein-dependent manner. Furthermore, celecoxib treatment induces SMN expression in brain and spinal cord samples of wild-type mice in vivo. Critically, celecoxib treatment increased SMN levels, improved motor function and enhanced survival in a severe SMA mouse model. Our results identify low dose celecoxib as a potential new member of the SMA therapeutic armamentarium.
Effects of acoustic wave resonance oscillation on immobilized enzyme
NASA Astrophysics Data System (ADS)
Nishiyama, Hiroshi; Watanabe, Tomoya; Inoue, Yasunobu
2014-03-01
In aiming at developing a new method to artificially activate enzyme catalysts immobilized on surface, the effects of resonance oscillation of bulk acoustic waves were studied. Glucose oxidase (GOD) was immobilized by a covalent coupling method on a ferroelectric lead zirconate titanate (PZT) device that was able to generate thickness-extensional resonance oscillation (TERO). Glucose oxidation by the GOD enzyme was studied in a microreactor. The generation of TERO immediately increased the catalytic activity of immobilized GOD by a factor of 2-3. With turn-off of TERO, no significant activity decrease occurred, and 80-90% of the enhanced activity was maintained while the reaction proceeded. The almost complete reversion of the activity to the original low level before TERO generation was observed when the immobilized GOD was exposed to a glucose substrate-free solution. These results indicated that the presence of glucose substrate was essential for TERO-induced GOD activation and preservation of the increased activity level. The influences of reaction temperature, glucose concentration, pH, and rf electric power on the TERO activation showed that TERO strengthened the interactions of the immobilized enzyme with glucose substrate and hence promoted the formation of an activation complex.
Unipolar atrial electrogram morphology from an epicardial and endocardial perspective.
van der Does, Lisette J M E; Knops, Paul; Teuwen, Christophe P; Serban, Corina; Starreveld, Roeliene; Lanters, Eva A H; Mouws, Elisabeth M J P; Kik, Charles; Bogers, Ad J J C; de Groot, Natasja M S
2018-02-22
Endo-epicardial asynchrony (EEA) and the interplay between the endocardial and epicardial layers could be important in the pathophysiology of atrial arrhythmias. The morphologic differences between epicardial and endocardial atrial electrograms have not yet been described, and electrogram morphology may hold information about the presence of EEA. The purpose of this study was to directly compare epicardial to endocardial unipolar electrogram morphology during sinus rhythm (SR) and to evaluate whether EEA contributes to electrogram fractionation by correlating fractionation to spatial activation patterns. In 26 patients undergoing cardiac surgery, unipolar electrograms were simultaneously recorded from the epicardium and endocardium at the inferior, middle, and superior right atrial (RA) free wall during SR. Potentials were analyzed for epi-endocardial differences in local activation time, voltage, RS ratio, and fractionation. The surrounding and opposite electrograms of fractionated deflections were evaluated for corresponding local activation times in order to determine whether fractionation originated from EEA. The superior RA was predisposed to delayed activation, EEA, and fractionation. Both epicardial and endocardial electrograms demonstrated an S-predominance. Fractionation was mostly similar between the 2 sides; however, incidentally deflections up to 4 mV on 1 side could be absent on the other side. Remote activation was responsible for most fractionated deflections (95%) in SR, of which 4% could be attributed to EEA. Local epi-endocardial differences in electrogram fractionation occur occasionally during SR but will likely increase during arrhythmias due to increasing EEA and (functional) conduction disorders. Electrogram fractionation can originate from EEA, and this study demonstrated that unipolar electrogram fractionation can potentially identify EEA. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Wang, Hui; Long, Lindsey; Kumar, Arun; Wang, Wanqiu; Schemm, Jae-Kyung E.; Zhao, Ming; Vecchi, Gabriel A.; LaRow, Timorhy E.; Lim, Young-Kwon; Schubert, Siegfried D.;
2013-01-01
The variability of Atlantic tropical cyclones (TCs) associated with El Nino-Southern Oscillation (ENSO) in model simulations is assessed and compared with observations. The model experiments are 28-yr simulations forced with the observed sea surface temperature from 1982 to 2009. The simulations were coordinated by the U.S. CLIVAR Hurricane Working Group and conducted with five global climate models (GCMs) with a total of 16 ensemble members. The model performance is evaluated based on both individual model ensemble means and multi-model ensemble mean. The latter has the highest anomaly correlation (0.86) for the interannual variability of TCs. Previous observational studies show a strong association between ENSO and Atlantic TC activity, as well as distinctions in the TC activities during eastern Pacific (EP) and central Pacific (CP) El Nino events. The analysis of track density and TC origin indicates that each model has different mean biases. Overall, the GCMs simulate the variability of Atlantic TCs well with weaker activity during EP El Nino and stronger activity during La Nina. For CP El Nino, there is a slight increase in the number of TCs as compared with EP El Nino. However, the spatial distribution of track density and TC origin is less consistent among the models. Particularly, there is no indication of increasing TC activity over the U.S. southeast coastal region as in observations. The difference between the models and observations is likely due to the bias of vertical wind shear in response to the shift of tropical heating associated with CP El Nino, as well as the model bias in the mean circulation.
ERIC Educational Resources Information Center
Ronsley, Rebecca; Lee, Andrew S.; Kuzeljevic, Boris; Panagiotopoulos, Constadina
2013-01-01
Background: Aboriginal children are at increased risk for obesity and type 2 diabetes. Healthy Buddies [TM]-First Nations (HB) is a curriculum-based, peer-led program promoting healthy eating, physical activity, and self-esteem. Methods: Although originally designed as a pilot pre-/post-analysis of 3 remote Aboriginal schools that requested and…
Ackel-Eisnach, Kristina; Raes, Patricia; Hönikl, Lisa; Bauer, Daniel; Wagener, Stefan; Möltner, Andreas; Jünger, Jana; Fischer, Martin R
2015-01-01
The point of departure for the present work is the observation that, in comparison with Anglo-American countries or the Netherlands, Germany was responsible for only a marginal number of international publications in the field of medical education research before 2004. Recent years, however, have seen an increase in the importance of medical education research in Germany. The objective of this article is to evaluate the extent to which this trend can be substantiated by increased German publishing activity since the year 2004 in international, English-language journals in the subject area of "medical education research". In the framework of a literature and content analysis, German-author articles from the years 2004 to 2013 in six international, English-language medical education research journals were evaluated. In order to obtain an overview of German research activity in this area, all project and original works with German first and last authors were identified and subjected to a more in-depth content analysis. In total, 10,055 articles were examined. The evaluation shows that between the years 2004 and 2013 179 articles (of which 145 are project or original works) by German authors were published in the journals examined. Fluctuations over the course of time were evidenced. The project and original works are primarily cross-sectional studies (27.8%) and randomised control studies (25.6%) on the subject of "teaching and learning methods" (43.6%). In comparison with the years 2004-2008, a significant rise can be seen in the number of publications by German education researchers in international journals since the year 2009.
Matsuda, Daisuke; Tomoda, Hiroshi
2007-10-01
Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Diacylglycerol acyltransferase (DGAT) catalyzes the final reaction of triacylgycerol synthesis. Two isozymes of DGAT, DGAT1 and DGAT2, have been reported. Increased DGAT2 activity has a role in steatosis, while DGAT1 plays a role in very (V)LDL synthesis; increased plasma VLDL concentrations may promote obesity and thus DGAT1 is considered a potential therapeutic target of inhibition for obesity control. Several DGAT inhibitors of natural and synthetic origin have been reported, and their future prospect as anti-obesity drugs is discussed in this review.
Studies of long-term noopept and afobazol treatment in rats with learned helplessness neurosis.
Uyanaev, A A; Fisenko, V P
2006-08-01
Long-lasting effects of new Russian psychotropic drugs Noopept and Afobazol on active avoidance conditioning and formation of learned helplessness neurosis were studied on an original experimental model in rats. Noopept eliminated the manifestations of learned helplessness after long-term (21-day) treatment by increasing the percent of trained animals. Afobazol was low effective in preventing manifestations of learned helplessness, but if used for a long time, it reduced the incidence of learned helplessness development by increasing the percent of untrained animals.
SMART-FDIR: Use of Artificial Intelligence in the Implementation of a Satellite FDIR
NASA Astrophysics Data System (ADS)
Guiotto, A.; Martelli, A.; Paccagnini, C.
Nowadays space activities are characterized by increased constraints in terms of on-board computing power and functional complexity combined with reduction of costs and schedule. This scenario necessarily originates impacts on the on-board software with particular emphases to the interfaces between on-board software and system/mission level requirements. The questions are: How can the effectiveness of Space System Software design be improved? How can we increase sophistication in the area of autonomy and failure tolerance, maintaining the necessary quality with acceptable risks?
Liu, Peize; Chen, Zhen; Yang, Lijie; Li, Qingbiao; He, Ning
2017-09-26
Polysaccharides and poly-γ-glutamic acid (γ-PGA) are biomacromolecules that have been reported as bioflocculants, and they exhibit high flocculating activity in many industrial applications. Bacillus licheniformis CGMCC 2876 can produce polysaccharide and γ-PGA bioflocculants under different culture conditions. Several key genes are involved in the metabolic pathway of polysaccharides in B. licheniformis, but the impacts of the regulation of these genes on the production of polysaccharide bioflocculants have not been illustrated completely. To increase the bioflocculant production and identify the correlation between the synthesis of polysaccharides and γ-PGA in B. licheniformis, a few key genes were investigated to explore their influence on the synthesis of the bioflocculants. Overexpressing epsB from the eps gene cluster not only improved the bioflocculant crude yield by 13.98% but also enhanced the flocculating activity by 117.92%. The composition of the bioflocculant from the epsB recombinant strain was 28.95% total sugar, 3.464% protein and 44.03% γ-PGA, while in the original strain, these components represented 53.67%, 3.246% and 34.13%, respectively. In combination with an analysis of the transcriptional levels of several key genes involved in γ-PGA synthesis in B. licheniformis, we inferred that epsB played a key role in the synthesis of both polysaccharide and γ-PGA. The bioflocculant production of the epsB recombinant strain was further evaluated during batch fermentation in a 2 L fermenter; the flocculating activity reached 9612.75 U/mL, and the bioflocculant yield reached 10.26 g/L after 72 h, representing increases of 224% and 36.62%, respectively, compared with the original strain. Moreover, we found that the tandem expression of phosphoglucomutase (pgcA) and UTP-glucose-1-phosphate uridylyltransferase (gtaB1) could enhance the crude yield of the bioflocculant by 20.77% and that the overexpression of epsA could enhance the bioflocculant yield by 23.70% compared with the original strain. This study provides a new method to greatly increase the bioflocculant production in B. licheniformis, and it demonstrates the correlation between the biosynthesis of polysaccharide and γ-PGA during EPS fermentation by regulating the expression of EpsB.
Active commuting to and from school among Swedish children--a national and regional study.
Johansson, Klara; Laflamme, Lucie; Hasselberg, Marie
2012-04-01
Active commuting to school by walking or cycling can have positive impact on children's health and development. The study investigates the prevalence of active commuting to school in Sweden, a setting where it is facilitated and promoted; and how active commuting varies according to socio-demographic and socio-economic characteristics. Self-reports from a national sample of Swedish children (11- to 15-year-olds, n = 4415) and a regional one from Stockholm County (13-year-olds, n = 1008) on transport to school were compared. The association that active commuting has with socio-demographic (gender, school grade, Swedish origin, type of housing, urbanicity in the local area), and socio-economic characteristics (household socio-economic status, family car ownership) was studied using logistic regression, controlling for car ownership and urbanicity, respectively. Active commuting was high (62.9% in the national sample) but decreased with age-76% at the age of 11 years, 62% at the age of 13 years and 50% at the age of 15 years-whereas public transport increased (19-43%). Living in an apartment or row-house (compared with detached house) and living in a medium-sized city (compared with a metropolitan area) was associated with active commuting. In urban areas, active commuting was more common in worker households compared with intermediate- to high-level salaried employees. Active commuting is common but decreases with age. Active commuting differed based on housing and urbanicity but not based on gender or Swedish origin, and impact of socio-economic factors differed depending on level of urbanicity.
Engel, Dominique; Seutin, Vincent
2015-11-15
The hyperpolarization-activated cation current Ih is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown. We used cell-attached patch recordings to determine the localization profile of Ih along the somatodendritic axis of nigral dopamine neurons in slices from young rats. Ih density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma and axon-lacking dendrites. Dual current-clamp recordings revealed a similar contribution of Ih to the waveform of single excitatory postsynaptic potentials throughout the somatodendritic domain. The Ih blocker ZD 7288 increased the temporal summation in all dendrites with a comparable effect in axon- and non-axon dendrites. The strategic position of Ih in the proximity of the axon may influence importantly transitions between pacemaker and bursting activities and consequently the downstream release of dopamine. Dendrites of most neurons express voltage-gated ion channels in their membrane. In combination with passive properties, active currents confer to dendrites a high computational potential. The hyperpolarization-activated cation current Ih present in the dendrites of some pyramidal neurons affects their membrane and integration properties, synaptic plasticity and higher functions such as memory. A gradient of increasing h-channel density towards distal dendrites has been found to be responsible for the location independence of excitatory postsynaptic potential (EPSP) waveform and temporal summation in cortical and hippocampal pyramidal cells. However, reports on other cell types revealed that smoother gradients or even linear distributions of Ih can achieve homogeneous temporal summation. Although the existence of a robust, slowly activating Ih current has been repeatedly demonstrated in nigral dopamine neurons, its subcellular distribution and precise role in synaptic integration are unknown. Using cell-attached patch-clamp recordings, we find a higher Ih current density in the axon-bearing dendrite than in the soma or in dendrites without axon in nigral dopamine neurons. Ih is mainly concentrated in the dendritic membrane area surrounding the axon origin and decreases with increasing distances from this site. Single EPSPs and temporal summation are similarly affected by blockade of Ih in axon- and non-axon-bearing dendrites. The presence of Ih close to the axon is pivotal to control the integrative functions and the output signal of dopamine neurons and may consequently influence the downstream coding of movement. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
Effect of water activity on rates of serpentinization of olivine.
Lamadrid, Hector M; Rimstidt, J Donald; Schwarzenbach, Esther M; Klein, Frieder; Ulrich, Sarah; Dolocan, Andrei; Bodnar, Robert J
2017-07-14
The hydrothermal alteration of mantle rocks (referred to as serpentinization) occurs in submarine environments extending from mid-ocean ridges to subduction zones. Serpentinization affects the physical and chemical properties of oceanic lithosphere, represents one of the major mechanisms driving mass exchange between the mantle and the Earth's surface, and is central to current origin of life hypotheses as well as the search for microbial life on the icy moons of Jupiter and Saturn. In spite of increasing interest in the serpentinization process by researchers in diverse fields, the rates of serpentinization and the controlling factors are poorly understood. Here we use a novel in situ experimental method involving olivine micro-reactors and show that the rate of serpentinization is strongly controlled by the salinity (water activity) of the reacting fluid and demonstrate that the rate of serpentinization of olivine slows down as salinity increases and H 2 O activity decreases.
Effect of water activity on rates of serpentinization of olivine
NASA Astrophysics Data System (ADS)
Lamadrid, Hector M.; Rimstidt, J. Donald; Schwarzenbach, Esther M.; Klein, Frieder; Ulrich, Sarah; Dolocan, Andrei; Bodnar, Robert J.
2017-07-01
The hydrothermal alteration of mantle rocks (referred to as serpentinization) occurs in submarine environments extending from mid-ocean ridges to subduction zones. Serpentinization affects the physical and chemical properties of oceanic lithosphere, represents one of the major mechanisms driving mass exchange between the mantle and the Earth's surface, and is central to current origin of life hypotheses as well as the search for microbial life on the icy moons of Jupiter and Saturn. In spite of increasing interest in the serpentinization process by researchers in diverse fields, the rates of serpentinization and the controlling factors are poorly understood. Here we use a novel in situ experimental method involving olivine micro-reactors and show that the rate of serpentinization is strongly controlled by the salinity (water activity) of the reacting fluid and demonstrate that the rate of serpentinization of olivine slows down as salinity increases and H2O activity decreases.
Effect of water activity on rates of serpentinization of olivine
Lamadrid, Hector M.; Rimstidt, J. Donald; Schwarzenbach, Esther M.; Klein, Frieder; Ulrich, Sarah; Dolocan, Andrei; Bodnar, Robert J.
2017-01-01
The hydrothermal alteration of mantle rocks (referred to as serpentinization) occurs in submarine environments extending from mid-ocean ridges to subduction zones. Serpentinization affects the physical and chemical properties of oceanic lithosphere, represents one of the major mechanisms driving mass exchange between the mantle and the Earth’s surface, and is central to current origin of life hypotheses as well as the search for microbial life on the icy moons of Jupiter and Saturn. In spite of increasing interest in the serpentinization process by researchers in diverse fields, the rates of serpentinization and the controlling factors are poorly understood. Here we use a novel in situ experimental method involving olivine micro-reactors and show that the rate of serpentinization is strongly controlled by the salinity (water activity) of the reacting fluid and demonstrate that the rate of serpentinization of olivine slows down as salinity increases and H2O activity decreases. PMID:28706268
Arctic Storms and Their Influence on Surface Climate in the Chukchi-Beaufort Seas
NASA Astrophysics Data System (ADS)
Yang, Y.; Zhang, X.; Rinke, A.; Zhang, J.
2017-12-01
Increases in the frequency and intensity of Arctic storms and resulting weather hazards may endanger the offshore environment, coastal community, and energy infrastructure in the Arctic as sea ice retreats. Advancing ability to identify fine-scale variations in surface climate produced by progressively stronger storm would be extremely helpful to resources management and sustainable development for coastal community. In this study, we analyzed the storms and their impacts on surface climate over the Beaufort-Chukchi seas by employing the date sets from both the hindcast simulations of the coupled Arctic regional climate model HIRHAM-NAOSIM and the recently developed Chukchi-Beaufort High-resolution Atmospheric Reanalysis (CBHAR). Based on the characteristics of spatial pattern and temporal variability of the Arctic storm activity, we categorized storms to three groups with their different origins: the East Siberia Sea, Alaska and the central Arctic Ocean. The storms originating from the central Arctic Ocean have the strongest intensity in winter with relatively less storm number. Storms traveling from Alaska to the Beaufort Sea most frequently occurred in autumn with weaker intensity. A large portion of storms originated from the East Siberia Sea region in summer. Further statistical analysis suggests that increase in surface air temperature and wind speed could be attributed to the increased frequency of storm occurrence in autumn (September to November) along the continental shelf in the Beaufort Sea.
Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe.
Pratihar, Aditya S; Tripathi, Vishnu P; Yadav, Mukesh P; Dubey, Dharani D
2015-12-01
Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2004, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2004 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727- associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2004 or ars727 remains unaltered by the extended chromosomal context.
Umstattd Meyer, M Renée; Walsh, Shana M; Sharkey, Joseph R; Morgan, Grant B; Nalty, Courtney C
2014-09-16
Colonias are substandard residential areas along the U.S.-Mexico border. Families of Mexican-origin living in colonias face health burdens characterized by environmental and socioeconomic hardships. Mexican Americans and low-income families, including colonias children, do not frequently participate in physical activity despite the known link to disease risk reduction. For colonias children, schools are the most commonly reported location for physical activity. School closures and extreme temperatures during summer months create a need to explore seasonal differences in environmental supports and barriers in this population. The purpose of this study was to examine the effect of seasonality on perceived environmental barriers, opportunities, and social support for physical activity among colonias children. As a secondary aim, mother-child discordance for each factor was analyzed. Promotora-researchers recruited mother-child dyads (n=101 dyads, n=202 participants) from colonias in Hidalgo County, Texas. Mothers and children were separately administered surveys at two time points to capture perceived barriers, opportunities, and social support for physical activity (school-year: February-May; summertime: July-August). Summative scores for each outcome were calculated and three multilevel longitudinal models for continuous outcomes were examined; children were nested within households. Mother-child discordance was measured using Cohen's Kappa statistic. Physical activity barriers and environmental opportunities (household and neighborhood) increased from school-year to summer by 1.16 and 2.83 points respectively (p≤0.01), after adjusting for covariates. Significant predictors of increased barriers included household income of >$900/month and having more household members. Children of mothers with significant others who were employed part-time or full-time saw significant decreases in barriers. Mother-child agreement of barriers, environmental opportunities, and social support across seasons was slight to fair (range: median κ=0.047 to κ=0.262). These results suggest a complex relationship between dimensions of economic hardship (employment status, household income, etc…) and perceived opportunities and barriers of children's physical activity engagement during the school-year and summer. In this study, both barriers and opportunities increased from school-year to summer, further demonstrating that interactions among these characteristics need to be better understood and addressed when considering physical activity initiatives for colonias and other Mexican-American children, specifically during summer when school-based physical activity resources are unavailable.
Duplication of the genome in normal and cancer cell cycles.
Bandura, Jennifer L; Calvi, Brian R
2002-01-01
It is critical to discover the mechanisms of normal cell cycle regulation if we are to fully understand what goes awry in cancer cells. The normal eukaryotic cell tightly regulates the activity of origins of DNA replication so that the genome is duplicated exactly once per cell cycle. Over the last ten years much has been learned concerning the cell cycle regulation of origin activity. It is now clear that the proteins and cell cycle mechanisms that control origin activity are largely conserved from yeast to humans. Despite this conservation, the composition of origins of DNA replication in higher eukaryotes remains ill defined. A DNA consensus for predicting origins has yet to emerge, and it is of some debate whether primary DNA sequence determines where replication initiates. In this review we outline what is known about origin structure and the mechanism of once per cell cycle DNA replication with an emphasis on recent advances in mammalian cells. We discuss the possible relevance of these regulatory pathways for cancer biology and therapy.
Replication in hydroxyurea: it's a matter of time.
Alvino, Gina M; Collingwood, David; Murphy, John M; Delrow, Jeffrey; Brewer, Bonita J; Raghuraman, M K
2007-09-01
Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.
Reflex control of discharge in motor fibres to the larynx
Głogowska, Maria; Stransky, A.; Widdicombe, J. G.
1974-01-01
1. Action potentials have been recorded from single laryngeal motor fibres, with expiratory or inspiratory phases, in cats anaesthetized with pentobarbitone and breathing through a tracheal cannula. 2. Pneumothorax increased the discharge of both inspiratory and expiratory units, the inspiratory response being greatly reduced by bilateral vagotomy below the origin of the recurrent laryngeal nerves. 3. Addition of a `viscous' resistance to breathing, or asphyxial rebreathing through an added dead space, increased the activity of inspiratory units and decreased that of expiratory units. 4. Induction of pulmonary oedema decreased the discharge of inspiratory units and increased that of expiratory units. After vagotomy the response of inspiratory units was reversed. 5. Intravenous injections of potassium cyanide increased the activity of both types of unit. 6. Chemical irritation of the laryngeal mucosa decreased the discharge of inspiratory units and increased that of expiratory units, whether the vagi were intact or cut. 7. It is concluded that expiratory unit discharge can be correlated with expiratory laryngeal resistance, but that inspiratory unit discharge does not correlate so well with inspiratory laryngeal resistance. 8. The relationship between laryngeal motor-fibre activity and the contractions of the inspiratory and expiratory muscles of breathing is discussed. PMID:4415512
Excretion of lead and its biological activity several years after termination of exposure
Přerovská, I.; Teisinger, J.
1970-01-01
Přerovská, and Teisinger, J. (1970).Brit. J. industr. Med.,27, 352-355. Excretion of lead and its biological activity several years after termination of exposure. A group of 27 persons who had been treated some years previously for chronic lead poisoning at our clinic, and who had not come into occupational contact with lead since, was examined. Half of them had had no occupational exposure to lead for 3 to 5 years and the others for 8 to 17 years. In most of these persons there is still an increased lead excretion, originating from an increased deposit in the bones. The mobilization test after calcium versenate (CaEDTA) injection was greater than 0·350 mg/24 hours. The values found for haemoglobin, punctate basophilia, coproporphyrin and ALA in urine were normal, but there was, in all cases, a decreased ALA-D activity. This finding suggests biological activity of such negligible lead flow many years after termination of exposure. PMID:5488694
Oxygen Vacancies in ZnO Nanosheets Enhance CO2 Electrochemical Reduction to CO.
Geng, Zhigang; Kong, Xiangdong; Chen, Weiwei; Su, Hongyang; Liu, Yan; Cai, Fan; Wang, Guoxiong; Zeng, Jie
2018-05-22
As electron transfer to CO 2 is generally considered to be the critical step during the activation of CO 2 , it is important to develop approaches to engineer the electronic properties of catalysts to improve their performance in CO 2 electrochemical reduction. Herein, we developed an efficient strategy to facilitate CO 2 activation by introducing oxygen vacancies into electrocatalysts with electronic-rich surface. ZnO nanosheets rich in oxygen vacancies exhibited a current density of -16.1 mA cm -2 with a Faradaic efficiency of 83 % for CO production. Based on density functional theory (DFT) calculations, the introduction of oxygen vacancies increased the charge density of ZnO around the valence band maximum, resulting in the enhanced activation of CO 2 . Mechanistic studies further revealed that the enhancement of CO production by introducing oxygen vacancies into ZnO nanosheets originated from the increased binding strength of CO 2 and the eased CO 2 activation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hoggett, J G; Brierley, I
1992-01-01
The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid. PMID:1445251
Hoggett, J G; Brierley, I
1992-11-01
The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid.
Mapping replication origins in yeast chromosomes.
Brewer, B J; Fangman, W L
1991-07-01
The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.
Lateral Spread of Orientation Selectivity in V1 is Controlled by Intracortical Cooperativity
Chavane, Frédéric; Sharon, Dahlia; Jancke, Dirk; Marre, Olivier; Frégnac, Yves; Grinvald, Amiram
2011-01-01
Neurons in the primary visual cortex receive subliminal information originating from the periphery of their receptive fields (RF) through a variety of cortical connections. In the cat primary visual cortex, long-range horizontal axons have been reported to preferentially bind to distant columns of similar orientation preferences, whereas feedback connections from higher visual areas provide a more diverse functional input. To understand the role of these lateral interactions, it is crucial to characterize their effective functional connectivity and tuning properties. However, the overall functional impact of cortical lateral connections, whatever their anatomical origin, is unknown since it has never been directly characterized. Using direct measurements of postsynaptic integration in cat areas 17 and 18, we performed multi-scale assessments of the functional impact of visually driven lateral networks. Voltage-sensitive dye imaging showed that local oriented stimuli evoke an orientation-selective activity that remains confined to the cortical feedforward imprint of the stimulus. Beyond a distance of one hypercolumn, the lateral spread of cortical activity gradually lost its orientation preference approximated as an exponential with a space constant of about 1 mm. Intracellular recordings showed that this loss of orientation selectivity arises from the diversity of converging synaptic input patterns originating from outside the classical RF. In contrast, when the stimulus size was increased, we observed orientation-selective spread of activation beyond the feedforward imprint. We conclude that stimulus-induced cooperativity enhances the long-range orientation-selective spread. PMID:21629708
Trends in the epidemiology of childhood tuberculosis in Greece.
Syridou, G; Mavrikou, M; Amanatidou, V; Spyridis, N; Prasad, P; Papaventsis, D; Kanavaki, S; Zaoutis, Th; Tsolia, M N
2012-06-01
A hospital referral center for childhood tuberculosis (TB). To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade. We retrospectively reviewed the medical records of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed. A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001). In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent.
Increasing seismicity in the U. S. midcontinent: Implications for earthquake hazard
Ellsworth, William L.; Llenos, Andrea L.; McGarr, Arthur F.; Michael, Andrew J.; Rubinstein, Justin L.; Mueller, Charles S.; Petersen, Mark D.; Calais, Eric
2015-01-01
Earthquake activity in parts of the central United States has increased dramatically in recent years. The space-time distribution of the increased seismicity, as well as numerous published case studies, indicates that the increase is of anthropogenic origin, principally driven by injection of wastewater coproduced with oil and gas from tight formations. Enhanced oil recovery and long-term production also contribute to seismicity at a few locations. Preliminary hazard models indicate that areas experiencing the highest rate of earthquakes in 2014 have a short-term (one-year) hazard comparable to or higher than the hazard in the source region of tectonic earthquakes in the New Madrid and Charleston seismic zones.
Scholar Quest: A Residency Research Program Aligned with Faculty Goals
Panchal, Ashish R.; Stolz, Uwe; Denninghoff, Kurt R.; Munger, Benson
2014-01-01
Introduction: The ACGME requires that residents perform scholarly activities prior to graduation, but this is difficult to complete and challenging to support. We describe a residency research program, taking advantage of environmental change aligning resident and faculty goals, to become a contributor to departmental cultural change and research development. Methods: A research program, Scholar Quest (SQ), was developed as a part of an Information Mastery program. The goal of SQ is for residents to gain understanding of scholarly activity through a mentor-directed experience in original research. This curriculum is facilitated by providing residents protected time for didactics, seed grants and statistical/staff support. We evaluated total scholarly activity and resident/faculty involvement before and after implementation (PRE-SQ; 2003–2005 and POST-SQ; 2007–2009). Results: Scholarly activity was greater POST-SQ versus PRE-SQ (123 versus 27) (p<0.05) with an incidence rate ratio (IRR)=2.35. Resident and faculty involvement in scholarly activity also increased PRE-SQ to POST-SQ (22 to 98 residents; 10 to 39 faculty, p<0.05) with an IRR=2.87 and 2.69, respectively. Conclusion: Implementation of a program using department environmental change promoting a resident longitudinal research curriculum yielded increased resident and faculty scholarly involvement, as well as an increase in total scholarly activity. PMID:24868308
The Narrative Impact of Active Video Games on Physical Activity Among Children: A Feasibility Study.
Lu, Amy Shirong; Baranowski, Tom; Hong, S Lee; Buday, Richard; Thompson, Debbe; Beltran, Alicia; Dadabhoy, Hafza Razak; Chen, Tzu-An
2016-10-14
Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children's AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influence behaviors. The objective of this study was to test the hypothesis that a narrative would motivate increased AVG play, though a feasibility study that investigated the motivational effect of adding a previously developed narrative cutscene to an originally nonnarrative AVG, Nintendo Wii Sports Resort: Swordplay Showdown. A total of 40 overweight and obese 8- to 11-year-olds equally divided by sex played the AVG. Half (n=20) were randomly assigned to a narrative group that watched the narrative cutscene before game play. The other half played the game without watching it. Children in the narrative group had significantly (P<.05) more steps per 10-second period (mean 3.2, SD 0.7) and overall (mean 523, SD 203) during game play compared with the nonnarrative group (10-second period: mean 2.7, SD 0.7; overall: mean 366, SD 172). The AVG with narrative induced increased physical activity. Additional research is needed to understand the mechanisms through which narrative increases physical activity during AVG game play.
The Narrative Impact of Active Video Games on Physical Activity Among Children: A Feasibility Study
Baranowski, Tom; Hong, S Lee; Buday, Richard; Thompson, Debbe; Beltran, Alicia; Dadabhoy, Hafza Razak; Chen, Tzu-An
2016-01-01
Background Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children’s AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influence behaviors. Objective The objective of this study was to test the hypothesis that a narrative would motivate increased AVG play, though a feasibility study that investigated the motivational effect of adding a previously developed narrative cutscene to an originally nonnarrative AVG, Nintendo Wii Sports Resort: Swordplay Showdown. Methods A total of 40 overweight and obese 8- to 11-year-olds equally divided by sex played the AVG. Half (n=20) were randomly assigned to a narrative group that watched the narrative cutscene before game play. The other half played the game without watching it. Results Children in the narrative group had significantly (P<.05) more steps per 10-second period (mean 3.2, SD 0.7) and overall (mean 523, SD 203) during game play compared with the nonnarrative group (10-second period: mean 2.7, SD 0.7; overall: mean 366, SD 172). Conclusions The AVG with narrative induced increased physical activity. Additional research is needed to understand the mechanisms through which narrative increases physical activity during AVG game play. PMID:27742605
Razumnikova, O M; Vol'f, N V; Tarasova, I V
2007-01-01
Effect of extrinsic motivation stimulating the most original problem solving during verbal and figurative divergent thinking was studied by EEG mapping. The righthanded university students (27 males and 26 females) participated in the experiments. An instruction "to create the most original solution" as compared to condition with an instruction "to create any solution" induced an increase in the baseline power of the alpha 1 and alpha 2 rhythms most pronounced in the posterior cortex. Task-related desynchronization of the alpha rhythms was higher but the beta-2 synchronization was lower after the former than after the latter instruction. Differences in the asymmetry of the alpha 1 and alpha 2 rhythms in the parietal and temporal regions of hemispheres suggested the right hemisphere dominance in intrinsic alertness and evoked activation related to divergent thinking. The findings were common and gender-independent in both figurative and verbal tasks suggesting a generalized influence of extrinsic motivation on creative activity.
Evidence-based lifestyle interventions in the workplace--an overview.
Schröer, S; Haupt, J; Pieper, C
2014-01-01
Lifestyle-related health issues affect the economic position of organizations and contribute to reduced productivity, increased absenteeism and health care costs. To summarize the effectiveness of different workplace health interventions for promoting healthy lifestyle, preventing diseases and reducing health care costs. We searched MEDLINE via Pubmed, EMBASE, Cochrane Library, NelH, HighWire Press and Google Scholar in March 2012. Systematic reviews and meta-analyses of workplace interventions aimed at promoting physical activity, healthy weight and good nutrition were included. Three authors assessed the quality of the reviews and extracted data on methods, interventions, outcomes, results and effect sizes. We identified 15 publications covering a total of 379 original studies. Three systematic reviews found beneficial effects of workplace nutrition interventions on employees' dietary behaviour. Three reviews found multi-component physical activity interventions to be effective in increasing employees' physical activity and fitness. The other activity promotion interventions were less effective regarding physical activity and weight-related outcomes. In terms of weight management, our findings favour multi-component interventions that focus on both physical activity and nutrition over single dietary programmes. Workplace health promotion interventions may improve physical activity, dietary behaviour and healthy weight. There is no evidence of increased efficacy associated with specific intervention types. Workplace health promotion should focus on either physical activity or weight or nutrition behaviour to maximize effectiveness. Best evidence is available for multi-component interventions.
Concurrent activation of striatal direct and indirect pathways during action initiation.
Cui, Guohong; Jun, Sang Beom; Jin, Xin; Pham, Michael D; Vogel, Steven S; Lovinger, David M; Costa, Rui M
2013-02-14
The basal ganglia are subcortical nuclei that control voluntary actions, and they are affected by a number of debilitating neurological disorders. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum--the so-called direct and indirect pathways--have opposing effects on movement: activity of direct-pathway SPNs is thought to facilitate movement, whereas activity of indirect-pathway SPNs is presumed to inhibit movement. This model has been difficult to test owing to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. Here we develop a novel in vivo method to specifically measure direct- and indirect-pathway SPN activity, using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCaMP3 in the dorsal striatum of D1-Cre (direct-pathway-specific) and A2A-Cre (indirect-pathway-specific) mice. Using fibre optics and time-correlated single-photon counting (TCSPC) in mice performing an operant task, we observed transient increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.
Viviani, Vadim R; Scorsato, Valeria; Prado, Rogilene A; Pereira, Jose G C; Niwa, Kazuki; Ohmiya, Yoshihiro; Barbosa, João A R G
2010-08-01
Beetle luciferases evolved from AMP/CoA-ligases. However, it is unclear how the new luciferase activity evolved. In order to clarify this question, we compared the luminescence and catalytic properties of a recently cloned luciferase-like enzyme from Zophobas mealworm, an AMP/CoA-ligase displaying weak luminescence activity, with those of cloned luciferases from the three main families of luminescent beetles: Phrixthrix hirtus railroad worm; Pyrearinus termitilluminans click beetle and Photinus pyralis firefly. The catalytic constant of the mealworm enzyme was 2-4 orders of magnitude lower than that of beetle luciferases, but 3 orders of magnitude above the non-catalyzed chemiluminescence of luciferyl-adenylate in buffer. Studies with D- and L-luciferin and their adenylates show that the luminescence reaction of the luciferase-like enzyme and beetle luciferases are stereoselective for D-luciferin and its adenylate, and that the selectivity is determined mainly at the adenylation step. Modelling studies showed that the luciferin binding site cavity of this enzyme is smaller and more hydrophobic than that of beetle luciferases. Therefore Zophobas mealworm enzyme displays true luciferase activity, keeping the attributes of an ancient protoluciferase. These results suggest that stereoselectivity for D-luciferin may have been a key event for the origin of oxygenase/luciferase activity in AMP/CoA-ligases, and that efficient luciferase activity may have further evolved mainly by increasing the catalytic constant of the oxidative reaction and the quantum yield of bioluminescence.
Relationship between human physiological parameters and geomagnetic variations of solar origin
NASA Astrophysics Data System (ADS)
Dimitrova, S.
Results presented concern influence of increased geomagnetic activity on some human physiological parameters. The blood pressure and heart rate of 86 volunteers were measured on working days in autumn 2001 (01/10 09/11) and in spring 2002 (08/04 28/05). These periods were chosen because of maximal expected geomagnetic activity. Altogether 2799 recordings were obtained and analysed. Questionnaire information about subjective psycho-physiological complaints was also gathered. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The factors were the following: (1) planetary geomagnetic activity level estimated by Ap-index and divided into five levels; (2) gender males and females; (3) blood pressure degree persons in the group examined were divided into hypotensive, normotensive and hypertensive. Post hoc analysis was performed to elicit the significance of differences in the factors’ levels. The average arterial blood pressure of the group was found to increase significantly with the increase of geomagnetic activity level. The average increment of systolic and diastolic blood pressure of the group examined reached 9%. This effect was present irrespectively of gender. Results obtained suppose that hypertensive persons have the highest sensitivity and the hypotensive persons have the lowest sensitivity of the arterial blood pressure to increase of geomagnetic activity. The results did not show significant changes in the heart rate. The percentage of the persons who reported subjective psycho-physiological complaints was also found to increase significantly with the geomagnetic activity increase and the highest sensitivity was revealed for the hypertensive females.
Code of Federal Regulations, 2013 CFR
2013-07-01
... management activities under a RAP at a location removed from the area where the remediation wastes originated... management activities under a RAP at a location removed from the area where the remediation wastes originated? (a) You may request a RAP for remediation waste management activities at a location removed from the...
Code of Federal Regulations, 2012 CFR
2012-07-01
... management activities under a RAP at a location removed from the area where the remediation wastes originated... management activities under a RAP at a location removed from the area where the remediation wastes originated? (a) You may request a RAP for remediation waste management activities at a location removed from the...
Cadmium removal from wastewater by sponge iron sphere prepared by hydrogen reduction.
Li, Junguo; Wei, Linghong; Li, Yungang; Bi, Na; Song, Fangfang
2011-06-01
A new type of sponge iron sphere (NSIS) with 1-5 mm diameter, made of concentrated iron powder and possessed high activity and intension, was prepared by mini-pellet sintering integrated with H2 direct reduction. Static state experiment has been carried on to investigate the Cd(2+) removal efficiency from wastewater by the NSIS and to explore the Cd(2+) removal reaction kinetics. It was suggested that initial pH value and Cd(2+) original concentration had significant influence on Cd(2+) removal percentage. Cd(2+) removal percentage decreased significantly with the increasing of Cd(2+)original concentration whether the original pH value be adjusted to 3.0 or without adjustment. The results showed that the Cd(2+) removal process followed the first order reaction because the reaction order was from 0.803 to 0.996. The apparent reaction rate constant between Cd(2+) and NSIS was from 0.0025 to 0.1000 (mg·L(-1))(1-n)·min(-1). Compared with SIS reduced by charcoal reduction, NSIS deoxided by hydrogen possessed higher activity, and could remove the same quantity of Cd(2+) within a shorter period of time. Copyright © 2011 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.
Natural thorium isotopes in marine sediment core off Labuan port
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hafidz, B. Y.; Asnor, A. S.; Terence, R. C.
2014-02-12
Sediment core was collected from Labuan port and analyzed to determine the radioactivity of thorium (Th) isotopes. The objectives of this study are to determine the possible sources of Th isotopes at Labuan port and estimates the sedimentation rate based on {sup 228}Th/{sup 232}Th model. The results suggest the {sup 230}Th and {sup 232}Th might be originated from terrestrial sedimentary rock while {sup 228}Th originated by authigenic origin. High ratio value of {sup 230}Th/{sup 232}Th detected at the top surface sediment indicates the increasing of {sup 230}Th at the recent years which might be contributed from the anthropogenic sources. Themore » sedimentation rate of core sediment from Labuan Port was successfully estimated by using {sup 228}Th/{sup 232}Th model. The result show high sedimentation rate with 4.67 cm/year indicates rapid deposition occurred at this study area due to the high physical activity at the Labuan port. By assume the constant sedimentation rate at this area; we estimated the age of 142 cm core sediment obtained from Labuan port is 32 years started from 1981 to 2012. This chronology will be used in forthcoming research to investigate the historical profile of anthropogenic activities affecting the Labuan port.« less
Influence of local vibration on plasma creatine phosphokinase (CPK) activity.
Okada, A; Okuda, H; Inaba, R; Ariizumi, M
1985-01-01
This study was designed to obtain basic information about the mechanism of the occurrence of muscular disorders after exposure to vibration. The hind legs of rats were exposed to acute and chronic local vibration at frequencies of 30, 60, 120, 240, 480, and 960 Hz with a constant acceleration of 50 m/sec2. The exposure time was four hours for acute, and four hours a day for two weeks continuously for chronic exposure. Blood was collected after exposure to measure plasma creatine phosphokinase (CPK) activity. In both exposure groups the activity of plasma CPK was significantly higher at 30, 60, 120, 240, and 480 Hz compared with the control group and was especially high at 30 Hz; there was no significant change at 960 Hz. As a result of an analysis of the CPK isoenzymes, the increase in plasma CPK activity was shown to be due to the activity of the plasma CPK-MM fraction, originating in the skeletal muscle. Plasma CPK activity showed a tendency to decrease gradually with the increase in vibration frequency during acute exposure but showed no such tendency during chronic exposure. There was no remarkable pathohistological change in muscle preparations from the hind legs, hence it was presumed that the increase in plasma CPK activity was caused not by the morphological changes of muscle but by other mechanisms, such as an increase in the permeability of the cell membrane. Images PMID:4041385
NASA Astrophysics Data System (ADS)
Schelkanova, Irina; Toronov, Vladislav
2011-07-01
Although near infrared spectroscopy (NIRS) is now widely used both in emerging clinical techniques and in cognitive neuroscience, the development of the apparatuses and signal processing methods for these applications is still a hot research topic. The main unresolved problem in functional NIRS is the separation of functional signals from the contaminations by systemic and local physiological fluctuations. This problem was approached by using various signal processing methods, including blind signal separation techniques. In particular, principal component analysis (PCA) and independent component analysis (ICA) were applied to the data acquired at the same wavelength and at multiple sites on the human or animal heads during functional activation. These signal processing procedures resulted in a number of principal or independent components that could be attributed to functional activity but their physiological meaning remained unknown. On the other hand, the best physiological specificity is provided by broadband NIRS. Also, a comparison with functional magnetic resonance imaging (fMRI) allows determining the spatial origin of fNIRS signals. In this study we applied PCA and ICA to broadband NIRS data to distill the components correlating with the breath hold activation paradigm and compared them with the simultaneously acquired fMRI signals. Breath holding was used because it generates blood carbon dioxide (CO2) which increases the blood-oxygen-level-dependent (BOLD) signal as CO2 acts as a cerebral vasodilator. Vasodilation causes increased cerebral blood flow which washes deoxyhaemoglobin out of the cerebral capillary bed thus increasing both the cerebral blood volume and oxygenation. Although the original signals were quite diverse, we found very few different components which corresponded to fMRI signals at different locations in the brain and to different physiological chromophores.
Lewan, M.D.; Warden, A.; Dias, R.F.; Lowry, Z.K.; Hannah, T.L.; Lillis, P.G.; Kokaly, R.F.; Hoefen, T.M.; Swayze, G.A.; Mills, C.T.; Harris, S.H.; Plumlee, G.S.
2014-01-01
The composition and content of asphaltenes in spilled and original wellhead oils from the Deepwater Horizon (DWH) incident provide information on the amount of original oil lost and the processes most responsible for the losses within the first 80 days of the active spill. Spilled oils were collected from open waters, coastal waters and coastal sediments during the incident. Asphaltenes are the most refractory component of crude oils but their alteration in the spilled oils during weathering prevents them from being used directly as a conservative component to calculate original oil losses. The alteration is reflected by their increase in oxygen content and depletion in 12C. Reconnaissance experiments involving evaporation, photo-oxidation, microbial degradation, dissolution, dispersion and burning indicate that the combined effects of photo-oxidation and evaporation are responsible for these compositional changes. Based on measured losses and altered asphaltenes from these experiments, a mean of 61 ± 3 vol% of the original oil was lost from the surface spilled oils during the incident. This mean percentage of original oil loss is considerably larger than previous estimates of evaporative losses based on only gas chromatography (GC) amenable hydrocarbons (32–50 vol%), and highlights the importance of using asphaltenes, as well as GC amenable parameters in evaluating original oil losses and the processes responsible for the losses.
Reconstructing Global-scale Ionospheric Outflow With a Satellite Constellation
NASA Astrophysics Data System (ADS)
Liemohn, M. W.; Welling, D. T.; Jahn, J. M.; Valek, P. W.; Elliott, H. A.; Ilie, R.; Khazanov, G. V.; Glocer, A.; Ganushkina, N. Y.; Zou, S.
2017-12-01
The question of how many satellites it would take to accurately map the spatial distribution of ionospheric outflow is addressed in this study. Given an outflow spatial map, this image is then reconstructed from a limited number virtual satellite pass extractions from the original values. An assessment is conducted of the goodness of fit as a function of number of satellites in the reconstruction, placement of the satellite trajectories relative to the polar cap and auroral oval, season and universal time (i.e., dipole tilt relative to the Sun), geomagnetic activity level, and interpolation technique. It is found that the accuracy of the reconstructions increases sharply from one to a few satellites, but then improves only marginally with additional spacecraft beyond 4. Increased dwell time of the satellite trajectories in the auroral zone improves the reconstruction, therefore a high-but-not-exactly-polar orbit is most effective for this task. Local time coverage is also an important factor, shifting the auroral zone to different locations relative to the virtual satellite orbit paths. The expansion and contraction of the polar cap and auroral zone with geomagnetic activity influences the coverage of the key outflow regions, with different optimal orbit configurations for each level of activity. Finally, it is found that reconstructing each magnetic latitude band individually produces a better fit to the original image than 2-D image reconstruction method (e.g., triangulation). A high-latitude, high-altitude constellation mission concept is presented that achieves acceptably accurate outflow reconstructions.
On the Origin of Cortical Dopamine: Is it a Co-Transmitter in Noradrenergic Neurons?
Devoto, Paola; Flore, Giovanna
2006-01-01
Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA. To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter. Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas. Systemic administration or intra-cortical perfusion of α2-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex. Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC. Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced. Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of α2-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex. Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration. Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex. The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions. PMID:18615131
On the origin of cortical dopamine: is it a co-transmitter in noradrenergic neurons?
Devoto, Paola; Flore, Giovanna
2006-04-01
Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA.To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter.Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas.Systemic administration or intra-cortical perfusion of alpha(2)-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex.Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC.Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced.Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of alpha(2)-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex.Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration.Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex.The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions.
Zhang, Zhengping; Sun, Junting; Dou, Meiling; Ji, Jing; Wang, Feng
2017-05-17
To replace high-cost platinum group metal (PGM) electrocatalysts for oxygen reduction reaction (ORR) that is the crucial cathode reaction in fuel cell technology and metal-air battery, the development of low-cost and high-efficiency non-PGM catalysts for ORR has attracted much attention during the past decades. As one of the promising candidates, N-doped carbon is highly desirable for its strong designability and outstanding catalytic activity and stability. In this work, a facile and rational strategy is demonstrated for preparation of N,P-codoped mesoporous carbon (N,P-MC) for ORR by the direct pyrolysis treatment of polypyrrole with phytic acid as P-dopant and polystyrene sphere as template. The resultant N,P-MC exhibits a mesoporous structure with the optimized ORR active sites originating from the N,P-codoping. Owing to these features, N,P-MC exhibits excellent ORR activity, remarkable electrochemical stability, and superior methanol tolerance, comparable or even better than that of commercial Pt/C catalyst. The origin of enhanced ORR performance can be attributed to both the increased active sites and the mesoporous structure, which is expected to guide the future preparation of more capable carbon-based electrocatalysts for oxygen reduction and other electrocatalytic application.
[Gastrointestinal bleeding and potentially inappropriate medication by NSAIDs].
Pastor Cano, Josep; Aranda García, Ana; Sánchez Ruiz, José Francisco; Rausell Rausell, Víctor José; Tobaruela Soto, Mariana; Gascón Cánovas, Juan José
2018-05-28
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are widely used but they increase the risk of gastrointestinal haemorrage among other adverse effects. The objective of this study was to compare potentially inappropriate medications (PIM) by NSAIDs using the original Beers Criteria, a global reference for evaluating elderly people's prescriptions, and the Spanish adaptation of the same; and the relation between PIM of NSAIDs and gastrointestinal bleeding. The study was a retrospective observational study carried out located in a primary care district in the province of de Murcia, south-eastern Spain. The study population (n=7.856) were citizens aged 65 and above, with at least one drug prescribed in a Spanish health district during the study period . We analized illnesses and treatments registered in the primary care's electronic medical history of patients and hospital admissions, during the 12 month study period (2012). The original Beers Criteria and their Spanish adaptation were used to evaluate PIM of NSAIDs in patients considering the medication globally and also each active substance. Gastrointestinal bleeding events recorded in the data bases studied were evaluated. Detection of PIM of NSAIDs was 5,6% with the original version and 7,0% (Δ=25,5%; p less than 0,001) with the adapted one. PIM of NSAIDs was related with an increased incidence of gastrointestinal bleeding without significant differences between PIM exposed and NSAID exposed patients AINE (RR=1,6; IC:0,2-14,5). The Spanish adaptation of the Beers criteria identified a greater degree of PIM of NSAIDs than the original version, and in both versions the detection of PIM was not related with a significant increase of gastrointestinal bleeding compared to patients exposed to NSAIDs.
Bovo, Barbara; Carlot, Milena; Fontana, Federico; Lombardi, Angiolella; Soligo, Stefano; Giacomini, Alessio; Corich, Viviana
2015-04-01
Nowadays grape marc represents one of the main by-product of winemaking. Many South Europe countries valorize this ligno-cellulosic waste through fermentation and distillation for industrial alcoholic beverage production. The storage of marcs is a crucial phase in the distillation process, due to the physicochemical transformations ascribed to microbial activity. Among the methods adopted by distillers to improve the quality of spirits, the use of selected yeasts has not been explored so far, therefore in this work we evaluated the selection criteria of Saccharomyces cerevisiae strains for grape marc fermentation. The proposed selection procedure included three steps: characterization of phenotypical traits, evaluation of selected strains on pasteurised grape marc at lab-scale (100 g) and pilot-scale fermentation (350 kg). This selection process was applied on 104 strains isolated from grape marcs of different origins and technological treatment. Among physiological traits, β-glucosidase activity level as quality trait seems to be only partially involved in increasing varietal flavour. More effective in describing yeast impact on distillate quality is the ratio higher alcohols/esters that indicates strain ability to increase positive flavours. Finally, evaluating grape marc as source of selected yeasts, industrial treatment rather than varietal origin seems to shape strain technological and quality traits. Copyright © 2014 Elsevier Ltd. All rights reserved.
Composition of Coronal Mass Ejections
NASA Technical Reports Server (NTRS)
Zurbuchen, T. H.; Weberg, M.; von Steiger, R.; Mewaldt, R. A.; Lepri, S. T.; Antiochos, S. K.
2016-01-01
We analyze the physical origin of plasmas that are ejected from the solar corona. To address this issue, we perform a comprehensive analysis of the elemental composition of interplanetary coronal mass ejections (ICMEs) using recently released elemental composition data for Fe, Mg, Si, S, C, N, Ne, and He as compared to O and H. We find that ICMEs exhibit a systematic abundance increase of elements with first ionization potential (FIP) less than 10 electronvolts, as well as a significant increase of Ne as compared to quasi-stationary solar wind. ICME plasmas have a stronger FIP effect than slow wind, which indicates either that an FIP process is active during the ICME ejection or that a different type of solar plasma is injected into ICMEs. The observed FIP fractionation is largest during times when the Fe ionic charge states are elevated above Q (sub Fe) is greater than 12.0. For ICMEs with elevated charge states, the FIP effect is enhanced by 70 percent over that of the slow wind. We argue that the compositionally hot parts of ICMEs are active region loops that do not normally have access to the heliosphere through the processes that give rise to solar wind. We also discuss the implications of this result for solar energetic particles accelerated during solar eruptions and for the origin of the slow wind itself.
Composition of Coronal Mass Ejections
NASA Astrophysics Data System (ADS)
Zurbuchen, T. H.; Weberg, M.; von Steiger, R.; Mewaldt, R. A.; Lepri, S. T.; Antiochos, S. K.
2016-07-01
We analyze the physical origin of plasmas that are ejected from the solar corona. To address this issue, we perform a comprehensive analysis of the elemental composition of interplanetary coronal mass ejections (ICMEs) using recently released elemental composition data for Fe, Mg, Si, S, C, N, Ne, and He as compared to O and H. We find that ICMEs exhibit a systematic abundance increase of elements with first ionization potential (FIP) < 10 eV, as well as a significant increase of Ne as compared to quasi-stationary solar wind. ICME plasmas have a stronger FIP effect than slow wind, which indicates either that an FIP process is active during the ICME ejection or that a different type of solar plasma is injected into ICMEs. The observed FIP fractionation is largest during times when the Fe ionic charge states are elevated above Q Fe > 12.0. For ICMEs with elevated charge states, the FIP effect is enhanced by 70% over that of the slow wind. We argue that the compositionally hot parts of ICMEs are active region loops that do not normally have access to the heliosphere through the processes that give rise to solar wind. We also discuss the implications of this result for solar energetic particles accelerated during solar eruptions and for the origin of the slow wind itself.
Propofol Anesthesia and Sleep: A High-Density EEG Study
Murphy, Michael; Bruno, Marie-Aurelie; Riedner, Brady A.; Boveroux, Pierre; Noirhomme, Quentin; Landsness, Eric C.; Brichant, Jean-Francois; Phillips, Christophe; Massimini, Marcello; Laureys, Steven; Tononi, Giulio; Boly, Melanie
2011-01-01
Study Objectives: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep. Design: 256-channel EEG recordings in humans during propofol anesthesia. Setting: Hospital operating room. Patients or Participants: 8 healthy subjects (4 males) Interventions: N/A Measurements and Results: Initially, propofol induced increases in EEG power from 12–25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25–40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness. Conclusions: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity. Citation: Murphy M; Bruno MA; Riedner BA; Boveroux P; Noirhomme Q; Landsness EC; Brichant JF; Phillips C; Massimini M; Laureys S; Tononi G; Boly M. Propofol anesthesia and sleep: a high-density EEG study. SLEEP 2011;34(3):283-291. PMID:21358845
Theory of carbon nanocones: mechanical chiral inversion of a micron-scale three-dimensional object.
Jordan, Stephen P; Crespi, Vincent H
2004-12-17
Graphene cones have two degenerate configurations: their original shape and its inverse. When the apex is depressed by an external probe, the simulated mechanical response is highly nonlinear, with a broad constant-force mode appearing after a short initial Hooke's law regime. For chiral cones, the final state is an atomically exact chiral invert of the original system. If the local reflection symmetry of the graphene sheet is broken by the chemisorption of just five hydrogen atoms to the apex, then the maximal yield strength of the cone increases by approximately 40%. The high symmetry of the conical geometry can concentrate micron-scale mechanical work with atomic precision, providing a way to activate specific chemical bonds.
NASA Astrophysics Data System (ADS)
Rudolf, Pavel; Litera, Jiří; Alejandro Ibarra Bolanos, Germán; Štefan, David
2018-06-01
Vortex rope, which induces substantial pressure pulsations, arises in the draft tube (diffuser) of Francis turbine for off-design operating conditions. Present paper focuses on mitigation of those pulsations using active water jet injection control. Several modifications of the original Susan-Resiga's idea were proposed. All modifications are driven by manipulation of the shear layer region, which is believed to play important role in swirling flow instability. While some of the methods provide results close to the original one, none of them works in such a wide range. Series of numerical experiments support the idea that the necessary condition for vortex rope pulsation mitigation is increasing the fluid momentum along the draft tube axis.
Effects of Alprazolam on Cortical Activity and Tremors in Patients with Essential Tremor
Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A.; Romero, Juan P.; Saíz-Díaz, Rosana A.; Benito-León, Julián; Rocon, Eduardo
2014-01-01
Background Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4–12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. Methods We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Results Alprazolam significantly attenuated tremors (EMG: 76.2±22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. Conclusions This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor. PMID:24667763
Code of Federal Regulations, 2010 CFR
2010-07-01
... services authorized; activities related to certain visa categories authorized. 560.505 Section 560.505...; activities related to certain visa categories authorized. (a) The importation of Iranian-origin services into... with that purpose. (b) Persons otherwise qualified for a non-immigrant visa under categories A-3 and G...
Code of Federal Regulations, 2012 CFR
2012-07-01
... services authorized; activities related to certain visa categories authorized. 560.505 Section 560.505...; activities related to certain visa categories authorized. (a) The importation of Iranian-origin services into... with that purpose. (b) Persons otherwise qualified for a non-immigrant visa under categories A-3 and G...
Code of Federal Regulations, 2011 CFR
2011-07-01
... services authorized; activities related to certain visa categories authorized. 560.505 Section 560.505...; activities related to certain visa categories authorized. (a) The importation of Iranian-origin services into... with that purpose. (b) Persons otherwise qualified for a non-immigrant visa under categories A-3 and G...
Bonnard, M; Galléa, C; De Graaf, J B; Pailhous, J
2007-02-01
The corticospinal system (CS) is well known to be of major importance for controlling the thumb-index grip, in particular for force grading. However, for a given force level, the way in which the involvement of this system could vary with increasing demands on precise force control is not well-known. Using transcranial magnetic stimulation and functional magnetic resonance imagery, the present experiments investigated whether increasing the precision demands while keeping the averaged force level similar during an isometric dynamic low-force control task, involving the thumb-index grip, does affect the corticospinal excitability to the thumb-index muscles and the activation of the motor cortices, primary and non-primary (supplementary motor area, dorsal and ventral premotor and in the contralateral area), at the origin of the CS. With transcranial magnetic stimulation, we showed that, when precision demands increased, the CS excitability increased to either the first dorsal interosseus or the opponens pollicis, and never to both, for similar ongoing electromyographic activation patterns of these muscles. With functional magnetic resonance imagery, we demonstrated that, for the same averaged force level, the amplitude of blood oxygen level-dependent signal increased in relation to the precision demands in the hand area of the contralateral primary motor cortex in the contralateral supplementary motor area, ventral and dorsal premotor area. Together these results show that, during the course of force generation, the CS integrates online top-down information to precisely fit the motor output to the task's constraints and that its multiple cortical origins are involved in this process, with the ventral premotor area appearing to have a special role.
ATR prohibits replication catastrophe by preventing global exhaustion of RPA.
Toledo, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt; Lukas, Claudia; Larsen, Dorthe Helena; Povlsen, Lou Klitgaard; Bekker-Jensen, Simon; Mailand, Niels; Bartek, Jiri; Lukas, Jiri
2013-11-21
ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.
Voloh, Benjamin; Womelsdorf, Thilo
2016-01-01
Short periods of oscillatory activation are ubiquitous signatures of neural circuits. A broad range of studies documents not only their circuit origins, but also a fundamental role for oscillatory activity in coordinating information transfer during goal directed behavior. Recent studies suggest that resetting the phase of ongoing oscillatory activity to endogenous or exogenous cues facilitates coordinated information transfer within circuits and between distributed brain areas. Here, we review evidence that pinpoints phase resetting as a critical marker of dynamic state changes of functional networks. Phase resets: (1) set a “neural context” in terms of narrow band frequencies that uniquely characterizes the activated circuits; (2) impose coherent low frequency phases to which high frequency activations can synchronize, identifiable as cross-frequency correlations across large anatomical distances; (3) are critical for neural coding models that depend on phase, increasing the informational content of neural representations; and (4) likely originate from the dynamics of canonical E-I circuits that are anatomically ubiquitous. These multiple signatures of phase resets are directly linked to enhanced information transfer and behavioral success. We survey how phase resets re-organize oscillations in diverse task contexts, including sensory perception, attentional stimulus selection, cross-modal integration, Pavlovian conditioning, and spatial navigation. The evidence we consider suggests that phase-resets can drive changes in neural excitability, ensemble organization, functional networks, and ultimately, overt behavior. PMID:27013986
Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro-Junior, Ernesto Lopes; Zoccal, Karina Furlani; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Peigneur, Steve; Vriens, Kim; Thevissen, Karin; Cammue, Bruno Philippe Angelo; Júnior, Ronaldo Bragança Martins; Arruda, Eurico; Faccioli, Lúcia Helena; Tytgat, Jan; Arantes, Eliane Candiani
2016-08-01
The present study purifies two T. serrulatus non-disulfide-bridged peptides (NDBPs), named venom peptides 7.2 (RLRSKG) and 8 (KIWRS) and details their synthesis and biological activity, comparing to the synthetic venom peptide 7.1 (RLRSKGKK), previously identified. The synthetic replicate peptides were subjected to a range of biological assays: hemolytic, antifungal, antiviral, electrophysiological, immunological and angiotensin-converting enzyme (ACE) inhibition activities. All venom peptides neither showed to be cytolytic nor demonstrated significant antifungal or antiviral activities. Interestingly, peptides were able to modulate macrophages' responses, increasing IL-6 production. The three venom peptides also demonstrated potential to inhibit ACE in the following order: 7.2>7.1>8. The ACE inhibition activity was unexpected, since peptides that display this function are usually proline-rich peptides. In attempt to understand the origin of such small peptides, we discovered that the isolated peptides 7.2 and 8 are fragments of the same molecule, named Pape peptide precursor. Furthermore, the study discusses that Pape fragments could be originated from a post-splitting mechanism resulting from metalloserrulases and other proteinases cleavage, which can be seen as a clever mechanism used by the scorpion to enlarge its repertoire of venom components. Scorpion venom remains as an interesting source of bioactive proteins and this study advances our knowledge about three NDBPs and their biological activities. Copyright © 2016. Published by Elsevier Inc.
Dynamics of Sensorimotor Oscillations in a Motor Task
NASA Astrophysics Data System (ADS)
Pfurtscheller, Gert; Neuper, Christa
Many BCI systems rely on imagined movement. The brain activity associated with real or imagined movement produces reliable changes in the EEG. Therefore, many people can use BCI systems by imagining movements to convey information. The EEG has many regular rhythms. The most famous are the occipital alpha rhythm and the central mu and beta rhythms. People can desynchronize the alpha rhythm (that is, produce weaker alpha activity) by being alert, and can increase alpha activity by closing their eyes and relaxing. Sensory processing or motor behavior leads to EEG desynchronization or blocking of central beta and mu rhythms, as originally reported by Berger [1], Jasper and Andrew [2] and Jasper and Penfield [3]. This desynchronization reflects a decrease of oscillatory activity related to an internally or externally-paced event and is known as Event-Related Desynchronization (ERD, [4]). The opposite, namely the increase of rhythmic activity, was termed Event-Related Synchronization (ERS, [5]). ERD and ERS are characterized by fairly localized topography and frequency specificity [6]. Both phenomena can be studied through topographiuthc maps, time courses, and time-frequency representations (ERD maps, [7]).
Asakura, H; Makino, S; Kobori, H; Watarai, M; Shirahata, T; Ikeda, T; Takeshi, K
2001-08-01
Nucleotide sequences of Shiga toxin (Stx) genes in STEC from various origins were determined and characterized by phylogenetic analysis based on Shiga toxin (Stx) with those deposited in GenBank. The phylogenetic trees placed Stx1 and Stx2 into two and five groups respectively, and indicated that Stx1 in sheep-origin STEC were placed into a different group from those in other STEC, and that Stx2 of deer-origin STEC also belonged to the unique group and appeared to be distantly related to human-origin STEC. On the other hand, Stx of STEC isolated from cattle, seagulls and flies were closely related to those of human-origin STEC. Such a diversity of Stx suggested that STEC might be widely disseminated in many animal species, and be dependent on their host species or their habitat. In addition, the active sites in both toxins were compared; the active sites in both subunits of Stx in all the animal-origin STEC were identical to those in human-origin STEC, suggesting that all the toxin of STEC from animals might be also cytotoxic, and therefore, such animal-origin STEC might have potential pathogenicity for humans.
Asakura, H.; Makino, S.; Kobori, H.; Watarai, M.; Shirahata, T.; Ikeda, T.; Takeshi, K.
2001-01-01
Nucleotide sequences of Shiga toxin (Stx) genes in STEC from various origins were determined and characterized by phylogenetic analysis based on Shiga toxin (Stx) with those deposited in GenBank. The phylogenetic trees placed Stx1 and Stx2 into two and five groups respectively, and indicated that Stx1 in sheep-origin STEC were placed into a different group from those in other STEC, and that Stx2 of deer-origin STEC also belonged to the unique group and appeared to be distantly related to human-origin STEC. On the other hand, Stx of STEC isolated from cattle, seagulls and flies were closely related to those of human-origin STEC. Such a diversity of Stx suggested that STEC might be widely disseminated in many animal species, and be dependent on their host species or their habitat. In addition, the active sites in both toxins were compared; the active sites in both subunits of Stx in all the animal-origin STEC were identical to those in human-origin STEC, suggesting that all the toxin of STEC from animals might be also cytotoxic, and therefore, such animal-origin STEC might have potential pathogenicity for humans. PMID:11561972
[Adsorption of perfluorooctanesulfonate (PFOS) onto modified activated carbons].
Tong, Xi-Zhen; Shi, Bao-You; Xie, Yue; Wang, Dong-Sheng
2012-09-01
Modified coal and coconut shell based powdered activated carbons (PACs) were prepared by FeCl3 and medium power microwave treatment, respectively. Batch experiments were carried out to evaluate the characteristics of adsorption equilibrium and kinetics of perfluorooctanesulfonate (PFOS) onto original and modified PACs. Based on pore structure and surface functional groups characterization, the adsorption behaviors of modified and original PACs were compared. The competitive adsorption of humic acid (HA) and PFOS on original and modified coconut shell PACs were also investigated. Results showed that both Fe3+ and medium power microwave treatments changed the pore structure and surface functional groups of coal and coconut shell PACs, but the changing effects were different. The adsorption of PFOS on two modified coconut shell-based PACs was significantly improved. While the adsorption of modified coal-based activated carbons declined. The adsorption kinetics of PFOS onto original and modified coconut shell-based activated carbons were the same, and the time of reaching adsorption equilibrium was about 6 hours. In the presence of HA, the adsorption of PFOS by modified PAC was reduced but still higher than that of the original.
Tan, Lu; Li, Linyun; Ashbolt, Nicholas; Wang, Xiaolong; Cui, Yuxiao; Zhu, Xiao; Xu, Yan; Yang, Yang; Mao, Daqing; Luo, Yi
2018-04-15
The increasing global prevalence of antibiotic resistance genes (ARGs) in the environment is attributed to anthropogenic activities, particularly the misuse of antimicrobial drugs in human care and animal production. In the present study, we first examined Arctic/sub-Arctic (polar) sediments for the abundance and diversity of 30 ARGs against sulfonamide, tetracycline, aminoglycoside, quinolone, macrolide, and β-lactam antibiotics. Polar sediment ARGs were detected by qPCR at relatively low levels (10 -9 to 10 -5 copies/16S rRNA gene copies) compared to the reference sites, which were heavily impacted regions of China (the Haihe River, the Tianjin Water Park water and the Qilihai Wetland water, at 10 -8 to 10 -2 copies/16S rRNA gene copies). A human mitochondrial gene target, Hmt, was first used to aid in the identification of ARGs associated with anthropogenic activities, being relatively persistent, in high copy number and a human-specific molecular marker. Hmt was consistently present in easily quantifiable amounts in the polar sediment samples, indicating their relationship with human-impact, and it was also positively correlated with the relative abundance of ARGs and to the concentrations of modern-day antibiotics. Phylogenetic analyses of resistance sequences from both the Arctic marine sediments and a major database of human pathogens indicated that the ARGs in polar region were the result of a mix of human influence and natural origins. To our knowledge, this is the first study to show that ARGs in Arctic marine sediments appear to be a mixture of both natural origins and recent human influence. This study provides a significant reference regarding the global reach of antibiotic resistance, which is associated with anthropogenic activities. Copyright © 2017 Elsevier B.V. All rights reserved.
Extracellular polymers of ozonized waste activated sludge.
Liu, J C; Lee, C H; Lai, J Y; Wang, K C; Hsu, Y C; Chang, B V
2001-01-01
Effect of ozonation on characteristics of waste activated sludge was investigated in the current study. Concentrations of cell-bound extracellular polymers (washed ECPs) did not change much upon ozonation, whereas the sum of cell-bound and soluble extracellular polymers (unwashed ECPs) increased with increasing ozone dose. Washed ECPs in original sludge as divided by molecular weight distribution was 39% < 1,000 Da (low MW), 30% from 1,000 to 10,000 Da (medium MW), and 31% > 10,000 Da (high MW). It was observed that the low-MW fraction decreased, and the high-MW fraction increased in ozonized sludge. The unwashed ECPs were characterized as 44% in low MW, 30% in medium MW, and 26% in high MW. Both low-MW and medium-MW fractions of unwashed ECPs decreased while high-MW fraction increased in ozonized sludge. The dewaterability of ozonized sludge, assessed by capillary suction time (CST) and specific resistance to filtration (SRF), deteriorated with ozone dose. The optimal dose of cationic polyelectrolyte increased with increasing ozone dose. The production rate and the accumulated amount of methane gas of ozonized sludge were also higher.
Gastroprotective effects of flavonoids in plant extracts.
Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Konturek, P C; Brzozowski, T; Ghegotsky, M R
2005-03-01
The purpose of this paper is to overview the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulcer activities. In addition, we assessed whether these compounds are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically (i.g.). The following plant-originated flavonoid substances were considered; Solon (Sophoradin extract), Amaranth seed extract, grapefruit-seed extract (GSE) and capsaicin (extract of chilly pepper). The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). Male Wistar rats, weighing 180-220 g fasted for 24 h before the study where used 100% ethanol was applied i.g. to induce gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment with L-NNA. We conclude that plant-originated flavonoid substances are highly gastroprotective probably due to enhancement of the expression of constitutive NOS and release of NO and neuropeptides such as calcitonin gene related peptide (CGRP) released from sensory afferent nerves increasing gastric microcirculation.
Two Seating Systems' Effects on an Adolescent With Cerebral Palsy and Severe Scoliosis.
Lephart, Kim; Kaplan, Sandra L
2015-01-01
To compare physiological functioning, communication switch activation, and response accuracy in a 19-year-old young man with quadriplegic cerebral palsy and neurological scoliosis using 2 seating systems within the school setting. Prospective single-subject alternating treatment design with 2 conditions: baseline phase with standard planar inserts (A1), custom-molded back with original seat (B), and return to baseline (A2). Measures included oxygen saturation (SaO2), heart rate (HR), respiration rate (RR), body temperature (BT), processing time to activate switches, and response accuracy. SaO2 levels increased from "distressed" to "normal"; variability decreased. HR, RR, and BT fluctuations decreased with the custom-molded back. Processing time decreased with increased variability, affected by subject's motivation; accuracy improved slightly. Reported social approachability and student-initiated communication increased. SaO2 increased and HR, RR, and BT fluctuations decreased with a custom-molded back. Graphing data may help determine seating effect with complex clients.
Gahr, M; Schröter, W; Sturzenegger, M; Bornhalm, D; Marti, H R
1976-08-01
A new variant of erythrocytic glucose-6-phosphate dehydrogenase has been found in a family of Swiss origin. It is associated with chronic nonsphaerocytic haemolytic anaemia. The enzyme from the erythrocytes of a young boy of this family was partially purified 110-fold and characterized. It revealed reduced catalytic activity, increased thermolability and two maxima of the pH activity curve at pH 7.0 and 8.5. The Km value for glucose-6-phosphate was reduced, that for NADP was normal. The enzyme showed an increased inhibitor constant for NADPH with respect to NADP. Electrophoretic mobility was normal (B+). 2-Desoxyglucose-6-phosphate and galactose-6-phosphate were utilized at normal rates, whereas the analogue deamino-NADP gave an increased utilization rate. The mother of the propositus could be identified as heterozygous for this enzyme deficiency. Chronic haemolysis is possibly due to the increased thermolability of the variant enzyme.
mTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in mammalian cells.
Eid, Walaa; Dauner, Kristin; Courtney, Kevin C; Gagnon, AnneMarie; Parks, Robin J; Sorisky, Alexander; Zha, Xiaohui
2017-07-25
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER. We report here that mTORC1 activation is accompanied by low ER cholesterol and an increase of SREBP-2 activation. Conversely, a decrease in mTORC1 activity coincides with a rise in ER cholesterol and a decrease in SERBP-2 activity. This rise in ER cholesterol is of lysosomal origin: blocking the exit of cholesterol from lysosomes by U18666A or NPC1 siRNA prevents ER cholesterol from increasing and, consequently, SREBP-2 is activated without mTORC1 activation. Furthermore, when mTORC1 activity is low, cholesterol is delivered to lysosomes through two membrane trafficking pathways: autophagy and rerouting of endosomes to lysosomes. Indeed, with dual blockade of both pathways by Atg5 -/- and dominant-negative rab5, ER cholesterol fails to increase when mTORC1 activity is low, and SREBP-2 is activated. Conversely, overexpressing constitutively active Atg7, which forces autophagy and raises ER cholesterol even when mTORC1 activity is high, suppresses SREBP-2 activation. We conclude that mTORC1 actively suppresses autophagy and maintains endosomal recycling, thereby preventing endosomes and autophagosomes from reaching lysosomes. This results in a reduction of cholesterol in the ER and activation of SREBP-2.
Schuster, Sarah; Hawelka, Stefan; Hutzler, Florian; Kronbichler, Martin; Richlan, Fabio
2016-01-01
Word length, frequency, and predictability count among the most influential variables during reading. Their effects are well-documented in eye movement studies, but pertinent evidence from neuroimaging primarily stem from single-word presentations. We investigated the effects of these variables during reading of whole sentences with simultaneous eye-tracking and functional magnetic resonance imaging (fixation-related fMRI). Increasing word length was associated with increasing activation in occipital areas linked to visual analysis. Additionally, length elicited a U-shaped modulation (i.e., least activation for medium-length words) within a brain stem region presumably linked to eye movement control. These effects, however, were diminished when accounting for multiple fixation cases. Increasing frequency was associated with decreasing activation within left inferior frontal, superior parietal, and occipito-temporal regions. The function of the latter region—hosting the putative visual word form area—was originally considered as limited to sublexical processing. An exploratory analysis revealed that increasing predictability was associated with decreasing activation within middle temporal and inferior frontal regions previously implicated in memory access and unification. The findings are discussed with regard to their correspondence with findings from single-word presentations and with regard to neurocognitive models of visual word recognition, semantic processing, and eye movement control during reading. PMID:27365297
The contribution of working memory to divided attention.
Santangelo, Valerio; Macaluso, Emiliano
2013-01-01
Previous studies have indicated that increasing working memory (WM) load can affect the attentional selection of signals originating from one object/location. Here we assessed whether WM load affects also the selection of multiple objects/locations (divided attention). Participants monitored either two object-categories (vs. one category; object-based divided attention) or two locations (vs. one location; space-based divided attention) while maintaining in WM either a variable number of objects (object-based WM load) or locations (space-based WM load). Behavioural results showed that WM load affected attentional performance irrespective of divided or focused attention. However, fMRI results showed that the activity associated with object-based divided attention increased linearly with increasing object-based WM load in the left and right intraparietal sulcus (IPS); while, in the same areas, activity associated with space-based divided attention was not affected by any type of WM load. These findings support the hypothesis that WM contributes to the maintenance of resource-demanding attentional sets in a domain-specific manner. Moreover, the dissociable impact of WM load on performance and brain activity suggests that increased IPS activation reflects a recruitment of additional, domain-specific processing resources that enable dual-task performance under conditions of high WM load and high attentional demand. Copyright © 2011 Wiley Periodicals, Inc.
Gavrilović, Anja; Ilijin, Larisa; Mrdaković, Marija; Vlahović, Milena; Mrkonja, Aleksandra; Matić, Dragana; Perić-Mataruga, Vesna
2017-07-01
Anthropogenic activity in industrial development has imposed great threats to the environment and wildlife in the form of persistent organic pollutants. Polycyclic aromatic hydrocarbons (PAH) tend to accumulate in vegetation foliage which is the main food source of polyphagous insect species Lymantria dispar L. Origin and multigenerational adaptation of L. dispar population to environmental challenges strongly condition the enzymes' sensitivity to pollutants. In this study, our aim was to investigate response of the superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) to the chronic dietary exposure of benzo[a]pyrene in the midgut tissues and hemolymph of two L. dispar populations originating from unpolluted and polluted forest habitat. Midgut tissue of the larvae from the polluted forest showed significant increase in SOD, CAT and GST activity, while in unpolluted forest's larvae SOD and CAT showed elevated activities in hemolymph. L. dispar populations adapted to different level of pollution in their environment and expressed distinct tissue-dependent antioxidative enzyme sensitivity to benzo[a]pyrene diet, implying high potential for further elucidation of these enzymes as molecular biomarkers. Copyright © 2017 Elsevier Ltd. All rights reserved.
Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato
2011-01-01
The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209
Active transportation as a way to increase physical activity among children.
Morency, C; Demers, M
2010-05-01
This study examines how active transportation could help increase the daily physical activity volume of school-aged children. Using data from the 2003 Origin-Destination Survey carried out among 5% of the 3.5 million residents of the Greater Montreal Area, we determined the proportion of short motorized trips made daily by children 5-14 years old (16 837 children sampled) and estimated the number of steps these trips would account for if they were travelled by foot, taking into account variables such as age, sex and height of children. Modal choice and trip purpose were also examined. In 2003, 31.2% of the daily trips made by children aged 5-14 years in the Greater Montreal Area were 1 km or less (0.6 mile). Of these, 33.0% were motorized trips. Overall, 13.1% of the children in the area had 'steps in reserve', an average of 2238 steps per child per day. If they were performed, these steps would account for 16.6% of the daily recommended volume of physical activity for children. Replacing short motorized trips with walking could increase the physical activity level of children and contribute to meet the recommended guidelines, as long as these walking trips add to their daily physical activity volume. It could also reduce their dependence towards adults for moving around.
Physical activity and body mass index among women who have experienced infertility
Esmaeilzadeh, Seddigheh; Basirat, Zahra; Shafi, Hamid
2013-01-01
Introduction The experience of infertility is a common medical condition in the developing countries. The aim of this retrospective epidemiologic study was to determine fertility status and parity in Babol, Iran and then identify physical activity and body mass index (BMI) among women who have experienced infertility. Material and methods A total of 1,081 women aged 20-45 years were selected using cluster sampling. The current physical activity was measured using the original International Physical Activity Questionnaire short form. Lifestyle factors were compared between those who had experienced infertility (n = 168) and the rest of the women. A face-to-face household interview was conducted using a specially designed interview questionnaire. Results After adjusting for suspected confounding factors, women with infertility experience had a 4.8-fold increased risk of obesity (OR = 2.02, CI = 0.70, 5.84) and almost a 3.8-fold increased risk of being overweight (OR = 2.11, CI = 0.72, 6.17) compared to women without infertility. No significant differences were found in Met-minutes of sedentary activity, intensity of walking, moderate, vigorous, and total physical activity, self-reported dietary intake, exercise, and level of physical activity between women with and without experience of infertility. Conclusions Since both obesity and infertility are increasing public health issues in Iranian women, more attention should be paid to lifestyle behaviors, especially gaining weight in women who have experienced infertility. PMID:23847673
Han, Y M; Wei, C; Bandowe, B A M; Wilcke, W; Cao, J J; Xu, B Q; Gao, S P; Tie, X X; Li, G H; Jin, Z D; An, Z S
2015-04-07
Elemental carbon (EC) and polycyclic aromatic compounds (PACs) are potential proxies for the reconstruction of change in human activities and the origin of air masses in historic times. In this study, the historic deposition of char and soot (the two subtypes of EC) and PACs in a 150-year sediment core from different topographic subbasins of Lake Qinghai on the Qinghai Tibetan Plateau (QTP) were reconstructed. The objective was to explore how the variations in the concentrations of EC and PACs, in the ratios of char to soot and of oxygenated polycyclic aromatic hydrocarbons (OPAHs) to parent PAHs, and in the composition of the PAC mixtures reflect historical changes in climate and human activity and the origin of air masses arriving at the QTP. The deposition fluxes of soot in the different subbasins were similar, averaging 0.18 (range of 0.15-0.25) and 0.16 (0.13-0.23) g m(-2) year(-1), respectively, but they varied for char (averaging 0.11 and 0.22 g m(-2) year(-1), respectively), suggesting ubiquitous atmospheric deposition of soot and local river inputs of char. The different vertical distributions of the char/soot ratios in the different subbasins can be interpreted in terms of the different transport mechanisms of char and soot. An abrupt increase in soot concentrations since 1980 coincides with results from the QTP ice cores that were interpreted to be indicative of soot transport from South Asia. Similar concentration patterns of PAHs with soot and 9,10-anthraquinone/anthracene (9,10-AQ/ANT) ratios all >2.0 suggest regional PAC sources. Increasing PAH/soot ratios and decreasing 9,10-AQ/ANT ratios since the beginning of the 1970s indicate increasing local emissions. The historical trends of these diagnostic ratios indicate an increase in the fossil-fuel contribution since the beginning of the 1970s. The increase of perylene concentrations with increasing core depth and the ratio of perylene to its penta-aromatic isomers indicate that perylene originates mainly from in situ biogenic diagenesis. We demonstrate that the concentrations of EC, char, soot, and PACs in sediments can be used to reconstruct local, regional, and remote sources and transport pathways of pollutants to the QTP.
NASA Astrophysics Data System (ADS)
Lin, Y.; Hillers, G.; Ma, K.; Campillo, M.
2011-12-01
We study tectonic tremor activity in the Taichung area, Taiwan, analyzing continuous seismic records from 6 short-period sensors of the TCDP borehole array situated around 1 km depth. The low background noise level facilitates the detection of low-amplitude tectonic tremor and low-frequency earthquake (LFE) waveforms. We apply a hierarchical analysis to first detect transient amplitude increases, and to subsequently verify its tectonic origin, i.e. to associate it with tremor signals. The frequency content of tremor usually exceeds the background noise around 2-8 Hz; hence, in the first step, we use BHS1, BHS4 and BHS7 (top, center, bottom sensor) records to detect amplitude anomalies in this frequency range. We calculate the smoothed spectra of 30 second non-overlapping windows taken daily from 5 night time hours to avoid increased day time amplitudes associated with cultural activities. Amplitude detection is then performed on frequency dependent median values of 5 minute advancing, 10 minute long time windows, yielding a series of threshold dependent increased-energy spectra-envelopes, indicating teleseismic waveforms, potential tremor records, or other transients related to anthropogenic or natural sources. To verify the transients' tectonic origin, potential tremor waveforms detected by the amplitude method are manually picked in the time domain. We apply the Brown et al. (2008) LFE matched filter technique to three-component data from the 6 available sensors. Initial few-second templates are taken from the analyst-picked, minute-long segments, and correlated component-wise with 24-h data. Significantly increased similarity between templates and matched waveform segments is detected using the array-average 7-fold MAD measure. Harvested waveforms associated with this initial `weak' detection are stacked, and the thus created master templates are used in an iterative correlation procedure to arrive at robust LFE detections. The increased similarity of waveforms, showing essentially no moveout across the array, suggests a common source and path effect, therefore increasing the likelihood of a tectonic origin. Preliminary results from a pilot analysis confirm the existence of tremor-like signals in the tremor-typical frequency range. We present results from a comprehensive analysis of at least 2 years of continuous data. A limited resolution location procedure is applied, testament to the receiver geometry, and the inferred locations are discussed in relation to the tectonic situation.
Neutron activation analysis traces copper artifacts to geographical point of origin
NASA Technical Reports Server (NTRS)
Conway, M.; Fields, P.; Friedman, A.; Kastner, M.; Metta, D.; Milsted, J.; Olsen, E.
1967-01-01
Impurities remaining in the metallic copper are identified and quantified by spectrographic and neutron activation analysis. Determination of the type of ore used for the copper artifact places the geographic point of origin of the artifact.
Adsorption of SO2 and NO from incineration flue gas onto activated carbon fibers.
Liu, Zhen-Shu
2008-11-01
Activated carbon fibers (ACFs) were used to remove SO2 and NO from incineration flue gas. Three types of ACFs in their origin state and after pretreatment with HNO3, NaOH, and KOH were investigated. The removal efficiencies of SO2 and NO were determined experimentally at defined SO2 and NO concentrations and at temperatures of 150, 200 and 260 degrees C. Experimental results indicated that the removal efficiencies of SO2 and NO using the original ACFs were < 56% and < 27%, respectively. All ACFs modified with HNO3, NaOH, and KOH solution could increase the removal efficiencies of SO(2) and NO. The mesopore volumes and functional groups of ACFs are important in determining the removal of SO2 and NO. When the mesopore volumes of the ACFs are insufficient for removing SO2 and NO, the functional groups on the ACFs are not important in determining the removal of SO2 and NO. On the contrary, the effects of the functional groups on the removal of SO2 and NO are more important than the mesopore volumes as the amount of mesopores on the ACFs is sufficient to remove SO2 and NO. Moreover, the removal efficiencies of SO2 and NO were greatest at 200 degrees C. When the inlet concentration of SO2 increased to 600 ppm, the removal efficiency of SO2 increased slightly and the removal efficiency of NO decreased.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Klein, Stefanie; Sommer, Anja; Distel, Luitpold V.R.
Highlights: Black-Right-Pointing-Pointer Ultrasmall citrate-coated SPIONs with {gamma}Fe{sub 2}O{sub 3} and Fe{sub 3}O{sub 4} structure were prepared. Black-Right-Pointing-Pointer SPIONs uptaken by MCF-7 cells increase the ROS production for about 240%. Black-Right-Pointing-Pointer The SPION induced ROS production is due to released iron ions and catalytically active surfaces. Black-Right-Pointing-Pointer Released iron ions and SPION surfaces initiate the Fenton and Haber-Weiss reaction. Black-Right-Pointing-Pointer X-ray irradiation of internalized SPIONs leads to an increase of catalytically active surfaces. -- Abstract: Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolicmore » and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces.« less
Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.
Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S
2016-04-01
A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Santiago, Rocío; Alarcón, Borja; de Armas, Roberto; Vicente, Carlos; Legaz, María Estrella
2012-06-01
This study describes a method for determining cinnamyl alcohol dehydrogenase activity in sugarcane stems using reverse phase (RP) high-performance liquid chromatography to elucidate their possible lignin origin. Activity is assayed using the reverse mode, the oxidation of hydroxycinnamyl alcohols into hydroxycinnamyl aldehydes. Appearance of the reaction products, coniferaldehyde and sinapaldehyde is determined by measuring absorbance at 340 and 345 nm, respectively. Disappearance of substrates, coniferyl alcohol and sinapyl alcohol is measured at 263 and 273 nm, respectively. Isocratic elution with acetonitrile:acetic acid through an RP Mediterranea sea C18 column is performed. As case examples, we have examined two different cultivars of sugarcane; My 5514 is resistant to smut, whereas B 42231 is susceptible to the pathogen. Inoculation of sugarcane stems elicits lignification and produces significant increases of coniferyl alcohol dehydrogenase (CAD) and sinapyl alcohol dehydrogenase (SAD). Production of lignin increases about 29% in the resistant cultivar and only 13% in the susceptible cultivar after inoculation compared to uninoculated plants. Our results show that the resistance of My 5514 to smut is likely derived, at least in part, to a marked increase of lignin concentration by the activation of CAD and SAD. Copyright © Physiologia Plantarum 2012.
Fundamental molecules of life are pigments which arose and evolved to dissipate the solar spectrum
NASA Astrophysics Data System (ADS)
Michaelian, K.; Simeonov, A.
2015-02-01
The driving force behind the origin and evolution of life has been the thermodynamic imperative of increasing the entropy production of the biosphere through increasing the global solar photon dissipation rate. In the upper atmosphere of today, oxygen and ozone derived from life processes are performing the short wavelength UVC and UVB dissipation. On Earth's surface, water and organic pigments in water facilitate the near UV and visible photon dissipation. The first organic pigments probably formed, absorbed, and dissipated at those photochemically active wavelengths in the UVC that could have reached Earth's surface during the Archean. Proliferation of these pigments can be understood as an autocatalytic photochemical process obeying non-equilibrium thermodynamic directives related to increasing solar photon dissipation rate. Under these directives, organic pigments would have evolved over time to increase the global photon dissipation rate by; (1) increasing the ratio of their effective photon cross sections to their physical size, (2) decreasing their electronic excited state life times, (3) quenching radiative de-excitation channels (e.g. fluorescence), (4) covering ever more completely the prevailing solar spectrum, and (5) proliferating and dispersing to cover an ever greater surface area of Earth. From knowledge of the evolution of the spectrum of G-type stars, and considering the most probable history of the transparency of Earth's atmosphere, we construct the most probable Earth surface solar spectrum as a function of time and compare this with the history of molecular absorption maxima obtained from the available data in the literature. This comparison supports the conjecture that many fundamental molecules of life are pigments which arose and evolved to dissipate the solar spectrum, supports the thermodynamic dissipation theory for the origin of life, constrains models for Earth's early atmosphere, and sheds some new light on the origin of photosynthesis.
Sex Hormone Effects on Physical Activity Levels: Why Doesn’t Jane Run as Much as Dick?
Bowen, Robert S.; Turner, Michael J.; Lightfoot, J. Timothy
2010-01-01
The relationship between physical activity levels and disease rates have become an important health related concern in the developed world. Heart disease, certain cancers, and obesity persist at epidemic rates in the United States and Western Europe. Increased physical activity levels have been shown to reduce the occurrence of many chronic diseases leading to reductions in the burden on the health care system. Activity levels in humans are affected by many cultural and environmental factors, nevertheless current research points to a strong biological input with potential genetic, neurological, and endocrinological origins. Of unique interest, the sex hormones appear to have a very strong influence on activity levels. The current animal literature suggests that females tend to be more active than males due to biological pathways of estrogenic origin. The majority of human epidemiological and anthropological data, on the contrary, suggest women are less active than men in spite of this inherent activity-increasing mechanism. The purpose of this manuscript was to review the current literature regarding the control of physical activity levels by the sex hormones in humans. Using the natural transitional phases of the aging endocrine system, natural periodicity of the menstrual cycle, and pharmacological/hormone replacement therapy as variable experimental stages, some authors have been able to provide some information regarding the existence of an inherent activity-increasing mechanism in humans. In brief, activity levels during life stages prior to and after menopause do not significantly differ, despite the vast changes in sex hormone levels and function. Activity difference throughout a regular menstrual cycle do not appear to influence activity levels in humans either—an effect that is pronounced in the female rodent. The use of hormone replacement therapies provide researchers with more systematic controls over hormone modulation in human subjects; however, this benefit comes with additional confounding variables, mostly due to disease or other states of malfunction. Despite the addition of these confounding factors, minor changes to the activity pattern have been observed in women, especially during the initial administration for the therapy. Observations are yet to be made in male subjects during replacement therapy. In general, some evidence exists suggesting that a biological mechanism—extending from the sex hormones—influences activity in humans. Unfortunately, despite a small number of investigative reports, the paucity of human research investigating how the sex hormones affect activity levels in humans prevents conclusive delineation of the mechanisms involved. Future research in this unique sub-field of endocrinology and exercise science utilizing more appropriate research protocols and effective techniques will provide definitive evidence of such mechanisms. PMID:21142285
Owen, C G; Nightingale, C M; Rudnicka, A R; Sattar, N; Cook, D G; Ekelund, U; Whincup, P H
2010-08-01
Physical inactivity is implicated in unfavourable patterns of obesity and cardiometabolic risk in childhood. However, few studies have quantified these associations using objective physical activity measurements in children from different ethnic groups. We examined these associations in UK children of South Asian, black African-Caribbean and white European origin. This was a cross-sectional study of 2,049 primary school children in three UK cities, who had standardised anthropometric measurements, provided fasting blood samples and wore activity monitors for up to 7 days. Data were analysed using multilevel linear regression and allowing for measurement error. Overall physical activity levels showed strong inverse graded associations with adiposity markers (particularly sum of skinfold thicknesses), fasting insulin, HOMA insulin resistance, triacylglycerol and C-reactive protein; for an increase of 100 counts of physical activity per min of registered time, levels of these factors were 12.2% (95% CI 10.2-14.1%), 10.2% (95% CI 7.5-12.8%), 10.2% (95% CI 7.5-12.8%), 5.8% (95% CI 4.0-7.5%) and 19.2% (95% CI 13.9-24.2%) lower, respectively. Similar increments in physical activity levels were associated with lower diastolic blood pressure (1.0 mmHg, 95% CI 0.6-1.5 mmHg) and LDL-cholesterol (0.04 mmol/l, 95% CI 0.01-0.07 mmol/l), and higher HDL-cholesterol (0.02 mmol/l, 95% CI 0.01-0.04 mmol/l). Moreover, associations were broadly similar in strength in all ethnic groups. All associations between physical activity and cardiometabolic risk factors were reduced (albeit variably) after adjustment for adiposity. Objectively measured physical activity correlates at least as well with obesity and cardiometabolic risk factors in South Asian and African-Caribbean children as in white European children, suggesting that efforts to increase activity levels in such groups would have equally beneficial effects.
[Purity Detection Model Update of Maize Seeds Based on Active Learning].
Tang, Jin-ya; Huang, Min; Zhu, Qi-bing
2015-08-01
Seed purity reflects the degree of seed varieties in typical consistent characteristics, so it is great important to improve the reliability and accuracy of seed purity detection to guarantee the quality of seeds. Hyperspectral imaging can reflect the internal and external characteristics of seeds at the same time, which has been widely used in nondestructive detection of agricultural products. The essence of nondestructive detection of agricultural products using hyperspectral imaging technique is to establish the mathematical model between the spectral information and the quality of agricultural products. Since the spectral information is easily affected by the sample growth environment, the stability and generalization of model would weaken when the test samples harvested from different origin and year. Active learning algorithm was investigated to add representative samples to expand the sample space for the original model, so as to implement the rapid update of the model's ability. Random selection (RS) and Kennard-Stone algorithm (KS) were performed to compare the model update effect with active learning algorithm. The experimental results indicated that in the division of different proportion of sample set (1:1, 3:1, 4:1), the updated purity detection model for maize seeds from 2010 year which was added 40 samples selected by active learning algorithm from 2011 year increased the prediction accuracy for 2011 new samples from 47%, 33.75%, 49% to 98.89%, 98.33%, 98.33%. For the updated purity detection model of 2011 year, its prediction accuracy for 2010 new samples increased by 50.83%, 54.58%, 53.75% to 94.57%, 94.02%, 94.57% after adding 56 new samples from 2010 year. Meanwhile the effect of model updated by active learning algorithm was better than that of RS and KS. Therefore, the update for purity detection model of maize seeds is feasible by active learning algorithm.
Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.
Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M
2013-09-01
Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.
Deletion of creB in Aspergillus oryzae Increases Secreted Hydrolytic Enzyme Activity
Hunter, A. J.; Morris, T. A.; Jin, B.; Saint, C. P.
2013-01-01
Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes. PMID:23835170
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ethelfeld, J.
The report is made to help the owners and the technical personnel of old wind mills: to make a new induction sensor which gives a quick activation of the original brake activation system; to build a new brake activation system, with its own new independent induction sensor system; and to change the (original) centrifugal switch for the brake so that a quicker activation is obtained.
Active retrieval facilitates across-episode binding by modulating the content of memory
Bridge, Donna J.; Voss, Joel L.
2014-01-01
The contents of memory can be updated when information from the current episode is bound with content retrieved from previous episodes. Little is known regarding factors that determine the memory content that is subject to this across-episode binding. We tested whether across-episode binding preferentially occurs for memory content that is currently “active” and identified relevant neural correlates. After studying objects at specific locations on scene backgrounds, subjects performed one of two retrieval tasks for the objects on different scene backgrounds. In an active condition, subjects recalled object locations, whereas subjects merely dragged objects to predetermined locations in a passive condition. Immediately following each object-location retrieval event, a novel face appeared on a blank screen. We hypothesized that the original episode content would be active in memory during face encoding in the active condition, but not in the passive condition (despite seeing the same content in both conditions). A ramification of the active condition would thus be preferential binding of original episode content to novel faces, with no such across-episode binding in the passive condition. Indeed, memory for faces was better when tested on the original background scenes in the active relative to passive condition, indicating that original episode content was bound with the active condition faces, whereas this occurred to a lesser extent for the passive condition faces. Likewise, early-onset negative ERP effects reflected binding of the face to the original episode content in the active but not the passive condition. In contrast, binding in the passive condition occurred only when faces were physically displayed on the original scenes during recognition testing, and a very similar early-onset negative ERP effect signaled binding in this condition. ERP correlates of binding were thus similar for across-episode and within-episode binding (and were distinct from other encoding and retrieval ERP signals in both cases), indicating that active retrieval modulated when binding occurred, not the nature of the binding process per se. These results suggest that active retrieval promotes binding of new information with contents of memory, whereas without active retrieval, these unrelated pieces of information might be bound only when they are physically paired. PMID:25173711
The sleep slow oscillation as a traveling wave.
Massimini, Marcello; Huber, Reto; Ferrarelli, Fabio; Hill, Sean; Tononi, Giulio
2004-08-04
During much of sleep, virtually all cortical neurons undergo a slow oscillation (<1 Hz) in membrane potential, cycling from a hyperpolarized state of silence to a depolarized state of intense firing. This slow oscillation is the fundamental cellular phenomenon that organizes other sleep rhythms such as spindles and slow waves. Using high-density electroencephalogram recordings in humans, we show here that each cycle of the slow oscillation is a traveling wave. Each wave originates at a definite site and travels over the scalp at an estimated speed of 1.2-7.0 m/sec. Waves originate more frequently in prefrontal-orbitofrontal regions and propagate in an anteroposterior direction. Their rate of occurrence increases progressively reaching almost once per second as sleep deepens. The pattern of origin and propagation of sleep slow oscillations is reproducible across nights and subjects and provides a blueprint of cortical excitability and connectivity. The orderly propagation of correlated activity along connected pathways may play a role in spike timing-dependent synaptic plasticity during sleep.
Tiengwe, Calvin; Marcello, Lucio; Farr, Helen; Dickens, Nicholas; Kelly, Steven; Swiderski, Michal; Vaughan, Diane; Gull, Keith; Barry, J. David; Bell, Stephen D.; McCulloch, Richard
2012-01-01
Summary Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion. PMID:22840408
Temperate mountain grasslands: a climate-herbivore hypothesis for origins and persistence.
Weigl, Peter D; Knowles, Travis W
2014-05-01
Temperate montane grasslands and their unique biotas are declining worldwide as they are increasingly being invaded by forests. The origin and persistence of these landscapes have been the focus of such controversy that in many areas their conservation is in doubt. In the USA some biologists have largely dismissed the grass balds of the Southern Appalachians as human artifacts or anomalous and transitory elements of regional geography, worthy of only limited preservation efforts. On the basis of information from biogeography, community ecology, regional history and palaeontology and from consideration of two other montane grassland ecosystems-East Carpathian poloninas and Oregon Coast Range grass balds-we hypothesize that these landscapes are more widespread than was formerly recognized; they are, in many cases, natural and ancient and largely owe their origin and persistence to past climatic extremes and the activities of large mammalian herbivores. © 2013 The Authors. Biological Reviews published by John Wiley © Sons Ltd on behalf of Cambridge Philosophical Society.
Zhang, Yan; Guo, Jingjing; Li, Lanlan; Liu, Xuewei; Yao, Xiaojun; Liu, Huanxiang
2016-10-01
The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d-CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d-CR2 interaction. Many studies have indicated C3d-CR2 interactions are ionic strength-dependent. To investigate the molecular mechanism of C3d-CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d-CR2 complex together with the energetic and structural analysis were performed. Our results revealed the increased interactions between charged protein and ions weaken C3d-CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths. Our results reveal the origins of the effects of ionic strengths on C3d-CR2 interactions are due to the changes of water, ion occupancies and distributions. This study uncovers the origin of the effect of ionic strength on C3d-CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.
Ackel-Eisnach, Kristina; Raes, Patricia; Hönikl, Lisa; Bauer, Daniel; Wagener, Stefan; Möltner, Andreas; Jünger, Jana; Fischer, Martin R.
2015-01-01
Objectives: The point of departure for the present work is the observation that, in comparison with Anglo-American countries or the Netherlands, Germany was responsible for only a marginal number of international publications in the field of medical education research before 2004. Recent years, however, have seen an increase in the importance of medical education research in Germany. The objective of this article is to evaluate the extent to which this trend can be substantiated by increased German publishing activity since the year 2004 in international, English-language journals in the subject area of “medical education research”. Methods: In the framework of a literature and content analysis, German-author articles from the years 2004 to 2013 in six international, English-language medical education research journals were evaluated. In order to obtain an overview of German research activity in this area, all project and original works with German first and last authors were identified and subjected to a more in-depth content analysis. Results: In total, 10,055 articles were examined. The evaluation shows that between the years 2004 and 2013 179 articles (of which 145 are project or original works) by German authors were published in the journals examined. Fluctuations over the course of time were evidenced. The project and original works are primarily cross-sectional studies (27.8%) and randomised control studies (25.6%) on the subject of “teaching and learning methods” (43.6%). Conclusions: In comparison with the years 2004-2008, a significant rise can be seen in the number of publications by German education researchers in international journals since the year 2009. PMID:26413168
Liu, Dong; Yuan, Weiwei; Deng, Liangliang; Yu, Wenbin; Sun, Hongjuan; Yuan, Peng
2014-06-15
In this study, KOH activation was performed to enhance the porosity of the diatomite-templated carbon and to increase its adsorption capacity of methylene blue (MB). In addition to serving as the activation agent, KOH was also used as the etchant to remove the diatomite templates. Zeolite K-H was synthesized as a byproduct via utilization of the resultant silicon- and potassium-containing solutions created from the KOH etching of the diatomite templates. The obtained diatomite-based carbons were composed of macroporous carbon pillars and tubes, which were derived from the replication of the diatomite templates and were well preserved after KOH activation. The abundant micropores in the walls of the carbon pillars and tubes were derived from the break and reconfiguration of carbon films during both the removal of the diatomite templates and KOH activation. Compared with the original diatomite-templated carbons and CO2-activated carbons, the KOH-activated carbons had much higher specific surface areas (988 m(2)/g) and pore volumes (0.675 cm(3)/g). Moreover, the KOH-activated carbons possessed larger MB adsorption capacity (the maximum Langmuir adsorption capacity: 645.2 mg/g) than those of the original carbons and CO2-activated carbons. These results showed that KOH activation was a high effective activation method. The zeolite K-H byproduct was obtained by utilizing the silicon- and potassium-containing solution as the silicon and potassium sources. The zeolite exhibited a stick-like morphology and possessed nanosized particles with a mesopore-predominant porous structure which was observed by TEM for the first time. Copyright © 2014 Elsevier Inc. All rights reserved.
Giacomantonio, Nicholas B; Bredin, Shannon S D; Foulds, Heather J A; Warburton, Darren E R
2013-04-01
This systematic review sought to evaluate critically the health benefits of physical activity among persons with atrial fibrillation (AF). AF is increasing in Western society. While health benefits of physical activity are well established, benefits of physical activity among individuals with AF are not clearly identified. Literature was retrieved systematically through searching electronic databases (MEDLINE, EMBASE, Cochrane), cross-referencing, and drawing on the authors' knowledge. Identified original research articles evaluated health benefits of physical activity among persons with AF or effects of physical activity on AF incidence. From 1056 individual citations, 36 eligible articles were identified. Moderate-intensity physical activity was found to improve exercise capacity, quality of life, and the ability to carry out activities of daily living among persons with AF (n = 6). Increased incidence of AF was not associated with physical activity among the general population (n = 2), although long-term vigorous endurance exercise may be associated with increased incidence of AF (n = 7), and greater risks may be associated with high-intensity physical activity among those with AF (n = 2). Moderate-intensity physical activity among individuals with AF does not adversely alter training outcomes, functional capacity, morbidity, or mortality compared with those in sinus rhythm (n = 12). Physical activity may improve management and treatment of AF (n = 6) and, among at-risk populations, may reduce incidence of AF (n = 3). In conclusion, moderate-intensity physical activity should be encouraged among persons with or at risk of AF. Further research is needed. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Nicotinamide extends replicative lifespan of human cells.
Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong
2006-10-01
We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.
Bi, Xiufang; Hemar, Yacine; Balaban, Murat O; Liao, Xiaojun
2015-11-01
The effect of ultrasound treatment on particle size, color, viscosity, polyphenol oxidase (PPO) activity and microstructure in diluted avocado puree was investigated. The treatments were carried out at 20 kHz (375 W/cm(2)) for 0-10 min. The surface mean diameter (D[3,2]) was reduced to 13.44 μm from an original value of 52.31 μm by ultrasound after 1 min. A higher L(∗) value, ΔE value and lower a(∗) value was observed in ultrasound treated samples. The avocado puree dilution followed pseudoplastic flow behavior, and the viscosity of diluted avocado puree (at 100 s(-1)) after ultrasound treatment for 1 min was 6.0 and 74.4 times higher than the control samples for dilution levels of 1:2 and 1:9, respectively. PPO activity greatly increased under all treatment conditions. A maximum increase of 25.1%, 36.9% and 187.8% in PPO activity was found in samples with dilution ratios of 1:2, 1:5 and 1:9, respectively. The increase in viscosity and measured PPO activity might be related to the decrease in particle size. The microscopy images further confirmed that ultrasound treatment induced disruption of avocado puree structure. Copyright © 2015 Elsevier B.V. All rights reserved.
Yomo, H; Srinivasan, K
1973-12-01
In contrast to earlier reported results of similar experiments in peas, in which almost no increase in protease activity occurred in incubated detached cotyledons, we report here an increase in protease activity in both attached and detached bean cotyledons. Detached bean cotyledons showed continually increasing protease activity up to the 12th day, while that in attached cotyledons declined after 6 days. The free amino acid level in detached cotyledons reached a maximum at the 11th day; protease formation leveled off after 50% of the original seed protein was digested. These data suggest that high free amino acid levels may inhibit protease formation.The activity of partially purified protease in aqueous extracts was enhanced by 10 mm 2-mercaptoethanol or cysteine, indicating a sulfhydryl requirement for activation. Protease formation in detached cotyledons was inhibited 30% by 10 mug/ml cycloheximide and 50% by 100 mum abscisic acid. In contrast, alpha-amylase formation was inhibited 90% by 10 mug/ml cycloheximide and 95% by 20 mum abscisic acid. The cycloheximide data suggest that only a part of the protease, but all of the alpha-amylase, is synthesized de novo; the similar pattern of inhibition by abscisic acid emphasizes the concept that protease may exist in two forms.
Yomo, Harugoro; Srinivasan, Komala
1973-01-01
In contrast to earlier reported results of similar experiments in peas, in which almost no increase in protease activity occurred in incubated detached cotyledons, we report here an increase in protease activity in both attached and detached bean cotyledons. Detached bean cotyledons showed continually increasing protease activity up to the 12th day, while that in attached cotyledons declined after 6 days. The free amino acid level in detached cotyledons reached a maximum at the 11th day; protease formation leveled off after 50% of the original seed protein was digested. These data suggest that high free amino acid levels may inhibit protease formation. The activity of partially purified protease in aqueous extracts was enhanced by 10 mm 2-mercaptoethanol or cysteine, indicating a sulfhydryl requirement for activation. Protease formation in detached cotyledons was inhibited 30% by 10 μg/ml cycloheximide and 50% by 100 μm abscisic acid. In contrast, α-amylase formation was inhibited 90% by 10 μg/ml cycloheximide and 95% by 20 μm abscisic acid. The cycloheximide data suggest that only a part of the protease, but all of the α-amylase, is synthesized de novo; the similar pattern of inhibition by abscisic acid emphasizes the concept that protease may exist in two forms. PMID:16658628
Tian, Yue; Guo, Shanbin; Zhang, Yan; Xu, Ying; Zhao, Ping; Zhao, Xiaochun
2017-05-01
This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p < 0.05). The surgery also increased the contents of TNF-α, IL-1β, and NF-κB activity at all time points after surgery (p < 0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.
Clejan, S; Dotson, R S; Wolf, E W; Corb, M P; Ide, C F
1996-04-10
Quantitative changes in the lipid second messenger diacylglycerol (DAG) were studied in the rat neuroblastoma N1E-115 following exposure to the differentiating agent dimethylsulfoxide (DMSO). Relatively high basal levels of DAG are present in these cells, and addition of 2% DMSO elicited a biphasic increase in DAG levels, dependent on the presence of extracellular Ca2+. Exposure to DMSO also elicited a rapid increase in inositol phosphate and a slight increase in phosphatidic acid (PA), trailing that of DAG. The molecular species (MS) of DAG were analyzed. Within 60 s of DMSO application there were transient increases of DAG representative of phosphatidylinositol (PI) hydrolysis. At longer intervals, more DAG originated from phosphatidylcholine. The MS composition of newly formed PA resembled that of PI and native DAG. Inhibition studies indicated that DAG is formed in the DMSO-treated cells by phospholipases C and that PA formed later is a result of DAG phosphorylation and not activity of phospholipase D (PLD). Undifferentiated cells exhibited an active PLD pathway. In contrast, PLD in DMSO-differentiated cells was not active. In examining the involvement of the sphingomyelin pathway, DMSO exposure was found to increase ceramide levels with a concomitant decrease in sphingomyelin. Addition of the exogenous, soluble analog C6-ceramide to undifferentiated cells resulted in dramatic reductions in DAG and PA levels and PLD activity. These results indicate that DMSO treatment inactivates PLD while activating phospholipases C and the sphingomyelin pathway, suggesting a "switch" between signal transduction pathways in the undifferentiated and differentiated states of N1E-115.
Bioleaching of Arsenic-Rich Gold Concentrates by Bacterial Flora before and after Mutation
Xie, Xuehui; Yuan, Xuewu; Liu, Na; Chen, Xiaoguang; Abdelgadir, Awad; Liu, Jianshe
2013-01-01
In order to improve the bioleaching efficiency of arsenic-rich gold concentrates, a mixed bacterial flora had been developed, and the mutation breeding method was adopted to conduct the research. The original mixed bacterial flora had been enrichedin acid mine drainage of Dexing copper mine, Jiangxi Province, China. It was induced by UV (ultraviolet), ultrasonic, and microwave, and their combination mutation. The most efficient bacterial flora after mutation was collected for further bioleaching of arsenic-rich gold concentrates. Results indicated that the bacterial flora after mutation by UV 60 s combined with ultrasonic 10 min had the best oxidation rate of ferrous, the biggest density of cells, and the most activity of total protein. During bioleaching of arsenic-rich gold concentrates, the density of the mutant bacterial cells reached to 1.13 × 108 cells/mL at 15 days, more than 10 times compared with that of the original culture. The extraction of iron reached to 95.7% after 15 days, increased by 9.9% compared with that of the original culture. The extraction of arsenic reached to 92.6% after 12 days, which was increased by 46.1%. These results suggested that optimum combined mutation could improve leaching ability of the bacterial flora more significantly. PMID:24381948
The physics of functional magnetic resonance imaging (fMRI)
NASA Astrophysics Data System (ADS)
Buxton, Richard B.
2013-09-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.
The physics of functional magnetic resonance imaging (fMRI)
Buxton, Richard B
2015-01-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology. PMID:24006360
The physics of functional magnetic resonance imaging (fMRI).
Buxton, Richard B
2013-09-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm(3) spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.
NASA Astrophysics Data System (ADS)
Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido
2016-11-01
The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.
Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido
2016-11-08
The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.
Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido
2016-01-01
The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity. PMID:27824075
Biophotons Contribute to Retinal Dark Noise.
Li, Zehua; Dai, Jiapei
2016-06-01
The discovery of dark noise in retinal photoreceptors resulted in a long-lasting controversy over its origin and the underlying mechanisms. Here, we used a novel ultra-weak biophoton imaging system (UBIS) to detect biophotonic activity (emission) under dark conditions in rat and bullfrog (Rana catesbeiana) retinas in vitro. We found a significant temperature-dependent increase in biophotonic activity that was completely blocked either by removing intracellular and extracellular Ca(2+) together or inhibiting phosphodiesterase 6. These findings suggest that the photon-like component of discrete dark noise may not be caused by a direct contribution of the thermal activation of rhodopsin, but rather by an indirect thermal induction of biophotonic activity, which then activates the retinal chromophore of rhodopsin. Therefore, this study suggests a possible solution regarding the thermal activation energy barrier for discrete dark noise, which has been debated for almost half a century.
Pourkarimi, Ehsan; Bellush, James M; Whitehouse, Iestyn
2016-01-01
The primary task of developing embryos is genome replication, yet how DNA replication is integrated with the profound cellular changes that occur through development is largely unknown. Using an approach to map DNA replication at high resolution in C. elegans, we show that replication origins are marked with specific histone modifications that define gene enhancers. We demonstrate that the level of enhancer associated modifications scale with the efficiency at which the origin is utilized. By mapping replication origins at different developmental stages, we show that the positions and activity of origins is largely invariant through embryogenesis. Contrary to expectation, we find that replication origins are specified prior to the broad onset of zygotic transcription, yet when transcription initiates it does so in close proximity to the pre-defined replication origins. Transcription and DNA replication origins are correlated, but the association breaks down when embryonic cell division ceases. Collectively, our data indicate that replication origins are fundamental organizers and regulators of gene activity through embryonic development. DOI: http://dx.doi.org/10.7554/eLife.21728.001 PMID:28009254
Report to Congress on Sustainable Ranges
2007-07-01
B-106 July 2007 Military Training Route Inventory MTR Originating Agency* Scheduling Agency* Effective Times Length ** (NM) SR847 Alpena CRTC/OTM...ANG), 5884 A Street, Alpena MI 49707-8125 DSN 741-3509/3226. Same as Originating Activity 0700-2300 local daily 119 SR867 Alpena CRTC/OTM (ANG...5884 A Street, Alpena MI 49707-8125 DSN 741-3509/3226. Same as Originating Activity 0700-2300 local daily 152 SR871 440 AW/DOO, General Mitchell IAP
Brudzynski, Katrina; Miotto, Danielle
2011-08-01
Size-exclusion chromatography (SEC) and activity-guided fractionation of honeys allowed the isolation of high molecular weight brown compounds, ranging in size from 66 to 235kDa that exhibited peroxyl radical-scavenging activity. Their concentrations, antioxidant activity and degree of browning increased after heat-treatment of honeys, suggesting that they represent melanoidins. Chemical analysis of melanoidins demonstrated the presence of proteins, polyphenols and oligosaccharides. Heat-treatment caused an increased incorporation of phenolics into high molecular weight melanoidins and drastically decreased the protein content in these fractions with a concomitant appearance of high molecular weight protein-polyphenol complexes of reduced solubility. LC-ESI-MS demonstrated the presence of oligosaccharide moieties, supporting the postulated origin of melanoidins. The changes in the phenolic content of melanoidins from heated honeys were strongly correlated with their oxygen radical absorbance capacity (ORAC) values (R=0.75, p<0.0001), indicating that polyphenols contribute to the antioxidant activity of melanoidins. In summary, honey melanoidins are multi-component polymers consisting of protein-polyphenol-oligosaccharide complexes. A direct interaction between polyphenols and melanoidins resulted in a loss or gain of function for melanoidin antioxidant activity. Copyright © 2011 Elsevier Ltd. All rights reserved.
THE ELECTRICAL ACTIVATION OF PASSIVE IRON WIRES IN NITRIC ACID
Lillie, Ralph S.
1935-01-01
1. The relation between the E. M. F. and the minimal duration of an activating current has been determined for passive iron wires in nitric acid under varying conditions of concentration of acid, duration of recovery period, and presence of surface-action compounds. 2. The characteristic intensity-duration curves resemble those of irritable living tissues with moderate speeds of response to stimulation (with chronaxies of the order of 10 to 30σ). 3. The intensity of the current required for activation, as well as its minimal effective duration for a given intensity, increases rapidly with increase in the concentration of HNO3. 4. The responsiveness of the iron wire to brief currents is low immediately after activation and returns progressively to the original level during the immediately following period, at first rapidly and then slowly, following a time curve resembling the corresponding curve of living tissues during the relative refractory period. 5. Surface-active compounds decrease reversibly, to a degree dependent on concentration, the responsiveness of iron wires to brief currents. 6. Conditions are described under which the iron wire is activated by the break of an already flowing constant current. PMID:19872905
The Garden of Eden: Implications for cardiovascular disease prevention.
Jenkins, D J; Jenkins, A L; Kendall, C W; Vuksan, V; Vidgen, E
2000-09-01
Creationists and evolutionists acknowledge that the human diet has passed through at least four phases. The original plant food-based diet; a second phase of increasing meat consumption; a third phase of agricultural dependence on starchy foods; and, finally, the supermarket high-saturated fat, low-fibre phase with minimal energy expenditure. Our aim is to define the value of the original or 'Garden of Eden' diet and to speculate on which components should be retained in the modern supermarket diet. The original plant-based diet would have been high in vegetable proteins, plant sterols, dietary fibre and antioxidants, and low in saturated fats with no trans fatty acids. This diet would increase fecal cholesterol losses from the body as bile acids and neutral sterols, while providing little stimulus to cholesterol synthesis. To replace the bile acid losses we would have adapted to a relatively high capacity for cholesterol synthesis. Now, in the high-saturated fat, low-fibre supermarket age, this may be a disadvantage and predisposes consumers to high serum cholesterol and increased risk of cardiovascular disease. We believe part of the solution is a return to the plant-based 'Garden of Eden' diet combined with physical activity. A lipid-lowering portfolio containing vegetable proteins, especially soy, plant sterols and high fibre intakes combined with low saturated and trans fatty acids and cholesterol, would go a long way to reducing serum lipids and coronary heart disease risk seen in the modern Western diet.
McCune, Heather J; Danielson, Laura S; Alvino, Gina M; Collingwood, David; Delrow, Jeffrey J; Fangman, Walton L; Brewer, Bonita J; Raghuraman, M K
2008-12-01
Temporal regulation of origin activation is widely thought to explain the pattern of early- and late-replicating domains in the Saccharomyces cerevisiae genome. Recently, single-molecule analysis of replication suggested that stochastic processes acting on origins with different probabilities of activation could generate the observed kinetics of replication without requiring an underlying temporal order. To distinguish between these possibilities, we examined a clb5Delta strain, where origin firing is largely limited to the first half of S phase, to ask whether all origins nonspecifically show decreased firing (as expected for disordered firing) or if only some origins ("late" origins) are affected. Approximately half the origins in the mutant genome show delayed replication while the remainder replicate largely on time. The delayed regions can encompass hundreds of kilobases and generally correspond to regions that replicate late in wild-type cells. Kinetic analysis of replication in wild-type cells reveals broad windows of origin firing for both early and late origins. Our results are consistent with a temporal model in which origins can show some heterogeneity in both time and probability of origin firing, but clustering of temporally like origins nevertheless yields a genome that is organized into blocks showing different replication times.
Combet, S; Miyata, T; Moulin, P; Pouthier, D; Goffin, E; Devuyst, O
2000-04-01
Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (<18 mo, n = 6) or long-term(>18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca(2+)-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.
Lin, Yi; Chen, Jianglei; Sun, Zhongjie
2016-03-01
Klotho was originally discovered as an aging-suppressor gene. The objective of this study is to investigate whether klotho gene deficiency affects high-fat diet (HFD)-induced arterial stiffening. Heterozygous Klotho-deficient (KL(+/-)) mice and WT littermates were fed on HFD or normal diet. HFD increased pulse wave velocity within 5 weeks in KL(+/-) mice but not in wild-type mice, indicating that klotho deficiency accelerates and exacerbates HFD-induced arterial stiffening. A greater increase in blood pressure was found in KL(+/-) mice fed on HFD. Protein expressions of phosphorylated AMP-activated protein kinase-α (AMPKα), phosphorylated endothelial nitric oxide synthase (eNOS), and manganese-dependent superoxide dismutase (Mn-SOD) were decreased, whereas protein expressions of collagen I, transforming growth factor-β1, and Runx2 were increased in aortas of KL(+/-) mice fed on HFD. Interestingly, daily injections of an AMPKα activator, 5-aminoimidazole-4-carboxamide-3-ribonucleoside, abolished the increases in pulse wave velocity, blood pressure, and blood glucose in KL(+/-) mice fed on HFD. Treatment with 5-aminoimidazole-4-carboxamide-3-ribonucleoside for 2 weeks not only abolished the downregulation of phosphorylated AMPKα, phosphorylated eNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, transforming growth factor-β1, Runx2, superoxide, elastic lamellae breaks, and calcification in aortas of KL(+/-) mice fed on HFD. In cultured mouse aortic smooth muscle cells, cholesterol plus KL-deficient serum decreased phosphorylation levels of AMPKα and LKB1 (an important upstream regulator of AMPKα activity) but increased collagen I synthesis, which can be eliminated by activation of AMPKα by 5-aminoimidazole-4-carboxamide-3-ribonucleoside. In conclusions, Klotho deficiency promoted HFD-induced arterial stiffening and hypertension via downregulation of AMPKα activity. © 2016 American Heart Association, Inc.
Hoang, Margaret L; Leon, Ronald P; Pessoa-Brandao, Luis; Hunt, Sonia; Raghuraman, M K; Fangman, Walton L; Brewer, Bonita J; Sclafani, Robert A
2007-11-01
Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all origins in G(1) phase, and yet only a subset of complexes is activated during S phase by DDK (for Dbf4-dependent kinase) (Cdc7-Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in reduced intrinsic firing efficiency at 11 endogenous origins and at origins located on minichromosomes. Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predicted from the atomic structure of an archaeal MCM (for minichromosome maintenance) homologue. Similarly, an intragenic mutation in a residue predicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype. We propose DDK phosphorylation of the MCM complex normally results in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, only one of which is permissive for origin activation. Random adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occurs independently of DDK and why origin efficiency is reduced. Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation.
Selection of homeotic proteins for binding to a human DNA replication origin.
de Stanchina, E; Gabellini, D; Norio, P; Giacca, M; Peverali, F A; Riva, S; Falaschi, A; Biamonti, G
2000-06-09
We have previously shown that a cell cycle-dependent nucleoprotein complex assembles in vivo on a 74 bp sequence within the human DNA replication origin associated to the Lamin B2 gene. Here, we report the identification, using a one-hybrid screen in yeast, of three proteins interacting with the 74 bp sequence. All of them, namely HOXA13, HOXC10 and HOXC13, are orthologues of the Abdominal-B gene of Drosophila melanogaster and are members of the homeogene family of developmental regulators. We describe the complete open reading frame sequence of HOXC10 and HOXC13 along with the structure of the HoxC13 gene. The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells. We also show that HOXC10 expression is cell-type-dependent and positively correlates with cell proliferation. Copyright 2000 Academic Press.
NASA Technical Reports Server (NTRS)
Kremser, G.; Wilken, B.; Gloeckler, G.; Hamilton, D. C.; Ipavich, F. M.; Kistler, L. M.; Tanskanen, P.
1993-01-01
Data from the ion charge-energy-mass spectrometer CHEM flown on AMPTE/CCE spacecraft are used to investigate the origin, transport, and losses of energetic He(+) and He(2+) ions in the earth's magnetosphere. The L profiles of the average ion phase space density f were determined as a function of the magnetic momentum. It is shown that the L profiles have an inner part, where f increases with L for both He(+) adn He(2+) and where steady-state conditions are fulfilled. The outer boundary L(lim) of this region is located at a distance that depends on the ion species and the geomagnetic activity level. Steady-state conditions continue outside L(lim) for He(+) ions, while the He(2+) ion distribution outside L(lim) is strongly influenced by ion convection causing a lack of steady-state conditions. It is concluded that solar wind is the origin of the He(2+), while a mixed origin is suggested for the He(+) ions, in which the major contribution is from the solar wind via charge exchange production from the He(2+) ions.
Developmental origins of NAFLD: a womb with a clue
Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.
2017-01-01
Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972
Johnson, T S; Scholfield, C I; Parry, J; Griffin, M
1998-01-01
Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se, since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage. PMID:9512467
Concurrent Activation of Striatal Direct and Indirect Pathways During Action Initiation
Cui, Guohong; Jun, Sang Beom; Jin, Xin; Pham, Michael D.
2014-01-01
Summary The basal ganglia are subcortical nuclei that control voluntary actions, and are affected by a number of debilitating neurological disorders1–4. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum5,6 - the so-called direct and indirect pathways - have opposing effects on movement: while activity of direct-pathway SPNs purportedly facilitates movement, activity of indirect-pathway SPNs inhibits movement1,2. This model has been difficult to test due to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. We developed a novel in-vivo method that allowed us to specifically measure direct- and indirect-pathway SPN activity using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCAMP3 in the dorsal striatum of D1-Cre (direct-pathway specific6,7) and A2A-Cre (indirect-pathway specific8,9) mice10. Using fiber optics and time-correlated single photon counting (TCSPC) in mice performing an operant task, we observed transient increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements, and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function, and may have implications for understanding the origin of motor symptoms in basal ganglia disorders. PMID:23354054
78 FR 32356 - United States-Korea Free Trade Agreement
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-30
... possesses the required origin information; (2) the consistent application of the rules of origin to UKFTA... finding of either (a) repeated unlawful activity or (b) willful presentation of inaccurate origin... that a claim of origin for a textile or apparel good is accurate) or Article 4.3.5 (verification to...
Schmueck-Henneresse, Michael; Omer, Bilal; Shum, Thomas; Tashiro, Haruko; Mamonkin, Maksim; Lapteva, Natalia; Sharma, Sandhya; Rollins, Lisa; Dotti, Gianpietro; Reinke, Petra; Volk, Hans-Dieter; Rooney, Cliona M
2017-07-01
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO + CCR7 - effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population. We show that all subsets are sensitive to CAR transduction, and each developed a distinct T cell functional profile during culture. Naive-derived T cells showed the greatest rate of proliferation but had more limited effector functions and reduced killing compared with memory-derived populations. When cultured in the presence of memory T cells, naive-derived T cells show increased differentiation, reduced effector cytokine production, and a reduced reproliferative response to CAR stimulation. CD3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells and central memory T cell-derived T cells compared with IL-2. Our strategy provides a powerful tool to elucidate the characteristics of CAR-modified T cells, regardless of the protocol used for expansion, reveals the functional properties of each expanded T cell subset, and paves the way for a more detailed evaluation of the effects of manufacturing changes on the subset contribution to in vitro-expanded T cells. Copyright © 2017 by The American Association of Immunologists, Inc.
Buds of the tree: the highway to the last universal common ancestor
NASA Astrophysics Data System (ADS)
de Farias, Savio Torres; Prosdocimi, Francisco
2017-04-01
The last universal common ancestor (LUCA) has been considered as the branching point on which Bacteria, Archaea and Eukaryotes have diverged. However, the increased information relating to viruses' genomes and the perception that many virus genes do not have homologs in other organisms opened a new discussion. Based on these facts, there has emerged the idea of an early LUCA that should be moved further into the past to include viruses, implicating that life should have originated before the appearance of cellular life forms. Another point of view from advocates of the RNA-world suggests that the origin of life happened a long time before organisms were capable of organizing themselves into cellular entities. Relevant data about the origin of ribosomes indicate that the catalytic unit of the large ribosomal subunit is what should actually be considered as the turning point that separated chemistry from biology. Other researchers seem to think that a tRNA was probably some sort of a strange attractor on which life has originated. Here we propose a theoretical synthesis that tries to provide a crosstalk among the theories and define important points on which the origin of life could have been originated and made more complex, taking into account gradualist assumptions. Thus, discussions involving the origin of biological activities in the RNA-world might lead into a world of progenotes on which viruses have been taken part until the appearance of the very first cells. Along this route of complexification, we identified some key points on which researchers may consider life as an emerging principle.
Allelopathic effect of a native species on a major plant invader in Europe
NASA Astrophysics Data System (ADS)
Christina, Mathias; Rouifed, Soraya; Puijalon, Sara; Vallier, Félix; Meiffren, Guillaume; Bellvert, Floriant; Piola, Florence
2015-04-01
Biological invasions have become a major global issue in ecosystem conservation. As formalized in the "novel weapon hypothesis", the allelopathic abilities of species are actively involved in invasion success. Here, we assume that allelopathy can also increase the biotic resistance of native species against invasion. We tested this hypothesis by studying the impact of the native species Sambucus ebulus on the colonization of propagules of the invasive species Fallopia x bohemica and the subsequent development of plants from these. Achenes and rhizome fragments from two natural populations were grown in a greenhouse experiment for 50 days. We used an experimental design that involved "donor" and "target" pots in order to separate resource competition from allelopathy. An allelopathic treatment effect was observed for plant growth but not for propagule establishment. Treatment affected, in particular, the growth of Fallopia plants originating from achenes, but there was less influence on plants originating from rhizomes. By day 50, shoot height had decreased by 27 % for plants originating from rhizomes and by 38 % for plants originating from achenes. The number of leaves for plants originating from achenes had only decreased by 20 %. Leaf and above- and below-ground dry masses decreased with treatment by 40, 41 and 25 % for plants originating from rhizomes and 70, 61 and 55 % for plants originating from achenes, respectively. S. ebulus extracts were analysed using high-performance chromatography, and the choice of test molecules was narrowed down. Our results suggest native species use allelopathy as a biotic containment mechanism against the naturalization of invasive species.
Creating a false memory in the hippocampus.
Ramirez, Steve; Liu, Xu; Lin, Pei-Ann; Suh, Junghyup; Pignatelli, Michele; Redondo, Roger L; Ryan, Tomás J; Tonegawa, Susumu
2013-07-26
Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram-bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.
Boekhoudt, Linde; Wijbrans, Ellen C; Man, Jodie H K; Luijendijk, Mieneke C M; de Jong, Johannes W; van der Plasse, Geoffrey; Vanderschuren, Louk J M J; Adan, Roger A H
2018-01-01
Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.
Hawkins, C Matthew; Duszak, Richard; Rawson, James V
2014-04-01
Twitter is a social media microblogging platform that allows rapid exchange of information between individuals. Despite its widespread acceptance and use at various other medical specialty meetings, there are no published data evaluating its use at radiology meetings. The purpose of this study is to quantitatively and qualitatively evaluate the use of Twitter as a microblogging platform at recent RSNA annual meetings. Twitter activity meta-data tagged with official meeting hashtags #RSNA11 and #RSNA12 were collected and analyzed. Multiple metrics were evaluated, including daily and hourly Twitter activity, frequency of microblogging activity over time, characteristics of the 100 most active Twitter users at each meeting, characteristics of meeting-related tweets, and the geographic origin of meeting microbloggers. The use of Twitter microblogging increased by at least 30% by all identifiable meaningful metrics between the 2011 and 2012 RSNA annual meetings, including total tweets, tweets per day, activity of the most active microbloggers, and total number of microbloggers. Similar increases were observed in numbers of North American and international microbloggers. Markedly increased use of the Twitter microblogging platform at recent RSNA annual meetings demonstrates the potential to leverage this technology to engage meeting attendees, improve scientific sessions, and promote improved collaboration at national radiology meetings. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.
Synthesis, antimicrobial activity and toxicity of analogs of the scorpion venom BmKn peptides.
Bea, Roberto de la Salud; Petraglia, Adam Fine; Johnson, Laura Elena Luque de
2015-07-01
Two analogs of the natural peptide BmKn1 and four of BmKn2 found in the venom of the scorpion Buthus martensii Karsh have been synthesized and tested to compare their antimicrobial and hemolytic activity with the natural ones. Modifications of the natural sequence were done on the hydrophobic side of the alpha helix by increasing the size and hydrophobicity of the residues with alanine (BmKn2A1), valine (BmKn2V1) and leucine (BmKn2L1) respectively, and on the hydrophilic side by increasing the charge from +2 to +3 with two lysines (BmKn2K7). In order to study observed peptide aggregation, two peptides with one (BmKn1-6Lys) and two (BmKn1L2K2) positive charges respectively in the hydrophobic side have been also designed. Results show that the valine substituted analog BmKn2V1 and lysine substituted analog BmKn2K7 have in general, the highest antibiotic and hemolytic activity of the group. Introduction of one positive charge on the hydrophobic side shows a significant increase in antibacterial activity compared with the original sequence except for Bacillus and Enterobacter where, unexpectedly, the activity flats-off. In contrast, the analog with two positive charges has minimal antibacterial or hemolytic activity. Copyright © 2015 Elsevier Ltd. All rights reserved.
Levé, Marine; Sueur, Cédric; Petit, Odile; Matsuzawa, Tetsuro; Hirata, Satoshi
2016-01-01
Many chimpanzees throughout the world are housed in captivity, and there is an increasing effort to recreate social groups by mixing individuals with captive origins with those with wild origins. Captive origins may entail restricted rearing conditions during early infant life, including, for example, no maternal rearing and a limited social life. Early rearing conditions have been linked with differences in tool-use behavior between captive- and wild-born chimpanzees. If physical cognition can be impaired by non-natural rearing, what might be the consequences for social capacities? This study describes the results of network analysis based on grooming interactions in chimpanzees with wild and captive origins living in the Kumamoto Sanctuary in Kumamoto, Japan. Grooming is a complex social activity occupying up to 25% of chimpanzees' waking hours and plays a role in the emergence and maintenance of social relationships. We assessed whether the social centralities and roles of chimpanzees might be affected by their origin (captive vs wild). We found that captive- and wild-origin chimpanzees did not differ in their grooming behavior, but that theoretical removal of individuals from the network had differing impacts depending on the origin of the individual. Contrary to findings that non-natural early rearing has long-term effects on physical cognition, living in social groups seems to compensate for the negative effects of non-natural early rearing. Social network analysis (SNA) and, in particular, theoretical removal analysis, were able to highlight differences between individuals that would have been impossible to show using classical methods. The social environment of captive animals is important to their well-being, and we are only beginning to understand how SNA might help to enhance animal welfare.
Morley, Iain
2014-01-01
Archaeological evidence for musical activities pre-dates even the earliest-known cave art and it remains the case that no human culture has yet been encountered that does not practise some recognisably musical activity. Yet the human abilities to make and appreciate music have been described as "amongst the most mysterious with which [we are] endowed" (Charles Darwin, 1872) and music itself as "the supreme mystery of the science of man" (Claude Levi-Strauss, 1970). Like language, music has been the subject of keen investigation across a great diversity of fields, from neuroscience and psychology, to ethnography, to studies of its structures in its own dedicated field, musicology; unlike the evolution of human language abilities, it is only recently that the origins of musical capacities have begun to receive dedicated attention. It is increasingly clear that human musical abilities are fundamentally related to other important human abilities, yet much remains mysterious about this ubiquitous human phenomenon, not least its prehistoric origins. It is evident that no single field of investigation can address the wide range of issues relevant to answering the question of music's origins. This review brings together evidence from a wide range of anthropological and human sciences, including palaeoanthropology, archaeology, neuroscience, primatology and developmental psychology, in an attempt to elucidate the nature of the foundations of music, how they have evolved, and how they are related to capabilities underlying other important human behaviours. It is proposed that at their most fundamental level musical behaviours (including both vocalisation and dance) are forms of deliberate metrically-organised gesture, and constitute a specialised use of systems dedicated to the expression and comprehension of social and emotional information between individuals. The abilities underlying these behaviours are selectively advantageous themselves; in addition, various mechanisms by which the practice of musical activities themselves could be advantageous are outlined.
Li, J-C; Yamaguchi, S; Kondo, Y; Funahashi, H
2011-04-15
The objective was to examine the effects of caffeine, dibutyryl cyclic AMP, and heparin on the chemotaxis and/or phagocytosis of PMNs for porcine sperm. The chemotactic activity of PMNs, determined in a blind well chamber, increased (P < 0.05) when fresh serum was added to the medium (control containing BSA, 1109.5 cells/mm(2) vs serum, 1226.3 cells/mm(2)), regardless of the presence of sperm (control, 1121.1 cells/mm(2) vs serum, 1245.8 cells/mm(2)), whereas heat-inactivated serum did not affect activity (without sperm, 1099.4 cells/mm(2) and with sperm, 1132.6 cells/mm(2)). Regardless of live and dead sperm and of the origin of PMNs (boars vs sows), the phagocytotic activity of PMNs, as determined by co-culture of PMNs with sperm for 60 min, increased (P < 0.05) in the presence of fresh serum containing active complement (46.7 and 43.0%, respectively), but stimulation was decreased (P < 0.05) when 1 mM or higher concentrations of caffeine was added to the medium (from 40.7 to 20.8-31.6%). The origin of PMNs (sows vs boars) did not significantly affect phagocytotic activity. The percentage of PMNs that phagocytized polystyrene latex beads decreased when 2 mM caffeine was added to the medium containing porcine serum (from 43.7 to 21.5%). Serum-stimulated chemotactic activity of PMNs (1089.9 cells/mm(2)) was also reduced (P < 0.05) with 2 mM caffeine (942.5 cells/mm(2)). Furthermore, dibutyryl cAMP at ≥ 0.1 mM or heparin at ≥ 100 μg/mL decreased phagocytotic activity, in a concentration-dependent manner (P < 0.05). Supplementation of PMNs with heparin at 100 or 500 μg/mL decreased (P < 0.05) chemotactic activity in the presence of serum (from 1137.1 cells/mm(2) to 1008.8-1026.3 cells/mm(2)). We inferred that opsonization in the presence of active complement stimulated phagocytotic and chemotactic activities of PMNs, whereas supplementation with caffeine and dibutyryl cAMP (which could be associated with the intracellular cAMP level of PMNs) or adding heparin decreased serum-stimulated phagocytotic and chemotactic activities. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
Summary of evidence for an anticodonic basis for the origin of the genetic code
NASA Technical Reports Server (NTRS)
Lacey, J. C., Jr.; Mullins, D. W., Jr.
1981-01-01
This article summarizes data supporting the hypothesis that the genetic code origin was based on relationships (probably affinities) between amino acids and their anticodon nucleotides. Selective activation seems to follow from selective affinity and consequently, incorporation of amino acids into peptides can also be selective. It is suggested that these selectivities in affinity and activation, coupled with the base pairing specificities, allowed the origin of the code and the process of translation.
Structure and biological activity of endogenous and synthetic agonists of GPR119
NASA Astrophysics Data System (ADS)
Tyurenkov, I. N.; Ozerov, A. A.; Kurkin, D. V.; Logvinova, E. O.; Bakulin, D. A.; Volotova, E. V.; Borodin, D. D.
2018-02-01
A G-protein-coupled receptor, GPR119, is a promising pharmacological target for a new class of hypoglycaemic drugs with an original mechanism of action, namely, increase in the glucose-dependent incretin and insulin secretion. In 2005, the first ligands were found and in the subsequent years, a large number of GPR119 agonists were synthesized in laboratories in various countries; the safest and most promising agonists have entered phase I and II clinical trials as agents for the treatment of type 2 diabetes mellitus and obesity. The review describes the major endogenous GPR119 agonists and the main trends in the design and modification of synthetic structures for increasing the hypoglycaemic activity. The data on synthetic agonists are arranged according to the type of the central core of the molecules. The bibliography includes 104 references.
Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009.
Harman, Denham
2009-12-01
Aging is the progressive accumulation in an organism of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical process underlying aging was first advanced by the free radical theory of aging (FRTA) in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. The initial low acceptance of the FRTA by the scientific community, its slow growth, manifested by meetings and occasional papers based on the theory, prompted this account of the intermittent growth of acceptance of the theory over the past nearly 55 years.
Influence of Pokémon Go on Physical Activity: Study and Implications.
Althoff, Tim; White, Ryen W; Horvitz, Eric
2016-12-06
Physical activity helps people maintain a healthy weight and reduces the risk for several chronic diseases. Although this knowledge is widely recognized, adults and children in many countries around the world do not get recommended amounts of physical activity. Although many interventions are found to be ineffective at increasing physical activity or reaching inactive populations, there have been anecdotal reports of increased physical activity due to novel mobile games that embed game play in the physical world. The most recent and salient example of such a game is Pokémon Go, which has reportedly reached tens of millions of users in the United States and worldwide. The objective of this study was to quantify the impact of Pokémon Go on physical activity. We study the effect of Pokémon Go on physical activity through a combination of signals from large-scale corpora of wearable sensor data and search engine logs for 32,000 Microsoft Band users over a period of 3 months. Pokémon Go players are identified through search engine queries and physical activity is measured through accelerometers. We find that Pokémon Go leads to significant increases in physical activity over a period of 30 days, with particularly engaged users (ie, those making multiple search queries for details about game usage) increasing their activity by 1473 steps a day on average, a more than 25% increase compared with their prior activity level (P<.001). In the short time span of the study, we estimate that Pokémon Go has added a total of 144 billion steps to US physical activity. Furthermore, Pokémon Go has been able to increase physical activity across men and women of all ages, weight status, and prior activity levels showing this form of game leads to increases in physical activity with significant implications for public health. In particular, we find that Pokémon Go is able to reach low activity populations, whereas all 4 leading mobile health apps studied in this work largely draw from an already very active population. Mobile apps combining game play with physical activity lead to substantial short-term activity increases and, in contrast to many existing interventions and mobile health apps, have the potential to reach activity-poor populations. Future studies are needed to investigate potential long-term effects of these applications. ©Tim Althoff, Ryen W White, Eric Horvitz. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.12.2016.
Strobel, Oliver; Dadabaeva, Nigora; Felix, Klaus; Hackert, Thilo; Giese, Nathalia A; Jesenofsky, Ralf; Werner, Jens
2016-02-01
Pancreatic stellate cells (PSCs) play a critical role in pancreatic ductal adenocarcinoma (PDAC). Activated PSCs are the main source of fibrosis in chronic pancreatitis and of desmoplasia in PDAC. The majority of studies on PSC are based on in vitro experiments relying on immortalized cell lines derived from diseased human pancreas or from animal models. These PSCs are usually activated and may not represent the biological context of their tissue of origin. (1) To isolate and culture primary human PSC from different disease contexts with minimal impact on their state of activation. (2) To perform a comparative analysis of phenotypes of PSC derived from different contexts. PSCs were isolated from normal pancreas, chronic pancreatitis, and PDAC using a hybrid method of digestion and outgrowth. To minimize activation by serum compounds, cells were cultured in a low-serum environment (2.5 % fetal bovine serum (FBS)). Expression patterns of commonly used markers for PSC phenotype and activity were compared between primary PSC lines derived from different contexts and correlated to expression in their original tissues. Isolation was successful from 14 of 17 tissues (82 %). Isolated PSC displayed stable viability and phenotype in low-serum environment. Expression profiles of isolated PSC and matched original tissues were closely correlated. PDAC-derived PSC tended to have a higher status of activation if compared to PSC derived from non-cancerous tissues. Primary human PSCs isolated from different contexts and cultured in a low-serum environment maintain a phenotype that reflects the stromal activity present in their tissue of origin.
Antioxidant potential of commercially available cumin (Cuminum cyminuml inn) in Pakistan.
Bukhari, S Birjees; Iqbal, Shahid; Bhanger, M I
2009-05-01
Owing to increased safety concerns about synthetic antioxidants, exploitation of safer antioxidants based on natural origin is the focus of research nowadays. Cumin is a common spice and is used as a routine supportive cooking agent. Extracts of cumin were prepared in methanol, ethanol, dichloromethane and hexane by employing Soxhlet extraction apparatus. Determination of the total phenolic content, chelating activity, reducing power and free radical scavenging activity were taken as parameters for the assessment of antioxidant properties. The findings of this study suggest cumin to be a potent source of antioxidants. Results from the different parameters were in agreement with one another.
The Sugar Model: Autocatalytic Activity of the Triose-Ammonia Reaction
NASA Technical Reports Server (NTRS)
Weber, Arthur L.
2006-01-01
Reaction of triose sugars with ammonia under anaerobic conditions yielded autocatalytic products. The autocatalytic behavior of the products was examined by measuring the effect of the crude triose-ammonia reaction product on the kinetics of a second identical triose-ammonia reaction. The reaction product showed autocatalytic activity by increasing both the rate of disappearance of triose and the rate formation of pyruvaldehyde, the product of triose dehydration. This synthetic process is considered a reasonable model of origin-of-life chemistry because it uses plausible prebiotic substrates, and resembles modern biosynthesis by employing the energized carbon groups of sugars to drive the synthesis of autocatalytic molecules.
The Sugar Model: Autocatalytic Activity of the Triose Ammonia Reaction
NASA Astrophysics Data System (ADS)
Weber, Arthur L.
2007-04-01
Reaction of triose sugars with ammonia under anaerobic conditions yielded autocatalytic products. The autocatalytic behavior of the products was examined by measuring the effect of the crude triose ammonia reaction product on the kinetics of a second identical triose ammonia reaction. The reaction product showed autocatalytic activity by increasing both the rate of disappearance of triose and the rate of formation of pyruvaldehyde, the product of triose dehydration. This synthetic process is considered a reasonable model of origin-of-life chemistry because it uses plausible prebiotic substrates, and resembles modern biosynthesis by employing the energized carbon groups of sugars to drive the synthesis of autocatalytic molecules.
Active retrieval facilitates across-episode binding by modulating the content of memory.
Bridge, Donna J; Voss, Joel L
2014-10-01
The contents of memory can be updated when information from the current episode is bound with content retrieved from previous episodes. Little is known regarding factors that determine the memory content that is subject to this across-episode binding. We tested whether across-episode binding preferentially occurs for memory content that is currently "active" and identified relevant neural correlates. After studying objects at specific locations on scene backgrounds, subjects performed one of two retrieval tasks for the objects on different scene backgrounds. In an active condition, subjects recalled object locations, whereas subjects merely dragged objects to predetermined locations in a passive condition. Immediately following each object-location retrieval event, a novel face appeared on a blank screen. We hypothesized that the original episode content would be active in memory during face encoding in the active condition, but not in the passive condition (despite seeing the same content in both conditions). A ramification of the active condition would thus be preferential binding of original episode content to novel faces, with no such across-episode binding in the passive condition. Indeed, memory for faces was better when tested on the original background scenes in the active relative to passive condition, indicating that original episode content was bound with the active condition faces, whereas this occurred to a lesser extent for the passive condition faces. Likewise, early-onset negative ERP effects reflected binding of the face to the original episode content in the active but not the passive condition. In contrast, binding in the passive condition occurred only when faces were physically displayed on the original scenes during recognition testing, and a very similar early-onset negative ERP effect signaled binding in this condition. ERP correlates of binding were thus similar for across-episode and within-episode binding (and were distinct from other encoding and retrieval ERP signals in both cases), indicating that active retrieval modulated when binding occurred, not the nature of the binding process per se. These results suggest that active retrieval promotes binding of new information with contents of memory, whereas without active retrieval, these unrelated pieces of information might be bound only when they are physically paired. Copyright © 2014 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Pingree-Shippee, K. A.; Zwiers, F. W.; Atkinson, D. E.
2016-12-01
Extratropical cyclones (ETCs) often produce extreme hazardous weather conditions, such as high winds, blizzard conditions, heavy precipitation, and flooding, all of which can have detrimental socio-economic impacts. The North American east and west coastal regions are both strongly influenced by ETCs and, subsequently, land-based, coastal, and maritime economic sectors in Canada and the USA all experience strong adverse impacts from extratropical storm activity from time to time. Society would benefit if risks associated with ETCs and storm activity variability could be reliably predicted for the upcoming season. Skillful prediction would enable affected sectors to better anticipate, prepare for, manage, and respond to storm activity variability and the associated risks and impacts. In this study, the potential predictability of seasonal variations in extratropical storm activity is investigated using analysis of variance to provide quantitative and geographical observational evidence indicative of whether it may be possible to predict storm activity on the seasonal timescale. This investigation will also identify origins of the potential predictability using composite analysis and large-scale teleconnections (Southern Oscillation, Pacific Decadal Oscillation, and North Atlantic Oscillation), providing the basis upon which seasonal predictions can be developed. Seasonal potential predictability and its origins are investigated for the cold seasons (OND, NDJ, DJF, JFM) during the 1979-2015 time period using daily mean sea level pressure, absolute pressure tendency, and 10-m wind speed from the ECMWF ERA-Interim reanalysis as proxies for extratropical storm activity. Results indicate potential predictability of seasonal variations in storm activity in areas strongly influenced by ETCs and with origins in the investigated teleconnections. For instance, the North Pacific storm track has considerable potential predictability and with notable origins in the SO and PDO.
Tracking the unconscious generation of free decisions using ultra-high field fMRI.
Bode, Stefan; He, Anna Hanxi; Soon, Chun Siong; Trampel, Robert; Turner, Robert; Haynes, John-Dylan
2011-01-01
Recently, we demonstrated using functional magnetic resonance imaging (fMRI) that the outcome of free decisions can be decoded from brain activity several seconds before reaching conscious awareness. Activity patterns in anterior frontopolar cortex (BA 10) were temporally the first to carry intention-related information and thus a candidate region for the unconscious generation of free decisions. In the present study, the original paradigm was replicated and multivariate pattern classification was applied to functional images of frontopolar cortex, acquired using ultra-high field fMRI at 7 Tesla. Here, we show that predictive activity patterns recorded before a decision was made became increasingly stable with increasing temporal proximity to the time point of the conscious decision. Furthermore, detailed questionnaires exploring subjects' thoughts before and during the decision confirmed that decisions were made spontaneously and subjects were unaware of the evolution of their decision outcomes. These results give further evidence that FPC stands at the top of the prefrontal executive hierarchy in the unconscious generation of free decisions.
von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica L; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A; Moskowitz, Michael A; Lo, Eng H; Dreier, Jens P; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk
2015-03-04
Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes stroke patients to PIDs as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. Copyright © 2015 Elsevier Inc. All rights reserved.
von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A.; Moskowitz, Michael A.; Lo, Eng H.; Dreier, Jens P.; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk
2015-01-01
SUMMARY Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes to PIDs in human stroke as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. PMID:25741731
NASA Astrophysics Data System (ADS)
Imran, M.; Ikram, M.; Dilpazir, S.; Nafees, M.; Ali, S.; Geng, J.
2017-11-01
The article investigates the effects of NiO (p-type) and TiO2 (n-type) nanoparticles (NPs) on the performance of poly(3-hexylthiophene) (P3HT) and (phenyl-C61-butyric acid methylester) (PCBM) based devices with an inverse geometry. Various weight ratios of these nanoparticles were mixed in the polymer solution using 1,2-dichlorobenzene as solvent. An optimal amount of NPs-doped active layer exhibited higher power conversion efficiency (PCE) of 3.85% as compared to the reference cell, which exhibited an efficiency of 3.40% under white light illumination intensity of 100 mW/cm2. Enhanced PCE originates from increased film roughness and light harvesting due to increased absorption range upon mixing an optimal amount of NPs in the organic-based active layer. Further addition of NiO and TiO2 concentration relative to PCBM resulted in significant agglomeration of nanoparticles leading to degraded device parameters.
Synthesis of organic/inorganic hybrid gel with acid activated clay after γ-ray radiation.
Kim, Donghyun; Lee, Hoik; Sohn, Daewon
2014-08-01
A hybrid gel was prepared from acid activated clay (AA clay) and acrylic acid by gamma ray irradiation. Irradiated inorganic particles which have peroxide groups act as initiator because it generates oxide radicals by increasing temperature. Inorganic nanoparticles which are rigid part in hybrid gel also contribute to increase the mechanical property as a crosslinker. We prepared two hybrid gels to compare the effect of acid activated treatment of clay; one is synthesized with raw clay particles and another is synthesized with AA clay particles. The composition and structure of AA clay particles and raw clay particles were confirmed by X-ray diffraction (XRD), X-ray fluorescence instrument and surface area analyzer. And chemical and physical property of hybrid gel with different ratios of acrylic acid and clay particle was tested by Raman spectroscope and universal testing machine (UTM). The synthesized hydrogel with 76% gel contents can elongated approximately 1000% of its original size.
Kim, Eun-Ha; Choi, Young-Ki; Kim, Chul-Joong; Sung, Moon-Hee; Poo, Haryoung
2015-10-06
The global outbreak of a novel swine-origin strain of the 2009 H1N1 influenza A virus and the sudden, worldwide increase in oseltamivir-resistant H1N1 influenza A viruses highlight the urgent need for novel antiviral therapy. Here, we investigated the antiviral efficacy of poly-gamma glutamate (γ-PGA), a safe and edible biomaterial that is naturally synthesized by Bacillus subtilis, against A/Puerto Rico/8/1934 (PR8) and A/California/04/2009 (CA04) H1N1 influenza A virus infections in C57BL/6 mice. Intranasal administration of γ-PGA for 5 days post-infection improved survival, increased production of antiviral cytokines including interferon-beta (IFN-β) and interleukin-12 (IL-12), and enhanced activation of natural killer (NK) cells and influenza antigen-specific cytotoxic T lymphocytes (CTL) activity. These results suggest that γ-PGA protects mice against H1N1 influenza A virus by enhancing antiviral immune responses.
NASA Astrophysics Data System (ADS)
Ortego, Pedro; Rodriguez, Alain; Töre, Candan; Compadre, José Luis de Diego; Quesada, Baltasar Rodriguez; Moreno, Raul Orive
2017-09-01
In order to increase the storage capacity of the East Spent Fuel Pool at the Cofrentes NPP, located in Valencia province, Spain, the existing storage stainless steel racks were replaced by a new design of compact borated stainless steel racks allowing a 65% increase in fuel storing capacity. Calculation of the activation of the used racks was successfully performed with the use of MCNP4B code. Additionally the dose rate at contact with a row of racks in standing position and behind a wall of shielding material has been calculated using MCNP4B code as well. These results allowed a preliminary definition of the burnker required for the storage of racks. Recently the activity in the racks has been recalculated with SEACAB system which combines the mesh tally of MCNP codes with the activation code ACAB, applying the rigorous two-step method (R2S) developed at home, benchmarked with FNG irradiation experiments and usually applied in fusion calculations for ITER project.
Fibrin Formation, Structure and Properties
Weisel, John W.; Litvinov, Rustem I.
2017-01-01
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin. PMID:28101869
Perry, Carlton; Blake, Pamela; Buettner, Catherine; Papavassiliou, Efstathios; Schain, Aaron; Bhasin, Manoj; Burstein, Rami
2016-01-01
Objective Chronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. In fact, a distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches. Methods We biopsied and measured the expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses in affected (i.e., where the head hurts) calvarial periosteum of (a) patients whose CMs are associated with muscle tenderness and (b) patients with no history of headache. Results Expression of proinflammatory genes (e.g., CCL8, TLR2) in the calvarial periosteum significantly increases in CM patients attesting to muscle tenderness, whereas expression of genes that suppress inflammation and immune cell differentiation (e.g., IL10RA, CSF1R) decreased. Interpretation Because the up-regulated genes were linked to activation of white blood cells, production of cytokines, and inhibition of NFKB, and the down-regulated genes linked to prevention of macrophage activation and cell lysis, we suggest that the molecular environment surrounding periosteal pain fibers is inflamed and in turn activates trigeminovascular nociceptors that reach the affected periosteum through suture branches of intracranial meningeal nociceptors and/or somatic branches of the occipital nerve. This study provides the first set of evidence for localized extracranial pathophysiology in chronic migraine. PMID:27091721
ERIC Educational Resources Information Center
Barr, Marilynn G.
This seasonal idea/activity book for grades 1-6 features interesting facts on the origins of traditions and customs of spring and summer festivals from around the world. There are numerous hands-on art activities, a map of each country or continent of the activity's origin, and a brief explanation of each tradition. Areas and countries of the…
Mesner, Larry D.; Valsakumar, Veena; Karnani, Neerja; Dutta, Anindya; Hamlin, Joyce L.; Bekiranov, Stefan
2011-01-01
We have used a novel bubble-trapping procedure to construct nearly pure and comprehensive human origin libraries from early S- and log-phase HeLa cells, and from log-phase GM06990, a karyotypically normal lymphoblastoid cell line. When hybridized to ENCODE tiling arrays, these libraries illuminated 15.3%, 16.4%, and 21.8% of the genome in the ENCODE regions, respectively. Approximately half of the origin fragments cluster into zones, and their signals are generally higher than those of isolated fragments. Interestingly, initiation events are distributed about equally between genic and intergenic template sequences. While only 13.2% and 14.0% of genes within the ENCODE regions are actually transcribed in HeLa and GM06990 cells, 54.5% and 25.6% of zonal origin fragments overlap transcribed genes, most with activating chromatin marks in their promoters. Our data suggest that cell synchronization activates a significant number of inchoate origins. In addition, HeLa and GM06990 cells activate remarkably different origin populations. Finally, there is only moderate concordance between the log-phase HeLa bubble map and published maps of small nascent strands for this cell line. PMID:21173031
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-16
... techniques or other forms of information technology. DATES: Written comments should be submitted by July 15... DEPARTMENT OF TRANSPORTATION Research & Innovative Technology Administration [Docket ID Number RITA 2008-0002] Agency Information Collection; Activity Under OMB Review; Passenger Origin-Destination...
Role of the hydrophilic channels of simian virus 40 T-antigen helicase in DNA replication.
Wang, Weiping; Manna, David; Simmons, Daniel T
2007-05-01
The simian virus 40 (SV40) hexameric helicase consists of a central channel and six hydrophilic channels located between adjacent large tier domains within each hexamer. To study the function of the hydrophilic channels in SV40 DNA replication, a series of single-point substitutions were introduced at sites not directly involved in protein-protein contacts. The mutants were characterized biochemically in various ways. All mutants oligomerized normally in the absence of DNA. Interestingly, 8 of the 10 mutants failed to unwind an origin-containing DNA fragment and nine of them were totally unable to support SV40 DNA replication in vitro. The mutants fell into four classes based on their biochemical properties. Class A mutants bound DNA normally and had normal ATPase and helicase activities but failed to unwind origin DNA and support SV40 DNA replication. Class B mutants were compromised in single-stranded DNA and origin DNA binding at low protein concentrations. They were defective in helicase activity and unwinding of the origin and in supporting DNA replication. Class C and D mutants possessed higher-than-normal single-stranded DNA binding activity at low protein concentrations. The class C mutants failed to separate origin DNA and support DNA replication. The class D mutants unwound origin DNA normally but were compromised in their ability to support DNA replication. Taken together, these results suggest that the hydrophilic channels have an active role in the unwinding of SV40 DNA from the origin and the placement of the resulting single strands within the helicase.
Thomas, H.E.
1970-01-01
Throughout human history various laws and customs have developed concerning the individual rights and rights in common to the waters of the earth. Many existing laws and concepts are clearly influenced by the environment in which they originated and reflect the relative abundance or scarcity of water. Many concepts reflect the people's original interests in the water and once established have been passed from generation to generation with little modification. Some laws and concepts have been carried by people in their migrations and colonial expansions to vastly different environments, with rather curious consequences. In many places water laws that had been well adapted to the natural environment have become less tenable because of man's activities in modifying that environment, or because of increasing use of water: Increasing consumptive use shifts the water economy toward lesser abundance or increasing deficiency; increasing nonconsumptive use results in pollution of the water resources, so that they become less suitable for other users. The water-rights systems in the United States vary from State to State: some are reasonably fitted to their environment, some have outlived their place in history, some are wasteful of water, some show favoritism to certain special interests or segments of the population. Water-use rights are universally recognized as real property, with constitutional protection against deprivation without due process of law.
Piulats, Jose M; Kondo, Jumpei; Endo, Hiroko; Ono, Hiromasa; Hagihara, Takeshi; Okuyama, Hiroaki; Nishizawa, Yasuko; Tomita, Yasuhiko; Ohue, Masayuki; Okita, Kouki; Oyama, Hidejiro; Bono, Hidemasa; Masuko, Takashi; Inoue, Masahiro
2018-03-23
Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell-cell contact. After the disruption, 9 spheroid lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines exhibited accelerated spheroid growth. Marker expression, spheroid forming capacity, and tumorigenesis indicated that stemness increased after spheroid disruption. In addition, the spheroid forming capacity increased in 6 of 11 spheroid lines. The disruption signature determined by gene expression profiling supported the incidence of remodeling and predicted the prognosis of patients with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increased proliferation and stemness after the disruption. Overall, the disruption and subsequent reformation of cancer spheroids promoted malignancy-related phenotypes through the activation of the WNT and ERBB pathways.
Endo, Hiroko; Ono, Hiromasa; Hagihara, Takeshi; Okuyama, Hiroaki; Nishizawa, Yasuko; Tomita, Yasuhiko; Ohue, Masayuki; Okita, Kouki; Oyama, Hidejiro; Bono, Hidemasa; Masuko, Takashi; Inoue, Masahiro
2018-01-01
Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell–cell contact. After the disruption, 9 spheroid lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines exhibited accelerated spheroid growth. Marker expression, spheroid forming capacity, and tumorigenesis indicated that stemness increased after spheroid disruption. In addition, the spheroid forming capacity increased in 6 of 11 spheroid lines. The disruption signature determined by gene expression profiling supported the incidence of remodeling and predicted the prognosis of patients with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increased proliferation and stemness after the disruption. Overall, the disruption and subsequent reformation of cancer spheroids promoted malignancy-related phenotypes through the activation of the WNT and ERBB pathways. PMID:29662620
Serum prolactin in coeliac disease: a marker for disease activity
Reifen, R.; Buskila, D.; Maislos, M.; Press, J.; Lerner, A.
1997-01-01
Accepted 21 April 1997 Prolactin, a polypeptide hormone of anterior pituitary origin, has pronounced physiological effects on growth, reproduction, and osmoregulation. Increasing evidence indicates that prolactin also has an immunomodulatory influence on the immune system. The status of prolactin in patients with coeliac disease was investigated by obtaining serum samples from 48 patients with active and non-active coeliac disease. These were compared with samples from 20 children with familial Mediterranean fever and 65 normal controls. Serum prolactin in patients with active coeliac disease was significantly higher than in the other groups studied and reference values. Serum prolactin correlated well with the degree of mucosal atrophy and with the serum concentration of antiendomysial antibodies. Prolactin may play a part in immune modulation in the intestinal damage of coeliac disease and serve as a potential marker for disease activity. PMID:9301358
Hayano, Motoshi; Kanoh, Yutaka; Matsumoto, Seiji; Masai, Hisao
2011-01-01
How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1Δ cells (and in swi1Δ cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1Δ cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein. PMID:21518960
MacAlpine, Heather K.; Lubelsky, Yoav; Hartemink, Alexander J.
2015-01-01
Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2–7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replication origins. To reveal how the chromatin architecture modulates origin selection and activation, we “footprinted” nucleosomes, transcription factors, and replication proteins at multiple points during the Saccharomyces cerevisiae cell cycle. Our nucleotide-resolution protein occupancy profiles resolved a precise ORC-dependent footprint at 269 origins in G2. A separate class of inefficient origins exhibited protein occupancy only in G1, suggesting that stable ORC chromatin association in G2 is a determinant of origin efficiency. G1 nucleosome remodeling concomitant with pre-RC assembly expanded the origin nucleosome-free region and enhanced activation efficiency. Finally, the local chromatin environment restricts the loading of the Mcm2–7 double hexamer either upstream of or downstream from the ARS consensus sequence (ACS). PMID:25593310
Ji, Sang Min; Borse, Pramod H; Kim, Hyun Gyu; Hwang, Dong Won; Jang, Jum Suk; Bae, Sang Won; Lee, Jae Sung
2005-03-21
Nitrogen-doped perovskite type materials, Sr2Nb2O7-xNx (0, 1.5 < x < 2.8), have been studied as visible light-active photocatalysts for hydrogen production from methanol-water mixtures. Nitrogen doping in Sr2Nb2O7 red-shifted the light absorption edge into the visible light range and induced visible light photocatalytic activity. There existed an optimum amount of nitrogen doping that showed the maximum rate of hydrogen production. Among the potential variables that might cause this activity variation, the crystal structure appeared to be the most important. Thus, as the extent of N-doping increased, the original orthorhombic structure of the layered perovskite was transformed into an unlayered cubic oxynitride structure. The most active catalytic phase was an intermediate phase still maintaining the original layered perovskite structure, but with a part of its oxygen replaced by nitrogen and oxygen vacancy to adjust the charge difference between oxygen and doped nitrogen. These experimental observations were explained by density functional theory calculations. Thus, in Sr2Nb2O7-xNx, N2p orbital was the main contributor to the top of the valence band, causing band gap narrowing while the bottom of conduction band due to Nb 4d orbital remained almost unchanged.
Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.
Wiley, Jenny L; Marusich, Julie A; Thomas, Brian F
2017-01-01
Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB 1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ 9 -tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB 1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.
OORT-Cloud and Kuiper-Belt Comets
NASA Technical Reports Server (NTRS)
Whipple, Fred L.
1998-01-01
This paper follows the broadly accepted theory that Oort-Cloud Comets originated in the Solar Nebula in the general region where the major planets, Jupiter and Saturn, were formed while the Kuiper-Belt Comets originated farther out where the temperatures were lower. The Oort-Cloud Comets are identified orbitally by long periods and random inclinations and, including the Halley-type comets, comets with a Tisserand Criterion less than 2.0. Kuiper-Belt comets are identified by short periods, usually much less than 200 years, and small inclinations to the ecliptic. Here two criteria for comet activity are found to separate the two classes of comets. These quantities NG1 and NG2, were intended to measure theoretical nongravitaional effects on comet orbits. They are only, mildly successful in correlations with observed cases of measured non-gravitational forces. But, in fact, their variations with perihelion distance separate the two classes of comets. The results are consistent with the theory that the activity or intrinsic brightness of Oort-Cloud Comets fall off faster with increasing perihelion distance that does the intrinsic brightness of short-period Kuiper-Belt Comets.
Faster proton transfer dynamics of water on SnO2 compared to TiO2.
Kumar, Nitin; Kent, Paul R C; Bandura, Andrei V; Kubicki, James D; Wesolowski, David J; Cole, David R; Sofo, Jorge O
2011-01-28
Proton jump processes in the hydration layer on the iso-structural TiO(2) rutile (110) and SnO(2) cassiterite (110) surfaces were studied with density functional theory molecular dynamics. We find that the proton jump rate is more than three times faster on cassiterite compared with rutile. A local analysis based on the correlation between the stretching band of the O-H vibrations and the strength of H-bonds indicates that the faster proton jump activity on cassiterite is produced by a stronger H-bond formation between the surface and the hydration layer above the surface. The origin of the increased H-bond strength on cassiterite is a combined effect of stronger covalent bonding and stronger electrostatic interactions due to differences of its electronic structure. The bridging oxygens form the strongest H-bonds between the surface and the hydration layer. This higher proton jump rate is likely to affect reactivity and catalytic activity on the surface. A better understanding of its origins will enable methods to control these rates.
Bokhorst, Leonard P; Roobol, Monique J; Bangma, Chris H; van Leenders, Geert J
2017-07-01
To investigate if pathologic biopsy reevaluation and implementation of immunohistochemical biomarkers could improve prediction of radical prostatectomy outcome in men initially on active surveillance. Biopsy specimens from diagnosis until switching to radical prostatectomy in men initially on active surveillance in the Dutch part of the Prostate cancer Research International Active Surveillance (PRIAS) study were collected and revised by a single pathologist. Original and revised biopsy Gleason score were compared and correlated with radical prostatectomy Gleason score. Biopsy specimens were immunohistochemically stained for Ki67 and ERG. Predictive ability of clinical characteristics and biomarkers on Gleason ≥7 or ≥pT3 on radical prostatectomy was tested using logistic regression and ROC curve analysis. A total of 150 biopsies in 95 men were revised. In 13% of diagnostic or second-to-last biopsies and 20% of the last biopsies on active surveillance revision of Gleason score resulted in change of recommendation (ie, active treatment or active surveillance). Concordance with Gleason score on radical prostatectomy was however similar for both the revised and original Gleason on biopsy. Ki67 and ERG were not statistically significant predictors of Gleason ≥7 or ≥pT3 on radical prostatectomy. Although interobserver differences in pathology reporting on biopsy could result in a change of management strategy in approximately 13-20% of men on active surveillance, both pathological revision and tested biomarkers (Ki67 and ERG) did not improve prediction of outcome on radical prostatectomy. Undersampling of most aggressive tumor remains the main focus in order to increase accurate grading at time of treatment decision making. © 2017 Wiley Periodicals, Inc.
Riber, Leise; Fujimitsu, Kazuyuki; Katayama, Tsutomu; Løbner-Olesen, Anders
2009-01-01
Initiation of chromosome replication in Escherichia coli is limited by the initiator protein DnaA associated with ATP. Within the replication origin, binding sites for DnaA associated with ATP or ADP (R boxes) and the DnaA(ATP) specific sites (I-boxes, tau-boxes and 6-mer sites) are found. We analysed chromosome replication of cells carrying mutations in conserved regions of oriC. Cells carrying mutations in DnaA-boxes I2, I3, R2, R3 and R5 as well as FIS and IHF binding sites resembled wild-type cells with respect to origin concentration. Initiation of replication in these mutants occurred in synchrony or with slight asynchrony only. Furthermore, lack of Hda stimulated initiation in all these mutants. The DnaA(ATP) containing complex that leads to initiation can therefore be formed in the absence of several of the origin DnaA binding sites including both DnaA(ATP) specific I-boxes. However, competition between I-box mutant and wild-type origins, revealed a positive role of I-boxes on initiation. On the other hand, mutations affecting DnaA-box R4 were found to be compromised for initiation and could not be augmented by an increase in cellular DnaA(ATP)/DnaA(ADP) ratio. Compared with the sites tested here, R4 therefore seems to contribute to initiation most critically.
2013-05-01
A well-regulated militia was advocated by Washington, Jefferson, and Madison, and attempts were made to enable a law to insure an effective...Shadow Warriors: OSS and the Origins of the CIA, 11–12, 15, 21. The now known to be myth of Germany fifth column activities were persuasive enough...contractually, yet re-sell their CRAF flights. The combined impacts of deregulation and corporate financing require predictability in the “fixed buy
Rep. Bishop, Rob [R-UT-1
2009-06-19
House - 06/26/2009 Referred to the Subcommittee on Federal Workforce, Post Office, and the District of Columbia. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:
Rep. Bishop, Rob [R-UT-1
2011-05-12
House - 05/13/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy . (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:
The abundance of nitrogen in starburst nucleus galaxies
NASA Astrophysics Data System (ADS)
Coziol, R.; Reyes, R. E. Carlos; Considère, S.; Davoust, E.; Contini, T.
1999-05-01
We show that the excess of nitrogen emission observed in a large sample of Starburst Nucleus Galaxies (SBNGs) can only be explained at a given metallicity by an overabundance of nitrogen with respect to normal H ii regions in the disks of late-type spirals. The N/O ratios in the SBNGs are comparable to the values found in the bulges of normal early-type spirals, which suggests that what we observe could be the main production of nitrogen in the bulges of these galaxies. The variation of the N/O ratio as a function of metallicity in SBNGs follows a primary + secondary relation, but the increase of nitrogen does not appear as a continuous process. In SBNGs, nitrogen is probably produced by different populations of intermediate-mass stars, which were formed during past sequences of bursts of star formation. This assumption pushes the origin of the main bursts 2-3 Gyrs back in the past. On a cosmological scale, this time interval corresponds to redshifts z ~ 0.2-0.3, where a significant increase of star formation activity occurred. The origin of the SBNG phenomenon would thus have cosmological implications, it would be related to a more active phase of star formation in the Universe sometime in its recent past. Based on observations obtained at the 193cm telescope of Observatoire de Haute-Provence, operated by INSU (CNRS)
Nitrogen Deposition: A Component of Global Change Analyses
DOE Office of Scientific and Technical Information (OSTI.GOV)
Norby, Richard J.
1997-12-31
The global cycles of carbon and nitrogen are being perturbed by human activities that increase the transfer from large pools of nonreactive forms of the elements to reactive forms that are essential to the functioning of the terrestrial biosphere. The cycles are closely linked at all scales, and global change analyses must consider carbon and nitrogen cycles together. The increasing amount of nitrogen originating from fossil fuel combustion and deposited to terrestrial ecosystems as nitrogen oxides could increase the capacity of ecosystems to sequester carbon thereby removing some of the excess carbon dioxide from the atmosphere and slowing the developmentmore » of greenhouse warming. Several global and ecosystem models have calculated the amount of carbon sequestration that can be attributed to nitrogen deposition based on assumptions about the allocation of nitrogen among ecosystem components with different carbon-nitrogen ratios. They support the premise that nitrogen deposition is responsible for a an increasing terrestrial carbon sink since industrialization began, but there are large uncertainties related to the continued capacity of ecosystems to retain exogenous nitrogen. Whether terrestrial ecosystems continue to sequester additional carbon will depend in part on their response to increasing atmospheric carbon dioxide concentrations, which is widely thought to be constrained by limited nitrogen availability. Ecosystem models generally support the conclusion that the responses of ecosystems to increasing concentrations of carbon dioxide will be larger, and the range of possible responses will be wider, in ecosystems with increased nitrogen inputs originating as atmospheric deposition.« less
Weaver, Sally P; Lastrapes, Ellie
2014-06-01
Scholarly activity in the form of original research presentations is valuable to the discipline of family medicine. Two major venues for family medicine researchers to present their work are the Society of Teachers of Family Medicine (STFM) Annual Spring Conference and the North American Primary Care Research Group (NAPCRG) Annual Meeting. Both of these organizations have seen increasing numbers of submissions and subsequent presentations in recent years. The purpose of this project was to analyze the trend in increasing presentations and document the incidence of duplicate research presentations across these two meetings. Numbers of primary authors and coauthors were assessed and compared across meetings from 2009 to 2012. Abstracts from the same author(s) presenting at consecutive meetings were compared for originality. STFM has had a nearly 50% increase in numbers of presentations from 2009 to 2012, and NAPCRG has seen a 17.6% increase. There has been an 88.2% increase in the number of presentation authors and coauthors who present at consecutive meetings during the same time frame. Four duplicate research presentations were found from 2009 through spring of 2012. Numbers of author and coauthor presenters at STFM and NAPCRG annual meetings have increased greatly since 2009. Very little duplication of research presentations was found. It appears that, for the most part, presenters at both STFM and NAPCRG are not presenting duplicate research projects. This is even more important now with limited space at meetings due to record numbers of presentations.
Hemmati, Roohullah; Hosseinkhani, Saman; Sajedi, Reza H; Azad, Taha; Tashakor, Amin; Bakhtiari, Nuredin; Ataei, Farangis
2015-01-01
Luciferin-regenerating enzyme (LRE) contributes to in vitro recycling of D-luciferin. In this study, reinvestigation of the luciferase-based LRE assay is reported. Here, using quick change site-directed mutagenesis seven T-LRE (Lampyris turkestanicusLRE) mutants were constructed and the most functional mutant of T-LRE (T(69)R) was selected for this research and the effects of D- and L-cysteine on T(69)R T-LRE-luciferase-coupled assay are examined. Our results demonstrate that bioluminescent signal of T(69)R T-LRE-luciferase-coupled assay increases and then reach equilibrium state in the presence of 5 mm D-cysteine. In addition, results reveal that 5 mm D- and L-cysteine in the absence of T(69)R T-LRE cause a significant increase in bioluminescence intensity of luciferase over a long time as well as decrease in decay rate. Based on activity measurements, far-UV CD analysis, ANS fluorescence and DLS (Dynamic light scattering) results, D-cysteine increases the activity of luciferase due to weak redox potential, antiaggregatory effects, induction of changes in conformational structure and kinetics properties. In conclusion, in spite of previous reports on the effect of LRE on luciferase bioluminescent intensity, the majority of increase in luciferase light output and time-course originate from the direct effects of D-cysteine on structure and activity of firefly luciferase. © 2015 The American Society of Photobiology.
Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities
Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M
2008-01-01
Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery. PMID:19696873
Scale Development for Perceived School Climate for Girls' Physical Activity
ERIC Educational Resources Information Center
Birnbaum, Amanda S.; Evenson, Kelly R.; Motl, Robert W.; Dishman, Rod K.; Voorhees, Carolyn C.; Sallis, James F.; Elder, John P.; Dowda, Marsha
2005-01-01
Objectives: To test an original scale assessing perceived school climate for girls' physical activity in middle school girls. Methods: Confirmatory factor analysis (CFA) and structural equation modeling (SEM). Results: CFA retained 5 of 14 original items. A model with 2 correlated factors, perceptions about teachers' and boys' behaviors,…
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2010-01-20
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Tune Up to Literacy: Original Songs and Activities for Kids
ERIC Educational Resources Information Center
Balkin, Al
2009-01-01
Encourage literacy with twenty original songs by musician and educator Al Balkin! Children's and school librarians will welcome "Tune Up to Literacy", a handy package of music and activities that musically introduces and reinforces crucial literacy concepts such as the alphabet, vowels, consonants, nouns, verbs, adjectives, sentence construction,…
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-12
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Spreading activation in emotional memory networks and the cumulative effects of somatic markers.
Foster, Paul S; Hubbard, Tyler; Campbell, Ransom W; Poole, Jonathan; Pridmore, Michael; Bell, Chris; Harrison, David W
2017-06-01
The theory of spreading activation proposes that the activation of a semantic memory node may spread along bidirectional associative links to other related nodes. Although this theory was originally proposed to explain semantic memory networks, a similar process may be said to exist with episodic or emotional memory networks. The Somatic Marker hypothesis proposes that remembering an emotional memory activates the somatic sensations associated with the memory. An integration of these two models suggests that as spreading activation in emotional memory networks increases, a greater number of associated somatic markers would become activated. This process would then result in greater changes in physiological functioning. We sought to investigate this possibility by having subjects recall words associated with sad and happy memories, in addition to a neutral condition. The average ages of the memories and the number of word memories recalled were then correlated with measures of heart rate and skin conductance. The results indicated significant positive correlations between the number of happy word memories and heart rate (r = .384, p = .022) and between the average ages of the sad memories and skin conductance (r = .556, p = .001). Unexpectedly, a significant negative relationship was found between the number of happy word memories and skin conductance (r = -.373, p = .025). The results provide partial support for our hypothesis, indicating that increasing spreading activation in emotional memory networks activates an increasing number of somatic markers and this is then reflected in greater physiological activity at the time of recalling the memories.
Entropy-scaling laws for diffusion coefficients in liquid metals under high pressures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cao, Qi-Long, E-mail: qlcao@mail.ustc.edu.cn; Shao, Ju-Xiang; Wang, Fan-Hou, E-mail: eatonch@gmail.com
2015-04-07
Molecular dynamic simulations on the liquid copper and tungsten are used to investigate the empirical entropy-scaling laws D{sup *}=A exp(BS{sub ex}), proposed independently by Rosenfeld and Dzugutov for diffusion coefficient, under high pressure conditions. We show that the scaling laws hold rather well for them under high pressure conditions. Furthermore, both the original diffusion coefficients and the reduced diffusion coefficients exhibit an Arrhenius relationship D{sub M}=D{sub M}{sup 0} exp(−E{sub M}/K{sub B}T), (M=un,R,D) and the activation energy E{sub M} increases with increasing pressure, the diffusion pre-exponential factors (D{sub R}{sup 0} and D{sub D}{sup 0}) are nearly independent of the pressure and element. Themore » pair correlation entropy, S{sub 2}, depends linearly on the reciprocal temperature S{sub 2}=−E{sub S}/T, and the activation energy, E{sub S}, increases with increasing pressure. In particular, the ratios of the activation energies (E{sub un}, E{sub R}, and E{sub D}) obtained from diffusion coefficients to the activation energy, E{sub S}, obtained from the entropy keep constants in the whole pressure range. Therefore, the entropy-scaling laws for the diffusion coefficients and the Arrhenius law are linked via the temperature dependence of entropy.« less
The Irish contribution to the plastic surgery literature: 21 years of publications.
Rahmani, G; Joyce, C W; Jones, D M; Kelly, J L; Hussey, A J; Regan, P J
2015-09-01
The Republic of Ireland has always had an influence on medicine and has produced many renowned doctors who have helped shape its history. Furthermore, many clinical articles that have originated from Ireland have changed clinical practice throughout the world. The Irish have also had an impact on the plastic surgery literature yet it has never specifically been analyzed before. The purpose of this study was to identify and analyze all papers that have originated from the plastic surgery units in the Republic of Ireland in the medical literature over the past 21 years. Twenty-four well-known plastic surgery, hand surgery and burns journals were selected for this study. By utilizing Scopus, the largest abstract and citation database of peer-reviewed literature, we analyzed each of our chosen 24 journals looking for Irish publications. Each paper was examined for article type, authorship, year of publication, institution of origin and level of evidence. Papers from the Republic of Ireland were published in 20 of the 24 journals over the past 21 years. A total of 245 articles from Ireland were published in the plastic surgery, hand surgery and burns literature over the 21-year period. Of these, 111 were original articles and 73 were case reports. The institution that published the most papers over the past 21 years was University Hospital Galway (66 publications) followed by Cork University Hospital with 54 papers. The journal with the most Irish articles was the Journal of Plastic, Reconstructive and Aesthetic Surgery with 56 papers. 2014 was the year with the most publications (28 papers). Authorship numbers also increased over time as the average number of authors in 1994 was 3.5, whereas it was 5.54 in 2014. The number of publications per year continues to increase along with authorship numbers. This mirrors the trend in other specialties. Publications are now no longer required for selection on to a higher surgical training scheme. There is now a fear that the academic output of trainees will decrease as a consequence. To prevent this, each unit must actively support and encourage research activity with their trainees.
Waste activated sludge fermentation: effect of solids retention time and biomass concentration.
Yuan, Q; Sparling, R; Oleszkiewicz, J A
2009-12-01
Laboratory scale, room temperature, semi-continuous reactors were set-up to investigate the effect of solids retention time (SRT, equal to HRT hydraulic retention time) and biomass concentration on generation of volatile fatty acids (VFA) from the non-methanogenic fermentation of waste activated sludge (WAS) originating from an enhanced biological phosphorus removal process. It was found that VFA yields increased with SRT. At the longest SRT (10d), improved biomass degradation resulted in the highest soluble to total COD ratio and the highest VFA yield from the influent COD (0.14g VFA-COD/g TCOD). It was also observed that under the same SRT, VFA yields increased when the biomass concentration decreased. At a 10d SRT the VFA yield increased by 46%, when the biomass concentration decreased from 13g/L to 4.8g/L. Relatively high nutrient release was observed during fermentation. The average phosphorus release was 17.3mg PO(4)-P/g TCOD and nitrogen release was 25.8mg NH(4)-N/g TCOD.
Production, thermal stability and immobilisation of inulinase from Fusarium oxysporum.
Gupta, A K; Rathore, P; Kaur, N; Singh, R
1990-01-01
Fusarium oxysporum produced maximum extracellular inulinase after 9 days of its growth at 25 degrees C on a medium (pH 5.5) containing 3% fructan and 0.2% sodium nitrate. The level of this enzyme decreased on the addition of either glucose, fructose, galactose or sucrose to F. oxysporum already growing on a fructan-containing medium. A significant increase in invertase production which resulted in an increase of the invertase/inulinase (S/I) ratio, was observed on addition of inulin to this fungus growing on other carbon sources. Glycerol (10%) gave better protection to inulinase against thermal denaturation at 50 degrees C compared to ethylene glycol and sorbitol. Inulinase immobilised in polyacrylamide gel retained 45% of its original activity. The immobilised enzyme showed a higher optimum temperature (45 degrees C) compared to free enzyme (37 degrees C). The immobilised enzyme after storage at 25 degrees C for 96 h showed 58% activity. Thermal stability of entrapped inulinase increased in the presence of inulin.
Analysis of creative mathematical thinking ability by using model eliciting activities (MEAs)
NASA Astrophysics Data System (ADS)
Winda, A.; Sufyani, P.; Elah, N.
2018-05-01
Lack of creative mathematical thinking ability can lead to not accustomed with open ended problem. Students’ creative mathematical thinking ability in the first grade at one of junior high school in Tangerang City is not fully developed. The reason of students’ creative mathematical thinking ability is not optimally developed is so related with learning process which has done by the mathematics teacher, maybe the learning design that teacher use is unsuitable for increasing students’ activity in the learning process. This research objective is to see the differences in students’ ways of answering the problems in terms of students’ creative mathematical thinking ability during the implementation of Model Eliciting Activities (MEAs). This research use post-test experimental class design. The indicators for creative mathematical thinking ability in this research arranged in three parts, as follow: (1) Fluency to answer the problems; (2) Flexibility to solve the problems; (3) Originality of answers. The result of this research found that by using the same learning model and same instrument from Model Eliciting Activities (MEAs) there are some differences in the way students answer the problems and Model Eliciting Activities (MEAs) can be one of approach used to increase students’ creative mathematical thinking ability.
Spina-Cruz, Mylena; Maniero, Milena Guedes; Guimarães, José Roberto
2018-05-08
Advanced oxidation processes (AOPs) have been highly efficient in degrading contaminants of emerging concern (CEC). This study investigated the efficiency of photolysis, peroxidation, photoperoxidation, and ozonation at different pH values to degrade doxycycline (DC) in three aqueous matrices: fountain, tap, and ultrapure water. More than 99.6% of DC degradation resulted from the UV/H 2 O 2 and ozonation processes. Also, to evaluate the toxicity of the original solution and throughout the degradation time, antimicrobial activity tests were conducted using Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria, and acute toxicity test using the bioluminescent marine bacterium (Vibrio fischeri). Antimicrobial activity reduced as the drug degradation increased in UV/H 2 O 2 and ozonation processes, wherein the first process only 6 min was required to reduce 100% of both bacteria activity. In ozonation, 27.7 mg L -1 of ozone was responsible for reducing 100% of the antimicrobial activity. When applied the photoperoxidation process, an increase in the toxicity occurred as the high levels of degradation were achieved; it means that toxic intermediates were formed. The ozonated solutions did not present toxicity.
Yokoyama, Ayaka; Miyamoto, Hiroko; Kajihara, Masahiro; Maruyama, Junki; Nao, Naganori; Manzoor, Rashid; Takada, Ayato
2014-01-01
Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity. PMID:24465606
Mols, J; Peeters-Joris, C; Wattiez, R; Agathos, S N; Schneider, Y-J
2005-01-01
Biosafety requirements increasingly restrict the cultivation of mammalian cells producing therapeutic glycoproteins to conditions that are devoid of any compound of animal origin. On cultivation in serum-free media, the proteases inhibitors, usually found in serum, cannot protect secreted recombinant proteins against unwanted endogenous proteolysis. Chinese hamster ovary (CHO) cells, secreting recombinant human interferon-gamma (CHO-320 cell line) and cultivated in suspension in an original protein-free medium, expressed at least two members of the matrix metalloproteinases (MMP), either at the cell surface (proMMP-14 and MMP-14) or secreted (proMMP-9). In addition, tissue- and urinary-type plasminogen activators were also secreted in such culture conditions. At the cell surface, dipeptidyl peptidase IV and tripeptidyl peptidase II (TPPII) activities were also detected, and their activities decreased during time course of batch cultures. The proteolytic activities of these proteins were counterbalanced by (1) their expression as zymogens (proMMP-9, proMMP-14), (2) the expression of their natural inhibitors, tissue inhibitors of metalloproteinases-1 and -2 and plasminogen activator inhibitor-1 (PAI-1), or (3) the addition of plant protein hydrolysates to the culture medium, acting as a nonspecific source of TPPII inhibitors. This study points out that, even in protein-free media, recombinant proteins secreted by CHO cells are actively protected against physiological and unwanted extracellular proteolysis either by endogenous or by exogenous inhibitors.
Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats
NASA Technical Reports Server (NTRS)
Moffitt, Julia A.; Heesch, Cheryl M.; Hasser, Eileen M.
2002-01-01
Attenuated baroreflex-mediated increases in renal sympathetic nerve activity (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition of the rostral ventrolateral medulla (RVLM) is increased after hindlimb unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)-bicuculline methiodide (BIC) into the RVLM were examined before and during caudal ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in response to BIC in the RVLM were significantly enhanced in HU rats. Responses to bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in the RVLM was blocked by BIC during CVLM inhibition, the additional increases in MAP and RSNA were significantly greater in HU rats. These data indicate that GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb unloading. Effects of input from the CVLM were unaltered. Thus, after cardiovascular deconditioning in rodents, the attenuated increase in sympathetic nerve activity in response to hypotension is associated with greater GABA(A) receptor-mediated inhibition of RVLM neurons originating at least in part from sources other than the CVLM.
Co-expression of five genes in E coli for L-phenylalanine in Brevibacterium flavum
Wu, Yong-Qing; Jiang, Pei-Hong; Fan, Chang-Sheng; Wang, Jian-Gang; Shang, Liang; Huang, Wei-Da
2003-01-01
AIM: To study the effect of co-expression of ppsA, pckA, aroG, pheA and tyrB genes on the production of L-phenylalanine, and to construct a genetic engineering strain for L-phenylalanine. METHODS: ppsA and pckA genes were amplified from genomic DNA of E. coli by polymerase chain reaction, and then introduced into shuttle vectors between E coli and Brevibacterium flavum to generate constructs pJN2 and pJN5. pJN2 was generated by inserting ppsA and pckA genes into vector pCZ; whereas pJN5 was obtained by introducing ppsA and pckA genes into pCZ-GAB, which was originally constructed for co-expression of aroG, pheA and tyrB genes. The recombinant plasmids were then introduced into B. flavum by electroporation and the transformants were used for L-phenylalanine fermentation. RESULTS: Compared with the original B. flavum cells, all the transformants were showed to have increased five enzyme activities specifically, and have enhanced L-phenylalanine biosynthesis ability variably. pJN5 transformant was observed to have the highest elevation of L-phenylalanine production by a 3.4-fold. Co-expression of ppsA and pckA increased activity of DAHP synthetase significantly. CONCLUSION: Co-expression of ppsA and pckA genes in B. flavum could remarkably increase the expression of DAHP synthetase; Co-expression of ppsA, pckA, aroG, pheA and tyrB of E. coli in B. flavum was a feasible approach to construct a strain for phenylalanine production. PMID:12532463
Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi
2017-10-01
Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.
Morgan, N K; Walk, C L; Bedford, M R; Burton, E J
2015-07-01
There is little consensus as to the capability of poultry to utilize dietary phytate without supplemental phytase. Therefore, an experiment was conducted to examine the extent to which endogenous phytase of intestinal and cereal origin contributes to phytate degradation in birds aged 0 to 14 d posthatch. Ross 308 broilers (n = 720) were fed one of 4 experimental diets with differing dietary ingredient combinations and approximate total phytate levels of 10 g/kg, dietary phytase activity analyzed at 460 U/kg, dietary calcium (Ca) levels of 11 g/kg, and nonphytate-phosphorus (P) levels of 4 g/kg. Broiler performance, gizzard, duodenum, jejunum and ileum pH, Ca and P digestibility and solubility, amount of dietary phytate hydrolyzed in the gizzard, jejunum, and ileal digesta phytase activity were analyzed at d 4, 6, 8, 10, 12, and 14 posthatch. Intestinal endogenous phytase activity increased significantly (P < 0.001) between d 4 and 6, resulting in increased phytate hydrolysis in the gizzard (P = 0.003), jejunum (P < 0.001), and ileum (P < 0.001). Phytase activity and phytate hydrolysis continued to increase with age, with a greater phytase activity and associated increase in phytate hydrolysis and mineral utilization between d 10 and 12. Gizzard and jejunum Ca and P solubility and ileal Ca and P digestibility increased significantly (P < 0.001), and gastrointestinal pH decreased significantly (P < 0.001) between d 4 and 6. By d 14, phytase activity recovered in the ileum was approximately 45 U/kg. There were strong correlations between phytase activity measured in the ileum and phytate hydrolyzed in the gizzard (r = 0.905, P < 0.001), jejunum (r = 0.901, P = 0.023), and ileum (r = 0.938, P = 0.042). This study shows intestinal- and dietary-derived endogenous phytase activity is responsible for phytate-P hydrolysis in broilers. © 2015 Poultry Science Association Inc.
Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain
2009-01-01
For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions ∼300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as ‘master’ replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these ‘master’ origins are likely to play a key role in genome dynamics during evolution and in pathological situations. PMID:19671527
Anning, David W.; Flynn, Marilyn E.
2014-01-01
Results from the trend analysis and from the SPARROW model indicate that, compared to monitoring stations with no trends or decreasing trends, stations with increasing trends are associated with a smaller percentage of the predicted dissolved-solids load originating from geologic sources, and a larger percentage originating from urban lands and road deicers. Conversely, compared to stations with increasing trends or no trends, stations with decreasing trends have a larger percentage of the predicted dissolved-solids load originating from geologic sources and a smaller percentage originating from urban lands and road deicers. Stations with decreasing trends also have larger percentages of predicted dissolved-solids load originating from cultivated lands and pasture lands, compared to stations with increasing trends or no trends.
Systematic dissemination of a preschool physical activity intervention to the control preschools
Howie, Erin K.; Brewer, Alisa E.; Brown, William H.; Saunders, Ruth P.; Pate, Russell R.
2016-01-01
For public health interventions to have a meaningful impact on public health, they must be disseminated to the wider population. Systematic planning and evaluation of dissemination efforts can aid translation from experimental trials to larger dissemination programs. The Study of Health and Activity in Preschool Environments (SHAPES) was a group-randomized intervention trial conducted in 16 preschools that successfully increased the physical activity of preschool age children. Following the completion of the research study protocol, the intervention was abbreviated, modified and implemented in four preschools who participated as control preschools in the original research study. The purposes of the current study were to describe the process of refining the intervention for dissemination to the control preschools, and to assess the acceptability of the resulting abbreviated intervention delivery. Five overarching behavioral objectives, informed by process evaluation, data from the original trial and collaboration with intervention teachers, were used to guide the implementation. Teachers in the dissemination classrooms reported high levels of acceptability, potential for sustainability of the program, and positive results in knowledge, skills, and child outcomes. Researchers can include a systematic approach to dissemination of effective intervention elements to the control participants in experimental studies to inform future dissemination efforts and begin to bridge the dissemination gap. PMID:27107302
Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction
Richart, Adèle; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Guerin, Coralie; Gautier, Gregory; Blank, Ulrich; Heymes, Christophe; Luche, Elodie; Cousin, Béatrice; Rodewald, Hans-Reimer
2016-01-01
Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID:27353089
Subbaiah, P V; Chen, C H; Bagdade, J D; Albers, J J
1985-01-01
The effect of various chemical and enzymatic modifications of low density lipoprotein (LDL) on its ability to activate the isolated human plasma lysolecithin acyltransferase (LAT) was studied. Removal of all lipids from LDL resulted in the complete loss of LAT activation. Removal of only neutral lipids by extraction with heptane retained up to 50% of the original activity, which was not increased further by reconstitution of the LDL with the extracted lipids. Hydrolysis of the diacylphosphoglycerides of the LDL with phospholipases resulted in complete loss of LAT activation which was partially restored by the addition of egg lecithin. Hydrolysis of more than 4% of LDL protein by trypsin led to a linear decrease in activity with complete loss of activity occurring when about 25% of the LDL protein is hydrolyzed. Modification of the arginine groups of LDL reversibly inhibited the activation of LAT. Modification of lysine residues of LDL by acetylation, acetoacetylation or succinylation also abolished its ability to activate lysolecithin acylation.
Siddiqui, Khawar Sohail
2017-05-01
The biotechnological applications of enzymes are limited due to the activity-stability trade-off, which implies that an increase in activity is accompanied by a concomitant decrease in protein stability. This premise is based on thermally adapted homologous enzymes where cold-adapted enzymes show high intrinsic activity linked to enhanced thermolability. In contrast, thermophilic enzymes show low activity around ambient temperatures. Nevertheless, genetically and chemically modified enzymes are beginning to show that the activity-stability trade-off can be overcome. In this review, the origin of the activity-stability trade-off, the thermodynamic basis for enhanced activity and stability, and various approaches for escaping the activity-stability trade-off are discussed. The role of entropy in enhancing both the activity and the stability of enzymes is highlighted with a special emphasis placed on the involvement of solvent water molecules. This review is concluded with suggestions for further research, which underscores the implications of these findings in the context of productivity curves, the Daniel-Danson equilibrium model, catalytic antibodies, and life on cold planets.
Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.
Lan, Junjie; Huang, Lan; Lou, Huayong; Chen, Chao; Liu, Tangjingjun; Hu, Shengcao; Yao, Yao; Song, Junrong; Luo, Jun; Liu, Yazhou; Xia, Bin; Xia, Lei; Zeng, Xueyi; Ben-David, Yaacov; Pan, Weidong
2018-01-01
Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC 50 value of 0.64 μM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Garfin, Phillip M.; Min, Dullei; Bryson, Jerrod L.; Serwold, Thomas; Edris, Badreddin; Blackburn, Clare C.; Richie, Ellen R.; Weinberg, Kenneth I.; Manley, Nancy R.; Viatour, Patrick
2013-01-01
Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients. PMID:23669396
Lidar investigations of M-zone
NASA Technical Reports Server (NTRS)
Ovezgeldiyev, O. G.; Kurbanmuradov, K.; Lagutin, M. F.; Zarudny, A. A.; Meghel, Yu. E.; Torba, A. A.; Melnikov, V. E.
1987-01-01
The creation of pulse dye lasers tuned to resonant line of meteor produced admixtures of atmospheric constituents has made it possible to begin lidar investigations of the vertical distribution of mesospheric sodium concentration and its dynamics in the upper atmosphere. The observed morning increase of sodium concentration in the vertical column is probably caused by diurnal variations of sporadic meteors. The study of the dynamics of the sodium column concentration in the period of meteor streams activity confirms the suggestion of cosmic origin of these atoms. The short lived increase of sodium concentration brought about by a meteor stream, however, exceeds by one order the level of the sporadic background.
[Psychogenetic neurological disorders in draft age personnel].
Akhmetianov, L A; Ovchinnikov, A V
2012-07-01
The tendency of psychogenetic neurological disorders increases with predominance in young persons being students of high schools, students of military, technical and other lyceum was shown. The origin of diseases are psychotraumas (family, work), stress. Also genetic and hereditary factors take place that are indicative for individual rehabilitation organization. The basics of psychosomatic diseases pathogenesis are the disintegration mechanisms in brain structure activity,the disorders of integrative apparatus which provides the relationship between somatic, emotional and vegetative functions. The confirmation of brain work disintegration is achieved by modern computer diagnostic systems. As psychogenic diseases increase the need in methods of computer electroencephalography, evoked potentials, and rheoencephalography application is more actual.
Scharsack, Jörn Peter; Gossens, Anabel; Franke, Frederik; Kurtz, Joachim
2013-12-01
Helminth parasites have evolved remarkable strategies to manipulate the immune system of their hosts. During infections of three-spined stickleback (Gasterosteus aculeatus) with the cestode Schistocephalus solidus prominent immunological changes occur, presumably due to manipulative activity of the parasite. We hypothesise that excretory/secretory products of the parasite are involved in the manipulation of the stickleback's immune system and that this may depend on the individual parasite and its origin. We therefore produced S. solidus conditioned cell culture media (SSCM) with parasites from different origins (Norway, Spain and Germany) and exposed head kidney leukocytes (HKL) from un-infected sticklebacks in cell cultures to SSCM. After in vitro culture, HKL were subjected to differential cell counts (granulocytes/lymphocytes) by means of flow cytometry. Leukocyte sub-populations were analysed for cell viability and changes in cell morphology. The respiratory burst activity was measured with a luminescence assay. Exposure of HKL to SSCM induced an up-regulation of respiratory burst activity after already 1 h, which was still elevated at 24 h, but which was in some cases significantly down-regulated after 96 h. Respiratory burst was positively correlated with the number of live granulocytes in the culture, suggesting that the respiratory burst activity was changed by SSCM effects on granulocyte viability. After 1 h and 24 h of HKL culture, no lymphocyte responses to SSCM were detectable, but after 96 h lymphocyte viability was significantly decreased with SSCM from Spanish S. solidus. In these cultures, residual lymphocytes increased in size, suggesting that cell death and activation might have occurred in parallel. The highest respiratory burst activity was induced by SSCM from Spanish parasites, in particular when they were grown in sympatric sticklebacks. The in vitro HKL responses to SSCM depended on the individual parasite and its population of origin, suggesting that in vivo, S. solidus excretory products are regulated individually, possibly to balance the interplay of each individual host-parasite pair. Copyright © 2013 Elsevier Ltd. All rights reserved.
Noopept normalizes parameters of the incretin system in rats with experimental diabetes.
Ostrovskaya, R U; Zolotov, N N; Ozerova, I V; Ivanova, E A; Kapitsa, I G; Taraban, K V; Michunskaya, A M; Voronina, T A; Gudasheva, T A; Seredenin, S B
2014-07-01
Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations.
Hamley, Madeleine; Franke, Frederik; Kurtz, Joachim; Scharsack, Jörn Peter
2017-09-01
The evolutionary arms race of hosts and parasites often results in adaptations, which may differ between populations. Investigation of such local adaptation becomes increasingly important to understand dynamics of host-parasite interactions and co-evolution. To this end we performed an infection experiment involving pairs of three-spined sticklebacks and their tapeworm parasite Schistocephalus solidus from three geographically separated origins (Germany, Spain and Iceland) in a fully-crossed design for sympatric and allopatric host/parasite combinations. We hypothesized that local adaptation of the hosts results in differences in parasite resistance with variation in parasite infection rates and leukocyte activation, whereas parasites from different origins might differ in virulence reflected in host exploitation rates (parasite indices) and S. solidus excretory-secretory products (SsESP) involved in immune manipulation. In our experimental infections, sticklebacks from Iceland were more resistant to S. solidus infection compared to Spanish and German sticklebacks. Higher resistance of Icelandic sticklebacks seemed to depend on adaptive immunity, whereas sticklebacks of German origin, which were more heavily afflicted by S. solidus, showed elevated activity of innate immune traits. German S. solidus were less successful in infecting and exploiting allopatric hosts compared to their Icelandic and Spanish conspecifics. Nevertheless, exclusively SsESP from German S. solidus triggered significant in vitro responses of leukocytes from naïve sticklebacks. Interestingly, parasite indices were almost identical across the sympatric combinations. Differences in host resistance and parasite virulence between the origins were most evident in allopatric combinations and were consistent within origin; i.e. Icelandic sticklebacks were more resistant and their S. solidus were more virulent in all allopatric combinations, whereas German sticklebacks were less resistant and their parasites less virulent. Despite such differences between origins, the degree of host exploitation was almost identical in the sympatric host-parasite combinations, suggesting that the local evolutionary arms race of hosts and parasites resulted in an optimal virulence, maximising parasite fitness while avoiding host overexploitation. Copyright © 2017 Elsevier Inc. All rights reserved.
Ferrada, Carla; Sotomayor-Zárate, Ramón; Abarca, Jorge; Gysling, Katia
2017-01-01
The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens, among others, and it originates in the dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives glutamatergic inputs from the prefrontal cortex and several subcortical regions. The glutamate released activates dopaminergic neurons and its action depends on the activation of ionotropic and metabotropic glutamate receptors. VTA dopaminergic neurons release dopamine (DA) from axon terminals in the innervated regions and somatodendritically in the VTA itself. DA release in the VTA is directly correlated with the activity of dopaminergic neurons. We hypothesized that metabotropic glutamate 5 receptors (mGlu5) directly regulate the activity of VTA dopaminergic neurons. To test this hypothesis, the extracellular levels of VTA DA and glutamate were studied by in-vivo microdialysis after an intra-VTA perfusion of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), selective mGlu5 agonist. We observed that CHPG induced a significant increase in VTA DA and glutamate extracellular levels. To determine whether the effect of CHPG on DA levels is because of the increase in glutamate release, we perfused kynurenic acid, an ionotropic glutamate receptor antagonist, through the probe. Our results showed that kynurenic acid did not block the ability of CHPG to cause DA release. Thus, our results suggest that CHPG acts directly on mGlu5 in dopaminergic neurons to induce the release of DA.
Qiutong, Xu; Mingkui, Zhang
2017-08-01
Vegetable production in China is suffering increasingly heavy metal damages from various pollution sources including agricultural, industrial and other activities. It is of practical significance to understand the effects of human activities on the accumulation and exchangeability of soil heavy metals in vegetable fields. In this study, seventy-two arable layer samples of vegetable soils were collected from the Shaoxing coastal plain, a representative region of the coastal plain of eastern Zhejiang province, China for characterizing the effects of fertilization methods on accumulation and exchangeable heavy metals in soils (Exchangeable heavy metals in the soil samples were extracted by 0.01molL -1 CaCl 2 ). The different origins of heavy metals in the vegetable soils were investigated by multivariate statistical techniques, including principal component analysis (PCA) and cluster analysis (CA). Marked increases were noted for soil heavy metals due to long-term manure or chemical fertilizer application. Three significant components were extracted by PCA, explaining 78.86% of total variance. Mn, Co, Ni, Fe, and Al were associated in lithogenic components, while an anthropogenic origin was identified for Cu, Cr, Pb, Zn, Cd, Hg. However, As level was due to the geochemical background and was not linked to soil management. The results obtained by cluster analysis elucidated individual relationships between metals and agreed with PCA. Cu, Cr, Pb, and Zn in the soils that were mainly associated with the application of chemical fertilizers, organic manures or other activities regarding soil management. Although the origin of Cd, Hg, and As was also attributed to soil management, other sources like vehicle exhaust or aerial depositions were not discarded as possible contributors. Soil amended with organic fertilizer contained more Cu, Pb, Zn and Cr; whereas the soil amended with chemical fertilizer had more Cd. Application of fertilizers also had significant effect on the concentrations of exchangeable heavy metals. Higher mean concentrations of exchangeable Cd and Pb were found in the soils amended with chemical fertilizers, while those of exchangeable Cu and Zn were found in the soils amended with organic fertilizers. Copyright © 2017 Elsevier Inc. All rights reserved.
Lecendreux, Michel; Churlaud, Guillaume; Pitoiset, Fabien; Regnault, Armelle; Tran, Tu Anh; Liblau, Roland; Klatzmann, David; Rosenzwajg, Michelle
2017-01-01
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.
Combating the illegal trade in African elephant ivory with DNA forensics.
Wasser, Samuel K; Joseph Clark, William; Drori, Ofir; Stephen Kisamo, Emily; Mailand, Celia; Mutayoba, Benezeth; Stephens, Matthew
2008-08-01
International wildlife crime is burgeoning in this climate of global trade. We contend that the most effective way to contain this illegal trade is to determine where the wildlife is being removed. This allows authorities to direct law enforcement to poaching hot spots, potentially stops trade before the wildlife is actually killed, prevents countries from denying their poaching problems at home, and thwarts trade before it enters into an increasingly complex web of international criminal activity. Forensic tools have been limited in their ability to determine product origin because the information they can provide typically begins only at the point of shipment. DNA assignment analyses can determine product origin, but its use has been limited by the inability to assign samples to locations where reference samples do not exist. We applied new DNA assignment methods that can determine the geographic origin(s) of wildlife products from anywhere within its range. We used these methods to examine the geographic origin(s) of 2 strings of seizures involving large volumes of elephant ivory, 1 string seized in Singapore and Malawi and the other in Hong Kong and Cameroon. These ivory traffickers may comprise 2 of the largest poaching rings in Africa. In both cases all ivory seized in the string had common origins, which indicates that crime syndicates are targeting specific populations for intense exploitation. This result contradicts the dominant belief that dealers are using a decentralized plan of procuring ivory stocks as they became available across Africa. Large quantities of ivory were then moved, in multiple shipments, through an intermediate country prior to shipment to Asia, as a risk-reduction strategy that distances the dealer from the poaching locale. These smuggling strategies could not have been detected by forensic information, which typically begins only at the shipping source.
Couzinet, S; Dubremetz, J F; David, L; Prensier, G
1994-06-01
Polyether ionophorous antibiotics are widely used prophylactically to prevent coccidiosis in livestock production. The study of the effects of the nigericin on tachyzoites of Toxoplasma gondii clearly demonstrated that very low concentrations of this ionophore (0.05 microgram/ml) were sufficient to inhibit strongly the penetration and totally inhibit the intracellular development of parasites. Both nigericin and epinigericin showed a similar activity against tachyzoite development. However, the activity of abierixicin was 50-fold lower. Such antibiotic concentrations did not seem to affect host cells. Immunofluorescence and electron microscopy showed important changes in the cytology of the antibiotic-treated parasites: they were vacuolated or swollen and were sometimes found burst open, having lost their original shape. The magnitude and the frequency of alterations rose as concentrations in ionophore increased.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Alaskan Native. National origin. A prohibited basis for discrimination. An individual's place of origin or his or her ancestor's place of origin or the possession of physical, cultural, or linguistic... disabilities. (b) Major life activities. Functions such as caring for one's self, performing manual tasks...
Code of Federal Regulations, 2012 CFR
2012-07-01
... Alaskan Native. National origin. A prohibited basis for discrimination. An individual's place of origin or his or her ancestor's place of origin or the possession of physical, cultural, or linguistic... disabilities. (b) Major life activities. Functions such as caring for one's self, performing manual tasks...
Elevation of oleate-activated phospholipase D activity during thymic atrophy
Lee, Youngkyun; Song, Soo-Mee; Park, Heung Soon; Kim, Sungyeol; Koh, Eun-Hee; Choi, Myung Sun; Choi, Myung-Un
2002-01-01
Various phospholipases are thought to be associated with the in vitro apoptosis of thymocytes. In the present study, the in vivo phospholipase D (PLD) activity of rat thymus was studied after whole-body X-irradiation or injection of dexamethasone (DEX). Using exogenous [14C]dipalmitoyl phosphatidylcholine (PC) as the substrate, an elevation of oleate-activated PLD activity was observed during thymic atrophy. The activity increases were sevenfold at 48 hr after 5-Gy irradiation and fourfold at 72 hr after injection of 5 mg/kg DEX. The elevation of PLD activity appeared to parallel extensive thymus shrinkage. An increased level of thymic phosphatidic acid (PA), the presumed physiological product of PLD action on PC, was also detected. By comparing the acyl chains of PA with those of other phospholipids, PA appeared to originate from PC. To assess the role of PLD during thymic atrophy, thymocytes and stromal cells were isolated. Although thymocytes themselves exhibited significant PLD activation, the major elevation in PLD activity (greater than fourfold) was found in isolated stromal cells. PLD was also activated during in vitro phagocytosis of apoptotic thymocytes by the macrophage-like cell line P388D1. This in vitro phagocytosis was significantly inhibited by PLD action blockers, such as 2,3-diphosphoglycerate and 1-butanol. These observations strongly suggest that the alteration of oleate-activated PLD activity is part of an in vivo event in the progression of thymic atrophy, including phagocytic clearance of apoptotic thymocytes. PMID:12460188
Sibling Behaviors and Mexican-Origin Adolescents' After-School Activities
ERIC Educational Resources Information Center
Price, Chara D.; Simpkins, Sandra D.; Menjívar, Cecilia
2017-01-01
Families are theorized to influence adolescents' participation in skill-based after-school activities, but research has focused on the role of parents while neglecting the role of siblings. Siblings might be especially critical for Mexican-origin youth, the fastest growing youth population in the United States, due to a high value of family as…
Perspectives of Mexican-Origin Smokers on Healthy Eating and Physical Activity
ERIC Educational Resources Information Center
Strong, Larkin L.; Hoover, Diana S.; Heredia, Natalia I.; Krasny, Sarah; Spears, Claire A.; Correa-Fernández, Virmarie; Wetter, David W.; Fernandez, Maria E.
2016-01-01
Key modifiable risk behaviors such as smoking, poor diet and physical inactivity often cluster and may have multiplicative adverse effects on health. This study investigated barriers and facilitators to healthy eating and physical activity (PA) in overweight Mexican-origin smokers to inform the adaptation of an evidence-based smoking cessation…
Enteric bacterial proteases in inflammatory bowel disease- pathophysiology and clinical implications
Carroll, Ian M; Maharshak, Nitsan
2013-01-01
Numerous reports have identified a dysbiosis in the intestinal microbiota in patients suffering from inflammatory bowel diseases (IBD), yet the mechanism(s) in which this complex microbial community initiates or perpetuates inflammation remains unclear. The purpose of this review is to present evidence for one such mechanism that implicates enteric microbial derived proteases in the pathogenesis of IBD. We highlight and discuss studies demonstrating that proteases and protease receptors are abundant in the digestive system. Additionally, we investigate studies demonstrating an association between increased luminal protease activity and activation of protease receptors, ultimately resulting in increased intestinal permeability and exacerbation of colitis in animal models as well as in human IBD. Proteases are essential for the normal functioning of bacteria and in some cases can serve as virulence factors for pathogenic bacteria. Although not classified as traditional virulence factors, proteases originating from commensal enteric bacteria also have a potential association with intestinal inflammation via increased enteric permeability. Reports of increased protease activity in stools from IBD patients support a possible mechanism for a dysbiotic enteric microbiota in IBD. A better understanding of these pathways and characterization of the enteric bacteria involved, their proteases, and protease receptors may pave the way for new therapeutic approaches for these diseases. PMID:24431894
Dubey, M L; Hegde, Ramakrishna; Ganguly, N K; Mahajan, R C
2003-04-01
2,3-Diphosphoglycerate (2,3-DPG), an intracellular metabolite of glycolytic pathway is known to affect the oxygen binding capacity of haemoglobin and mechanical properties of the red blood cells. 2,3-DPG levels have been reported to be elevated during anaemic conditions including visceral leishmaniasis. 2,3-DPG activity in P. falciparum infected red blood cells, particularly in cells infected with different stages of the parasite and its relationship with structural integrity of the cells is not known. Chloroquine sensitive and resistant strains of P. falciparum were cultured in vitro and synchronized cultures of ring, trophozoite and schizont stage rich cells along with the uninfected control erythrocytes were assayed for 2,3-DPG activity and osmotic fragility. It was observed that in both the strains, in infected erythrocytes the 2,3-DPG activity gradually decreased and osmotic fragility gradually increased as the parasite matured from ring to schizont stage. The decrease in 2,3-DPG may probably be due to increased pyruvate kinase activity of parasite origin, which has been shown in erythrocytes infected with several species of Plasmodium. The absence of compensatory increase in 2,3-DPG in P. falciparum infected erythrocytes may aggravate hypoxia due to anaemia in malaria and probably may contribute to hypoxia in cerebral malaria. As 2,3-DPG was not found to be increased in erythrocytes parasitized with P. falciparum, the increased osmotic fragility observed in these cells is not due to increased 2,3-DPG as has been suggested in visceral leishmaniasis.
Lima, Vanessa Pereira; Iamonti, Vinicius C; Velloso, Marcelo; Janaudis-Ferreira, Tania
The mechanisms underlying physiological limitations during arm activity in individuals with chronic obstructive pulmonary disease (COPD) are unknown. The objective of this systematic review was to describe cardiorespiratory responses, symptoms, chest wall kinematics, muscle activity, and lung volumes during arm activity in individuals with COPD relative to the responses of healthy controls. Original research articles that compared cardiorespiratory responses, symptoms, muscle activity, chest wall kinematics, and lung function during arm activity between individuals with COPD and healthy controls were identified after searches of 5 electronic databases and reference lists of pertinent articles. Two reviewers performed the electronic and manual searches with 1 screening title and abstracts. Two investigators screened the full texts to determine eligibility for inclusion. One reviewer performed the data extraction and tabulation using a standardized form with a second reviewer double-checking the data extracted. Of the 54 full-text articles assessed for eligibility, 6 met the inclusion criteria. Reduced cardiorespiratory responses during peak arm exercise in individuals with COPD compared with healthy controls were evident. Compared with healthy controls, individuals with COPD had increased dyspnea and hyperinflation during peak arm exercise. Increased effort of the trapezius muscle during arm activities was also found in persons with COPD compared with healthy controls. There is limited evidence describing physiological responses during arm activity in individuals with COPD. Findings of this systematic review suggest that individuals with COPD have decreased cardiorespiratory responses during peak arm exercise compared with controls but increased dyspnea, hyperinflation, and arm muscle effort.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martinez-Salgado, Carlos; Fuentes-Calvo, Isabel; Instituto 'Reina Sofia' de Investigacion Nefrologica, Universidad de Salamanca, 37007 Salamanca
2006-07-01
Transforming growth factor {beta}1 (TGF-{beta}1) has a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-{beta} and Ras signaling pathways are closely related: TGF-{beta}1 overcomes Ras mitogenic effects and Ras counteracts TGF-{beta} signaling. Tubule-interstitial fibrosis is associated to increases in Ras, Erk, and Akt activation in a renal fibrosis model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras effectors Erk and Akt, in TGF-{beta}1-mediated extracellular matrix (ECM) synthesis and proliferation, using embrionary fibroblasts from double knockout (KO) mice for H- and N-Ras (H-ras {sup -/-}/N-ras {sup -/-}) isoforms andmore » from heterozygote mice (H-ras {sup +/-}/N-ras {sup +/-}). ECM synthesis is increased in basal conditions in H-ras {sup -/-}/N-ras {sup -/-} fibroblasts, this increase being higher after stimulation with TGF-{beta}1. TGF-{beta}1-induced fibroblast proliferation is smaller in H-ras {sup -/-}/N-ras {sup -/-} than in H-ras {sup +/-}/N-ras {sup +/-} fibroblasts. Erk activation is decreased in H-ras {sup -/-}/N-ras {sup -/-} fibroblasts; inhibition of Erk activation reduces fibroblast proliferation. Akt activation is higher in double KO fibroblasts than in heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation may be involved in the increase in ECM synthesis observed in the absence of H- and N-Ras.« less
Lynagh, Timothy; Lynch, Joseph W.
2010-01-01
The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light-activated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human α1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G α1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID:20308070
Rosas-Luis, Rigoberto
2016-12-15
Squids are active and opportunistic predators that feed on a wide range of prey. Their active movements in the water column and their voracity promote a high consumption of food. In the pelagic environment off Ecuador, marine pollution is characterized by plastic debris with a mainland origin, including plastics trash of fishing gears. The objective of this work was to describe the presence of plastic remains in the stomach contents of Dosidicus gigas caught off the coast of Ecuador. Results demonstrated that 12% of the stomachs contained plastic remains. These plastics were identified as multifilament of polyethylene lines and polyvinyl chloride remains. Findings of this work could be related to an increase in the discharge of solid materials in the water column, increasing the probability to be ingested by the jumbo squid. Copyright © 2016 Elsevier Ltd. All rights reserved.
2008-01-01
Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors. PMID:18684881
D-dimer: An Overview of Hemostasis and Fibrinolysis, Assays, and Clinical Applications.
Olson, John D
2015-01-01
D-dimer is the smallest fibrinolysis-specific degradation product found in the circulation. The origins, assays, and clinical use of D-dimer will be addressed. Hemostasis (platelet and vascular function, coagulation, fibrinolysis, hemostasis) is briefly reviewed. D-dimer assays are reviewed. The D-dimer is very sensitive to intravascular thrombus and may be markedly elevated in disseminated intravascular coagulation, acute aortic dissection, and pulmonary embolus. Because of its exquisite sensitivity, negative tests are useful in the exclusion venous thromboembolism. Elevations occur in normal pregnancy, rising two- to fourfold by delivery. D-dimer also rises with age, limiting its use in those >80 years old. There is a variable rise in D-dimer in active malignancy and indicates increased thrombosis risk in active disease. Elevated D-dimer following anticoagulation for a thrombotic event indicates increased risk of recurrent thrombosis. These and other issues are addressed. © 2015 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Willard, K.E.; Thorsrud, A.K.; Munthe, E.
Human leukocyte proteins from more than 150 patients with rheumatoid arthritis, together with age- and sex-matched controls, were analyzed by use of the ISO-DALT technique of two-dimensional polyacrylamide gel electrophoresis. Patients with ankylosing spondylitis, polymyalgia rheumatica, psoriatic arthritis, calcium tendinitis, post-infectious arthritis, and asymmetrical seronegative arthritis were also included as positive controls. Synthesis of several proteins, referred to by number as members of the Rheuma set, is shown to increase in the leukocyte preparations from patients with classical rheumatoid arthritis. Several of these proteins are specific to monocytes or granulocytes; others are of unknown cellular origin, but appear to bemore » unique to rheumatoid arthritis. The Rheuma proteins appear to be indicators of disease activity, because their increased synthesis can be correlated with sedimentation rate and other clinical indices of rheumatoid disease activity.« less
Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation
Koch, Sheryl E.; Gao, Xiaoqian; Haar, Lauren; Jiang, Min; Lasko, Valerie M.; Robbins, Nathan; Cai, Wenfeng; Brokamp, Cole; Varma, Priyanka; Tranter, Michael; Liu, Yong; Ren, Xiaoping; Lorenz, John N.; Wang, Hong-Sheng; Jones, W. Keith; Rubinstein, Jack
2012-01-01
Probenecid is a highly lipid soluble benzoic acid derivative originally used to increase serum antibiotic concentrations. It was later discovered to have uricosuric effects and was FDA approved for gout therapy. It has recently been found to be a potent agonist of Transient Receptor Potential Vanilloid 2 (TRPV2). We have shown that this receptor is in the cardiomyocyte and report a positive inotropic effect of the drug. Using echocardiography, Langendorff and isolated myocytes, we measured the change in contractility and, using TRPV2−/− mice, proved that the effect was mediated by TRPV2 channels in the cardiomyocytes. Analysis of the expression of Ca2+ handling and β-adrenergic signaling pathway proteins showed that the contractility was not increased through activation of the β-ADR. We propose that the response to probenecid is due to activation of TRPV2 channels secondary to SR release of Ca2+. PMID:22561103
ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia
NASA Technical Reports Server (NTRS)
Heybach, J. P.; Vernikos, J.
1981-01-01
The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.
Cohesin organizes chromatin loops at DNA replication factories
Guillou, Emmanuelle; Ibarra, Arkaitz; Coulon, Vincent; Casado-Vela, Juan; Rico, Daniel; Casal, Ignacio; Schwob, Etienne; Losada, Ana; Méndez, Juan
2010-01-01
Genomic DNA is packed in chromatin fibers organized in higher-order structures within the interphase nucleus. One level of organization involves the formation of chromatin loops that may provide a favorable environment to processes such as DNA replication, transcription, and repair. However, little is known about the mechanistic basis of this structuration. Here we demonstrate that cohesin participates in the spatial organization of DNA replication factories in human cells. Cohesin is enriched at replication origins and interacts with prereplication complex proteins. Down-regulation of cohesin slows down S-phase progression by limiting the number of active origins and increasing the length of chromatin loops that correspond with replicon units. These results give a new dimension to the role of cohesin in the architectural organization of interphase chromatin, by showing its participation in DNA replication. PMID:21159821
McConnell, Kristopher H.; Dixon, Michael; Calvi, Brian R.
2012-01-01
DNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs. PMID:22951641
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chang, Young-Chae, E-mail: ycchang@cu.ac.kr; Cho, Hyun-Ji, E-mail: hjcho.dr@gmail.com
2012-06-08
Highlights: Black-Right-Pointing-Pointer Ascofuranone increases expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Inhibitors for MEK and JNK increased the expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Ascofuranone significantly suppressed phosho-ERK, while increasing phospho-p38. -- Abstract: Ascofuranone, an isoprenoid antibiotic, was originally isolated as a hypolipidemic substance from a culture broth of the phytopathogenic fungus, Ascochyta visiae. Adiponectin is mainly synthesized by adipocytes. It relieves insulin resistance by decreasing the plasma triglycerides and improving glucose uptake, and has anti-atherogenic properties. Here, we found that ascofuranone increases expression of adiponectin and PPAR{gamma}, a major transcription factor for adiponectin, in 3T3-L1, murine pre-adipocytes cell line, withoutmore » promoting accumulation of lipid droplets. Ascofuranone induced expression of adiponectin, and increases the promoter activity of adiponectin and PPRE, PPAR response element, as comparably as a PPAR{gamma} agonist, rosiglitazone, that stimulates lipid accumulation in the preadipocyte cell line. Moreover, inhibitors for MEK and JNK, like ascofuranone, considerably increased the expression of adiponectin and PPAR{gamma}, while a p38 inhibitor significantly suppressed. Ascofuranone significantly suppressed ERK phosphorylation, while increasing p38 phosphorylation, during adipocyte differentiation program. These results suggest that ascofuranone regulates the expression of adiponectin and PPAR{gamma} through the modulation of MAP kinase family members.« less
Sources and implications of lead ammunition and fishing tackle on natural resources
Rattner, B.A.; Franson, J. Christian; Sheffield, S.R.; Goddard, C.I.; Leonard, N.J.; Stang, D.; Wingate, P.J.
2008-01-01
A technical review of lead sources that originate from hunting, shooting sports, and fishing activities was undertaken by the American Fisheries Society and The Wildlife Society. The report addresses (1) sources of lead that originate from hunting, shooting sports, and fishing activities, (2) the hazard and risk that lead from these activities pose to natural resources, and (3) the management implications for fish and wildlife professionals and policy makers.
Sympathetic nervous system and the kidney in hypertension.
DiBona, Gerald F
2002-03-01
Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.
Humidity-activated shape memory effect on plasticized starch-based biomaterials.
Sessini, Valentina; Arrieta, Marina P; Fernández-Torres, Alberto; Peponi, Laura
2018-01-01
Humidity-activated shape memory behavior of plasticized starch-based films reinforced with the innovative combination of starch nanocrystals (SNCs) and catechin as antioxidant were studied. In a previous work, we reported the processing of gelatinized starch-based films filled with SNCs and catechin as antioxidant agent, and we observed that this novel combination leads to starch-based film with enhanced thermal and mechanical performance. In this work, the humidity-activated shape memory behavior of the previous developed starch-based films was characterized. The moisture loss as well as the moisture absorption were studied since they are essential parameters in humidity-activated shape memory polymers to fix the temporary shape and to recover the original shape, respectively. Therefore, the effect of the incorporation of SNCs and catechin on the humidity-activated shape memory properties of plasticized starch was also studied. Moreover, the effectiveness of catechin to increase the polymer stability under oxidative atmosphere and the thermo-mechanical relaxation of all the starch-based materials were studied. The combination of plasticized starch matrix loaded with both, SNCs and catechin, leads to a multifunctional starch-based films with increased hydrophilicity and with excellent humidity-activated shape memory behavior with interest for potential biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cisplatin: mode of cytotoxic action and molecular basis of resistance.
Siddik, Zahid H
2003-10-20
Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatin-based chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologic-based mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.
Kulikova, Vitalia V; Zakomirdina, Ludmila N; Dementieva, Irene S; Phillips, Robert S; Gollnick, Paul D; Demidkina, Tatyana V; Faleev, Nicolai G
2006-04-01
Tyr72 is located at the active site of tryptophanase (Trpase) from Proteus vulgaris. For the wild-type Trpase Tyr72 might be considered as the general acid catalyst at the stage of elimination of the leaving groups. The replacement of Tyr72 by Phe leads to a decrease in activity for L-tryptophan by 50,000-fold and to a considerable rearrangement of the active site of Trpase. This rearrangement leads to an increase of room around the alpha-C atom of any bound amino acid, such that covalent binding of alpha-methyl-substituted amino acids becomes possible (which cannot be realized in wild-type Trpase). The changes in reactivities of S-alkyl-L-cysteines provide evidence for an increase of congestion in the proximity of their side groups in the mutant enzyme as compared to wild-type enzyme. The observed alteration of catalytic properties in a large degree originates from a conformational change in the active site. The Y72F Trpase retains significant activity for L-serine, which allowed us to conclude that in the mutant enzyme, some functional group is present which fulfills the role of the general acid catalyst in reactions associated with elimination of small leaving groups.
Sloan, Robert A; Kim, Youngdeok; Sahasranaman, Aarti; Müller-Riemenschneider, Falk; Biddle, Stuart J H; Finkelstein, Eric A
2018-03-22
A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity. We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P < 0.05). Increases in step counts were concomitantly associated with decreases in ST and PSB, regardless of intervention (P < 0.05). Caution should be taken when considering consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 2012.
Silva, Gláucia Alves E; Siqueira, José O; Stürmer, Sidney L; Moreira, Fatima M S
2018-01-01
Arbuscular mycorrhizal fungi provide several ecosystem services, including increase in plant growth and nutrition. The occurrence, richness, and structure of arbuscular mycorrhizal fungi communities are influenced by human activities, which may affect the functional benefits of these components of the soil biota. In this study, 13 arbuscular mycorrhizal fungi isolates originating from soils with different land uses in the Alto Solimões-Amazon region were evaluated regarding their effect on growth, nutrition, and cowpea yield in controlled conditions using two soils. Comparisons with reference isolates and a mixture of isolates were also performed. Fungal isolates exhibited a wide variability associated with colonization, sporulation, production of aboveground biomass, nitrogen and phosphorus uptake, and grain yield, indicating high functional diversity within and among fungal species. A generalized effect of isolates in promoting phosphorus uptake, increase in biomass, and cowpea yield was observed in both soils. The isolates of Glomus were the most efficient and are promising isolates for practical inoculation programs. No relationship was found between the origin of fungal isolate (i.e. land use) and their symbiotic performance in cowpea.
Exposure to ultrafine particles in asphalt work.
Elihn, Karine; Ulvestad, Bente; Hetland, Siri; Wallen, Anna; Randem, Britt Grethe
2008-12-01
An epidemiologic study has demonstrated that asphalt workers show increased loss of lung function and an increase of biomarkers of inflammation over the asphalt paving season. The aim of this study was to investigate which possible agent(s) causes the inflammatory reaction, with emphasis on ultrafine particles. The workers' exposure to total dust, polycyclic aromatic hydrocarbons, and NO(2) was determined by personal sampling. Exposure to ultrafine particles was measured by means of particle counters and scanning mobility particle sizer mounted on a van following the paving machine. The fractions of organic and elemental carbon were determined. Asphalt paving workers were exposed to ultrafine particles with medium concentration of about 3.4 x 10(4)/cm(3). Ultrafine particles at the paving site originated mainly from asphalt paving activities and traffic exhaust; most seemed to originate from asphalt fumes. Oil mist exceeded occupational limits on some occasions. Diesel particulate matter was measured as elemental carbon, which was low, around 3 microg/m(3). NO(2) and total dust did not exceed limits. Asphalt pavers were exposed to relatively high concentrations of ultrafine particles throughout their working day, with possible adverse health effects.
Practical considerations in the management of proton-pump inhibitors.
Aguilera-Castro, Lara; Martín-de-Argila-dePrados, Carlos; Albillos-Martínez, Agustín
2016-03-01
Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.
Global warming of the mantle at the origin of flood basalts over supercontinents
NASA Astrophysics Data System (ADS)
Coltice, N.; Phillips, B. R.; Bertrand, H.; Ricard, Y.; Rey, P.
2007-05-01
Continents episodically cluster together into a supercontinent, eventually breaking up with intense magmatic activity supposedly caused by mantle plumes (Morgan, 1983; Richards et al., 1989; Condie, 2004). The breakup of Pangea, the last supercontinent, was accompanied by the emplacement of the largest known continental flood basalt, the Central Atlantic Magmatic Province, which caused massive extinctions at the Triassic-Jurassic boundary (Marzoli et al., 1999). However, there is little support for a plume origin for this catastrophic event (McHone, 2000). On the basis of convection modeling in an internally heated mantle, this paper shows that continental aggregation promotes large-scale melting without requiring the involvement of plumes. When only internal heat sources in the mantle are considered, the formation of a supercontinent causes the enlargement of flow wavelength and a subcontinental increase in temperature as large as 100 °C. This temperature increase may lead to large-scale melting without the involvement of plumes. Our results suggest the existence of two distinct types of continental flood basalts, caused by plume or by mantle global warming.
Combined strategies for improving expression of Citrobacter amalonaticus phytase in Pichia pastoris.
Li, Cheng; Lin, Ying; Zheng, Xueyun; Pang, Nuo; Liao, Xihao; Liu, Xiaoxiao; Huang, Yuanyuan; Liang, Shuli
2015-09-26
Phytase is used as an animal feed additive that degrades phytic acid and reduces feeding costs and pollution caused by fecal excretion of phosphorus. Some phytases have been expressed in Pichia pastoris, among which the phytase from Citrobacter amalonaticus CGMCC 1696 had high specific activity (3548 U/mg). Improvement of the phytase expression level will contribute to facilitate its industrial applications. To improve the phytase expression, we use modification of P AOX1 and the α-factor signal peptide, increasing the gene copy number, and overexpressing HAC1 (i) to enhance folding and secretion of the protein in the endoplasmic reticulum. The genetic stability and fermentation in 10-L scaled-up fed-batch fermenter was performed to prepare for the industrial production. The phytase gene from C. amalonaticus CGMCC 1696 was cloned under the control of the AOX1 promoter (P AOX1 ) and expressed in P. pastoris. The phytase activity achieved was 414 U/mL. Modifications of P AOX1 and the α-factor signal peptide increased the phytase yield by 35 and 12%, respectively. Next, on increasing the copy number of the Phy gene to six, the phytase yield was 141% higher than in the strain containing only a single gene copy. Furthermore, on overexpression of HAC1 (i) (i indicating induced), a gene encoding Hac1p that regulates the unfolded protein response, the phytase yield achieved was 0.75 g/L with an activity of 2119 U/mL, 412% higher than for the original strain. The plasmids in this high-phytase expression strain were stable during incubation at 30 °C in Yeast Extract Peptone Dextrose (YPD) Medium. In a 10-L scaled-up fed-batch fermenter, the phytase yield achieved was 9.58 g/L with an activity of 35,032 U/mL. The production of a secreted protein will reach its limit at a specific gene copy number where further increases in transcription and translation due to the higher abundance of gene copies will not enhance the secretion process any further. Enhancement of protein folding in the ER can alleviate bottlenecks in the folding and secretion pathways during the overexpression of heterologous proteins in P. pastoris. Using modification of P AOX1 and the α-factor signal peptide, increasing the gene copy number, and overexpressing HAC1 (i) to enhance folding and secretion of the protein in the endoplasmic reticulum, we have successfully increased the phytase yield 412% relative to the original strain. In a 10-L fed-batch fermenter, the phytase yield achieved was 9.58 g/L with an activity of 35,032 U/mL. Large-scale production of phytase can be applied towards different biocatalytic and feed additive applications.
RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells
Im, Jun-Sub; Park, Soon-Young; Cho, Won-Ho; Bae, Sung-Ho; Hurwitz, Jerard; Lee, Joon-Kyu
2015-01-01
Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells. PMID:25602958
Replication profile of Saccharomyces cerevisiae chromosome VI.
Friedman, K L; Brewer, B J; Fangman, W L
1997-11-01
An understanding of the replication programme at the genome level will require the identification and characterization of origins of replication through large, contiguous regions of DNA. As a step toward this goal, origin efficiencies and replication times were determined for 10 ARSs spanning most of the 270 kilobase (kb) chromosome VI of Saccharomyces cerevisiae. Chromosome VI shows a wide variation in the percentage of cell cycles in which different replication origins are utilized. Most of the origins are activated in only a fraction of cells, suggesting that the pattern of origin usage on chromosome VI varies greatly within the cell population. The replication times of fragments containing chromosome VI origins show a temporal pattern that has been recognized on other chromosomes--the telomeres replicate late in S phase, while the central region of the chromosome replicates early. As demonstrated here for chromosome VI, analysis of the direction of replication fork movement along a chromosome and determination of replication time by measuring a period of hemimethylation may provide an efficient means of surveying origin activity over large regions of the genome.
The Risky Shift Toward Online Activism: Do Hacktivists Pose an Increased Threat to the Homeland?
2014-09-01
Cow and was intended to refer to the use of technology to foster human rights and the open exchange of information.11 The term has since evolved to...Orbit Ion Cannon (LOIC) has become a favorite of the hacktivist group Anonymous. The tool, originally created to perform witting stress tests of...that were generating the enormous heat , the enormous pressure, the enormous growth, and really shaping the political.”249 This failed approach to align
1986-01-01
and in some cases -body fat ), are measured twice yearly in the U.S. Army through age 60. Field measures are defined as those conducted by army units...weight and fat standards were originally part of the fitness program and fitness regulations. Because of a considerable increase in emphasis in this...service. Absolute b max is 4/0% less in women but only15% less when adjusted for difference in fat free weight. The relatively small overlap between
Exploring the Accretion Model of M87 and 3C 84 with the Faraday Rotation Measure Observations
NASA Astrophysics Data System (ADS)
Li, Ya-Ping; Yuan, Feng; Xie, Fu-Guo
2016-10-01
Low-luminosity active galactic nuclei (LLAGNs) are believed to be powered by an accretion-jet model, consisting of an inner advection-dominated accretion flow (ADAF), an outer truncated standard thin disk, and a jet; however, model degeneracy still exists in this framework. For example, the X-ray emission can originate from either the ADAF or the jet. The aim of the present work is to check these models with the Faraday rotation measure (RM) observations recently detected for two LLAGNs, M87 and 3C 84, in the sub-mm band. For M87, we find that the RM predicted by the model in which the X-ray emission originates from the ADAF is larger than the observed upper limit of RM by over two orders of magnitude, while the model in which the X-ray emission originates from the jet predicts a RM lower than the observed upper limit. For 3C 84, the sub-mm emission is found to be dominated by the jet component, while the Faraday screen is attributed to the ADAFs. This scenario can naturally explain the observed external origin of the RM and why the RM is found to be stable during a two-year interval although the sub-mm emission increases at the same period.
Kurita, N; Frassoni, F; Chiba, S; Podestà, M
2015-06-01
As the history of the cord blood banking system has lengthened, the number of cord blood units (CBUs) cryopreserved for years has increased. The global expansion of cord blood banking resulted in active international exchange of CBUs. To determine whether long-term cryopreservation and international shipment of CBUs affect the quality of the units and outcome after transplantation, we retrospectively analyzed the quality of 95 CBUs and the hematologic recovery of 127 patients with hematological malignancy following single-unit cord blood transplantation. Of the 127 CBUs used to transplant, 42 units were cryopreserved for long periods (5-11.8 years), and 44 units were shipped from distant countries. We found that length of cryopreservation and origin of CBUs did not affect the ratio of viable total-nucleated cells after thawing. Also, neutrophil engraftment was not affected by long-term cryopreservation (> 5 years) or origin (from distant countries), (hazard ratio, 0.91 and 1.2; P=0.65 and 0.41; respectively). The number of CD34(+) cells before freezing (> 1.4 cells/kg recipient) was the only factor that enhanced neutrophil engraftment (hazard ratio, 1.8; P<0.01). This suggests that length of cryopreservation and origin need not be prioritized over the CD34(+) cell dose when selecting CBUs.
Tone mapping infrared images using conditional filtering-based multi-scale retinex
NASA Astrophysics Data System (ADS)
Luo, Haibo; Xu, Lingyun; Hui, Bin; Chang, Zheng
2015-10-01
Tone mapping can be used to compress the dynamic range of the image data such that it can be fitted within the range of the reproduction media and human vision. The original infrared images that captured with infrared focal plane arrays (IFPA) are high dynamic images, so tone mapping infrared images is an important component in the infrared imaging systems, and it has become an active topic in recent years. In this paper, we present a tone mapping framework using multi-scale retinex. Firstly, a Conditional Gaussian Filter (CGF) was designed to suppress "halo" effect. Secondly, original infrared image is decomposed into a set of images that represent the mean of the image at different spatial resolutions by applying CGF of different scale. And then, a set of images that represent the multi-scale details of original image is produced by dividing the original image pointwise by the decomposed image. Thirdly, the final detail image is reconstructed by weighted sum of the multi-scale detail images together. Finally, histogram scaling and clipping is adopted to remove outliers and scale the detail image, 0.1% of the pixels are clipped at both extremities of the histogram. Experimental results show that the proposed algorithm efficiently increases the local contrast while preventing "halo" effect and provides a good rendition of visual effect.
Marthick, Michael; Dhillon, Haryana M; Alison, Jennifer A; Cheema, Birinder S; Shaw, Tim
2018-05-15
Significant benefits accrue from increasing physical activity levels in people with a history of cancer. Physical activity levels can be increased using behavioral change interventions in this population. Access to Web portals and provision of activity monitors to provide feedback may support behavior change by encouraging patient engagement in physical therapy. The Web portal evaluated in this study will provide a system to monitor physical activity and sleep, for use by both clinician and patient, along with symptom and health-related quality of life tracking capabilities. The aim of this study was to outline a protocol for a feasibility study focused on a Web-based portal that provides activity monitoring and personalized messaging to increase physical activity in people with cancer. Using a longitudinal cohort design, people with cancer will be serially allocated to 3 intervention cohorts of 20 participants each and followed for 10 weeks. Cohort 1 will be provided a wearable activity monitor and access to a Web-based portal. Cohort 2 will receive the same content as Cohort 1 and in addition will receive a weekly activity summary message. Cohort 3 will receive the same content as Cohorts 1 and 2 and in addition will receive a personalized weekly coaching message. Feasibility of the use of the portal is the primary outcome. Results are expected in early 2018. Outcome measures will include goal attainment and completion rate. This study will provide information about the feasibility of investigating eHealth initiatives to promote physical activity in people with cancer. RR1-10.2196/9586. ©Michael Marthick, Haryana M Dhillon, Jennifer A Alison, Birinder S Cheema, Tim Shaw. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.05.2018.
Kołtowski, Michał; Hilber, Isabel; Bucheli, Thomas D; Oleszczuk, Patryk
2016-10-01
The aim of this study was to determine the effect of steam activation of biochars on the immobilization of freely dissolved (Cfree) and bioaccessible fraction (Cbioacc) of PAHs in soils. Additionally, the toxicity to various organisms like Vibrio fischeri, Lepidium sativum and Folsomia candida was measured before and after the amendment of biochars to soils. Three biochars produced from willow, coconut and wheat straw were steam activated and added to three different soils with varying content and origin of PAHs (coke vs. bitumen). The soils with the addition of the biochars (activated and non-activated) were incubated for a period of 60days. Steam activation of the biochars resulted in more pronounced reduction of both Cfree and Cbioacc. The range of the increase in effectiveness was from 10 to 84% for Cfree and from 50 to 99% for Cbioacc. In contrast, the effect of activation on the toxicity of the soils studied varied greatly and was specific to a particular test and soil type. Essentially, biochar activation did not result in a change of phytotoxicity, but it increased or decreased (depending on the parameter, type of biochar, contaminant source, and soil and soil type) the toxic effect to F. candida, and decreased the toxicity of leachates to V. fischeri. Copyright © 2016 Elsevier B.V. All rights reserved.
Pohl, Thomas J; Brewer, Bonita J; Raghuraman, M K
2012-01-01
The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in early replicating domains, a property conserved among centromeres in fungi and some higher eukaryotes. Surprisingly, little is known about the biological significance or the mechanism of early centromere replication; however, the extensive conservation suggests that it is important for chromosome maintenance. Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time. Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain. We used a modified Meselson-Stahl density transfer assay to measure the kinetics of replication for regions of chromosome XIV in which either the functional centromere or a point-mutated version had been moved near origins that reside in a late replication region. We show that a functional centromere acts in cis over a distance as great as 19 kb to advance the initiation time of origins. Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation.
Pohl, Thomas J.; Brewer, Bonita J.; Raghuraman, M. K.
2012-01-01
The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in early replicating domains, a property conserved among centromeres in fungi and some higher eukaryotes. Surprisingly, little is known about the biological significance or the mechanism of early centromere replication; however, the extensive conservation suggests that it is important for chromosome maintenance. Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time. Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain. We used a modified Meselson-Stahl density transfer assay to measure the kinetics of replication for regions of chromosome XIV in which either the functional centromere or a point-mutated version had been moved near origins that reside in a late replication region. We show that a functional centromere acts in cis over a distance as great as 19 kb to advance the initiation time of origins. Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation. PMID:22589733
Kołtowski, Michał; Charmas, Barbara; Skubiszewska-Zięba, Jadwiga; Oleszczuk, Patryk
2017-02-01
The objective of the study was to determine the effect of various methods of biochar activation on the ecotoxicity of soils with various properties and with various content and origin of contaminants. The biochar produced from willow (at 700°C) was activated by 1) microwaves (in a microwave reactor under an atmosphere of water vapour), 2) carbon dioxide (in the quartz fluidized bed reactor) and 3) superheated steam (in the quartz fluidized bed reactor). Three different soils were collected from industrial areas. The soils were mixed with biochar and activated biochars at the dose of 5% and ecotoxicological parameters of mixture was evaluated using two solid phase test - Phytotoxkit F (Lepidium sativum) and Collembolan test (Folsomia candida) and one liquid phase test - Microtox® (Vibrio fischeri). Biochar activation had both positive and negative impacts, depending on the activation method, kind of bioassay and kind of soil. Generally, biochar activated by microwaves increased the effectiveness of ecotoxicity reduction relative to non-activated biochars. Whereas, biochar activated with CO 2 most often cause a negative effect manifested by deterioration or as a lack of improvement in relation to non-activated biochar or to non-amended soil. It was also demonstrated that the increase of biochar specific surface area caused a significant reduction of toxicity of water leachates from the studied soils. Effectiveness of the reduction of leachate toxicity was weakened in the presence of dissolved organic carbon in the soil. Copyright © 2016 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko
2014-09-26
Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore » by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.« less
Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class.
Lemieszek, Marta; Rzeski, Wojciech
2012-01-01
Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known.
Two-Dimensional Perovskite Activation with an Organic Luminophore.
Jemli, Khaoula; Audebert, Pierre; Galmiche, Laurent; Trippé-Allard, Gaelle; Garrot, Damien; Lauret, Jean-Sébastien; Deleporte, Emmanuelle
2015-10-07
A great advantage of the hybrid organic-inorganic perovskites is the chemical flexibility and the possibility of a molecular engineering of each part of the material (the inorganic part and the organic part respectively) in order to improve or add some functionalities. An adequately chosen organic luminophore has been introduced inside a lead bromide type organic-inorganic perovskite, while respecting the two-dimensional perovskite structure. A substantial increase of the brilliance of the perovskite is obtained. This activation of the perovskite luminescence by the adequate engineering of the organic part is an original approach, and is particularly interesting in the framework of the light-emitting devices such as organic light-emitting diodes (OLEDs) or lasers.
Aureusimines in Staphylococcus aureus are not involved in virulence.
Sun, Fei; Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; He, Chuan; Bae, Taeok
2010-12-29
Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS), raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process. Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment. Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal virulence.
Study of ⁷Be and ²¹⁰Pb as radiotracers of African intrusions in Malaga (Spain).
Gordo, E; Liger, E; Dueñas, C; Fernández, M C; Cañete, S; Pérez, M
2015-10-01
The relationship between the particulate matter in the atmosphere of Malaga and the origin of air masses with special attention to African intrusions was analyzed. The concentrations of PM10 and the activities of some radionuclides ((7)Be and (210)Pb) as tracers of these intrusions are discussed. The origin of these radiotracers is completely different. (210)Pb is a good tracer of air masses traveling close to the ground and come from inland areas. On the other hand, the production of (7)Be is very low in the vicinity of the Earth's surface, and increases with altitude, making it a great tracer of stratospheric air masses in the troposphere. Studies of radionuclide activities in aerosol particles provide a means for evaluating the integrated effects of transport and meteorology on the atmospheric loadings of substances with different sources. Measurements of aerosol mass concentration and specific activities of (7)Be and (210)Pb in aerosols at Malaga (36° 43' 40″ N; 4° 28' 8″ W) for the period 2009-2011 were used to obtain the relationships between radionuclide activities and airflow patterns by comparing the data grouped by air mass trajectory. The average concentration values of (7)Be and (210)Pb over the 3-year period have been found to be 5.05 and 0.55 mBq m(-3), respectively, with mean aerosol mass concentration of 53.6 μg m(-3). Taking into account the outbreaks of the daily values limits of PM10 in the study period (2009-2011), the origin of air masses is studied to explain three different situations of both radionuclides (7)Be and (210)Pb: 1) high concentrations of (7)Be and low concentrations of (210)Pb; 2) high concentrations of (210)Pb and low concentrations of (7)Be and 3) high concentrations of (7)Be and (210)Pb. Copyright © 2015 Elsevier Ltd. All rights reserved.
Smetana, K; Karban, J; Trneny, M
2010-01-01
The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or bodies of the lymphocytic origin, the "frozen" nucleolar RNA concentration accompanied by a reduced RNA concentration in the cytoplasm exhibited a remarkable similarity to the apoptotic process induced in vitro by the cytostatic treatment. B-chronic lymphocytic leukemia; lymphocytes; nucleolar classes; size; nucleolar RNA image density -concentration.
Global cost of child survival: estimates from country-level validation
van Ekdom, Liselore; Scherpbier, Robert W; Niessen, Louis W
2011-01-01
Abstract Objective To cross-validate the global cost of scaling up child survival interventions to achieve the fourth Millennium Development Goal (MDG4) as estimated by the World Health Organization (WHO) in 2007 by using the latest country-provided data and new assumptions. Methods After the main cost categories for each country were identified, validation questionnaires were sent to 32 countries with high child mortality. Publicly available estimates for disease incidence, intervention coverage, prices and resources for individual-level and programme-level activities were validated against local data. Nine updates to the 2007 WHO model were generated using revised assumptions. Finally, estimates were extrapolated to 75 countries and combined with cost estimates for immunization and malaria programmes and for programmes for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV). Findings Twenty-six countries responded. Adjustments were largest for system- and programme-level data and smallest for patient data. Country-level validation caused a 53% increase in original cost estimates (i.e. 9 billion 2004 United States dollars [US$]) for 26 countries owing to revised system and programme assumptions, especially surrounding community health worker costs. The additional effect of updated population figures was small; updated epidemiologic figures increased costs by US$ 4 billion (+15%). New unit prices in the 26 countries that provided data increased estimates by US$ 4.3 billion (+16%). Extrapolation to 75 countries increased the original price estimate by US$ 33 billion (+80%) for 2010–2015. Conclusion Country-level validation had a significant effect on the cost estimate. Price adaptations and programme-related assumptions contributed substantially. An additional 74 billion US$ 2005 (representing a 12% increase in total health expenditure) would be needed between 2010 and 2015. Given resource constraints, countries will need to prioritize health activities within their national resource envelope. PMID:21479091
The CK2 Kinase Stabilizes CLOCK and Represses Its Activity in the Drosophila Circadian Oscillator
Szabó, Áron; Papin, Christian; Zorn, Daniela; Ponien, Prishila; Weber, Frank; Raabe, Thomas; Rouyer, François
2013-01-01
Phosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity. Here we show that CK2 also targets the CLK activator directly. Downregulating the activity of the catalytic α subunit of CK2 induces CLK degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory β subunit of the CK2 holoenzyme is not required for the regulation of CLK stability. In addition, downregulation of CK2α activity decreases CLK phosphorylation and increases per and tim transcription. These results indicate that CK2 inhibits CLK degradation while reducing its activity. Since the CK1 kinase promotes CLK degradation, we suggest that CLK stability and transcriptional activity result from counteracting effects of CK1 and CK2. PMID:24013921
Tarkiainen, Lasse; Martikainen, Pekka; Laaksonen, Mikko
2016-03-01
First, to quantify trends in the contribution of alcohol-related mortality to mortality disparity in Finland by income quintiles. Secondly, to estimate the degree to which education, social class and economic activity explain the income-mortality association in alcohol-related and other mortality in four periods within 1988-2012. Register-based longitudinal study using an 11% random sample of Finnish residents linked to socio-economic and mortality data in 1988-2012 augmented with an 80% sample of all deaths during 1988-2007. Mortality rates and discrete time survival regression models were used to assess the income-mortality association following adjustment for covariates in 6-year periods after baseline years of 1988, 1994, 2001, and 2007. Finland. Individuals aged 35-64 years at baselines. For the four study periods for men/women, the final data set comprised, respectively, 26,360/12,825, 22,561/11,423, 20,342/11,319 and 2651/1514 deaths attributable to other causes and 7517/1217, 8199/1450, 9807/2116, 1431/318 deaths attributable to alcohol-related causes. Alcohol-related deaths were analysed with household income, education, social class and economic activity as covariates. The income disparity in mortality originated increasingly from alcohol-related causes of death, in the lowest quintile the contribution increasing from 28 to 49% among men and from 11 to 28% among women between periods 1988-93 and 2007-12. Among men, socio-economic characteristics attenuated the excess mortality during each study period in the lowest income quintile by 51-62% in alcohol-related and other causes. Among women, in the lowest quintile the attenuation was 47-76% in other causes, but there was a decreasing tendency in the proportion explained by the covariates in alcohol-related mortality. The income disparity in mortality among working-age Finns originates increasingly from alcohol-related causes of death. Roughly half the excess mortality in the lowest income quintile during 2007-12 is explained by the covariates of household income, education, social class and economic activity. © 2015 Society for the Study of Addiction.
Evidence for a neural law of effect.
Athalye, Vivek R; Santos, Fernando J; Carmena, Jose M; Costa, Rui M
2018-03-02
Thorndike's law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation. Learning was accompanied by gradual shaping of these patterns, with participating neurons progressively increasing and aligning their covariance to that of the target pattern. Motor cortex patterns that lead to phasic dopaminergic VTA activity are progressively reinforced and shaped, suggesting a mechanism by which animals select and shape actions to reliably achieve reinforcement. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
NASA Technical Reports Server (NTRS)
Misulis, K. E.; Dettbarn, W. D.
1985-01-01
An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.
A Bit of Fit: Minimalist Intervention in Adolescents Based on a Physical Activity Tracker.
Gaudet, Jeffrey; Gallant, François; Bélanger, Mathieu
2017-07-06
Only 5% of Canadian youth meet the recommended 60 minutes of moderate to vigorous physical activity (MVPA) per day, with leisure time being increasingly allocated to technology usage. Direct-to-consumer mHealth devices that promote physical activity, such as wrist-worn physical activity trackers, have features with potential appeal to youth. The primary purpose of this study was to determine whether a minimalist physical activity tracker-based intervention would lead to an increase in physical activity in young adolescents. A secondary aim of this study was to assess change in physical activity across a 7-week intervention, as measured by the tracker. Using a quasi-experimental crossover design, two groups of 23 young adolescents (aged 13-14 years) were randomly assigned to immediate intervention or delayed intervention. The intervention consisted of wearing a Fitbit-Charge-HR physical activity tracker over a 7-week period. Actical accelerometers were used to measure participants' levels of MVPA before and at the end of intervention periods for each group. Covariates such as age, sex, stage of change for physical activity behavior, and goal commitment were also measured. There was an increase in physical activity over the course of the study period, though it was not related to overall physical activity tracker use. An intervention response did, however, occur in a subset of participants. Specifically, exposure to the physical activity tracker was associated with an average daily increase in MVPA by more than 15 minutes (P=.01) among participants who reported being in the action and maintenance stages of behavior change in relation to participation in physical activity. Participants in the precontemplation, contemplation, and preparation stages of behavior change had no change in their level of MVPA (P=.81). These results suggest that physical activity trackers may elicit improved physical activity related behavior in young adolescents demonstrating a readiness to be active. Future studies should seek to investigate if integrating physical activity trackers as part of more intensive interventions leads to greater increases in physical activity across different levels of stages of behavior change and if these changes can be sustained over longer periods of time. ©Jeffrey Gaudet, François Gallant, Mathieu Bélanger. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.07.2017.
2016-09-01
Reports an error in "Meta-analysis of dropout in treatments for posttraumatic stress disorder" by Zac E. Imel, Kevin Laska, Matthew Jakupcak and Tracy L. Simpson ( Journal of Consulting and Clinical Psychology , 2013[Jun], Vol 81[3], 394-404). There are two errors in the Results section. Each is described alongside the corrected results. Corrections did not influence interpretation of the results. Neither the magnitude of effects nor statistical significance of any results is substantively altered. (The following abstract of the original article appeared in record 2013-01522-001.) Objective: Many patients drop out of treatments for posttraumatic stress disorder (PTSD); some clinicians believe that trauma-focused treatments increase dropout. We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). The average dropout rate was 18%, but it varied significantly across studies. Group modality and greater number of sessions, but not trauma focus, predicted increased dropout. When the meta-analysis was restricted to direct comparisons of active treatments, there were no differences in dropout. Differences in trauma focus between treatments in the same study did not predict dropout. However, trauma-focused treatments resulted in higher dropout compared with present-centered therapy (PCT), a treatment originally designed as a control but now listed as a research-supported intervention for PTSD. Dropout varies between active interventions for PTSD across studies, but variability is primarily driven by differences between studies. There do not appear to be systematic differences across active interventions when they are directly compared in the same study. The degree of clinical attention placed on the traumatic event does not appear to be a primary cause of dropout from active treatments. However, comparisons of PCT may be an exception to this general pattern, perhaps because of a restriction of variability in trauma focus among comparisons of active treatments. More research is needed comparing trauma-focused interventions to trauma-avoidant treatments such as PCT. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sun, Z.
Electron Backscatter Diffraction technique is used to characterize the microstructure of 316L steel generated by Surface Mechanical Attrition Treatment (SMAT) before and after low cycle fatigue tests. A grain size gradient is generated from the top surface to the interior of the samples after SMAT so that three main regions can be distinguished below the treated surface: (i) the ultra-fine grain area within 5 μm under the top surface with preferably oriented grains, (ii) the intermediate area where the original grains are partially transformed, and (iii) the edge periphery area where the original grains are just mechanically deformed with themore » presence of plastic slips. Fatigue tests show that cyclic loading does not change the grain orientation spread and does not activate any plastic slip in the ultra-fine grain top surface area induced by SMAT. On the opposite, in the plastically SMAT affected region including the intermediate area and the edge periphery area, new slip systems are activated by low cycle fatigue while the grain orientation spread is increased. These results represent a first very interesting step towards the characterization and understanding of mechanical mechanisms involved during the fatigue of a grain size gradient material. - Highlights: •LCF tests are carried out on specimens processed by SMAT. •EBSD is used to investigate microstructural changes induced by LCF. •A grain size gradient is generated by SMAT from surface to the bulk of the fatigue samples. •New slip systems are activated by LCF and GOS is increased in plastically deformed region. •However, these phenomena are not observed in the top surface ultra-fine grain area.« less
van Brabant, A J; Hunt, S Y; Fangman, W L; Brewer, B J
1998-06-01
DNA fragments that contain an active origin of replication generate bubble-shaped replication intermediates with diverging forks. We describe two methods that use two-dimensional (2-D) agarose gel electrophoresis along with DNA sequence information to identify replication origins in natural and artificial Saccharomyces cerevisiae chromosomes. The first method uses 2-D gels of overlapping DNA fragments to locate an active chromosomal replication origin within a region known to confer autonomous replication on a plasmid. A variant form of 2-D gels can be used to determine the direction of fork movement, and the second method uses this technique to find restriction fragments that are replicated by diverging forks, indicating that a bidirectional replication origin is located between the two fragments. Either of these two methods can be applied to the analysis of any genomic region for which there is DNA sequence information or an adequate restriction map.
NASA Astrophysics Data System (ADS)
Michaelian, K.; Simeonov, A.
2015-08-01
The driving force behind the origin and evolution of life has been the thermodynamic imperative of increasing the entropy production of the biosphere through increasing the global solar photon dissipation rate. In the upper atmosphere of today, oxygen and ozone derived from life processes are performing the short-wavelength UV-C and UV-B dissipation. On Earth's surface, water and organic pigments in water facilitate the near-UV and visible photon dissipation. The first organic pigments probably formed, absorbed, and dissipated at those photochemically active wavelengths in the UV-C and UV-B that could have reached Earth's surface during the Archean. Proliferation of these pigments can be understood as an autocatalytic photochemical process obeying non-equilibrium thermodynamic directives related to increasing solar photon dissipation rate. Under these directives, organic pigments would have evolved over time to increase the global photon dissipation rate by (1) increasing the ratio of their effective photon cross sections to their physical size, (2) decreasing their electronic excited state lifetimes, (3) quenching radiative de-excitation channels (e.g., fluorescence), (4) covering ever more completely the prevailing solar spectrum, and (5) proliferating and dispersing to cover an ever greater surface area of Earth. From knowledge of the evolution of the spectrum of G-type stars, and considering the most probable history of the transparency of Earth's atmosphere, we construct the most probable Earth surface solar spectrum as a function of time and compare this with the history of molecular absorption maxima obtained from the available data in the literature. This comparison supports the conjecture that many fundamental molecules of life are pigments which arose, proliferated, and co-evolved as a response to dissipating the solar spectrum, supports the thermodynamic dissipation theory for the origin of life, constrains models for Earth's early atmosphere, and sheds some new light on the origin of photosynthesis.