Sample records for activity showed similar

  1. Bipolar I disorder and major depressive disorder show similar brain activation during depression.

    PubMed

    Cerullo, Michael A; Eliassen, James C; Smith, Christopher T; Fleck, David E; Nelson, Erik B; Strawn, Jeffrey R; Lamy, Martine; DelBello, Melissa P; Adler, Caleb M; Strakowski, Stephen M

    2014-11-01

    Despite different treatments and courses of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions, with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    PubMed

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  3. Methanol extract of grain dust shows complement fixing activity and other characteristics similar to tannic acid.

    PubMed Central

    Skea, D; Broder, I

    1986-01-01

    We have found several similarities between tannic acid and grain dust extract prepared with methanol. Both formed a precipitate with IgG, and these interactions were inhibited by albumin. In addition, both preparations fixed complement; this activity was heat stable and was removed by prior adsorption of the preparations with hide powder. Adsorption with polyvinyl polypyrrolidone reduced the complement-fixing activity of tannic acid but not that of the methanol grain dust extract. The similarities between tannic acid and the methanol grain dust extract are consistent with the presence of a tannin or tanninlike material in grain dust. Images FIGURE 1. PMID:3709479

  4. Intrinsic atopic dermatitis (AD) shows similar Th2 and higher Th17 immune activation compared to extrinsic AD

    PubMed Central

    Suárez-Fariñas, M; Dhingra, N; Gittler, J; Shemer, A; Cardinale, I; de Guzman Strong, C; Krueger, JG; Guttman-Yassky, E

    2013-01-01

    Background Atopic dermatitis (AD) is classified as extrinsic (ADe) and intrinsic (ADi), representing approximately 80% and 20% of patients, respectively. While sharing a similar clinical phenotype, only ADe is characterized by high serum IgE. Since most AD patients exhibit high IgE, an “allergic”/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly Th2/Th22 polarization, and epidermal barrier defects. Objective To define if both variants share a common pathogenesis. Methods We stratified 51 severe AD patients as ADe (42) and ADi (9) (with similar mean disease activity/SCORAD), and analyzed the molecular and cellular skin pathology of lesional and non-lesional ADi and ADe using gene-expression (RT-PCR) and immunohistochemistry. Results A significant correlation between IgE levels and SCORAD (r=0.76, p<10−5) was found only in ADe. Marked infiltrates of T-cells and dendritic cells and corresponding epidermal alterations (K16, Mki67, S100A7/A8/A9) defined lesional skin of both variants. However, higher activation of all inflammatory axes (including Th2) was detected in ADi, particularly Th17 and Th22-cytokines. Positive correlations between Th17-related molecules and SCORAD were only found in ADi, while only ADe showed positive correlations between SCORAD and Th2-cytokines (IL-4, IL-5), and negative correlations with differentiation products (loricrin, periplakin). Conclusions Although differences in Th17 and Th22 activation exist between ADi and ADe, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a Th2 bias is not the sole cause of high IgE in ADe, with important implications for similar therapeutic interventions. Clinical Implications Both extrinsic and intrinsic AD variants might be treated with T-cell targeted therapeutics or agents that modify keratinocyte

  5. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.

    PubMed

    Suárez-Fariñas, Mayte; Dhingra, Nikhil; Gittler, Julia; Shemer, Avner; Cardinale, Irma; de Guzman Strong, Cristina; Krueger, James G; Guttman-Yassky, Emma

    2013-08-01

    Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an "allergic"/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. We sought to define whether both variants share a common pathogenesis. We stratified 51 patients with severe AD into extrinsic AD (n = 42) and intrinsic AD (n = 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. A significant correlation between IgE levels and SCORAD scores (r = 0.76, P < 10(-5)) was found only in patients with extrinsic AD. Marked infiltrates of T cells and dendritic cells and corresponding epidermal alterations (keratin 16, Mki67, and S100A7/A8/A9) defined lesional skin of patients with both variants. However, higher activation of all inflammatory axes (including TH2) was detected in patients with intrinsic AD, particularly TH17 and TH22 cytokines. Positive correlations between TH17-related molecules and SCORAD scores were only found in patients with intrinsic AD, whereas only patients with extrinsic AD showed positive correlations between SCORAD scores and TH2 cytokine (IL-4 and IL-5) levels and negative correlations with differentiation products (loricrin and periplakin). Although differences in TH17 and TH22 activation exist between patients with intrinsic AD and those with extrinsic AD, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a

  6. Lemurs and macaques show similar numerical sensitivity.

    PubMed

    Jones, Sarah M; Pearson, John; DeWind, Nicholas K; Paulsen, David; Tenekedjieva, Ana-Maria; Brannon, Elizabeth M

    2014-05-01

    We investigated the precision of the approximate number system (ANS) in three lemur species (Lemur catta, Eulemur mongoz, and Eulemur macaco flavifrons), one Old World monkey species (Macaca mulatta) and humans (Homo sapiens). In Experiment 1, four individuals of each nonhuman primate species were trained to select the numerically larger of two visual arrays on a touchscreen. We estimated numerical acuity by modeling Weber fractions (w) and found quantitatively equivalent performance among all four nonhuman primate species. In Experiment 2, we tested adult humans in a similar procedure, and they outperformed the four nonhuman species but showed qualitatively similar performance. These results indicate that the ANS is conserved over the primate order.

  7. Face and body recognition show similar improvement during childhood.

    PubMed

    Bank, Samantha; Rhodes, Gillian; Read, Ainsley; Jeffery, Linda

    2015-09-01

    Adults are proficient in extracting identity cues from faces. This proficiency develops slowly during childhood, with performance not reaching adult levels until adolescence. Bodies are similar to faces in that they convey identity cues and rely on specialized perceptual mechanisms. However, it is currently unclear whether body recognition mirrors the slow development of face recognition during childhood. Recent evidence suggests that body recognition develops faster than face recognition. Here we measured body and face recognition in 6- and 10-year-old children and adults to determine whether these two skills show different amounts of improvement during childhood. We found no evidence that they do. Face and body recognition showed similar improvement with age, and children, like adults, were better at recognizing faces than bodies. These results suggest that the mechanisms of face and body memory mature at a similar rate or that improvement of more general cognitive and perceptual skills underlies improvement of both face and body recognition. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Active browsing using similarity pyramids

    NASA Astrophysics Data System (ADS)

    Chen, Jau-Yuen; Bouman, Charles A.; Dalton, John C.

    1998-12-01

    In this paper, we describe a new approach to managing large image databases, which we call active browsing. Active browsing integrates relevance feedback into the browsing environment, so that users can modify the database's organization to suit the desired task. Our method is based on a similarity pyramid data structure, which hierarchically organizes the database, so that it can be efficiently browsed. At coarse levels, the similarity pyramid allows users to view the database as large clusters of similar images. Alternatively, users can 'zoom into' finer levels to view individual images. We discuss relevance feedback for the browsing process, and argue that it is fundamentally different from relevance feedback for more traditional search-by-query tasks. We propose two fundamental operations for active browsing: pruning and reorganization. Both of these operations depend on a user-defined relevance set, which represents the image or set of images desired by the user. We present statistical methods for accurately pruning the database, and we propose a new 'worm hole' distance metric for reorganizing the database, so that members of the relevance set are grouped together.

  9. Common marmosets show social plasticity and group-level similarity in personality

    PubMed Central

    Koski, Sonja E.; Burkart, Judith M.

    2015-01-01

    The social environment influences animal personality on evolutionary and immediate time scales. However, studies of animal personality rarely assess the effects of the social environment, particularly in species that live in stable groups with individualized relationships. We assessed personality experimentally in 17 individuals of the common marmoset, living in four groups. We found their personality to be considerably modified by the social environment. Marmosets exhibited relatively high plasticity in their behaviour, and showed ‘group-personality’, i.e. group-level similarity in the personality traits. In exploratory behaviour this was maintained only in the social environment but not when individuals were tested alone, suggesting that exploration tendency is subjected to social facilitation. Boldness, in contrast, showed higher consistency across the social and solitary conditions, and the group-level similarity in trait scores was sustained also outside of the immediate social environment. The ‘group-personality’ was not due to genetic relatedness, supporting that it was produced by social effects. We hypothesize that ‘group-personality’ may be adaptive for highly cooperative animals through facilitating cooperation among individuals with similar behavioural tendency. PMID:25743581

  10. Tridacna Derived ENSO Records From The Philippines During The Last Interglacial Show Similar ENSO Activity To The Present Day

    NASA Astrophysics Data System (ADS)

    Welsh, K.; Morgan, Z.; Suzuki, A.

    2016-12-01

    Although modeled predictions for the relative strength and frequency of ENSO under mean warming conditions suggest an increase in the number and strength of ENSO event, however there are limited seasonally resolved records of ENSO variability during previous warm periods for example the last interglacial to test these models as reliable archives such as corals are not generally well preserved over these time periods. Presented here are two multi decadal Tridacna gigas derived stable isotopic time series from a coral terrace on the island of Cebu in the Philippines that formed during MIS5e based upon geomorphology and open-system corrected U/Th dating of corals. The ENSO activity observed in these time well preserved records indicate a similar level of ENSO activity during the last interglacial period as the present day based upon comparisons with recent coral derived stable isotopic records. Though these are relatively short records they provide further windows into ENSO activity from this important time period and demonstrate this area may be provide more opportunities to gather these archives.

  11. Women show similar central and peripheral fatigue to men after half-marathon.

    PubMed

    Boccia, Gennaro; Dardanello, Davide; Tarperi, Cantor; Festa, Luca; La Torre, Antonio; Pellegrini, Barbara; Schena, Federico; Rainoldi, Alberto

    2018-06-01

    Women are known to be less fatigable than men in single-joint exercises, but fatigue induced by running has not been well understood. Here we investigated sex differences in central and peripheral fatigue and in rate of force development (RFD) in the knee extensors after a half-marathon run. Ten male and eight female amateur runners (aged 25-50 years) were evaluated before and immediately after a half-marathon race. Knee extensors forces were obtained under voluntary and electrically evoked isometric contractions. Maximal voluntary isometric contraction (MVC) force and peak RFD were recorded. Electrically doublet stimuli were delivered during the MVC and at rest to calculate the level of voluntary activation and the resting doublet twitch. After the race, decreases in MVC force (males: -11%, effect size [ES] 0.52; females: -11% ES 0.33), voluntary activation (males: -6%, ES 0.87; females: -4%, ES 0.72), and resting doublet twitch (males: -6%, ES 0.34; females: -8%, ES 0.30) were found to be similar between males and females. The decrease in peak RFD was found to be similar between males and females (males: -14%, ES 0.43; females: -15%, ES 0.14). Half-marathon run induced both central and peripheral fatigue, without any difference between men and women. The maximal and explosive strength loss was found similar between sexes. Together, these findings do not support the need of sex-specific training interventions to increase the tolerance to neuromuscular fatigue in half-marathoners.

  12. Pollinators show flower colour preferences but flowers with similar colours do not attract similar pollinators

    PubMed Central

    Reverté, Sara; Retana, Javier; Gómez, José M.; Bosch, Jordi

    2016-01-01

    Background and aims Colour is one of the main floral traits used by pollinators to locate flowers. Although pollinators show innate colour preferences, the view that the colour of a flower may be considered an important predictor of its main pollinators is highly controversial because flower choice is highly context-dependent, and initial innate preferences may be overridden by subsequent associative learning. Our objective is to establish whether there is a relationship between flower colour and pollinator composition in natural communities. Methods We measured the flower reflectance spectrum and pollinator composition in four plant communities (85 plant species represented by 109 populations, and 32 305 plant–pollinator interactions in total). Pollinators were divided into six taxonomic groups: bees, ants, wasps, coleopterans, dipterans and lepidopterans. Key Results We found consistent associations between pollinator groups and certain colours. These associations matched innate preferences experimentally established for several pollinators and predictions of the pollination syndrome theory. However, flowers with similar colours did not attract similar pollinator assemblages. Conclusions The explanation for this paradoxical result is that most flower species are pollination generalists. We conclude that although pollinator colour preferences seem to condition plant–pollinator interactions, the selective force behind these preferences has not been strong enough to mediate the appearance and maintenance of tight colour-based plant–pollinator associations. PMID:27325897

  13. Pollinators show flower colour preferences but flowers with similar colours do not attract similar pollinators.

    PubMed

    Reverté, Sara; Retana, Javier; Gómez, José M; Bosch, Jordi

    2016-08-01

    Colour is one of the main floral traits used by pollinators to locate flowers. Although pollinators show innate colour preferences, the view that the colour of a flower may be considered an important predictor of its main pollinators is highly controversial because flower choice is highly context-dependent, and initial innate preferences may be overridden by subsequent associative learning. Our objective is to establish whether there is a relationship between flower colour and pollinator composition in natural communities. We measured the flower reflectance spectrum and pollinator composition in four plant communities (85 plant species represented by 109 populations, and 32 305 plant-pollinator interactions in total). Pollinators were divided into six taxonomic groups: bees, ants, wasps, coleopterans, dipterans and lepidopterans. We found consistent associations between pollinator groups and certain colours. These associations matched innate preferences experimentally established for several pollinators and predictions of the pollination syndrome theory. However, flowers with similar colours did not attract similar pollinator assemblages. The explanation for this paradoxical result is that most flower species are pollination generalists. We conclude that although pollinator colour preferences seem to condition plant-pollinator interactions, the selective force behind these preferences has not been strong enough to mediate the appearance and maintenance of tight colour-based plant-pollinator associations. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks

    PubMed Central

    García-Hernández, Alejandra; Galván-Tejada, Jorge I.; Celaya-Padilla, José M.; Velasco-Elizondo, Perla; Cárdenas-Vargas, Rogelio

    2017-01-01

    Human Activity Recognition (HAR) is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location. PMID:29160799

  15. Global mammal beta diversity shows parallel assemblage structure in similar but isolated environments

    PubMed Central

    Graham, Catherine H.; Brooks, Thomas M.; Rondinini, Carlo; Hedges, S. Blair; Davidson, Ana D.; Costa, Gabriel C.

    2016-01-01

    The taxonomic, phylogenetic and trait dimensions of beta diversity each provide us unique insights into the importance of historical isolation and environmental conditions in shaping global diversity. These three dimensions should, in general, be positively correlated. However, if similar environmental conditions filter species with similar trait values, then assemblages located in similar environmental conditions, but separated by large dispersal barriers, may show high taxonomic, high phylogenetic, but low trait beta diversity. Conversely, we expect lower phylogenetic diversity, but higher trait biodiversity among assemblages that are connected but are in differing environmental conditions. We calculated all pairwise comparisons of approximately 110 × 110 km grid cells across the globe for more than 5000 mammal species (approx. 70 million comparisons). We considered realms as units representing geographical distance and historical isolation and biomes as units with similar environmental conditions. While beta diversity dimensions were generally correlated, we highlight geographical regions of decoupling among beta diversity dimensions. Our analysis shows that assemblages from tropical forests in different realms had low trait dissimilarity while phylogenetic beta diversity was significantly higher than expected, suggesting potential convergent evolution. Low trait beta diversity was surprisingly not found between isolated deserts, despite harsh environmental conditions. Overall, our results provide evidence for parallel assemblage structure of mammal assemblages driven by environmental conditions at a global scale. PMID:27559061

  16. Liberals and conservatives can show similarities in negativity bias.

    PubMed

    Brandt, Mark J; Wetherell, Geoffrey; Reyna, Christine

    2014-06-01

    Negativity bias may underlie the development of political ideologies, but liberals and conservatives are likely to respond to threats similarly. We review evidence from research on intolerance, motivated reasoning, and basic psychological threats that suggest liberals and conservatives are more similar than different when confronting threatening groups, situations, and information.

  17. Glyceraldehyde-3-phosphate dehydrogenase from Chironomidae showed differential activity towards metals.

    PubMed

    Chong, Isaac K W; Ho, Wing S

    2013-09-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known to interact with different biomolecules and was implicated in many novel cellular activities including programmed cell death, nuclear RNA transport unrelated to the commonly known carbohydrate metabolism. We reported here the purification of GAPDH from Chironomidae larvae (Insecta, Diptera) that showed different biologic activity towards heavy metals. It was inhibited by copper, cobalt nickel, iron and lead but was activated by zinc. The GAPDH was purified by ammonium sulphate fractionation and Chelating Sepharose CL-6B chromatography followed by Blue Sepharose CL-6B chromatography. The 150-kDa tetrameric GAPDH showed optimal activity at pH 8.5 and 37°C. The multiple alignment of sequence of the Chironomidae GAPDH with other known species showed 78 - 88% identity to the conserved regions of the GADPH. Bioinformatic analysis unveils substantial N-terminal sequence similarity of GAPDH of Chironomidae larvae to mammalian GADPHs. However, the GADPH of Chironomidae larvae showed different biologic activities and cytotoxicity towards heavy metals. The GAPDH enzyme would undergo adaptive molecular changes through binding at the active site leading to higher tolerance to heavy metals.

  18. Similarity of Cortical Activity Patterns Predicts generalization Behavior

    PubMed Central

    Engineer, Crystal T.; Perez, Claudia A.; Carraway, Ryan S.; Chang, Kevin Q.; Roland, Jarod L.; Sloan, Andrew M.; Kilgard, Michael P.

    2013-01-01

    Humans and animals readily generalize previously learned knowledge to new situations. Determining similarity is critical for assigning category membership to a novel stimulus. We tested the hypothesis that category membership is initially encoded by the similarity of the activity pattern evoked by a novel stimulus to the patterns from known categories. We provide behavioral and neurophysiological evidence that activity patterns in primary auditory cortex contain sufficient information to explain behavioral categorization of novel speech sounds by rats. Our results suggest that category membership might be encoded by the similarity of the activity pattern evoked by a novel speech sound to the patterns evoked by known sounds. Categorization based on featureless pattern matching may represent a general neural mechanism for ensuring accurate generalization across sensory and cognitive systems. PMID:24147140

  19. Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

    PubMed Central

    Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

    2014-01-01

    Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

  20. [-25]A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks.

    PubMed

    García-Hernández, Alejandra; Galván-Tejada, Carlos E; Galván-Tejada, Jorge I; Celaya-Padilla, José M; Gamboa-Rosales, Hamurabi; Velasco-Elizondo, Perla; Cárdenas-Vargas, Rogelio

    2017-11-21

    Human Activity Recognition (HAR) is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location.

  1. Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

    PubMed

    Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

    2014-10-01

    Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

  2. Similarity of scattering rates in metals showing T-linear resistivity.

    PubMed

    Bruin, J A N; Sakai, H; Perry, R S; Mackenzie, A P

    2013-02-15

    Many exotic compounds, such as cuprate superconductors and heavy fermion materials, exhibit a linear in temperature (T) resistivity, the origin of which is not well understood. We found that the resistivity of the quantum critical metal Sr(3)Ru(2)O(7) is also T-linear at the critical magnetic field of 7.9 T. Using the precise existing data for the Fermi surface topography and quasiparticle velocities of Sr(3)Ru(2)O(7), we show that in the region of the T-linear resistivity, the scattering rate per kelvin is well approximated by the ratio of the Boltzmann constant to the Planck constant divided by 2π. Extending the analysis to a number of other materials reveals similar results in the T-linear region, in spite of large differences in the microscopic origins of the scattering.

  3. Corrective jitter motion shows similar individual frequencies for the arm and the finger.

    PubMed

    Noy, Lior; Alon, Uri; Friedman, Jason

    2015-04-01

    A characteristic of visuomotor tracking of non-regular oscillating stimuli are high-frequency jittery corrective motions, oscillating around the tracked stimuli. However, the properties of these corrective jitter responses are not well understood. For example, does the jitter response show an idiosyncratic signature? What is the relationship between stimuli properties and jitter properties? Is the jitter response similar across effectors with different inertial properties? To answer these questions, we measured participants' jitter frequencies in two tracking tasks in the arm and the finger. Thirty participants tracked the same set of eleven non-regular oscillating stimuli, vertically moving on a screen, once with forward-backward arm movements (holding a tablet stylus) and once with upward-downward index finger movements (with a motion tracker attached). Participants' jitter frequencies and tracking errors varied systematically as a function of stimuli frequency and amplitude. Additionally, there were clear individual differences in average jitter frequencies between participants, ranging from 0.7 to 1.15 Hz, similar to values reported previously. A comparison of individual jitter frequencies in the two tasks showed a strong correlation between participants' jitter frequencies in the finger and the arm, despite the very different inertial properties of the two effectors. This result suggests that the corrective jitter response stems from common neural processes.

  4. Candida tropicalis from veterinary and human sources shows similar in vitro hemolytic activity, antifungal biofilm susceptibility and pathogenesis against Caenorhabditis elegans.

    PubMed

    Brilhante, Raimunda Sâmia Nogueira; Oliveira, Jonathas Sales de; Evangelista, Antônio José de Jesus; Serpa, Rosana; Silva, Aline Lobão da; Aguiar, Felipe Rodrigues Magalhães de; Pereira, Vandbergue Santos; Castelo-Branco, Débora de Souza Collares Maia; Pereira-Neto, Waldemiro Aquino; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha

    2016-08-30

    The aim of this study was to evaluate the in vitro hemolytic activity and biofilm antifungal susceptibility of veterinary and human Candida tropicalis strains, as well as their pathogenesis against Caenorhabditis elegans. Twenty veterinary isolates and 20 human clinical isolates of C. tropicalis were used. The strains were evaluated for their hemolytic activity and biofilm production. Biofilm susceptibility to itraconazole, fluconazole, voriconazole, amphotericin B and caspofungin was assessed using broth microdilution assay. The in vivo evaluation of strain pathogenicity was investigated using the nematode C. elegans. Hemolytic factor was observed in 95% of the strains and 97.5% of the isolates showed ability to form biofilm. Caspofungin and amphotericin B showed better results than azole antifungals against mature biofilms. Paradoxical effect on mature biofilm metabolic activity was observed at elevated concentrations of caspofungin (8-64μg/mL). Azole antifungals were not able to inhibit mature C. tropicalis biofilms, even at the higher tested concentrations. High mortality rates of C. elegans were observed when the worms were exposed to with C. tropicalis strains, reaching up to 96%, 96h after exposure of the worms to C. tropicalis strains. These results reinforce the high pathogenicity of C. tropicalis from veterinary and human sources and show the effectiveness of caspofungin and amphotericin B against mature biofilms of this species. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Osteomyelitis Treatment with Nanometer-Sized Hydroxyapatite Particles as a Delivery Vehicle for a Ciprofloxacin- Bisphosphonate Conjugate; New Fluoroquinolone-Bisphosphonate Derivatives Show Similar Binding Affinity to Hydroxyapatite and Improved Antibacterial Activity Against Drug-Resistant Pathogens

    DTIC Science & Technology

    2008-12-01

    1 OSTEOMYELITIS TREATMENT WITH NANOMETER-SIZED HYDROXYAPATITE PARTICLES AS A DELIVERY VEHICLE FOR A CIPROFLOXACIN- BISPHOSPHONATE CONJUGATE; NEW...FLUOROQUINOLONE-BISPHOSPHONATE DERIVATIVES SHOW SIMILAR BINDING AFFINITY TO HYDROXYAPATITE AND IMPROVED ANTIBACTERIAL ACTIVITY AGAINST DRUG-RESISTANT...vivo OM model. Current studies contrast two CP homeostatic bone-substitute particles, nanometer-sized hydroxyapatite NanOss™ (Nan), and µ-sized

  6. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    PubMed Central

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  7. Predicting activity approach based on new atoms similarity kernel function.

    PubMed

    Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

    2015-07-01

    Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Females and males are highly similar in language performance and cortical activation patterns during verb generation.

    PubMed

    Allendorfer, Jane B; Lindsell, Christopher J; Siegel, Miriam; Banks, Christi L; Vannest, Jennifer; Holland, Scott K; Szaflarski, Jerzy P

    2012-10-01

    To test the existence of sex differences in cortical activation during verb generation when performance is controlled for. Twenty male and 20 female healthy adults underwent functional magnetic resonance imaging (fMRI) using a covert block-design verb generation task (BD-VGT) and its event-related version (ER-VGT) that allowed for intra-scanner recordings of overt responses. Task-specific activations were determined using the following contrasts: BD-VGT covert generation>finger-tapping; ER-VGT overt generation>repetition; ER-VGT overt>covert generation. Lateral cortical regions activated during each contrast were used for calculating language lateralization index scores. Voxelwise regressions were used to determine sex differences in activation, with and without controlling for performance. Each brain region showing male/female activation differences for ER-VGT overt generation>repetition (isolating noun-verb association) was defined as a region of interest (ROI). For each subject, the signal change in each ROI was extracted, and the association between ER-VGT activation related to noun-verb association and performance was assessed separately for each sex. Males and females performed similarly on language assessments, had similar patterns of language lateralization, and exhibited similar activation patterns for each fMRI task contrast. Regression analysis controlling for overt intra-scanner performance either abolished (BD-VGT) or reduced (ER-VGT) the observed differences in activation between sexes. The main difference between sexes occurred during ER-VGT processing of noun-verb associations, where males showed greater activation than females in the right middle/superior frontal gyrus (MFG/SFG) and the right caudate/anterior cingulate gyrus (aCG) after controlling for performance. Better verb generation performance was associated with increased right caudate/aCG activation in males and with increased right MFG/SFG activation in females. Males and females exhibit

  9. Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets

    PubMed Central

    Akala, Hoseah M.; Macharia, Rosaline W.; Juma, Dennis W.; Cheruiyot, Agnes C.; Andagalu, Ben; Brown, Mathew L.; El-Shemy, Hany A.; Nyanjom, Steven G.

    2017-01-01

    Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens. PMID:29088219

  10. Engaging narratives evoke similar neural activity and lead to similar time perception.

    PubMed

    Cohen, Samantha S; Henin, Simon; Parra, Lucas C

    2017-07-04

    It is said that we lose track of time - that "time flies" - when we are engrossed in a story. How does engagement with the story cause this distorted perception of time, and what are its neural correlates? People commit both time and attentional resources to an engaging stimulus. For narrative videos, attentional engagement can be represented as the level of similarity between the electroencephalographic responses of different viewers. Here we show that this measure of neural engagement predicted the duration of time that viewers were willing to commit to narrative videos. Contrary to popular wisdom, engagement did not distort the average perception of time duration. Rather, more similar brain responses resulted in a more uniform perception of time across viewers. These findings suggest that by capturing the attention of an audience, narrative videos bring both neural processing and the subjective perception of time into synchrony.

  11. Eye movements show similar adaptations in temporal coordination to movement planning conditions in both people with and without cerebral palsy.

    PubMed

    Payne, Alexander R; Plimmer, Beryl; McDaid, Andrew; Davies, T Claire

    2017-05-01

    The effects of cerebral palsy on movement planning for simple reaching tasks are not well understood. Movement planning is complex and entails many processes which could be affected. This study specifically sought to evaluate integrating task information, decoupling movements, and adjusting to altered mapping. For a reaching task, the asynchrony between the eye onset and the hand onset was measured across different movement planning conditions for participants with and without cerebral palsy. Previous research shows people without cerebral palsy vary this temporal coordination for different planning conditions. Our measurements show similar adaptations in temporal coordination for groups with and without cerebral palsy, to three of the four variations in planning condition tested. However, movement durations were still longer for the participants with cerebral palsy. Hence for simple goal-directed reaching, movement execution problems appear to limit activity more than movement planning deficits.

  12. White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

    PubMed Central

    2012-01-01

    Background There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. PMID:22852798

  13. Brain potentials show rapid activation of implicit attitudes towards young and old people.

    PubMed

    van der Lugt, Arie H; Banfield, Jane F; Osinsky, Roman; Münte, Thomas F

    2012-01-06

    While previous behavioural research suggests that attitudes, for example towards elderly people, may be activated automatically, this type of research does not provide information about the detailed time-course of such processing in the brain. We investigated the impact of age related attitude information in a Go/NoGo association task that paired photographs of elderly or young faces with positive or negative words. Event related brain potentials showed an N200 (NoGo) component, which appeared earlier in runs which required similar responses for congruent stimulus pairings (e.g. respond to pictures of elderly faces or negative words) than for incongruent pairings (e.g. respond to elderly faces or positive words). As information processing leading to a certain attitude must precede differential brain activity according to the congruence of the paired words and faces, we show that this type of information is activated almost immediately following the structural encoding of the face, between 170 and 230 ms after onset of the face. Copyright © 2011. Published by Elsevier B.V.

  14. McIntosh active-region class similarities and suggestions for mergers

    NASA Technical Reports Server (NTRS)

    Bornmann, P. L.; Kalmbach, D.; Kulhanek, D.

    1994-01-01

    McIntosh active-region classifications reported during a five-year period were examined to determine similarities among the classes. Two methods were used extensively to determine these similarities. The number of transitions among classes were used to determine the most frequent transitions out of each class, and the alternative classes reported for the same region by different sites were used to establish which classes were neighboring classes. These transition frequencies and neighboring classes were used to identify classes that could be eliminated or merged with other classes. Class similarities were used to investigate the relative importance of several pairs of decisions that occur within a single McIntosh parameter. In particular, the redundancy of parameters in some classes was examined, and the class similarities were used to identify which of these parameters could be eliminated. Infrequently reported classes were also considered, and suggestions for mergers were made when similarities between classes could be identified.

  15. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

    PubMed Central

    2013-01-01

    Background ‘Encephalomyelitis disseminata’ (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS. Discussion There are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels. Summary This review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to

  16. Similarities in neural activations of face and Chinese character discrimination.

    PubMed

    Liu, Jiangang; Tian, Jie; Li, Jun; Gong, Qiyong; Lee, Kang

    2009-02-18

    This study compared Chinese participants' visual discrimination of Chinese faces with that of Chinese characters, which are highly similar to faces on a variety of dimensions. Both Chinese faces and characters activated the bilateral middle fusiform with high levels of correlations. These findings suggest that although the expertise systems for faces and written symbols are known to be anatomically differentiated at the later stages of processing to serve face processing or written-symbol-specific processing purposes, they may share similar neural structures in the ventral occipitotemporal cortex at the stages of visual processing.

  17. Immunomodulatory Activity of Dietary Fiber: Arabinoxylan and Mixed-Linked Beta-Glucan Isolated from Barley Show Modest Activities in Vitro

    PubMed Central

    Samuelsen, Anne Berit; Rieder, Anne; Grimmer, Stine; Michaelsen, Terje E.; Knutsen, Svein H.

    2011-01-01

    High intake of dietary fiber is claimed to protect against development of colorectal cancer. Barley is a rich source of dietary fiber, and possible immunomodulatory effects of barley polysaccharides might explain a potential protective effect. Dietary fiber was isolated by extraction and enzyme treatment. A mixed-linked β-glucan (WSM-TPX, 96.5% β-glucan, Mw 886 kDa), an arabinoxylan (WUM-BS-LA, 96.4% arabinoxylan, Mw 156 kDa), a mixed-linked β-glucan rich fraction containing 10% arabinoxylan (WSM-TP) and an arabinoxylan rich fraction containing 30% mixed-linked β-glucan (WUM-BS) showed no significant effect on IL-8 secretion and proliferation of two intestinal epithelial cell lines, Caco-2 and HT-29, and had no significant effect on the NF-κB activity in the monocytic cell line U937-3κB-LUC. Further enriched arabinoxylan fractions (WUM-BS-LA) from different barley varieties (Tyra, NK96300, SB94897 and CDCGainer) were less active than the mixed-linked β-glucan rich fractions (WSM-TP and WSM-TPX) in the complement-fixing test. The mixed-linked β-glucan rich fraction from NK96300 and CDCGainer showed similar activities as the positive control while mixed-linked β-glucan rich fractions from Tyra and SB94897 were less active. From these results it is concluded that the isolated high molecular weight mixed-linked β-glucans and arabinoxylans from barley show low immunological responses in selected in vitro test systems and thus possible anti-colon cancer effects of barley dietary fiber cannot be explained by our observations. PMID:21340001

  18. Noncontiguous atom matching structural similarity function.

    PubMed

    Teixeira, Ana L; Falcao, Andre O

    2013-10-28

    Measuring similarity between molecules is a fundamental problem in cheminformatics. Given that similar molecules tend to have similar physical, chemical, and biological properties, the notion of molecular similarity plays an important role in the exploration of molecular data sets, query-retrieval in molecular databases, and in structure-property/activity modeling. Various methods to define structural similarity between molecules are available in the literature, but so far none has been used with consistent and reliable results for all situations. We propose a new similarity method based on atom alignment for the analysis of structural similarity between molecules. This method is based on the comparison of the bonding profiles of atoms on comparable molecules, including features that are seldom found in other structural or graph matching approaches like chirality or double bond stereoisomerism. The similarity measure is then defined on the annotated molecular graph, based on an iterative directed graph similarity procedure and optimal atom alignment between atoms using a pairwise matching algorithm. With the proposed approach the similarities detected are more intuitively understood because similar atoms in the molecules are explicitly shown. This noncontiguous atom matching structural similarity method (NAMS) was tested and compared with one of the most widely used similarity methods (fingerprint-based similarity) using three difficult data sets with different characteristics. Despite having a higher computational cost, the method performed well being able to distinguish either different or very similar hydrocarbons that were indistinguishable using a fingerprint-based approach. NAMS also verified the similarity principle using a data set of structurally similar steroids with differences in the binding affinity to the corticosteroid binding globulin receptor by showing that pairs of steroids with a high degree of similarity (>80%) tend to have smaller differences

  19. TRAIL-CM4 fusion protein shows in vitro antibacterial activity and a stronger antitumor activity than solo TRAIL protein.

    PubMed

    Sang, Ming; Zhang, Jiaxin; Li, Bin; Chen, Yuqing

    2016-06-01

    A TRAIL-CM4 fusion protein in soluble form with tumor selective apoptosis and antibacterial functions was expressed in the Escherichia coli expression system and isolated through dialysis refolding and histidine-tag Nickel-affinity purification. Fresh Jurkat cells were treated with the TRAIL-CM4 fusion protein. Trypan blue staining and MTT analyses showed that, similar to a TRAIL positive control, Jurkat cell proliferation was significantly inhibited. Flow cytometry analyses using Annexin V-fluorescein revealed that Jurkat cells treated with the TRAIL-CM4 fusion protein exhibited increased apoptosis. Laser confocal microscopy showed that APB-CM4 and the fusion protein TRAIL-CM4 can bind to Jurkat cell membranes and initiate their destruction. ABP-CM4 enhances the antitumor activity of TRAIL by targeting and damaging the tumor cell membrane. In antibacterial experiments, agar well diffusion and bacterial growth inhibition curve assays revealed concentration-dependent TRAIL-CM4 antibacterial activity against Escherichia coli K12D31. The expressed TRAIL-CM4 fusion protein exhibited enhanced antitumor and antibacterial activities. Fusion protein expression allowed the two different proteins to function in combination. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Active and passive heat stress similarly compromise tolerance to a simulated hemorrhagic challenge.

    PubMed

    Pearson, J; Lucas, R A I; Schlader, Z J; Zhao, J; Gagnon, D; Crandall, C G

    2014-10-01

    Passive heat stress increases core and skin temperatures and reduces tolerance to simulated hemorrhage (lower body negative pressure; LBNP). We tested whether exercise-induced heat stress reduces LBNP tolerance to a greater extent relative to passive heat stress, when skin and core temperatures are similar. Eight participants (6 males, 32 ± 7 yr, 176 ± 8 cm, 77.0 ± 9.8 kg) underwent LBNP to presyncope on three separate and randomized occasions: 1) passive heat stress, 2) exercise in a hot environment (40°C) where skin temperature was moderate (36°C, active 36), and 3) exercise in a hot environment (40°C) where skin temperature was matched relative to that achieved during passive heat stress (∼38°C, active 38). LBNP tolerance was quantified using the cumulative stress index (CSI). Before LBNP, increases in core temperature from baseline were not different between trials (1.18 ± 0.20°C; P > 0.05). Also before LBNP, mean skin temperature was similar between passive heat stress (38.2 ± 0.5°C) and active 38 (38.2 ± 0.8°C; P = 0.90) trials, whereas it was reduced in the active 36 trial (36.6 ± 0.5°C; P ≤ 0.05 compared with passive heat stress and active 38). LBNP tolerance was not different between passive heat stress and active 38 trials (383 ± 223 and 322 ± 178 CSI, respectively; P = 0.12), but both were similarly reduced relative to active 36 (516 ± 147 CSI, both P ≤ 0.05). LBNP tolerance is not different between heat stresses induced either passively or by exercise in a hot environment when skin temperatures are similarly elevated. However, LBNP tolerance is influenced by the magnitude of the elevation in skin temperature following exercise induced heat stress. Copyright © 2014 the American Physiological Society.

  1. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Qualified convention and trade show activity. 1... Organizations § 1.513-3 Qualified convention and trade show activity. (a) Introduction—(1) In general. Section 513(d) and § 1.513-3(b) provide that convention and trade show activities carried on by a qualifying...

  2. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Qualified convention and trade show activity. 1... Organizations § 1.513-3 Qualified convention and trade show activity. (a) Introduction—(1) In general. Section 513(d) and § 1.513-3(b) provide that convention and trade show activities carried on by a qualifying...

  3. 27 CFR 478.35 - Skeet, trap, target, and similar shooting activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Skeet, trap, target, and... FIREARMS AND AMMUNITION Administrative and Miscellaneous Provisions § 478.35 Skeet, trap, target, and... records, for skeet, trap, target, and similar organized activities shall be determined by the Director of...

  4. 27 CFR 478.35 - Skeet, trap, target, and similar shooting activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Skeet, trap, target, and... FIREARMS AND AMMUNITION Administrative and Miscellaneous Provisions § 478.35 Skeet, trap, target, and... records, for skeet, trap, target, and similar organized activities shall be determined by the Director of...

  5. Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems.

    PubMed

    White, Sarah J; Frith, Uta; Rellecke, Julian; Al-Noor, Zainab; Gilbert, Sam J

    2014-04-01

    Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM- group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Thyroid hyperfunctioning adenomas with and without Gsp/TSH receptor mutations show similar clinical features.

    PubMed

    Arturi, F; Capula, C; Chiefari, E; Filetti, S; Russo, D

    1998-01-01

    Activating mutations of Gs alpha protein (gsp) and TSH receptor (TSH-R) identified in autonomously hyperfunctioning thyroid adenomas have been proposed as the primary event responsible for this disease. Since mutations have not been detected in 100% (ranging from less than 10% to 90%) of the patients, we evaluated whether the presence of gsp and TSH-R mutations cause differences in the clinical and biochemical parameters of the affected patients. Fifteen consecutive patients (11 women and 4 men) with autonomously hyperfunctioning thyroid adenomas who underwent thyroidectomy, previously examined for the presence of gsp or TSH-R mutations, were investigated. In all of the patients we examined plasma free T3, free T4, TSH levels and ultrasound volume of the nodules. The patients with mutations in gsp or TSH-R were similar to the patients without mutations for clinical presentation, sex distribution and mean age. Furthermore, basal serum FT3, TSH and tumor volume in the patients with mutations were not significantly different from the group without mutations. Our preliminary data demonstrate that no significant differences are present in the two groups of patients examined, suggesting that factors other than gsp or TSH-R mutations play a role in the clinical presentation of the disease.

  7. Mutagenicity, anticancer activity and blood brain barrier: similarity and dissimilarity of molecular alerts.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Benfenati, Emilio; Salmona, Mario

    2018-06-01

    The aim of the present work is an attempt to define computable measure of similarity between different endpoints. The similarity of structural alerts of different biochemical endpoints can be used to solve tasks of medicinal chemistry. Optimal descriptors are a tool to build up models for different endpoints. The optimal descriptor is calculated with simplified molecular input-line entry system (SMILES). A group of elements (single symbol or pair of symbols) can represent any SMILES. Each element of SMILES can be represented by so-called correlation weight i.e. coefficient that should be used to calculate descriptor. Numerical data on the correlation weights are calculated by the Monte Carlo method, i.e. by optimization procedure, which gives maximal correlation coefficient between the optimal descriptor and endpoint for the training set. Statistically stable correlation weights observed in several runs of the optimization can be examined as structural alerts, which are promoters of the increase or the decrease of a biochemical activity of a substance. Having data on several runs of the optimization correlation weights, one can extract list of promoters of increase and list of promoters of decrease for an endpoint. The study of similarity and dissimilarity of the above lists has been carried out for the following pairs of endpoints: (i) mutagenicity and anticancer activity; (ii) mutagenicity and blood brain barrier; and (iii) blood brain barrier and anticancer activity. The computational experiment confirms that similarity and dissimilarity for pairs of endpoints can be measured.

  8. Structural similarity based kriging for quantitative structure activity and property relationship modeling.

    PubMed

    Teixeira, Ana L; Falcao, Andre O

    2014-07-28

    Structurally similar molecules tend to have similar properties, i.e. closer molecules in the molecular space are more likely to yield similar property values while distant molecules are more likely to yield different values. Based on this principle, we propose the use of a new method that takes into account the high dimensionality of the molecular space, predicting chemical, physical, or biological properties based on the most similar compounds with measured properties. This methodology uses ordinary kriging coupled with three different molecular similarity approaches (based on molecular descriptors, fingerprints, and atom matching) which creates an interpolation map over the molecular space that is capable of predicting properties/activities for diverse chemical data sets. The proposed method was tested in two data sets of diverse chemical compounds collected from the literature and preprocessed. One of the data sets contained dihydrofolate reductase inhibition activity data, and the second molecules for which aqueous solubility was known. The overall predictive results using kriging for both data sets comply with the results obtained in the literature using typical QSPR/QSAR approaches. However, the procedure did not involve any type of descriptor selection or even minimal information about each problem, suggesting that this approach is directly applicable to a large spectrum of problems in QSAR/QSPR. Furthermore, the predictive results improve significantly with the similarity threshold between the training and testing compounds, allowing the definition of a confidence threshold of similarity and error estimation for each case inferred. The use of kriging for interpolation over the molecular metric space is independent of the training data set size, and no reparametrizations are necessary when more compounds are added or removed from the set, and increasing the size of the database will consequentially improve the quality of the estimations. Finally it is shown

  9. DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

    PubMed

    Brucoli, Federico; Guzman, Juan D; Basher, Mohammad A; Evangelopoulos, Dimitrios; McMahon, Eleanor; Munshi, Tulika; McHugh, Timothy D; Fox, Keith R; Bhakta, Sanjib

    2016-12-01

    New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H 37 Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H 37 Rv, with compound 4 showing MIC values (MIC=0.08 mg l -1 ) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

  10. Peptide deformylases from Vibrio parahaemolyticus phage and bacteria display similar deformylase activity and inhibitor binding clefts.

    PubMed

    Grzela, Renata; Nusbaum, Julien; Fieulaine, Sonia; Lavecchia, Francesco; Desmadril, Michel; Nhiri, Naima; Van Dorsselaer, Alain; Cianferani, Sarah; Jacquet, Eric; Meinnel, Thierry; Giglione, Carmela

    2018-02-01

    Unexpected peptide deformylase (PDF) genes were recently retrieved in numerous marine phage genomes. While various hypotheses dealing with the occurrence of these intriguing sequences have been made, no further characterization and functional studies have been described thus far. In this study, we characterize the bacteriophage Vp16 PDF enzyme, as representative member of the newly identified C-terminally truncated viral PDFs. We show here that conditions classically used for bacterial PDFs lead to an enzyme exhibiting weak activity. Nonetheless, our integrated biophysical and biochemical approaches reveal specific effects of pH and metals on Vp16 PDF stability and activity. A novel purification protocol taking in account these data allowed strong improvement of Vp16 PDF specific activity to values similar to those of bacterial PDFs. We next show that Vp16 PDF is as sensitive to the natural inhibitor compound of PDFs, actinonin, as bacterial PDFs. Comparison of the 3D structures of Vp16 and E. coli PDFs bound to actinonin also reveals that both PDFs display identical substrate binding mode. We conclude that bacteriophage Vp16 PDF protein has functional peptide deformylase activity and we suggest that encoded phage PDFs might be important for viral fitness. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Molecular similarity measures.

    PubMed

    Maggiora, Gerald M; Shanmugasundaram, Veerabahu

    2011-01-01

    Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

  12. Reforestation Sites Show Similar and Nested AMF Communities to an Adjacent Pristine Forest in a Tropical Mountain Area of South Ecuador

    PubMed Central

    Haug, Ingeborg; Setaro, Sabrina; Suárez, Juan Pablo

    2013-01-01

    Arbuscular mycorrhizae are important for growth and survival of tropical trees. We studied the community of arbuscular mycorrhizal fungi in a tropical mountain rain forest and in neighbouring reforestation plots in the area of Reserva Biológica San Francisco (South Ecuador). The arbuscular mycorrhizal fungi were analysed with molecular methods sequencing part of the 18 S rDNA. The sequences were classified as Operational Taxonomic Units (OTUs). We found high fungal species richness with OTUs belonging to Glomerales, Diversisporales and Archaeosporales. Despite intensive sampling, the rarefaction curves are still unsaturated for the pristine forest and the reforestation plots. The communities consisted of few frequent and many rare species. No specific interactions are recognizable. The plant individuals are associated with one to ten arbuscular mycorrhizal fungi and mostly with one to four. The fungal compositions associated with single plant individuals show a great variability and variety within one plant species. Planted and naturally occurring plants show high similarities in their fungal communities. Pristine forest and reforestation plots showed similar richness, similar diversity and a significantly nested structure of plant-AMF community. The results indicate that small-scale fragmentation presently found in this area has not destroyed the natural AMF community, at least yet. Thus, the regeneration potential of natural forest vegetation at the tested sites is not inhibited by a lack of appropriate mycobionts. PMID:23671682

  13. Greater neural pattern similarity across repetitions is associated with better memory.

    PubMed

    Xue, Gui; Dong, Qi; Chen, Chuansheng; Lu, Zhonglin; Mumford, Jeanette A; Poldrack, Russell A

    2010-10-01

    Repeated study improves memory, but the underlying neural mechanisms of this improvement are not well understood. Using functional magnetic resonance imaging and representational similarity analysis of brain activity, we found that, compared with forgotten items, subsequently remembered faces and words showed greater similarity in neural activation across multiple study in many brain regions, including (but not limited to) the regions whose mean activities were correlated with subsequent memory. This result addresses a longstanding debate in the study of memory by showing that successful episodic memory encoding occurs when the same neural representations are more precisely reactivated across study episodes, rather than when patterns of activation are more variable across time.

  14. The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

    PubMed

    Marcos-Zambrano, Laura Judith; Gómez-Perosanz, Marta; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2017-07-01

    We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital. The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay. SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P  <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P  <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment. Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Reinstatement of Individual Past Events Revealed by the Similarity of Distributed Activation Patterns during Encoding and Retrieval

    PubMed Central

    Wing, Erik A.; Ritchey, Maureen; Cabeza, Roberto

    2015-01-01

    Neurobiological memory models assume memory traces are stored in neocortex, with pointers in the hippocampus, and are then reactivated during retrieval, yielding the experience of remembering. Whereas most prior neuroimaging studies on reactivation have focused on the reactivation of sets or categories of items, the current study sought to identify cortical patterns pertaining to memory for individual scenes. During encoding, participants viewed pictures of scenes paired with matching labels (e.g., “barn,” “tunnel”), and, during retrieval, they recalled the scenes in response to the labels and rated the quality of their visual memories. Using representational similarity analyses, we interrogated the similarity between activation patterns during encoding and retrieval both at the item level (individual scenes) and the set level (all scenes). The study yielded four main findings. First, in occipitotemporal cortex, memory success increased with encoding-retrieval similarity (ERS) at the item level but not at the set level, indicating the reactivation of individual scenes. Second, in ventrolateral pFC, memory increased with ERS for both item and set levels, indicating the recapitulation of memory processes that benefit encoding and retrieval of all scenes. Third, in retrosplenial/posterior cingulate cortex, ERS was sensitive to individual scene information irrespective of memory success, suggesting automatic activation of scene contexts. Finally, consistent with neurobiological models, hippocampal activity during encoding predicted the subsequent reactivation of individual items. These findings show the promise of studying memory with greater specificity by isolating individual mnemonic representations and determining their relationship to factors like the detail with which past events are remembered. PMID:25313659

  16. Conventional physical therapy and physical therapy based on reflex stimulation showed similar results in children with myelomeningocele.

    PubMed

    Aizawa, Carolina Y P; Morales, Mariana P; Lundberg, Carolina; Moura, Maria Clara D Soares de; Pinto, Fernando C G; Voos, Mariana C; Hasue, Renata H

    2017-03-01

    We aimed to investigate whether infants with myelomeningocele would improve their motor ability and functional independence after ten sessions of physical therapy and compare the outcomes of conventional physical therapy (CPT) to a physical therapy program based on reflex stimulation (RPT). Twelve children were allocated to CPT (n = 6, age 18.3 months) or RPT (n = 6, age 18.2 months). The RPT involved proprioceptive neuromuscular facilitation. Children were assessed with the Gross Motor Function Measure and the Pediatric Evaluation of Disability Inventory before and after treatment. Mann-Whitney tests compared the improvement on the two scales of CPT versus RPT and the Wilcoxon test compared CPT to RPT (before vs. after treatment). Possible correlations between the two scales were tested with Spearman correlation coefficients. Both groups showed improvement on self-care and mobility domains of both scales. There were no differences between the groups, before, or after intervention. The CPT and RPT showed similar results after ten weeks of treatment.

  17. Your Library--Greatest Show of All! Activity Manual.

    ERIC Educational Resources Information Center

    Jackson, Mary, Ed.

    Intended as a companion volume for librarians planning a children's summer reading program, this activity manual provides ideas for games, puzzles, puppet shows, story reading, and more, all based on the theme of "Circus Summer." The manual suggests ways to promote the program, such as visits to schools, and provides directions for…

  18. Post-cranial skeletons of hypothyroid cretins show a similar anatomical mosaic as Homo floresiensis.

    PubMed

    Oxnard, Charles; Obendorf, Peter J; Kefford, Ben J

    2010-09-27

    Human remains, some as recent as 15 thousand years, from Liang Bua (LB) on the Indonesian island of Flores have been attributed to a new species, Homo floresiensis. The definition includes a mosaic of features, some like modern humans (hence derived: genus Homo), some like modern apes and australopithecines (hence primitive: not species sapiens), and some unique (hence new species: floresiensis). Conversely, because only modern humans (H. sapiens) are known in this region in the last 40 thousand years, these individuals have also been suggested to be genetic human dwarfs. Such dwarfs resemble small humans and do not show the mosaic combination of the most complete individuals, LB1 and LB6, so this idea has been largely dismissed. We have previously shown that some features of the cranium of hypothyroid cretins are like those of LB1. Here we examine cretin postcrania to see if they show anatomical mosaics like H. floresiensis. We find that hypothyroid cretins share at least 10 postcranial features with Homo floresiensis and unaffected humans not found in apes (or australopithecines when materials permit). They share with H. floresiensis, modern apes and australopithecines at least 11 postcranial features not found in unaffected humans. They share with H. floresiensis, at least 8 features not found in apes, australopithecines or unaffected humans. Sixteen features can be rendered metrically and multivariate analyses demonstrate that H. floresiensis co-locates with cretins, both being markedly separate from humans and chimpanzees (P<0.001: from analysis of similarity (ANOSIM) over all variables, ANOSIM, global R>0.999). We therefore conclude that LB1 and LB6, at least, are, most likely, endemic cretins from a population of unaffected Homo sapiens. This is consistent with recent hypothyroid endemic cretinism throughout Indonesia, including the nearby island of Bali.

  19. Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens

    PubMed Central

    Runyon, Justin B; Mescher, Mark C

    2010-01-01

    Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens—notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)—also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across kingdoms. PMID:20495380

  20. Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens.

    PubMed

    Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

    2010-08-01

    Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling, and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens--notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)--also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across Kingdoms.

  1. Spike-train communities: finding groups of similar spike trains.

    PubMed

    Humphries, Mark D

    2011-02-09

    Identifying similar spike-train patterns is a key element in understanding neural coding and computation. For single neurons, similar spike patterns evoked by stimuli are evidence of common coding. Across multiple neurons, similar spike trains indicate potential cell assemblies. As recording technology advances, so does the urgent need for grouping methods to make sense of large-scale datasets of spike trains. Existing methods require specifying the number of groups in advance, limiting their use in exploratory analyses. I derive a new method from network theory that solves this key difficulty: it self-determines the maximum number of groups in any set of spike trains, and groups them to maximize intragroup similarity. This method brings us revealing new insights into the encoding of aversive stimuli by dopaminergic neurons, and the organization of spontaneous neural activity in cortex. I show that the characteristic pause response of a rat's dopaminergic neuron depends on the state of the superior colliculus: when it is inactive, aversive stimuli invoke a single pattern of dopaminergic neuron spiking; when active, multiple patterns occur, yet the spike timing in each is reliable. In spontaneous multineuron activity from the cortex of anesthetized cat, I show the existence of neural ensembles that evolve in membership and characteristic timescale of organization during global slow oscillations. I validate these findings by showing that the method both is remarkably reliable at detecting known groups and can detect large-scale organization of dynamics in a model of the striatum.

  2. Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

    PubMed Central

    da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

    2016-01-01

    Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

  3. Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

    PubMed

    Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

    2016-09-12

    Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions

  4. Apg-2 has a chaperone-like activity similar to Hsp110 and is overexpressed in hepatocellular carcinomas.

    PubMed

    Gotoh, Kazuhisa; Nonoguchi, Kohsuke; Higashitsuji, Hiroaki; Kaneko, Yoshiyuki; Sakurai, Toshiharu; Sumitomo, Yasuhiko; Itoh, Katsuhiko; Subjeck, John R; Fujita, Jun

    2004-02-27

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. We constructed subtracted cDNA libraries enriched with genes overexpressed in HCCs. Among the 17 genes identified were molecular chaperones, Hsp110, Hsp90B, and Hsp70-1. Expression of the Hsp110 family members was further analyzed, and increased transcript levels of Hsp110 and Apg-2, but not Apg-1, were found in 12 and 14, respectively, of 18 HCCs. Immunohistochemical analysis demonstrated the overexpression of the proteins in tumor cells. Apg-2 had chaperone ability similar to Hsp110 in a thermal denaturation assay using luciferase, and showed anti-apoptotic activity. These results suggest that the Hsp110 family members play important roles in hepatocarcinogenesis through their chaperoning activities.

  5. Non-human Primate and Rat Cardiac Fibroblasts show similar Extracellular Matrix-related and Cellular Adhesion Gene Responses to Substance P

    PubMed Central

    Meléndez, Giselle C.; Manteufel, Edward J.; Dehlin, Heather M.; Register, Thomas C.; Levick, Scott P.

    2015-01-01

    Background The sensory nerve neuropeptide substance P (SP) regulates cardiac fibrosis in rodents under pressure overload conditions. Interestingly, SP induces transient increase expression of specific genes in isolated rat cardiac fibroblasts, without resultant changes in cell function. This suggests that SP ‘primes’ fibroblasts, but does not directly activate them. We investigated whether these unusual findings are specific to rodent fibroblasts or are translatable to a larger animal model more closely related to humans. Methods We compared the effects of SP on genes associated with extracellular matrix (ECM) regulation, cell-cell adhesion, cell-matrix adhesion and ECM in cardiac fibroblasts isolated from a non-human primate and Sprague-Dawley rats. Results We found that rodent and non-human primate cardiac fibroblasts showed similar ECM regulation and cell adhesion gene expression responses to SP. There were, however, large discrepancies in ECM genes which did not result in collagen or laminin synthesis in rat or non-human primate fibroblasts in response to SP. Conclusions This study further supports the notion that SP serves as a ‘primer’ for fibroblasts rather than initiating direct effects and suggests that rodent fibroblasts are a suitable model for studying gene and functional responses to SP in the absence of human or non-human primate fibroblasts. PMID:25550118

  6. Wavelet energy-guided level set-based active contour: a segmentation method to segment highly similar regions.

    PubMed

    Achuthan, Anusha; Rajeswari, Mandava; Ramachandram, Dhanesh; Aziz, Mohd Ezane; Shuaib, Ibrahim Lutfi

    2010-07-01

    This paper introduces an approach to perform segmentation of regions in computed tomography (CT) images that exhibit intra-region intensity variations and at the same time have similar intensity distributions with surrounding/adjacent regions. In this work, we adapt a feature computed from wavelet transform called wavelet energy to represent the region information. The wavelet energy is embedded into a level set model to formulate the segmentation model called wavelet energy-guided level set-based active contour (WELSAC). The WELSAC model is evaluated using several synthetic and CT images focusing on tumour cases, which contain regions demonstrating the characteristics of intra-region intensity variations and having high similarity in intensity distributions with the adjacent regions. The obtained results show that the proposed WELSAC model is able to segment regions of interest in close correspondence with the manual delineation provided by the medical experts and to provide a solution for tumour detection. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Context-dependent similarity effects in letter recognition.

    PubMed

    Kinoshita, Sachiko; Robidoux, Serje; Guilbert, Daniel; Norris, Dennis

    2015-10-01

    In visual word recognition tasks, digit primes that are visually similar to letter string targets (e.g., 4/A, 8/B) are known to facilitate letter identification relative to visually dissimilar digits (e.g., 6/A, 7/B); in contrast, with letter primes, visual similarity effects have been elusive. In the present study we show that the visual similarity effect with letter primes can be made to come and go, depending on whether it is necessary to discriminate between visually similar letters. The results support a Bayesian view which regards letter recognition not as a passive activation process driven by the fixed stimulus properties, but as a dynamic evidence accumulation process for a decision that is guided by the task context.

  8. Butterfly extracts show antibacterial activity

    USDA-ARS?s Scientific Manuscript database

    Extracts of several British butterfly species were tested and shown to possess powerful bactericidal activity against the gram-positive bacteria Staphylococcus aureus (S. aureus). The active compounds were identified as hydroxylated pyrrolizidine alkaloids (PAs) related to loline with nitrogen at C-...

  9. U.S. Department of Agriculture: Similarities Between the Activities of the Department and Other Federal Agencies

    DTIC Science & Technology

    1998-12-09

    food safety and land management, that are carried out by more than one agency; examined previous GAO reports that highlight these similarities; and reviewed the goals of the Government Performance and Results Act and USDA’S efforts to comply with it. Our analysis highlights many of the activities that are apparently similar. However, USDA’S activities may not be directed at the same clientele as those carried out by other federal agencies, and other agencies’ activities may be only a part of their overall mission. Our analysis did not determine all of the

  10. Similar or Different? The Role of the Ventrolateral Prefrontal Cortex in Similarity Detection

    PubMed Central

    Garcin, Béatrice; Volle, Emmanuelle; Dubois, Bruno; Levy, Richard

    2012-01-01

    Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., “both have peel”), while others continue to look for differences between these objects (e.g., “one is yellow, the other is orange”). These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC). We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI) study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1) Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2) Abstraction per se activates the left dorsolateral PFC. PMID:22479551

  11. Coupling effect of nodes popularity and similarity on social network persistence

    PubMed Central

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-01-01

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes’ popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology. PMID:28220840

  12. Coupling effect of nodes popularity and similarity on social network persistence

    NASA Astrophysics Data System (ADS)

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-02-01

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes’ popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology.

  13. Coupling effect of nodes popularity and similarity on social network persistence.

    PubMed

    Jin, Xiaogang; Jin, Cheng; Huang, Jiaxuan; Min, Yong

    2017-02-21

    Network robustness represents the ability of networks to withstand failures and perturbations. In social networks, maintenance of individual activities, also called persistence, is significant towards understanding robustness. Previous works usually consider persistence on pre-generated network structures; while in social networks, the network structure is growing with the cascading inactivity of existed individuals. Here, we address this challenge through analysis for nodes under a coevolution model, which characterizes individual activity changes under three network growth modes: following the descending order of nodes' popularity, similarity or uniform random. We show that when nodes possess high spontaneous activities, a popularity-first growth mode obtains highly persistent networks; otherwise, with low spontaneous activities, a similarity-first mode does better. Moreover, a compound growth mode, with the consecutive joining of similar nodes in a short period and mixing a few high popularity nodes, obtains the highest persistence. Therefore, nodes similarity is essential for persistent social networks, while properly coupling popularity with similarity further optimizes the persistence. This demonstrates the evolution of nodes activity not only depends on network topology, but also their connective typology.

  14. Similarly shaped letters evoke similar colors in grapheme-color synesthesia.

    PubMed

    Brang, David; Rouw, Romke; Ramachandran, V S; Coulson, Seana

    2011-04-01

    Grapheme-color synesthesia is a neurological condition in which viewing numbers or letters (graphemes) results in the concurrent sensation of color. While the anatomical substrates underlying this experience are well understood, little research to date has investigated factors influencing the particular colors associated with particular graphemes or how synesthesia occurs developmentally. A recent suggestion of such an interaction has been proposed in the cascaded cross-tuning (CCT) model of synesthesia, which posits that in synesthetes connections between grapheme regions and color area V4 participate in a competitive activation process, with synesthetic colors arising during the component-stage of grapheme processing. This model more directly suggests that graphemes sharing similar component features (lines, curves, etc.) should accordingly activate more similar synesthetic colors. To test this proposal, we created and regressed synesthetic color-similarity matrices for each of 52 synesthetes against a letter-confusability matrix, an unbiased measure of visual similarity among graphemes. Results of synesthetes' grapheme-color correspondences indeed revealed that more similarly shaped graphemes corresponded with more similar synesthetic colors, with stronger effects observed in individuals with more intense synesthetic experiences (projector synesthetes). These results support the CCT model of synesthesia, implicate early perceptual mechanisms as driving factors in the elicitation of synesthetic hues, and further highlight the relationship between conceptual and perceptual factors in this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity.

    PubMed

    Jensen-Otsu, Elsbeth; Austin, Gregory L

    2015-11-20

    Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09-2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

  16. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

    PubMed Central

    Jensen-Otsu, Elsbeth; Austin, Gregory L.

    2015-01-01

    Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use. PMID:26610562

  17. A novel subtilase inhibitor in plants shows structural and functional similarities to protease propeptides.

    PubMed

    Hohl, Mathias; Stintzi, Annick; Schaller, Andreas

    2017-04-14

    The propeptides of subtilisin-like serine proteinases (subtilases, SBTs) serve dual functions as intramolecular chaperones that are required for enzyme folding and as inhibitors of the mature proteases. SBT propeptides are homologous to the I9 family of protease inhibitors that have only been described in fungi. Here we report the identification and characterization of subtilisin propeptide-like inhibitor 1 (SPI-1) from Arabidopsis thaliana Sequence similarity and the shared β-α-β-β-α-β core structure identified SPI-1 as a member of the I9 inhibitor family and as the first independent I9 inhibitor in higher eukaryotes. SPI-1 was characterized as a high-affinity, tight-binding inhibitor of Arabidopsis subtilase SBT4.13 with K d and K i values in the picomolar range. SPI-1 acted as a stable inhibitor of SBT4.13 over the physiologically relevant range of pH, and its inhibitory profile included many other SBTs from plants but not bovine chymotrypsin or bacterial subtilisin A. Upon binding to SBT4.13, the C-terminal extension of SPI-1 was proteolytically cleaved. The last four amino acids at the newly formed C terminus of SPI-1 matched both the cleavage specificity of SBT4.13 and the consensus sequence of Arabidopsis SBTs at the junction of the propeptide with the catalytic domain. The data suggest that the C terminus of SPI-1 acts as a competitive inhibitor of target proteases as it remains bound to the active site in a product-like manner. SPI-1 thus resembles SBT propeptides with respect to its mode of protease inhibition. However, in contrast to SBT propeptides, SPI-1 could not substitute as a folding assistant for SBT4.13. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

    NASA Astrophysics Data System (ADS)

    Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

    2011-08-01

    The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

  19. Relative to Quinine and Quinidine, Their 9-Epimers Exhibit Decreased Cytostatic Activity and Altered Heme Binding but Similar Cytocidal Activity versus Plasmodium falciparum

    PubMed Central

    Gorka, Alexander P.; Sherlach, Katy S.; de Dios, Angel C.

    2013-01-01

    The 9-epimers of quinine (QN) and quinidine (QD) are known to exhibit poor cytostatic potency against P. falciparum (Karle JM, Karle IL, Gerena L, Milhous WK, Antimicrob. Agents Chemother. 36:1538–1544, 1992). We synthesized 9-epi-QN (eQN) and 9-epi-QD (eQD) via Mitsunobu esterification-saponification and evaluated both cytostatic and cytocidal antimalarial activities. Relative to the cytostatic activity of QN and QD, we observed a large decrease in cytostatic activity (higher 50% inhibitory concentration [IC50s]) against QN-sensitive strain HB3, QN-resistant strain Dd2, and QN-hypersensitive strain K76I, consistent with previous work. However, we observed relatively small changes in cytocidal activity (the 50% lethal dose), similar to observations with chloroquine (CQ) analogues with a wide range of IC50s (see the accompanying paper [A. P. Gorka, J. N. Alumasa, K. S. Sherlach, L. M. Jacobs, K. B. Nickley, J. P. Brower, A. C. de Dios, and P. D. Roepe, Antimicrob. Agents Chemother. 57:356–364, 2013]). Compared to QN and QD, the 9-epimers had significantly reduced hemozoin inhibition efficiency and did not affect pH-dependent aggregation of ferriprotoporphyrin IX (FPIX) heme. Magnetic susceptibility measurements showed that the 9-epimers perturb FPIX monomer-dimer equilibrium in favor of monomer, and UV-visible (VIS) titrations showed that eQN and eQD bind monomer with similar affinity relative to QN and QD. However, unique ring proton shifts in the presence of zinc(II) protoporphyrin IX (ZnPIX) indicate that binding of the 9-epimers to monomeric heme is via a distinct geometry. We isolated eQN- and eQD-FPIX complexes formed under aqueous conditions and analyzed them by mass, fluorescence, and UV-VIS spectroscopies. The 9-epimers produced low-fluorescent adducts with a 2:1 stoichiometry (drug to FPIX) which did not survive electrospray ionization, in contrast to QN and QD complexes. The data offer important insight into the relevance of heme interactions as a

  20. How similar are recognition memory and inductive reasoning?

    PubMed

    Hayes, Brett K; Heit, Evan

    2013-07-01

    Conventionally, memory and reasoning are seen as different types of cognitive activities driven by different processes. In two experiments, we challenged this view by examining the relationship between recognition memory and inductive reasoning involving multiple forms of similarity. A common study set (members of a conjunctive category) was followed by a test set containing old and new category members, as well as items that matched the study set on only one dimension. The study and test sets were presented under recognition or induction instructions. In Experiments 1 and 2, the inductive property being generalized was varied in order to direct attention to different dimensions of similarity. When there was no time pressure on decisions, patterns of positive responding were strongly affected by property type, indicating that different types of similarity were driving recognition and induction. By comparison, speeded judgments showed weaker property effects and could be explained by generalization based on overall similarity. An exemplar model, GEN-EX (GENeralization from EXamples), could account for both the induction and recognition data. These findings show that induction and recognition share core component processes, even when the tasks involve flexible forms of similarity.

  1. Gender similarities and differences in brain activation strategies: Voxel-based meta-analysis on fMRI studies.

    PubMed

    AlRyalat, Saif Aldeen

    2017-01-01

    Gender similarities and differences have long been a matter of debate in almost all human research, especially upon reaching the discussion about brain functions. This large scale meta-analysis was performed on functional MRI studies. It included more than 700 active brain foci from more than 70 different experiments to study gender related similarities and differences in brain activation strategies for three of the main brain functions: Visual-spatial cognition, memory, and emotion. Areas that are significantly activated by both genders (i.e. core areas) for the tested brain function are mentioned, whereas those areas significantly activated exclusively in one gender are the gender specific areas. During visual-spatial cognition task, and in addition to the core areas, males significantly activated their left superior frontal gyrus, compared with left superior parietal lobule in females. For memory tasks, several different brain areas activated by each gender, but females significantly activated two areas from the limbic system during memory retrieval tasks. For emotional task, males tend to recruit their bilateral prefrontal regions, whereas females tend to recruit their bilateral amygdalae. This meta-analysis provides an overview based on functional MRI studies on how males and females use their brain.

  2. Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.

    PubMed Central

    Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G

    1998-01-01

    The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125

  3. Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity.

    PubMed

    Cedars, Ari M; Stefanescu Schmidt, Ada; Broberg, Craig; Zaidi, Ali; Opotowsky, Alexander; Grewal, Jasmine; Kay, Joseph; Bhatt, Ami B; Novak, Eric; Spertus, John

    2016-03-01

    There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s). We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms. This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments. © 2016 American Heart Association, Inc.

  4. The three catalases in Deinococcus radiodurans: Only two show catalase activity

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

    Jeong, Sun-Wook; Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon, 305-764; Jung, Jong-Hyun

    2016-01-15

    Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H{sub 2}O{sub 2}) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H{sub 2}O{sub 2} treatments, whereas ΔdrA0146 showed no change in its H{sub 2}O{sub 2} resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the threemore » bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H{sub 2}O{sub 2}, but DRA0146 does not have catalase activity and is not involved in the resistance to H{sub 2}O{sub 2} stress. - Highlights: • The dr1998 mutant strain lost 90% of its total catalase activity. • Increased ROS levels and decreased H{sub 2}O{sub 2} resistance were observed in dr1998 mutants. • Lack of drA0146 did not affect any oxidative stress-related phenotypes. • The purified DRA0146 did not show catalase activity.« less

  5. Disorders with similar clinical phenotypes reveal underlying genetic interaction: SATB2 acts as an activator of the UPF3B gene

    PubMed Central

    Leoyklang, Petcharat; Suphapeetiporn, Kanya; Srichomthong, Chalurmpon; Tongkobpetch, Siraprapa; Fietze, Stefanie; Dorward, Heidi; Cullinane, Andrew R.; Gahl, William A.; Huizing, Marjan; Shotelersuk, Vorasuk

    2014-01-01

    Two syndromic cognitive impairment disorders have very similar craniofacial dysmorphisms. One is caused by mutations of SATB2, a transcription regulator, and the other by heterozygous mutations leading to premature stop codons in UPF3B, encoding a member of the nonsense-mediated mRNA decay complex. Here we demonstrate that the products of these two causative genes function in the same pathway. We show that the SATB2 nonsense mutation in our patient leads to a truncated protein that localizes to the nucleus, forms a dimer with wild-type SATB2 and interferes with its normal activity. This suggests that the SATB2 nonsense mutation has a dominant negative effect. The patient’s leukocytes had significantly decreased UPF3B mRNA compared to controls. This effect was replicated both in vitro, where siRNA knockdown of SATB2 in HEK293 cells resulted in decreased UPF3B expression, and in vivo, where embryonic tissue of Satb2 knock-out mice showed significantly decreased Upf3b expression. Furthermore, chromatin immunoprecipitation demonstrates that SATB2 binds to the UPF3B promoter, and a luciferase reporter assay confirmed that SATB2 expression significantly activates gene transcription using the UPF3B promoter. These findings indicate that SATB2 acts as an activator UPF3B expression through binding to its promoter. This study emphasizes the value of recognizing disorders with similar clinical phenotypes to explore underlying mechanisms of genetic interaction. PMID:23925499

  6. Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence, full structure, and active site microenvironment similarity

    PubMed Central

    Leuthaeuser, Janelle B; Knutson, Stacy T; Kumar, Kiran; Babbitt, Patricia C; Fetrow, Jacquelyn S

    2015-01-01

    The development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity-based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM-Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well-studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence- or structure-based networks. Sequence- and structure-based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity-based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity-based methods. PMID:26073648

  7. Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.

    PubMed

    Hernández-Vázquez, A; Wolf, B; Pindolia, K; Ortega-Cuellar, D; Hernández-González, R; Heredia-Antúnez, A; Ibarra-González, I; Velázquez-Arellano, A

    2013-11-01

    Biotin is the prosthetic group of carboxylases that have important roles in the metabolism of glucose, fatty acids and amino acids. Biotinidase has a key role in the reutilization of the biotin, catalyzing the hydrolysis of biocytin (ε-N-biotinyl-l-lysine) and biocytin-containing peptides derived from carboxylase turnover, thus contributing substantially to the bioavailability of this vitamin. Deficient activity of biotinidase causes late-onset multiple carboxylase in humans, whose pathogenic mechanisms are poorly understood. Here we show that a knock-out biotinidase-deficient mouse from a C57BL/6 background that was fed a low biotin diet develops severe ATP deficit with activation of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK), inhibition of the signaling protein mTOR, driver of protein synthesis and growth, and affecting the expression of central-carbon metabolism genes. In addition, sensitivity to insulin is augmented. These changes are similar to those observed in nutritionally biotin-starved rats. These findings further our understanding of the pathogenesis of human biotinidase deficiency. © 2013 Elsevier Inc. All rights reserved.

  8. B-ring-aryl substituted luotonin A analogues with a new binding mode to the topoisomerase 1-DNA complex show enhanced cytotoxic activity.

    PubMed

    González-Ruiz, Víctor; Pascua, Irene; Fernández-Marcelo, Tamara; Ribelles, Pascual; Bianchini, Giulia; Sridharan, Vellaisamy; Iniesta, Pilar; Ramos, M Teresa; Olives, Ana I; Martín, M Antonia; Menéndez, J Carlos

    2014-01-01

    Topoisomerase 1 inhibition is an important strategy in targeted cancer chemotherapy. The drugs currently in use acting on this enzyme belong to the family of the camptothecins, and suffer severe limitations because of their low stability, which is associated with the hydrolysis of the δ-lactone moiety in their E ring. Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity. Therefore, the development of luotonin A analogues with an increased potency is important for progress in this area. In the present paper, a small library of luotonin A analogues modified at their A and B rings was generated by cerium(IV) ammonium nitrate-catalyzed Friedländer reactions. All analogues showed an activity similar or higher than the natural luotonin A in terms of topoisomerase 1 inhibition and some compounds had an activity comparable to that of camptothecin. Furthermore, most compounds showed a better activity than luotonin A in cell cytotoxicity assays. In order to rationalize these results, the first docking studies of luotonin-topoisomerase 1-DNA ternary complexes were undertaken. Most compounds bound in a manner similar to luotonin A and to standard topoisomerase poisons such as topotecan but, interestingly, the two most promising analogues, bearing a 3,5-dimethylphenyl substituent at ring B, docked in a different orientation. This binding mode allows the hydrophobic moiety to be shielded from the aqueous environment by being buried between the deoxyribose belonging to the G(+1) guanine and Arg364 in the scissile strand and the surface of the protein and a hydrogen bond between the D-ring carbonyl and the basic amino acid. The discovery of this new binding mode and its associated higher inhibitory potency is a significant advance in the design of new topoisomerase 1 inhibitors.

  9. Hyperthermophilic archaeal prefoldin shows refolding activity at low temperature.

    PubMed

    Zako, Tamotsu; Banba, Shinya; Sahlan, Muhamad; Sakono, Masafumi; Terada, Naofumi; Yohda, Masafumi; Maeda, Mizuo

    2010-01-01

    Prefoldin is a molecular chaperone that captures a protein-folding intermediate and transfers it to a group II chaperonin for correct folding. Previous studies of archaeal prefoldins have shown that prefoldin only possesses holdase activity and is unable to fold unfolded proteins by itself. In this study, we have demonstrated for the first time that a prefoldin from hyperthermophilic archaeon, Pyrococcus horikoshii OT3 (PhPFD), exhibits refolding activity for denatured lysozyme at temperatures relatively lower than physiologically active temperatures. The interaction between PhPFD and denatured lysozyme was investigated by use of a surface plasmon resonance sensor at various temperatures. Although PhPFD showed strong affinity for denatured lysozyme at high temperature, it exhibited relatively weak interactions at lower temperature. The protein-folding seems to occur through binding and release from PhPFD by virtue of the weak affinity. Our results also imply that prefoldin might be able to contribute to the folding of some cellular proteins whose affinity with prefoldin is weak. Copyright 2009 Elsevier Inc. All rights reserved.

  10. Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence, full structure, and active site microenvironment similarity.

    PubMed

    Leuthaeuser, Janelle B; Knutson, Stacy T; Kumar, Kiran; Babbitt, Patricia C; Fetrow, Jacquelyn S

    2015-09-01

    The development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity-based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM-Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well-studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence- or structure-based networks. Sequence- and structure-based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity-based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity-based methods. © 2015 The Authors Protein Science

  11. Meta-Analysis of Quantification Methods Shows that Archaea and Bacteria Have Similar Abundances in the Subseafloor

    PubMed Central

    May, Megan K.; Kevorkian, Richard T.; Steen, Andrew D.

    2013-01-01

    There is no universally accepted method to quantify bacteria and archaea in seawater and marine sediments, and different methods have produced conflicting results with the same samples. To identify best practices, we compiled data from 65 studies, plus our own measurements, in which bacteria and archaea were quantified with fluorescent in situ hybridization (FISH), catalyzed reporter deposition FISH (CARD-FISH), polyribonucleotide FISH, or quantitative PCR (qPCR). To estimate efficiency, we defined “yield” to be the sum of bacteria and archaea counted by these techniques divided by the total number of cells. In seawater, the yield was high (median, 71%) and was similar for FISH, CARD-FISH, and polyribonucleotide FISH. In sediments, only measurements by CARD-FISH in which archaeal cells were permeabilized with proteinase K showed high yields (median, 84%). Therefore, the majority of cells in both environments appear to be alive, since they contain intact ribosomes. In sediments, the sum of bacterial and archaeal 16S rRNA gene qPCR counts was not closely related to cell counts, even after accounting for variations in copy numbers per genome. However, qPCR measurements were precise relative to other qPCR measurements made on the same samples. qPCR is therefore a reliable relative quantification method. Inconsistent results for the relative abundance of bacteria versus archaea in deep subsurface sediments were resolved by the removal of CARD-FISH measurements in which lysozyme was used to permeabilize archaeal cells and qPCR measurements which used ARCH516 as an archaeal primer or TaqMan probe. Data from best-practice methods showed that archaea and bacteria decreased as the depth in seawater and marine sediments increased, although archaea decreased more slowly. PMID:24096423

  12. Improved collaborative filtering recommendation algorithm of similarity measure

    NASA Astrophysics Data System (ADS)

    Zhang, Baofu; Yuan, Baoping

    2017-05-01

    The Collaborative filtering recommendation algorithm is one of the most widely used recommendation algorithm in personalized recommender systems. The key is to find the nearest neighbor set of the active user by using similarity measure. However, the methods of traditional similarity measure mainly focus on the similarity of user common rating items, but ignore the relationship between the user common rating items and all items the user rates. And because rating matrix is very sparse, traditional collaborative filtering recommendation algorithm is not high efficiency. In order to obtain better accuracy, based on the consideration of common preference between users, the difference of rating scale and score of common items, this paper presents an improved similarity measure method, and based on this method, a collaborative filtering recommendation algorithm based on similarity improvement is proposed. Experimental results show that the algorithm can effectively improve the quality of recommendation, thus alleviate the impact of data sparseness.

  13. Current statins show calcium channel blocking activity through voltage gated channels.

    PubMed

    Ali, Niaz; Begum, Robina; Faisal, Muhammad Saleh; Khan, Aslam; Nabi, Muhammad; Shehzadi, Gulfam; Ullah, Shakir; Ali, Waqar

    2016-09-21

    Statins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin). Effects of the current statins were studied on spontaneous activity of isolated rabbits' jejunal preparations. Different molar concentrations (10(-12)-10(-2)M) of the statins were applied on spontaneously contracting rabbits' jejunal preparations. As statins relaxed spontaneous activity, so we tested the statins on KCl (80 mM) induced contractions in similar test concentrations. Positive relaxant statins were tested again through construction of Calcium Concentration Response Curves (CCRCs) in the absence and presence of the statins using verapamil, a standard calcium channel blocker. CCRCs of statins were compared with CCRCs of verapamil. Simvastatin, atorvastatin, fluvastatin and rosuvastatin relaxed the spontaneous and KCl-induced contractions. IC50 for simvastatin on spontaneous rabbit's jejunal preparations is -5.08 ± 0.1 Log 10 M. Similarly, IC50 for KCl-induced contractions is -4.25 ± 0.01 Log 10 M. Mean IC50 (Log 10 M) for atorvastatin on spontaneous rabbit's jejunal preparations and KCl-induced contractions are -5.19 ± 0.07 and -4.37 ± 0.09, respectively. Fluvastatin relaxed spontaneous activity of rabbits' jejunal preparations with an IC50 (Log 10 M) -4.5 ± 0.03. Rosuvastatin relaxed spontaneous as well as KCl (80 mM) induced contractions with respective IC50 (Log 10 M) -3.62 ± 0.04 and -4.57 ± 0.06. In case of CCRCs, tissues pre-treated with 4.6 μg/ml of simvastatin, have IC50 = -1.84 ± 0.03 [log (Ca(++)) M] vs control IC50 = -2.54 ± 0.04 [log (Ca(++)) M]. Similarly, atorvastatin, fluvastatin and rosuvastatin produced

  14. Characterization of two geraniol synthases from Valeriana officinalis and Lippia dulcis: similar activity but difference in subcellular localization.

    PubMed

    Dong, Lemeng; Miettinen, Karel; Goedbloed, Miriam; Verstappen, Francel W A; Voster, Alessandra; Jongsma, Maarten A; Memelink, Johan; van der Krol, Sander; Bouwmeester, Harro J

    2013-11-01

    Two geraniol synthases (GES), from Valeriana officinalis (VoGES) and Lippia dulcis (LdGES), were isolated and were shown to have geraniol biosynthetic activity with Km values of 32 µM and 51 µM for GPP, respectively, upon expression in Escherichia coli. The in planta enzymatic activity and sub-cellular localization of VoGES and LdGES were characterized in stable transformed tobacco and using transient expression in Nicotiana benthamiana. Transgenic tobacco expressing VoGES or LdGES accumulate geraniol, oxidized geraniol compounds like geranial, geranic acid and hexose conjugates of these compounds to similar levels. Geraniol emission of leaves was lower than that of flowers, which could be related to higher levels of competing geraniol-conjugating activities in leaves. GFP-fusions of the two GES proteins show that VoGES resides (as expected) predominantly in the plastids, while LdGES import into to the plastid is clearly impaired compared to that of VoGES, resulting in both cytosolic and plastidic localization. Geraniol production by VoGES and LdGES in N. benthamiana was nonetheless very similar. Expression of a truncated version of VoGES or LdGES (cytosolic targeting) resulted in the accumulation of 30% less geraniol glycosides than with the plastid targeted VoGES and LdGES, suggesting that the substrate geranyl diphosphate is readily available, both in the plastids as well as in the cytosol. The potential role of GES in the engineering of the TIA pathway in heterologous hosts is discussed. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Soya bean tempe extracts show antibacterial activity against Bacillus cereus cells and spores.

    PubMed

    Roubos-van den Hil, P J; Dalmas, E; Nout, M J R; Abee, T

    2010-07-01

    Tempe, a Rhizopus ssp.-fermented soya bean food product, was investigated for bacteriostatic and/or bactericidal effects against cells and spores of the food-borne pathogen Bacillus cereus. Tempe extract showed a high antibacterial activity against B. cereus ATCC 14579 based on optical density and viable count measurements. This growth inhibition was manifested by a 4 log CFU ml(-1) reduction, within the first 15 min of exposure. Tempe extracts also rapidly inactivated B. cereus spores upon germination. Viability and membrane permeability assessments using fluorescence probes showed rapid inactivation and permeabilization of the cytoplasmic membrane confirming the bactericidal mode of action. Cooked beans and Rhizopus grown on different media did not show antibacterial activity, indicating the unique association of the antibacterial activity with tempe. Subsequent characterization of the antibacterial activity revealed that heat treatment and protease addition nullified the bactericidal effect, indicating the proteinaceous nature of the bioactive compound. During fermentation of soya beans with Rhizopus, compounds are released with extensive antibacterial activity against B. cereus cells and spores. The results show the potential of producing natural antibacterial compounds that could be used as ingredients in food preservation and pathogen control. © 2009 The Authors. Journal compilation © 2009 The Society for Applied Microbiology.

  16. Similarity increases altruistic punishment in humans

    PubMed Central

    Mussweiler, Thomas; Ockenfels, Axel

    2013-01-01

    Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics—a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others’ uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions. PMID:24218611

  17. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

    PubMed

    Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

    2008-01-01

    Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease. Copyright (c) 2007 John Wiley & Sons, Ltd.

  18. Location of the redox-active thiols of ribonucleotide reductase: sequences similarity between the Escherichia coli and Lactobacillus leichmannii enzymes

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

    Lin, A.N.I.; Ashley, G.W.; Stubbe, J.

    1987-11-03

    The redox-active thiols of Escherichia coli ribonucleoside diphosphate reductase and of Lactobacillus leichmannii ribonucleoside triphosphate reductase have been located by a procedure involving (1) prereduction of enzyme with dithiothreitol, (2) specific oxidation of the redox-active thiols by treatment with substrate in the absence of exogenous reductant, (3) alkylation of other thiols with iodoacetamide, and (4) reduction of the disulfides with dithiothreitol and alkylation with (1-/sup 14/C)iodoacetamide. The dithiothreitol-reduce E. coli B1 subunit is able to convert 3 equiv of CDP to dCDP and is labeled with 5.4 equiv of /sup 14/C. Sequencing of tryptic peptides shows that 2.8 equiv ofmore » /sup 14/C is on cysteines-752 and -757 at the C-terminus of B1, while 1.0-1.5 equiv of /sup 14/C is on cysteines-222 and -227. It thus appears that two sets of redox-active dithiols are involved in substrate reduction. The L. leichmannii reductase is able to convert 1.1 equiv of CTP to dCTP and is labeled with 2.1 equiv of /sup 14/C. Sequencing of tryptic peptides shows that 1.4 equiv of /sup 14/C is located on the two cysteines of C-E-G-G-A-C-P-I-K. This peptide shows remarkable and unexpected similarity to the thiol-containing region of the C-terminal peptide of E. coli B1, C-E-S-G-A-C-K-I.« less

  19. The three catalases in Deinococcus radiodurans: Only two show catalase activity.

    PubMed

    Jeong, Sun-Wook; Jung, Jong-Hyun; Kim, Min-Kyu; Seo, Ho Seong; Lim, Heon-Man; Lim, Sangyong

    2016-01-15

    Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H2O2) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H2O2 treatments, whereas ΔdrA0146 showed no change in its H2O2 resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the three bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H2O2, but DRA0146 does not have catalase activity and is not involved in the resistance to H2O2 stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks

    DOE PAGES

    Zhao, Suwen; Sakai, Ayano; Zhang, Xinshuai; ...

    2014-06-30

    Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins inmore » 12 families in the PRS that represent ~85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.« less

  1. Higher similarity in beta topography between tasks than subjects.

    PubMed

    Basile, Luis F H; Sato, João R; Pasquini, Henrique A; Velasques, Bruna; Ribeiro, Pedro; Anghinah, Renato

    2018-05-01

    We have recently provided evidence for highly idiosyncratic topographic distributions of beta oscillations (as well as slow potentials) across individuals. More recently, by emphasizing the analysis of similarity instead of differences across tasks, we concluded that differences between an attention task and quiet resting may be negligible or at least unsystematic across subjects. Due to the possibility that individual differences could be due to noise in a wide sense or some inherent instability of beta activity, we designed a replication study to explicitly test whether pairs of individuals matched for head size and shape would still present less similar beta topography than each individual between sessions or tasks. We used independent component analysis (ICA) for an exhaustive decomposition of beta activity in a visual attention task and in quiet resting, recorded by 256-channel EEG in 20 subjects, on two separate days. We evaluated whether each ICA component obtained in one task and in one given individual could be explained by a linear regression model based on the topographic patterns of the complementary task (correlation between one component with a linear combination of components from complementary conditions), of the same task in a second session and of a matched individual. Results again showed a high topographic similarity between conditions, as previously seen between reasoning and simple visual attention beta correlates. From an overall number of 16 components representing brain activity obtained for the tasks (out of 60 originally computed where the remaining were considered noise), over 92% could satisfactorily be explained by the complementary task. Although the similarity between sessions was significantly smaller than between tasks on each day, the similarity between sessions was statistically higher than that between subjects in a highly significant way. We discuss the possible biases of group spatial averaging and the emphasis on differences

  2. Men and women show similar survival outcome in stage IV breast cancer.

    PubMed

    Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

    2017-08-01

    To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

    PubMed

    Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

    2010-01-01

    The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P < .001). Key barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

  4. Stretch and interleukin 1 beta: pro-labour factors with similar mitogen-activated protein kinase effects but differential patterns of transcription factor activation and gene expression.

    PubMed

    Sooranna, S R; Engineer, N; Liang, Z; Bennett, P R; Johnson, M R

    2007-07-01

    IL-1beta and stretch increase uterine smooth muscle cell (USMC) prostaglandin H synthase 2 (PGHS-2) and interleukin (IL)-8 mRNA expression in a mitogen-activated protein kinase (MAPK) dependent mechanism. We have tested our hypothesis that stretch and IL-1beta activate different components of the MAPK cascade in USMC and investigated the effects of specific MAPK inhibitors on these components. Further, we have used a Jun N-terminal kinase (JNK) and p38 activator, anisomycin, to compare the effect of differential MAPK activation on the expression of PGHS-2, IL-8 and oxytocin receptor (OTR) mRNA with that seen in response to stretch and IL-1beta. Stretch, IL-1beta and anisomycin activated similar components of the MAPK cascade and specific inhibitors of MAPK altered phosphorylation of MAPK and downstream cascade components as expected. Expression of OTR mRNA was increased by stretch and anisomycin in a MAPK-independent manner. All three stimuli increased PGHS-2 and IL-8 mRNA expression in a MAPK-dependent manner, but while the MAPK inhibitors reduced the IL-1beta-induced activation of activating transcription factor (ATF)-2, liver activating protein (LAP) and c-jun, the stretch-induced increase in LAP was unaffected by MAPK-inhibition and only JNK inhibition appeared to reduce c-jun activation. These observations show that stretch, IL-1beta and anisomycin activate the same components of the MAPK cascade, but differentially activate LAP and liver inhibitory protein (LIP) perhaps accounting for the increase in OTR by stretch and anisomycin but not IL-1beta observed in this study.

  5. Structure at every scale: A semantic network account of the similarities between unrelated concepts.

    PubMed

    De Deyne, Simon; Navarro, Daniel J; Perfors, Amy; Storms, Gert

    2016-09-01

    Similarity plays an important role in organizing the semantic system. However, given that similarity cannot be defined on purely logical grounds, it is important to understand how people perceive similarities between different entities. Despite this, the vast majority of studies focus on measuring similarity between very closely related items. When considering concepts that are very weakly related, little is known. In this article, we present 4 experiments showing that there are reliable and systematic patterns in how people evaluate the similarities between very dissimilar entities. We present a semantic network account of these similarities showing that a spreading activation mechanism defined over a word association network naturally makes correct predictions about weak similarities, whereas, though simpler, models based on direct neighbors between word pairs derived using the same network cannot. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  6. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Qualified convention and trade show activity. 1.513-3 Section 1.513-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt...

  7. The parietal memory network activates similarly for true and associative false recognition elicited via the DRM procedure.

    PubMed

    McDermott, Kathleen B; Gilmore, Adrian W; Nelson, Steven M; Watson, Jason M; Ojemann, Jeffrey G

    2017-02-01

    Neuroimaging investigations of human memory encoding and retrieval have revealed that multiple regions of parietal cortex contribute to memory. Recently, a sparse network of regions within parietal cortex has been identified using resting state functional connectivity (MRI techniques). The regions within this network exhibit consistent task-related responses during memory formation and retrieval, leading to its being called the parietal memory network (PMN). Among its signature patterns are: deactivation during initial experience with an item (e.g., encoding); activation during subsequent repetitions (e.g., at retrieval); greater activation for successfully retrieved familiar words than novel words (e.g., hits relative to correctly-rejected lures). The question of interest here is whether novel words that are subjectively experienced as having been recently studied would elicit PMN activation similar to that of hits. That is, we compared old items correctly recognized to two types of novel items on a recognition test: those correctly identified as new and those incorrectly labeled as old due to their strong associative relation to the studied words (in the DRM false memory protocol). Subjective oldness plays a strong role in driving activation, as hits and false alarms activated similarly (and greater than correctly-rejected lures). Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Mice with cancer-induced bone pain show a marked decline in day/night activity.

    PubMed

    Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W

    2017-09-01

    Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

  9. Wordform Similarity Increases With Semantic Similarity: An Analysis of 100 Languages.

    PubMed

    Dautriche, Isabelle; Mahowald, Kyle; Gibson, Edward; Piantadosi, Steven T

    2017-11-01

    Although the mapping between form and meaning is often regarded as arbitrary, there are in fact well-known constraints on words which are the result of functional pressures associated with language use and its acquisition. In particular, languages have been shown to encode meaning distinctions in their sound properties, which may be important for language learning. Here, we investigate the relationship between semantic distance and phonological distance in the large-scale structure of the lexicon. We show evidence in 100 languages from a diverse array of language families that more semantically similar word pairs are also more phonologically similar. This suggests that there is an important statistical trend for lexicons to have semantically similar words be phonologically similar as well, possibly for functional reasons associated with language learning. Copyright © 2016 Cognitive Science Society, Inc.

  10. 17 CFR 8.27 - Violations of rules regarding decorum, submission of records or other similar activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Violations of rules regarding decorum, submission of records or other similar activities. 8.27 Section 8.27 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION EXCHANGE PROCEDURES FOR DISCIPLINARY, SUMMARY, AND MEMBERSHIP...

  11. The great American medicine show revisited.

    PubMed

    Tomes, Nancy

    2005-01-01

    Since the late 1800s, changes in the advertising and marketing of medicinal drugs have produced heated debates in the United States. With the emergence of the modern prescription drug between 1938 and 1951, concerns that once focused primarily on patients' use of over-the-counter drugs were broadened to include physicians and their "doctors' drugs" as well. The medical profession's growing control over their patients' drug choices inevitably heightened the scrutiny of their own performance as consumers. Although deeply divided over issues of the patient's role in medical decision making, consumer activists and physician reformers expressed similar concerns about the impact of aggressive pharmaceutical marketing and advertising on the doctor-patient relationship, and starting in the late 1950s they employed strikingly similar strategies to counter the new corporate "medicine show." Yet their efforts to promote a more rational use of prescription drugs have usually been too little and too late to offset the effectiveness of pharmaceutical advertising and mar-keting activities.

  12. Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

    PubMed

    Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

    2017-01-01

    Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

  13. Detection of activity similar to that of early pregnancy factor after mating sows with a vasectomized boar.

    PubMed

    Koch, E; Ellendorff, F

    1985-05-01

    Incubation of normal pig lymphocytes in serum samples collected from 10 sows immediately before, and at daily intervals after mating with a vasectomized boar significantly elevated the rosette inhibition titre (RIT) of a standard antilymphocyte serum in 6 animals on the first but not on the 2nd and 3rd day after copulation. Infusion of seminal plasma without mating into 5 sows induced an obvious, but not statistically significant, transient rise of titres in 3 pigs. Neither sodium chloride infusion (N = 5), nor sham copulation with diverted penis (N = 5) influenced serum RITs. Porcine seminal plasma showed an inherent rosette-inhibiting property. A depression of rosette formation was evident in a concentration-dependent fashion up to a dilution of 1 in 320. Similarly, preincubation of lymphocytes in serial dilutions of seminal plasma in a non-pregnancy serum sample led to an amplification of the rosette inhibiting capacity of the antilymphocyte serum. Non-specific activation of the eggs to release a signal which induces the production of early pregnancy factor (EPF) or the resorption of seminal plasma components into the blood circulation are considered as possible explanations for the EPF-like activity after mating with a vasectomized boar.

  14. Functional and biochemical properties of Mal de Río Cuarto virus (Fijivirus, Reoviridae) P9-1 viroplasm protein show further similarities to animal reovirus counterparts.

    PubMed

    Maroniche, Guillermo A; Mongelli, Vanesa C; Peralta, Andrea V; Distéfano, Ana J; Llauger, Gabriela; Taboga, Oscar A; Hopp, Esteban H; del Vas, Mariana

    2010-09-01

    Mal de Río Cuarto virus (MRCV) is a plant virus of the genus Fijivirus within the family Reoviridae that infects several monocotyledonous species and is transmitted by planthoppers in a persistent and propagative manner. Other members of the family replicate in viral inclusion bodies (VIBs) termed viroplasms that are formed in the cytoplasm of infected plant and insect cells. In this study, the protein coded by the first ORF of MRCV segment S9 (P9-1) was shown to establish cytoplasmic inclusion bodies resembling viroplasms after transfection of Spodoptera frugiperda insect cells. In accordance, MRCV P9-1 self-associates giving rise to high molecular weight complexes when expressed in bacteria. Strong self-interaction was also evidenced by yeast two-hybrid assays. Furthermore, biochemical characterization showed that MRCV P9-1 bound single stranded RNA and had ATPase activity. Finally, the MRCV P9-1 region required for the formation of VIB-like structures was mapped to the protein carboxy-terminal half. This extensive functional and biochemical characterization of MRCV P9-1 revealed further similarities between plant and animal reovirus viroplasm proteins. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. Benzoxazine derivatives of phytophenols show anti-plasmodial activity via sodium homeostasis disruption.

    PubMed

    Sharma, Vijeta; Amarnath, Nagarjuna; Shukla, Swapnil; Ayana, R; Kumar, Naveen; Yadav, Nisha; Kannan, Deepika; Sehrawat, Seema; Pati, Soumya; Lochab, Bimlesh; Singh, Shailja

    2018-05-15

    Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na + levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490 nM from 17.54 µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Love flows downstream: mothers' and children's neural representation similarity in perceiving distress of self and family.

    PubMed

    Lee, Tae-Ho; Qu, Yang; Telzer, Eva H

    2017-12-01

    The current study aimed to capture empathy processing in an interpersonal context. Mother-adolescent dyads (N = 22) each completed an empathy task during fMRI, in which they imagined the target person in distressing scenes as either themselves or their family (i.e. child for the mother, mother for the child). Using multi-voxel pattern approach, we compared neural pattern similarity for the self and family conditions and found that mothers showed greater perceptual similarity between self and child in the fusiform face area (FFA), representing high self-child overlap, whereas adolescents showed significantly less self-mother overlap. Adolescents' pattern similarity was dependent upon family relationship quality, such that they showed greater self-mother overlap with higher relationship quality, whereas mothers' pattern similarity was independent of relationship quality. Furthermore, adolescents' perceptual similarity in the FFA was associated with increased social brain activation (e.g. temporal parietal junction). Mediation analyses indicated that high relationship quality was associated with greater social brain activation, which was mediated by greater self-mother overlap in the FFA. Our findings suggest that adolescents show more distinct neural patterns in perceiving their own vs their mother's distress, and such distinction is sensitive to mother-child relationship quality. In contrast, mothers' perception for their own and child's distress is highly similar and unconditional. © The Author (2017). Published by Oxford University Press.

  17. Evidence for similar patterns of neural activity elicited by picture- and word-based representations of natural scenes.

    PubMed

    Kumar, Manoj; Federmeier, Kara D; Fei-Fei, Li; Beck, Diane M

    2017-07-15

    A long-standing core question in cognitive science is whether different modalities and representation types (pictures, words, sounds, etc.) access a common store of semantic information. Although different input types have been shown to activate a shared network of brain regions, this does not necessitate that there is a common representation, as the neurons in these regions could still differentially process the different modalities. However, multi-voxel pattern analysis can be used to assess whether, e.g., pictures and words evoke a similar pattern of activity, such that the patterns that separate categories in one modality transfer to the other. Prior work using this method has found support for a common code, but has two limitations: they have either only examined disparate categories (e.g. animals vs. tools) that are known to activate different brain regions, raising the possibility that the pattern separation and inferred similarity reflects only large scale differences between the categories or they have been limited to individual object representations. By using natural scene categories, we not only extend the current literature on cross-modal representations beyond objects, but also, because natural scene categories activate a common set of brain regions, we identify a more fine-grained (i.e. higher spatial resolution) common representation. Specifically, we studied picture- and word-based representations of natural scene stimuli from four different categories: beaches, cities, highways, and mountains. Participants passively viewed blocks of either phrases (e.g. "sandy beach") describing scenes or photographs from those same scene categories. To determine whether the phrases and pictures evoke a common code, we asked whether a classifier trained on one stimulus type (e.g. phrase stimuli) would transfer (i.e. cross-decode) to the other stimulus type (e.g. picture stimuli). The analysis revealed cross-decoding in the occipitotemporal, posterior parietal and

  18. Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

    PubMed Central

    Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

    2017-01-01

    Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

  19. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Qualified convention and trade show activity. 1.513-3 Section 1.513-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.513-3 Qualified convention and...

  20. Classification of auxin plant hormones by interaction property similarity indices

    NASA Astrophysics Data System (ADS)

    Tomić, Sanja; Gabdoulline, Razif R.; Kojić-Prodić, Biserka; Wade, Rebecca C.

    1998-01-01

    Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were modeled in two low-energy conformations, `P' and `T', so as to obtain the best match to the `planar' and `tilted' conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides.

  1. Mice with cancer-induced bone pain show a marked decline in day/night activity

    PubMed Central

    Majuta, Lisa A.; Guedon, Jean-Marc G.; Mitchell, Stefanie A.T.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2017-01-01

    Abstract Introduction: Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. Objectives: To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Methods: Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. Results: As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Conclusion: Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status. PMID:29392229

  2. Similar ventral occipito-temporal cortex activations in literate and illiterate adults during the Chinese character matching task: an fMRI study.

    PubMed

    Qi, Geqi; Li, Xiujun; Yan, Tianyi; Wang, Bin; Yang, Jiajia; Wu, Jinglong; Guo, Qiyong

    2014-04-30

    Visual word expertise is typically associated with enhanced ventral occipito-temporal (vOT) cortex activation in response to written words. Previous study utilized a passive viewing task and found that vOT response to written words was significantly stronger in literate compared to the illiterate subjects. However, recent neuroimaging findings have suggested that vOT response properties are highly dependent upon the task demand. Thus, it is unknown whether literate adults would show stronger vOT response to written words compared to illiterate adults during other cognitive tasks, such as perceptual matching. We addressed this issue by comparing vOT activations between literate and illiterate adults during a Chinese character and simple figure matching task. Unlike passive viewing, a perceptual matching task requires active shape comparison, therefore minimizing automatic word processing bias. We found that although the literate group performed better at Chinese character matching task, the two subject groups showed similar strong vOT responses during this task. Overall, the findings indicate that the vOT response to written words is not affected by expertise during a perceptual matching task, suggesting that the association between visual word expertise and vOT response may depend on the task demand. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Factor analysis shows association between family activity environment and children's health behaviour.

    PubMed

    Hendrie, Gilly A; Coveney, John; Cox, David N

    2011-12-01

    To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  4. Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer.

    PubMed

    Kodama, Tatsushi; Tsukaguchi, Toshiyuki; Satoh, Yasuko; Yoshida, Miyuki; Watanabe, Yoshiaki; Kondoh, Osamu; Sakamoto, Hiroshi

    2014-12-01

    Alectinib/CH5424802 is a known inhibitor of anaplastic lymphoma kinase (ALK) and is being evaluated in clinical trials for the treatment of ALK fusion-positive non-small cell lung cancer (NSCLC). Recently, some RET and ROS1 fusion genes have been implicated as driver oncogenes in NSCLC and have become molecular targets for antitumor agents. This study aims to explore additional target indications of alectinib by testing its ability to inhibit the activity of kinases other than ALK. We newly verified that alectinib inhibited RET kinase activity and the growth of RET fusion-positive cells by suppressing RET phosphorylation. In contrast, alectinib hardly inhibited ROS1 kinase activity unlike other ALK/ROS1 inhibitors such as crizotinib and LDK378. It also showed antitumor activity in mouse models of tumors driven by the RET fusion. In addition, alectinib showed kinase inhibitory activity against RET gatekeeper mutations (RET V804L and V804M) and blocked cell growth driven by the KIF5B-RET V804L and V804M. Our results suggest that alectinib is effective against RET fusion-positive tumors. Thus, alectinib might be a therapeutic option for patients with RET fusion-positive NSCLC. ©2014 American Association for Cancer Research.

  5. A Quantum-Based Similarity Method in Virtual Screening.

    PubMed

    Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

    2015-10-02

    One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays a vital role in the development of quantum-based similarity approach. One of the key concepts of quantum theory is the use of complex numbers. Hence, this study proposed three various techniques to embed and to re-represent the molecular compounds to correspond with complex numbers format. The quantum-based similarity method that developed in this study depending on complex pure Hilbert space of molecules called Standard Quantum-Based (SQB). The recall of retrieved active molecules were at top 1% and top 5%, and significant test is used to evaluate our proposed methods. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiment show that the effectiveness of SQB method was significantly increased due to the role of representational power of molecular compounds in complex numbers forms compared to Tanimoto benchmark similarity measure.

  6. Benzotriazole UV 328 and UV-P showed distinct antiandrogenic activity upon human CYP3A4-mediated biotransformation.

    PubMed

    Zhuang, Shulin; Lv, Xuan; Pan, Liumeng; Lu, Liping; Ge, Zhiwei; Wang, Jiaying; Wang, Jingpeng; Liu, Jinsong; Liu, Weiping; Zhang, Chunlong

    2017-01-01

    Benzotriazole ultraviolet stabilizers (BUVSs) are prominent chemicals widely used in industrial and consumer products to protect against ultraviolet radiation. They are becoming contaminants of emerging concern since their residues are frequently detected in multiple environmental matrices and their toxicological implications are increasingly reported. We herein investigated the antiandrogenic activities of eight BUVSs prior to and after human CYP3A4-mediated metabolic activation/deactivation by the two-hybrid recombinant human androgen receptor yeast bioassay and the in vitro metabolism assay. More potent antiandrogenic activity was observed for the metabolized UV-328 in comparison with UV-328 at 0.25 μM ((40.73 ± 4.90)% vs. (17.12 ± 3.00)%), showing a significant metabolic activation. In contrast, the metabolized UV-P at 0.25 μM resulted in a decreased antiandrogenic activity rate from (16.08 ± 0.95)% to (6.91 ± 2.64)%, indicating a metabolic deactivation. Three mono-hydroxylated (OH) and three di-OH metabolites of UV-328 were identified by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS), which were not reported previously. We further surmised that the hydroxylation of UV-328 occurs mainly at the alicyclic hydrocarbon atoms based on the in silico prediction of the lowest activation energies of hydrogen abstraction from C-H bond. Our results for the first time relate antiandrogenic activity to human CYP3A4 enzyme-mediated hydroxylated metabolites of BUVSs. The biotransformation through hydroxylation should be fully considered during the health risk assessment of structurally similar analogs of BUVSs and other emerging contaminants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Love flows downstream: mothers’ and children’s neural representation similarity in perceiving distress of self and family

    PubMed Central

    Qu, Yang

    2017-01-01

    Abstract The current study aimed to capture empathy processing in an interpersonal context. Mother–adolescent dyads (N = 22) each completed an empathy task during fMRI, in which they imagined the target person in distressing scenes as either themselves or their family (i.e. child for the mother, mother for the child). Using multi-voxel pattern approach, we compared neural pattern similarity for the self and family conditions and found that mothers showed greater perceptual similarity between self and child in the fusiform face area (FFA), representing high self–child overlap, whereas adolescents showed significantly less self–mother overlap. Adolescents’ pattern similarity was dependent upon family relationship quality, such that they showed greater self–mother overlap with higher relationship quality, whereas mothers’ pattern similarity was independent of relationship quality. Furthermore, adolescents’ perceptual similarity in the FFA was associated with increased social brain activation (e.g. temporal parietal junction). Mediation analyses indicated that high relationship quality was associated with greater social brain activation, which was mediated by greater self–mother overlap in the FFA. Our findings suggest that adolescents show more distinct neural patterns in perceiving their own vs their mother’s distress, and such distinction is sensitive to mother–child relationship quality. In contrast, mothers’ perception for their own and child’s distress is highly similar and unconditional. PMID:29069521

  8. Beyond conventional dose-response curves: Sensorgram comparison in SPR allows single concentration activity and similarity assessment.

    PubMed

    Gassner, C; Karlsson, R; Lipsmeier, F; Moelleken, J

    2018-05-30

    Previously we have introduced two SPR-based assay principles (dual-binding assay and bridging assay), which allow the determination of two out of three possible interaction parameters for bispecific molecules within one assay setup: two individual interactions to both targets, and/or one simultaneous/overall interaction, which potentially reflects the inter-dependency of both individual binding events. However, activity and similarity are determined by comparing report points over a concentration range, which also mirrors the way data is generated by conventional ELISA-based methods So far, binding kinetics have not been specifically considered in generic approaches for activity assessment. Here, we introduce an improved slope-ratio model which, together with a sensorgram comparison based similarity assessment, allows the development of a detailed, USP-conformal ligand binding assay using only a single sample concentration. We compare this novel analysis method to the usual concentration-range approach for both SPR-based assay principles and discuss its impact on data quality and increased sample throughput. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Are calanco landforms similar to river basins?

    PubMed

    Caraballo-Arias, N A; Ferro, V

    2017-12-15

    In the past badlands have been often considered as ideal field laboratories for studying landscape evolution because of their geometrical similarity to larger fluvial systems. For a given hydrological process, no scientific proof exists that badlands can be considered a model of river basin prototypes. In this paper the measurements carried out on 45 Sicilian calanchi, a type of badlands that appears as a small-scale hydrographic unit, are used to establish their morphological similarity with river systems whose data are available in the literature. At first the geomorphological similarity is studied by identifying the dimensionless groups, which can assume the same value or a scaled one in a fixed ratio, representing drainage basin shape, stream network and relief properties. Then, for each property, the dimensionless groups are calculated for the investigated calanchi and the river basins and their corresponding scale ratio is evaluated. The applicability of Hack's, Horton's and Melton's laws for establishing similarity criteria is also tested. The developed analysis allows to conclude that a quantitative morphological similarity between calanco landforms and river basins can be established using commonly applied dimensionless groups. In particular, the analysis showed that i) calanchi and river basins have a geometrically similar shape respect to the parameters Rf and Re with a scale factor close to 1, ii) calanchi and river basins are similar respect to the bifurcation and length ratios (λ=1), iii) for the investigated calanchi the Melton number assumes values less than that (0.694) corresponding to the river case and a scale ratio ranging from 0.52 and 0.78 can be used, iv) calanchi and river basins have similar mean relief ratio values (λ=1.13) and v) calanchi present active geomorphic processes and therefore fall in a more juvenile stage with respect to river basins. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. What difference reveals about similarity.

    PubMed

    Sagi, Eyal; Gentner, Dedre; Lovett, Andrew

    2012-08-01

    Detecting that two images are different is faster for highly dissimilar images than for highly similar images. Paradoxically, we showed that the reverse occurs when people are asked to describe how two images differ--that is, to state a difference between two images. Following structure-mapping theory, we propose that this disassociation arises from the multistage nature of the comparison process. Detecting that two images are different can be done in the initial (local-matching) stage, but only for pairs with low overlap; thus, "different" responses are faster for low-similarity than for high-similarity pairs. In contrast, identifying a specific difference generally requires a full structural alignment of the two images, and this alignment process is faster for high-similarity pairs. We described four experiments that demonstrate this dissociation and show that the results can be simulated using the Structure-Mapping Engine. These results pose a significant challenge for nonstructural accounts of similarity comparison and suggest that structural alignment processes play a significant role in visual comparison. Copyright © 2012 Cognitive Science Society, Inc.

  11. Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows similarities to human bacterial vaginosis: implications for use as an animal model for HIV vaginal infection.

    PubMed

    Spear, Gregory T; Gilbert, Douglas; Sikaroodi, Masoumeh; Doyle, Lara; Green, Linda; Gillevet, Patrick M; Landay, Alan L; Veazey, Ronald S

    2010-02-01

    The composition of the lower genital tract microbiota in women is believed to affect the risk of sexually acquiring HIV. Since macaque genital microbiota could similarly impact vaginal infection with SIV we identified microbiota in 11 rhesus macaques using multitag pyrosequencing of the 16S rRNA gene. The microbiota was polymicrobial with a median of nine distinct bacterial taxa per macaque (range 3-16 taxa, each constituting 1% or more of the sequences). Taxa frequently found included Peptoniphilus, Sneathia, Porphyromonas, Mobiluncus, Atopobacter, Dialister, Thioreductor, Prevotella, and Streptococcus, many of which are also frequently found in women with bacterial vaginosis. Lactobacillus sequences (mostly L. johnsonii) were found in only four macaques but were not predominant in any (median of 0% of sequences, range 0-39%). All macaques were resampled 6 months after the first time point to determine the stability of the microbiota. The microbiota remained polymicrobial with a median of 10 taxa (range 6-18). Microbial patterns remained similar for six of the macaques, changed substantially in two, and had a mixed pattern in three. Significant sialidase enzyme activity, a marker of bacteria vaginosis in women, was detected in genital fluid from 9/11 and 8/11 macaques from the first and second time points, respectively. These results show that the macaque lower genital microbiota resembled a bacteria vaginosis-type microbiota in women and suggest that the microbiota of macaques in captivity promote rather than protect against vaginal infection with SIV. These results also suggest macaques could be used as an animal model to study some aspects of bacterial vaginosis.

  12. Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation.

    PubMed

    Keegan, A D; Johnston, J A; Tortolani, P J; McReynolds, L J; Kinzer, C; O'Shea, J J; Paul, W E

    1995-08-15

    The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a substrate called 4PS, and of the Janus kinase (JAK) family members JAK1 and JAK3. Because IL-13 has many functional effects similar to those of IL-4, we compared the ability of IL-4 and IL-13 to activate these signaling molecules in the human multifactor-dependent cell line TF-1. In this report we demonstrate that both IL-4 and IL-13 induced the tyrosine phosphorylation of 4PS and JAK1. Interestingly, although IL-4 induced the tyrosine phosphorylation of JAK3, we did not detect JAK3 phosphorylation in response to IL-13. These data suggest that IL-4 and IL-13 signal in similar ways via the activation of JAK1 and 4PS. However, our data further indicate that there are significant differences because IL-13 does not activate JAK3.

  13. Pulmonary parenchyma segmentation in thin CT image sequences with spectral clustering and geodesic active contour model based on similarity

    NASA Astrophysics Data System (ADS)

    He, Nana; Zhang, Xiaolong; Zhao, Juanjuan; Zhao, Huilan; Qiang, Yan

    2017-07-01

    While the popular thin layer scanning technology of spiral CT has helped to improve diagnoses of lung diseases, the large volumes of scanning images produced by the technology also dramatically increase the load of physicians in lesion detection. Computer-aided diagnosis techniques like lesions segmentation in thin CT sequences have been developed to address this issue, but it remains a challenge to achieve high segmentation efficiency and accuracy without much involvement of human manual intervention. In this paper, we present our research on automated segmentation of lung parenchyma with an improved geodesic active contour model that is geodesic active contour model based on similarity (GACBS). Combining spectral clustering algorithm based on Nystrom (SCN) with GACBS, this algorithm first extracts key image slices, then uses these slices to generate an initial contour of pulmonary parenchyma of un-segmented slices with an interpolation algorithm, and finally segments lung parenchyma of un-segmented slices. Experimental results show that the segmentation results generated by our method are close to what manual segmentation can produce, with an average volume overlap ratio of 91.48%.

  14. Does similarity in educational level between health promotion volunteers and local residents affect activity involvement of the volunteers?

    PubMed

    Murayama, Hiroshi; Taguchi, Atsuko; Murashima, Sachiyo

    2012-01-01

    This study examined whether similarity in educational level, as a socioeconomic background factor, between health promotion volunteers (HPVs) and residents in the district where HPVs work encourages the volunteers' involvement in providing activities. Cross-sectional questionnaire survey. A total of 512 HPVs in a Japanese city with 5 districts. We focused on the number of activities related to working as an HPV as an aspect of involvement in the HPV role. HPV individual educational level was collected from a questionnaire. District educational level was obtained from the Japanese census database. Of 512 questionnaires, 363 were returned and used for the analysis. Multiple regression analysis stratified by district educational level indicated that a higher educational level in HPVs was significantly associated with a greater number of self-motivated activities in the districts with a higher educational level, although the association between a lower HPV educational level and more activity involvement was not found in districts with a lower educational level. It is important to consider similarity in educational level, as a socioeconomic status factor, between HPVs and the districts in which they will work when recruiting new members and when allocating HPVs to work areas. © 2011 Wiley Periodicals, Inc.

  15. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria.

    PubMed

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Standard, ATCC, strains of four anaerobic bacteria ( Clostridium difficile , Clostridium perfringens , Bacteroides fragilis , and Bacteroides thetaiotaomicron ), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections.

  16. From genus to phylum: large-subunit and internal transcribed spacer rRNA operon regions show similar classification accuracies influenced by database composition.

    PubMed

    Porras-Alfaro, Andrea; Liu, Kuan-Liang; Kuske, Cheryl R; Xie, Gary

    2014-02-01

    We compared the classification accuracy of two sections of the fungal internal transcribed spacer (ITS) region, individually and combined, and the 5' section (about 600 bp) of the large-subunit rRNA (LSU), using a naive Bayesian classifier and BLASTN. A hand-curated ITS-LSU training set of 1,091 sequences and a larger training set of 8,967 ITS region sequences were used. Of the factors evaluated, database composition and quality had the largest effect on classification accuracy, followed by fragment size and use of a bootstrap cutoff to improve classification confidence. The naive Bayesian classifier and BLASTN gave similar results at higher taxonomic levels, but the classifier was faster and more accurate at the genus level when a bootstrap cutoff was used. All of the ITS and LSU sections performed well (>97.7% accuracy) at higher taxonomic ranks from kingdom to family, and differences between them were small at the genus level (within 0.66 to 1.23%). When full-length sequence sections were used, the LSU outperformed the ITS1 and ITS2 fragments at the genus level, but the ITS1 and ITS2 showed higher accuracy when smaller fragment sizes of the same length and a 50% bootstrap cutoff were used. In a comparison using the larger ITS training set, ITS1 and ITS2 had very similar accuracy classification for fragments between 100 and 200 bp. Collectively, the results show that any of the ITS or LSU sections we tested provided comparable classification accuracy to the genus level and underscore the need for larger and more diverse classification training sets.

  17. From Genus to Phylum: Large-Subunit and Internal Transcribed Spacer rRNA Operon Regions Show Similar Classification Accuracies Influenced by Database Composition

    PubMed Central

    Liu, Kuan-Liang; Kuske, Cheryl R.

    2014-01-01

    We compared the classification accuracy of two sections of the fungal internal transcribed spacer (ITS) region, individually and combined, and the 5′ section (about 600 bp) of the large-subunit rRNA (LSU), using a naive Bayesian classifier and BLASTN. A hand-curated ITS-LSU training set of 1,091 sequences and a larger training set of 8,967 ITS region sequences were used. Of the factors evaluated, database composition and quality had the largest effect on classification accuracy, followed by fragment size and use of a bootstrap cutoff to improve classification confidence. The naive Bayesian classifier and BLASTN gave similar results at higher taxonomic levels, but the classifier was faster and more accurate at the genus level when a bootstrap cutoff was used. All of the ITS and LSU sections performed well (>97.7% accuracy) at higher taxonomic ranks from kingdom to family, and differences between them were small at the genus level (within 0.66 to 1.23%). When full-length sequence sections were used, the LSU outperformed the ITS1 and ITS2 fragments at the genus level, but the ITS1 and ITS2 showed higher accuracy when smaller fragment sizes of the same length and a 50% bootstrap cutoff were used. In a comparison using the larger ITS training set, ITS1 and ITS2 had very similar accuracy classification for fragments between 100 and 200 bp. Collectively, the results show that any of the ITS or LSU sections we tested provided comparable classification accuracy to the genus level and underscore the need for larger and more diverse classification training sets. PMID:24242255

  18. A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif.

    PubMed

    Kandimalla, Ekambar R; Bhagat, Lakshmi; Zhu, Fu-Gang; Yu, Dong; Cong, Yan-Ping; Wang, Daqing; Tang, Jimmy X; Tang, Jin-Yan; Knetter, Cathrine F; Lien, Egil; Agrawal, Sudhir

    2003-11-25

    Bacterial and synthetic DNAs containing CpG dinucleotides in specific sequence contexts activate the vertebrate immune system through Toll-like receptor 9 (TLR9). In the present study, we used a synthetic nucleoside with a bicyclic heterobase [1-(2'-deoxy-beta-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; R] to replace the C in CpG, resulting in an RpG dinucleotide. The RpG dinucleotide was incorporated in mouse- and human-specific motifs in oligodeoxynucleotides (oligos) and 3'-3-linked oligos, referred to as immunomers. Oligos containing the RpG motif induced cytokine secretion in mouse spleen-cell cultures. Immunomers containing RpG dinucleotides showed activity in transfected-HEK293 cells stably expressing mouse TLR9, suggesting direct involvement of TLR9 in the recognition of RpG motif. In J774 macrophages, RpG motifs activated NF-kappa B and mitogen-activated protein kinase pathways. Immunomers containing the RpG dinucleotide induced high levels of IL-12 and IFN-gamma, but lower IL-6 in time- and concentration-dependent fashion in mouse spleen-cell cultures costimulated with IL-2. Importantly, immunomers containing GTRGTT and GARGTT motifs were recognized to a similar extent by both mouse and human immune systems. Additionally, both mouse- and human-specific RpG immunomers potently stimulated proliferation of peripheral blood mononuclear cells obtained from diverse vertebrate species, including monkey, pig, horse, sheep, goat, rat, and chicken. An immunomer containing GTRGTT motif prevented conalbumin-induced and ragweed allergen-induced allergic inflammation in mice. We show that a synthetic bicyclic nucleotide is recognized in the C position of a CpG dinucleotide by immune cells from diverse vertebrate species without bias for flanking sequences, suggesting a divergent nucleotide motif recognition pattern of TLR9.

  19. Antimalarial activity of synthetic 1,2,4-trioxanes and cyclic peroxy ketals, a quantum similarity study

    NASA Astrophysics Data System (ADS)

    Gironés, X.; Gallegos, A.; Carbó-Dorca, R.

    2001-12-01

    In this work, the antimalarial activity of two series of 20 and 7 synthetic 1,2,4-trioxanes and a set of 20 cyclic peroxy ketals are tested for correlation search by means of Molecular Quantum Similarity Measures (MQSM). QSAR models, dealing with different biological responses (IC90, IC50 and ED90) of the parasite Plasmodium Falciparum, are constructed using MQSM as molecular descriptors and are satisfactorily correlated. The statistical results of the 20 1,2,4-trioxanes are deeply analyzed to elucidate the relevant structural features in the biological activity, revealing the importance of phenyl substitutions.

  20. Physical therapy activities in stroke, knee arthroplasty, and traumatic brain injury rehabilitation: their variation, similarities, and association with functional outcomes.

    PubMed

    DeJong, Gerben; Hsieh, Ching-Hui; Putman, Koen; Smout, Randall J; Horn, Susan D; Tian, Wenqiang

    2011-12-01

    The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. This was a prospective observational cohort study. The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. The study focused primarily on physical therapy without

  1. Physical Therapy Activities in Stroke, Knee Arthroplasty, and Traumatic Brain Injury Rehabilitation: Their Variation, Similarities, and Association With Functional Outcomes

    PubMed Central

    Hsieh, Ching-Hui; Putman, Koen; Smout, Randall J.; Horn, Susan D.; Tian, Wenqiang

    2011-01-01

    Background The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. Objective The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. Design This was a prospective observational cohort study. Methods The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. Results All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. Limitations The study

  2. Fusion of Protegrin-1 and Plectasin to MAP30 Shows Significant Inhibition Activity against Dengue Virus Replication

    PubMed Central

    Rothan, Hussin A.; Bahrani, Hirbod; Mohamed, Zulqarnain; Abd Rahman, Noorsaadah; Yusof, Rohana

    2014-01-01

    Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities. PMID:24722532

  3. The pronociceptive dorsal reticular nucleus contains mostly tonic neurons and shows a high prevalence of spontaneous activity in block preparation.

    PubMed

    Sousa, Mafalda; Szucs, Peter; Lima, Deolinda; Aguiar, Paulo

    2014-04-01

    Despite the importance and significant clinical impact of understanding information processing in the nociceptive system, the functional properties of neurons in many parts of this system are still unknown. In this work we performed whole cell patch-clamp recording in rat brain stem blocks to characterize the electrophysiological properties of neurons in the dorsal reticular nucleus (DRt), a region known to be involved in pronociceptive modulation. We also compared properties of DRt neurons with those in the adjacent parvicellular reticular nucleus and in neighboring regions outside the reticular formation. We found that neurons in the DRt and parvicellular reticular nucleus had similar electrophysiological properties and exhibited mostly toniclike firing patterns, whereas neurons outside the reticular formation showed a larger diversity of firing patterns. Interestingly, more than one-half of the neurons also showed spontaneous activity. While the general view of the reticular formation, being a loosely associated mesh of groups of neurons with diverse function, and earlier reports suggests more electrophysiological heterogeneity, we showed that this is indeed not the case. Our results indicate that functional difference of neurons in the reticular formation may mostly be determined by their connectivity profiles and not by their intrinsic electrophysiological properties. The dominance of tonic neurons in the DRt supports previous conclusions that these neurons encode stimulus intensity through their firing frequency, while the high prevalence of spontaneous activity most likely shapes nociceptive modulation by this brain stem region.

  4. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase.

    PubMed

    Abrahim, Noor Nazirahanie; Kanthimathi, M S; Abdul-Aziz, Azlina

    2012-11-15

    Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense

  5. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

    PubMed Central

    2012-01-01

    Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells

  6. Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis.

    PubMed

    Dewei, Song; Min, Chen; Haiming, Cheng

    2016-11-01

    Candida rugosa lipases were immobilized onto collagen fibers through glutaraldehyde cross-linking method. The immobilization process has been optimized. Under the optimal immobilization conditions, the activity of the collagen-immobilized lipase reached 340 U/g. The activity was recovered of 28.3 % by immobilization. The operational stability of the obtained collagen-immobilized lipase for hydrolysis of olive oil emulsion was determined. The collagen-immobilized lipase showed good tolerance to temperature and pH variations in comparison to free lipase. The collagen-immobilized lipase was also applied as biocatalyst for synthesis of butyl butyrate from butyric acid and 1-butanol in n-hexane. The conversion yield was 94 % at the optimal conditions. Of its initial activity, 64 % was retained after 5 cycles for synthesizing butyl butyrate in n-hexane.

  7. A brain phantom for motion-corrected PROPELLER showing image contrast and construction similar to those of in vivo MRI.

    PubMed

    Saotome, Kousaku; Matsushita, Akira; Matsumoto, Koji; Kato, Yoshiaki; Nakai, Kei; Murata, Koichi; Yamamoto, Tetsuya; Sankai, Yoshiyuki; Matsumura, Akira

    2017-02-01

    A fast spin-echo sequence based on the Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) technique is a magnetic resonance (MR) imaging data acquisition and reconstruction method for correcting motion during scans. Previous studies attempted to verify the in vivo capabilities of motion-corrected PROPELLER in real clinical situations. However, such experiments are limited by repeated, stray head motion by research participants during the prescribed and precise head motion protocol of a PROPELLER acquisition. Therefore, our purpose was to develop a brain phantom set for motion-corrected PROPELLER. The profile curves of the signal intensities on the in vivo T 2 -weighted image (T 2 WI) and 3-D rapid prototyping technology were used to produce the phantom. In addition, we used a homemade driver system to achieve in-plane motion at the intended timing. We calculated the Pearson's correlation coefficient (R 2 ) between the signal intensities of the in vivo T 2 WI and the phantom T 2 WI and clarified the rotation precision of the driver system. In addition, we used the phantom set to perform initial experiments to show the rotational angle and frequency dependences of PROPELLER. The in vivo and phantom T 2 WIs were visually congruent, with a significant correlation (R 2 ) of 0.955 (p<.001). The rotational precision of the driver system was within 1 degree of tolerance. The experiment on the rotational angle dependency showed image discrepancies between the rotational angles. The experiment on the rotational frequency dependency showed that the reconstructed images became increasingly blurred by the corruption of the blades as the number of motions increased. In this study, we developed a phantom that showed image contrasts and construction similar to the in vivo T 2 WI. In addition, our homemade driver system achieved precise in-plane motion at the intended timing. Our proposed phantom set could perform systematic experiments with a

  8. Surface similarity-based molecular query-retrieval

    PubMed Central

    Singh, Rahul

    2007-01-01

    Background Discerning the similarity between molecules is a challenging problem in drug discovery as well as in molecular biology. The importance of this problem is due to the fact that the biochemical characteristics of a molecule are closely related to its structure. Therefore molecular similarity is a key notion in investigations targeting exploration of molecular structural space, query-retrieval in molecular databases, and structure-activity modelling. Determining molecular similarity is related to the choice of molecular representation. Currently, representations with high descriptive power and physical relevance like 3D surface-based descriptors are available. Information from such representations is both surface-based and volumetric. However, most techniques for determining molecular similarity tend to focus on idealized 2D graph-based descriptors due to the complexity that accompanies reasoning with more elaborate representations. Results This paper addresses the problem of determining similarity when molecules are described using complex surface-based representations. It proposes an intrinsic, spherical representation that systematically maps points on a molecular surface to points on a standard coordinate system (a sphere). Molecular surface properties such as shape, field strengths, and effects due to field super-positioningcan then be captured as distributions on the surface of the sphere. Surface-based molecular similarity is subsequently determined by computing the similarity of the surface-property distributions using a novel formulation of histogram-intersection. The similarity formulation is not only sensitive to the 3D distribution of the surface properties, but is also highly efficient to compute. Conclusion The proposed method obviates the computationally expensive step of molecular pose-optimisation, can incorporate conformational variations, and facilitates highly efficient determination of similarity by directly comparing molecular surfaces

  9. Characterization of a gene family abundantly expressed in Oenothera organensis pollen that shows sequence similarity to polygalacturonase.

    PubMed Central

    Brown, S M; Crouch, M L

    1990-01-01

    We have isolated and characterized cDNA clones of a gene family (P2) expressed in Oenothera organensis pollen. This family contains approximately six to eight family members and is expressed at high levels only in pollen. The predicted protein sequence from a near full-length cDNA clone shows that the protein products of these genes are at least 38,000 daltons. We identified the protein encoded by one of the cDNAs in this family by using antibodies to beta-galactosidase/pollen cDNA fusion proteins. Immunoblot analysis using these antibodies identifies a family of proteins of approximately 40 kilodaltons that is present in mature pollen, indicating that these mRNAs are not stored solely for translation after pollen germination. These proteins accumulate late in pollen development and are not detectable in other parts of the plant. Although not present in unpollinated or self-pollinated styles, the 40-kilodalton to 45-kilodalton antigens are detectable in extracts from cross-pollinated styles, suggesting that the proteins are present in pollen tubes growing through the style during pollination. The proteins are also present in pollen tubes growing in vitro. Both nucleotide and amino acid sequences are similar to the published sequences for cDNAs encoding the enzyme polygalacturonase, which suggests that the P2 gene family may function in depolymerizing pectin during pollen development, germination, and tube growth. Cross-hybridizing RNAs and immunoreactive proteins were detected in pollen from a wide variety of plant species, which indicates that the P2 family of polygalacturonase-like genes are conserved and may be expressed in the pollen from many angiosperms. PMID:2152116

  10. Use of similarity scoring in the development of oral solid dosage forms.

    PubMed

    Ferreira, Ana P; Olusanmi, Dolapo; Sprockel, Omar; Abebe, Admassu; Nikfar, Faranak; Tobyn, Mike

    2016-12-05

    In the oral solid dosage form space, material physical properties have a strong impact on the behaviour of the formulation during processing. The ability to identify materials with similar characteristics (and thus expected to exhibit similar behaviour) within the company's portfolio can help accelerate drug development by enabling early assessment and prediction of potential challenges associated with the powder properties of a new active pharmaceutical ingredient. Such developments will aid the production of robust dosage forms, in an efficient manner. Similarity scoring metrics are widely used in a number of scientific fields. This study proposes a practical implementation of this methodology within pharmaceutical development. The developed similarity metrics is based on the Mahalanobis distance. Scanning electron microscopy was used to confirm morphological similarity between the reference material and the closest matches identified by the metrics proposed. The results show that the metrics proposed are able to successfully identify material with similar physical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Marital assortment for genetic similarity.

    PubMed

    Eckman, Ronael E; Williams, Robert; Nagoshi, Craig

    2002-10-01

    The present study involved analyses of a Caucasian American sample (n=949) and a Japanese American sample (n=400) for factors supporting Genetic Similarity Theory (GST). The analyses found no evidence for the presence of genetic similarity between spouses in either sample for the blood group analyses of nine loci. All results indicated random mating for blood group genes. The results did not provide consistent substantial support to show that spousal similarity is correlated with the degree of genetic component of a trait for a set of seventeen individual differences variables, with only the Caucasian sample yielding significant correlations for this analysis. A third analysis examining the correlation between presence of spousal genetic similarity and spousal similarity on observable traits was not performed because spousal genetic similarity was not observed in either sample. The overall implication of the study is that GST is not supported as an explanation for spousal similarity in humans.

  12. Tax-1 and Tax-2 similarities and differences: focus on post-translational modifications and NF-κB activation

    PubMed Central

    Shirinian, Margret; Kfoury, Youmna; Dassouki, Zeina; El-Hajj, Hiba; Bazarbachi, Ali

    2013-01-01

    Although human T cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2) share similar genetic organization, they have major differences in their pathogenesis and disease manifestation. HTLV-1 is capable of transforming T lymphocytes in infected patients resulting in adult T cell leukemia/lymphoma whereas HTLV-2 is not clearly associated with lymphoproliferative diseases. Numerous studies have provided accumulating evidence on the involvement of the viral transactivators Tax-1 versus Tax-2 in T cell transformation. Tax-1 is a potent transcriptional activator of both viral and cellular genes. Tax-1 post-translational modifications and specifically ubiquitylation and SUMOylation have been implicated in nuclear factor-kappaB (NF-κB) activation and may contribute to its transformation capacity. Although Tax-2 has similar protein structure compared to Tax-1, the two proteins display differences both in their protein–protein interaction and activation of signal transduction pathways. Recent studies on Tax-2 have suggested ubiquitylation and SUMOylation independent mechanisms of NF-κB activation. In this present review, structural and functional differences between Tax-1 and Tax-2 will be summarized. Specifically, we will address their subcellular localization, nuclear trafficking and their effect on cellular regulatory proteins. A special attention will be given to Tax-1/Tax-2 post-translational modification such as ubiquitylation, SUMOylation, phosphorylation, acetylation, NF-κB activation, and protein–protein interactions involved in oncogenecity both in vivo and in vitro. PMID:23966989

  13. Show Yourself, Asparaginase: An Enzymatic Reaction Explained through a Hands-On Interactive Activity

    PubMed Central

    2017-01-01

    Determining the catalytic activity of an enzyme can be the perfect method for its identification, for example during purification procedures or for isolation purposes. Herein, we used a pharmaceutically relevant protein to bring the concept of enzymatic activity to the classroom. We designed a hands-on interactive activity in which a medically relevant enzyme, asparaginase, was distinguished from a nonenzymatic protein based on its specific enzymatic activity. The experiment was carried out in the classroom, designed to impact different educational levels from elementary to high school. Our main purposes were to promote the emerging field of protein-based drugs as a source of scientific careers in bionanotechnology and to show the students an image of a “scientist” as that of a common and educated person working in an exciting profession. In addition of being inexpensive, this activity proved to be adaptable for various educational levels and can be easily implemented in different scenarios, for example, scientific fairs, some schools, and so forth. PMID:29599566

  14. Do false belief and verb non-factivity share similar neural circuits?

    PubMed

    Chen, Lan; Cheung, Him; Szeto, Ching-Yee; Zhu, Zude; Wang, Suiping

    2012-02-21

    The present study investigates whether the complement falsity elicited by strong non-factive verbs and the false belief activated by a standard nonverbal false belief task produce similar electrophysiological activities in the brain. The hypothesis is based on the notion that both complement falsity and false belief involve decoupling a false mental representation from reality. Some previous studies have reported a behavioral correlation between children's false belief reasoning and interpretation of strong non-factive verbs together with their false complements, but a neural basis for this correlation has not been found. Our event-related potential (ERP) results with normal adults showed that both nonverbal false belief and strong non-factive verb comprehension elicited a negative late slow waveform divergence compared to their respective baselines. Although these slow waves due to the two types of stimuli had slightly different scalp distributions, both were regarded as reflecting primarily frontal activation. Such ERP similarity provides evidence for a common neural basis shared by nonverbal false belief reasoning and comprehension of strong non-factive verbs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Antiaflatoxigenic and Antimicrobial Activities of Schiff Bases of 2-Hydroxy-4-methoxybenzaldehyde, Cinnamaldehyde, and Similar Aldehydes.

    PubMed

    Harohally, Nanishankar V; Cherita, Chris; Bhatt, Praveena; Anu Appaiah, K A

    2017-10-11

    2-Hydroxy-4-methoxybenzaldehyde (HMBA) is a nontoxic phenolic flavor from dietary source Decalipus hamiltonii and Hemidesmus indicus. HMBA is an excellent antimicrobial agent with additional antiaflatoxigenic potency. On the other hand, cinnamaldehyde from cinnamon is a widely employed flavor with significant antiaflatoxigenic activity. We have attempted the enhancement of antiaflatoxigenic and antimicrobial properties of HMBA, cinnamaldehyde, and similar molecules via Schiff base formation accomplished from condensation reaction with amino sugar (d-glucamine). HMBA derived Schiff bases exhibited commendable antiaflatoxigenic activity at the concentration 0.1 mg/mL resulting in 9.6 ± 1.9% growth of Aspergillus flavus and subsequent 91.4 ± 3.9% reduction of aflatoxin B 1 with respect to control.

  16. Detecting distortion: bridging visual and quantitative reasoning on similarity tasks

    NASA Astrophysics Data System (ADS)

    Cox, Dana C.; Lo, Jane-Jane

    2014-03-01

    This study is focused on identifying and describing the reasoning patterns of middle grade students when examining potentially similar figures. Described here is a framework that includes 11 strategies that students used during clinical interview to differentiate similar and non-similar figures. Two factors were found to influence the strategies students selected: the complexity of the figures being compared and the type of distortion present in nonsimilar pairings. Data from this study support the theory that distortions are identified as a dominant property of figures and that students use the presence and absence of distortion to visually decide if two figures are similar. Furthermore, this study shows that visual reasoning is not as primitive or nonconstructive as represented in earlier literature and supports students who are developing numeric reasoning strategies. This illuminates possible pathways students may take when advancing from using visual and additive reasoning strategies to using multiplicative proportional reasoning on similarity tasks. In particular, distortion detection is a visual activity that enables students to reflect upon and evaluate the validity and accuracy of differentiation and quantify perceived relationships leading to ratio. This study has implications for curriculum developers as well as future research.

  17. Assessing similarity analysis of chromatographic fingerprints of Cyclopia subternata extracts as potential screening tool for in vitro glucose utilisation.

    PubMed

    Schulze, Alexandra E; De Beer, Dalene; Mazibuko, Sithandiwe E; Muller, Christo J F; Roux, Candice; Willenburg, Elize L; Nyunaï, Nyemb; Louw, Johan; Manley, Marena; Joubert, Elizabeth

    2016-01-01

    Similarity analysis of the phenolic fingerprints of a large number of aqueous extracts of Cyclopia subternata, obtained by high-performance liquid chromatography (HPLC), was evaluated as a potential tool to screen extracts for relative bioactivity. The assessment was based on the (dis)similarity of their fingerprints to that of a reference active extract of C. subternata, proven to enhance glucose uptake in vitro and in vivo. In vitro testing of extracts, selected as being most similar (n = 5; r ≥ 0.962) and most dissimilar (n = 5; r ≤ 0.688) to the reference active extract, showed that no clear pattern in terms of relative glucose uptake efficacy in C2C12 myocytes emerged, irrespective of the dose. Some of the most dissimilar extracts had higher glucose-lowering activity than the reference active extract. Principal component analysis revealed the major compounds responsible for the most variation within the chromatographic fingerprints, as mangiferin, isomangiferin, iriflophenone-3-C-β-D-glucoside-4-O-β-D-glucoside, iriflophenone-3-C-β-D-glucoside, scolymoside, and phloretin-3',5'-di-C-β-D-glucoside. Quantitative analysis of the selected extracts showed that the most dissimilar extracts contained the highest mangiferin and isomangiferin levels, whilst the most similar extracts had the highest scolymoside content. These compounds demonstrated similar glucose uptake efficacy in C2C12 myocytes. It can be concluded that (dis)similarity of chromatographic fingerprints of extracts of unknown activity to that of a proven bioactive extract does not necessarily translate to lower or higher bioactivity.

  18. Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

    PubMed

    Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

    2015-07-15

    The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Adding small differences can increase similarity and choice.

    PubMed

    Kim, Jongmin; Novemsky, Nathan; Dhar, Ravi

    2013-02-01

    Similarity plays a critical role in many judgments and choices. Traditional models of similarity posit that increasing the number of differences between objects cannot increase judged similarity between them. In contrast to these previous models, the present research shows that introducing a small difference in an attribute that previously was identical across objects can increase perceived similarity between those objects. We propose an explanation based on the idea that small differences draw more attention than identical attributes do and that people's perceptions of similarity involve averaging attributes that are salient. We provide evidence that introducing small differences between objects increases perceived similarity. We also show that an increase in similarity decreases the difficulty of choice and the likelihood that a choice will be deferred.

  20. Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy.

    PubMed

    Sideman, Noah; Chaitanya, Ganne; He, Xiaosong; Doucet, Gaelle; Kim, Na Young; Sperling, Michael R; Sharan, Ashwini D; Tracy, Joseph I

    2018-04-01

    In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several

  1. Structural analysis of the alcohol acyltransferase protein family from Cucumis melo shows that enzyme activity depends on an essential solvent channel.

    PubMed

    Galaz, Sebastián; Morales-Quintana, Luis; Moya-León, María Alejandra; Herrera, Raúl

    2013-03-01

    Alcohol acyltransferases (AAT) play a key role in ester biosynthesis. In Cucumis melo var. cantalupensis, AATs are encoded by a gene family of four members (CmAAT1-4). CmAAT1, CmAAT3 and CmAAT4 are capable of synthesizing esters, with CmAAT1 the most active. CmAAT2 is inactive and has an Ala268 residue instead of a threonine which is present in all other active AATs, although the role of this residue is still unclear. The present work aims to understand the molecular mechanism involved in ester biosynthesis in melon fruit and to clarify the importance of the Ala268 residue. First, structural models for each protein were built by comparative modelling methodology. Afterwards, conformational interaction between the protein and several ligands, alcohols and acyl-CoAs was explored by molecular docking and molecular dynamics simulation. Structural analysis showed that CmAATs share a similar structure. Also, well-defined solvent channels were described in the CmAATs except for CmAAT2 which does not have a proper channel and instead has a small pocket around Ala268. Residues of the catalytic HxxxD motif interact with substrates within the solvent channel, with Ser363 also important. Strong binding interaction energies were described for the best substrate couple of each CmAAT (hexyl-, benzyl- and cinnamyl-acetate for CmAAT1, 3 and 4 respectively). CmAAT1 and CmAAT2 protein surfaces share similar electrostatic potentials; nevertheless the entrance channels for the substrates differ in location and electrostatic character, suggesting that Ala268 might be responsible for that. This could partly explain the major differences in activity reported for these two enzymes. © 2013 The Authors Journal compilation © 2013 FEBS.

  2. Psychoacoustic Tinnitus Loudness and Tinnitus-Related Distress Show Different Associations with Oscillatory Brain Activity

    PubMed Central

    Balkenhol, Tobias; Wallhäusser-Franke, Elisabeth; Delb, Wolfgang

    2013-01-01

    Background The phantom auditory perception of subjective tinnitus is associated with aberrant brain activity as evidenced by magneto- and electroencephalographic studies. We tested the hypotheses (1) that psychoacoustically measured tinnitus loudness is related to gamma oscillatory band power, and (2) that tinnitus loudness and tinnitus-related distress are related to distinct brain activity patterns as suggested by the distinction between loudness and distress experienced by tinnitus patients. Furthermore, we explored (3) how hearing impairment, minimum masking level, and (4) psychological comorbidities are related to spontaneous oscillatory brain activity in tinnitus patients. Methods and Findings Resting state oscillatory brain activity recorded electroencephalographically from 46 male tinnitus patients showed a positive correlation between gamma band oscillations and psychoacoustic tinnitus loudness determined with the reconstructed tinnitus sound, but not with the other psychoacoustic loudness measures that were used. Tinnitus-related distress did also correlate with delta band activity, but at electrode positions different from those associated with tinnitus loudness. Furthermore, highly distressed tinnitus patients exhibited a higher level of theta band activity. Moreover, mean hearing loss between 0.125 kHz and 16 kHz was associated with a decrease in gamma activity, whereas minimum masking levels correlated positively with delta band power. In contrast, psychological comorbidities did not express significant correlations with oscillatory brain activity. Conclusion Different clinically relevant tinnitus characteristics show distinctive associations with spontaneous brain oscillatory power. Results support hypothesis (1), but exclusively for the tinnitus loudness derived from matching to the reconstructed tinnitus sound. This suggests to preferably use the reconstructed tinnitus spectrum to determine psychoacoustic tinnitus loudness. Results also support

  3. Calcium imaging in the ant Camponotus fellah reveals a conserved odour-similarity space in insects and mammals

    PubMed Central

    2010-01-01

    Background Olfactory systems create representations of the chemical world in the animal brain. Recordings of odour-evoked activity in the primary olfactory centres of vertebrates and insects have suggested similar rules for odour processing, in particular through spatial organization of chemical information in their functional units, the glomeruli. Similarity between odour representations can be extracted from across-glomerulus patterns in a wide range of species, from insects to vertebrates, but comparison of odour similarity in such diverse taxa has not been addressed. In the present study, we asked how 11 aliphatic odorants previously tested in honeybees and rats are represented in the antennal lobe of the ant Camponotus fellah, a social insect that relies on olfaction for food search and social communication. Results Using calcium imaging of specifically-stained second-order neurons, we show that these odours induce specific activity patterns in the ant antennal lobe. Using multidimensional analysis, we show that clustering of odours is similar in ants, bees and rats. Moreover, odour similarity is highly correlated in all three species. Conclusion This suggests the existence of similar coding rules in the neural olfactory spaces of species among which evolutionary divergence happened hundreds of million years ago. PMID:20187931

  4. An electrophysiological signature of summed similarity in visual working memory.

    PubMed

    van Vugt, Marieke K; Sekuler, Robert; Wilson, Hugh R; Kahana, Michael J

    2013-05-01

    Summed-similarity models of short-term item recognition posit that participants base their judgments of an item's prior occurrence on that item's summed similarity to the ensemble of items on the remembered list. We examined the neural predictions of these models in 3 short-term recognition memory experiments using electrocorticographic/depth electrode recordings and scalp electroencephalography. On each experimental trial, participants judged whether a test face had been among a small set of recently studied faces. Consistent with summed-similarity theory, participants' tendency to endorse a test item increased as a function of its summed similarity to the items on the just-studied list. To characterize this behavioral effect of summed similarity, we successfully fit a summed-similarity model to individual participant data from each experiment. Using the parameters determined from fitting the summed-similarity model to the behavioral data, we examined the relation between summed similarity and brain activity. We found that 4-9 Hz theta activity in the medial temporal lobe and 2-4 Hz delta activity recorded from frontal and parietal cortices increased with summed similarity. These findings demonstrate direct neural correlates of the similarity computations that form the foundation of several major cognitive theories of human recognition memory. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  5. Neural pattern similarity underlies the mnemonic advantages for living words.

    PubMed

    Xiao, Xiaoqian; Dong, Qi; Chen, Chuansheng; Xue, Gui

    2016-06-01

    It has been consistently shown that words representing living things are better remembered than words representing nonliving things, yet the underlying cognitive and neural mechanisms have not been clearly elucidated. The present study used both univariate and multivariate pattern analyses to examine the hypotheses that living words are better remembered because (1) they draw more attention and/or (2) they share more overlapping semantic features. Subjects were asked to study a list of living and nonliving words during a semantic judgment task. An unexpected recognition test was administered 30 min later. We found that subjects recognized significantly more living words than nonliving words. Results supported the overlapping semantic feature hypothesis by showing that (a) semantic ratings showed greater semantic similarity for living words than for nonliving words, (b) there was also significantly greater neural global pattern similarity (nGPS) for living words than for nonliving words in the posterior portion of left parahippocampus (LpPHG), (c) the nGPS in the LpPHG reflected the rated semantic similarity, and also mediated the memory differences between two semantic categories, and (d) greater univariate activation was found for living words than for nonliving words in the left hippocampus (LHIP), which mediated the better memory performance for living words and might reflect greater semantic context binding. In contrast, although living words were processed faster and elicited a stronger activity in the dorsal attention network, these differences did not mediate the animacy effect in memory. Taken together, our results provide strong support to the overlapping semantic features hypothesis, and emphasize the important role of semantic organization in episodic memory encoding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities.

    PubMed

    Ohtana, Yuki; Abdullah, Azian Azamimi; Altaf-Ul-Amin, Md; Huang, Ming; Ono, Naoaki; Sato, Tetsuo; Sugiura, Tadao; Horai, Hisayuki; Nakamura, Yukiko; Morita Hirai, Aki; Lange, Klaus W; Kibinge, Nelson K; Katsuragi, Tetsuo; Shirai, Tsuyoshi; Kanaya, Shigehiko

    2014-12-01

    Developing database systems connecting diverse species based on omics is the most important theme in big data biology. To attain this purpose, we have developed KNApSAcK Family Databases, which are utilized in a number of researches in metabolomics. In the present study, we have developed a network-based approach to analyze relationships between 3D structure and biological activity of metabolites consisting of four steps as follows: construction of a network of metabolites based on structural similarity (Step 1), classification of metabolites into structure groups (Step 2), assessment of statistically significant relations between structure groups and biological activities (Step 3), and 2-dimensional clustering of the constructed data matrix based on statistically significant relations between structure groups and biological activities (Step 4). Applying this method to a data set consisting of 2072 secondary metabolites and 140 biological activities reported in KNApSAcK Metabolite Activity DB, we obtained 983 statistically significant structure group-biological activity pairs. As a whole, we systematically analyzed the relationship between 3D-chemical structures of metabolites and biological activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Serving Up Activities for TV Cooking Shows.

    ERIC Educational Resources Information Center

    Katchen, Johanna E.

    This paper documents a presentation given on the use of English-language television cooking shows in English-as-a-Second-Language (ESL) and English-as-a-Foreign-Language (EFL) classrooms in Taiwan. Such shows can be ideal for classroom use, since they have a predictable structure consisting of short segments, are of interest to most students,…

  8. Scale-Similar Models for Large-Eddy Simulations

    NASA Technical Reports Server (NTRS)

    Sarghini, F.

    1999-01-01

    Scale-similar models employ multiple filtering operations to identify the smallest resolved scales, which have been shown to be the most active in the interaction with the unresolved subgrid scales. They do not assume that the principal axes of the strain-rate tensor are aligned with those of the subgrid-scale stress (SGS) tensor, and allow the explicit calculation of the SGS energy. They can provide backscatter in a numerically stable and physically realistic manner, and predict SGS stresses in regions that are well correlated with the locations where large Reynolds stress occurs. In this paper, eddy viscosity and mixed models, which include an eddy-viscosity part as well as a scale-similar contribution, are applied to the simulation of two flows, a high Reynolds number plane channel flow, and a three-dimensional, nonequilibrium flow. The results show that simulations without models or with the Smagorinsky model are unable to predict nonequilibrium effects. Dynamic models provide an improvement of the results: the adjustment of the coefficient results in more accurate prediction of the perturbation from equilibrium. The Lagrangian-ensemble approach [Meneveau et al., J. Fluid Mech. 319, 353 (1996)] is found to be very beneficial. Models that included a scale-similar term and a dissipative one, as well as the Lagrangian ensemble averaging, gave results in the best agreement with the direct simulation and experimental data.

  9. 36 CFR 3.12 - May I use a vessel to tow a person for water skiing or other similar activities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.12 May I use a vessel to tow a person for water skiing or other similar activities? (a) The towing of a person... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false May I use a vessel to tow a...

  10. 36 CFR 3.12 - May I use a vessel to tow a person for water skiing or other similar activities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.12 May I use a vessel to tow a person for water skiing or other similar activities? (a) The towing of a person... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false May I use a vessel to tow a...

  11. Anxiety patients show reduced working memory related dlPFC activation during safety and threat

    PubMed Central

    Balderston, Nicholas L.; Vytal, Katherine E.; O’Connell, Katherine; Torrisi, Salvatore; Letkiewicz, Allison; Ernst, Monique; Grillon, Christian

    2016-01-01

    Background Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these deficits reflect threat-related processes or symptoms of the disorder. Here we distinguish between these hypotheses by determining the effect of shock threat vs. safety on the neural substrates of WM performance in anxiety patients and healthy controls. Methods Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N-back WM task during periods of safety and threat of shock. We recorded BOLD activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load-related BOLD activation. Results Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load-related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load-related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat. Conclusions This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat. PMID:27110997

  12. High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict Compound Activity.

    PubMed

    De Wolf, Hans; Cougnaud, Laure; Van Hoorde, Kirsten; De Bondt, An; Wegner, Joerg K; Ceulemans, Hugo; Göhlmann, Hinrich

    2018-04-01

    By adding biological information, beyond the chemical properties and desired effect of a compound, uncharted compound areas and connections can be explored. In this study, we add transcriptional information for 31K compounds of Janssen's primary screening deck, using the HT L1000 platform and assess (a) the transcriptional connection score for generating compound similarities, (b) machine learning algorithms for generating target activity predictions, and (c) the scaffold hopping potential of the resulting hits. We demonstrate that the transcriptional connection score is best computed from the significant genes only and should be interpreted within its confidence interval for which we provide the stats. These guidelines help to reduce noise, increase reproducibility, and enable the separation of specific and promiscuous compounds. The added value of machine learning is demonstrated for the NR3C1 and HSP90 targets. Support Vector Machine models yielded balanced accuracy values ≥80% when the expression values from DDIT4 & SERPINE1 and TMEM97 & SPR were used to predict the NR3C1 and HSP90 activity, respectively. Combining both models resulted in 22 new and confirmed HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and pyrazolo-pyrimidine), which could potentially be of interest in the treatment of depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while leaving its chaperone, HSP90, unaffected). As such, the initial hit rate increased by a factor 300, as less, but more specific chemistry could be screened, based on the upfront computed activity predictions.

  13. Multiple search methods for similarity-based virtual screening: analysis of search overlap and precision

    PubMed Central

    2011-01-01

    Background Data fusion methods are widely used in virtual screening, and make the implicit assumption that the more often a molecule is retrieved in multiple similarity searches, the more likely it is to be active. This paper tests the correctness of this assumption. Results Sets of 25 searches using either the same reference structure and 25 different similarity measures (similarity fusion) or 25 different reference structures and the same similarity measure (group fusion) show that large numbers of unique molecules are retrieved by just a single search, but that the numbers of unique molecules decrease very rapidly as more searches are considered. This rapid decrease is accompanied by a rapid increase in the fraction of those retrieved molecules that are active. There is an approximately log-log relationship between the numbers of different molecules retrieved and the number of searches carried out, and a rationale for this power-law behaviour is provided. Conclusions Using multiple searches provides a simple way of increasing the precision of a similarity search, and thus provides a justification for the use of data fusion methods in virtual screening. PMID:21824430

  14. Perceiving similarity and comprehending metaphor.

    PubMed

    Marks, L E; Hammeal, R J; Bornstein, M H

    1987-01-01

    We conducted a series of 3 experiments to assess the comprehension of 4 types of cross-modal (synesthetic) similarities in nearly 500 3.5-13.5-year-old children and more than 100 adults. We tested both perceptual and verbal (metaphoric) modes. Children of all ages and adults matched pitch to brightness and loudness to brightness, thereby showing that even very young children recognize perceptual similarities between hearing and vision. Children did not consistently recognize similarity between pitch and size until about age 11. This difference in developmental timetables is compatible with the view that pitch-brightness and loudness-brightness similarities are intrinsic characteristics of perception (characteristics based, perhaps, on common sensory codes), whereas pitch-size similarity may be learned (perhaps through association of size with resonance properties). In a parallel verbal task, even 4-year-old children showed at least some capacity to translate meanings metaphorically from one modality to another (e.g., rating "low pitched" as dim and "high pitched" as bright). But not all literal meanings produced metaphoric equivalents in the youngest children (e.g., rating "sunlight" brighter but not louder than "moonlight"). Improvements with age in making metaphoric translations of synesthetic expressions paralleled increasing differentiation of meanings along literal dimensions and increasing capacity to integrate meanings of components in compound expressions. We postulate that perceptual knowledge about objects and events is represented in terms of locations in a multidimensional space; cross-modal similarities imply that the space is also multimodal. Verbal processes later gain access to this graded perceptual knowledge, thus permitting the interpretation of synesthetic metaphors according to the rules of cross-modal perception.

  15. Learning to distinguish similar objects

    NASA Astrophysics Data System (ADS)

    Seibert, Michael; Waxman, Allen M.; Gove, Alan N.

    1995-04-01

    This paper describes how the similarities and differences among similar objects can be discovered during learning to facilitate recognition. The application domain is single views of flying model aircraft captured in silhouette by a CCD camera. The approach was motivated by human psychovisual and monkey neurophysiological data. The implementation uses neural net processing mechanisms to build a hierarchy that relates similar objects to superordinate classes, while simultaneously discovering the salient differences between objects within a class. Learning and recognition experiments both with and without the class similarity and difference learning show the effectiveness of the approach on this visual data. To test the approach, the hierarchical approach was compared to a non-hierarchical approach, and was found to improve the average percentage of correctly classified views from 77% to 84%.

  16. Sensitivity to Relational Similarity and Object Similarity in Apes and Children.

    PubMed

    Christie, Stella; Gentner, Dedre; Call, Josep; Haun, Daniel Benjamin Moritz

    2016-02-22

    Relational reasoning is a hallmark of sophisticated cognition in humans. Does it exist in other primates? Despite some affirmative answers, there appears to be a wide gap in relational ability between humans and other primates--even other apes. Here, we test one possible explanation for this gap, motivated by developmental research showing that young humans often fail at relational reasoning tasks because they focus on objects instead of relations. When asked, "duck:duckling is like tiger:?," preschool children choose another duckling (object match) rather than a cub. If other apes share this focus on concrete objects, it could undermine their relational reasoning in similar ways. To test this, we compared great apes and 3-year-old humans' relational reasoning on the same spatial mapping task, with and without competing object matches. Without competing object matches, both children and Pan species (chimpanzees and bonobos) spontaneously used relational similarity, albeit children more so. But when object matches were present, only children responded strongly to them. We conclude that the relational gap is not due to great apes' preference for concrete objects. In fact, young humans show greater object focus than nonhuman apes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Trastuzumab-Resistant Luminal B Breast Cancer Cells Show Basal-Like Cell Growth Features Through NF-κB-Activation

    PubMed Central

    Kanzaki, Hirotaka; Mukhopadhya, Nishit K.; Cui, Xiaojiang; Ramanujan, V. Krishnan

    2016-01-01

    A major clinical problem in the treatment of breast cancer is mortality due to metastasis. Understanding the molecular mechanisms associated with metastasis should aid in designing new therapeutic approaches for breast cancer. Trastuzumab is the main therapeutic option for HER2+ breast cancer patients; however, the molecular basis for trastuzumab resistance (TZR) and subsequent metastasis is not known. Earlier, we found expression of basal-like molecular markers in TZR tissues from patients with invasive breast cancer.(1) The basal-like phenotype is a particularly aggressive form of breast cancer. This observation suggests that TZR might contribute to an aggressive phenotype. To understand if resistance to TZR can lead to basal-like phenotype, we generated a trastuzumab-resistant human breast cancer cell line (BT-474-R) that maintained human epidermal growth factor receptor 2 (HER2) overexpression and HER2 mediated signaling. Analysis showed that nuclear factor-kappa B (NF-κB) was constitutively activated in the BT-474-R cells, a feature similar to the basal-like tumor phenotype. Pharmacologic inhibition of NF-κB improved sensitivity of BT-474-R cells to trastuzumab. Interestingly, activation of HER2 independent NF-κB is not shown in luminal B breast cancer cells. Our study suggests that by activating the NF-κB pathway, luminal B cells may acquire a HER2+ basal-like phenotype in which NF-κB is constitutively activated; this notion is consistent with the recently proposed “progression through grade” or “evolution of resistance” hypothesis. Furthermore, we identified IKK-α/IKK-β and nuclear accumulation of RelA/p65 as the major determinants in the resistant cells. Thus our study additionally suggests that the nuclear accumulation of p65 may be a useful marker for identifying metastasis-initiating tumor cells and targeting RelA/p65 may limit metastasis of breast and other cancers associated with NF-κB activation. PMID:26871511

  18. Feline bone marrow-derived mesenchymal stromal cells (MSCs) show similar phenotype and functions with regards to neuronal differentiation as human MSCs.

    PubMed

    Munoz, Jessian L; Greco, Steven J; Patel, Shyam A; Sherman, Lauren S; Bhatt, Suresh; Bhatt, Rekha S; Shrensel, Jeffrey A; Guan, Yan-Zhong; Xie, Guiqin; Ye, Jiang-Hong; Rameshwar, Pranela; Siegel, Allan

    2012-09-01

    Mesenchymal stromal cells (MSCs) show promise for treatment of a variety of neurological and other disorders. Cat has a high degree of linkage with the human genome and has been used as a model for analysis of neurological disorders such as stroke, Alzheimer's disease and motor disorders. The present study was designed to characterize bone marrow-derived MSCs from cats and to investigate the capacity to generate functional peptidergic neurons. MSCs were expanded with cells from the femurs of cats and then characterized by phenotype and function. Phenotypically, feline and human MSCs shared surface markers, and lacked hematopoietic markers, with similar morphology. As compared to a subset of human MSCs, feline MSCs showed no evidence of the major histocompatibility class II. Since the literature suggested Stro-1 as an indicator of pluripotency, we compared early and late passages feline MSCs and found its expression in >90% of the cells. However, the early passage cells showed two distinct populations of Stro-1-expressing cells. At passage 5, the MSCs were more homogeneous with regards to Stro-1 expression. The passage 5 MSCs differentiated to osteogenic and adipogenic cells, and generated neurons with electrophysiological properties. This correlated with the expression of mature neuronal markers with concomitant decrease in stem cell-associated genes. At day 12 induction, the cells were positive for MAP2, Neuronal Nuclei, tubulin βIII, Tau and synaptophysin. This correlated with electrophysiological maturity as presented by excitatory postsynaptic potentials (EPSPs). The findings indicate that the cat may constitute a promising biomedical model for evaluation of novel therapies such as stem cell therapy in such neurological disorders as Alzheimer's disease and stroke. Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  19. Cranial measures and ancient DNA both show greater similarity of Neandertals to recent modern Eurasians than to recent modern sub-Saharan Africans.

    PubMed

    Relethford, John H; Smith, Fred H

    2018-05-01

    Ancient DNA analysis has shown that present-day humans of Eurasian ancestry are more similar to Neandertals than are present-day humans of sub-Saharan African ancestry, reflecting interbreeding after modern humans first left Africa. We use craniometric data to test the hypothesis that the crania of recent modern humans show the same pattern. We computed Mahalanobis squared distances between a published Neandertal centroid based on 37 craniometric traits and each of 2,413 recent modern humans from the Howells global data set (N = 373 sub-Saharan Africans, N = 2,040 individuals of Eurasian descent). The average distance to the Neandertal centroid is significantly lower for Eurasian crania than for sub-Saharan African crania as expected from the findings of ancient DNA (p < 0.001). This result holds when examining distances for separate geographic regions of humans of Eurasian descent (Europeans, Asians, Australasians, Native Americans, and Pacific Islanders). Most of these results are also seen when examining distances partitioning size and shape variation. Our results show that the genetic difference in Neandertal ancestry seen in the DNA of present-day sub-Saharan Africans and Eurasians is also found in patterns of recent modern human craniometric variation. © 2018 Wiley Periodicals, Inc.

  20. ASD Is Not DLI: Individuals With Autism and Individuals With Syntactic DLI Show Similar Performance Level in Syntactic Tasks, but Different Error Patterns.

    PubMed

    Sukenik, Nufar; Friedmann, Naama

    2018-01-01

    Do individuals with autism have a developmental syntactic impairment, DLI (formerly known as SLI)? In this study we directly compared the performance of 18 individuals with Autism Spectrum Disorder (ASD) aged 9;0-18;0 years with that of 93 individuals with Syntactic-Developmental Language Impairment (SyDLI) aged 8;8-14;6 (and with 166 typically-developing children aged 5;2-18;1). We tested them using three syntactic tests assessing the comprehension and production of syntactic structures that are known to be sensitive to syntactic impairment: elicitation of subject and object relative clauses, reading and paraphrasing of object relatives, and repetition of complex syntactic structures including Wh questions, relative clauses, topicalized sentences, sentences with verb movement, sentences with A-movement, and embedded sentences. The results were consistent across the three tasks: the overall rate of correct performance on the syntactic tasks is similar for the children with ASD and those with SyDLI. However, once we look closer, they are very different. The types of errors of the ASD group differ from those of the SyDLI group-the children with ASD provide various types of pragmatically infelicitous responses that are not evinced in the SyDLI or in the age equivalent typically-developing groups. The two groups (ASD and SyDLI) also differ in the pattern of performance-the children with SyDLI show a syntactically-principled pattern of impairment, with selective difficulty in specific sentence types (such as sentences derived by movement of the object across the subject), and normal performance on other structures (such as simple sentences). In contrast, the ASD participants showed generalized low performance on the various sentence structures. Syntactic performance was far from consistent within the ASD group. Whereas all ASD participants had errors that can originate in pragmatic/discourse difficulties, seven of them had completely normal syntax in the structures we

  1. ASD Is Not DLI: Individuals With Autism and Individuals With Syntactic DLI Show Similar Performance Level in Syntactic Tasks, but Different Error Patterns

    PubMed Central

    Sukenik, Nufar; Friedmann, Naama

    2018-01-01

    Do individuals with autism have a developmental syntactic impairment, DLI (formerly known as SLI)? In this study we directly compared the performance of 18 individuals with Autism Spectrum Disorder (ASD) aged 9;0–18;0 years with that of 93 individuals with Syntactic-Developmental Language Impairment (SyDLI) aged 8;8–14;6 (and with 166 typically-developing children aged 5;2–18;1). We tested them using three syntactic tests assessing the comprehension and production of syntactic structures that are known to be sensitive to syntactic impairment: elicitation of subject and object relative clauses, reading and paraphrasing of object relatives, and repetition of complex syntactic structures including Wh questions, relative clauses, topicalized sentences, sentences with verb movement, sentences with A-movement, and embedded sentences. The results were consistent across the three tasks: the overall rate of correct performance on the syntactic tasks is similar for the children with ASD and those with SyDLI. However, once we look closer, they are very different. The types of errors of the ASD group differ from those of the SyDLI group—the children with ASD provide various types of pragmatically infelicitous responses that are not evinced in the SyDLI or in the age equivalent typically-developing groups. The two groups (ASD and SyDLI) also differ in the pattern of performance—the children with SyDLI show a syntactically-principled pattern of impairment, with selective difficulty in specific sentence types (such as sentences derived by movement of the object across the subject), and normal performance on other structures (such as simple sentences). In contrast, the ASD participants showed generalized low performance on the various sentence structures. Syntactic performance was far from consistent within the ASD group. Whereas all ASD participants had errors that can originate in pragmatic/discourse difficulties, seven of them had completely normal syntax in the

  2. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.

    PubMed

    Zhao, Genshi; Li, Wei-Ying; Chen, Daohong; Henry, James R; Li, Hong-Yu; Chen, Zhaogen; Zia-Ebrahimi, Mohammad; Bloem, Laura; Zhai, Yan; Huss, Karen; Peng, Sheng-Bin; McCann, Denis J

    2011-11-01

    The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.

  3. Developing rods transplanted into the degenerating retina of Crx-knockout mice exhibit neural activity similar to native photoreceptors

    PubMed Central

    Homma, Kohei; Okamoto, Satoshi; Mandai, Michiko; Gotoh, Norimoto; Rajasimha, Harsha K.; Chang, Yi-Sheng; Chen, Shan; Li, Wei; Cogliati, Tiziana; Swaroop, Anand; Takahashi, Masayo

    2013-01-01

    Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with GFP driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina, and exhibit Ca2+ responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within two weeks after transplantation into the retina of Crx-knockout mice, and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell replacement therapy. PMID:23495178

  4. A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa.

    PubMed

    Thakur, Rupamoni; Kumar, Ashok; Bose, Biplab; Panda, Dulal; Saikia, Debashree; Chattopadhyay, Pronobesh; Mukherjee, Ashis K

    2014-10-01

    Compounds showing dual inhibition of thrombin and factor Xa (FXa) are the subject of great interest owing to their broader specificity for effective anticoagulation therapy against cardiovascular disorders. This is the first report on the functional characterization and assessment of therapeutic potential of a 4423.6 Da inhibitory peptide (Ruviprase) purified from Daboia russelii russelii venom. The secondary structure of Ruviprase is composed of α-helices (61.9%) and random coils (38.1%). The partial N-terminal sequence (E(1)-V(2)-X(3)-W(4)-W(5)-W(6)-A(7)-Q(8)-L(9)-S(10)) of Ruviprase demonstrated significant similarity (80.0%) with an internal sequence of apoptosis-stimulating protein reported from the venom of Ophiophagus hannah and Python bivittatus; albeit Ruviprase did not show sequence similarity with existing thrombin/FXa inhibitors, suggesting its uniqueness. Ruviprase demonstrated a potent in vitro anticoagulant property and inhibited both thrombin and FXa following slow binding kinetics. Ruviprase inhibited thrombin by binding to its active site via an uncompetitive mechanism with a Ki value and dissociation constant (KD) of 0.42 μM and 0.46 μM, respectively. Conversely, Ruviprase demonstrated mixed inhibition (Ki = 0.16 μM) of FXa towards its physiological substrate prothrombin. Furthermore, the biological properties of Ruviprase could not be neutralized by commercial polyvalent or monovalent antivenom. Ruviprase at a dose of 2.0 mg/kg was non-toxic and showed potent in vivo anticoagulant activity after 6 h of intraperitoneal treatment in mice. Because of the potent anticoagulant property as well as non-toxic nature of Ruviprase, the possible application of the peptide as an antithrombotic agent for combating thrombosis-associated ailments appears promising. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Representation of Semantic Similarity in the Left Intraparietal Sulcus: Functional Magnetic Resonance Imaging Evidence

    PubMed Central

    Neyens, Veerle; Bruffaerts, Rose; Liuzzi, Antonietta G.; Kalfas, Ioannis; Peeters, Ronald; Keuleers, Emmanuel; Vogels, Rufin; De Deyne, Simon; Storms, Gert; Dupont, Patrick; Vandenberghe, Rik

    2017-01-01

    According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions that have been previously implicated in visuospatial attention, and how it compares to effects of object identity and location. Forty-six subjects participated. Subjects passively viewed pictures from two categories, musical instruments and vehicles. Semantic similarity between entities was estimated based on a concept-feature matrix obtained in more than 1,000 subjects. Visuoperceptual similarity was modeled based on the HMAX model, the AlexNet deep convolutional learning model, and thirdly, based on subjective visuoperceptual similarity ratings. Among the IPS regions examined, only left middle IPS showed a semantic similarity effect. The effect was significant in hIP1, hIP2, and hIP3. Visuoperceptual similarity did not correlate with similarity of activity patterns in left middle IPS. The semantic similarity effect in left middle IPS was significantly stronger than in the right middle IPS and also stronger than in the left or right posterior IPS. The semantic similarity effect was similar to that seen in the angular gyrus. Object identity effects were much more widespread across nearly all parietal areas examined. Location effects were relatively specific for posterior IPS and area 7 bilaterally. To conclude, the current findings replicate the semantic similarity effect in left middle IPS under passive viewing conditions, and demonstrate its anatomical specificity within a cytoarchitectonic reference frame. We propose that the semantic similarity effect in left middle IPS reflects the transient uploading of semantic representations in working memory. PMID:28824405

  6. Econo-ESA in semantic text similarity.

    PubMed

    Rahutomo, Faisal; Aritsugi, Masayoshi

    2014-01-01

    Explicit semantic analysis (ESA) utilizes an immense Wikipedia index matrix in its interpreter part. This part of the analysis multiplies a large matrix by a term vector to produce a high-dimensional concept vector. A similarity measurement between two texts is performed between two concept vectors with numerous dimensions. The cost is expensive in both interpretation and similarity measurement steps. This paper proposes an economic scheme of ESA, named econo-ESA. We investigate two aspects of this proposal: dimensional reduction and experiments with various data. We use eight recycling test collections in semantic text similarity. The experimental results show that both the dimensional reduction and test collection characteristics can influence the results. They also show that an appropriate concept reduction of econo-ESA can decrease the cost with minor differences in the results from the original ESA.

  7. 36 CFR 3.12 - May I use a vessel to tow a person for water skiing or other similar activities?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false May I use a vessel to tow a person for water skiing or other similar activities? 3.12 Section 3.12 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.12 May I use a vessel to tow a person for water skiing o...

  8. 36 CFR 3.12 - May I use a vessel to tow a person for water skiing or other similar activities?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false May I use a vessel to tow a person for water skiing or other similar activities? 3.12 Section 3.12 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.12 May I use a vessel to tow a person for water skiing o...

  9. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures

    PubMed Central

    Someswara Rao, Chinta; Viswanadha Raju, S.

    2016-01-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc. PMID:26981409

  10. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures.

    PubMed

    Someswara Rao, Chinta; Viswanadha Raju, S

    2016-03-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc.

  11. The plant G box promoter sequence activates transcription in Saccharomyces cerevisiae and is bound in vitro by a yeast activity similar to GBF, the plant G box binding factor.

    PubMed Central

    Donald, R G; Schindler, U; Batschauer, A; Cashmore, A R

    1990-01-01

    G box and I box sequences of the Arabidopsis thaliana ribulose-bisphosphate-1,5-carboxylase small subunit (RBCS) promoter are required for expression mediated by the Arabidopsis rbcS-1A promoter in transgenic tobacco plants and are bound in vitro by factors from plant nuclear extracts termed GBF and GA-1, respectively. We show here that a -390 to -60 rbcS-1A promoter fragment containing the G box and two I boxes activates transcription from a truncated iso-1-cytochrome c (CYC1) gene promoter in Saccharomyces cerevisiae. Mutagenesis of either the rbcS-1A G box or both I box sequences eliminated the expression mediated by this fragment. When polymerized, I box oligonucleotides were also capable of enhancing expression from the truncated CYC1 promoter. Single-copy G box sequences from the Arabidopsis rbcS-1A, Arabidopsis Adh and tomato rbcS-3A promoters were more potent activators and were used in mobility shift assays to identify a DNA binding activity in yeast functionally similar to GBF. In methylation interference experiments, the binding specificity of the yeast protein was indistinguishable from that obtained with plant nuclear extracts. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:2161333

  12. APETALA2 like genes from Picea abies show functional similarities to their Arabidopsis homologues.

    PubMed

    Nilsson, Lars; Carlsbecker, Annelie; Sundås-Larsson, Annika; Vahala, Tiina

    2007-02-01

    In angiosperm flower development the identity of the floral organs is determined by the A, B and C factors. Here we present the characterisation of three homologues of the A class gene APETALA2 (AP2) from the conifer Picea abies (Norway spruce), Picea abies APETALA2 LIKE1 (PaAP2L1), PaAP2L2 and PaAP2L3. Similar to AP2 these genes contain sequence motifs complementary to miRNA172 that has been shown to regulate AP2 in Arabidopsis. The genes display distinct expression patterns during plant development; in the female-cone bud PaAP2L1 and PaAP2L3 are expressed in the seed-bearing ovuliferous scale in a pattern complementary to each other, and overlapping with the expression of the C class-related gene DAL2. To study the function of PaAP2L1 and PaAP2L2 the genes were expressed in Arabidopsis. The transgenic PaAP2L2 plants were stunted and flowered later than control plants. Flowers were indeterminate and produced an excess of floral organs most severely in the two inner whorls, associated with an ectopic expression of the meristem-regulating gene WUSCHEL. No homeotic changes in floral-organ identities occurred, but in the ap2-1 mutant background PaAP2L2 was able to promote petal identity, indicating that the spruce AP2 gene has the capacity to substitute for an A class gene in Arabidopsis. In spite of the long evolutionary distance between angiosperms and gymnosperms and the fact that gymnosperms lack structures homologous to sepals and petals our data supports a functional conservation of AP2 genes among the seed plants.

  13. Mortality risk factors show similar trends in modern and historic populations exposed to plague.

    PubMed

    Rubini, Mauro; Gualdi-Russo, Emanuela; Manzon, Vanessa S; Rinaldo, Natascia; Bianucci, Raffaella

    2016-05-31

    Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered. The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted. The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults). Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

  14. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity.

    PubMed

    Amara, A A; El-Masry, M H; Bogdady, H H

    2008-04-01

    Screening active compounds from plants lead to discover new medicinal drugs which have efficient protection and treatment roles against various diseases including cancer. In our study, extracts from different plants represent seeds of: Gossypium barbadense, Ricinus communis, Sesamum indicum, Nigella sativa, Vinca rosea and Melia azedarah; fruits of: Xanthium occidental; flowers of: Atriplex nummularia; barks of: Cinnamomum zeylanicum; latex of: Ficus carica and rhizomes of: Curcuma longa and Zingiber officinale were tested in vivo using three subsequent bioassays: the BST (Brine Shrimp Toxicity bioassay), AWD (Agar well diffusion antimicrobial bioassay) and AtPDT (Agrobacterium tumefaciens Potato Disc Tumor bioassay). AWD technique omitted any extracts have antimicrobial activities while BST omitted any extract did not has physiological activity and determined the various LC(50) of each plant extract. For the first time, using a range of concentrations in the AtPDT modified protocol allowed the detection of tumor promotion caused by extract represented by A. nummularia. Using cluster analysis leads to classifying the different plant extracts activities to six groups regarding to their toxicity, antitumor activities and both of them. The extracts from edible plants represent 50% of the first and the second group which have the highest antitumor activities represented in F. caraica (group 1) and C. longa (group 2) as well as the non-edible plant extracts of Gossypium barbadense and Ricinus communis. A comparison study between the edible and herbaceous plants different extracts for their antitumor activities was performed. We recommended using the modified protocols used in this study for investigating more plants and using crude plant extracts which have antitumor activities in cancer treatment. Edible plants, which show in vivo antitumor activities, are recommended as save sources for antitumor compounds.

  15. Similarity of Mars and Mercury for terraforming and settling of people

    NASA Astrophysics Data System (ADS)

    Steklov, A. F.; Vidmachenko, A. P.

    2018-05-01

    We compared the main characteristics of the planets Mars and Mercury in the form normalized on the parameters of the planet Earth. Both planets turned out to be similar and close in terms of terraforming techniques, and conditions of comfortable human habitation in long term endo-planetary stations under the surface of a particular planetoid. Mars and Mercury also turned out to be similar on the vital activity of some other representatives of the Earth's biosphere. Our detailed analysis of the temperature distribution both over the entire surface of these planets, and in the conditions of their diurnal and annual variations on different latitudes and on Mars and on Mercury - showed that each of these planets has its advantages for the first terraforming.

  16. Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy.

    PubMed

    Bahia El Idrissi, N; Hakobyan, S; Ramaglia, V; Geluk, A; Morgan, B Paul; Das, P Kumar; Baas, F

    2016-06-01

    Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi-bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci-bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions. © 2016 British Society for Immunology.

  17. 2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib.

    PubMed

    Gohlke, Bjoern-Oliver; Overkamp, Tim; Richter, Anja; Richter, Antje; Daniel, Peter T; Gillissen, Bernd; Preissner, Robert

    2015-09-24

    Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral "multi-targeted" small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib.

  18. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

    NASA Astrophysics Data System (ADS)

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

    2016-05-01

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

  19. Hilar cholangiocarcinoma is pathologically similar to pancreatic duct adenocarcinoma: suggestions of similar background and development.

    PubMed

    Nakanuma, Yasuni; Sato, Yasunori

    2014-07-01

    Routine experiences suggest that cholangiocarcinomas (CCAs) show different clinicopathological behaviors along the biliary tree, and hilar CCA apparently resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for these similarities were reviewed. While all cases of PDAC, hilar CCA, intrahepatic CCA (ICCA) and CCA components of combined hepatocellular-cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular components and cuboidal carcinoma cells were common in ICCA and CCA components of cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA, although their expression was rare and mild in CCA components in cHC-CCA and ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA components of cHC-CCA but have a similar development to PDAC. These similarities may be explained by the unique anatomical, embryological and reactive nature of the pancreatobiliary tract. Further studies of these intractable malignancies are warranted. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. Bench press and push-up at comparable levels of muscle activity results in similar strength gains.

    PubMed

    Calatayud, Joaquin; Borreani, Sebastien; Colado, Juan C; Martin, Fernando; Tella, Victor; Andersen, Lars L

    2015-01-01

    Electromyography (EMG) exercise evaluation is commonly used to measure the intensity of muscle contraction. Although researchers assume that biomechanically comparable resistance exercises with similar high EMG levels will produce similar strength gains over the long term, no studies have actually corroborated this hypothesis. This study evaluated EMG levels during 6 repetition maximum (6RM) bench press and push-up, and subsequently performed a 5-week training period where subjects were randomly divided into 3 groups (i.e., 6RM bench press group, 6RM elastic band push-up group, or control group) to evaluate muscle strength gains. Thirty university students with advanced resistance training experience participated in the 2-part study. During the training period, exercises were performed using the same loads and variables that were used during the EMG data collection. At baseline, EMG amplitude showed no significant difference between 6RM bench press and band push-up. Significant differences among the groups were found for percent change (Δ) between pretest and posttest for 6RM (p = 0.017) and for 1 repetition maximum (1RM) (p < 0.001). Six repetition maximum bench press group and 6RM elastic band push-up group improved their 1RM and 6RM (Δ ranging from 13.65 to 22.21) tests significantly with similar gains, whereas control group remains unchanged. Thus, when the EMG values are comparable and the same conditions are reproduced, the aforementioned exercises can provide similar muscle strength gains.

  1. Meta-analysis shows similar re-bleeding rates among Western and Eastern populations after index video capsule endoscopy.

    PubMed

    Tziatzios, Georgios; Gkolfakis, Paraskevas; Hassan, Cesare; Toth, Ervin; Zullo, Angelo; Koulaouzidis, Anastasios; Dimitriadis, George D; Triantafyllou, Konstantinos

    2018-03-01

    Video capsule endoscopy (VCE) is the first-line diagnostic procedure for investigating obscure gastrointestinal bleeding (OGIB). Different re-bleeding rates following index VCE have been reported among Western and Eastern studies. We conducted a comprehensive literature search to identify studies examining re-bleeding rates after VCE for OGIB. Meta-analysis assessed the pooled proportion of re-bleeding events after VCE for OGIB according to study's origin (Western vs. Eastern) and according to the length of follow-up (≥24 months vs. <24 months). We also calculated the re-bleeding odds ratios (OR; 95% CI) after positive vs. negative index VCE, overt vs. occult initial presentation of bleeding and after interventional treatment for positive index cases, according to the study's origin. We included 46 (30 Western and 16 Eastern) studies with 5796 patients. Significant heterogeneity was detected among meta-analyzed studies. Overall, the pooled re-bleeding rate was similar between Western (29%; 95% CI: 23-34) and Eastern (21%; 95% CI: 15-27) populations, irrespective of the length of follow-up. The odds of re-bleeding was significantly higher after positive as compared to negative index VCE in Eastern studies (OR: 1.77; 95% CI: 1.07-2.94). Application of specific treatment after positive index VCE was associated with lower re-bleeding odds in both Western (OR: 0.37; 95% CI: 0.16-0.87) and Eastern (OR: 0.39; 95% CI: 0.21-0.72) populations. Patients undergoing VCE for OGIB have similar re-bleeding rates in the East and the West, regardless of the length of follow-up. However, increased re-bleeding odds after positive index VCE is observed in Eastern studies. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. Processes of Overall Similarity Sorting in Free Classification

    ERIC Educational Resources Information Center

    Milton, Fraser; Longmore, Christopher A.; Wills, A. J.

    2008-01-01

    The processes of overall similarity sorting were investigated in 5 free classification experiments. Experiments 1 and 2 demonstrated that increasing time pressure can reduce the likelihood of overall similarity categorization. Experiment 3 showed that a concurrent load also reduced overall similarity sorting. These findings suggest that overall…

  3. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei

    PubMed Central

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa

    2015-01-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca2+, and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. PMID:26195527

  4. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.

    PubMed

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa; Gamarro, Francisco; Pérez-Victoria, José M

    2015-10-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca(2+), and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. High and low sensation seeking adolescents show distinct patterns of brain activity during reward processing

    PubMed Central

    Cservenka, Anita; Herting, Megan M.; Seghete, Kristen L. Mackiewicz; Hudson, Karen A.; Nagel, Bonnie J.

    2012-01-01

    Previous research has shown that personality characteristics, such as sensation seeking (SS), are strong predictors of risk-taking behavior during adolescence. However, the relationship between levels of SS and brain response has not been studied during this time period. Given the prevalence of risky behavior during adolescence, it is important to understand neurobiological differences in reward sensitivity between youth with high and low SS personalities. To this end, we used functional magnetic resonance imaging (fMRI) to examine differences in brain activity in an adolescent sample that included 27 high (HSS) and 27 low sensation seekers (LSS), defined by the Impulsive Sensation Seeking scale of the Zuckerman-Kuhlman Personality Questionnaire (Zuckerman et al., 1993). In the scanner, participants played a modified Wheel of Fortune decision-making task (Cservenka and Nagel, 2012) that resulted in trials with monetary Wins or No Wins. We compared age- and sex-matched adolescent HSS and LSS (mean age = 13.94 ± 1.05) on brain activity by contrasting Win versus No Win trials. Our findings indicate that HSS show greater bilateral insular and prefrontal cortex (PFC) brain response on Win vs. No Win compared to LSS. Analysis of simple effects showed that while LSS showed comparable brain activity in these areas during Wins and No Wins, HSS showed significant differences in brain response to winning (activation) versus not winning (deactivation), with between-group comparison suggesting significant differences in brain response, largely to reward absence. Group differences in insular activation between reward receipt and absence may suggest weak autonomic arousal to negative outcomes in HSS compared with LSS. Additionally, since the PFC is important for goal-directed behavior and attention, the current results may reflect that HSS allocate fewer attentional resources to negative outcomes than LSS. This insensitivity to reward absence in HSS may lead to a greater

  6. When is Chemical Similarity Significant? The Statistical Distribution of Chemical Similarity Scores and Its Extreme Values

    PubMed Central

    Baldi, Pierre

    2010-01-01

    As repositories of chemical molecules continue to expand and become more open, it becomes increasingly important to develop tools to search them efficiently and assess the statistical significance of chemical similarity scores. Here we develop a general framework for understanding, modeling, predicting, and approximating the distribution of chemical similarity scores and its extreme values in large databases. The framework can be applied to different chemical representations and similarity measures but is demonstrated here using the most common binary fingerprints with the Tanimoto similarity measure. After introducing several probabilistic models of fingerprints, including the Conditional Gaussian Uniform model, we show that the distribution of Tanimoto scores can be approximated by the distribution of the ratio of two correlated Normal random variables associated with the corresponding unions and intersections. This remains true also when the distribution of similarity scores is conditioned on the size of the query molecules in order to derive more fine-grained results and improve chemical retrieval. The corresponding extreme value distributions for the maximum scores are approximated by Weibull distributions. From these various distributions and their analytical forms, Z-scores, E-values, and p-values are derived to assess the significance of similarity scores. In addition, the framework allows one to predict also the value of standard chemical retrieval metrics, such as Sensitivity and Specificity at fixed thresholds, or ROC (Receiver Operating Characteristic) curves at multiple thresholds, and to detect outliers in the form of atypical molecules. Numerous and diverse experiments carried in part with large sets of molecules from the ChemDB show remarkable agreement between theory and empirical results. PMID:20540577

  7. Modelling the perceptual similarity of facial expressions from image statistics and neural responses.

    PubMed

    Sormaz, Mladen; Watson, David M; Smith, William A P; Young, Andrew W; Andrews, Timothy J

    2016-04-01

    The ability to perceive facial expressions of emotion is essential for effective social communication. We investigated how the perception of facial expression emerges from the image properties that convey this important social signal, and how neural responses in face-selective brain regions might track these properties. To do this, we measured the perceptual similarity between expressions of basic emotions, and investigated how this is reflected in image measures and in the neural response of different face-selective regions. We show that the perceptual similarity of different facial expressions (fear, anger, disgust, sadness, happiness) can be predicted by both surface and feature shape information in the image. Using block design fMRI, we found that the perceptual similarity of expressions could also be predicted from the patterns of neural response in the face-selective posterior superior temporal sulcus (STS), but not in the fusiform face area (FFA). These results show that the perception of facial expression is dependent on the shape and surface properties of the image and on the activity of specific face-selective regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Subunits of the Snf1 kinase heterotrimer show interdependence for association and activity.

    PubMed

    Elbing, Karin; Rubenstein, Eric M; McCartney, Rhonda R; Schmidt, Martin C

    2006-09-08

    The Snf1 kinase and its mammalian orthologue, the AMP-activated protein kinase (AMPK), function as heterotrimers composed of a catalytic alpha-subunit and two non-catalytic subunits, beta and gamma. The beta-subunit is thought to hold the complex together and control subcellular localization whereas the gamma-subunit plays a regulatory role by binding to and blocking the function of an auto-inhibitory domain (AID) present in the alpha-subunit. In addition, catalytic activity requires phosphorylation by a distinct upstream kinase. In yeast, any one of three Snf1-activating kinases, Sak1, Tos3, or Elm1, can fulfill this role. We have previously shown that Sak1 is the only Snf1-activating kinase that forms a stable complex with Snf1. Here we show that the formation of the Sak1.Snf1 complex requires the beta- and gamma-subunits in vivo. However, formation of the Sak1.Snf1 complex is not necessary for glucose-regulated phosphorylation of the Snf1 activation loop. Snf1 kinase purified from cells lacking the beta-subunits do not contain any gamma-subunit, indicating that the Snf1 kinase does not form a stable alphagamma dimer in vivo. In vitro kinase assays using purified full-length and truncated Snf1 proteins demonstrate that the kinase domain, which lacks the AID, is significantly more active than the full-length Snf1 protein. Addition of purified beta- and gamma-subunits could stimulate the kinase activity of the full-length alpha-subunit but only when all three subunits were present, suggesting an interdependence of all three subunits for assembly of a functional complex.

  9. Similarities and Differences in Neurobiology.

    PubMed

    Chen, Manli; Sun, Yan; Lu, Lin; Shi, Jie

    2017-01-01

    Substance addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite harmful consequences. Non-substance addiction is defined recently that people may compulsively engage in an activity despite any negative consequences to their lives. Despite differences with respect to their addictive object, substance addiction and non-substance addiction may share similarities with respect to biological, epidemiological, clinical, genetic and other features. Here we review the similarities and differences in neurobiology between these two addictions with a focus on dopamine, serotonin, opioid, glutamate and norepinephrine systems. Studies suggest the involvement of all these systems in both substance addiction and non-substance addiction while differences may exist with respect to their contributions.

  10. The Left Occipitotemporal Cortex Does Not Show Preferential Activity for Words

    PubMed Central

    Petersen, Steven E.; Schlaggar, Bradley L.

    2012-01-01

    Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high–spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters. PMID:22235035

  11. Distributive Education--Fashion Show. Kit No. 88. Instructor's Manual [and] Student Learning Activity Guide.

    ERIC Educational Resources Information Center

    Walters, Brenda B.

    An instructor's manual and student activity guide on fashion shows are provided in this set of prevocational education materials which focuses on the vocational area of distributive education. (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven vocational offerings: agriculture, home…

  12. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

    PubMed

    Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

    2014-04-04

    α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The Production and Perception of Emotionally Expressive Walking Sounds: Similarities between Musical Performance and Everyday Motor Activity

    PubMed Central

    Giordano, Bruno L.; Egermann, Hauke; Bresin, Roberto

    2014-01-01

    Several studies have investigated the encoding and perception of emotional expressivity in music performance. A relevant question concerns how the ability to communicate emotions in music performance is acquired. In accordance with recent theories on the embodiment of emotion, we suggest here that both the expression and recognition of emotion in music might at least in part rely on knowledge about the sounds of expressive body movements. We test this hypothesis by drawing parallels between musical expression of emotions and expression of emotions in sounds associated with a non-musical motor activity: walking. In a combined production-perception design, two experiments were conducted, and expressive acoustical features were compared across modalities. An initial performance experiment tested for similar feature use in walking sounds and music performance, and revealed that strong similarities exist. Features related to sound intensity, tempo and tempo regularity were identified as been used similarly in both domains. Participants in a subsequent perception experiment were able to recognize both non-emotional and emotional properties of the sound-generating walkers. An analysis of the acoustical correlates of behavioral data revealed that variations in sound intensity, tempo, and tempo regularity were likely used to recognize expressed emotions. Taken together, these results lend support the motor origin hypothesis for the musical expression of emotions. PMID:25551392

  14. The production and perception of emotionally expressive walking sounds: similarities between musical performance and everyday motor activity.

    PubMed

    Giordano, Bruno L; Egermann, Hauke; Bresin, Roberto

    2014-01-01

    Several studies have investigated the encoding and perception of emotional expressivity in music performance. A relevant question concerns how the ability to communicate emotions in music performance is acquired. In accordance with recent theories on the embodiment of emotion, we suggest here that both the expression and recognition of emotion in music might at least in part rely on knowledge about the sounds of expressive body movements. We test this hypothesis by drawing parallels between musical expression of emotions and expression of emotions in sounds associated with a non-musical motor activity: walking. In a combined production-perception design, two experiments were conducted, and expressive acoustical features were compared across modalities. An initial performance experiment tested for similar feature use in walking sounds and music performance, and revealed that strong similarities exist. Features related to sound intensity, tempo and tempo regularity were identified as been used similarly in both domains. Participants in a subsequent perception experiment were able to recognize both non-emotional and emotional properties of the sound-generating walkers. An analysis of the acoustical correlates of behavioral data revealed that variations in sound intensity, tempo, and tempo regularity were likely used to recognize expressed emotions. Taken together, these results lend support the motor origin hypothesis for the musical expression of emotions.

  15. Tobacco-expressed Brassica juncea chitinase BjCHI1 shows antifungal activity in vitro.

    PubMed

    Fung, King-Leung; Zhao, Kai-Jun; He, Zhu-Mei; Chye, Mee-Len

    2002-09-01

    We have previously isolated a Brassica juncea cDNA encoding BjCHI1, a novel chitinase with two chitin-binding domains, and have shown that its mRNA is induced by wounding and methyl jasmonate treatment (K.-J. Zhao and M.-L. Chye, Plant Mol. Biol. 40 (1999) 1009-1018). By the presence of two chitin-binding domains, BjCHI1 resembles the precursor of UDA (Urtica dioica agglutinin) but, unlike UDA, BjCHI1 retains its chitinase catalytic domain after post-translational processing. Here, we indicate the role of BjCHI1 in plant defense by demonstrating its mRNA induction upon Aspergillus niger infection or caterpillar Pieris rapae (L.) feeding. To further investigate the biological properties of BjCHI1, we transformed tobacco with a construct expressing the BjCHI1 cDNA from the CaMV 35S promoter. Subsequently, we purified BjCHI1 from the resultant transgenic Ro plants using a regenerated chitin column followed by fast protein liquid chromatography (FPLC). Also, the significance of the second chitin-binding domain in BjCHI1 was investigated by raising transgenic tobacco plants expressing BjCHI2, a deletion derivative of BjCHI1 lacking one chitin-binding domain. Colorimetric chitinase assays at 25 degrees C, pH 5, showed no significant differences between the activities of BjCHI1 and BjCHI2, suggesting that chitinase activity, due to the catalytic domain, is not enhanced by the presence of a second chitin-binding domain. Both BjCHI1 and BjCHI2 show in vitro anti-fungal activity toward Trichoderma viride, causing reductions in hyphal diameter, hyphal branching and conidia size.

  16. Stability of similarity measurements for bipartite networks

    PubMed Central

    Liu, Jian-Guo; Hou, Lei; Pan, Xue; Guo, Qiang; Zhou, Tao

    2016-01-01

    Similarity is a fundamental measure in network analyses and machine learning algorithms, with wide applications ranging from personalized recommendation to socio-economic dynamics. We argue that an effective similarity measurement should guarantee the stability even under some information loss. With six bipartite networks, we investigate the stabilities of fifteen similarity measurements by comparing the similarity matrixes of two data samples which are randomly divided from original data sets. Results show that, the fifteen measurements can be well classified into three clusters according to their stabilities, and measurements in the same cluster have similar mathematical definitions. In addition, we develop a top-n-stability method for personalized recommendation, and find that the unstable similarities would recommend false information to users, and the performance of recommendation would be largely improved by using stable similarity measurements. This work provides a novel dimension to analyze and evaluate similarity measurements, which can further find applications in link prediction, personalized recommendation, clustering algorithms, community detection and so on. PMID:26725688

  17. Stability of similarity measurements for bipartite networks.

    PubMed

    Liu, Jian-Guo; Hou, Lei; Pan, Xue; Guo, Qiang; Zhou, Tao

    2016-01-04

    Similarity is a fundamental measure in network analyses and machine learning algorithms, with wide applications ranging from personalized recommendation to socio-economic dynamics. We argue that an effective similarity measurement should guarantee the stability even under some information loss. With six bipartite networks, we investigate the stabilities of fifteen similarity measurements by comparing the similarity matrixes of two data samples which are randomly divided from original data sets. Results show that, the fifteen measurements can be well classified into three clusters according to their stabilities, and measurements in the same cluster have similar mathematical definitions. In addition, we develop a top-n-stability method for personalized recommendation, and find that the unstable similarities would recommend false information to users, and the performance of recommendation would be largely improved by using stable similarity measurements. This work provides a novel dimension to analyze and evaluate similarity measurements, which can further find applications in link prediction, personalized recommendation, clustering algorithms, community detection and so on.

  18. Representational Similarity of Body Parts in Human Occipitotemporal Cortex.

    PubMed

    Bracci, Stefania; Caramazza, Alfonso; Peelen, Marius V

    2015-09-23

    Regions in human lateral and ventral occipitotemporal cortices (OTC) respond selectively to pictures of the human body and its parts. What are the organizational principles underlying body part responses in these regions? Here we used representational similarity analysis (RSA) of fMRI data to test multiple possible organizational principles: shape similarity, physical proximity, cortical homunculus proximity, and semantic similarity. Participants viewed pictures of whole persons, chairs, and eight body parts (hands, arms, legs, feet, chests, waists, upper faces, and lower faces). The similarity of multivoxel activity patterns for all body part pairs was established in whole person-selective OTC regions. The resulting neural similarity matrices were then compared with similarity matrices capturing the hypothesized organizational principles. Results showed that the semantic similarity model best captured the neural similarity of body parts in lateral and ventral OTC, which followed an organization in three clusters: (1) body parts used as action effectors (hands, feet, arms, and legs), (2) noneffector body parts (chests and waists), and (3) face parts (upper and lower faces). Whole-brain RSA revealed, in addition to OTC, regions in parietal and frontal cortex in which neural similarity was related to semantic similarity. In contrast, neural similarity in occipital cortex was best predicted by shape similarity models. We suggest that the semantic organization of body parts in high-level visual cortex relates to the different functions associated with the three body part clusters, reflecting the unique processing and connectivity demands associated with the different types of information (e.g., action, social) different body parts (e.g., limbs, faces) convey. Significance statement: While the organization of body part representations in motor and somatosensory cortices has been well characterized, the principles underlying body part representations in visual cortex

  19. Is nevtral NEUTRAL? Visual similarity effects in the early phases of written-word recognition.

    PubMed

    Marcet, Ana; Perea, Manuel

    2017-08-01

    For simplicity, contemporary models of written-word recognition and reading have unspecified feature/letter levels-they predict that the visually similar substituted-letter nonword PEQPLE is as effective at activating the word PEOPLE as the visually dissimilar substituted-letter nonword PEYPLE. Previous empirical evidence on the effects of visual similarly across letters during written-word recognition is scarce and nonconclusive. To examine whether visual similarity across letters plays a role early in word processing, we conducted two masked priming lexical decision experiments (stimulus-onset asynchrony = 50 ms). The substituted-letter primes were visually very similar to the target letters (u/v in Experiment 1 and i/j in Experiment 2; e.g., nevtral-NEUTRAL). For comparison purposes, we included an identity prime condition (neutral-NEUTRAL) and a dissimilar-letter prime condition (neztral-NEUTRAL). Results showed that the similar-letter prime condition produced faster word identification times than the dissimilar-letter prime condition. We discuss how models of written-word recognition should be amended to capture visual similarity effects across letters.

  20. Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical Activity and Fracture Rate as Controls.

    PubMed

    Diarbakerli, Elias; Grauers, Anna; Danielsson, Aina; Gerdhem, Paul

    2017-04-01

    Cross-sectional. To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n = 360, brace n = 460, and surgically treated n = 458) were compared. Furthermore, a comparison based on onset (juvenile n = 169 or adolescent n = 976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P = 0.40). The scoliosis patients reported 2016 MET-minutes/week (median value) and the controls 2456 (P = 0.06). Fracture rates did not differ (P = 0.72). Fewer surgically treated individuals achieved moderate activity level (P = 0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P = 0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P ≥ 0.05). Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated

  1. Pharmacophore-Based Similarity Scoring for DOCK

    PubMed Central

    2015-01-01

    Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein–ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK. PMID:25229837

  2. Similarity to the self influences cortical recruitment during impression formation

    PubMed Central

    Leshikar, Eric D.; Cassidy, Brittany S.; Gutchess, Angela H.

    2015-01-01

    Prior work has shown that whether or not someone is similar to the self influences person memory—a type of self-reference effect for others. In this study, we were interested in understanding the neural regions supporting the generation of impressions and subsequent memory for targets who vary in similarity to the self. Participants underwent fMRI scanning while forming positive or negative impressions of face-behavior pairs. We tested participants’ memory for their generated impressions, and then back-sorted the impression trials (encoding) into different levels of self-similarity (high, medium, low) using a self-similarity post-test that came after recognition. Extending prior behavioral work, our data confirmed our hypothesis that memory would be highest for self-similar others and lowest for self-dissimilar others. Dorsal anterior cingulate cortex (dACC) activity increased with self-similarity (high > medium > low) to targets, regardless of later memory for them. An analysis of regions supporting impression memory revealed a double dissociation within medial temporal lobe regions: for similar others, amygdala recruitment supported memory, whereas for dissimilar others, hippocampal activation supported memory. These results suggest that self-similarity influences evaluation and memory for targets, but also affects the underlying neural resources engaged when thinking about others who vary in self-similarity. PMID:26558615

  3. Learning, memory and exploratory similarities in genetically identical cloned dogs.

    PubMed

    Shin, Chi Won; Kim, Geon A; Park, Won Jun; Park, Kwan Yong; Jeon, Jeong Min; Oh, Hyun Ju; Kim, Min Jung; Lee, Byeong Chun

    2016-12-30

    Somatic cell nuclear transfer allows generation of genetically identical animals using donor cells derived from animals with particular traits. To date, few studies have investigated whether or not these cloned dogs will show identical behavior patterns. To address this question, learning, memory and exploratory patterns were examined using six cloned dogs with identical nuclear genomes. The variance of total incorrect choice number in the Y-maze test among cloned dogs was significantly lower than that of the control dogs. There was also a significant decrease in variance in the level of exploratory activity in the open fields test compared to age-matched control dogs. These results indicate that cloned dogs show similar cognitive and exploratory patterns, suggesting that these behavioral phenotypes are related to the genotypes of the individuals.

  4. Scalar Similarity for Relaxed Eddy Accumulation Methods

    NASA Astrophysics Data System (ADS)

    Ruppert, Johannes; Thomas, Christoph; Foken, Thomas

    2006-07-01

    The relaxed eddy accumulation (REA) method allows the measurement of trace gas fluxes when no fast sensors are available for eddy covariance measurements. The flux parameterisation used in REA is based on the assumption of scalar similarity, i.e., similarity of the turbulent exchange of two scalar quantities. In this study changes in scalar similarity between carbon dioxide, sonic temperature and water vapour were assessed using scalar correlation coefficients and spectral analysis. The influence on REA measurements was assessed by simulation. The evaluation is based on observations over grassland, irrigated cotton plantation and spruce forest. Scalar similarity between carbon dioxide, sonic temperature and water vapour showed a distinct diurnal pattern and change within the day. Poor scalar similarity was found to be linked to dissimilarities in the energy contained in the low frequency part of the turbulent spectra ( < 0.01 Hz). The simulations of REA showed significant change in b-factors throughout the diurnal course. The b-factor is part of the REA parameterisation scheme and describes a relation between the concentration difference and the vertical flux of a trace gas. The diurnal course of b-factors for carbon dioxide, sonic temperature and water vapour matched well. Relative flux errors induced in REA by varying scalar similarity were generally below ± 10%. Systematic underestimation of the flux of up to - 40% was found for the use of REA applying a hyperbolic deadband (HREA). This underestimation was related to poor scalar similarity between the scalar of interest and the scalar used as proxy for the deadband definition.

  5. Proteins with similar architecture exhibit similar large-scale dynamic behavior.

    PubMed Central

    Keskin, O; Jernigan, R L; Bahar, I

    2000-01-01

    We have investigated the similarities and differences in the computed dynamic fluctuations exhibited by six members of a protein fold family with a coarse-grained Gaussian network model. Specifically, we consider the cofactor binding fragment of CysB; the lysine/arginine/ornithine-binding protein (LAO); the enzyme porphobilinogen deaminase (PBGD); the ribose-binding protein (RBP); the N-terminal lobe of ovotransferrin in apo-form (apo-OVOT); and the leucine/isoleucine/valine-binding protein (LIVBP). All have domains that resemble a Rossmann fold, but there are also some significant differences. Results indicate that similar global dynamic behavior is preserved for the members of a fold family, and that differences usually occur in regions only where specific function is localized. The present work is a computational demonstration that the scaffold of a protein fold may be utilized for diverse purposes. LAO requires a bound ligand before it conforms to the large-scale fluctuation behavior of the three other members of the family, CysB, PBGD, and RBP, all of which contain a substrate (cofactor) at the active site cleft. The dynamics of the ligand-free enzymes LIVBP and apo-OVOT, on the other hand, concur with that of unliganded LAO. The present results suggest that it is possible to construct structure alignments based on dynamic fluctuation behavior. PMID:10733987

  6. Cytorhabdovirus phosphoprotein shows RNA silencing suppressor activity in plants, but not in insect cells.

    PubMed

    Mann, Krin S; Johnson, Karyn N; Dietzgen, Ralf G

    2015-02-01

    RNA silencing in plants and insects provides an antiviral defense and as a countermeasure most viruses encode RNA silencing suppressors (RSS). For the family Rhabdoviridae, no detailed functional RSS studies have been reported in plant hosts and insect vectors. In agroinfiltrated Nicotiana benthamiana leaves we show for the first time for a cytorhabdovirus, lettuce necrotic yellows virus (LNYV), that one of the nucleocapsid core proteins, phosphoprotein (P) has relatively weak local RSS activity and delays systemic silencing of a GFP reporter. Analysis of GFP small RNAs indicated that the P protein did not prevent siRNA accumulation. To explore RSS activity in insects, we used a Flock House virus replicon system in Drosophila S2 cells. In contrast to the plant host, LNYV P protein did not exhibit RSS activity in the insect cells. Taken together our results suggest that P protein may target plant-specific components of RNA silencing post siRNA biogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA.

    PubMed

    Tran, Kieu-Nhi; Rybak, Michael J

    2018-06-01

    Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) strains. In vitro data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible Staphylococcus aureus (VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal ( P < 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin-beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these Staphylococcus strains. Copyright © 2018 American Society for Microbiology.

  8. Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

    PubMed

    Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

    2013-03-25

    Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

  9. Simulated rRNA/DNA Ratios Show Potential To Misclassify Active Populations as Dormant

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

    Steven, Blaire; Hesse, Cedar; Soghigian, John

    The use of rRNA/DNA ratios derived from surveys of rRNA sequences in RNA and DNA extracts is an appealing but poorly validated approach to infer the activity status of environmental microbes. To improve the interpretation of rRNA/DNA ratios, we performed simulations to investigate the effects of community structure, rRNA amplification, and sampling depth on the accuracy of rRNA/DNA ratios in classifying bacterial populations as “active” or “dormant.” Community structure was an insignificant factor. In contrast, the extent of rRNA amplification that occurs as cells transition from dormant to growing had a significant effect (P < 0.0001) on classification accuracy, withmore » misclassification errors ranging from 16 to 28%, depending on the rRNA amplification model. The error rate increased to 47% when communities included a mixture of rRNA amplification models, but most of the inflated error was false negatives (i.e., active populations misclassified as dormant). Sampling depth also affected error rates (P < 0.001). Inadequate sampling depth produced various artifacts that are characteristic of rRNA/DNA ratios generated from real communities. These data show important constraints on the use of rRNA/DNA ratios to infer activity status. Whereas classification of populations as active based on rRNA/DNA ratios appears generally valid, classification of populations as dormant is potentially far less accurate.« less

  10. Simulated rRNA/DNA Ratios Show Potential To Misclassify Active Populations as Dormant

    DOE PAGES

    Steven, Blaire; Hesse, Cedar; Soghigian, John; ...

    2017-03-31

    The use of rRNA/DNA ratios derived from surveys of rRNA sequences in RNA and DNA extracts is an appealing but poorly validated approach to infer the activity status of environmental microbes. To improve the interpretation of rRNA/DNA ratios, we performed simulations to investigate the effects of community structure, rRNA amplification, and sampling depth on the accuracy of rRNA/DNA ratios in classifying bacterial populations as “active” or “dormant.” Community structure was an insignificant factor. In contrast, the extent of rRNA amplification that occurs as cells transition from dormant to growing had a significant effect (P < 0.0001) on classification accuracy, withmore » misclassification errors ranging from 16 to 28%, depending on the rRNA amplification model. The error rate increased to 47% when communities included a mixture of rRNA amplification models, but most of the inflated error was false negatives (i.e., active populations misclassified as dormant). Sampling depth also affected error rates (P < 0.001). Inadequate sampling depth produced various artifacts that are characteristic of rRNA/DNA ratios generated from real communities. These data show important constraints on the use of rRNA/DNA ratios to infer activity status. Whereas classification of populations as active based on rRNA/DNA ratios appears generally valid, classification of populations as dormant is potentially far less accurate.« less

  11. Neuromuscular fatigue following isometric contractions with similar torque time integral.

    PubMed

    Rozand, V; Cattagni, T; Theurel, J; Martin, A; Lepers, R

    2015-01-01

    Torque time integral (TTI) is the combination of intensity and duration of a contraction. The aim of this study was to compare neuromuscular alterations following different isometric sub-maximal contractions of the knee extensor muscles but with similar TTI. Sixteen participants performed 3 sustained contractions at different intensities (25%, 50%, and 75% of Maximal Voluntary Contraction (MVC) torque) with different durations (68.5±33.4 s, 35.1±16.8 s and 24.8±12.9 s, respectively) but similar TTI value. MVC torque, maximal voluntary activation level (VAL), M-wave characteristics and potentiated doublet amplitude were assessed before and immediately after the sustained contractions. EMG activity of the vastus lateralis (VL) and -rectus femoris (RF) muscles was recorded during the sustained contractions. MVC torque reduction was similar in the 3 conditions after the exercise (-23.4±2.7%). VAL decreased significantly in a similar extent (-3.1±1.3%) after the 3 sustained contractions. Potentiated doublet amplitude was similarly reduced in the 3 conditions (-19.7±1.5%), but VL and RF M-wave amplitudes remained unchanged. EMG activity of VL and RF muscles increased in the same extent during the 3 contractions (VL: 54.5±40.4%; RF: 53.1±48.7%). These results suggest that central and peripheral alterations accounting for muscle fatigue are similar following isometric contractions with similar TTI. TTI should be considered in the exploration of muscle fatigue during sustained isometric contractions. © Georg Thieme Verlag KG Stuttgart · New York.

  12. New similarity of triangular fuzzy number and its application.

    PubMed

    Zhang, Xixiang; Ma, Weimin; Chen, Liping

    2014-01-01

    The similarity of triangular fuzzy numbers is an important metric for application of it. There exist several approaches to measure similarity of triangular fuzzy numbers. However, some of them are opt to be large. To make the similarity well distributed, a new method SIAM (Shape's Indifferent Area and Midpoint) to measure triangular fuzzy number is put forward, which takes the shape's indifferent area and midpoint of two triangular fuzzy numbers into consideration. Comparison with other similarity measurements shows the effectiveness of the proposed method. Then, it is applied to collaborative filtering recommendation to measure users' similarity. A collaborative filtering case is used to illustrate users' similarity based on cloud model and triangular fuzzy number; the result indicates that users' similarity based on triangular fuzzy number can obtain better discrimination. Finally, a simulated collaborative filtering recommendation system is developed which uses cloud model and triangular fuzzy number to express users' comprehensive evaluation on items, and result shows that the accuracy of collaborative filtering recommendation based on triangular fuzzy number is higher.

  13. Using a Simple Optical Rangefinder To Teach Similar Triangles.

    ERIC Educational Resources Information Center

    Cuicchi, Paul M.; Hutchison, Paul S.

    2003-01-01

    Describes how the concept of similar triangles was taught using an optical method of estimating large distances as a corresponding activity. Includes the derivation of a formula to calculate one source of measurement error and is a nice exercise in the use of the properties of similar triangles. (Author/NB)

  14. Free-Standing Metal Oxide Nanoparticle Superlattices Constructed with Engineered Protein Containers Show in Crystallo Catalytic Activity.

    PubMed

    Lach, Marcel; Künzle, Matthias; Beck, Tobias

    2017-12-11

    The construction of defined nanostructured catalysts is challenging. In previous work, we established a strategy to assemble binary nanoparticle superlattices with oppositely charged protein containers as building blocks. Here, we show that these free-standing nanoparticle superlattices are catalytically active. The metal oxide nanoparticles inside the protein scaffold are accessible for a range of substrates and show oxidase-like and peroxidase-like activity. The stable superlattices can be reused for several reaction cycles. In contrast to bulk nanoparticle-based catalysts, which are prone to aggregation and difficult to characterize, nanoparticle superlattices based on engineered protein containers provide an innovative synthetic route to structurally defined heterogeneous catalysts with control over nanoparticle size and composition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. What Difference Reveals about Similarity

    ERIC Educational Resources Information Center

    Sagi, Eyal; Gentner, Dedre; Lovett, Andrew

    2012-01-01

    Detecting that two images are different is faster for highly dissimilar images than for highly similar images. Paradoxically, we showed that the reverse occurs when people are asked to describe "how" two images differ--that is, to state a difference between two images. Following structure-mapping theory, we propose that this…

  16. Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab.

    PubMed

    Velayudhan, Jyoti; Chen, Yuh-Feng; Rohrbach, Amanda; Pastula, Christina; Maher, Gwen; Thomas, Heather; Brown, Ryan; Born, Teresa L

    2016-08-01

    Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity. A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity. The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities. Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.

  17. iPads and LCDs show similar performance in the detection of pulmonary nodules

    NASA Astrophysics Data System (ADS)

    McEntee, Mark F.; Lowe, Joanna; Butler, Marie Louise; Pietrzyk, Mariusz; Evanoff, Michael G.; Ryan, John; Brennan, Patrick C.; Rainford, Louise A.

    2012-02-01

    In February 2011 the University of Chicago Medical School distributed iPads to its trainee doctors for use when reviewing clinical information and images on the ward or clinics. The use of tablet computing devices is becoming widespread in medicine with Apple™ heralding them as "revolutionary" in medicine. The question arises, just because it is technical achievable to use iPads for clinical evaluation of images, should we do so? The current work assesses the diagnostic efficacy of iPads when compared with LCD secondary display monitors for identifying lung nodules on chest x-rays. Eight examining radiologists of the American Board of Radiology were involved in the assessment, reading chest images on both the iPad and the an off-the-shelf LCD monitor. Thirty chest images were shown to each observer, of which 15 had one or more lung nodules. Radiologists were asked to locate the nodules and score how confident they were with their decision on a scale of 1-5. An ROC and JAFROC analysis was performed and modalities were compared using DBM MRMC. The results demonstrate no significant differences in performance between the iPad and the LCD for the ROC AUC (p<0.075) or JAFROC FOM (p<0.059) for random readers and random cases. Sample size estimation showed that this result is significant at a power of 0.8 and an effect size of 0.05 for ROC and 0.07 for JAFROC. This work demonstrates that for the task of identifying pulmonary nodules, the use of the iPad does not significantly change performance compared to an off-the-shelf LCD.

  18. The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.

    PubMed

    Roszniowski, Bartosz; Latka, Agnieszka; Maciejewska, Barbara; Vandenheuvel, Dieter; Olszak, Tomasz; Briers, Yves; Holt, Giles S; Valvano, Miguel A; Lavigne, Rob; Smith, Darren L; Drulis-Kawa, Zuzanna

    2017-02-01

    Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.

  19. Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease

    PubMed Central

    2013-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development. PMID:24304150

  20. Learning deep similarity in fundus photography

    NASA Astrophysics Data System (ADS)

    Chudzik, Piotr; Al-Diri, Bashir; Caliva, Francesco; Ometto, Giovanni; Hunter, Andrew

    2017-02-01

    Similarity learning is one of the most fundamental tasks in image analysis. The ability to extract similar images in the medical domain as part of content-based image retrieval (CBIR) systems has been researched for many years. The vast majority of methods used in CBIR systems are based on hand-crafted feature descriptors. The approximation of a similarity mapping for medical images is difficult due to the big variety of pixel-level structures of interest. In fundus photography (FP) analysis, a subtle difference in e.g. lesions and vessels shape and size can result in a different diagnosis. In this work, we demonstrated how to learn a similarity function for image patches derived directly from FP image data without the need of manually designed feature descriptors. We used a convolutional neural network (CNN) with a novel architecture adapted for similarity learning to accomplish this task. Furthermore, we explored and studied multiple CNN architectures. We show that our method can approximate the similarity between FP patches more efficiently and accurately than the state-of- the-art feature descriptors, including SIFT and SURF using a publicly available dataset. Finally, we observe that our approach, which is purely data-driven, learns that features such as vessels calibre and orientation are important discriminative factors, which resembles the way how humans reason about similarity. To the best of authors knowledge, this is the first attempt to approximate a visual similarity mapping in FP.

  1. C8-Linked Pyrrolobenzodiazepine Monomers with Inverted Building Blocks Show Selective Activity against Multidrug Resistant Gram-Positive Bacteria.

    PubMed

    Andriollo, Paolo; Hind, Charlotte K; Picconi, Pietro; Nahar, Kazi S; Jamshidi, Shirin; Varsha, Amrit; Clifford, Melanie; Sutton, J Mark; Rahman, Khondaker Miraz

    2018-02-09

    Antimicrobial resistance has become a major global concern. Development of novel antimicrobial agents for the treatment of infections caused by multidrug resistant (MDR) pathogens is an urgent priority. Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents initially discovered and isolated from natural sources. Recently, C8-linked PBD biaryl conjugates have been shown to be active against some MDR Gram-positive strains. To explore the role of building block orientations on antibacterial activity and obtain structure activity relationship (SAR) information, four novel structures were synthesized in which the building blocks of previously reported compounds were inverted, and their antibacterial activity was studied. The compounds showed minimum inhibitory concentrations (MICs) in the range of 0.125-32 μg/mL against MDR Gram-positive strains with a bactericidal mode of action. The results showed that a single inversion of amide bonds reduces the activity while the double inversion restores the activity against MDR pathogens. All inverted compounds did not stabilize DNA and lacked eukaryotic toxicity. The compounds inhibit DNA gyrase in vitro, and the most potent compound was equally active against both wild-type and mutant DNA gyrase in a biochemical assay. The observed activity of the compounds against methicillin resistant S. aureus (MRSA) strains with equivalent gyrase mutations is consistent with gyrase inhibition being the mechanism of action in vivo, although this has not been definitively confirmed in whole cells. This conclusion is supported by a molecular modeling study showing interaction of the compounds with wild-type and mutant gyrases. This study provides important SAR information about this new class of antibacterial agents.

  2. Dimensional analysis, similarity, analogy, and the simulation theory

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

    Davis, A.A.

    1978-01-01

    Dimensional analysis, similarity, analogy, and cybernetics are shown to be four consecutive steps in application of the simulation theory. This paper introduces the classes of phenomena which follow the same formal mathematical equations as models of the natural laws and the interior sphere of restraints groups of phenomena in which one can introduce simplfied nondimensional mathematical equations. The simulation by similarity in a specific field of physics, by analogy in two or more different fields of physics, and by cybernetics in nature in two or more fields of mathematics, physics, biology, economics, politics, sociology, etc., appears as a unique theorymore » which permits one to transport the results of experiments from the models, convenably selected to meet the conditions of researches, constructions, and measurements in the laboratories to the originals which are the primary objectives of the researches. Some interesting conclusions which cannot be avoided in the use of simplified nondimensional mathematical equations as models of natural laws are presented. Interesting limitations on the use of simulation theory based on assumed simplifications are recognized. This paper shows as necessary, in scientific research, that one write mathematical models of general laws which will be applied to nature in its entirety. The paper proposes the extent of the second law of thermodynamics as the generalized law of entropy to model life and its activities. This paper shows that the physical studies and philosophical interpretations of phenomena and natural laws cannot be separated in scientific work; they are interconnected and one cannot be put above the others.« less

  3. Domain similarity based orthology detection.

    PubMed

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  4. Recognition memory is modulated by visual similarity.

    PubMed

    Yago, Elena; Ishai, Alumit

    2006-06-01

    We used event-related fMRI to test whether recognition memory depends on visual similarity between familiar prototypes and novel exemplars. Subjects memorized portraits, landscapes, and abstract compositions by six painters with a unique style, and later performed a memory recognition task. The prototypes were presented with new exemplars that were either visually similar or dissimilar. Behaviorally, novel, dissimilar items were detected faster and more accurately. We found activation in a distributed cortical network that included face- and object-selective regions in the visual cortex, where familiar prototypes evoked stronger responses than new exemplars; attention-related regions in parietal cortex, where responses elicited by new exemplars were reduced with decreased similarity to the prototypes; and the hippocampus and memory-related regions in parietal and prefrontal cortices, where stronger responses were evoked by the dissimilar exemplars. Our findings suggest that recognition memory is mediated by classification of novel exemplars as a match or a mismatch, based on their visual similarity to familiar prototypes.

  5. Phonological similarity and orthographic similarity affect probed serial recall of Chinese characters.

    PubMed

    Lin, Yi-Chen; Chen, Hsiang-Yu; Lai, Yvonne C; Wu, Denise H

    2015-04-01

    The previous literature on working memory (WM) has indicated that verbal materials are dominantly retained in phonological representations, whereas other linguistic information (e.g., orthography, semantics) only contributes to verbal WM minimally, if not negligibly. Although accumulating evidence has suggested that multiple linguistic components jointly support verbal WM, the visual/orthographic contribution has rarely been addressed in alphabetic languages, possibly due to the difficulty of dissociating the effects of word forms from the effects of their pronunciations in relatively shallow orthography. In the present study, we examined whether the orthographic representations of Chinese characters support the retention of verbal materials in this language of deep orthography. In Experiments 1a and 2, we independently manipulated the phonological and orthographic similarity of horizontal and vertical characters, respectively, and found that participants' accuracy of probed serial recall was reduced by both similar pronunciations and shared phonetic radicals in the to-be-remembered stimuli. Moreover, Experiment 1b showed that only the effect of phonological, but not that of orthographic, similarity was affected by concurrent articulatory suppression. Taken together, the present results indicate the indispensable contribution of orthographic representations to verbal WM of Chinese characters, and suggest that the linguistic characteristics of a specific language not only determine long-term linguistic-processing mechanisms, but also delineate the organization of verbal WM for that language.

  6. The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo.

    PubMed

    Wendel, Torunn; Zhen, Yan; Suo, Zenhe; Bruheim, Skjalg; Wiedlocha, Antoni

    2016-01-15

    HSP90 is a molecular chaperone essential for stability, activity and intracellular sorting of many proteins, including oncoproteins, such as tyrosine kinases, transcription factors and cell cycle regulatory proteins. Therefore, inhibitors of HSP90 are being investigated for their potential as anti-cancer drugs. Here we show that the HSP90 inhibitor NVP-AUY922 induced degradation of the fusion oncoprotein FOP2-FGFR1 in a human acute myeloid leukemia (AML) cell line, KG-1a. Concordantly, downstream signaling cascades, such as STAT1, STAT3 and PLCγ were abrogated. At concentrations that caused FOP2-FGFR1 degradation and signaling abrogation, NVP-AUY922 treatment caused significant cell death and inhibition of proliferation of KG-1a cells in vitro. In an animal model for AML, NVP-AUY922 administrated alone showed no anti-leukemic activity. However, when NVP-AUY922 was administered in combination with cytarabine, the two compounds showed significant synergistic anti-leukemic activity in vivo. Thus NVP-AUY922 and cytarabine combination therapy might be a prospective strategy for AML treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Temperature Dependence of Field-Effect Mobility in Organic Thin-Film Transistors: Similarity to Inorganic Transistors.

    PubMed

    Okada, Jun; Nagase, Takashi; Kobayashi, Takashi; Naito, Hiroyoshi

    2016-04-01

    Carrier transport in solution-processed organic thin-film transistors (OTFTs) based on dioctylbenzothienobenzothiophene (C8-BTBT) has been investigated in a wide temperature range from 296 to 10 K. The field-effect mobility shows thermally activated behavior whose activation energy becomes smaller with decreasing temperature. The temperature dependence of field-effect mobility found in C8-BTBT is similar to that of others materials: organic semiconducting polymers, amorphous oxide semiconductors and hydrogenated amorphous silicon. These results indicate that hopping transport between isoenergetic localized states becomes dominated in a low temperature regime in these materials.

  8. Similarity Based Semantic Web Service Match

    NASA Astrophysics Data System (ADS)

    Peng, Hui; Niu, Wenjia; Huang, Ronghuai

    Semantic web service discovery aims at returning the most matching advertised services to the service requester by comparing the semantic of the request service with an advertised service. The semantic of a web service are described in terms of inputs, outputs, preconditions and results in Ontology Web Language for Service (OWL-S) which formalized by W3C. In this paper we proposed an algorithm to calculate the semantic similarity of two services by weighted averaging their inputs and outputs similarities. Case study and applications show the effectiveness of our algorithm in service match.

  9. Large-scale variation in subsurface stream biofilms: a cross-regional comparison of metabolic function and community similarity.

    PubMed

    Findlay, S; Sinsabaugh, R L

    2006-10-01

    We examined bacterial metabolic activity and community similarity in shallow subsurface stream sediments distributed across three regions of the eastern United States to assess whether there were parallel changes in functional and structural attributes at this large scale. Bacterial growth, oxygen consumption, and a suite of extracellular enzyme activities were assayed to describe functional variability. Community similarity was assessed using randomly amplified polymorphic DNA (RAPD) patterns. There were significant differences in streamwater chemistry, metabolic activity, and bacterial growth among regions with, for instance, twofold higher bacterial production in streams near Baltimore, MD, compared to Hubbard Brook, NH. Five of eight extracellular enzymes showed significant differences among regions. Cluster analyses of individual streams by metabolic variables showed clear groups with significant differences in representation of sites from different regions among groups. Clustering of sites based on randomly amplified polymorphic DNA banding resulted in groups with generally less internal similarity although there were still differences in distribution of regional sites. There was a marginally significant (p = 0.09) association between patterns based on functional and structural variables. There were statistically significant but weak (r2 approximately 30%) associations between landcover and measures of both structure and function. These patterns imply a large-scale organization of biofilm communities and this structure may be imposed by factor(s) such as landcover and covariates such as nutrient concentrations, which are known to also cause differences in macrobiota of stream ecosystems.

  10. Semantic similarity between ontologies at different scales

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

    Zhang, Qingpeng; Haglin, David J.

    In the past decade, existing and new knowledge and datasets has been encoded in different ontologies for semantic web and biomedical research. The size of ontologies is often very large in terms of number of concepts and relationships, which makes the analysis of ontologies and the represented knowledge graph computational and time consuming. As the ontologies of various semantic web and biomedical applications usually show explicit hierarchical structures, it is interesting to explore the trade-offs between ontological scales and preservation/precision of results when we analyze ontologies. This paper presents the first effort of examining the capability of this idea viamore » studying the relationship between scaling biomedical ontologies at different levels and the semantic similarity values. We evaluate the semantic similarity between three Gene Ontology slims (Plant, Yeast, and Candida, among which the latter two belong to the same kingdom—Fungi) using four popular measures commonly applied to biomedical ontologies (Resnik, Lin, Jiang-Conrath, and SimRel). The results of this study demonstrate that with proper selection of scaling levels and similarity measures, we can significantly reduce the size of ontologies without losing substantial detail. In particular, the performance of Jiang-Conrath and Lin are more reliable and stable than that of the other two in this experiment, as proven by (a) consistently showing that Yeast and Candida are more similar (as compared to Plant) at different scales, and (b) small deviations of the similarity values after excluding a majority of nodes from several lower scales. This study provides a deeper understanding of the application of semantic similarity to biomedical ontologies, and shed light on how to choose appropriate semantic similarity measures for biomedical engineering.« less

  11. Predicting the performance of fingerprint similarity searching.

    PubMed

    Vogt, Martin; Bajorath, Jürgen

    2011-01-01

    Fingerprints are bit string representations of molecular structure that typically encode structural fragments, topological features, or pharmacophore patterns. Various fingerprint designs are utilized in virtual screening and their search performance essentially depends on three parameters: the nature of the fingerprint, the active compounds serving as reference molecules, and the composition of the screening database. It is of considerable interest and practical relevance to predict the performance of fingerprint similarity searching. A quantitative assessment of the potential that a fingerprint search might successfully retrieve active compounds, if available in the screening database, would substantially help to select the type of fingerprint most suitable for a given search problem. The method presented herein utilizes concepts from information theory to relate the fingerprint feature distributions of reference compounds to screening libraries. If these feature distributions do not sufficiently differ, active database compounds that are similar to reference molecules cannot be retrieved because they disappear in the "background." By quantifying the difference in feature distribution using the Kullback-Leibler divergence and relating the divergence to compound recovery rates obtained for different benchmark classes, fingerprint search performance can be quantitatively predicted.

  12. Lecithin retinol acyltransferase and its S175R mutant have a similar secondary structure content and maximum insertion pressure but different enzyme activities.

    PubMed

    Bussières, Sylvain; Cantin, Line; Salesse, Christian

    2011-11-01

    Recent work on Lecithin:retinol acyltransferase (LRAT) allowed to gather a large amount of information on its secondary structure, enzymatic properties and membrane binding. A truncated form of LRAT (tLRAT) as well as its S175R mutant leading to retinis pigmentosa, a severe form of retinal dystrophy, were studied to understand the role of this mutation on the dysfunction of this protein. Consistently with previous reports, the S175R-tLRAT mutant was shown to lack enzyme activity. However, very similar secondary structures probed by circular dichroism have been obtained with the S175R-tLRAT mutant and tLRAT. Moreover, similar values of maximum insertion pressure of the S175R-tLRAT mutant and tLRAT have been obtained using Langmuir monolayers, thus suggesting that the S175R mutation has no effect on the membrane binding properties of tLRAT. These findings leave open the possibility that the loss of enzymatic activity associated with the S175R mutant is related to loss of an essential nucleophile near the active site, or alternatively, to steric obstruction of the active site that impedes substrate binding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    PubMed

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

  14. Exploiting Data Similarity to Reduce Memory Footprints

    DTIC Science & Technology

    2011-01-01

    leslie3d Fortran Computational Fluid Dynamics (CFD) application 122. tachyon C Parallel Ray Tracing application 128.GAPgeofem C and Fortran Simulates...benefits most from SBLLmalloc; LAMMPS, which shows moderate similarity from primarily zero pages; and 122. tachyon , a parallel ray- tracing application...similarity across MPI tasks. They primarily are zero- pages although a small fraction (≈10%) are non-zero pages. 122. tachyon is an image rendering

  15. Focusing of noncircular self-similar shock waves.

    PubMed

    Betelu, S I; Aronson, D G

    2001-08-13

    We study the focusing of noncircular shock waves in a perfect gas. We construct an explicit self-similar solution by combining three convergent plane waves with regular shock reflections between them. We then show, with a numerical Riemann solver, that there are initial conditions with smooth shocks whose intermediate asymptotic stage is described by the exact solution. Unlike the focusing of circular shocks, our self-similar shocks have bounded energy density.

  16. The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

    PubMed Central

    Molinari, Agnese; Parisi, Chiara; Bozzuto, Giuseppina; Toccacieli, Laura; Formisano, Giuseppe; De Orsi, Daniela; Paradisi, Silvia; Grober, OlÌ Maria Victoria; Ravo, Maria; Weisz, Alessandro; Arcieri, Romano; Vella, Stefano; Gaudi, Simona

    2010-01-01

    Background Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines. Principal Findings ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. Conclusions Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications. PMID:21151977

  17. Similar call signs

    DOT National Transportation Integrated Search

    2010-08-18

    This presentation was given at the Partnership for Safety Meeting in Washington, DC. It examines the similarities that are found when calls signs are visually similar or similar sounding. Visually similar call signs increase the chances of controller...

  18. Shift workers have similar leisure-time physical activity levels as day workers but are more sedentary at work.

    PubMed

    Hulsegge, Gerben; Gupta, Nidhi; Holtermann, Andreas; Jørgensen, Marie Birk; Proper, Karin I; van der Beek, Allard J

    2017-03-01

    Objective Physical inactivity has been hypothesized as an underlying factor for the association between shift work and adverse health outcomes. We compared leisure-time and occupational physical activity and sedentary behavior between day, night, and non-night shift workers. Methods We identified 612 day workers, 139 night shift workers and 61 non-night shift workers aged 18-65 years (54% men) in two Danish studies: the New method for Objective Measurements of physical Activity in Daily living (NOMAD) and the Danish Physical ACTivity cohort with Objective measurements (DPhacto) between 2011-2013. Sedentary behavior, light, and moderate-to-vigorous physical activity were measured using an accelerometer. Physical activity was expressed as percentage of leisure and work time spent in each activity. Linear regression analyses were used to test differences in physical activity and sedentary behavior between day, night, and non-night shift workers. Results No differences in leisure-time sedentary behavior and physical activity were observed between day and shift workers (P>0.05). Non-night shift workers spent 7.2% [95% confidence interval (95% CI) 2.3-12.1) more time in occupational sedentary behavior than day workers and 5.9% (95% CI -10.1- -1.7) and 1.9% (95% CI -3.7- -0.2) less time in occupational light and moderate-to-vigorous physical activity, respectively. Compared to day workers, night shift workers spent 4.3% (95% CI 2.4-6.1) more time at work in uninterrupted sedentary periods of ≥30 minutes. Conclusions Shift workers had similar leisure-time physical activity patterns as day workers, but were more sedentary at work. Future research should elucidate whether occupational physical inactivity and sedentary behavior contributes to shift work-related adverse health effects.

  19. The baryonic self similarity of dark matter

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

    Alard, C., E-mail: alard@iap.fr

    2014-06-20

    The cosmological simulations indicates that dark matter halos have specific self-similar properties. However, the halo similarity is affected by the baryonic feedback. By using momentum-driven winds as a model to represent the baryon feedback, an equilibrium condition is derived which directly implies the emergence of a new type of similarity. The new self-similar solution has constant acceleration at a reference radius for both dark matter and baryons. This model receives strong support from the observations of galaxies. The new self-similar properties imply that the total acceleration at larger distances is scale-free, the transition between the dark matter and baryons dominatedmore » regime occurs at a constant acceleration, and the maximum amplitude of the velocity curve at larger distances is proportional to M {sup 1/4}. These results demonstrate that this self-similar model is consistent with the basics of modified Newtonian dynamics (MOND) phenomenology. In agreement with the observations, the coincidence between the self-similar model and MOND breaks at the scale of clusters of galaxies. Some numerical experiments show that the behavior of the density near the origin is closely approximated by a Einasto profile.« less

  20. Limiting similarity of competitive species and demographic stochasticity

    NASA Astrophysics Data System (ADS)

    Zheng, Xiu-Deng; Deng, Ling-Ling; Qiang, Wei-Ya; Cressman, Ross; Tao, Yi

    2017-04-01

    The limiting similarity of competitive species and its relationship with the competitive exclusion principle is still one of the most important concepts in ecology. In the 1970s, May [R. M. May, Stability and Complexity in Model Ecosystems (Princeton University, Princeton, NJ, 1973)] developed a concise theoretical framework to investigate the limiting similarity of competitive species. His theoretical results show that no limiting similarity threshold of competitive species can be identified in the deterministic model system whereby species more similar than this threshold never coexist. Theoretically, for competitive species coexisting in an unvarying environment, deterministic interspecific interactions and demographic stochasticity can be considered two sides of a coin. To investigate how the "tension" between these two forces affects the coexistence of competing species, a simple two-species competitive system based only on May's model system is transformed into an equivalent replicator equation. The effect of demographic stochasticity on the system stability is measured by the expected drift of the Lyapunov function. Our main results show that the limiting similarity of competitive species should not be considered to be an absolute measure. Specifically, very similar competitive species should be able to coexist in an environment with a high productivity level but big differences between competitive species should be necessary in an ecosystem with a low productivity level.

  1. Human Object-Similarity Judgments Reflect and Transcend the Primate-IT Object Representation

    PubMed Central

    Mur, Marieke; Meys, Mirjam; Bodurka, Jerzy; Goebel, Rainer; Bandettini, Peter A.; Kriegeskorte, Nikolaus

    2013-01-01

    Primate inferior temporal (IT) cortex is thought to contain a high-level representation of objects at the interface between vision and semantics. This suggests that the perceived similarity of real-world objects might be predicted from the IT representation. Here we show that objects that elicit similar activity patterns in human IT (hIT) tend to be judged as similar by humans. The IT representation explained the human judgments better than early visual cortex, other ventral-stream regions, and a range of computational models. Human similarity judgments exhibited category clusters that reflected several categorical divisions that are prevalent in the IT representation of both human and monkey, including the animate/inanimate and the face/body division. Human judgments also reflected the within-category representation of IT. However, the judgments transcended the IT representation in that they introduced additional categorical divisions. In particular, human judgments emphasized human-related additional divisions between human and non-human animals and between man-made and natural objects. hIT was more similar to monkey IT than to human judgments. One interpretation is that IT has evolved visual-feature detectors that distinguish between animates and inanimates and between faces and bodies because these divisions are fundamental to survival and reproduction for all primate species, and that other brain systems serve to more flexibly introduce species-dependent and evolutionarily more recent divisions. PMID:23525516

  2. Human active X-specific DNA methylation events showing stability across time and tissues

    PubMed Central

    Joo, Jihoon Eric; Novakovic, Boris; Cruickshank, Mark; Doyle, Lex W; Craig, Jeffrey M; Saffery, Richard

    2014-01-01

    The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression. The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a ‘patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping. Such genes are therefore potentially subject to sex-specific imbalance between males and females. Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa). Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin. Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans. Further work is needed to investigate these phenomena. PMID:24713664

  3. Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.

    PubMed

    Di Pisa, Flavio; Landi, Giacomo; Dello Iacono, Lucia; Pozzi, Cecilia; Borsari, Chiara; Ferrari, Stefania; Santucci, Matteo; Santarem, Nuno; Cordeiro-da-Silva, Anabela; Moraes, Carolina B; Alcantara, Laura M; Fontana, Vanessa; Freitas-Junior, Lucio H; Gul, Sheraz; Kuzikov, Maria; Behrens, Birte; Pöhner, Ina; Wade, Rebecca C; Costi, Maria Paola; Mangani, Stefano

    2017-03-08

    Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues ( 1 - 3 ) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes ( Trypanosoma brucei PTR1- Tb PTR1 and Leishmania major-Lm PTR1) and parasites ( Trypanosoma brucei and Leishmania infantum ). A crystal structure of Tb PTR1 in complex with compound 1 and the first crystal structures of Lm PTR1-flavanone complexes (compounds 1 and 3 ) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.

  4. Correlation between social proximity and mobility similarity.

    PubMed

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao

    2017-09-20

    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  5. A common neural code for similar conscious experiences in different individuals

    PubMed Central

    Naci, Lorina; Cusack, Rhodri; Anello, Mimma; Owen, Adrian M.

    2014-01-01

    The interpretation of human consciousness from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. We asked whether there is a common neural code that underpins similar conscious experiences, which could be used to decode these experiences in the absence of behavior. To this end, we used richly evocative stimulation (an engaging movie) portraying real-world events to elicit a similar conscious experience in different people. Common neural correlates of conscious experience were quantified and related to measurable, quantitative and qualitative, executive components of the movie through two additional behavioral investigations. The movie’s executive demands drove synchronized brain activity across healthy participants’ frontal and parietal cortices in regions known to support executive function. Moreover, the timing of activity in these regions was predicted by participants’ highly similar qualitative experience of the movie’s moment-to-moment executive demands, suggesting that synchronization of activity across participants underpinned their similar experience. Thus we demonstrate, for the first time to our knowledge, that a neural index based on executive function reliably predicted every healthy individual’s similar conscious experience in response to real-world events unfolding over time. This approach provided strong evidence for the conscious experience of a brain-injured patient, who had remained entirely behaviorally nonresponsive for 16 y. The patient’s executive engagement and moment-to-moment perception of the movie content were highly similar to that of every healthy participant. These findings shed light on the common basis of human consciousness and enable the interpretation of conscious experience in the absence of behavior. PMID:25225384

  6. DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae.

    PubMed

    Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko

    2016-09-01

    Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans.

  7. Kernel approach to molecular similarity based on iterative graph similarity.

    PubMed

    Rupp, Matthias; Proschak, Ewgenij; Schneider, Gisbert

    2007-01-01

    Similarity measures for molecules are of basic importance in chemical, biological, and pharmaceutical applications. We introduce a molecular similarity measure defined directly on the annotated molecular graph, based on iterative graph similarity and optimal assignments. We give an iterative algorithm for the computation of the proposed molecular similarity measure, prove its convergence and the uniqueness of the solution, and provide an upper bound on the required number of iterations necessary to achieve a desired precision. Empirical evidence for the positive semidefiniteness of certain parametrizations of our function is presented. We evaluated our molecular similarity measure by using it as a kernel in support vector machine classification and regression applied to several pharmaceutical and toxicological data sets, with encouraging results.

  8. Structural variants of yeast prions show conformer-specific requirements for chaperone activity

    PubMed Central

    Stein, Kevin C.; True, Heather L.

    2016-01-01

    Summary Molecular chaperones monitor protein homeostasis and defend against the misfolding and aggregation of proteins that is associated with protein conformational disorders. In these diseases, a variety of different aggregate structures can form. These are called prion strains, or variants, in prion diseases, and cause variation in disease pathogenesis. Here, we use variants of the yeast prions [RNQ+] and [PSI+] to explore the interactions of chaperones with distinct aggregate structures. We found that prion variants show striking variation in their relationship with Hsp40s. Specifically, the yeast Hsp40 Sis1, and its human ortholog Hdj1, had differential capacities to process prion variants, suggesting that Hsp40 selectivity has likely changed through evolution. We further show that such selectivity involves different domains of Sis1, with some prion conformers having a greater dependence on particular Hsp40 domains. Moreover, [PSI+] variants were more sensitive to certain alterations in Hsp70 activity as compared to [RNQ+] variants. Collectively, our data indicate that distinct chaperone machinery is required, or has differential capacity, to process different aggregate structures. Elucidating the intricacies of chaperone-client interactions, and how these are altered by particular client structures, will be crucial to understanding how this system can go awry in disease and contribute to pathological variation. PMID:25060529

  9. A Content Analysis of Physical Activity in TV Shows Popular Among Adolescents

    PubMed Central

    Gietzen, Megan S.; Gollust, Sarah E.; Linde, Jennifer A.; Neumark-Sztainer, Dianne; Eisenberg, Marla E.

    2017-01-01

    Purpose Previous research demonstrates that television has the potential to influence youth behaviors, but little evidence exists on how television depicts physical activity (PA), an important public health priority for youth. This mixed-methods study investigates depictions of television characters’ participation in PA in the top 25 favorite shows ranked by a diverse sample of 2,793 adolescents. Method Randomly selected episodes from each show were content analyzed for PA incidents, reasons and context, and in relation to the gender and weight status of participating characters. Results A total of 374 incidents of PA were coded across 75 episodes, with an average of 5.0 incidents per episode. Although male and female characters were equally likely to engage in at least one incident of PA, male characters were involved in a statistically significantly larger proportion of PA incidents than female characters and were more likely to engage in PA for competitive sport. There was no statistically significant difference in engagement in PA or the proportion of PA incidents for characters coded as overweight compared to non-overweight characters. Conclusions Although female characters tended to be underrepresented in PA, this study reveals positive messages for how gender and weight are portrayed in relation to PA on TV. PMID:28151062

  10. Privacy-preserving matching of similar patients.

    PubMed

    Vatsalan, Dinusha; Christen, Peter

    2016-02-01

    The identification of similar entities represented by records in different databases has drawn considerable attention in many application areas, including in the health domain. One important type of entity matching application that is vital for quality healthcare analytics is the identification of similar patients, known as similar patient matching. A key component of identifying similar records is the calculation of similarity of the values in attributes (fields) between these records. Due to increasing privacy and confidentiality concerns, using the actual attribute values of patient records to identify similar records across different organizations is becoming non-trivial because the attributes in such records often contain highly sensitive information such as personal and medical details of patients. Therefore, the matching needs to be based on masked (encoded) values while being effective and efficient to allow matching of large databases. Bloom filter encoding has widely been used as an efficient masking technique for privacy-preserving matching of string and categorical values. However, no work on Bloom filter-based masking of numerical data, such as integer (e.g. age), floating point (e.g. body mass index), and modulus (numbers wrap around upon reaching a certain value, e.g. date and time), which are commonly required in the health domain, has been presented in the literature. We propose a framework with novel methods for masking numerical data using Bloom filters, thereby facilitating the calculation of similarities between records. We conduct an empirical study on publicly available real-world datasets which shows that our framework provides efficient masking and achieves similar matching accuracy compared to the matching of actual unencoded patient records. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. A cry in the dark: depressed mothers show reduced neural activation to their own infant’s cry

    PubMed Central

    Ablow, Jennifer C.

    2012-01-01

    This study investigated depression-related differences in primiparous mothers’ neural response to their own infant’s distress cues. Mothers diagnosed with major depressive disorder (n = 11) and comparison mothers with no diagnosable psychopathology (n = 11) were exposed to their own 18-months-old infant’s cry sound, as well as unfamiliar infant’s cry and control sound, during functional neuroimaging. Depressed mothers’ response to own infant cry greater than other sounds was compared to non-depressed mothers’ response in the whole brain [false discovery rate (FDR) corrected]. A continuous measure of self-reported depressive symptoms (CESD) was also tested as a predictor of maternal response. Non-depressed mothers activated to their own infant’s cry greater than control sound in a distributed network of para/limbic and prefrontal regions, whereas depressed mothers as a group failed to show activation. Non-depressed compared to depressed mothers showed significantly greater striatal (caudate, nucleus accumbens) and medial thalamic activation. Additionally, mothers with lower depressive symptoms activated more strongly in left orbitofrontal, dorsal anterior cingulate and medial superior frontal regions. Non-depressed compared to depressed mothers activated uniquely to own infant greater than other infant cry in occipital fusiform areas. Disturbance of these neural networks involved in emotional response and regulation may help to explain parenting deficits in depressed mothers. PMID:21208990

  12. Do Parents Treat Siblings Similarly or Differently with Regard to Feeding Practices, Weight-Related Conversations, and Support for Physical Activity? An Exploratory Analysis

    PubMed Central

    Meyer, Craig; MacLehose, Richard F.; Loth, Katie; Neumark-Sztainer, Dianne

    2016-01-01

    Abstract Background: It is unknown if parents with more than one adolescent child use similar or different parenting practices of relevance to weight-related health with different children. In particular, it is unclear whether parenting practices differ based on whether siblings are discordant on weight status (i.e., one is overweight/obese, one is nonoverweight/obese) or are different sexes. Methods: Data from two linked population-based studies, Eating and Activity in Teens (EAT) 2010 and Families and Eating and Activity in Teens (F-EAT), were used in this exploratory cross-sectional analysis. Participants included socioeconomically and racially/ethnically diverse parents (n = 57; 93% females) and adolescent siblings (n = 57 pairs; 60% girls; mean age = 14.5, range = 11–18). Students filled out surveys and had anthropometric measures taken in school. Parents filled out mailed surveys in their homes. Results: Overall, results from this exploratory study showed limited evidence that parents use different parenting practices with adolescents of different weight status or sex. However, potentially important patterns emerged when exploring parenting practices and siblings' weight status. For example, within sibling dyads with discordant weight status, parents reported significantly more negative weight-related conversations with overweight/obese siblings compared to nonoverweight/obese siblings (p < 0.05). Although observed differences were not statistically significant, parents also reported higher levels of food restriction (p = 0.05) and encouragement to diet (p = 0.07) with overweight/obese siblings compared to nonoverweight/obese siblings. There were no significant differences in parenting practices by adolescent sex. Conclusions: Results generally suggest that parents use similar parenting practices with adolescent siblings. However, notable patterns emerged when examining parenting practices and siblings' weight status that may be

  13. Mononuclear nonheme iron(III) complexes that show superoxide dismutase-like activity and antioxidant effects against menadione-mediated oxidative stress.

    PubMed

    Hitomi, Yutaka; Iwamoto, Yuji; Kashida, Akihiro; Kodera, Masahito

    2015-05-21

    This communication describes the superoxide dismutase (SOD)-like activity of mononuclear iron(III) complexes with pentadentate monocarboxylamido ligands. The SOD activity can be controlled by the electronic nature of the substituent group on the ligand. The nitro-substituted complex showed clear cytoprotective activity against menadione-mediated oxidative stress in cultured cells.

  14. A motor similarity effect in object memory.

    PubMed

    Downing-Doucet, Frédéric; Guérard, Katherine

    2014-08-01

    In line with theories of embodied cognition (e.g., Versace et al. European Journal of Cognitive Psychology, 21, 522-560, 2009), several studies have suggested that the motor system used to interact with objects in our environment is involved in object recognition (e.g., Helbig, Graf, & Kiefer Experimental Brain Research, 174, 221-228, 2006). However, the role of the motor system in immediate memory for objects is more controversial. The objective of the present study was to investigate the role of the motor system in object memory by manipulating the similarity between the actions associated to series of objects to be retained in memory. In Experiment 1, we showed that lists of objects associated to dissimilar actions were better recalled than lists associated to similar actions. We then showed that this effect was abolished when participants were required to perform a concurrent motor suppression task (Experiment 2) and when the objects to be memorized were unmanipulable (Experiment 3). The motor similarity effect provides evidence for the role of motor affordances in object memory.

  15. Virtual screening by a new Clustering-based Weighted Similarity Extreme Learning Machine approach

    PubMed Central

    Kudisthalert, Wasu

    2018-01-01

    Machine learning techniques are becoming popular in virtual screening tasks. One of the powerful machine learning algorithms is Extreme Learning Machine (ELM) which has been applied to many applications and has recently been applied to virtual screening. We propose the Weighted Similarity ELM (WS-ELM) which is based on a single layer feed-forward neural network in a conjunction of 16 different similarity coefficients as activation function in the hidden layer. It is known that the performance of conventional ELM is not robust due to random weight selection in the hidden layer. Thus, we propose a Clustering-based WS-ELM (CWS-ELM) that deterministically assigns weights by utilising clustering algorithms i.e. k-means clustering and support vector clustering. The experiments were conducted on one of the most challenging datasets–Maximum Unbiased Validation Dataset–which contains 17 activity classes carefully selected from PubChem. The proposed algorithms were then compared with other machine learning techniques such as support vector machine, random forest, and similarity searching. The results show that CWS-ELM in conjunction with support vector clustering yields the best performance when utilised together with Sokal/Sneath(1) coefficient. Furthermore, ECFP_6 fingerprint presents the best results in our framework compared to the other types of fingerprints, namely ECFP_4, FCFP_4, and FCFP_6. PMID:29652912

  16. New sub-family of lysozyme-like proteins shows no catalytic activity: crystallographic and biochemical study of STM3605 protein from Salmonella Typhimurium

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

    Michalska, Karolina; Brown, Roslyn N.; Li, Hui

    Phage viruses that infect prokaryotes integrate their genome into the host chromosome; thus, microbial genomes typically contain genetic remnants of both recent and ancient phage infections. Often phage genes occur in clusters of atypical G+C content that reflect integration of the foreign DNA. However, some phage genes occur in isolation without other phage gene neighbors, probably resulting from horizontal gene transfer. In these cases, the phage gene product is unlikely to function as a component of a mature phage particle, and instead may have been co-opted by the host for its own benefit. The product of one such gene frommore » Salmonella enterica serovar Typhimurium, STM3605, encodes a protein with modest sequence similarity to phage-like lysozyme (N-acetylmuramidase) but appears to lack essential catalytic residues that are strictly conserved in all lysozymes. Close homologs in other bacteria share this characteristic. The structure of the STM3605 protein was characterized by X-ray crystallography, and functional assays showed that it is a stable, folded protein whose structure closely resembles lysozyme. However, this protein is unlikely to hydrolyze peptidoglycan. Instead, STM3605 is presumed to have evolved an alternative function because it shows some lytic activity and partitions to micelles.« less

  17. Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61.

    PubMed

    Huang, Kuan-Chun; Chen, Zhihong; Jiang, Yimin; Akare, Sandeep; Kolber-Simonds, Donna; Condon, Krista; Agoulnik, Sergei; Tendyke, Karen; Shen, Yongchun; Wu, Kuo-Ming; Mathieu, Steven; Choi, Hyeong-Wook; Zhu, Xiaojie; Shimizu, Hajime; Kotake, Yoshihiko; Gerwick, William H; Uenaka, Toshimitsu; Woodall-Jappe, Mary; Nomoto, Kenichi

    2016-06-01

    Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A-treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a (3)H-labeled apratoxin A probe and specific Sec 61α/β antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure. Mol Cancer Ther; 15(6); 1208-16. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

    PubMed

    Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice

    2015-08-01

    Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly

  19. A Paradox of Syntactic Priming: Why Response Tendencies Show Priming for Passives, and Response Latencies Show Priming for Actives

    PubMed Central

    Segaert, Katrien; Menenti, Laura; Weber, Kirsten; Hagoort, Peter

    2011-01-01

    Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing. PMID:22022352

  20. Towards Personalized Medicine: Leveraging Patient Similarity and Drug Similarity Analytics

    PubMed Central

    Zhang, Ping; Wang, Fei; Hu, Jianying; Sorrentino, Robert

    2014-01-01

    The rapid adoption of electronic health records (EHR) provides a comprehensive source for exploratory and predictive analytic to support clinical decision-making. In this paper, we investigate how to utilize EHR to tailor treatments to individual patients based on their likelihood to respond to a therapy. We construct a heterogeneous graph which includes two domains (patients and drugs) and encodes three relationships (patient similarity, drug similarity, and patient-drug prior associations). We describe a novel approach for performing a label propagation procedure to spread the label information representing the effectiveness of different drugs for different patients over this heterogeneous graph. The proposed method has been applied on a real-world EHR dataset to help identify personalized treatments for hypercholesterolemia. The experimental results demonstrate the effectiveness of the approach and suggest that the combination of appropriate patient similarity and drug similarity analytics could lead to actionable insights for personalized medicine. Particularly, by leveraging drug similarity in combination with patient similarity, our method could perform well even on new or rarely used drugs for which there are few records of known past performance. PMID:25717413

  1. An Experimental Study on the Iso-Content-Based Angle Similarity Measure.

    ERIC Educational Resources Information Center

    Zhang, Jin; Rasmussen, Edie M.

    2002-01-01

    Retrieval performance of the iso-content-based angle similarity measure within the angle, distance, conjunction, disjunction, and ellipse retrieval models is compared with retrieval performance of the distance similarity measure and the angle similarity measure. Results show the iso-content-based angle similarity measure achieves satisfactory…

  2. Honey shows potent inhibitory activity against the bovine testes hyaluronidase.

    PubMed

    Kolayli, Sevgi; Sahin, Huseyin; Can, Zehra; Yildiz, Oktay; Sahin, Kübra

    2016-08-01

    The purpose of this study was to investigate the anti-hyaluronidase activities of honeys from different botanical origins honeys in order to determine their anti-inflammatory properties. The total phenolic contents, total flavonoids and total tannin levels of six types of honey, chestnut, oak, heather, pine, buckwheat and mixed blossom, were determined. Concentration-related inhibition values were tested turbidimetrically on bovine testis hyaluronidase (BTHase) as IC50 (mg/mL). All honeys exhibited various concentration-dependent degrees of inhibition against BTHase. Inhibition values varied significantly depending on honeys' levels of phenolic contents, flavonoid and tannin. The honeys with the highest anti-hyaluronidase activity were oak, chestnut and heather. In conclusion, polyphenol-rich honeys have high anti-hyaluronidase activity, and these honeys have high protective and complementary potential against hyaluronidase-induced anti-inflammatory failures.

  3. Genome Compositional Organization in Gars Shows More Similarities to Mammals than to Other Ray-Finned Fish.

    PubMed

    Symonová, Radka; Majtánová, Zuzana; Arias-Rodriguez, Lenin; Mořkovský, Libor; Kořínková, Tereza; Cavin, Lionel; Pokorná, Martina Johnson; Doležálková, Marie; Flajšhans, Martin; Normandeau, Eric; Ráb, Petr; Meyer, Axel; Bernatchez, Louis

    2017-11-01

    Genomic GC content can vary locally, and GC-rich regions are usually associated with increased DNA thermostability in thermophilic prokaryotes and warm-blooded eukaryotes. Among vertebrates, fish and amphibians appeared to possess a distinctly less heterogeneous AT/GC organization in their genomes, whereas cytogenetically detectable GC heterogeneity has so far only been documented in mammals and birds. The subject of our study is the gar, an ancient "living fossil" of a basal ray-finned fish lineage, known from the Cretaceous period. We carried out cytogenomic analysis in two gar genera (Atractosteus and Lepisosteus) uncovering a GC chromosomal pattern uncharacteristic for fish. Bioinformatic analysis of the spotted gar (Lepisosteus oculatus) confirmed a GC compartmentalization on GC profiles of linkage groups. This indicates a rather mammalian mode of compositional organization on gar chromosomes. Gars are thus the only analyzed extant ray-finned fishes with a GC compartmentalized genome. Since gars are cold-blooded anamniotes, our results contradict the generally accepted hypothesis that the phylogenomic onset of GC compartmentalization occurred near the origin of amniotes. Ecophysiological findings of other authors indicate a metabolic similarity of gars with mammals. We hypothesize that gars might have undergone convergent evolution with the tetrapod lineages leading to mammals on both metabolic and genomic levels. Their metabolic adaptations might have left footprints in their compositional genome evolution, as proposed by the metabolic rate hypothesis. The genome organization described here in gars sheds new light on the compositional genome evolution in vertebrates generally and contributes to better understanding of the complexities of the mechanisms involved in this process. © 2016 Wiley Periodicals, Inc.

  4. Regular Fat and Reduced Fat Dairy Products Show Similar Associations with Markers of Adolescent Cardiometabolic Health

    PubMed Central

    O’Sullivan, Therese A.; Bremner, Alexandra P.; Mori, Trevor A.; Beilin, Lawrence J.; Wilson, Charlotte; Hafekost, Katherine; Ambrosini, Gina L.; Huang, Rae Chi; Oddy, Wendy H.

    2016-01-01

    Reduced fat dairy products are generally recommended for adults and children over the age of two years. However, emerging evidence suggests that dairy fat may not have detrimental health effects. We aimed to investigate prospective associations between consumption of regular versus reduced fat dairy products and cardiometabolic risk factors from early to late adolescence. In the West Australian Raine Study, dairy intake was assessed using semi-quantitative food frequency questionnaires in 860 adolescents at 14 and 17-year follow-ups; 582 of these also had blood biochemistry at both points. Using generalized estimating equations, we examined associations with cardiometabolic risk factors. Models incorporated reduced fat and regular fat dairy together (in serves/day) and were adjusted for a range of factors including overall dietary pattern. In boys, there was a mean reduction in diastolic blood pressure of 0.66 mmHg (95% CI 0.23–1.09) per serve of reduced fat dairy and an independent, additional reduction of 0.47 mmHg (95% CI 0.04–0.90) per serve of regular fat dairy. Each additional serve of reduced fat dairy was associated with a 2% reduction in HDL-cholesterol (95% CI 0.97–0.995) and a 2% increase in total: HDL-cholesterol ratio (95% CI 1.002–1.03); these associations were not observed with regular fat products. In girls, there were no significant independent associations observed in fully adjusted models. Although regular fat dairy was associated with a slightly better cholesterol profile in boys, overall, intakes of both regular fat and reduced fat dairy products were associated with similar cardiometabolic associations in adolescents. PMID:26729163

  5. Inter- and Intrasubject Similarity of Muscle Synergies During Bench Press With Slow and Fast Velocity.

    PubMed

    Samani, Afshin; Kristiansen, Mathias

    2018-01-01

    We investigated the effect of low and high bar velocity on inter- and intrasubject similarity of muscle synergies during bench press. A total of 13 trained male subjects underwent two exercise conditions: a slow- and a fast-velocity bench press. Surface electromyography was recorded from 13 muscles, and muscle synergies were extracted using a nonnegative matrix factorization algorithm. The intrasubject similarity across conditions and intersubject similarity within conditions were computed for muscle synergy vectors and activation coefficients. Two muscle synergies were sufficient to describe the dataset variability. For the second synergy activation coefficient, the intersubject similarity within the fast-velocity condition was greater than the intrasubject similarity of the activation coefficient across the conditions. An opposite pattern was observed for the first muscle synergy vector. We concluded that the activation coefficients are robust within conditions, indicating a robust temporal pattern of muscular activity across individuals, but the muscle synergy vector seemed to be individually assigned.

  6. Song trait similarity in great tits varies with social structure.

    PubMed

    Snijders, Lysanne; van der Eijk, Jerine; van Rooij, Erica P; de Goede, Piet; van Oers, Kees; Naguib, Marc

    2015-01-01

    For many animals, long-range signalling is essential to maintain contact with conspecifics. In territorial species, individuals often have to balance signalling towards unfamiliar potential competitors (to solely broadcast territory ownership) with signalling towards familiar immediate neighbours (to also maintain so-called "dear enemy" relations). Hence, to understand how signals evolve due to these multilevel relationships, it is important to understand how general signal traits vary in relation to the overall social environment. For many territorial songbirds dawn is a key signalling period, with several neighbouring individuals singing simultaneously without immediate conflict. In this study we tested whether sharing a territory boundary, rather than spatial proximity, is related to similarity in dawn song traits between territorial great tits (Parus major) in a wild personality-typed population. We collected a large dataset of automatized dawn song recordings from 72 unique male great tits, during the fertile period of their mate, and compared specific song traits between neighbours and non-neighbours. We show here that both song rate and start time of dawn song were repeatable song traits. Moreover, neighbours were significantly more dissimilar in song rate compared to non-neighbours, while there was no effect of proximity on song rate similarity. Additionally, similarity in start time of dawn song was unrelated to sharing a territory boundary, but birds were significantly more similar in start time of dawn song when they were breeding in close proximity of each other. We suggest that the dissimilarity in dawn song rate between neighbours is either the result of neighbouring great tits actively avoiding similar song rates to possibly prevent interference, or a passive consequence of territory settlement preferences relative to the types of neighbours. Neighbourhood structuring is therefore likely to be a relevant selection pressure shaping variation in

  7. Topically Delivered Adipose Derived Stem Cells Show an Activated-Fibroblast Phenotype and Enhance Granulation Tissue Formation in Skin Wounds

    DTIC Science & Technology

    2013-01-31

    have similar surface markers . We found that topically delivered ASCs are engrafted and proliferate in the wounds. We showed that transplanted ASCs...Material Command (W81XWH-10-2-0054). Flow cytometry was supported by the Northwestern University Flow Cytometry Facility and a Cancer Center Support...blasticidin. GFP expressing cells were further selected by flow cytometry using the Northwestern University Flow Cytometry Facility. Treatment of MSCs

  8. Older adults show higher increases in lower-limb muscle activity during whole-body vibration exercise.

    PubMed

    Lienhard, Karin; Vienneau, Jordyn; Nigg, Sandro; Friesenbichler, Bernd; Nigg, Benno M

    2017-02-08

    The purpose of this study was to compare lower limb muscle activity during whole-body vibration (WBV) exercise between a young and an older study population. Thirty young (25.9±4.3yrs) and thirty older (64.2±5.3yrs) individuals stood on a side-alternating WBV platform while surface electromyography (sEMG) was measured for the tibialis anterior (TA), gastrocnemius medialis (GM), soleus (SOL), vastus lateralis (VL), vastus medialis (VM), and biceps femoris (BF). The WBV protocol included nine vibration settings consisting of three frequencies (6, 11, 16Hz) x three amplitudes (0.9, 2.5, 4.0mm), and three control trials without vibration (narrow, medium, wide stance). The vertical platform acceleration (peak values of maximal displacement from equilibrium) was quantified during each vibration exercise using an accelerometer. The outcomes of this study showed that WBV significantly increased muscle activity in both groups for most vibration conditions in the TA (averaged absolute increase: young: +3.9%, older: +18.4%), GM (young: +4.1%, older: +9.5%), VL (young: +6.3%, older: +12.6%) and VM (young: +5.4%, older: +8.0%), and for the high frequency-amplitude combinations in the SOL (young: +7.5%, older: +12.6%) and BF (young: +1.9%, older: +7.5%). The increases in sEMG activity were significantly higher in the older than the young adults for all muscles, i.e., TA (absolute difference: 13.8%, P<0.001), GM (4.6%, P=0.034), VL (7.6%, P=0.001), VM (6.7%, P=0.042), BF (6.4%, P<0.001), except for the SOL (0.3%, P=0.248). Finally, the vertical platform acceleration was a significant predictor of the averaged lower limb muscle activity in the young (r=0.917, P<0.001) and older adults (r=0.931, P<0.001). In conclusion, the older population showed greater increases in lower limb muscle activity during WBV exercise than their young counterparts, meaning that they might benefit more from WBV exercises. Additionally, training intensity can be increased by increasing the vertical

  9. Exploiting Pharmacological Similarity to Identify Safety Concerns - Listen to What the Data Tells You.

    PubMed

    Muthas, Daniel; Boyer, Scott

    2013-01-01

    Whilst most new drugs are designed to act on a single target or a small number of targets, many do show broad pharmacological activity. In some cases this can be beneficial and necessary for efficacy and in others it can be detrimental, leading to increased safety liability. To probe off-target pharmacology most drug discovery programs include screening against a broad panel of targets that represent known troublesome pharmacology. Hits against any one of these targets can then be subjected to a risk assessment for potential safety problems in preclinical or clinical studies. In addition, the secondary pharmacology profile can also be thought of as an alternative description of the compound and as such can be used as a method for assessing 'similarity'. Consequently, inspection of the in vivo findings of pharmacological neighbors can give important insights into potential safety liabilities that are neither identified by pure chemical similarity searches nor by risk assessment on individual targets. Here we show that the pharmacological profile contains additional information as compared to chemical similarity, and also demonstrate how this can be used in the hazard assessment done during drug discovery and development. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Dillapiole, isolated from Peperomia pellucida, shows gastroprotector activity against ethanol-induced gastric lesions in Wistar rats.

    PubMed

    Rojas-Martínez, Raúl; Arrieta, Jesús; Cruz-Antonio, Leticia; Arrieta-Baez, Daniel; Velázquez-Méndez, Antonio Magdiel; Sánchez-Mendoza, María Elena

    2013-09-13

    Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups.

  11. Phonological similarity in working memory span tasks.

    PubMed

    Chow, Michael; Macnamara, Brooke N; Conway, Andrew R A

    2016-08-01

    In a series of four experiments, we explored what conditions are sufficient to produce a phonological similarity facilitation effect in working memory span tasks. By using the same set of memoranda, but differing the secondary-task requirements across experiments, we showed that a phonological similarity facilitation effect is dependent upon the semantic relationship between the memoranda and the secondary-task stimuli, and is robust to changes in the representation, ordering, and pool size of the secondary-task stimuli. These findings are consistent with interference accounts of memory (Brown, Neath, & Chater, Psychological Review, 114, 539-576, 2007; Oberauer, Lewandowsky, Farrell, Jarrold, & Greaves, Psychonomic Bulletin & Review, 19, 779-819, 2012), whereby rhyming stimuli provide a form of categorical similarity that allows distractors to be excluded from retrieval at recall.

  12. Spatially Pooled Contrast Responses Predict Neural and Perceptual Similarity of Naturalistic Image Categories

    PubMed Central

    Groen, Iris I. A.; Ghebreab, Sennay; Lamme, Victor A. F.; Scholte, H. Steven

    2012-01-01

    The visual world is complex and continuously changing. Yet, our brain transforms patterns of light falling on our retina into a coherent percept within a few hundred milliseconds. Possibly, low-level neural responses already carry substantial information to facilitate rapid characterization of the visual input. Here, we computationally estimated low-level contrast responses to computer-generated naturalistic images, and tested whether spatial pooling of these responses could predict image similarity at the neural and behavioral level. Using EEG, we show that statistics derived from pooled responses explain a large amount of variance between single-image evoked potentials (ERPs) in individual subjects. Dissimilarity analysis on multi-electrode ERPs demonstrated that large differences between images in pooled response statistics are predictive of more dissimilar patterns of evoked activity, whereas images with little difference in statistics give rise to highly similar evoked activity patterns. In a separate behavioral experiment, images with large differences in statistics were judged as different categories, whereas images with little differences were confused. These findings suggest that statistics derived from low-level contrast responses can be extracted in early visual processing and can be relevant for rapid judgment of visual similarity. We compared our results with two other, well- known contrast statistics: Fourier power spectra and higher-order properties of contrast distributions (skewness and kurtosis). Interestingly, whereas these statistics allow for accurate image categorization, they do not predict ERP response patterns or behavioral categorization confusions. These converging computational, neural and behavioral results suggest that statistics of pooled contrast responses contain information that corresponds with perceived visual similarity in a rapid, low-level categorization task. PMID:23093921

  13. Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate

    PubMed Central

    Pieme, Constant Anatole; Ngoupayo, Joseph; Khou-Kouz Nkoulou, Claude Herve; Moukette Moukette, Bruno; Njinkio Nono, Borgia Legrand; Ama Moor, Vicky Jocelyne; Ze Minkande, Jacqueline; Yonkeu Ngogang, Jeanne

    2014-01-01

    The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities. PMID:26785075

  14. The Role of Familiarity, Priming and Perception in Similarity Judgments

    DTIC Science & Technology

    2013-08-01

    Goldstone, & Markman, 1995), and memory (Roediger, 1990). As with many aspects of human cognition, however, the mechanisms that determine similarity are...activation, which disperses activation be- tween different, associated concepts in declarative memory (Anderson, 1983; Harrison & Trafton, 2010). In...over time the model builds up declarative memories that may contribute to spreading activation in later trials. This explains the two main effects

  15. Nonlinear Analysis of Motor Activity Shows Differences between Schizophrenia and Depression: A Study Using Fourier Analysis and Sample Entropy

    PubMed Central

    Hauge, Erik R.; Berle, Jan Øystein; Oedegaard, Ketil J.; Holsten, Fred; Fasmer, Ole Bernt

    2011-01-01

    The purpose of this study has been to describe motor activity data obtained by using wrist-worn actigraphs in patients with schizophrenia and major depression by the use of linear and non-linear methods of analysis. Different time frames were investigated, i.e., activity counts measured every minute for up to five hours and activity counts made hourly for up to two weeks. The results show that motor activity was lower in the schizophrenic patients and in patients with major depression, compared to controls. Using one minute intervals the depressed patients had a higher standard deviation (SD) compared to both the schizophrenic patients and the controls. The ratio between the root mean square successive differences (RMSSD) and SD was higher in the schizophrenic patients compared to controls. The Fourier analysis of the activity counts measured every minute showed that the relation between variance in the low and the high frequency range was lower in the schizophrenic patients compared to the controls. The sample entropy was higher in the schizophrenic patients compared to controls in the time series from the activity counts made every minute. The main conclusions of the study are that schizophrenic and depressive patients have distinctly different profiles of motor activity and that the results differ according to period length analysed. PMID:21297977

  16. The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein family, shows similarity to type III secretion chaperones but suggests different cellular functions

    PubMed Central

    Bartho, Joseph D.; Bellini, Dom; Wuerges, Jochen; Demitri, Nicola; Toccafondi, Mirco; Schmitt, Armin O.; Zhao, Youfu; Walsh, Martin A.

    2017-01-01

    AmyR is a stress and virulence associated protein from the plant pathogenic Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora AmyR reveals a class I type III secretion chaperone-like fold, despite the lack of sequence similarity between these two classes of protein and lacking any evidence of a secretion-associated role. The results indicate that AmyR, and YbjN proteins in general, function through protein-protein interactions without any enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low sequence similarity with other members of the YbjN protein family in Eubacteria, yet a high level of structural conservation is observed. Across the YbjN protein family sequence conservation is limited to residues stabilising the protein core and dimerization interface, while interacting regions are only conserved between closely related species. This study presents the first structure of a YbjN protein from Enterobacteriaceae, the most highly divergent and well-studied subgroup of YbjN proteins, and an in-depth sequence and structural analysis of this important but poorly understood protein family. PMID:28426806

  17. The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein family, shows similarity to type III secretion chaperones but suggests different cellular functions.

    PubMed

    Bartho, Joseph D; Bellini, Dom; Wuerges, Jochen; Demitri, Nicola; Toccafondi, Mirco; Schmitt, Armin O; Zhao, Youfu; Walsh, Martin A; Benini, Stefano

    2017-01-01

    AmyR is a stress and virulence associated protein from the plant pathogenic Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora AmyR reveals a class I type III secretion chaperone-like fold, despite the lack of sequence similarity between these two classes of protein and lacking any evidence of a secretion-associated role. The results indicate that AmyR, and YbjN proteins in general, function through protein-protein interactions without any enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low sequence similarity with other members of the YbjN protein family in Eubacteria, yet a high level of structural conservation is observed. Across the YbjN protein family sequence conservation is limited to residues stabilising the protein core and dimerization interface, while interacting regions are only conserved between closely related species. This study presents the first structure of a YbjN protein from Enterobacteriaceae, the most highly divergent and well-studied subgroup of YbjN proteins, and an in-depth sequence and structural analysis of this important but poorly understood protein family.

  18. Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

    PubMed Central

    Kumar, Amit; Tripathi, Amit Kumar; Kathuria, Manoj; Shree, Sonal; Tripathi, Jitendra Kumar; Purshottam, R. K.; Ramachandran, Ravishankar; Mitra, Kalyan

    2016-01-01

    Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with

  19. Phylogeny, Traits, and Biodiversity of a Neotropical Bat Assemblage: Close Relatives Show Similar Responses to Local Deforestation.

    PubMed

    Frank, Hannah K; Frishkoff, Luke O; Mendenhall, Chase D; Daily, Gretchen C; Hadly, Elizabeth A

    2017-08-01

    If species' evolutionary pasts predetermine their responses to evolutionarily novel stressors, then phylogeny could predict species survival in an increasingly human-dominated world. To understand the role of phylogenetic relatedness in structuring responses to rapid environmental change, we focused on assemblages of Neotropical bats, an ecologically diverse and functionally important group. We examined how taxonomic and phylogenetic diversity shift between tropical forest and farmland. We then explored the importance of evolutionary history by ascertaining whether close relatives share similar responses to environmental change and which species traits might mediate these trends. We analyzed a 5-year data set (5,011 captures) from 18 sites in a countryside landscape in southern Costa Rica using statistical models that account and correct for imperfect detection of species across sites, spatial autocorrelation, and consideration of spatial scale. Taxonomic and phylogenetic diversity decreased with deforestation, and assemblages became more phylogenetically clustered. Species' responses to deforestation were strongly phylogenetically correlated. Body mass and absolute wing loading explained a substantial portion of species variation in species' habitat preferences, likely related to these traits' influence on maneuverability in cluttered forest environments. Our findings highlight the role that evolutionary history plays in determining which species will survive human impacts and the need to consider diversity metrics, evolutionary history, and traits together when making predictions about species persistence for conservation or ecosystem functioning.

  20. The Influence of Similarity on Visual Working Memory Representations

    PubMed Central

    Lin, Po-Han; Luck, Steven J.

    2007-01-01

    In verbal memory, similarity between items in memory often leads to interference and impaired memory performance. The present study sought to determine whether analogous interference effects would be observed in visual working memory by varying the similarity of the to-be-remembered objects in a color change-detection task. Instead of leading to interference and impaired performance, increased similarity among the items being held in memory led to improved performance. Moreover, when two similar colors were presented along with one dissimilar color, memory performance was better for the similar colors than for the dissimilar color. Similarity produced better performance even when the objects were presented sequentially and even when memory for the first item in the sequence was tested. These findings show that similarity does not lead to interference between representations in visual working memory. Instead, similarity may lead to improved task performance, possibly due to increased stability or precision of the memory representations during maintenance. PMID:19430536

  1. Similar Cerebral Motor Plans for Real and Virtual Actions

    PubMed Central

    Bozzacchi, Chiara; Giusti, Maria Assunta; Pitzalis, Sabrina; Spinelli, Donatella; Di Russo, Francesco

    2012-01-01

    A simple movement, such as pressing a button, can acquire different meanings by producing different consequences, such as starting an elevator or switching a TV channel. We evaluated whether the brain activity preceding a simple action is modulated by the expected consequences of the action itself. To further this aim, the motor-related cortical potentials were compared during two key-press actions that were identical from the kinematics point of view but different in both meaning and consequences. In one case (virtual grasp), the key-press started a video clip showing a hand moving toward a cup and grasping it; in the other case, the key-press did not produce any consequence (key-press). A third condition (real grasp) was also compared, in which subjects actually grasped the cup, producing the same action presented in the video clip. Data were collected from fifteen subjects. The results showed that motor preparation for virtual grasp (starting 3 s before the movement onset) was different from that of the key-press and similar to the real grasp preparation–as if subjects had to grasp the cup in person. In particular, both virtual and real grasp presented a posterior parietal negativity preceding activity in motor and pre-motor areas. In summary, this finding supports the hypothesis that motor preparation is affected by the meaning of the action, even when the action is only virtual. PMID:23112847

  2. Effects of psychosocial variables in the similarity and interdependence of physical activity levels among adolescent best friend dyads.

    PubMed

    Lopes, Vítor P; Gabbard, Carl; Rodrigues, Luis P

    2016-01-01

    Given that physical activity (PA) tends to decrease with age during adolescence, addressing factors that affect change is important. This study examined the similarity and interdependence of PA as influenced by psychosocial factors among adolescent best friend dyads. A total of 660 adolescents, representing 330 best friend dyads, completed questionnaires with regard to PA, sitting time, perceived exercise benefits and barriers, physical self-perception and social support for PA. Dyads were also identified as reciprocal and non-reciprocal best friends; reciprocal means that both considered each other best friends and non-reciprocal were those in which only one considered the other a best friend. Data were analysed using a hierarchical linear model framework. Results indicated significant similarities between reciprocal best friend dyads for PA and sitting time, and for sitting time in non-reciprocal best friends (P values <.01). Psychosocial variables were associated with PA in reciprocal best friend dyads and with sitting time in reciprocal and non-reciprocal best friend dyads. Best friend gender, regular sports practice of the person, perceived exercise barriers of the best friend and best friend social support were the best predictors for PA.

  3. Personality similarity in negotiations: Testing the dyadic effects of similarity in interpersonal traits and the use of emotional displays on negotiation outcomes.

    PubMed

    Wilson, Kelly Schwind; DeRue, D Scott; Matta, Fadel K; Howe, Michael; Conlon, Donald E

    2016-10-01

    We build on the small but growing literature documenting personality influences on negotiation by examining how the joint disposition of both negotiators with respect to the interpersonal traits of agreeableness and extraversion influences important negotiation processes and outcomes. Building on similarity-attraction theory, we articulate and demonstrate how being similarly high or similarly low on agreeableness and extraversion leads dyad members to express more positive emotional displays during negotiation. Moreover, because of increased positive emotional displays, we show that dyads with such compositions also tend to reach agreements faster, perceive less relationship conflict, and have more positive impressions of their negotiation partner. Interestingly, these results hold regardless of whether negotiating dyads are similar in normatively positive (i.e., similarly agreeable and similarly extraverted) or normatively negative (i.e., similarly disagreeable and similarly introverted) ways. Overall, these findings demonstrate the importance of considering the dyad's personality configuration when attempting to understand the affective experience as well as the downstream outcomes of a negotiation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  4. Diterpenes from buds of Wikstroemia chamaedaphne showing anti-hepatitis B virus activities.

    PubMed

    Li, Shi-Fei; Jiao, Ying-Ying; Zhang, Zhi-Qiang; Chao, Jian-Bin; Jia, Jie; Shi, Xun-Long; Zhang, Li-Wei

    2018-07-01

    Phytochemical study of the buds of Wikstroemia chamaedaphne Meisn. led to the isolation of seven previously undescribed diterpenes, including one tigliane diterpene (wikstchalide A), two daphnane diterpenes (wikstroelides W-X), and four lathyrane diterpenes (laurifoliosides A-B and 2-epi-laurifoliosides A-B), along with four known diterpenes. The structures of these compounds were established by extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. Wikstchalide A possesses a 5,6-epoxy ring in the tigliane skeleton. Two compounds exhibited potential anti-hepatitis B virus activities, with IC 50 values of 46.5 and 88.3 μg/mL against hepatitis B virus (HBV) surface antigen (HBsAg), and six compounds showed certain inhibitory effects on HBV-DNA replication with the inhibition ratios ranging from 2.0% to 33.0% at the concentrations ranging from 0.39 to 6.25 μg/mL. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Development of a NIR-based blend uniformity method for a drug product containing multiple structurally similar actives by using the quality by design principles.

    PubMed

    Lin, Yiqing; Li, Weiyong; Xu, Jin; Boulas, Pierre

    2015-07-05

    The aim of this study is to develop an at-line near infrared (NIR) method for the rapid and simultaneous determination of four structurally similar active pharmaceutical ingredients (APIs) in powder blends intended for the manufacturing of tablets. Two of the four APIs in the formula are present in relatively small amounts, one at 0.95% and the other at 0.57%. Such small amounts in addition to the similarity in structures add significant complexity to the blend uniformity analysis. The NIR method is developed using spectra from six laboratory-created calibration samples augmented by a small set of spectra from a large-scale blending sample. Applying the quality by design (QbD) principles, the calibration design included concentration variations of the four APIs and a main excipient, microcrystalline cellulose. A bench-top FT-NIR instrument was used to acquire the spectra. The obtained NIR spectra were analyzed by applying principal component analysis (PCA) before calibration model development. Score patterns from the PCA were analyzed to reveal relationship between latent variables and concentration variations of the APIs. In calibration model development, both PLS-1 and PLS-2 models were created and evaluated for their effectiveness in predicting API concentrations in the blending samples. The final NIR method shows satisfactory specificity and accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Representational Similarity Analysis – Connecting the Branches of Systems Neuroscience

    PubMed Central

    Kriegeskorte, Nikolaus; Mur, Marieke; Bandettini, Peter

    2008-01-01

    A fundamental challenge for systems neuroscience is to quantitatively relate its three major branches of research: brain-activity measurement, behavioral measurement, and computational modeling. Using measured brain-activity patterns to evaluate computational network models is complicated by the need to define the correspondency between the units of the model and the channels of the brain-activity data, e.g., single-cell recordings or voxels from functional magnetic resonance imaging (fMRI). Similar correspondency problems complicate relating activity patterns between different modalities of brain-activity measurement (e.g., fMRI and invasive or scalp electrophysiology), and between subjects and species. In order to bridge these divides, we suggest abstracting from the activity patterns themselves and computing representational dissimilarity matrices (RDMs), which characterize the information carried by a given representation in a brain or model. Building on a rich psychological and mathematical literature on similarity analysis, we propose a new experimental and data-analytical framework called representational similarity analysis (RSA), in which multi-channel measures of neural activity are quantitatively related to each other and to computational theory and behavior by comparing RDMs. We demonstrate RSA by relating representations of visual objects as measured with fMRI in early visual cortex and the fusiform face area to computational models spanning a wide range of complexities. The RDMs are simultaneously related via second-level application of multidimensional scaling and tested using randomization and bootstrap techniques. We discuss the broad potential of RSA, including novel approaches to experimental design, and argue that these ideas, which have deep roots in psychology and neuroscience, will allow the integrated quantitative analysis of data from all three branches, thus contributing to a more unified systems neuroscience. PMID:19104670

  7. The similarity of broad iron lines in X-ray binaries and active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Walton, D. J.; Reis, R. C.; Cackett, E. M.; Fabian, A. C.; Miller, J. M.

    2012-05-01

    We have compared the 2001 XMM-Newton spectra of the stellar mass black hole binary XTE J1650-500 and the active galaxy MCG-6-30-15, focusing on the broad, excess emission features at ˜4-7 keV displayed by both sources. Such features are frequently observed in both low-mass X-ray binaries and active galactic nuclei (AGN). For the former case it is generally accepted that the excess arises due to iron emission, but there is some controversy over whether their width is partially enhanced by instrumental processes, and hence also over the intrinsic broadening mechanism. Meanwhile, in the latter case, the origin of this feature is still subject to debate; physically motivated reflection and absorption interpretations are both able to reproduce the observed spectra. In this work we make use of the contemporaneous BeppoSAX data to demonstrate that the breadth of the excess observed in XTE J1650-500 is astrophysical rather than instrumental, and proceed to highlight the similarity of the excesses present in this source and MCG-6-30-15. Both optically thick accretion discs and optically thin coronae, which in combination naturally give rise to relativistically broadened iron lines when the disc extends close to the black hole, are commonly observed in both classes of object. The simplest solution is that the broad emission features present arise from a common process, which we argue must be reflection from the inner regions of an accretion disc around a rapidly rotating black hole; for XTE J1650-500 we find spin constraints of 0.84 ≤a*≤ 0.98 at the 90 per cent confidence level. Other interpretations proposed for AGN add potentially unnecessary complexities to the theoretical framework of accretion in strong gravity.

  8. Electrophysiological evidence showing muscarinic agonist-antagonist activities of N-desmethylclozapine using hippocampal excitatory and inhibitory neurons.

    PubMed

    Sugawara, Yuto; Kikuchi, Yui; Yoneda, Mitsugu; Ohno-Shosaku, Takako

    2016-07-01

    The atypical antipsychotic clozapine is widely used for treatment-resistant schizophrenic patients. Clozapine and its major active metabolite, N-desmethylclozapine (NDMC), have complex pharmacological properties, and interact with various neurotransmitter receptors. There are several biochemical studies reporting that NDMC exhibits a partial agonist profile at the human recombinant M1 muscarinic receptors. However, direct electrophysiological evidence showing the ability of NDMC to activate native M1 receptors in intact neurons is poor. Using rat hippocampal neurons, we previously demonstrated that activation of muscarinic receptors by a muscarinic agonist, oxotremorine M (oxo-M), induces a decrease in outward K(+)current at -40mV. In the present study, using this muscarinic current response we assessed agonist and antagonist activities of clozapine and NDMC at native muscarinic receptors in intact hippocampal excitatory and inhibitory neurons. Suppression of the oxo-M-induced current response by the M1 antagonist pirenzepine was evident only in excitatory neurons, while the M3 antagonist darifenacin was effective in both types of neurons. Muscarinic agonist activity of NDMC was higher than that of clozapine, higher in excitatory neurons than in inhibitory neurons, sensitive to pirenzepine, and partially masked when co-applied with clozapine. Muscarinic antagonist activity of clozapine as well as NDMC was not different between excitatory and inhibitory neurons, but clozapine was more effective than NDMC. These results demonstrate that NDMC has the ability to activate native M1 receptors expressed in hippocampal excitatory neurons, but its agonist activity might be limited in clozapine-treated patients because of the presence of excessive clozapine with muscarinic antagonist activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Alpha casein micelles show not only molecular chaperone-like aggregation inhibition properties but also protein refolding activity from the denatured state.

    PubMed

    Sakono, Masafumi; Motomura, Konomi; Maruyama, Tatsuo; Kamiya, Noriho; Goto, Masahiro

    2011-01-07

    Casein micelles are a major component of milk proteins. It is well known that casein micelles show chaperone-like activity such as inhibition of protein aggregation and stabilization of proteins. In this study, it was revealed that casein micelles also possess a high refolding activity for denatured proteins. A buffer containing caseins exhibited higher refolding activity for denatured bovine carbonic anhydrase than buffers including other proteins. In particular, a buffer containing α-casein showed about a twofold higher refolding activity compared with absence of α-casein. Casein properties of surface hydrophobicity, a flexible structure and assembly formation are thought to contribute to this high refolding activity. Our results indicate that casein micelles stabilize milk proteins by both chaperone-like activity and refolding properties. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Size distribution of dust grains: A problem of self-similarity

    NASA Technical Reports Server (NTRS)

    Henning, TH.; Dorschner, J.; Guertler, J.

    1989-01-01

    Distribution functions describing the results of natural processes frequently show the shape of power laws, e.g., mass functions of stars and molecular clouds, velocity spectrum of turbulence, size distributions of asteroids, micrometeorites and also interstellar dust grains. It is an open question whether this behavior is a result simply coming about by the chosen mathematical representation of the observational data or reflects a deep-seated principle of nature. The authors suppose the latter being the case. Using a dust model consisting of silicate and graphite grains Mathis et al. (1977) showed that the interstellar extinction curve can be represented by taking a grain radii distribution of power law type n(a) varies as a(exp -p) with 3.3 less than or equal to p less than or equal to 3.6 (example 1) as a basis. A different approach to understanding power laws like that in example 1 becomes possible by the theory of self-similar processes (scale invariance). The beta model of turbulence (Frisch et al., 1978) leads in an elementary way to the concept of the self-similarity dimension D, a special case of Mandelbrot's (1977) fractal dimension. In the frame of this beta model, it is supposed that on each stage of a cascade the system decays to N clumps and that only the portion beta N remains active further on. An important feature of this model is that the active eddies become less and less space-filling. In the following, the authors assume that grain-grain collisions are such a scale-invarient process and that the remaining grains are the inactive (frozen) clumps of the cascade. In this way, a size distribution n(a) da varies as a(exp -(D+1))da (example 2) results. It seems to be highly probable that the power law character of the size distribution of interstellar dust grains is the result of a self-similarity process. We can, however, not exclude that the process leading to the interstellar grain size distribution is not fragmentation at all. It could be, e

  11. Self-similar motion of a Nambu-Goto string

    NASA Astrophysics Data System (ADS)

    Igata, Takahisa; Houri, Tsuyoshi; Harada, Tomohiro

    2016-09-01

    We study the self-similar motion of a string in a self-similar spacetime by introducing the concept of a self-similar string, which is defined as the world sheet to which a homothetic vector field is tangent. It is shown that in Nambu-Goto theory, the equations of motion for a self-similar string reduce to those for a particle. Moreover, under certain conditions such as the hypersurface orthogonality of the homothetic vector field, the equations of motion for a self-similar string simplify to the geodesic equations on a (pseudo)Riemannian space. As a concrete example, we investigate a self-similar Nambu-Goto string in a spatially flat Friedmann-Lemaître-Robertson-Walker expanding universe with self-similarity and obtain solutions of open and closed strings, which have various nontrivial configurations depending on the rate of the cosmic expansion. For instance, we obtain a circular solution that evolves linearly in the cosmic time while keeping its configuration by the balance between the effects of the cosmic expansion and string tension. We also show the instability for linear radial perturbation of the circular solutions.

  12. Investigating Correlation between Protein Sequence Similarity and Semantic Similarity Using Gene Ontology Annotations.

    PubMed

    Ikram, Najmul; Qadir, Muhammad Abdul; Afzal, Muhammad Tanvir

    2018-01-01

    Sequence similarity is a commonly used measure to compare proteins. With the increasing use of ontologies, semantic (function) similarity is getting importance. The correlation between these measures has been applied in the evaluation of new semantic similarity methods, and in protein function prediction. In this research, we investigate the relationship between the two similarity methods. The results suggest absence of a strong correlation between sequence and semantic similarities. There is a large number of proteins with low sequence similarity and high semantic similarity. We observe that Pearson's correlation coefficient is not sufficient to explain the nature of this relationship. Interestingly, the term semantic similarity values above 0 and below 1 do not seem to play a role in improving the correlation. That is, the correlation coefficient depends only on the number of common GO terms in proteins under comparison, and the semantic similarity measurement method does not influence it. Semantic similarity and sequence similarity have a distinct behavior. These findings are of significant effect for future works on protein comparison, and will help understand the semantic similarity between proteins in a better way.

  13. Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling.

    PubMed

    Hatano, Atsushi; Matsumoto, Masaki; Nakayama, Keiichi I

    2016-10-01

    A key issue in the study of signal transduction is how multiple signaling pathways are systematically integrated into the cell. We have now performed multiple phosphoproteomics analyses focused on the dynamics of the T-cell receptor (TCR) signaling network and its subsystem mediated by the Ca 2+ signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca 2+ signaling showed unexpected phosphorylation kinetics for candidate substrates of the Ca 2+ -dependent phosphatase calcineurin (CN) during TCR stimulation. Detailed characterization of the TCR-induced phosphorylation of a novel CN substrate, Itpkb, showed that phosphorylation of this protein is regulated by both CN and the mitogen-activated protein kinase Erk in a competitive manner. Phosphorylation of additional CN substrates was also found to be regulated by Erk and CN in a similar manner. The combination of multiple phosphoproteomics approaches thus showed two major subsystems mediated by Erk and CN in the TCR signaling network, with these subsystems regulating the phosphorylation of a group of proteins in a competitive manner. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  14. Insurance Applications of Active Fault Maps Showing Epistemic Uncertainty

    NASA Astrophysics Data System (ADS)

    Woo, G.

    2005-12-01

    Insurance loss modeling for earthquakes utilizes available maps of active faulting produced by geoscientists. All such maps are subject to uncertainty, arising from lack of knowledge of fault geometry and rupture history. Field work to undertake geological fault investigations drains human and monetary resources, and this inevitably limits the resolution of fault parameters. Some areas are more accessible than others; some may be of greater social or economic importance than others; some areas may be investigated more rapidly or diligently than others; or funding restrictions may have curtailed the extent of the fault mapping program. In contrast with the aleatory uncertainty associated with the inherent variability in the dynamics of earthquake fault rupture, uncertainty associated with lack of knowledge of fault geometry and rupture history is epistemic. The extent of this epistemic uncertainty may vary substantially from one regional or national fault map to another. However aware the local cartographer may be, this uncertainty is generally not conveyed in detail to the international map user. For example, an area may be left blank for a variety of reasons, ranging from lack of sufficient investigation of a fault to lack of convincing evidence of activity. Epistemic uncertainty in fault parameters is of concern in any probabilistic assessment of seismic hazard, not least in insurance earthquake risk applications. A logic-tree framework is appropriate for incorporating epistemic uncertainty. Some insurance contracts cover specific high-value properties or transport infrastructure, and therefore are extremely sensitive to the geometry of active faulting. Alternative Risk Transfer (ART) to the capital markets may also be considered. In order for such insurance or ART contracts to be properly priced, uncertainty should be taken into account. Accordingly, an estimate is needed for the likelihood of surface rupture capable of causing severe damage. Especially where a

  15. Spousal Similarity in Life Satisfaction before and after Divorce

    PubMed Central

    Wortman, Jessica; Lucas, Richard E.

    2015-01-01

    Previous research has explored possible origins of individual differences in subjective well-being, focusing largely on stable, internal characteristics of traits as predictors of life satisfaction (Diener & Lucas, 1999). Although past work has demonstrated that life satisfaction is largely stable over the life span, other evidence has also demonstrated the lasting impact of life events. In this study, we use married couples as a test of the impact of life circumstances on life satisfaction, focusing on similarity in life satisfaction before and after divorce. If life satisfaction is impacted by shared life circumstances, married couples (who share life circumstances) should show greater similarity in life satisfaction before divorce than after. We tested this possibility using a dyadic latent-state-trait model that examined cross-spouse similarity in the stable and changing components of life satisfaction. Using a nationally representative panel study from Germany (Wagner, Frick & Schupp, 2007), we showed that similarity declined substantially following divorce. This suggests that life satisfaction is related to shared life circumstances. PMID:26436842

  16. Spousal similarity in life satisfaction before and after divorce.

    PubMed

    Wortman, Jessica; Lucas, Richard E

    2016-04-01

    Previous research has explored possible origins of individual differences in subjective well-being, focusing largely on stable, internal characteristics of traits as predictors of life satisfaction (Diener & Lucas, 1999). Although past work has demonstrated that life satisfaction is largely stable over the life span, other evidence has also demonstrated the lasting impact of life events. In this study, we use married couples as a test of the impact of life circumstances on life satisfaction, focusing on similarity in life satisfaction before and after divorce. If life satisfaction is impacted by shared life circumstances, married couples (who share life circumstances) should show greater similarity in life satisfaction before divorce than after. We tested this possibility using a dyadic latent-state-trait model that examined cross-spouse similarity in the stable and changing components of life satisfaction. Using a nationally representative panel study from Germany (Wagner, Frick & Schupp, 2007), we showed that similarity declined substantially following divorce. This suggests that life satisfaction is related to shared life circumstances. (c) 2016 APA, all rights reserved).

  17. Quantifying similarity of pore-geometry in nanoporous materials

    DOE PAGES

    Lee, Yongjin; Barthel, Senja D.; Dłotko, Paweł; ...

    2017-05-23

    In most applications of nanoporous materials the pore structure is as important as the chemical composition as a determinant of performance. For example, one can alter performance in applications like carbon capture or methane storage by orders of magnitude by only modifying the pore structure. For these applications it is therefore important to identify the optimal pore geometry and use this information to find similar materials. But, the mathematical language and tools to identify materials with similar pore structures, but different composition, has been lacking. We develop a pore recognition approach to quantify similarity of pore structures and classify themmore » using topological data analysis. This then allows us to identify materials with similar pore geometries, and to screen for materials that are similar to given top-performing structures. Using methane storage as a case study, we also show that materials can be divided into topologically distinct classes requiring different optimization strategies.« less

  18. Comparative analysis of topoisomerase IB inhibition and DNA intercalation by flavonoids and similar compounds: structural determinates of activity

    PubMed Central

    2004-01-01

    Flavonoids and other polyphenolic compounds have been shown to inhibit human topoisomerase IB (topo I) through both inhibition of relaxation activity and through stabilization of the cleavable complex (poisoning). Some flavonoids have also been shown to intercalate DNA, and an association of topoisomerase inhibition with intercalation has been noted. We surveyed 34 polyphenolic compounds, primarily flavonoid glycones and aglycones, for their ability to inhibit topo I and to intercalate DNA using an in vitro gel electrophoresis method. We show that the most potent topo I poisons are the flavones and flavonols, and that these generally, but not always, are found to be DNA intercalators. There was no clear correlation, however, of topo-I-poisoning activity with the degree of DNA unwinding. Surprisingly, both DNA intercalation and topo I poisoning were shown to occur with some flavone glycones, including the C-glycosylflavone orientin. Inhibition of relaxation activity by flavonoids was found to be difficult to quantify and was most likely to be due to non-specific inhibition through flavonoid aggregation. As part of a structure–activity analysis, we also investigated the acid–base chemistry of flavonoids and determined that many flavonoids show acid–base activity with a pKa in the physiological pH region. For this reason, subtle pH changes can have significant effects on solution activity of flavonoids and their concomitant biological activity. In addition, these effects may be complicated by pH-dependent aggregation and oxidative degradation. Finally, we develop a simple model for the intercalation of flavonoids into DNA and discuss possible consequences of intercalation and topoisomerase inhibition on a number of cellular processes. PMID:15312049

  19. Priming of disability and elderly stereotype in motor performance: similar or specific effects?

    PubMed

    Ginsberg, Frederik; Rohmer, Odile; Louvet, Eva

    2012-04-01

    In three experimental studies, the effects of priming participants with the disability stereotype were investigated with respect to their subsequent motor performance. Also explored were effects of activating two similar stereotypes, persons with a disability and elderly people. In Study 1, participants were primed with the disability stereotype versus with a neutral prime, and then asked to perform on a motor coordination task. In Studies 2 and 3, a third condition was introduced: priming participants with the elderly stereotype. Results indicated that priming participants with the disability stereotype altered their motor performance: they showed decreased manual dexterity and performed slower than the non-primed participants. Priming with the elderly stereotype decreased only performance speed. These findings underline that prime-to-behavior effects may depend on activation of specific stereotype content.

  20. simDEF: definition-based semantic similarity measure of gene ontology terms for functional similarity analysis of genes.

    PubMed

    Pesaranghader, Ahmad; Matwin, Stan; Sokolova, Marina; Beiko, Robert G

    2016-05-01

    Measures of protein functional similarity are essential tools for function prediction, evaluation of protein-protein interactions (PPIs) and other applications. Several existing methods perform comparisons between proteins based on the semantic similarity of their GO terms; however, these measures are highly sensitive to modifications in the topological structure of GO, tend to be focused on specific analytical tasks and concentrate on the GO terms themselves rather than considering their textual definitions. We introduce simDEF, an efficient method for measuring semantic similarity of GO terms using their GO definitions, which is based on the Gloss Vector measure commonly used in natural language processing. The simDEF approach builds optimized definition vectors for all relevant GO terms, and expresses the similarity of a pair of proteins as the cosine of the angle between their definition vectors. Relative to existing similarity measures, when validated on a yeast reference database, simDEF improves correlation with sequence homology by up to 50%, shows a correlation improvement >4% with gene expression in the biological process hierarchy of GO and increases PPI predictability by > 2.5% in F1 score for molecular function hierarchy. Datasets, results and source code are available at http://kiwi.cs.dal.ca/Software/simDEF CONTACT: ahmad.pgh@dal.ca or beiko@cs.dal.ca Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Neural activation in the "reward circuit" shows a nonlinear response to facial attractiveness.

    PubMed

    Liang, Xiaoyun; Zebrowitz, Leslie A; Zhang, Yi

    2010-01-01

    Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a "reward circuit" that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.

  2. Finding Protein and Nucleotide Similarities with FASTA

    PubMed Central

    Pearson, William R.

    2016-01-01

    The FASTA programs provide a comprehensive set of rapid similarity searching tools ( fasta36, fastx36, tfastx36, fasty36, tfasty36), similar to those provided by the BLAST package, as well as programs for slower, optimal, local and global similarity searches ( ssearch36, ggsearch36) and for searching with short peptides and oligonucleotides ( fasts36, fastm36). The FASTA programs use an empirical strategy for estimating statistical significance that accommodates a range of similarity scoring matrices and gap penalties, improving alignment boundary accuracy and search sensitivity (Unit 3.5). The FASTA programs can produce “BLAST-like” alignment and tabular output, for ease of integration into existing analysis pipelines, and can search small, representative databases, and then report results for a larger set of sequences, using links from the smaller dataset. The FASTA programs work with a wide variety of database formats, including mySQL and postgreSQL databases (Unit 9.4). The programs also provide a strategy for integrating domain and active site annotations into alignments and highlighting the mutational state of functionally critical residues. These protocols describe how to use the FASTA programs to characterize protein and DNA sequences, using protein:protein, protein:DNA, and DNA:DNA comparisons. PMID:27010337

  3. Finding Protein and Nucleotide Similarities with FASTA.

    PubMed

    Pearson, William R

    2016-03-24

    The FASTA programs provide a comprehensive set of rapid similarity searching tools (fasta36, fastx36, tfastx36, fasty36, tfasty36), similar to those provided by the BLAST package, as well as programs for slower, optimal, local, and global similarity searches (ssearch36, ggsearch36), and for searching with short peptides and oligonucleotides (fasts36, fastm36). The FASTA programs use an empirical strategy for estimating statistical significance that accommodates a range of similarity scoring matrices and gap penalties, improving alignment boundary accuracy and search sensitivity. The FASTA programs can produce "BLAST-like" alignment and tabular output, for ease of integration into existing analysis pipelines, and can search small, representative databases, and then report results for a larger set of sequences, using links from the smaller dataset. The FASTA programs work with a wide variety of database formats, including mySQL and postgreSQL databases. The programs also provide a strategy for integrating domain and active site annotations into alignments and highlighting the mutational state of functionally critical residues. These protocols describe how to use the FASTA programs to characterize protein and DNA sequences, using protein:protein, protein:DNA, and DNA:DNA comparisons. Copyright © 2016 John Wiley & Sons, Inc.

  4. Best Friends in Adolescence Show Similar Educational Careers in Early Adulthood

    ERIC Educational Resources Information Center

    Kiuru, Noona; Salmela-Aro, Katariina; Nurmi, Jari-Erik; Zettergren, Peter; Andersson, Hakan; Bergman, Lars

    2012-01-01

    The present study investigated the role of best friends in educational career development from adolescence to adulthood. Participants' (N=476) reciprocal best friendships were identified at age 15, while their educational attainment was investigated in early adulthood (age 26), their intelligence (IQ) at age 13, and parental education, educational…

  5. Cultural differences and similarities in beliefs, practices, and neural mechanisms of emotion regulation.

    PubMed

    Qu, Yang; Telzer, Eva H

    2017-01-01

    The current research examined whether culture shapes the beliefs, practices, and neural basis of emotion regulation. Twenty-nine American and Chinese participants reported their implicit theory of emotion and frequency of reappraisal use. They also underwent an fMRI scan while completing an emotion regulation task. Chinese (vs. American) participants reported more frequent use of reappraisal, which was mediated by their higher incremental theory of emotion (i.e., believing that emotion is changeable through effort). Although there were some cultural similarities in neural activation during emotion regulation, Chinese participants showed less ventrolateral prefrontal cortex (VLPFC) activation than American participants when regulating negative emotions. Lower VLPFC activation was associated with higher incremental theory of emotion and more frequent use of cognitive reappraisal. Findings suggest that culture may shape how individuals perceive and engage in emotion regulation, and ultimately, the neural mechanisms underlying emotion regulation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Query Auto-Completion Based on Word2vec Semantic Similarity

    NASA Astrophysics Data System (ADS)

    Shao, Taihua; Chen, Honghui; Chen, Wanyu

    2018-04-01

    Query auto-completion (QAC) is the first step of information retrieval, which helps users formulate the entire query after inputting only a few prefixes. Regarding the models of QAC, the traditional method ignores the contribution from the semantic relevance between queries. However, similar queries always express extremely similar search intention. In this paper, we propose a hybrid model FS-QAC based on query semantic similarity as well as the query frequency. We choose word2vec method to measure the semantic similarity between intended queries and pre-submitted queries. By combining both features, our experiments show that FS-QAC model improves the performance when predicting the user’s query intention and helping formulate the right query. Our experimental results show that the optimal hybrid model contributes to a 7.54% improvement in terms of MRR against a state-of-the-art baseline using the public AOL query logs.

  7. Characterization of an antimicrobial peptide produced by Bacillus subtilis subsp. spizezinii showing inhibitory activity towards Haemophilus parasuis.

    PubMed

    Teixeira, Mário Lettieri; Dalla Rosa, Andréia; Brandelli, Adriano

    2013-05-01

    Haemophilus parasuis is the pathogen that causes Glässer's disease, a major illness affecting young pigs. The aim of this work was to investigate the antagonistic activity of antimicrobial substances produced by Bacillus species against H. parasuis. Among the tested strains, only Bacillus subtilis ATCC 6633 inhibited H. parasuis growth. The antibacterial substance was purified by ammonium sulfate precipitation, gel filtration chromatography on Sephadex G-50 and ion-exchange chromatography on DEAE-cellulose. The purification was about 100-fold with a yield of 0.33 %. The purified substance was resistant up to 80 °C and pH ranging 3-7, but the substance lost its activity when it was treated with proteases. The peptide had a molecular mass of 1083 Da and its sequence was determined by MS as NRWCFAGDD, which showed no homology with other known antimicrobial peptides. The complete inhibition of H. parasuis growth was observed at 20 µg peptide ml(-1) after 20 min of exposure. The peptide obtained by chemical synthesis also showed antimicrobial activity on H. parasuis. The identification of antimicrobial substances that can be effective against H. parasuis is very relevant to combat this pathogen that causes important losses in swine production.

  8. Crystal structure of plant light-harvesting complex shows the active, energy-transmitting state

    PubMed Central

    Barros, Tiago; Royant, Antoine; Standfuss, Jörg; Dreuw, Andreas; Kühlbrandt, Werner

    2009-01-01

    Plants dissipate excess excitation energy as heat by non-photochemical quenching (NPQ). NPQ has been thought to resemble in vitro aggregation quenching of the major antenna complex, light harvesting complex of photosystem II (LHC-II). Both processes are widely believed to involve a conformational change that creates a quenching centre of two neighbouring pigments within the complex. Using recombinant LHC-II lacking the pigments implicated in quenching, we show that they have no particular role. Single crystals of LHC-II emit strong, orientation-dependent fluorescence with an emission maximum at 680 nm. The average lifetime of the main 680 nm crystal emission at 100 K is 1.31 ns, but only 0.39 ns for LHC-II aggregates under identical conditions. The strong emission and comparatively long fluorescence lifetimes of single LHC-II crystals indicate that the complex is unquenched, and that therefore the crystal structure shows the active, energy-transmitting state of LHC-II. We conclude that quenching of excitation energy in the light-harvesting antenna is due to the molecular interaction with external pigments in vitro or other pigment–protein complexes such as PsbS in vivo, and does not require a conformational change within the complex. PMID:19131972

  9. Biosimilars for psoriasis: clinical studies to determine similarity.

    PubMed

    Blauvelt, A; Puig, L; Chimenti, S; Vender, R; Rajagopalan, M; Romiti, R; Skov, L; Zachariae, C; Young, H; Prens, E; Cohen, A; van der Walt, J; Wu, J J

    2017-07-01

    Biosimilars are drugs that are similar, but not identical, to originator biologics. Preclinical analytical studies are required to show similarity on a molecular and structural level, but efficacy and safety studies in humans are essential to determining biosimilarity. In this review, written by members of the International Psoriasis Council, we discuss how biosimilars are evaluated in a clinical setting, with emphasis on extrapolation of indication, interchangeability and optimal clinical trial design. © 2016 British Association of Dermatologists.

  10. A literature-driven method to calculate similarities among diseases.

    PubMed

    Kim, Hyunjin; Yoon, Youngmi; Ahn, Jaegyoon; Park, Sanghyun

    2015-11-01

    "Our lives are connected by a thousand invisible threads and along these sympathetic fibers, our actions run as causes and return to us as results". It is Herman Melville's famous quote describing connections among human lives. To paraphrase the Melville's quote, diseases are connected by many functional threads and along these sympathetic fibers, diseases run as causes and return as results. The Melville's quote explains the reason for researching disease-disease similarity and disease network. Measuring similarities between diseases and constructing disease network can play an important role in disease function research and in disease treatment. To estimate disease-disease similarities, we proposed a novel literature-based method. The proposed method extracted disease-gene relations and disease-drug relations from literature and used the frequencies of occurrence of the relations as features to calculate similarities among diseases. We also constructed disease network with top-ranking disease pairs from our method. The proposed method discovered a larger number of answer disease pairs than other comparable methods and showed the lowest p-value. We presume that our method showed good results because of using literature data, using all possible gene symbols and drug names for features of a disease, and determining feature values of diseases with the frequencies of co-occurrence of two entities. The disease-disease similarities from the proposed method can be used in computational biology researches which use similarities among diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Volutin granules of Eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes

    PubMed Central

    Medeiros, Lia Carolina Soares; Gomes, Fabio; Maciel, Luis Renato Maia; Seabra, Sergio Henrique; Docampo, Roberto; Moreno, Silvia; Plattner, Helmut; Hentschel, Joachim; Kawazoe, Urara; Barrabin, Hector; de Souza, Wanderley; DaMatta, Renato Augusto; Miranda, Kildare

    2012-01-01

    The structural organization of parasites has been the subject of investigation by many groups and has lead to the identification of structures and metabolic pathways that may represent targets for anti-parasitic drugs. A specific group of organelles named acidocalcisomes has been identified in a number of organisms, including the apicomplexan parasites such as Toxoplasma and Plasmodium, where they have been shown to be involved in cation homeostasis, polyphosphate metabolism, and osmoregulation. Their structural counterparts in the apicomplexan parasite Eimeria have not been fully characterized. In this work, the ultrastructural and chemical properties of acidocalcisomes in Eimeria were characterized. Electron microscopy analysis of Eimeria parasites showed the dense organelles called volutin granules similar to acidocalcisomes. Immunolocalization of the vacuolar proton pyrophosphatase, considered as a marker for acidocalcisomes, showed labeling in vesicles of size and distribution similar to the dense organelles seen by electron microscopy. Spectrophotometric measurements of the kinetics of proton uptake showed a vacuolar proton pyrophosphatase activity. X-ray mapping revealed significant amounts of Na, Mg, P, K, Ca, and Zn in their matrix. The results suggest that volutin granules of Eimeria parasites are acidic, dense organelles and possess structural and chemical properties analogous to those of other acidocalcisomes, suggesting a similar functional role in these parasites. PMID:21699625

  12. Link-Based Similarity Measures Using Reachability Vectors

    PubMed Central

    Yoon, Seok-Ho; Kim, Ji-Soo; Ryu, Minsoo; Choi, Ho-Jin

    2014-01-01

    We present a novel approach for computing link-based similarities among objects accurately by utilizing the link information pertaining to the objects involved. We discuss the problems with previous link-based similarity measures and propose a novel approach for computing link based similarities that does not suffer from these problems. In the proposed approach each target object is represented by a vector. Each element of the vector corresponds to all the objects in the given data, and the value of each element denotes the weight for the corresponding object. As for this weight value, we propose to utilize the probability of reaching from the target object to the specific object, computed using the “Random Walk with Restart” strategy. Then, we define the similarity between two objects as the cosine similarity of the two vectors. In this paper, we provide examples to show that our approach does not suffer from the aforementioned problems. We also evaluate the performance of the proposed methods in comparison with existing link-based measures, qualitatively and quantitatively, with respect to two kinds of data sets, scientific papers and Web documents. Our experimental results indicate that the proposed methods significantly outperform the existing measures. PMID:24701188

  13. [Similarity system theory to evaluate similarity of chromatographic fingerprints of traditional Chinese medicine].

    PubMed

    Liu, Yongsuo; Meng, Qinghua; Jiang, Shumin; Hu, Yuzhu

    2005-03-01

    The similarity evaluation of the fingerprints is one of the most important problems in the quality control of the traditional Chinese medicine (TCM). Similarity measures used to evaluate the similarity of the common peaks in the chromatogram of TCM have been discussed. Comparative studies were carried out among correlation coefficient, cosine of the angle and an improved extent similarity method using simulated data and experimental data. Correlation coefficient and cosine of the angle are not sensitive to the differences of the data set. They are still not sensitive to the differences of the data even after normalization. According to the similarity system theory, an improved extent similarity method was proposed. The improved extent similarity is more sensitive to the differences of the data sets than correlation coefficient and cosine of the angle. And the character of the data sets needs not to be changed compared with log-transformation. The improved extent similarity can be used to evaluate the similarity of the chromatographic fingerprints of TCM.

  14. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

    PubMed Central

    Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

    2012-01-01

    Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction

  15. Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells

    PubMed Central

    2011-01-01

    Background Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. Crude mushroom extracts have been tested without detailed chemical analyses of its polysaccharide content. For the present study we decided to chemically determine the carbohydrate composition of semi-purified extracts from 2 closely related and well known basidiomycete species, i.e. Agaricus bisporus and A. brasiliensis and to study their effects on the innate immune system, in particular on the in vitro induction of pro-inflammatory cytokines, using THP-1 cells. Methods Mushroom polysaccharide extracts were prepared by hot water extraction and precipitation with ethanol. Their composition was analyzed by GC-MS and NMR spectroscopy. PMA activated THP-1 cells were treated with the extracts under different conditions and the production of pro-inflammatory cytokines was evaluated by qPCR. Results Semi-purified polysaccharide extracts of A. bisporus and A. brasiliensis (= blazei) were found to contain (1→6),(1→4)-linked α-glucan, (1→6)-linked β-glucan, and mannogalactan. Their proportions were determined by integration of 1H-NMR signs, and were considerably different for the two species. A. brasiliensis showed a higher content of β-glucan, while A. bisporus presented mannogalactan as its main polysaccharide. The extracts induced a comparable increase of transcription of the pro-inflammatory cytokine genes IL-1β and TNF-α as well as of COX-2 in PMA differentiated THP-1 cells. Pro-inflammatory effects of bacterial LPS in this assay could be reduced significantly by the simultaneous addition of A. brasiliensis extract. Conclusions The polysaccharide preparations from the closely related species A. bisporus and A. brasiliensis show major differences in composition: A. bisporus shows high mannogalactan content whereas A. brasiliensis has mostly β-glucan. Semi

  16. Readout from iconic memory and selective spatial attention involve similar neural processes.

    PubMed

    Ruff, Christian C; Kristjánsson, Arni; Driver, Jon

    2007-10-01

    Iconic memory and spatial attention are often considered separately, but they may have functional similarities. Here we provide functional magnetic resonance imaging evidence for some common underlying neural effects. Subjects judged three visual stimuli in one hemifield of a bilateral array comprising six stimuli. The relevant hemifield for partial report was indicated by an auditory cue, administered either before the visual array (precue, spatial attention) or shortly after the array (postcue, iconic memory). Pre- and postcues led to similar activity modulations in lateral occipital cortex contralateral to the cued side. This finding indicates that readout from iconic memory can have some neural effects similar to those of spatial attention. We also found common bilateral activation of a fronto-parietal network for postcue and precue trials. These neuroimaging data suggest that some common neural mechanisms underlie selective spatial attention and readout from iconic memory. Some differences were also found; compared with precues, postcues led to higher activity in the right middle frontal gyrus.

  17. Readout From Iconic Memory and Selective Spatial Attention Involve Similar Neural Processes

    PubMed Central

    Ruff, Christian C; Kristjánsson, Árni; Driver, Jon

    2007-01-01

    Iconic memory and spatial attention are often considered separately, but they may have functional similarities. Here we provide functional magnetic resonance imaging evidence for some common underlying neural effects. Subjects judged three visual stimuli in one hemifield of a bilateral array comprising six stimuli. The relevant hemifield for partial report was indicated by an auditory cue, administered either before the visual array (precue, spatial attention) or shortly after the array (postcue, iconic memory). Pre- and postcues led to similar activity modulations in lateral occipital cortex contralateral to the cued side. This finding indicates that readout from iconic memory can have some neural effects similar to those of spatial attention. We also found common bilateral activation of a fronto-parietal network for postcue and precue trials. These neuroimaging data suggest that some common neural mechanisms underlie selective spatial attention and readout from iconic memory. Some differences were also found; compared with precues, postcues led to higher activity in the right middle frontal gyrus. PMID:17894608

  18. A Little Similarity Goes a Long Way: The Effects of Peripheral but Self-Revealing Similarities on Improving and Sustaining Interracial Relationships

    PubMed Central

    West, Tessa V.; Magee, Joe C.; Gordon, Sarah H.; Gullett, Lindy

    2017-01-01

    Integrating theory on close relationships and intergroup relations, we construct a manipulation of similarity that we demonstrate can improve interracial interactions across different settings. We find that manipulating perceptions of similarity on self-revealing attributes that are peripheral to the interaction improves interactions in cross-race dyads and racially diverse task groups. In a getting-acquainted context, we demonstrate that the belief that one’s different-race partner is similar to oneself on self-revealing, peripheral attributes leads to less anticipatory anxiety than the belief that one’s partner is similar on peripheral, nonself-revealing attributes. In another dyadic context, we explore the range of benefits that perceptions of peripheral, self-revealing similarity can bring to different-race interaction partners and find (a) less anxiety during interaction, (b) greater interest in sustained contact with one’s partner, and (c) stronger accuracy in perceptions of one’s partners’ relationship intentions. By contrast, participants in same-race interactions were largely unaffected by these manipulations of perceived similarity. Our final experiment shows that among small task groups composed of racially diverse individuals, those whose members perceive peripheral, self-revealing similarity perform superior to those who perceive dissimilarity. Implications for using this approach to improve interracial interactions across different goal-driven contexts are discussed. PMID:24956315

  19. Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity.

    PubMed

    dos Santos, Alda E; Kuster, Ricardo M; Yamamoto, Kristie A; Salles, Tiago S; Campos, Renata; de Meneses, Marcelo D F; Soares, Márcia R; Ferreira, Davis

    2014-03-28

    The arthropod-borne Mayaro virus (MAYV) causes 'Mayaro fever', a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus.

  20. Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

    PubMed Central

    2014-01-01

    Background The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Methods Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. Results The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. Conclusions B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus. PMID:24678592

  1. Optimizing post activation potentiation for explosive activities in competitive sports

    PubMed Central

    Gołaś, Artur; Maszczyk, Adam; Mikołajec, Kazimierz; Stastny, Petr

    2016-01-01

    Abstract Post activation potentiation (PAP) has shown improved performance during movements requiring large muscular power output following contractions under near maximal load conditions. PAP can be described as an acute enhancement of performance or an enhancement of factors determining an explosive sports activity following a preload stimulus. In practice, PAP has been achieved by complex training, which involves a combination of a heavy loaded exercise followed by a biomechanically similar explosive activity, best if specific for a particular sport discipline. The main objective of this study was to investigate the effects of PAP on performance in explosive motor activities specific for basketball, luge and athletics throws. The novel approach to the experiments included individualized recovery time (IRT) between the conditioning exercise and the explosive activity. Additionally, the research groups were homogenous and included only competitive athletes of similar age and training experience. Thirty one well trained athletes from 3 different sport disciplines participated in the study. All athletes performed a heavy loaded conditioning activity (80-130%1RM) followed by a biomechanically similar explosive exercise, during which power (W) or the rate of power development (W/s/kg) was evaluated. The results of our experiment confirmed the effectiveness of PAP with well-trained athlets during explosive motor activities such as jumping, throwing and pushing. Additionally, our research showed that eccentric supramaximal intensities (130% 1RM) can be effective in eliciting PAP in strength trained athletes. Our experiments also showed that the IRT should be individualized because athletes differ in the strength level, training experience and muscle fiber structure. In the three experiments conducted with basketball players, track and field athletes and luge athletes, the optimal IRT equaled 6 min. This justifies the need to individualize the volume and intensity of the

  2. Construction and comparison of gene co-expression networks shows complex plant immune responses

    PubMed Central

    López, Camilo; López-Kleine, Liliana

    2014-01-01

    Gene co-expression networks (GCNs) are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA). Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses. PMID:25320678

  3. Similar prevalence and magnitude of auditory-evoked and visually evoked activity in the frontal eye fields: implications for multisensory motor control.

    PubMed

    Caruso, Valeria C; Pages, Daniel S; Sommer, Marc A; Groh, Jennifer M

    2016-06-01

    Saccadic eye movements can be elicited by more than one type of sensory stimulus. This implies substantial transformations of signals originating in different sense organs as they reach a common motor output pathway. In this study, we compared the prevalence and magnitude of auditory- and visually evoked activity in a structure implicated in oculomotor processing, the primate frontal eye fields (FEF). We recorded from 324 single neurons while 2 monkeys performed delayed saccades to visual or auditory targets. We found that 64% of FEF neurons were active on presentation of auditory targets and 87% were active during auditory-guided saccades, compared with 75 and 84% for visual targets and saccades. As saccade onset approached, the average level of population activity in the FEF became indistinguishable on visual and auditory trials. FEF activity was better correlated with the movement vector than with the target location for both modalities. In summary, the large proportion of auditory-responsive neurons in the FEF, the similarity between visual and auditory activity levels at the time of the saccade, and the strong correlation between the activity and the saccade vector suggest that auditory signals undergo tailoring to match roughly the strength of visual signals present in the FEF, facilitating accessing of a common motor output pathway. Copyright © 2016 the American Physiological Society.

  4. A Combination of Thematic and Similarity-Based Semantic Processes Confers Resistance to Deficit Following Left Hemisphere Stroke

    PubMed Central

    Kalénine, Solène; Mirman, Daniel; Buxbaum, Laurel J.

    2012-01-01

    Semantic knowledge may be organized in terms of similarity relations based on shared features and/or complementary relations based on co-occurrence in events. Thus, relationships between manipulable objects such as tools may be defined by their functional properties (what the objects are used for) or thematic properties (e.g., what the objects are used with or on). A recent study from our laboratory used eye-tracking to examine incidental activation of semantic relations in a word–picture matching task and found relatively early activation of thematic relations (e.g., broom–dustpan), later activation of general functional relations (e.g., broom–sponge), and an intermediate pattern for specific functional relations (e.g., broom–vacuum cleaner). Combined with other recent studies, these results suggest that there are distinct semantic systems for thematic and similarity-based knowledge and that the “specific function” condition drew on both systems. This predicts that left hemisphere stroke that damages either system (but not both) may spare specific function processing. The present experiment tested these hypotheses using the same experimental paradigm with participants with left hemisphere lesions (N = 17). The results revealed that, compared to neurologically intact controls (N = 12), stroke participants showed later activation of thematic and general function relations, but activation of specific function relations was spared and was significantly earlier for stroke participants than controls. Across the stroke participants, activation of thematic and general function relations was negatively correlated, further suggesting that damage tended to affect either one semantic system or the other. These results support the distinction between similarity-based and complementarity-based semantic relations and suggest that relations that draw on both systems are relatively more robust to damage. PMID:22586383

  5. Estimation for time-changed self-similar stochastic processes

    NASA Astrophysics Data System (ADS)

    Arroum, W.; Jones, O. D.

    2005-12-01

    We consider processes of the form X(t) = X ~(θ(t)) where X ~ is a self-similar process with stationary increments and θ is a deterministic subordinator with a periodic activity function a = θ'> 0. Such processes have been proposed as models for high-frequency financial data, such as currency exchange rates, where there are known to be daily and weekly periodic fluctuations in the volatility, captured here by the periodic activity function. We review an existing estimator for the activity function then propose three new methods for estimating it and present some experimental studies of their performance. We finish with an application to some foreign exchange and FTSE100 futures data.

  6. Energy intake adaptations to acute isoenergetic active video games and exercise are similar in obese adolescents.

    PubMed

    Chaput, J P; Schwartz, C; Boirie, Y; Duclos, M; Tremblay, A; Thivel, D

    2015-11-01

    Although the impact of passive video games (PVGs) on energy intake has been previously explored in lean adolescents, data are missing on the nutritional adaptations to passive and active video games (AVGs) in obese adolescents. It is also unknown whether isoenergetic AVGs and exercise (EX) differently affect food consumption in youth. Nineteen obese adolescent boys (12-15 years old) had to complete four 1-hour sessions in a crossover manner: control (CON; sitting on a chair), PVG (boxing game on Xbox 360), AVG (boxing game on Xbox Kinect 360) and EX (cycling). The EX was calibrated to generate the same energy expenditure as the AVG session. Energy expenditure was measured using a K4b2 portable indirect calorimeter. Ad libitum food intake (buffet-style meal) and appetite sensations (visual analogue scales) were assessed after the sessions. As expected, mean energy expenditure was similar between AVG (370±4 kcal) and EX (358±3 kcal), both of which were significantly higher than PVG (125±7 kcal) and CON (98±5 kcal) (P<0.001). However, ad libitum food intake after the sessions was not significantly different between CON (1174±282 kcal), PVG (1124±281 kcal), AVG (1098±265 kcal) and EX (1091±290 kcal). Likewise, the energy derived from fat, carbohydrate and protein was not significantly different between sessions, and appetite sensations were not affected. Energy intake and food preferences after an hour of AVG or PVG playing remain unchanged, and isoenergetic sessions of AVG and EX at moderate intensity induce similar nutritional responses in obese adolescent boys.

  7. Average is Boring: How Similarity Kills a Meme's Success

    NASA Astrophysics Data System (ADS)

    Coscia, Michele

    2014-09-01

    Every day we are exposed to different ideas, or memes, competing with each other for our attention. Previous research explained popularity and persistence heterogeneity of memes by assuming them in competition for limited attention resources, distributed in a heterogeneous social network. Little has been said about what characteristics make a specific meme more likely to be successful. We propose a similarity-based explanation: memes with higher similarity to other memes have a significant disadvantage in their potential popularity. We employ a meme similarity measure based on semantic text analysis and computer vision to prove that a meme is more likely to be successful and to thrive if its characteristics make it unique. Our results show that indeed successful memes are located in the periphery of the meme similarity space and that our similarity measure is a promising predictor of a meme success.

  8. Average is boring: how similarity kills a meme's success.

    PubMed

    Coscia, Michele

    2014-09-26

    Every day we are exposed to different ideas, or memes, competing with each other for our attention. Previous research explained popularity and persistence heterogeneity of memes by assuming them in competition for limited attention resources, distributed in a heterogeneous social network. Little has been said about what characteristics make a specific meme more likely to be successful. We propose a similarity-based explanation: memes with higher similarity to other memes have a significant disadvantage in their potential popularity. We employ a meme similarity measure based on semantic text analysis and computer vision to prove that a meme is more likely to be successful and to thrive if its characteristics make it unique. Our results show that indeed successful memes are located in the periphery of the meme similarity space and that our similarity measure is a promising predictor of a meme success.

  9. A Pilot Study: Dietary Energy Density is Similar between Active Women with and without Exercise-Associated Menstrual Dysfunction

    PubMed Central

    Hand, Taryn M.; Howe, Stephanie; Cialdella-Kam, Lynn; Hoffman, Charlotte P. Guebels; Manore, Melinda

    2016-01-01

    Low energy availability (EA) (e.g., insufficient energy intake (EI) to match energy needs, including exercise energy expenditure) has been identified as a primary contributor to exercise-associated menstrual dysfunction (ExMD) in active women. For health reasons, active women may self-select diets lower in energy density (ED, kcal/g), which can inadvertently contribute to inadequate EI. Using data from two studies, we compared the ED of active women with ExMD (n = 9; 24 ± 6 years) to eumenorrheic (EU) active controls (EU: n = 18, 27 ± 6 years). ED was calculated from 6 to 7 days weighted food records using two methods: with/without beverages. ANOVA and Wilcoxon Rank-Sum were used to test group differences. ED was not different between groups, but there was a trend toward a lower median ED (10%) (p = 0.049 unadjusted; p = 0.098 adjusted) in the ExMD-group (Method 1—all beverages: ExMD = 1.01 kcal/g (range = 0.52–1.41), EU = 1.22 kcal/g (range = 0.72–1.72); Method 2—without beverages: ExMD = 1.51 kcal/g (range = 1.26–2.06), EU = 1.69 kcal/g (range = 1.42–2.54)). This lower ED represents a 9% decrease (~219 kcal/day) in EI (ExMD = 2237 ± 378 kcal/day; EU = 2456 ± 470 kcal/day; p > 0.05). EI and macro/micronutrient intakes were similar for groups. In the ExMD-group, low ED could contribute to lower EI and EA. Future research should examine the interaction of ED and exercise on appetite, EI, and EA in active women, especially those with ExMD. PMID:27104560

  10. The Gestalt Principle of Similarity Benefits Visual Working Memory

    PubMed Central

    Peterson, Dwight J.; Berryhill, Marian E.

    2013-01-01

    Visual working memory (VWM) is essential for many cognitive processes yet it is notably limited in capacity. Visual perception processing is facilitated by Gestalt principles of grouping, such as connectedness, similarity, and proximity. This introduces the question: do these perceptual benefits extend to VWM? If so, can this be an approach to enhance VWM function by optimizing the processing of information? Previous findings demonstrate that several Gestalt principles (connectedness, common region, and spatial proximity) do facilitate VWM performance in change detection tasks (Woodman, Vecera, & Luck, 2003; Xu, 2002a, 2006; Xu & Chun, 2007; Jiang, Olson & Chun, 2000). One prevalent Gestalt principle, similarity, has not been examined with regard to facilitating VWM. Here, we investigated whether grouping by similarity benefits VWM. Experiment 1 established the basic finding that VWM performance could benefit from grouping. Experiment 2 replicated and extended this finding by showing that similarity was only effective when the similar stimuli were proximal. In short, the VWM performance benefit derived from similarity was constrained by spatial proximity such that similar items need to be near each other. Thus, the Gestalt principle of similarity benefits visual perception, but it can provide benefits to VWM as well. PMID:23702981

  11. The Gestalt principle of similarity benefits visual working memory.

    PubMed

    Peterson, Dwight J; Berryhill, Marian E

    2013-12-01

    Visual working memory (VWM) is essential for many cognitive processes, yet it is notably limited in capacity. Visual perception processing is facilitated by Gestalt principles of grouping, such as connectedness, similarity, and proximity. This introduces the question, do these perceptual benefits extend to VWM? If so, can this be an approach to enhance VWM function by optimizing the processing of information? Previous findings have demonstrated that several Gestalt principles (connectedness, common region, and spatial proximity) do facilitate VWM performance in change detection tasks (Jiang, Olson, & Chun, 2000; Woodman, Vecera, & Luck, 2003; Xu, 2002, 2006; Xu & Chun, 2007). However, one prevalent Gestalt principle, similarity, has not been examined with regard to facilitating VWM. Here, we investigated whether grouping by similarity benefits VWM. Experiment 1 established the basic finding that VWM performance could benefit from grouping. Experiment 2 replicated and extended this finding by showing that similarity was only effective when the similar stimuli were proximal. In short, the VWM performance benefit derived from similarity was constrained by spatial proximity, such that similar items need to be near each other. Thus, the Gestalt principle of similarity benefits visual perception, but it can provide benefits to VWM as well.

  12. Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

    PubMed

    Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

    2016-10-06

    Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Reconstituted High-Density Lipoprotein Containing Human Growth Hormone-1 Shows Potent Tissue Regeneration Activity with Enhancement of Anti-Oxidant and Anti-Atherosclerotic Activities.

    PubMed

    Lee, Eun-Young; Kim, So-Hee; Cho, Kyung-Hyun

    2015-06-01

    Human growth hormone-1 (GH-1), somatotropin, is a peptide hormone that stimulates cell division in tissues such as bone and cartilage. To compare physiological activities in lipid-free and lipid-bound states, we expressed and incorporated GH-1 in reconstituted high-density lipoprotein (rHDL). GH-1 was expressed and purified using the pET30(a) vector and an Escherichia coli expression system. Purified GH-1 (at least 98% purity, 23 kD) was characterized and synthesized with apolipoproteinA-I (apoA-I), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and cholesterol. Secondary structure analysis of GH-1 revealed 54% α-helical content in a lipid-free state and 65% α-helical content in a lipid-bound state along with blue-shifted tryptophan movement (around 2 nm). GH-1 caused less uptake of oxidized low-density lipoprotein (oxLDL) into macrophages and inhibited senescence of dermal cells in a dose-dependent manner. GH-1 in a lipid-bound state exerted stronger inhibitory activity than in a lipid-free state, indicating improved anti-atherosclerotic activity due to the lipid formulation. In a fin regeneration experiment using zebrafish (17 weeks old, n=9), GH-1 showed its highest regeneration speed without any side effects. GH-1-rHDL containing apoA-I showed 2.3-fold and 1.6-fold higher regeneration speeds than lipid-free GH-1 (in native state) and lipid-bound GH-1, respectively. Incorporation of GH-1 and apoA-I in HDL enhanced tissue regeneration activity of amputated tail fin, indicating a synergetic effect between GH-1 and apoA-I in a lipid-bound state.

  14. Common neighbour structure and similarity intensity in complex networks

    NASA Astrophysics Data System (ADS)

    Hou, Lei; Liu, Kecheng

    2017-10-01

    Complex systems as networks always exhibit strong regularities, implying underlying mechanisms governing their evolution. In addition to the degree preference, the similarity has been argued to be another driver for networks. Assuming a network is randomly organised without similarity preference, the present paper studies the expected number of common neighbours between vertices. A symmetrical similarity index is accordingly developed by removing such expected number from the observed common neighbours. The developed index can not only describe the similarities between vertices, but also the dissimilarities. We further apply the proposed index to measure of the influence of similarity on the wring patterns of networks. Fifteen empirical networks as well as artificial networks are examined in terms of similarity intensity and degree heterogeneity. Results on real networks indicate that, social networks are strongly governed by the similarity as well as the degree preference, while the biological networks and infrastructure networks show no apparent similarity governance. Particularly, classical network models, such as the Barabási-Albert model, the Erdös-Rényi model and the Ring Lattice, cannot well describe the social networks in terms of the degree heterogeneity and similarity intensity. The findings may shed some light on the modelling and link prediction of different classes of networks.

  15. Adapting Document Similarity Measures for Ligand-Based Virtual Screening.

    PubMed

    Himmat, Mubarak; Salim, Naomie; Al-Dabbagh, Mohammed Mumtaz; Saeed, Faisal; Ahmed, Ali

    2016-04-13

    Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.

  16. Clustering biomolecular complexes by residue contacts similarity.

    PubMed

    Rodrigues, João P G L M; Trellet, Mikaël; Schmitz, Christophe; Kastritis, Panagiotis; Karaca, Ezgi; Melquiond, Adrien S J; Bonvin, Alexandre M J J

    2012-07-01

    Inaccuracies in computational molecular modeling methods are often counterweighed by brute-force generation of a plethora of putative solutions. These are then typically sieved via structural clustering based on similarity measures such as the root mean square deviation (RMSD) of atomic positions. Albeit widely used, these measures suffer from several theoretical and technical limitations (e.g., choice of regions for fitting) that impair their application in multicomponent systems (N > 2), large-scale studies (e.g., interactomes), and other time-critical scenarios. We present here a simple similarity measure for structural clustering based on atomic contacts--the fraction of common contacts--and compare it with the most used similarity measure of the protein docking community--interface backbone RMSD. We show that this method produces very compact clusters in remarkably short time when applied to a collection of binary and multicomponent protein-protein and protein-DNA complexes. Furthermore, it allows easy clustering of similar conformations of multicomponent symmetrical assemblies in which chain permutations can occur. Simple contact-based metrics should be applicable to other structural biology clustering problems, in particular for time-critical or large-scale endeavors. Copyright © 2012 Wiley Periodicals, Inc.

  17. Ultrafast fiber lasers based on self-similar pulse evolution: a review of current progress

    PubMed Central

    Chong, Andy; Wright, Logan G; Wise, Frank W

    2016-01-01

    Self-similar fiber oscillators are a relatively new class of mode-locked lasers. In these lasers, the self-similar evolution of a chirped parabolic pulse in normally-dispersive passive, active, or dispersion-decreasing fiber (DDF) is critical. In active (gain) fiber and DDF, the novel role of local nonlinear attraction makes the oscillators fundamentally different from any mode-locked lasers considered previously. In order to reconcile the spectral and temporal expansion of a pulse in the self-similar segment with the self-consistency required by a laser cavity's periodic boundary condition, several techniques have been applied. The result is a diverse range of fiber oscillators which demonstrate the exciting new design possibilities based on the self-similar model. Here, we review recent progress on self-similar oscillators both in passive and active fiber, and extensions of self-similar evolution for surpassing the limits of rare-earth gain media. We discuss some key remaining research questions and important future directions. Self-similar oscillators are capable of exceptional performance among ultrashort pulsed fiber lasers, and may be of key interest in the development of future ultrashort pulsed fiber lasers for medical imaging applications, as well as for low-noise fiber-based frequency combs. Their uniqueness among mode-locked lasers motivates study into their properties and behaviors and raises questions about how to understand mode-locked lasers more generally. PMID:26496377

  18. Ultrafast fiber lasers based on self-similar pulse evolution: a review of current progress.

    PubMed

    Chong, Andy; Wright, Logan G; Wise, Frank W

    2015-11-01

    Self-similar fiber oscillators are a relatively new class of mode-locked lasers. In these lasers, the self-similar evolution of a chirped parabolic pulse in normally-dispersive passive, active, or dispersion-decreasing fiber (DDF) is critical. In active (gain) fiber and DDF, the novel role of local nonlinear attraction makes the oscillators fundamentally different from any mode-locked lasers considered previously. In order to reconcile the spectral and temporal expansion of a pulse in the self-similar segment with the self-consistency required by a laser cavity's periodic boundary condition, several techniques have been applied. The result is a diverse range of fiber oscillators which demonstrate the exciting new design possibilities based on the self-similar model. Here, we review recent progress on self-similar oscillators both in passive and active fiber, and extensions of self-similar evolution for surpassing the limits of rare-earth gain media. We discuss some key remaining research questions and important future directions. Self-similar oscillators are capable of exceptional performance among ultrashort pulsed fiber lasers, and may be of key interest in the development of future ultrashort pulsed fiber lasers for medical imaging applications, as well as for low-noise fiber-based frequency combs. Their uniqueness among mode-locked lasers motivates study into their properties and behaviors and raises questions about how to understand mode-locked lasers more generally.

  19. Emergent self-similarity of cluster coagulation

    NASA Astrophysics Data System (ADS)

    Pushkin, Dmtiri O.

    A wide variety of nonequilibrium processes, such as coagulation of colloidal particles, aggregation of bacteria into colonies, coalescence of rain drops, bond formation between polymerization sites, and formation of planetesimals, fall under the rubric of cluster coagulation. We predict emergence of self-similar behavior in such systems when they are 'forced' by an external source of the smallest particles. The corresponding self-similar coagulation spectra prove to be power laws. Starting from the classical Smoluchowski coagulation equation, we identify the conditions required for emergence of self-similarity and show that the power-law exponent value for a particular coagulation mechanism depends on the homogeneity index of the corresponding coagulation kernel only. Next, we consider the current wave of mergers of large American banks as an 'unorthodox' application of coagulation theory. We predict that the bank size distribution has propensity to become a power law, and verify our prediction in a statistical study of the available economical data. We conclude this chapter by discussing economically significant phenomenon of capital condensation and predicting emergence of power-law distributions in other economical and social data. Finally, we turn to apparent semblance between cluster coagulation and turbulence and conclude that it is not accidental: both of these processes are instances of nonlinear cascades. This class of processes also includes river network formation models, certain force-chain models in granular mechanics, fragmentation due to collisional cascades, percolation, and growing random networks. We characterize a particular cascade by three indicies and show that the resulting power-law spectrum exponent depends on the indicies values only. The ensuing algebraic formula is remarkable for its simplicity.

  20. Head direction cells in the postsubiculum do not show replay of prior waking sequences during sleep

    PubMed Central

    Brandon, Mark P.; Bogaard, Andrew; Andrews, Chris M.; Hasselmo, Michael E.

    2011-01-01

    During slow-wave sleep and REM sleep, hippocampal place cells in the rat show replay of sequences previously observed during waking. We tested the hypothesis from computational modelling that the temporal structure of REM sleep replay could arise from an interplay of place cells with head direction cells in the postsubiculum. Physiological single-unit recording was performed simultaneously from five or more head direction or place by head direction cells in the postsubiculum during running on a circular track allowing sampling of a full range of head directions, and during sleep periods before and after running on the circular track. Data analysis compared the spiking activity during individual REM periods with waking as in previous analysis procedures for REM sleep. We also used a new procedure comparing groups of similar runs during waking with REM sleep periods. There was no consistent evidence for a statistically significant correlation of the temporal structure of spiking during REM sleep with spiking during waking running periods. Thus, the spiking activity of head direction cells during REM sleep does not show replay of head direction cell activity occurring during a previous waking period of running on the task. In addition, we compared the spiking of postsubiculum neurons during hippocampal sharp wave ripple events. We show that head direction cells are not activated during sharp wave ripples, while neurons responsive to place in the postsubiculum show reliable spiking at ripple events. PMID:21509854

  1. Similarity analysis between quantum images

    NASA Astrophysics Data System (ADS)

    Zhou, Ri-Gui; Liu, XingAo; Zhu, Changming; Wei, Lai; Zhang, Xiafen; Ian, Hou

    2018-06-01

    Similarity analyses between quantum images are so essential in quantum image processing that it provides fundamental research for the other fields, such as quantum image matching, quantum pattern recognition. In this paper, a quantum scheme based on a novel quantum image representation and quantum amplitude amplification algorithm is proposed. At the end of the paper, three examples and simulation experiments show that the measurement result must be 0 when two images are same, and the measurement result has high probability of being 1 when two images are different.

  2. Both right- and left-handers show a bias to attend others' right arm.

    PubMed

    Marzoli, Daniele; Lucafò, Chiara; Pagliara, Alessandra; Cappuccio, Romina; Brancucci, Alfredo; Tommasi, Luca

    2015-02-01

    The common-coding hypothesis suggests that the more similar an observed action is to the way the observer would perform it, the stronger is the ensuing activation of motor representations. Therefore, producing actions could prime perception so that observers would be particularly responsive to (i.e. biased to perceive) actions that are related to, and share features with, their own actions. If this similarity principle also applies to handedness, right- and left-handers should be more likely to perceive actions as performed with their dominant rather than non-dominant hand. In two experiments, participants were required to indicate the perceived orientation (front or back view) of pictures of ambiguous human silhouettes performing one-handed manual actions. Experiment 1, in which 300 right-handers and 60 left-handers reported the orientation of a single silhouette seen for as much as they wished, showed that participants perceived the figures more frequently in an orientation congruent with a movement performed with the right rather than the left hand. Experiment 2, in which 12 right-handers and 12 left-handers reported the orientation of 52 silhouettes seen for 300 ms, showed similar results when multiple responses per participant were collected rather than only one. Contrary to our expectations, no difference was observed between right- and left-handers, which might suggest an attentional bias towards the right arm of human bodies in both groups. Moreover, participants were more likely to perceive the figure as front-facing than as back-facing, possibly due to the greater adaptive relevance of approaching compared to receding individuals.

  3. Average is Boring: How Similarity Kills a Meme's Success

    PubMed Central

    Coscia, Michele

    2014-01-01

    Every day we are exposed to different ideas, or memes, competing with each other for our attention. Previous research explained popularity and persistence heterogeneity of memes by assuming them in competition for limited attention resources, distributed in a heterogeneous social network. Little has been said about what characteristics make a specific meme more likely to be successful. We propose a similarity-based explanation: memes with higher similarity to other memes have a significant disadvantage in their potential popularity. We employ a meme similarity measure based on semantic text analysis and computer vision to prove that a meme is more likely to be successful and to thrive if its characteristics make it unique. Our results show that indeed successful memes are located in the periphery of the meme similarity space and that our similarity measure is a promising predictor of a meme success. PMID:25257730

  4. Similar GABAergic inputs in dentate granule cells born during embryonic and adult neurogenesis.

    PubMed

    Laplagne, Diego A; Kamienkowski, Juan E; Espósito, M Soledad; Piatti, Verónica C; Zhao, Chunmei; Gage, Fred H; Schinder, Alejandro F

    2007-05-01

    Neurogenesis in the dentate gyrus of the hippocampus follows a unique temporal pattern that begins during embryonic development, peaks during the early postnatal stages and persists through adult life. We have recently shown that dentate granule cells born in early postnatal and adult mice acquire a remarkably similar afferent connectivity and firing behavior, suggesting that they constitute a homogeneous functional population [Laplagne et al. (2006)PLoS Biol., 4, e409]. Here we extend our previous study by comparing mature neurons born in the embryonic and adult hippocampus, with a focus on intrinsic membrane properties and gamma-aminobutyric acid (GABA)ergic synaptic inputs. For this purpose, dividing neuroblasts of the ventricular wall were retrovirally labeled with green fluorescent protein at embryonic day 15 (E15), and progenitor cells of the subgranular zone were labeled with red fluorescent protein in the same mice at postnatal day 42 (P42, adulthood). Electrophysiological properties of mature neurons born at either stage were then compared in the same brain slices. Evoked and spontaneous GABAergic postsynaptic responses of perisomatic and dendritic origin displayed similar characteristics in both neuronal populations. Miniature GABAergic inputs also showed similar functional properties and pharmacological profile. A comparative analysis of the present data with our previous observations rendered no significant differences among GABAergic inputs recorded from neurons born in the embryonic, early postnatal and adult mice. Yet, embryo-born neurons showed a reduced membrane excitability, suggesting a lower engagement in network activity. Our results demonstrate that granule cells of different age, location and degree of excitability receive GABAergic inputs of equivalent functional characteristics.

  5. Consistency and similarity of MEG- and fMRI-signal time courses during movie viewing.

    PubMed

    Lankinen, Kaisu; Saari, Jukka; Hlushchuk, Yevhen; Tikka, Pia; Parkkonen, Lauri; Hari, Riitta; Koskinen, Miika

    2018-06-01

    Movie viewing allows human perception and cognition to be studied in complex, real-life-like situations in a brain-imaging laboratory. Previous studies with functional magnetic resonance imaging (fMRI) and with magneto- and electroencephalography (MEG and EEG) have demonstrated consistent temporal dynamics of brain activity across movie viewers. However, little is known about the similarities and differences of fMRI and MEG or EEG dynamics during such naturalistic situations. We thus compared MEG and fMRI responses to the same 15-min black-and-white movie in the same eight subjects who watched the movie twice during both MEG and fMRI recordings. We analyzed intra- and intersubject voxel-wise correlations within each imaging modality as well as the correlation of the MEG envelopes and fMRI signals. The fMRI signals showed voxel-wise within- and between-subjects correlations up to r = 0.66 and r = 0.37, respectively, whereas these correlations were clearly weaker for the envelopes of band-pass filtered (7 frequency bands below 100 Hz) MEG signals (within-subjects correlation r < 0.14 and between-subjects r < 0.05). Direct MEG-fMRI voxel-wise correlations were unreliable. Notably, applying a spatial-filtering approach to the MEG data uncovered consistent canonical variates that showed considerably stronger (up to r = 0.25) between-subjects correlations than the univariate voxel-wise analysis. Furthermore, the envelopes of the time courses of these variates up to about 10 Hz showed association with fMRI signals in a general linear model. Similarities between envelopes of MEG canonical variates and fMRI voxel time-courses were seen mostly in occipital, but also in temporal and frontal brain regions, whereas intra- and intersubject correlations for MEG and fMRI separately were strongest only in the occipital areas. In contrast to the conventional univariate analysis, the spatial-filtering approach was able to uncover associations between the MEG

  6. Quantifying the Diversity and Similarity of Surgical Procedures Among Hospitals and Anesthesia Providers.

    PubMed

    Dexter, Franklin; Ledolter, Johannes; Hindman, Bradley J

    2016-01-01

    In this Statistical Grand Rounds, we review methods for the analysis of the diversity of procedures among hospitals, the activities among anesthesia providers, etc. We apply multiple methods and consider their relative reliability and usefulness for perioperative applications, including calculations of SEs. We also review methods for comparing the similarity of procedures among hospitals, activities among anesthesia providers, etc. We again apply multiple methods and consider their relative reliability and usefulness for perioperative applications. The applications include strategic analyses (e.g., hospital marketing) and human resource analytics (e.g., comparisons among providers). Measures of diversity of procedures and activities (e.g., Herfindahl and Gini-Simpson index) are used for quantification of each facility (hospital) or anesthesia provider, one at a time. Diversity can be thought of as a summary measure. Thus, if the diversity of procedures for 48 hospitals is studied, the diversity (and its SE) is being calculated for each hospital. Likewise, the effective numbers of common procedures at each hospital can be calculated (e.g., by using the exponential of the Shannon index). Measures of similarity are pairwise assessments. Thus, if quantifying the similarity of procedures among cases with a break or handoff versus cases without a break or handoff, a similarity index represents a correlation coefficient. There are several different measures of similarity, and we compare their features and applicability for perioperative data. We rely extensively on sensitivity analyses to interpret observed values of the similarity index.

  7. A Segment-Based Trajectory Similarity Measure in the Urban Transportation Systems.

    PubMed

    Mao, Yingchi; Zhong, Haishi; Xiao, Xianjian; Li, Xiaofang

    2017-03-06

    With the rapid spread of built-in GPS handheld smart devices, the trajectory data from GPS sensors has grown explosively. Trajectory data has spatio-temporal characteristics and rich information. Using trajectory data processing techniques can mine the patterns of human activities and the moving patterns of vehicles in the intelligent transportation systems. A trajectory similarity measure is one of the most important issues in trajectory data mining (clustering, classification, frequent pattern mining, etc.). Unfortunately, the main similarity measure algorithms with the trajectory data have been found to be inaccurate, highly sensitive of sampling methods, and have low robustness for the noise data. To solve the above problems, three distances and their corresponding computation methods are proposed in this paper. The point-segment distance can decrease the sensitivity of the point sampling methods. The prediction distance optimizes the temporal distance with the features of trajectory data. The segment-segment distance introduces the trajectory shape factor into the similarity measurement to improve the accuracy. The three kinds of distance are integrated with the traditional dynamic time warping algorithm (DTW) algorithm to propose a new segment-based dynamic time warping algorithm (SDTW). The experimental results show that the SDTW algorithm can exhibit about 57%, 86%, and 31% better accuracy than the longest common subsequence algorithm (LCSS), and edit distance on real sequence algorithm (EDR) , and DTW, respectively, and that the sensitivity to the noise data is lower than that those algorithms.

  8. Application of Shape Similarity in Pose Selection and Virtual Screening in CSARdock2014 Exercise.

    PubMed

    Kumar, Ashutosh; Zhang, Kam Y J

    2016-06-27

    To evaluate the applicability of shape similarity in docking-based pose selection and virtual screening, we participated in the CSARdock2014 benchmark exercise for identifying the correct docking pose of inhibitors targeting factor XA, spleen tyrosine kinase, and tRNA methyltransferase. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. In the CSARdock2014 benchmark exercise, we have implemented an approach that uses ligand 3D shape similarity to facilitate docking-based pose selection and virtual screening. We showed here that ligand 3D shape similarity between bound poses could be used to identify the native-like pose from an ensemble of docking-generated poses. Our method correctly identified the native pose as the top-ranking pose for 73% of test cases in a blind testing environment. Moreover, the pose selection results also revealed an excellent correlation between ligand 3D shape similarity scores and RMSD to X-ray crystal structure ligand. In the virtual screening exercise, the average RMSD for our pose prediction was found to be 1.02 Å, and it was one of the top performances achieved in CSARdock2014 benchmark exercise. Furthermore, the inclusion of shape similarity improved virtual screening performance of docking-based scoring and ranking. The coefficient of determination (r(2)) between experimental activities and docking scores for 276 spleen tyrosine kinase inhibitors was found to be 0.365 but reached 0.614 when the ligand 3D shape similarity was included.

  9. Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic

    PubMed Central

    2010-01-01

    Background X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue. Results We examined expression of X-borne genes using quantitative PCR, revealing a range of dosage compensation for different loci. To assess the frequency of 1X- or 2X-active fibroblasts, we investigated expression of 32 X-borne genes at the cellular level using RNA-FISH. In female fibroblasts, two-color RNA-FISH showed that genes were coordinately expressed from the same X (active X) in nuclei in which both loci were inactivated. However, loci on the other X escape inactivation independently, with each locus showing a characteristic frequency of 1X-active and 2X-active nuclei, equivalent to stochastic escape. We constructed an activity map of the tammar wallaby inactive X chromosome, which identified no relationship between gene location and extent of inactivation, nor any correlation with the presence or absence of a Y-borne paralog. Conclusions In the tammar wallaby, one X (presumed to be maternal) is expressed in all cells, but genes on the other (paternal) X escape inactivation independently and at characteristic frequencies. The paternal and incomplete X chromosome inactivation in marsupials, with stochastic escape, appears to be quite distinct from the X chromosome inactivation process in eutherians. We find no evidence for a polar spread of inactivation from an X inactivation center. PMID:21182760

  10. Protein-protein interaction network-based detection of functionally similar proteins within species.

    PubMed

    Song, Baoxing; Wang, Fen; Guo, Yang; Sang, Qing; Liu, Min; Li, Dengyun; Fang, Wei; Zhang, Deli

    2012-07-01

    Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent. Copyright © 2012 Wiley Periodicals, Inc.

  11. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (golden apple snail).

    PubMed

    Plan, Manuel Rey R; Saska, Ivana; Cagauan, Arsenia G; Craik, David J

    2008-07-09

    Golden apple snails ( Pomacea canaliculata) are serious pests of rice in South East Asia. Cyclotides are backbone cyclized peptides produced by plants from Rubiaceae and Violaceae. In this study, we investigated the molluscicidal activity of cyclotides against golden apple snails. Crude cyclotide extracts from both Oldenlandia affinis and Viola odorata plants showed molluscicidal activity comparable to the synthetic molluscicide metaldehyde. Individual cyclotides from each extract demonstrated a range of molluscicidal activities. The cyclotides cycloviolacin O1, kalata B1, and kalata B2 were more toxic to golden apple snails than metaldehyde, while kalata B7 and kalata B8 did not cause significant mortality. The toxicity of the cyclotide kalata B2 on a nontarget species, the Nile tilapia ( Oreochromis niloticus), was three times lower than the common piscicide rotenone. Our findings suggest that the existing diversity of cyclotides in plants could be used to develop natural molluscicides.

  12. Niche similarities among introduced and native mountain ungulates.

    PubMed

    Lowrey, B; Garrott, R A; McWhirter, D E; White, P J; DeCesare, N J; Stewart, S T

    2018-03-24

    The niche concept provides a strong foundation for theoretical and applied research among a broad range of disciplines. When two ecologically similar species are sympatric, theory predicts they will occupy distinct ecological niches to reduce competition. Capitalizing on the increasing availability of spatial data, we built from single species habitat suitability models to a multispecies evaluation of the niche partitioning hypothesis with sympatric mountain ungulates: native bighorn sheep (BHS; Ovis canadensis) and introduced mountain goats (MTG; Oreamnos americanus) in the northeast Greater Yellowstone Area. We characterized seasonal niches using two-stage resource selection functions with a used-available design and descriptive summaries of the niche attributes associated with used GPS locations. We evaluated seasonal similarity in niche space according to confidence interval overlap of model coefficients and similarity in geographic space by comparing model predicted values with Schoener's D metric. Our sample contained 37,962 summer locations from 53 individuals (BHS = 31, MTG = 22), and 79,984 winter locations from 57 individuals (BHS = 35, MTG = 22). Slope was the most influential niche component for both species and seasons, and showed the strongest evidence of niche partitioning. Bighorn sheep occurred on steeper slopes than mountain goats in summer and mountain goats occurred on steeper slopes in winter. The pattern of differential selection among species was less prevalent for the remaining covariates, indicating similarity in niche space. Model predictions in geographic space showed broad seasonal similarity (summer D = 0.88, winter D = 0.87), as did niche characterizations from used GPS locations. The striking similarities in seasonal niches suggest that introduced mountain goats will continue to increase their spatial overlap with native bighorn. Our results suggest that reducing densities of mountain goats in hunted areas where they are

  13. Distribution in microbial genomes of genes similar to lodA and goxA which encode a novel family of quinoproteins with amino acid oxidase activity.

    PubMed

    Campillo-Brocal, Jonatan C; Chacón-Verdú, María Dolores; Lucas-Elío, Patricia; Sánchez-Amat, Antonio

    2015-03-24

    L-Amino acid oxidases (LAOs) have been generally described as flavoproteins that oxidize amino acids releasing the corresponding ketoacid, ammonium and hydrogen peroxide. The generation of hydrogen peroxide gives to these enzymes antimicrobial characteristics. They are involved in processes such as biofilm development and microbial competition. LAOs are of great biotechnological interest in different applications such as the design of biosensors, biotransformations and biomedicine. The marine bacterium Marinomonas mediterranea synthesizes LodA, the first known LAO that contains a quinone cofactor. LodA is encoded in an operon that contains a second gene coding for LodB, a protein required for the post-translational modification generating the cofactor. Recently, GoxA, a quinoprotein with sequence similarity to LodA but with a different enzymatic activity (glycine oxidase instead of lysine-ε-oxidase) has been described. The aim of this work has been to study the distribution of genes similar to lodA and/or goxA in sequenced microbial genomes and to get insight into the evolution of this novel family of proteins through phylogenetic analysis. Genes encoding LodA-like proteins have been detected in several bacterial classes. However, they are absent in Archaea and detected only in a small group of fungi of the class Agaromycetes. The vast majority of the genes detected are in a genome region with a nearby lodB-like gene suggesting a specific interaction between both partner proteins. Sequence alignment of the LodA-like proteins allowed the detection of several conserved residues. All of them showed a Cys and a Trp that aligned with the residues that are forming part of the cysteine tryptophilquinone (CTQ) cofactor in LodA. Phylogenetic analysis revealed that LodA-like proteins can be clustered in different groups. Interestingly, LodA and GoxA are in different groups, indicating that those groups are related to the enzymatic activity of the proteins detected. Genome

  14. What Fraction of Active Galaxies Actually Show Outflows?

    NASA Astrophysics Data System (ADS)

    Ganguly, Rajib; Brotherton, M. S.

    2007-12-01

    Outflows from active galactic nuclei (AGNs) seem to be common and are thought to be important from a variety of perspectives: as an agent of chemical enhancement of the interstellar and intergalactic media, as an agent of angular momentum removal from the accreting central engine, and as an agent limiting star formation in starbursting systems by blowing out gas and dust from the host galaxy. To understand these processes, we must determine what fraction of AGNs feature outflows and understand what forms they take. We examine recent surveys of outflows detected in ultraviolet absorption over the entire range of velocities and velocity widths (i.e., broad absorption lines, associated absorption lines, and high-velocity narrow absorption lines). While the fraction of specific forms of outflows depends on AGN properties, the overall fraction displaying outflows is fairly constant, approximately 60%, over many orders of magnitude in luminosity. We discuss implications of this result and ways to refine our understanding of outflows. We acknowledge support from the US National Science Foundation through grant AST 05-07781.

  15. A graph-based semantic similarity measure for the gene ontology.

    PubMed

    Alvarez, Marco A; Yan, Changhui

    2011-12-01

    Existing methods for calculating semantic similarities between pairs of Gene Ontology (GO) terms and gene products often rely on external databases like Gene Ontology Annotation (GOA) that annotate gene products using the GO terms. This dependency leads to some limitations in real applications. Here, we present a semantic similarity algorithm (SSA), that relies exclusively on the GO. When calculating the semantic similarity between a pair of input GO terms, SSA takes into account the shortest path between them, the depth of their nearest common ancestor, and a novel similarity score calculated between the definitions of the involved GO terms. In our work, we use SSA to calculate semantic similarities between pairs of proteins by combining pairwise semantic similarities between the GO terms that annotate the involved proteins. The reliability of SSA was evaluated by comparing the resulting semantic similarities between proteins with the functional similarities between proteins derived from expert annotations or sequence similarity. Comparisons with existing state-of-the-art methods showed that SSA is highly competitive with the other methods. SSA provides a reliable measure for semantics similarity independent of external databases of functional-annotation observations.

  16. Self-similar seismogenic structure of the crust: A review of the problem and a mathematical model

    NASA Astrophysics Data System (ADS)

    Stakhovsky, I. R.

    2007-12-01

    The paper presents a brief review of studies of the structural organization of a seismogenic medium showing that the crust of seismically active regions possesses a fractal structure. A new mathematical model of the self-similar seismogenic structure (SSS) of the crust generalizing the reviewed publications is proposed on the basis of the scaling correspondence between the fault, seismic, and seismic energy multifractal fields of the crust. Multifractal fields of other physical origin can also be incorporated in the SSS model.

  17. Global Neural Pattern Similarity as a Common Basis for Categorization and Recognition Memory

    PubMed Central

    Xue, Gui; Love, Bradley C.; Preston, Alison R.; Poldrack, Russell A.

    2014-01-01

    Familiarity, or memory strength, is a central construct in models of cognition. In previous categorization and long-term memory research, correlations have been found between psychological measures of memory strength and activation in the medial temporal lobes (MTLs), which suggests a common neural locus for memory strength. However, activation alone is insufficient for determining whether the same mechanisms underlie neural function across domains. Guided by mathematical models of categorization and long-term memory, we develop a theory and a method to test whether memory strength arises from the global similarity among neural representations. In human subjects, we find significant correlations between global similarity among activation patterns in the MTLs and both subsequent memory confidence in a recognition memory task and model-based measures of memory strength in a category learning task. Our work bridges formal cognitive theories and neuroscientific models by illustrating that the same global similarity computations underlie processing in multiple cognitive domains. Moreover, by establishing a link between neural similarity and psychological memory strength, our findings suggest that there may be an isomorphism between psychological and neural representational spaces that can be exploited to test cognitive theories at both the neural and behavioral levels. PMID:24872552

  18. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    PubMed

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  19. Four plant defensins from an indigenous South African Brassicaceae species display divergent activities against two test pathogens despite high sequence similarity in the encoding genes

    PubMed Central

    2011-01-01

    Background Plant defensins are an important component of the innate defence system of plants where they form protective antimicrobial barriers between tissue types of plant organs as well as around seeds. These peptides also have other activities that are important for agricultural applications as well as the medical sector. Amongst the numerous plant peptides isolated from a variety of plant species, a significant number of promising defensins have been isolated from Brassicaceae species. Here we report on the isolation and characterization of four defensins from Heliophila coronopifolia, a native South African Brassicaceae species. Results Four defensin genes (Hc-AFP1-4) were isolated with a homology based PCR strategy. Analysis of the deduced amino acid sequences showed that the peptides were 72% similar and grouped closest to defensins isolated from other Brassicaceae species. The Hc-AFP1 and 3 peptides shared high homology (94%) and formed a unique grouping in the Brassicaceae defensins, whereas Hc-AFP2 and 4 formed a second homology grouping with defensins from Arabidopsis and Raphanus. Homology modelling showed that the few amino acids that differed between the four peptides had an effect on the surface properties of the defensins, specifically in the alpha-helix and the loop connecting the second and third beta-strands. These areas are implicated in determining differential activities of defensins. Comparing the activities after recombinant production of the peptides, Hc-AFP2 and 4 had IC50 values of 5-20 μg ml-1 against two test pathogens, whereas Hc-AFP1 and 3 were less active. The activity against Botrytis cinerea was associated with membrane permeabilization, hyper-branching, biomass reduction and even lytic activity. In contrast, only Hc-AFP2 and 4 caused membrane permeabilization and severe hyper-branching against the wilting pathogen Fusarium solani, while Hc-AFP1 and 3 had a mild morphogenetic effect on the fungus, without any indication of

  20. Phoneme Similarity and Confusability

    ERIC Educational Resources Information Center

    Bailey, T.M.; Hahn, U.

    2005-01-01

    Similarity between component speech sounds influences language processing in numerous ways. Explanation and detailed prediction of linguistic performance consequently requires an understanding of these basic similarities. The research reported in this paper contrasts two broad classes of approach to the issue of phoneme similarity-theoretically…

  1. Stellar activity with LAMOST - II. Chromospheric activity in open clusters

    NASA Astrophysics Data System (ADS)

    Fang, Xiang-Song; Zhao, Gang; Zhao, Jing-Kun; Bharat Kumar, Yerra

    2018-05-01

    We use the LAMOST spectra of member stars in Pleiades, M34, Praesepe, and Hyades to study how chromospheric activity varies as a function of mass and rotation at different age. We measured excess equivalent widths of H α, H β, and Ca II K based on estimated chromospheric contributions from old and inactive field dwarfs, and excess luminosities are obtained by normalizing bolometric luminosity, for more than 700 late-type stars in these open clusters. Results indicate two activity sequences in cool spot coverage and H α excess emission among GK dwarfs in Pleiades and M dwarfs in Praesepe and Hyades, paralleling with well-known rotation sequences. A weak dependence of chromospheric emission on rotation exists among ultrafast rotators in saturated regime with Rossby number Ro ≲ 0.1. In the unsaturated regime, chromospheric and coronal emission show similar dependence on Ro, but with a shift towards larger Ro, indicating chromospheric emission gets easily saturated than coronal emission, and/or convective turnover time-scales based on X-ray data do not work well with chromospheric emission. More interestingly, our analysis shows fully convective slow rotators obey the rotation-chromospheric activity relation similar to hotter stars, confirming the previous finding. We found correlations among H α, H β, and Ca II K emissions, in which H α losses are more important than Ca II K for cooler and more active stars. In addition, a weak correlation is seen between chromospheric emission and photospheric activity that shows dependence on stellar spectral type and activity level, which provides some clues on how spot configuration varies as a function of mass and activity level.

  2. 20 CFR 404.1573 - General information about work activity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... working at the substantial gainful activity level. If you are unable, because of your impairments, to do... people doing similar work, this may show that you are not working at the substantial gainful activity..., this does not show that you are working at the substantial gainful activity level. (c) If your work is...

  3. A general method for computing Tutte polynomials of self-similar graphs

    NASA Astrophysics Data System (ADS)

    Gong, Helin; Jin, Xian'an

    2017-10-01

    Self-similar graphs were widely studied in both combinatorics and statistical physics. Motivated by the construction of the well-known 3-dimensional Sierpiński gasket graphs, in this paper we introduce a family of recursively constructed self-similar graphs whose inner duals are of the self-similar property. By combining the dual property of the Tutte polynomial and the subgraph-decomposition trick, we show that the Tutte polynomial of this family of graphs can be computed in an iterative way and in particular the exact expression of the formula of the number of their spanning trees is derived. Furthermore, we show our method is a general one that is easily extended to compute Tutte polynomials for other families of self-similar graphs such as Farey graphs, 2-dimensional Sierpiński gasket graphs, Hanoi graphs, modified Koch graphs, Apollonian graphs, pseudofractal scale-free web, fractal scale-free network, etc.

  4. Map showing recently active breaks along the San Andreas Fault between Pt. Delgada and Bolinas Bay, California

    USGS Publications Warehouse

    Brown, Robert D.; Wolfe, Edward W.

    1970-01-01

    This strip map is one of a series of maps showing recently active fault breaks along the San Andreas and other active faults in California. It is designed to inform persons who are concerned with land use near the fault of the location of those fault breaks that have moved recently. The lines on the map are lines of rupture and creep that can be identified by field evidence and that clearly affect the present surface of the land. Map users should keep in mind that these lines are intended primarily as guides to help locate the fault; the mapped lines are not necessarily shown with the precision demanded by some engineering or land utilization needs.

  5. A vertex similarity index for better personalized recommendation

    NASA Astrophysics Data System (ADS)

    Chen, Ling-Jiao; Zhang, Zi-Ke; Liu, Jin-Hu; Gao, Jian; Zhou, Tao

    2017-01-01

    Recommender systems benefit us in tackling the problem of information overload by predicting our potential choices among diverse niche objects. So far, a variety of personalized recommendation algorithms have been proposed and most of them are based on similarities, such as collaborative filtering and mass diffusion. Here, we propose a novel vertex similarity index named CosRA, which combines advantages of both the cosine index and the resource-allocation (RA) index. By applying the CosRA index to real recommender systems including MovieLens, Netflix and RYM, we show that the CosRA-based method has better performance in accuracy, diversity and novelty than some benchmark methods. Moreover, the CosRA index is free of parameters, which is a significant advantage in real applications. Further experiments show that the introduction of two turnable parameters cannot remarkably improve the overall performance of the CosRA index.

  6. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

    PubMed

    Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

    2003-08-01

    Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

  7. Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

    PubMed

    Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku

    2006-08-01

    The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.

  8. Cross-Language Distributions of High Frequency and Phonetically Similar Cognates

    PubMed Central

    Schepens, Job; Dijkstra, Ton; Grootjen, Franc; van Heuven, Walter J. B.

    2013-01-01

    The coinciding form and meaning similarity of cognates, e.g. ‘flamme’ (French), ‘Flamme’ (German), ‘vlam’ (Dutch), meaning ‘flame’ in English, facilitates learning of additional languages. The cross-language frequency and similarity distributions of cognates vary according to evolutionary change and language contact. We compare frequency and orthographic (O), phonetic (P), and semantic similarity of cognates, automatically identified in semi-complete lexicons of six widely spoken languages. Comparisons of P and O similarity reveal inconsistent mappings in language pairs with deep orthographies. The frequency distributions show that cognate frequency is reduced in less closely related language pairs as compared to more closely related languages (e.g., French-English vs. German-English). These frequency and similarity patterns may support a better understanding of cognate processing in natural and experimental settings. The automatically identified cognates are available in the supplementary materials, including the frequency and similarity measurements. PMID:23675449

  9. Similarity and Congruence.

    ERIC Educational Resources Information Center

    Herman, Daniel L.

    This instructional unit is an introduction to the common properties of similarity and congruence. Manipulation of objects leads to a recognition of these properties. The ASA, SAS, and SSS theorems are not mentioned. Limited use is made in the application of the properties of size and shape preserved by similarity or congruence. A teacher's guide…

  10. Self-similar conductance patterns in graphene Cantor-like structures.

    PubMed

    García-Cervantes, H; Gaggero-Sager, L M; Díaz-Guerrero, D S; Sotolongo-Costa, O; Rodríguez-Vargas, I

    2017-04-04

    Graphene has proven to be an ideal system for exotic transport phenomena. In this work, we report another exotic characteristic of the electron transport in graphene. Namely, we show that the linear-regime conductance can present self-similar patterns with well-defined scaling rules, once the graphene sheet is subjected to Cantor-like nanostructuring. As far as we know the mentioned system is one of the few in which a self-similar structure produces self-similar patterns on a physical property. These patterns are analysed quantitatively, by obtaining the scaling rules that underlie them. It is worth noting that the transport properties are an average of the dispersion channels, which makes the existence of scale factors quite surprising. In addition, that self-similarity be manifested in the conductance opens an excellent opportunity to test this fundamental property experimentally.

  11. Crude extract and fractions from Eugenia uniflora Linn leaves showed anti-inflammatory, antioxidant, and antibacterial activities.

    PubMed

    Falcão, Tamires Rocha; de Araújo, Aurigena Antunes; Soares, Luiz Alberto Lira; de Moraes Ramos, Rhayanne Thaís; Bezerra, Isabelle Cristinne Ferraz; Ferreira, Magda Rhayanny Assunção; de Souza Neto, Manoel André; Melo, Maria Celeste Nunes; de Araújo, Raimundo Fernandes; de Aguiar Guerra, Andreza Conceição Véras; de Medeiros, Juliana Silva; Guerra, Gerlane Coelho Bernardo

    2018-03-09

    This study showed phytochemical composition and evaluates the anti-inflammatory, and analgesic activities of crude extract (CE) and fractions from E. uniflora Linn leaves. Polyphenols present in crude extract (CE), in aqueous fraction (AqF), and ethyl acetate (EAF) treated fractions from E. uniflora Linn leaves were shown by chromatographic analysis in order to conduct a phytochemical characterization. Antibacterial activity was evaluated based on minimum inhibitory concentrations (MICs) determined using the agar dilution method. Doses of 50, 100, and 200 mg/kg of the CE and fractions were applied for conducting in vivo models (male Swiss mice, 8-10 weeks old). The peritonitis experimental model was induced by carrageenan following of Myeloperoxidase activity (MPO), Total glutathione and malondialdehyde (MDA), IL-1β and TNF-α levels by spectroscopic UV/VIS analysis. Antinociceptive activity was evaluated based on an abdominal writhing model and hot plate test. The results were statistically evaluated using one-way analysis of variance (ANOVA), followed by Bonferroni's post-hoc test. The level of statistical significance was p < 0.05. High-performance liquid chromatography with photodiode array detection (HPLC-DAD) detected varying concentrations of gallic acid, ellagic acid, and myricitrin in the CE and fractions obtained from E. uniflora Linn leaves (0.05-0.87%w/w, 0.20-0.32%w/w, and 1.71-6.56%w/w, respectively). In general, the CE had lower MIC values than the fractions, including the lowest MIC against the MRSA strain. The CE and AqF also significantly reduced leukocyte migration and MPO activity (p < 0.05). In addition, AqF significantly reduced IL-1β and TNF-α levels (p < 0.05). Furthermore, the CE and fractions exhibited an antioxidant effect (p < 0.05) and peripheral analgesic activity (p < 0.05). The CE and fractions from the studied E. uniflora Linn leaves exhibited antibacterial, anti-inflammatory, antioxidant, and analgesic

  12. Magnetic field effect in organic light emitting diodes based on donor-acceptor exciplexes showing thermally activated delayed fluorescence

    NASA Astrophysics Data System (ADS)

    Baniya, S.; Pang, Z.; Sun, D.; Basel, T.; Zhai, Y.; Kwon, O.; Choi, H.; Vardeny, Z. V.

    2016-09-01

    A new type of organic light-emitting diode (OLED) has emerged that shows enhanced operational stability and large internal quantum efficiency approaching 100%, which is based on exciplexes in donor-acceptor (D-A) blends having thermally activated delayed fluorescence (TADF) when doped with fluorescent emitters. We have investigated magnetoelectroluminescence (MEL) and magneto-conductivity in such TADF-based OLEDs, as well as magnetophotoluminescence (MPL) in thin films based on the OLEDs active layers, with various fluorescence emitters. We found that both MEL and MPL responses are thermally activated with substantially lower activation energy compared to that in the pristine undoped D-A exciplex host blend. In addition, both MPL and MEL steeply decrease with the emitters' concentration. This indicates the existence of a loss mechanism, whereby the triplet charge-transfer state in the D-A exciplex host blend may directly decay to the lowest, non-emissive triplet state of the additive fluorescent emitter molecules.

  13. Silk gland-specific proteinase inhibitor serpin16 from the Bombyx mori shows cysteine proteinase inhibitory activity.

    PubMed

    Guo, Peng-Chao; Dong, Zhaoming; Xiao, Li; Li, Tao; Zhang, Yan; He, Huawei; Xia, Qingyou; Zhao, Ping

    2015-01-30

    Serpins (serine proteinase inhibitors) are widely distributed in different species and are well known for their inhibitory activities towards serine proteinases. Here, we report the functional characterization of Bombyx mori serpin16. Expression analysis showed that serpin16 was specifically expressed at high levels in the silk gland at both the transcriptional and translational levels. Moreover, homology modeling and multi-sequence alignment suggested that serpin16 had a canonical serpin fold, but it contained a unique reactive center loop, which was obviously shorter than that of typical serpins. Inhibitory activity analyses revealed that the target proteinase of serpin18 is a cysteine proteinase, rather than a serine proteinase. Furthermore, a Michaelis complex model of serpin16 with its target proteinase was constructed to explain the structural basis of how serpin16 recognizes the cysteine proteinase and its target specificity. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Fuzzy measures on the Gene Ontology for gene product similarity.

    PubMed

    Popescu, Mihail; Keller, James M; Mitchell, Joyce A

    2006-01-01

    One of the most important objects in bioinformatics is a gene product (protein or RNA). For many gene products, functional information is summarized in a set of Gene Ontology (GO) annotations. For these genes, it is reasonable to include similarity measures based on the terms found in the GO or other taxonomy. In this paper, we introduce several novel measures for computing the similarity of two gene products annotated with GO terms. The fuzzy measure similarity (FMS) has the advantage that it takes into consideration the context of both complete sets of annotation terms when computing the similarity between two gene products. When the two gene products are not annotated by common taxonomy terms, we propose a method that avoids a zero similarity result. To account for the variations in the annotation reliability, we propose a similarity measure based on the Choquet integral. These similarity measures provide extra tools for the biologist in search of functional information for gene products. The initial testing on a group of 194 sequences representing three proteins families shows a higher correlation of the FMS and Choquet similarities to the BLAST sequence similarities than the traditional similarity measures such as pairwise average or pairwise maximum.

  15. Central effects of corticotropin releasing factor (CRF): evidence for similar interactions with environmental novelty and with caffeine.

    PubMed

    Britton, D R; Indyk, E

    1990-01-01

    Centrally administered rat/human corticotropin-releasing factor (rCRF) increases low levels of locomotor activity by rats tested in a familiar environment but suppresses the higher levels of activity associated with exposure of the animals to a novel environment. These opposing responses do not appear to be manifestations of a simple rate-dependent effect, since ICV-administered rCRF did not lower the higher levels of locomotor activity associated with the dark (active) phase of the animal's activity cycle. Caffeine, which has anxiogenic effects in man, produces effects in rats which are similar to those of rCRF. That is, both compounds elevate activity in a familiar environment but lower activity in a novel environment. Furthermore, caffeine appears to substitute for novelty in determining the direction of the locomotor effect of rCRF. Animals made hyperactive by caffeine show decreased activity when co-administered rCRF. These findings are consistent with the view that CRF acts through pathways which also subserve the responsiveness to novelty and to the anxiogenic compound caffeine.

  16. Investigating biological activity spectrum for novel quinoline analogues 2: hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity.

    PubMed

    Musiol, Robert; Tabak, Dominik; Niedbala, Halina; Podeszwa, Barbara; Jampilek, Josef; Kralova, Katarina; Dohnal, Jiri; Finster, Jacek; Mencel, Agnieszka; Polanski, Jaroslaw

    2008-04-15

    Two series of amides based on quinoline scaffold were designed and synthesized in search of photosynthesis inhibitors. The compounds were tested for their photosynthesis-inhibiting activity against Spinacia oleracea L. and Chlorella vulgaris Beij. The compounds lipophilicity was determined by the RP-HPLC method. Several compounds showed biological activity similar or even higher than that of the standard (DCMU). The structure-activity relationships are discussed.

  17. N-Acylated and D enantiomer derivatives of a nonamer core peptide of lactoferricin B showing improved antimicrobial activity.

    PubMed

    Wakabayashi, H; Matsumoto, H; Hashimoto, K; Teraguchi, S; Takase, M; Hayasawa, H

    1999-05-01

    N-acylated or D enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B.

  18. Morphological similarities between DBM and a microeconomic model of sprawl

    NASA Astrophysics Data System (ADS)

    Caruso, Geoffrey; Vuidel, Gilles; Cavailhès, Jean; Frankhauser, Pierre; Peeters, Dominique; Thomas, Isabelle

    2011-03-01

    We present a model that simulates the growth of a metropolitan area on a 2D lattice. The model is dynamic and based on microeconomics. Households show preferences for nearby open spaces and neighbourhood density. They compete on the land market. They travel along a road network to access the CBD. A planner ensures the connectedness and maintenance of the road network. The spatial pattern of houses, green spaces and road network self-organises, emerging from agents individualistic decisions. We perform several simulations and vary residential preferences. Our results show morphologies and transition phases that are similar to Dieletric Breakdown Models (DBM). Such similarities were observed earlier by other authors, but we show here that it can be deducted from the functioning of the land market and thus explicitly connected to urban economic theory.

  19. Dietary flavonoid aglycones and their glycosides: Which show better biological significance?

    PubMed

    Xiao, Jianbo

    2017-06-13

    flavonoids for human health. It is possible that the effects of glycosylation on flavonoid bioactivity in vitro may differ from that seen in vivo. With in vivo (oral) treatment, flavonoid glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones. Flavonoid glycosides keep higher plasma levels and have a longer mean residence time than those of aglycones. We should pay more attention to in vivo benefits of flavonoid glycosides, especially C-glycosides.

  20. Flomoxef showed excellent in vitro activity against clinically important gram-positive and gram-negative pathogens causing community- and hospital-associated infections.

    PubMed

    Yang, Qiwen; Zhang, Hui; Cheng, Jingwei; Xu, Zhipeng; Hou, Xin; Xu, Yingchun

    2015-04-01

    The objective of this study was to better understand the in vitro activity of flomoxef against clinical pathogens. A total of 545 clinical isolates, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus, Streptococcus pneumoniae, and Streptococcus pyogenes, were isolated consecutively from clinical specimens from Peking Union Medical College Hospital in 2013. MICs were determined using broth microdilution method. esbl and ampC genes were detected by polymerase chain reaction and sequencing. Flomoxef showed excellent activity against E. coli, K. pneumoniae, and P. mirabilis isolates, with susceptibility rate of 88.8%, 88.3%, and 97.7%, separately. Moreover, flomoxef exhibited great activity against extended-spectrum beta-lactamase (ESBL) producers, with MIC50/MIC90 of 0.125/(0.5-1) μg/mL. Flomoxef showed MIC50/MIC90 of 0.5/0.5 μg/mL against MSSA, 0.125/0.25 μg/mL against S. pyogenes, and 2/16 μg/mL against S. pneumoniae. In conclusion, flomoxef is one of the cephamycins showing excellent activity against ESBL-producing or ESBL-nonproducing E. coli, K. pneumoniae, and P. mirabilis and was also potent against MSSA, S. pyogenes, and S. pneumoniae. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    PubMed Central

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection. PMID:26579205

  2. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus.

    PubMed

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  3. Males and females show differential brain activation to taste when hungry and sated in gustatory and reward areas

    PubMed Central

    Haase, Lori; Green, Erin; Murphy, Claire

    2011-01-01

    Although males and females differ in eating behavior and prevalence rates for eating disorders and obesity, little is known about gender differences in cortical activation to pleasant and unpleasant pure tastes during the physiological states of hunger and satiety. Twenty-one healthy young adults (12 females and 9 males) underwent two functional magnetic resonance imaging scans. Using four pure tastants of differing qualities (i.e., salty, sour, bitter, sweet), the present study examined gender differences in fMRI activation during two motivational states (hunger and satiety). There was greater change in fMRI activation from hunger to satiety in males than females in response to all tastes within the middle frontal gyrus (BA 10), insula, and cerebellum. Males also had greater change in activation from hunger to satiety, relative to females, in limbic regions including dorsal striatum, amygdala, parahippocampal gyrus, and posterior and anterior cingulate; however, activation was stimulus dependent, despite equivalent ratings in perceived pleasantness and intensity. Interestingly, males and females showed significant change from hunger to satiety in response to citric acid, suggesting that in addition to gender and physiological condition, stimulus quality is an important factor in taste fMRI activation. These gender differences may have implications for the pathophysiology of eating disorders and obesity. PMID:21718731

  4. 50 CFR 17.52 - Permits-similarity of appearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... species designated as Endangered or Threatened due to its similarity of appearance. Such a permit may... information: Documentary evidence, sworn affidavits, or other information to show species identification and the origin of the wildlife or plant in question. This information may be in the form of hunting...

  5. 50 CFR 17.52 - Permits-similarity of appearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... species designated as Endangered or Threatened due to its similarity of appearance. Such a permit may... information: Documentary evidence, sworn affidavits, or other information to show species identification and the origin of the wildlife or plant in question. This information may be in the form of hunting...

  6. 50 CFR 17.52 - Permits-similarity of appearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... species designated as Endangered or Threatened due to its similarity of appearance. Such a permit may... information: Documentary evidence, sworn affidavits, or other information to show species identification and the origin of the wildlife or plant in question. This information may be in the form of hunting...

  7. 50 CFR 17.52 - Permits-similarity of appearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... species designated as Endangered or Threatened due to its similarity of appearance. Such a permit may... information: Documentary evidence, sworn affidavits, or other information to show species identification and the origin of the wildlife or plant in question. This information may be in the form of hunting...

  8. SGFSC: speeding the gene functional similarity calculation based on hash tables.

    PubMed

    Tian, Zhen; Wang, Chunyu; Guo, Maozu; Liu, Xiaoyan; Teng, Zhixia

    2016-11-04

    In recent years, many measures of gene functional similarity have been proposed and widely used in all kinds of essential research. These methods are mainly divided into two categories: pairwise approaches and group-wise approaches. However, a common problem with these methods is their time consumption, especially when measuring the gene functional similarities of a large number of gene pairs. The problem of computational efficiency for pairwise approaches is even more prominent because they are dependent on the combination of semantic similarity. Therefore, the efficient measurement of gene functional similarity remains a challenging problem. To speed current gene functional similarity calculation methods, a novel two-step computing strategy is proposed: (1) establish a hash table for each method to store essential information obtained from the Gene Ontology (GO) graph and (2) measure gene functional similarity based on the corresponding hash table. There is no need to traverse the GO graph repeatedly for each method with the help of the hash table. The analysis of time complexity shows that the computational efficiency of these methods is significantly improved. We also implement a novel Speeding Gene Functional Similarity Calculation tool, namely SGFSC, which is bundled with seven typical measures using our proposed strategy. Further experiments show the great advantage of SGFSC in measuring gene functional similarity on the whole genomic scale. The proposed strategy is successful in speeding current gene functional similarity calculation methods. SGFSC is an efficient tool that is freely available at http://nclab.hit.edu.cn/SGFSC . The source code of SGFSC can be downloaded from http://pan.baidu.com/s/1dFFmvpZ .

  9. Popularity versus similarity in growing networks

    NASA Astrophysics Data System (ADS)

    Krioukov, Dmitri; Papadopoulos, Fragkiskos; Kitsak, Maksim; Serrano, Mariangeles; Boguna, Marian

    2012-02-01

    Preferential attachment is a powerful mechanism explaining the emergence of scaling in growing networks. If new connections are established preferentially to more popular nodes in a network, then the network is scale-free. Here we show that not only popularity but also similarity is a strong force shaping the network structure and dynamics. We develop a framework where new connections, instead of preferring popular nodes, optimize certain trade-offs between popularity and similarity. The framework admits a geometric interpretation, in which preferential attachment emerges from local optimization processes. As opposed to preferential attachment, the optimization framework accurately describes large-scale evolution of technological (Internet), social (web of trust), and biological (E.coli metabolic) networks, predicting the probability of new links in them with a remarkable precision. The developed framework can thus be used for predicting new links in evolving networks, and provides a different perspective on preferential attachment as an emergent phenomenon.

  10. Global neural pattern similarity as a common basis for categorization and recognition memory.

    PubMed

    Davis, Tyler; Xue, Gui; Love, Bradley C; Preston, Alison R; Poldrack, Russell A

    2014-05-28

    Familiarity, or memory strength, is a central construct in models of cognition. In previous categorization and long-term memory research, correlations have been found between psychological measures of memory strength and activation in the medial temporal lobes (MTLs), which suggests a common neural locus for memory strength. However, activation alone is insufficient for determining whether the same mechanisms underlie neural function across domains. Guided by mathematical models of categorization and long-term memory, we develop a theory and a method to test whether memory strength arises from the global similarity among neural representations. In human subjects, we find significant correlations between global similarity among activation patterns in the MTLs and both subsequent memory confidence in a recognition memory task and model-based measures of memory strength in a category learning task. Our work bridges formal cognitive theories and neuroscientific models by illustrating that the same global similarity computations underlie processing in multiple cognitive domains. Moreover, by establishing a link between neural similarity and psychological memory strength, our findings suggest that there may be an isomorphism between psychological and neural representational spaces that can be exploited to test cognitive theories at both the neural and behavioral levels. Copyright © 2014 the authors 0270-6474/14/347472-13$15.00/0.

  11. N-Acylated and d Enantiomer Derivatives of a Nonamer Core Peptide of Lactoferricin B Showing Improved Antimicrobial Activity

    PubMed Central

    Wakabayashi, Hiroyuki; Matsumoto, Hiroshi; Hashimoto, Koichi; Teraguchi, Susumu; Takase, Mitsunori; Hayasawa, Hirotoshi

    1999-01-01

    N-acylated or d enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B. PMID:10223949

  12. Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis.

    PubMed

    Lakshmanan, Anupama; Cheong, Daniel W; Accardo, Angelo; Di Fabrizio, Enzo; Riekel, Christian; Hauser, Charlotte A E

    2013-01-08

    The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer's and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-β-type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer's amyloid-β, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of α-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-β, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed β-sheet aggregates without going through the α-helical intermediate step, giving a unique fiber-diffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation.

  13. Predicting cancer-relevant proteins using an improved molecular similarity ensemble approach.

    PubMed

    Zhou, Bin; Sun, Qi; Kong, De-Xin

    2016-05-31

    In this study, we proposed an improved algorithm for identifying proteins relevant to cancer. The algorithm was named two-layer molecular similarity ensemble approach (TL-SEA). We applied TL-SEA to analyzing the correlation between anticancer compounds (against cell lines K562, MCF7 and A549) and active compounds against separate target proteins listed in BindingDB. Several associations between cancer types and related proteins were revealed using this chemoinformatics approach. An analysis of the literature showed that 26 of 35 predicted proteins were correlated with cancer cell proliferation, apoptosis or differentiation. Additionally, interactions between proteins in BindingDB and anticancer chemicals were also predicted. We discuss the roles of the most important predicted proteins in cancer biology and conclude that TL-SEA could be a useful tool for inferring novel proteins involved in cancer and revealing underlying molecular mechanisms.

  14. Distance Decay of Similarity in Neotropical Diatom Communities

    PubMed Central

    Wetzel, Carlos E.; Bicudo, Denise de C.; Ector, Luc; Lobo, Eduardo A.; Soininen, Janne; Landeiro, Victor L.; Bini, Luis M.

    2012-01-01

    Background The regression of similarity against distance unites several ecological phenomena, and thus provides a highly useful approach for illustrating the spatial turnover across sites. Our aim was to test whether the rates of decay in community similarity differ between diatom growth forms suggested to show different dispersal ability. We hypothesized that the diatom group with lower dispersal ability (i.e. periphyton) would show higher distance decay rates than a group with higher dispersal ability (i.e. plankton). Methods/Principal findings Periphyton and phytoplankton samples were gathered at sites distributed over an area of approximately 800 km length in the Negro River, Amazon basin, Brazil, South America (3°08′00″S; 59°54′30″W). Distance decay relationships were then estimated using distance-based regressions, and the coefficients of these regressions were compared among the groups with different dispersal abilities to assess our predictions. We found evidence that different tributaries and reaches of the Negro River harbor different diatom communities. As expected, the rates of distance decay in community similarity were higher for periphyton than for phytoplankton indicating the lower dispersal ability of periphytic taxa. Conclusions/Significance Our study demonstrates that the comparison of distance decay relationships among taxa with similar ecological requirements, but with different growth form and thus dispersal ability provides a sound approach to evaluate the effects of dispersal ability on beta diversity patterns. Our results are also in line with the growing body of evidence indicating that microorganisms exhibit biogeographic patterns. Finally, we underscore that clumbing all microbial taxa into one group may be a flawed approach to test whether microbes exhibit biogeographic patterns. PMID:23028767

  15. Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

    PubMed

    Sundqvist, Martina; Christenson, Karin; Holdfeldt, André; Gabl, Michael; Mårtensson, Jonas; Björkman, Lena; Dieckmann, Regis; Dahlgren, Claes; Forsman, Huamei

    2018-05-01

    GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo. In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Personality Trait Similarity Between Spouses in Four Cultures

    PubMed Central

    Martin, Thomas A.; H⊆ebí ková, Martina; Urbánek, Tomáš; Boomsma, Dorret I.; Willemsen, Gonneke; Costa, Paul T.

    2008-01-01

    We examined patterns of trait similarity (assortative mating) in married couples in four cultures, using both self-reports and spouse ratings on versions of the Revised NEO Personality Inventory. There was evidence of a subtle but pervasive perceived contrast bias in the spouse rating data. However, there was strong agreement across methods of assessment and moderate agreement across cultures in the pattern of results. Most assortment effects were small, but correlations exceeding .40 were seen for a subset of traits, chiefly from the Openness and Agreeableness domains. Except in Russia, where more positive assortment was seen for younger couples, comparisons of younger and older cohorts showed little systematic difference. This suggested that mate selection, rather than convergence over time, accounted for similarity. Future research on personality similarity in dyads can utilize different designs, but should assess personality at both domain and the facet levels. PMID:18665894

  17. Can "CANISO" Activate "CASINO"? Transposed-Letter Similarity Effects with Nonadjacent Letter Positions

    ERIC Educational Resources Information Center

    Perea, Manuel; Lupker, Stephen J.

    2004-01-01

    Nonwords created by transposing two "adjacent" letters (i.e., transposed-letter (TL) nonwords like "jugde") are very effective at activating the lexical representation of their base words. This fact poses problems for most computational models of word recognition (e.g., the interactive-activation model and its extensions), which assume that exact…

  18. Functionally Similar WRKY Proteins Regulate Vacuolar Acidification in Petunia and Hair Development in Arabidopsis

    PubMed Central

    de Vries, Michel

    2016-01-01

    The WD40 proteins ANTHOCYANIN11 (AN11) from petunia (Petunia hybrida) and TRANSPARENT TESTA GLABRA1 (TTG1) from Arabidopsis thaliana and associated basic helix-loop-helix (bHLH) and MYB transcription factors activate a variety of differentiation processes. In petunia petals, AN11 and the bHLH protein AN1 activate, together with the MYB protein AN2, anthocyanin biosynthesis and, together with the MYB protein PH4, distinct genes, such as PH1 and PH5, that acidify the vacuole. To understand how AN1 and AN11 activate anthocyanin biosynthetic and PH genes independently, we isolated PH3. We found that PH3 is a target gene of the AN11-AN1-PH4 complex and encodes a WRKY protein that can bind to AN11 and is required, in a feed-forward loop, together with AN11-AN1-PH4 for transcription of PH5. PH3 is highly similar to TTG2, which regulates hair development, tannin accumulation, and mucilage production in Arabidopsis. Like PH3, TTG2 can bind to petunia AN11 and the Arabidopsis homolog TTG1, complement ph3 in petunia, and reactivate the PH3 target gene PH5. Our findings show that the specificity of WD40-bHLH-MYB complexes is in part determined by interacting proteins, such as PH3 and TTG2, and reveal an unanticipated similarity in the regulatory circuitry that controls petunia vacuolar acidification and Arabidopsis hair development. PMID:26977085

  19. Functionally Similar WRKY Proteins Regulate Vacuolar Acidification in Petunia and Hair Development in Arabidopsis.

    PubMed

    Verweij, Walter; Spelt, Cornelis E; Bliek, Mattijs; de Vries, Michel; Wit, Niek; Faraco, Marianna; Koes, Ronald; Quattrocchio, Francesca M

    2016-03-01

    The WD40 proteins ANTHOCYANIN11 (AN11) from petunia (Petunia hybrida) and TRANSPARENT TESTA GLABRA1 (TTG1) from Arabidopsis thaliana and associated basic helix-loop-helix (bHLH) and MYB transcription factors activate a variety of differentiation processes. In petunia petals, AN11 and the bHLH protein AN1 activate, together with the MYB protein AN2, anthocyanin biosynthesis and, together with the MYB protein PH4, distinct genes, such as PH1 and PH5, that acidify the vacuole. To understand how AN1 and AN11 activate anthocyanin biosynthetic and PH genes independently, we isolated PH3. We found that PH3 is a target gene of the AN11-AN1-PH4 complex and encodes a WRKY protein that can bind to AN11 and is required, in a feed-forward loop, together with AN11-AN1-PH4 for transcription of PH5. PH3 is highly similar to TTG2, which regulates hair development, tannin accumulation, and mucilage production in Arabidopsis. Like PH3, TTG2 can bind to petunia AN11 and the Arabidopsis homolog TTG1, complement ph3 in petunia, and reactivate the PH3 target gene PH5. Our findings show that the specificity of WD40-bHLH-MYB complexes is in part determined by interacting proteins, such as PH3 and TTG2, and reveal an unanticipated similarity in the regulatory circuitry that controls petunia vacuolar acidification and Arabidopsis hair development. © 2016 American Society of Plant Biologists. All rights reserved.

  20. The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans.

    PubMed

    Barks, Sarah K; Parr, Lisa A; Rilling, James K

    2015-02-01

    The human default mode network (DMN), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. The DMN and social cognitive networks overlap significantly in humans. We previously demonstrated that chimpanzees (Pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human DMN. Human DMN is defined by task-induced deactivations, not absolute resting metabolic levels; ergo, resting activity is insufficient to define a DMN in chimpanzees. Here, we assessed the chimpanzee DMN's deactivations relative to rest during cognitive tasks and the effect of social content on these areas' activity. Chimpanzees performed a match-to-sample task with conspecific behavioral stimuli of varying sociality. Using [(18)F]-FDG PET, brain activity during these tasks was compared with activity during a nonsocial task and at rest. Cortical midline areas in chimpanzees deactivated in these tasks relative to rest, suggesting a chimpanzee DMN anatomically and functionally similar to humans. Furthermore, when chimpanzees make social discriminations, these same areas (particularly precuneus) are highly active relative to nonsocial tasks, suggesting that, as in humans, the chimpanzee DMN may play a role in social cognition. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Ketamine-induced apoptosis in the mouse cerebral cortex follows similar characteristic of physiological apoptosis and can be regulated by neuronal activity.

    PubMed

    Wang, Qi; Shen, Feng-Yan; Zou, Rong; Zheng, Jing-Jing; Yu, Xiang; Wang, Ying-Wei

    2017-06-17

    The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry. To explore the effect of neural activity on ketamine-induced apoptosis, the approaches of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and an environmental enrichment (EE) were performed. Ketamine-induced apoptosis in S1 is most prominent at postnatal days 5 and 7 (P5 - P7), and becomes insignificant by P12. Physiological and ketamine-induced apoptosis follow similar developmental patterns, mostly comprised of layer V pyramidal neurons at P5 and shifting to mostly layer II to IV GABAergic neurons by P9. Changes in neuronal activity induced by the DREADD system bidirectionally regulated the pattern of ketamine-induced apoptosis, with reduced activity inducing increased apoptosis and shifting the lamination pattern to a more immature form. Importantly, rearing mice in an EE significantly reduced the magnitude of ketamine-induced apoptosis and shifted its developmental pattern to a more mature form. Together, these results demonstrate that lamination pattern and cell-type dependent vulnerability to ketamine-induced apoptosis follow the physiological apoptosis pattern and are age- and activity-dependent. Naturally elevating neuronal activity is a possible method for reducing the adverse effects of general anesthesia.

  2. Do Transit-Oriented Developments (TODs) and Established Urban Neighborhoods Have Similar Walking Levels in Hong Kong?

    PubMed

    Lu, Yi; Gou, Zhonghua; Xiao, Yang; Sarkar, Chinmoy; Zacharias, John

    2018-03-20

    A sharp drop in physical activity and skyrocketing obesity rate has accompanied rapid urbanization in China. The urban planning concept of transit-oriented development (TOD) has been widely advocated in China to promote physical activity, especially walking. Indeed, many design features thought to promote walking-e.g., mixed land use, densification, and well-connected street network-often characterize both TODs and established urban neighborhoods. Thus, it is often assumed that TODs have similar physical activity benefits as established urban neighborhoods. To verify this assumption, this study compared walking behaviors in established urban neighborhoods and transit-oriented new towns in Hong Kong. To address the limitation of self-selection bias, we conducted a study using Hong Kong citywide public housing scheme, which assigns residents to different housing estates by flat availability and family size rather than personal preference. The results show new town residents walked less for transportation purpose than urban residents. New town residents far from the transit station (800-1200 m) walked less for recreational purpose than TOD residents close to a rail transit station (<400 m) or urban residents. The observed disparity in walking behaviors challenges the common assumption that TOD and established urban neighborhoods have similar impact on walking behavior. The results suggest the necessity for more nuanced planning strategies, taking local-level factors into account to promote walking of TOD residents who live far from transit stations.

  3. Gender Similarities and Differences in Factors Associated with Adolescent Moderate-Vigorous Physical Activity

    PubMed Central

    Wenthe, Phyllis J.; Janz, Kathleen F; Levy, Stephen M.

    2010-01-01

    This study investigated the relationship between predisposing, reinforcing, and enabling factors conceptualized within the Youth Physical Activity Promotion Model (YPAP) and moderate to vigorous physical activity (MVPA) of adolescent males and females. Specifically, self-efficacy to overcome barriers, enjoyment of physical activity; family support, peer support, perceived school climate, neighborhood safety and access to physical activity were examined. The Physical Activity Questionnaire for Adolescents (PAQ-A) and the Actigraph 7164 were used to obtain three different measures of MVPA in 205 adolescents (102 males, 103 females). Family support emerged as the most significant and consistent factor associated with the MVPA of both adolescent males and females. This relationship was noted even when different methods of measuring MVPA were employed. These findings should increase the confidence of public health officials that family support has the potential to positively alter the physical activity behavior of adolescents. PMID:19827453

  4. Motor plan differs for young and older adults during similar movements.

    PubMed

    Casamento-Moran, Agostina; Chen, Yen-Ting; Lodha, Neha; Yacoubi, Basma; Christou, Evangelos A

    2017-04-01

    Older adults exhibit altered activation of the agonist and antagonist muscles during goal-directed movements compared with young adults. However, it remains unclear whether the differential activation of the antagonistic muscles in older adults results from an impaired motor plan or an altered ability of the muscle to contract. The purpose of this study, therefore, was to determine whether the motor plan differs for young and older adults. Ten young (26.1 ± 4.3 yr, 4 women) and 16 older adults (71.9 ± 6.9 yr, 9 women) participated in the study. Participants performed 100 trials of fast goal directed movements with ankle dorsiflexion while we recorded the electromyographic activity of the primary agonist (tibialis anterior; TA) and antagonist (soleus; SOL) muscles. From those 100 trials we selected 5 trials in each of 3 movement end-point categories (fast, accurate, and slow). We investigated age-associated differences in the motor plan by quantifying the individual activity and coordination of the agonist and antagonist muscles. During similar movement end points, older adults exhibited similar activation of the agonist (TA) and antagonist (SOL) muscles compared with young adults. In addition, the coordination of the agonist and antagonist muscles (TA and SOL) was different between the two age groups. Specifically, older adults exhibited lower TA-SOL overlap ( F 1,23 = 41.2, P < 0.001) and greater TA-SOL peak EMG delay ( F 1,25 = 35.5, P < 0.001). This finding suggests that although subjects in both age groups displayed similar movement end points, they exhibited a different motor plan, as demonstrated by altered coordination between the agonist and antagonist muscles. NEW & NOTEWORTHY We aimed to determine whether the altered activation of muscles in older adults compared with young adults during fast goal-directed movements is related to an altered motor plan. For matched movements, there were differences in the coordination of antagonistic muscles but no

  5. Design of chemical space networks on the basis of Tversky similarity

    NASA Astrophysics Data System (ADS)

    Wu, Mengjun; Vogt, Martin; Maggiora, Gerald M.; Bajorath, Jürgen

    2016-01-01

    Chemical space networks (CSNs) have been introduced as a coordinate-free representation of chemical space. In CSNs, nodes represent compounds and edges pairwise similarity relationships. These network representations are mostly used to navigate sections of biologically relevant chemical space. Different types of CSNs have been designed on the basis of alternative similarity measures including continuous numerical similarity values or substructure-based similarity criteria. CSNs can be characterized and compared on the basis of statistical concepts from network science. Herein, a new CSN design is introduced that is based upon asymmetric similarity assessment using the Tversky coefficient and termed TV-CSN. Compared to other CSNs, TV-CSNs have unique features. While CSNs typically contain separate compound communities and exhibit small world character, many TV-CSNs are also scale-free in nature and contain hubs, i.e., extensively connected central compounds. Compared to other CSNs, these hubs are a characteristic of TV-CSN topology. Hub-containing compound communities are of particular interest for the exploration of structure-activity relationships.

  6. Pomegranate (Punica granatum) Juice Shows Antioxidant Activity against Cutaneous Leishmaniasis-Induced Oxidative Stress in Female BALB/c Mice

    PubMed Central

    Alkathiri, Badriah; Metwally, Dina M.; Al-Olayan, Ebtesam M.; Bakhrebah, Muhammed A.

    2017-01-01

    Leishmania species are parasites that multiply within phagocytes and cause several clinical diseases characterized by single or multiple ulcerations. One of the complications that can induce tissue damage and the resulting scars is caused by secondary bacterial infections. Studies to find new, effective, and safe oral drugs for treating leishmaniasis are being conducted since several decades, owing to the problems associated with the use of antimonials available. Previously, the antiparasitic and antioxidant properties of Punica granatum (pomegranate, P. granatum) have been reported. Therefore, in the present study, we aimed to investigate the antileishmanial activity of pomegranate aqueous juice in vitro and in female BALB/c mice. A 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in Leishmania major promastigotes and alterations in the antioxidant status, liver function, and skin histological changes in L. major-infected mice orally treated with pomegranate juice alone and in combination with the antibiotic ciprofloxacin, were used to investigate the in vitro and in vivo antileishmanial activity of pomegranate juice, respectively. Oral P. granatum juice treatment significantly reduced the average size of cutaneous leishmaniasis lesions compared with that of the untreated mice. This antileishmanial activity of P. granatum was associated with enhanced antioxidant enzyme activities. Histopathological evaluation proved the antileishmanial activity of P. granatum, but did not reveal changes in the treated animals, compared to the positive control. In conclusion, P. granatum shows high and fast antileishmanial activity probably by boosting the endogenous antioxidant activity. PMID:29258248

  7. Clustering and visualizing similarity networks of membrane proteins.

    PubMed

    Hu, Geng-Ming; Mai, Te-Lun; Chen, Chi-Ming

    2015-08-01

    We proposed a fast and unsupervised clustering method, minimum span clustering (MSC), for analyzing the sequence-structure-function relationship of biological networks, and demonstrated its validity in clustering the sequence/structure similarity networks (SSN) of 682 membrane protein (MP) chains. The MSC clustering of MPs based on their sequence information was found to be consistent with their tertiary structures and functions. For the largest seven clusters predicted by MSC, the consistency in chain function within the same cluster is found to be 100%. From analyzing the edge distribution of SSN for MPs, we found a characteristic threshold distance for the boundary between clusters, over which SSN of MPs could be properly clustered by an unsupervised sparsification of the network distance matrix. The clustering results of MPs from both MSC and the unsupervised sparsification methods are consistent with each other, and have high intracluster similarity and low intercluster similarity in sequence, structure, and function. Our study showed a strong sequence-structure-function relationship of MPs. We discussed evidence of convergent evolution of MPs and suggested applications in finding structural similarities and predicting biological functions of MP chains based on their sequence information. © 2015 Wiley Periodicals, Inc.

  8. Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

    PubMed

    Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

    2018-01-01

    Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

  9. Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

    PubMed

    Vidal, A Cristina; Banca, Paula; Pascoal, Augusto G; Santo, Gustavo C; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

    2017-01-01

    Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

  10. Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin transporter inhibitory activity and 5-HT1A weak partial agonistic activity showing the antidepressant-like effect.

    PubMed

    Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru

    2017-01-01

    We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT 1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT 1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT 1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT 1A weak partial agonistic activity, which could work as a 5-HT 1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Haunted by a doppelgänger: irrelevant facial similarity affects rule-based judgments.

    PubMed

    von Helversen, Bettina; Herzog, Stefan M; Rieskamp, Jörg

    2014-01-01

    Judging other people is a common and important task. Every day professionals make decisions that affect the lives of other people when they diagnose medical conditions, grant parole, or hire new employees. To prevent discrimination, professional standards require that decision makers render accurate and unbiased judgments solely based on relevant information. Facial similarity to previously encountered persons can be a potential source of bias. Psychological research suggests that people only rely on similarity-based judgment strategies if the provided information does not allow them to make accurate rule-based judgments. Our study shows, however, that facial similarity to previously encountered persons influences judgment even in situations in which relevant information is available for making accurate rule-based judgments and where similarity is irrelevant for the task and relying on similarity is detrimental. In two experiments in an employment context we show that applicants who looked similar to high-performing former employees were judged as more suitable than applicants who looked similar to low-performing former employees. This similarity effect was found despite the fact that the participants used the relevant résumé information about the applicants by following a rule-based judgment strategy. These findings suggest that similarity-based and rule-based processes simultaneously underlie human judgment.

  12. Recombinant Human Melatonin Receptor MT1 Isolated in Mixed Detergents Shows Pharmacology Similar to That in Mammalian Cell Membranes

    PubMed Central

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A.; Ferry, Gilles

    2014-01-01

    The human melatonin MT1 receptor—belonging to the large family of G protein-coupled receptors (GPCRs)—plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches. PMID:24959712

  13. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    PubMed

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A; Ferry, Gilles; Simonin, Frédéric; Wagner, Renaud

    2014-01-01

    The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs)-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

  14. Males and females show differential brain activation to taste when hungry and sated in gustatory and reward areas.

    PubMed

    Haase, Lori; Green, Erin; Murphy, Claire

    2011-10-01

    Although males and females differ in eating behavior and prevalence rates for eating disorders and obesity, little is known about gender differences in cortical activation to pleasant and unpleasant pure tastes during the physiological states of hunger and satiety. Twenty-one healthy young adults (12 females and 9 males) underwent two functional magnetic resonance imaging scans. Using four pure tastants of differing qualities (i.e., salty, sour, bitter, sweet), the present study examined gender differences in fMRI activation during two motivational states (hunger and satiety). There was greater change in fMRI activation from hunger to satiety in males than females in response to all tastes within the middle frontal gyrus (BA 10), insula, and cerebellum. Males also had greater change in activation from hunger to satiety, relative to females, in limbic regions including dorsal striatum, amygdala, parahippocampal gyrus, and posterior and anterior cingulate; however, activation was stimulus dependent, despite equivalent ratings in perceived pleasantness and intensity. Interestingly, males and females showed significant change from hunger to satiety in response to citric acid, suggesting that in addition to gender and physiological condition, stimulus quality is an important factor in taste fMRI activation. These gender differences may have implications for the pathophysiology of eating disorders and obesity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Statistical self-similarity of hotspot seamount volumes modeled as self-similar criticality

    USGS Publications Warehouse

    Tebbens, S.F.; Burroughs, S.M.; Barton, C.C.; Naar, D.F.

    2001-01-01

    The processes responsible for hotspot seamount formation are complex, yet the cumulative frequency-volume distribution of hotspot seamounts in the Easter Island/Salas y Gomez Chain (ESC) is found to be well-described by an upper-truncated power law. We develop a model for hotspot seamount formation where uniform energy input produces events initiated on a self-similar distribution of critical cells. We call this model Self-Similar Criticality (SSC). By allowing the spatial distribution of magma migration to be self-similar, the SSC model recreates the observed ESC seamount volume distribution. The SSC model may have broad applicability to other natural systems.

  16. Young and Older Observers Show Similar Perceived Contrast Functions for Isoluminat Stimuli

    DTIC Science & Technology

    1991-01-01

    male subjects each. The young subjects were screened on the basis of admitted good general and ocular health . Subjects within the older aged group were...with the method of contrast estimation. Ten young and 10 older males (mean ages 20 and 64.5 yrs) viewed counterphase flickered gratings of 0.6 and...of the LGN, and if a selective attenuation of magno responses occurs with age , perceived contrast functions of young and older observers should

  17. Fathers Show Modifications of Infant-Directed Action Similar to that of Mothers

    ERIC Educational Resources Information Center

    Rutherford, M. D.; Przednowek, Malgorzata

    2012-01-01

    Mothers' actions are more enthusiastic, simple, and repetitive when demonstrating novel object properties to their infants than to adults, a behavioral modification called "infant-directed action" by Brand and colleagues (2002). The current study tested whether fathers also tailor their behavior when interacting with infants and whether this…

  18. Gender similarities and differences.

    PubMed

    Hyde, Janet Shibley

    2014-01-01

    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research.

  19. Similar alterations in brain function for phonological and semantic processing to visual characters in Chinese dyslexia.

    PubMed

    Liu, Li; Wang, Wenjing; You, Wenping; Li, Yi; Awati, Neha; Zhao, Xu; Booth, James R; Peng, Danling

    2012-07-01

    Dyslexia in alphabetic languages has been extensively investigated and suggests a central deficit in orthography to phonology mapping in the left hemisphere. Compared to dyslexia in alphabetic languages, the central deficit for Chinese dyslexia is still unclear. Because of the logographic nature of Chinese characters, some have suggested that Chinese dyslexia should have larger deficits in the semantic system. To investigate this, Chinese children with reading disability (RD) were compared to typically developing (TD) children using functional magnetic resonance imaging (fMRI) on a rhyming judgment task and on a semantic association judgment task. RD children showed less activation for both tasks in right visual (BA18, 19) and left occipito-temporal cortex (BA 37), suggesting a deficit in visuo-orthographic processing. RD children also showed less activation for both tasks in left inferior frontal gyrus (BA44), which additionally showed significant correlations with activation of bilateral visuo-orthographic regions in the RD group, suggesting that the abnormalities in frontal cortex and in posterior visuo-orthographic regions may reflect a deficit in the connection between brain regions. Analyses failed to reveal larger differences between groups for the semantic compared to the rhyming task, suggesting that Chinese dyslexia is similarly impaired in the access to phonology and to semantics from the visual orthography. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins

    PubMed Central

    Nakai, Shuryo; Li-Chan, Eunice CY; Dou, Jinglie

    2005-01-01

    Background Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families. Results Hydrophobicity and β-turn propensity of reference segments with 3–7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme. Conclusion Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available. PMID:15904486

  1. Transport of Alaskan Dust into the Gulf of Alaska and Comparison with Similar High-Latitude Dust Environments

    NASA Technical Reports Server (NTRS)

    Crusium, John; Levy, Rob; Wang, Jun; Campbell, Rob; Schroth, Andrew W.

    2012-01-01

    Transport of Alaskan dust into the Gulf of Alaska and comparison with similar high-latitude dust environments. An airborne flux of the micronutrient iron, derived from dust originating from coastal regions may be an important contributor of iron to the Gulf of Alaska's (GoA) oligotrophic waters. Dust blowing off glacier termini and dry riverbeds is a recurring phenomenon in Alaska, usually occurring in the autumn. Since previous studies assumed that dust originating in the deserts of Asia was the largest source of . airborne iron to the GoA, the budget of aeolian deposition of iron needs to be reassessed. Since late 20 I 0, our group has been monitoring dust activity using satellites over the Copper River Delta (CRD) where the most vigorous dust plumes have been observed. Since 2011, sample aerosol concentration and their composition are being collected at Middleton Island (100km off shore of CRD). This presentation will show a summary of the ongoing dust observations and compare with other similar environments (Patagonia, Iceland) by showing case studies. Common features will be highlighted

  2. Similarity Judgments: From Classical to Complex Vector Psychological Spaces

    NASA Astrophysics Data System (ADS)

    Barque Duran, Albert; Pothos, Emmanuel M.; Yearsley, James M.; Hampton, James A.; Busemeyer, Jerome R.; Trueblood, Jennifer S.

    This chapter reviews progress with applications of quantum theory in understanding human similarity judgments. We first motivate and subsequently describe the quantum similarity model (QSM), which was proposed by Pothos, Busemeyer and Trueblood (2013), primarily as a way to cover the empirical findings reported in Tversky (1977). We then show how the QSM encompasses Tversky's (1977) results, specifically in relation to violations of symmetry, violations of the triangle inequality and the diagnosticity effect. We next consider a list of challenges of the QSM and open issues for further research.

  3. Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ

    PubMed Central

    Moldes-Anaya, Angel; Sæther, Thomas; Uhlig, Silvio; Nebb, Hilde I.; Larsen, Terje; Eilertsen, Hans C.; Paulsen, Steinar M.

    2017-01-01

    The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug targets. However, for several of the PPAR drugs currently in use, adverse side effects have been reported. In an effort to identify compounds from marine organisms that may serve as molecular scaffolds for the development of novel and safer PPAR-targeting drugs, we performed a bioassay-guided screening of organic extracts made from organisms supplied by the Norwegian Biobank of Arctic Marine Organisms (Marbank). Among several interesting hits, we identified two poorly described isomeric oxo-fatty acids from the microalgae Chaetoceros karianus for which we provide the first evidence that they might display dual specificity towards human PPARα and PPARγ. Principal component analysis showed that C. karianus stood out from other Chaetoceros species, both with respect to the metabolic profile and the PPAR activity. The isolation of these compounds holds the potential of uncovering a PPAR pharmacophore with tunable activity and specificity. PMID:28587091

  4. Improved personalized recommendation based on a similarity network

    NASA Astrophysics Data System (ADS)

    Wang, Ximeng; Liu, Yun; Xiong, Fei

    2016-08-01

    A recommender system helps individual users find the preferred items rapidly and has attracted extensive attention in recent years. Many successful recommendation algorithms are designed on bipartite networks, such as network-based inference or heat conduction. However, most of these algorithms define the resource-allocation methods for an average allocation. That is not reasonable because average allocation cannot indicate the user choice preference and the influence between users which leads to a series of non-personalized recommendation results. We propose a personalized recommendation approach that combines the similarity function and bipartite network to generate a similarity network that improves the resource-allocation process. Our model introduces user influence into the recommender system and states that the user influence can make the resource-allocation process more reasonable. We use four different metrics to evaluate our algorithms for three benchmark data sets. Experimental results show that the improved recommendation on a similarity network can obtain better accuracy and diversity than some competing approaches.

  5. Similarity Theory and Dimensionless Numbers in Heat Transfer

    ERIC Educational Resources Information Center

    Marin, E.; Calderon, A.; Delgado-Vasallo, O.

    2009-01-01

    We present basic concepts underlying the so-called similarity theory that in our opinion should be explained in basic undergraduate general physics courses when dealing with heat transport problems, in particular with those involving natural or free convection. A simple example is described that can be useful in showing a criterion for neglecting…

  6. Self-Similar Subsets of Symmetric Cantor Sets

    NASA Astrophysics Data System (ADS)

    Zeng, Ying

    This paper concerns the affine embeddings of general symmetric Cantor sets. Under certain condition, we show that if a self-similar set F can be affinely embedded into a symmetric Cantor set E, then their contractions are rationally commensurable. Our result supports Conjecture 1.2 in [D. J. Feng, W. Huang and H. Rao, Affine embeddings and intersections of Cantor sets, J. Math. Pures Appl. 102 (2014) 1062-1079].

  7. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    PubMed

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  8. Analysis of Magnitude Correlations in a Self-Similar model of Seismicity

    NASA Astrophysics Data System (ADS)

    Zambrano, A.; Joern, D.

    2017-12-01

    A recent model of seismicity that incorporates a self-similar Omori-Utsu relation, which is used to describe the temporal evolution of earthquake triggering, has been shown to provide a more accurate description of seismicity in Southern California when compared to epidemic type aftershock sequence models. Forecasting of earthquakes is an active research area where one of the debated points is whether magnitude correlations of earthquakes exist within real world seismic data. Prior to this work, the analysis of magnitude correlations of the aforementioned self-similar model had not been addressed. Here we present statistical properties of the magnitude correlations for the self-similar model along with an analytical analysis of the branching ratio and criticality parameters.

  9. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    PubMed Central

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  10. Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

    PubMed

    Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

    ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

  11. Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab

    PubMed Central

    Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J.; Liu, Jennifer

    2018-01-01

    ABSTRACT ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab. PMID:29553864

  12. Identification of new members of the MAPK gene family in plants shows diverse conserved domains and novel activation loop variants.

    PubMed

    Mohanta, Tapan Kumar; Arora, Pankaj Kumar; Mohanta, Nibedita; Parida, Pratap; Bae, Hanhong

    2015-02-06

    Mitogen Activated Protein Kinase (MAPK) signaling is of critical importance in plants and other eukaryotic organisms. The MAPK cascade plays an indispensible role in the growth and development of plants, as well as in biotic and abiotic stress responses. The MAPKs are constitute the most downstream module of the three tier MAPK cascade and are phosphorylated by upstream MAP kinase kinases (MAPKK), which are in turn are phosphorylated by MAP kinase kinase kinase (MAPKKK). The MAPKs play pivotal roles in regulation of many cytoplasmic and nuclear substrates, thus regulating several biological processes. A total of 589 MAPKs genes were identified from the genome wide analysis of 40 species. The sequence analysis has revealed the presence of several N- and C-terminal conserved domains. The MAPKs were previously believed to be characterized by the presence of TEY/TDY activation loop motifs. The present study showed that, in addition to presence of activation loop TEY/TDY motifs, MAPKs are also contain MEY, TEM, TQM, TRM, TVY, TSY, TEC and TQY activation loop motifs. Phylogenetic analysis of all predicted MAPKs were clustered into six different groups (group A, B, C, D, E and F), and all predicted MAPKs were assigned with specific names based on their orthology based evolutionary relationships with Arabidopsis or Oryza MAPKs. We conducted global analysis of the MAPK gene family of plants from lower eukaryotes to higher eukaryotes and analyzed their genomic and evolutionary aspects. Our study showed the presence of several new activation loop motifs and diverse conserved domains in MAPKs. Advance study of newly identified activation loop motifs can provide further information regarding the downstream signaling cascade activated in response to a wide array of stress conditions, as well as plant growth and development.

  13. Perceptions of similarity and responsibility attributions to an acquaintance sexual assault victim.

    PubMed

    Amacker, Amanda M; Littleton, Heather L

    2013-11-01

    Individuals view similar rape victims as less responsible for the rape than victims perceived as dissimilar. However, it is unclear if individuals hold victims they perceive as similar less responsible for the assault, or if individuals view themselves as more similar to victims they do not view as responsible for the assault. The current study, therefore, examined the temporal relationship between these constructs. A total of 167 college women listened to a date narrative that ended in sexual assault, consensual sex, or no sexual activity (these last two served as controls). Results supported that participants viewed themselves as less similar to the woman in the narrative when the date ended in sexual assault. Only similarity ratings made following learning that the woman was sexually assaulted predicted responsibility attributions suggesting that viewing a victim as responsible for the assault results in decreased perceptions of similarity toward her. Implications and suggestions for future research are discussed.

  14. Personnel viewing posters showing how NASA activities have made an impact on Costa Rican people

    NASA Image and Video Library

    2004-03-03

    L-R; Jorge Andres Diaz, Director of the Costa Rican National Hangar for Airborne Research division of the National Center for High Technology(CENAT); NASA Administrator Sean O'Keefe; and Fernando Gutierrez, Costa Rican Minister of Science and Technology(MICIT), viewing posters showing how NASA activities have made an impact on Costa Rican people. Mr. O'Keefe was in Costa Rica to participate in the AirSAR 2004 Mesoamerica campaign, which used NASA DFRC's DC-8 airborne laboratory aircraft. AirSAR 2004 is a three-week expedition by an international team of scientists that will use an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), in a mission ranging from the tropical rain forests of Central America to frigid Antarctica.

  15. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase.

    PubMed

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2015-10-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 µM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl(-) and the decreased HCO3 (-) concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na-K-2Cl electroneutral cotransporter or Cl(-)/HCO3 (-) anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells.

  16. A community detection algorithm based on structural similarity

    NASA Astrophysics Data System (ADS)

    Guo, Xuchao; Hao, Xia; Liu, Yaqiong; Zhang, Li; Wang, Lu

    2017-09-01

    In order to further improve the efficiency and accuracy of community detection algorithm, a new algorithm named SSTCA (the community detection algorithm based on structural similarity with threshold) is proposed. In this algorithm, the structural similarities are taken as the weights of edges, and the threshold k is considered to remove multiple edges whose weights are less than the threshold, and improve the computational efficiency. Tests were done on the Zachary’s network, Dolphins’ social network and Football dataset by the proposed algorithm, and compared with GN and SSNCA algorithm. The results show that the new algorithm is superior to other algorithms in accuracy for the dense networks and the operating efficiency is improved obviously.

  17. Toxmatch-a new software tool to aid in the development and evaluation of chemically similar groups.

    PubMed

    Patlewicz, G; Jeliazkova, N; Gallegos Saliner, A; Worth, A P

    2008-01-01

    Chemical similarity is a widely used concept in toxicology, and is based on the hypothesis that similar compounds should have similar biological activities. This forms the underlying basis for performing read-across, forming chemical groups and developing (Quantitative) Structure-Activity Relationships ((Q)SARs). Chemical similarity is often perceived as structural similarity but in fact there are a number of other approaches that can be used to assess similarity. A systematic similarity analysis usually comprises two main steps. Firstly the chemical structures to be compared need to be characterised in terms of relevant descriptors which encode their physicochemical, topological, geometrical and/or surface properties. A second step involves a quantitative comparison of those descriptors using similarity (or dissimilarity) indices. This work outlines the use of chemical similarity principles in the formation of endpoint specific chemical groupings. Examples are provided to illustrate the development and evaluation of chemical groupings using a new software application called Toxmatch that was recently commissioned by the European Chemicals Bureau (ECB), of the European Commission's Joint Research Centre. Insights from using this software are highlighted with specific focus on the prospective application of chemical groupings under the new chemicals legislation, REACH.

  18. Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

    PubMed

    Diniz, Clarissa P; Landis, Patricia; Carter, H Ballentine; Epstein, Jonathan I; Mamawala, Mufaddal

    2017-09-01

    We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Motor Skills and Free-Living Physical Activity Showed No Association Among Preschoolers in 2012 U.S. National Youth Fitness Survey.

    PubMed

    Loprinzi, Paul D; Frith, Emily

    2017-04-01

    Albeit limited, some emerging work, using convenience-based samples, has demonstrated that greater motor skill development is associated with higher physical activity among preschool-aged children. The purpose of this study was to evaluate this topic using data from the 2012 National Youth Fitness Survey that included 329 preschool-aged children (3-5 years). Parents proxy-reported their child's physical activity, with motor skill level assessed from the Test of Gross Motor Development-Second Edition (TGMD2). Motor skill levels (Gross Motor Quotient, locomotor or object control) were not associated with preschool free-living physical activity in any analytic model. Thus, in this large sample of preschoolers, contrary to research with older children, motor skill level was not associated with physical activity. Findings are discussed in terms of study limitations of (a) a reliance on parent report of children's physical activity levels and (b) the possibility that physical activity data within the national survey were too limited in range to show possible associations to motor skill development with higher levels of free-living physical activity in preschoolers.

  20. Similarity of Symbol Frequency Distributions with Heavy Tails

    NASA Astrophysics Data System (ADS)

    Gerlach, Martin; Font-Clos, Francesc; Altmann, Eduardo G.

    2016-04-01

    Quantifying the similarity between symbolic sequences is a traditional problem in information theory which requires comparing the frequencies of symbols in different sequences. In numerous modern applications, ranging from DNA over music to texts, the distribution of symbol frequencies is characterized by heavy-tailed distributions (e.g., Zipf's law). The large number of low-frequency symbols in these distributions poses major difficulties to the estimation of the similarity between sequences; e.g., they hinder an accurate finite-size estimation of entropies. Here, we show analytically how the systematic (bias) and statistical (fluctuations) errors in these estimations depend on the sample size N and on the exponent γ of the heavy-tailed distribution. Our results are valid for the Shannon entropy (α =1 ), its corresponding similarity measures (e.g., the Jensen-Shanon divergence), and also for measures based on the generalized entropy of order α . For small α 's, including α =1 , the errors decay slower than the 1 /N decay observed in short-tailed distributions. For α larger than a critical value α*=1 +1 /γ ≤2 , the 1 /N decay is recovered. We show the practical significance of our results by quantifying the evolution of the English language over the last two centuries using a complete α spectrum of measures. We find that frequent words change more slowly than less frequent words and that α =2 provides the most robust measure to quantify language change.

  1. Does cross-taxon analysis show similarity in diversity patterns between vascular plants and bryophytes? Some answers from a literature review.

    PubMed

    Bagella, Simonetta

    2014-04-01

    The objective of this study was to clarify the taxon surrogacy hypothesis relative to vascular plants and bryophytes. A literature review was conducted to obtain papers that met the following criteria: (i) they examined species richness values; or (ii) they evaluated the species richness within the same study sites, or under the same spatial variation conditions. Twenty-seven papers were accessed. The richness of the two taxa, compared in 32 cases, positively co-varied in about half of the comparisons. The response to the spatial variation in environmental or human-induced factors of the two taxa in terms of species richness was rather variable. Based on current knowledge, the main documented findings regard forest habitats and nival gradients. In forest habitats, co-variation in species richness is likely when similar environments are analysed and seems to be strengthened for boreal forests. Along the nival gradient, a different response in terms of richness of the two taxa suggests that vascular plants cannot be considered good surrogates for bryophytes. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  2. Efficient dispersion tailoring by designing alternately arranged dispersion compensating fibers and fiber amplifiers to create self-similar parabolic pulses

    NASA Astrophysics Data System (ADS)

    Ghosh, Dipankar; Basu, Mousumi

    2010-11-01

    The parabolic similariton pulse formation by alternate arrangements of passive and active dispersion compensating fibers (DCFs) is presented here. These combinations of passive and active DCFs with constant core radii and constant nonlinearities are suggested as equivalent profiles of a dispersion tailored fiber amplifier in normal dispersion regime. The dispersion tailored fibers, usually known as dispersion decreasing fibers (DDFs) in normal dispersion regime, are capable of producing linearly chirped parabolic self-similar pulses. The DDF is designed and optimized with proper choice of fiber parameters so that considerable variation of nonlinearity can be achieved, which in turn enhances the effective gain coefficient of the fiber. Inclusion of this nonlinear variation along the DDF amplifier length leads to obtain the simulated output pulses with very small misfit parameters with respect to perfect parabolic pulse at sufficiently reduced optimum length. At the same time to avoid the fabrication difficulties of the DDF, the alternately arranged passive and active DCFs are suggested as suitable alternatives of the DDF. The performances of the cascaded systems for generation of self-similar parabolic pulses are compared with that of the DDF amplifier as well as combined systems consisting of DCFs with equal gain. The results show that the proposed alternately arranged cascaded system with less pumping requirements, are efficient enough to produce similar parabolic pulses as compared to the previously designed DDF, even when considerable amount of splice loss at each joint is included.

  3. Cross-format physical similarity effects and their implications for the numerical cognition architecture

    PubMed Central

    Cohen, Dale J.; Warren, Erin; Blanc-Goldhammer, Daryn

    2013-01-01

    The sound |faiv| is visually depicted as a written number word “five” and as an Arabic digit “5.” Here, we present four experiments – two quantity same/different experiments and two magnitude comparison experiments – that assess whether auditory number words (|faiv|), written number words (“five”), and Arabic digits (“5”) directly activate one another and/or their associated quantity. The quantity same/different experiments reveal that the auditory number words, written number words, and Arabic digits directly activate one another without activating their associated quantity. That is, there are cross-format physical similarity effects but no numerical distance effects. The cross-format magnitude comparison experiments reveal significant effects of both physical similarity and numerical distance. We discuss these results in relation to the architecture of numerical cognition. PMID:23624377

  4. Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.

    PubMed

    Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

    2016-07-01

    To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

  5. Similarity law and critical properties in ionic systems.

    NASA Astrophysics Data System (ADS)

    Desgranges, Caroline; Delhommelle, Jerome

    2017-11-01

    Using molecular simulations, we determine the locus of ideal compressibility, or Zeno line, for a series of ionic compounds. We find that the shape of this thermodynamic contour follows a linear law, leading to the determination of the Boyle parameters. We also show that a similarity law, based on the Boyle parameters, yields accurate critical data when compared to the experiment. Furthermore, we show that the Boyle density scales linearly with the size-asymmetry, providing a direct route to establish a correspondence between the thermodynamic properties of different ionic compounds.

  6. Homophily of Vocabulary Usage: Beneficial Effects of Vocabulary Similarity on Online Health Communities Participation

    PubMed Central

    Park, Albert; Hartzler, Andrea L.; Huh, Jina; McDonald, David W.; Pratt, Wanda

    2015-01-01

    Online health communities provide popular platforms for individuals to exchange psychosocial support and form ties. Although regular active participation (i.e., posting to interact with other members) in online health communities can provide important benefits, sustained active participation remains challenging for these communities. Leveraging previous literature on homophily (i.e., “love of those who are like themselves”), we examined the relationship between vocabulary similarity (i.e., homophily of word usage) of thread posts and members’ future interaction in online health communities. We quantitatively measured vocabulary similarity by calculating, in a vector space model, cosine similarity between the original post and the first reply in 20,499 threads. Our findings across five online health communities suggest that vocabulary similarity is a significant predictor of members’ future interaction in online health communities. These findings carry practical implications for facilitating and sustaining online community participation through beneficial effects of homophily in the vocabulary of essential peer support. PMID:26958240

  7. Narcissists of a Feather Flock Together: Narcissism and the Similarity of Friends.

    PubMed

    Maaß, Ulrike; Lämmle, Lena; Bensch, Doreen; Ziegler, Matthias

    2016-03-01

    Who is willing to expose himself or herself to narcissists on a long-term basis? Studies that address the interactions of narcissists focus mainly on their interactions with strangers. Hence, the aim of the present study was to investigate the extent to which two best friends' similarity in narcissism would influence their similarities in other personality profiles. A total of 290 best friends' dyads filled out measurements of the whole Dark Triad as well as the Big Five. For each personality domain, profile similarity and its dependence on the similarity in the Dark Triad were determined. Results showed that the friends' similarity in narcissism significantly predicted similarity in all Big Five domains. For the general Big Five similarity as well as extraversion, the effect of narcissism similarity was stronger for male than female or mixed friends. Similarity in psychopathy and Machiavellianism significantly predicted all domains except for openness and extraversion, respectively. © 2016 by the Society for Personality and Social Psychology, Inc.

  8. Representational similarity of social and valence information in the medial pFC.

    PubMed

    Chavez, Robert S; Heatherton, Todd F

    2015-01-01

    The human brain is remarkably adept at integrating complex information to form unified psychological representations of agents, objects, and events in the environment. Two domains in which this ability is particularly salient are the processing of social and valence information and are supported by common cortical areas in the medial pFC (MPFC). Because social information is often embedded within valenced emotional contexts, it is possible that activation patterns within the MPFC may represent both of these types of cognitive processes when presented simultaneously. The current study tested this possibility by employing a large-scale automated meta-analysis tool, together with multivoxel pattern analysis to investigate the representational similarity of social and valence information in the MPFC during fMRI. Using a representational similarity analysis, we found a high degree of representational similarity both within social dimensions and within valence dimensions, but not across them (e.g., positive social information was highly dissimilar to negative nonsocial information), in a ventral portion of the MPFC. These results were significantly correlated with a behaviorally measured similarity structure of the same stimuli, suggesting that a psychologically meaningful representation of social and valence information is reflected by multivoxel activation patterns in the ventral MPFC.

  9. Hyperphosphorylation of PP2A in colorectal cancer and the potential therapeutic value showed by its forskolin-induced dephosphorylation and activation.

    PubMed

    Cristóbal, Ion; Rincón, Raúl; Manso, Rebeca; Madoz-Gúrpide, Juan; Caramés, Cristina; del Puerto-Nevado, Laura; Rojo, Federico; García-Foncillas, Jesús

    2014-09-01

    The tumor suppressor protein phosphatase 2A (PP2A) is frequently inactivated in human cancer and phosphorylation of its catalytic subunit (p-PP2A-C) at tyrosine-307 (Y307) has been described to inhibit this phosphatase. However, its molecular and clinical relevance in colorectal cancer (CRC) remains unclear. p-PP2A-C Y307 was determined by immunoblotting in 7 CRC cell lines and 35 CRC patients. CRC cells were treated with the PP2A activator forskolin alone or combined with the PP2A inhibitor okadaic acid, 5-fluorouracil and oxaliplatin. We examined cell growth, colonosphere formation, caspase activity and AKT and ERK activation. PP2A-C was found hyperphosphorylated in CRC cell lines. Forskolin dephosphorylated and activated PP2A, impairing proliferation and colonosphere formation, and inducing activation of caspase 3/7 and changes in AKT and ERK phosphorylation. Moreover, forskolin showed additive effects with 5-fluorouracil and oxaliplatin treatments. Analysis of p-PP2A-C Y307 in primary tumors confirmed the presence of this alteration in a subgroup of CRC patients. Our data show that PP2A-C hyperphosphorylation is a frequent event that contributes to PP2A inhibition in CRC. Antitumoral effects of forskolin-mediated PP2A activation suggest that the analysis of p-PP2A-C Y307 status could be used to identify a subgroup of patients who would benefit from treatments based on PP2A activators. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Efficient similarity-based data clustering by optimal object to cluster reallocation.

    PubMed

    Rossignol, Mathias; Lagrange, Mathieu; Cont, Arshia

    2018-01-01

    We present an iterative flat hard clustering algorithm designed to operate on arbitrary similarity matrices, with the only constraint that these matrices be symmetrical. Although functionally very close to kernel k-means, our proposal performs a maximization of average intra-class similarity, instead of a squared distance minimization, in order to remain closer to the semantics of similarities. We show that this approach permits the relaxing of some conditions on usable affinity matrices like semi-positiveness, as well as opening possibilities for computational optimization required for large datasets. Systematic evaluation on a variety of data sets shows that compared with kernel k-means and the spectral clustering methods, the proposed approach gives equivalent or better performance, while running much faster. Most notably, it significantly reduces memory access, which makes it a good choice for large data collections. Material enabling the reproducibility of the results is made available online.

  11. Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.

    PubMed

    Wang, Tieshan; Su, Jianrong

    2016-12-28

    Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii . Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii . The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis . Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.

  12. Similarities in acute phase protein response during hibernation in black bears and major depression in humans: A response to underlying metabolic depression?

    USGS Publications Warehouse

    Tsiouris, J.A.; Chauhan, V.P.S.; Sheikh, A.M.; Chauhan, A.; Malik, M.; Vaughan, M.R.

    2004-01-01

    This study investigated the effects of hibernation with mild hypothermia and the stress of captivity on levels of six acute-phase proteins (APPs) in serial samples of serum from 11 wild and 6 captive black bears (Ursus americanus Pallas, 1780) during active and hibernating states. We hypothesize that during hibernation with mild hypothermia, bears would show an APP response similar to that observed in major depression. Enzyme-linked immunoabsorbent assay was used to measure alpha2-macroglobulin and C-reactive protein, and a nephelometer to measure alpha1-antitrypsin, haptoglobin, ceruloplasmin, and transferrin. Levels of all other proteins except ceruloplasmin were significantly elevated during hibernation in both wild and captive bears at the p < 0.05 to p < 0.001 level. Alpha 2-macroglobulin and C-reactive-protein levels were increased in captive versus wild bears in both active and hibernating states at the p < 0.01 to p < 0.0001 level. During hibernation with mild hypothermia, black bears do not show immunosuppression, but show an increased APP response similar to that in patients with major depression. This APP response is explained as an adaptive response to the underlying metabolic depression in both conditions. Metabolic depression in hibernating bears is suggested as a natural model for research to explain the neurobiology of depression.

  13. Does similarity in call structure or foraging ecology explain interspecific information transfer in wild Myotis bats?

    PubMed

    Hügel, Theresa; van Meir, Vincent; Muñoz-Meneses, Amanda; Clarin, B-Markus; Siemers, Björn M; Goerlitz, Holger R

    2017-01-01

    Animals can gain important information by attending to the signals and cues of other animals in their environment, with acoustic information playing a major role in many taxa. Echolocation call sequences of bats contain information about the identity and behaviour of the sender which is perceptible to close-by receivers. Increasing evidence supports the communicative function of echolocation within species, yet data about its role for interspecific information transfer is scarce. Here, we asked which information bats extract from heterospecific echolocation calls during foraging. In three linked playback experiments, we tested in the flight room and field if foraging Myotis bats approached the foraging call sequences of conspecifics and four heterospecifics that were similar in acoustic call structure only (acoustic similarity hypothesis), in foraging ecology only (foraging similarity hypothesis), both, or none. Compared to the natural prey capture rate of 1.3 buzzes per minute of bat activity, our playbacks of foraging sequences with 23-40 buzzes/min simulated foraging patches with significantly higher profitability. In the flight room, M. capaccinii only approached call sequences of conspecifics and of the heterospecific M. daubentonii with similar acoustics and foraging ecology. In the field, M. capaccinii and M. daubentonii only showed a weak positive response to those two species. Our results confirm information transfer across species boundaries and highlight the importance of context on the studied behaviour, but cannot resolve whether information transfer in trawling Myotis is based on acoustic similarity only or on a combination of similarity in acoustics and foraging ecology. Animals transfer information, both voluntarily and inadvertently, and within and across species boundaries. In echolocating bats, acoustic call structure and foraging ecology are linked, making echolocation calls a rich source of information about species identity, ecology and

  14. Competition and cooperation among similar representations: toward a unified account of facilitative and inhibitory effects of lexical neighbors.

    PubMed

    Chen, Qi; Mirman, Daniel

    2012-04-01

    One of the core principles of how the mind works is the graded, parallel activation of multiple related or similar representations. Parallel activation of multiple representations has been particularly important in the development of theories and models of language processing, where coactivated representations (neighbors) have been shown to exhibit both facilitative and inhibitory effects on word recognition and production. Researchers generally ascribe these effects to interactive activation and competition, but there is no unified explanation for why the effects are facilitative in some cases and inhibitory in others. We present a series of simulations of a simple domain-general interactive activation and competition model that is broadly consistent with more specialized domain-specific models of lexical processing. The results showed that interactive activation and competition can indeed account for the complex pattern of reversals. Critically, the simulations revealed a core computational principle that determines whether neighbor effects are facilitative or inhibitory: strongly active neighbors exert a net inhibitory effect, and weakly active neighbors exert a net facilitative effect.

  15. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    PubMed

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  16. Separation of Bombyxin from a neuropeptide of Bombyx mori showing Summer-morph-producing Hormone (SMPH) activity in the Asian Comma Butterfly, Polygonia c-aureum L.

    PubMed

    Endo, K; Yamanaka, A; Mitsumasu, K; Sakurama, T; Tanaka, D

    1997-02-21

    A neuropeptide from brain-suboesophageal ganglion (Br-SG) complexes of the silkmoth, Bombyx mori, shows summer-morph-producing hormone (SMPH) activity in the Asian comma butterfly, P. c-aureum. The SMPH-active peptide was extracted and demonstrated to be almost the same molecular size as bombyxin (4-5kD), a nueropeptide which shows prothoracicotropic hormone (PTTH) activity when assayed in vitro with prothoracic glands (PGs) of 4th-instar B. mori larvae in vitro. A Sephadex G-50 fraction of 3-8kD molecules prepared from Br-SG complexes of B. mori adults was applied to CM-, SP-, DEAE- or QAE- Toyoperal columns at pH 5.6 (or pH 6.9). The SMPH-activity could be separated from the PTTH-activity (or bombyxin) by subjecting a SMPH- and PTTH-active preparation of B. mori to anion-exchange chromatography at pH 6.9. By reversed-phase HPLC following an anion-exchange chromatography, SMPH-activity was recovered in two fractions of 40-45% acetonitril. Results demonstrate that the B. mori peptide showing the SMPH-activity in P. c-aureum is a different molecule than bombyxin.

  17. Characterization of CG6178 gene product with high sequence similarity to firefly luciferase in Drosophila melanogaster.

    PubMed

    Oba, Yuichi; Ojika, Makoto; Inouye, Satoshi

    2004-03-31

    This is the first identification of a long-chain fatty acyl-CoA synthetase in Drosophila by enzymatic characterization. The gene product of CG6178 (CG6178) in Drosophila melanogaster genome, which has a high sequence similarity to firefly luciferase, has been expressed and characterized. CG6178 showed long-chain fatty acyl-CoA synthetic activity in the presence of ATP, CoA and Mg(2+), suggesting a fatty acyl adenylate is an intermediate. Recently, it was revealed that firefly luciferase has two catalytic functions, monooxygenase (luciferase) and AMP-mediated CoA ligase (fatty acyl-CoA synthetase). However, unlike firefly luciferase, CG6178 did not show luminescence activity in the presence of firefly luciferin, ATP, CoA and Mg(2+). The enzymatic properties of CG6178 including substrate specificity, pH dependency and optimal temperature were close to those of firefly luciferase and rat fatty acyl-CoA synthetase. Further, phylogenic analyses strongly suggest that the firefly luciferase gene may have evolved from a fatty acyl-CoA synthetase gene as a common ancestral gene.

  18. Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential.

    PubMed

    Sakthivel, Ravi; Malar, Dicson Sheeja; Devi, Kasi Pandima

    2018-06-13

    In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC 50 value of 70.81 ± 0.32 μM and 60.7 ± 0.47 μM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 μM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. Processes of Similarity Judgment

    ERIC Educational Resources Information Center

    Larkey, Levi B.; Markman, Arthur B.

    2005-01-01

    Similarity underlies fundamental cognitive capabilities such as memory, categorization, decision making, problem solving, and reasoning. Although recent approaches to similarity appreciate the structure of mental representations, they differ in the processes posited to operate over these representations. We present an experiment that…

  20. Neural processing of race during imitation: self-similarity versus social status

    PubMed Central

    Reynolds Losin, Elizabeth A.; Cross, Katy A.; Iacoboni, Marco; Dapretto, Mirella

    2017-01-01

    People preferentially imitate others who are similar to them or have high social status. Such imitative biases are thought to have evolved because they increase the efficiency of cultural acquisition. Here we focused on distinguishing between self-similarity and social status as two candidate mechanisms underlying neural responses to a person’s race during imitation. We used fMRI to measure neural responses when 20 African American (AA) and 20 European American (EA) young adults imitated AA, EA and Chinese American (CA) models and also passively observed their gestures and faces. We found that both AA and EA participants exhibited more activity in lateral fronto-parietal and visual regions when imitating AAs compared to EAs or CAs. These results suggest that racial self-similarity is not likely to modulate neural responses to race during imitation, in contrast with findings from previous neuroimaging studies of face perception and action observation. Furthermore, AA and EA participants associated AAs with lower social status than EAs or CAs, suggesting that the social status associated with different racial groups may instead modulate neural activity during imitation of individuals from those groups. Taken together, these findings suggest that neural responses to race during imitation are driven by socially-learned associations rather than self-similarity. This may reflect the adaptive role of imitation in social learning, where learning from higher-status models can be more beneficial. This study provides neural evidence consistent with evolutionary theories of cultural acquisition. PMID:23813738

  1. Turkish Scorzonera Species Extracts Attenuate Cytokine Secretion via Inhibition of NF-κB Activation, Showing Anti-Inflammatory Effect in Vitro.

    PubMed

    Bahadır Acikara, Özlem; Hošek, Jan; Babula, Petr; Cvačka, Josef; Budešínský, Miloš; Dračinský, Martin; Saltan İşcan, Gülçin; Kadlecová, Daniela; Ballová, Ludmila; Šmejkal, Karel

    2015-12-30

    Scorzonera species are used in different folk medicines to combat many diseases, including the illnesses connected with inflammation. Previous experiments showed anti-inflammatory activity of Scorzonera extracts in vivo. S. latifolia, S. cana var. jacquiniana, S. tomentosa, S. mollis ssp. szowitsii, S. eriophora, S. incisa, S. cinerea, and S. parviflora extracts were, therefore, evaluated for their inhibitory activities of TNF-α and IL-1β production, and NF-κB nuclear translocation in THP-1 macrophages. The HPLC analysis was carried out to elucidate and to compare the composition of these extracts. Major compounds of the tested extracts have been isolated using different chromatographic techniques and further tested for their inhibitory activities on TNF-α and IL-1β production. Several extracts showed promising anti-inflammatory activity in these in vitro tests. Results of HPLC analysis revealed chlorogenic acid as a compound present in all tested extracts. Hyperoside, quercetin-3-O-β-d-glucoside and rutin were also present in varying amount in some Scorzonera species analyzed. Furthermore, eight phenolics which were identified as quercetin-3-O-β-d-glucoside (1), hyperoside (2), hydrangenol-8-O-glucoside (3), swertisin (4), 7-methylisoorientin (5), 4,5-O-dicaffeoyl-quinic acid (6), 3,5-di-O-caffeoyl-quinic acid (7), and chlorogenic acid (8) have been isolated as major phenolic compounds of the tested extracts and, together with eight terpenoids (9-16) previously obtained from different Scorzonera species, have been tested for the inhibition of TNF-α production, unfortunately with no activity comparable with standard.

  2. Cell-free synthesis of membrane subunits of ATP synthase in phospholipid bicelles: NMR shows subunit a fold similar to the protein in the cell membrane

    PubMed Central

    Uhlemann, Eva-Maria E; Pierson, Hannah E; Fillingame, Robert H; Dmitriev, Oleg Y

    2012-01-01

    NMR structure determination of large membrane proteins is hampered by broad spectral lines, overlap, and ambiguity of signal assignment. Chemical shift and NOE assignment can be facilitated by amino acid selective isotope labeling in cell-free protein synthesis system. However, many biological detergents are incompatible with the cell-free synthesis, and membrane proteins often have to be synthesized in an insoluble form. We report cell-free synthesis of subunits a and c of the proton channel of Escherichia coli ATP synthase in a soluble form in a mixture of phosphatidylcholine derivatives. In comparison, subunit a was purified from the cell-free system and from the bacterial cell membranes. NMR spectra of both preparations were similar, indicating that our procedure for cell-free synthesis produces protein structurally similar to that prepared from the cell membranes. PMID:22162071

  3. A chimeric protein of aluminum-activated malate transporter generated from wheat and Arabidopsis shows enhanced response to trivalent cations.

    PubMed

    Sasaki, Takayuki; Tsuchiya, Yoshiyuki; Ariyoshi, Michiyo; Ryan, Peter R; Yamamoto, Yoko

    2016-07-01

    TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana encode aluminum (Al)-activated malate transporters, which confer acid-soil tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes. Those studies showed that Al could activate malate efflux from the Ta::At chimera but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein Ta::At were compared in cultured tobacco BY-2 cells. We focused on the sensitivity and specificity of their activation by trivalent cations. The activation of malate efflux by Al was at least two-fold greater in the chimera than the native proteins. All proteins were also activated by lanthanides (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and erbium activated inward currents from the native TaALMT1 and the chimeric protein, but gadolinium only activated currents from the chimera. Lanthanum inhibited currents from both proteins. These results demonstrated that function of the chimera protein was altered compared to the native proteins and was more responsive to a range of trivalent cations when expressed in plant cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Transgenic alfalfa (Medicago sativa) with increased sucrose phosphate synthase activity shows enhanced growth when grown under N2-fixing conditions.

    PubMed

    Gebril, Sayed; Seger, Mark; Villanueva, Fabiola Muro; Ortega, Jose Luis; Bagga, Suman; Sengupta-Gopalan, Champa

    2015-10-01

    Overexpression of SPS in alfalfa is accompanied by early flowering, increased plant growth and an increase in elemental N and protein content when grown under N2-fixing conditions. Sucrose phosphate synthase (SPS; EC 2.3.1.14) is the key enzyme in the synthesis of sucrose in plants. The outcome of overexpression of SPS in different plants using transgenic approaches has been quite varied, but the general consensus is that increased SPS activity is associated with the production of new sinks and increased sink strength. In legumes, the root nodule is a strong C sink and in this study our objective was to see how increasing SPS activity in a legume would affect nodule number and function. Here we have transformed alfalfa (Medicago sativa, cv. Regen SY), with a maize SPS gene driven by the constitutive CaMV35S promoter. Our results showed that overexpression of SPS in alfalfa, is accompanied by an increase in nodule number and mass and an overall increase in nitrogenase activity at the whole plant level. The nodules exhibited an increase in the level of key enzymes contributing to N assimilation including glutamine synthetase and asparagine synthetase. Moreover, the stems of the transformants showed higher level of the transport amino acids, Asx, indicating increased export of N from the nodules. The transformants exhibited a dramatic increase in growth both of the shoots and roots, and earlier flowering time, leading to increased yields. Moreover, the transformants showed an increase in elemental N and protein content. The overall conclusion is that increased SPS activity improves the N status and plant performance, suggesting that the availability of more C in the form of sucrose enhances N acquisition and assimilation in the nodules.

  5. Alphabetic letter identification: Effects of perceivability, similarity, and bias☆

    PubMed Central

    Mueller, Shane T.; Weidemann, Christoph T.

    2012-01-01

    The legibility of the letters in the Latin alphabet has been measured numerous times since the beginning of experimental psychology. To identify the theoretical mechanisms attributed to letter identification, we report a comprehensive review of literature, spanning more than a century. This review revealed that identification accuracy has frequently been attributed to a subset of three common sources: perceivability, bias, and similarity. However, simultaneous estimates of these values have rarely (if ever) been performed. We present the results of two new experiments which allow for the simultaneous estimation of these factors, and examine how the shape of a visual mask impacts each of them, as inferred through a new statistical model. Results showed that the shape and identity of the mask impacted the inferred perceivability, bias, and similarity space of a letter set, but that there were aspects of similarity that were robust to the choice of mask. The results illustrate how the psychological concepts of perceivability, bias, and similarity can be estimated simultaneously, and how each make powerful contributions to visual letter identification. PMID:22036587

  6. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations.

    PubMed

    Cochran, Andrew J R; Percival, Michael E; Tricarico, Steven; Little, Jonathan P; Cermak, Naomi; Gillen, Jenna B; Tarnopolsky, Mark A; Gibala, Martin J

    2014-05-01

    High-intensity interval training (HIIT) performed in an 'all-out' manner (e.g. repeated Wingate tests) is a time-efficient strategy to induce skeletal muscle remodelling towards a more oxidative phenotype. A fundamental question that remains unclear, however, is whether the intermittent or 'pulsed' nature of the stimulus is critical to the adaptive response. In study 1, we examined whether the activation of signalling cascades linked to mitochondrial biogenesis was dependent on the manner in which an acute high-intensity exercise stimulus was applied. Subjects performed either four 30 s Wingate tests interspersed with 4 min of rest (INT) or a bout of continuous exercise (CONT) that was matched for total work (67 ± 7 kJ) and which required ∼4 min to complete as fast as possible. Both protocols elicited similar increases in markers of adenosine monophosphate-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase activation, as well as Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression (main effects for time, P ≤ 0.05). In study 2, we determined whether 6 weeks of the CONT protocol (3 days per week) would increase skeletal muscle mitochondrial content to a similar extent to what we have previously reported after 6 weeks of INT. Despite similar acute signalling responses to the CONT and INT protocols, training with CONT did not increase the maximal activity or protein content of a range of mitochondrial markers. However, peak oxygen uptake was higher after CONT training (from 45.7 ± 5.4 to 48.3 ± 6.5 ml kg(-1) min(-1); P < 0.05) and 250 kJ time trial performance was improved (from 26:32 ± 4:48 to 23:55 ± 4:16 min:s; P < 0.001) in our recreationally active participants. We conclude that the intermittent nature of the stimulus is important for maximizing skeletal muscle adaptations to low-volume, all-out HIIT. Despite the lack of skeletal muscle mitochondrial adaptations

  7. The gender similarities hypothesis.

    PubMed

    Hyde, Janet Shibley

    2005-09-01

    The differences model, which argues that males and females are vastly different psychologically, dominates the popular media. Here, the author advances a very different view, the gender similarities hypothesis, which holds that males and females are similar on most, but not all, psychological variables. Results from a review of 46 meta-analyses support the gender similarities hypothesis. Gender differences can vary substantially in magnitude at different ages and depend on the context in which measurement occurs. Overinflated claims of gender differences carry substantial costs in areas such as the workplace and relationships. Copyright (c) 2005 APA, all rights reserved.

  8. Relations between premise similarity and inductive strength.

    PubMed

    Heit, Evan; Feeney, Aidan

    2005-04-01

    According to the diversity principle, diverse evidence is strong evidence. There has been considerable evidence that people respect this principle in inductive reasoning. However, exceptions may be particularly informative. Medin, Coley, Storms, and Hayes (2003) introduced a relevance theory of inductive reasoning and used this theory to predict exceptions, including the nondiversity-by-property-reinforcement effect. A new experiment in which this phenomenon was investigated is reported here. Subjects made inductive strength judgments and similarity judgments for stimuli from Medin et al. (2003). The inductive strength judgments showed the same pattern as that in Medin et al. (2003); however, the similarity judgments suggested that the pattern should be interpreted as a diversity effect, rather than as a nondiversity effect. It is concluded that the evidence regarding the predicted nondiversity-by-property-reinforcement effect does not give distinctive support for relevance theory, although this theory does address other results.

  9. Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of intrinsic brain activity.

    PubMed

    Zhang, Jiuquan; Wei, Luqing; Hu, Xiaofei; Xie, Bing; Zhang, Yanling; Wu, Guo-Rong; Wang, Jian

    2015-01-01

    Parkinson's disease (PD) is a surprisingly heterogeneous neurodegenerative disorder. It is well established that different subtypes of PD present with different clinical courses and prognoses. However, the neural mechanism underlying these disparate presentations is uncertain. Here we used resting-state fMRI (rs-fMRI) and the regional homogeneity (ReHo) method to determine neural activity patterns in the two main clinical subgroups of PD (akinetic-rigid and tremor-dominant). Compared with healthy controls, akinetic-rigid (AR) subjects had increased ReHo mainly in right amygdala, left putamen, bilateral angular gyrus, bilateral medial prefrontal cortex (MPFC), and decreased ReHo in left post cingulate gyrus/precuneus (PCC/PCu) and bilateral thalamus. In contrast, tremor-dominant (TD) patients showed higher ReHo mostly in bilateral angular gyrus, left PCC, cerebellum_crus1, and cerebellum_6, while ReHo was decreased in right putamen, primary sensory cortex (S1), vermis_3, and cerebellum_4_5. These results indicate that AR and TD subgroups both represent altered spontaneous neural activity in default-mode regions and striatum, and AR subjects exhibit more changed neural activity in the mesolimbic cortex (amygdala) but TD in the cerebellar regions. Of note, direct comparison of the two subgroups revealed a distinct ReHo pattern primarily located in the striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) loops. Overall, our findings highlight the involvement of default mode network (DMN) and STC circuit both in AR and TD subtypes, but also underscore the importance of integrating mesolimbic-striatal and CTC loops in understanding neural systems of akinesia and rigidity, as well as resting tremor in PD. This study provides improved understanding of the pathophysiological models of different subtypes of PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Genome sequence of Lactobacillus salivarius SMXD51, a potential probiotic strain isolated from chicken cecum, showing anti-campylobacter activity.

    PubMed

    Kergourlay, Gilles; Messaoudi, Soumaya; Dousset, Xavier; Prévost, Hervé

    2012-06-01

    We report the draft genome sequence of Lactobacillus salivarius SMXD51, isolated from the cecum of healthy chickens showing an activity against Campylobacter--the food-borne pathogen that is the most common cause of gastroenteritis in the European Union (EU)--and potentially interesting features for a probiotic strain, explaining our interest in it.

  11. Do Transit-Oriented Developments (TODs) and Established Urban Neighborhoods Have Similar Walking Levels in Hong Kong?

    PubMed Central

    Xiao, Yang; Sarkar, Chinmoy; Zacharias, John

    2018-01-01

    A sharp drop in physical activity and skyrocketing obesity rate has accompanied rapid urbanization in China. The urban planning concept of transit-oriented development (TOD) has been widely advocated in China to promote physical activity, especially walking. Indeed, many design features thought to promote walking—e.g., mixed land use, densification, and well-connected street network—often characterize both TODs and established urban neighborhoods. Thus, it is often assumed that TODs have similar physical activity benefits as established urban neighborhoods. To verify this assumption, this study compared walking behaviors in established urban neighborhoods and transit-oriented new towns in Hong Kong. To address the limitation of self-selection bias, we conducted a study using Hong Kong citywide public housing scheme, which assigns residents to different housing estates by flat availability and family size rather than personal preference. The results show new town residents walked less for transportation purpose than urban residents. New town residents far from the transit station (800–1200 m) walked less for recreational purpose than TOD residents close to a rail transit station (<400 m) or urban residents. The observed disparity in walking behaviors challenges the common assumption that TOD and established urban neighborhoods have similar impact on walking behavior. The results suggest the necessity for more nuanced planning strategies, taking local-level factors into account to promote walking of TOD residents who live far from transit stations. PMID:29558379

  12. Partially resistant Cucurbita pepo showed late onset of the Zucchini yellow mosaic virus infection due to rapid activation of defense mechanisms as compared to susceptible cultivar

    PubMed Central

    Nováková, Slavomíra; Flores-Ramírez, Gabriela; Glasa, Miroslav; Danchenko, Maksym; Fiala, Roderik; Skultety, Ludovit

    2015-01-01

    Zucchini yellow mosaic virus (ZYMV) is an emerging viral pathogen in cucurbit-growing areas wordwide. Infection causes significant yield losses in several species of the family Cucurbitaceae. To identify proteins potentially involved with resistance toward infection by the severe ZYMV-H isolate, two Cucurbita pepo cultivars (Zelena susceptible and Jaguar partially resistant) were analyzed using a two-dimensional gel electrophoresis-based proteomic approach. Initial symptoms on leaves (clearing veins) developed 6–7 days post-inoculation (dpi) in the susceptible C. pepo cv. Zelena. In contrast, similar symptoms appeared on the leaves of partially resistant C. pepo cv. Jaguar only after 15 dpi. This finding was confirmed by immune-blot analysis which showed higher levels of viral proteins at 6 dpi in the susceptible cultivar. Leaf proteome analyses revealed 28 and 31 spots differentially abundant between cultivars at 6 and 15 dpi, respectively. The variance early in infection can be attributed to a rapid activation of proteins involved with redox homeostasis in the partially resistant cultivar. Changes in the proteome of the susceptible cultivar are related to the cytoskeleton and photosynthesis. PMID:25972878

  13. Comparative in vitro activity of the new oxacephem antibiotic, flomoxef (6315-S).

    PubMed

    Ruckdeschel, G; Eder, W

    1988-10-01

    The in vitro activity of flomoxef (6315-S) was determined and compared to that of different cephalosporins against 787 clinical isolates of staphylococci, Enterobacteriaceae and anaerobes. Flomoxef is similar in activity to latamoxef and cefotaxime against Enterobacteriaceae, slightly more active than cephalothin and cefamandole against oxacillin-sensitive strains of Staphylococcus aureus and minimally less active than cefamandole against oxacillin-resistant strains. Flomoxef showed similar or better activity than latamoxef and cefoxitin against most of the anaerobic species of medical importance.

  14. Thai Language Sentence Similarity Computation Based on Syntactic Structure and Semantic Vector

    NASA Astrophysics Data System (ADS)

    Wang, Hongbin; Feng, Yinhan; Cheng, Liang

    2018-03-01

    Sentence similarity computation plays an increasingly important role in text mining, Web page retrieval, machine translation, speech recognition and question answering systems. Thai language as a kind of resources scarce language, it is not like Chinese language with HowNet and CiLin resources. So the Thai sentence similarity research faces some challenges. In order to solve this problem of the Thai language sentence similarity computation. This paper proposes a novel method to compute the similarity of Thai language sentence based on syntactic structure and semantic vector. This method firstly uses the Part-of-Speech (POS) dependency to calculate two sentences syntactic structure similarity, and then through the word vector to calculate two sentences semantic similarity. Finally, we combine the two methods to calculate two Thai language sentences similarity. The proposed method not only considers semantic, but also considers the sentence syntactic structure. The experiment result shows that this method in Thai language sentence similarity computation is feasible.

  15. User recommendation in healthcare social media by assessing user similarity in heterogeneous network.

    PubMed

    Jiang, Ling; Yang, Christopher C

    2017-09-01

    The rapid growth of online health social websites has captured a vast amount of healthcare information and made the information easy to access for health consumers. E-patients often use these social websites for informational and emotional support. However, health consumers could be easily overwhelmed by the overloaded information. Healthcare information searching can be very difficult for consumers, not to mention most of them are not skilled information searcher. In this work, we investigate the approaches for measuring user similarity in online health social websites. By recommending similar users to consumers, we can help them to seek informational and emotional support in a more efficient way. We propose to represent the healthcare social media data as a heterogeneous healthcare information network and introduce the local and global structural approaches for measuring user similarity in a heterogeneous network. We compare the proposed structural approaches with the content-based approach. Experiments were conducted on a dataset collected from a popular online health social website, and the results showed that content-based approach performed better for inactive users, while structural approaches performed better for active users. Moreover, global structural approach outperformed local structural approach for all user groups. In addition, we conducted experiments on local and global structural approaches using different weight schemas for the edges in the network. Leverage performed the best for both local and global approaches. Finally, we integrated different approaches and demonstrated that hybrid method yielded better performance than the individual approach. The results indicate that content-based methods can effectively capture the similarity of inactive users who usually have focused interests, while structural methods can achieve better performance when rich structural information is available. Local structural approach only considers direct connections

  16. Characterization of an apple TT2-type R2R3 MYB transcription factor functionally similar to the poplar proanthocyanidin regulator PtMYB134.

    PubMed

    Gesell, Andreas; Yoshida, Kazuko; Tran, Lan T; Constabel, C Peter

    2014-09-01

    The apple MdMYB9 gene encodes a positive regulator of proanthocyanidin synthesis that activates anthocyanidin reductase promoters from apple and poplar via interaction with basic helix-loop-helix proteins. The regulation of proanthocyanidins (PAs, condensed tannins) is of great importance in food plants due to the many benefits of PAs in the human diet. Two candidate flavonoid MYB regulators, MdMYB9 and MdMYB11, were cloned from apple (Malus × domestica) based on their similarity to known MYB PA regulators. Transcript accumulation of both MdMYB9 and MdMYB11 was induced by high light and wounding, similar to the poplar (Populus spp) PA regulator PtMYB134. In transient activation assays with various basic helix-loop-helix (bHLH) co-regulators, MdMYB9 activated apple and poplar anthocyanidin reductase (ANR) promoters, while MdMYB11 showed no activity. Potential transcription factor binding elements were found within several ANR promoters, and the importance of the bHLH binding site (E-box) on ANR promoter activation was demonstrated via mutational analysis. The ability of MdMYB9 and PtMYB134 to reciprocally activate ANR promoters from both apple and poplar and to partner with heterologous bHLH co-factors from these plants confirms the high degree of conservation of PA regulatory complexes across species. The similarity in apple and poplar PA regulation suggests that regulatory genes from poplar could be effectively employed for metabolic engineering of the PA pathway in apple.

  17. Similar on the Inside (pre-grinding)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This approximate true-color image taken by the panoramic camera on the Mars Exploration Rover Opportunity show the rock called 'Pilbara' located in the small crater dubbed 'Fram.' The rock appears to be dotted with the same 'blueberries,' or spherules, found at 'Eagle Crater.' Spirit drilled into this rock with its rock abrasion tool. After analyzing the hole with the rover's scientific instruments, scientists concluded that Pilbara has a similar chemical make-up, and thus watery past, to rocks studied at Eagle Crater. This image was taken with the panoramic camera's 480-, 530- and 600-nanometer filters.

  18. An integrative approach for measuring semantic similarities using gene ontology.

    PubMed

    Peng, Jiajie; Li, Hongxiang; Jiang, Qinghua; Wang, Yadong; Chen, Jin

    2014-01-01

    Gene Ontology (GO) provides rich information and a convenient way to study gene functional similarity, which has been successfully used in various applications. However, the existing GO based similarity measurements have limited functions for only a subset of GO information is considered in each measure. An appropriate integration of the existing measures to take into account more information in GO is demanding. We propose a novel integrative measure called InteGO2 to automatically select appropriate seed measures and then to integrate them using a metaheuristic search method. The experiment results show that InteGO2 significantly improves the performance of gene similarity in human, Arabidopsis and yeast on both molecular function and biological process GO categories. InteGO2 computes gene-to-gene similarities more accurately than tested existing measures and has high robustness. The supplementary document and software are available at http://mlg.hit.edu.cn:8082/.

  19. Balancing the popularity bias of object similarities for personalised recommendation

    NASA Astrophysics Data System (ADS)

    Hou, Lei; Pan, Xue; Liu, Kecheng

    2018-03-01

    Network-based similarity measures have found wide applications in recommendation algorithms and made significant contributions for uncovering users' potential interests. However, existing measures are generally biased in terms of popularity, that the popular objects tend to have more common neighbours with others and thus are considered more similar to others. Such popularity bias of similarity quantification will result in the biased recommendations, with either poor accuracy or poor diversity. Based on the bipartite network modelling of the user-object interactions, this paper firstly calculates the expected number of common neighbours of two objects with given popularities in random networks. A Balanced Common Neighbour similarity index is accordingly developed by removing the random-driven common neighbours, estimated as the expected number, from the total number. Recommendation experiments in three data sets show that balancing the popularity bias in a certain degree can significantly improve the recommendations' accuracy and diversity simultaneously.

  20. Children with social anxiety and other anxiety disorders show similar deficits in habitual emotional regulation: evidence for a transdiagnostic phenomenon.

    PubMed

    Keil, Verena; Asbrand, Julia; Tuschen-Caffier, Brunna; Schmitz, Julian

    2017-07-01

    Deficits in emotion regulation (ER) are an important factor in maintaining social anxiety disorder (SAD) in adults. As SAD and ER problems typically develop during childhood and adolescence, and are maintained dynamically within the parent-child dyad, research on families can help to reveal the role ER plays in the early development of SAD. The current study assessed self-reported habitual ER in dyads of children with SAD (n = 31), children with mixed anxiety disorders (MAD; n = 41) and healthy control children (HC; n = 36), and their parents. Results indicate a transdiagnostic quality of ER in that, children with SAD and children with MAD similarly reported less adaptive and more maladaptive ER strategies than HC children, whereas no group differences in parental ER strategies emerged. Furthermore, children's ER strategies aggressive action, withdrawal and self-devaluation and the parental ER strategy reappraisal were associated with social anxiety symptoms. These results suggest that there may be deficits in ER which generalize across childhood anxiety disorders. Our results are discussed in relation to current theories and their implications for treatment of childhood SAD.