Development of speed qualities of skilled water-polo players

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Ostrovsky M.V.

2010-02-01

Full Text Available Swimming preparation of water-polo players is the basic factor of victory of command. There are a few variants of development of speed swimming preparation. The effective pedagogical mean of stimulation of speed qualities is brief exercises at the end of employments after long aerobic work. The purpose of work is an improvement of method of speed preparation of skilled water-polo players. 26 skilled water-polo players (MS -14 and KMS - 12 took part in an experiment in age from 21 to 32 years. The results of correction of structure of training employment are in-process presented in micro cycle. They are directed on the improvement of speed qualities of water-polo players.

The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus

Czech Academy of Sciences Publication Activity Database

Andrysík, Zdeněk; Bernstein, W.Z.; Deng, L.; Myer, D.L.; Li, Y.-Q.; Tischfield, J.A.; Stambrook, P.J.; Bahassi, E.M.

2010-01-01

Roč. 38, č. 9 (2010), s. 2931-2943 ISSN 0305-1048 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Polo * DNA damage * Plk5 Subject RIV: BO - Biophysics Impact factor: 7.836, year: 2010

Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.

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Miyazaki, Seira; Kim, Jihye; Yamagishi, Yuya; Ishiguro, Tadashi; Okada, Yuki; Tanno, Yuji; Sakuno, Takeshi; Watanabe, Yoshinori

2017-06-01

In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

FancJ regulates interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1

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Jianqiu Zou

2013-08-01

DNA damage response (DDR and the centrosome cycle are two of the most critical processes for maintaining a stable genome in animals. Sporadic evidence suggests a connection between these two processes. Here, we report our findings that six Fanconi Anemia (FA proteins, including FancI and FancJ, localize to the centrosome. Intriguingly, we found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC. We further show that, in addition to its role in interstrand crosslinking (ICL repair, FancJ also regulates the normal centrosome cycle as well as ICL induced centrosome amplification by activating the polo-like kinase 1 (PLK1. We have uncovered a novel function of FancJ in centrosome biogenesis and established centrosome amplification as an integral part of the ICL response.

Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain.

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Cizmecioglu, Onur; Warnke, Silke; Arnold, Marc; Duensing, Stefan; Hoffmann, Ingrid

2008-11-15

In mammalian cells, the centrosome consists of a pair of centrioles and amorphous pericentriolar material. The centrosome duplicates once per cell cycle. Polo like kinases (Plks) perform crucial functions in cell cycle progression and during mitosis. The polo-like kinase-2, Plk2, is activated near the G(1)/S phase transition, and plays an important role in the reproduction of centrosomes. In this study, we show that the polo-box of Plk2 is required both for association to the centrosome and centriole duplication. Mutation of critical sites in the Plk2 polo-box prevents centrosomal localization and impairs centriole duplication. Plk2 is localized to centrosomes during early G(1) phase where it only associates to the mother centriole and then distributes equally to both mother and daughter centrioles at the onset of S phase. Furthermore, our results imply that Plk2 mediated centriole duplication is dependent on Plk4 function. In addition, we find that siRNA-mediated downregulation of Plk2 leads to the formation of abnormal mitotic spindles confirming that Plk2 may have a function in the reproduction of centrioles.

The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression

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Duensing Stefan

2011-05-01

Full Text Available Abstract Background Infection with high-risk human papillomaviruses (HPVs such as HPV-16 is intimately associated with squamous cell carcinomas (SCCs of the anogenital tract and a subset of oropharyngeal carcinomas. Such lesions, including pre-invasive precursors, frequently show multipolar mitoses and aneuploidy. The high-risk HPV-16-encoded E7 oncoprotein has been shown to rapidly induce centrosome abnormalities thereby causing the formation of supernumerary mitotic spindle poles and increasing the risk for chromosome missegregation. HPV-16 E7 has been found to rapidly induce centriole overduplication, in part, through the simultaneous formation of more than one daughter centriole at single maternal centrioles (centriole multiplication. The precise molecular mechanism that underlies HPV-16 E7-induced centriole multiplication, however, remains poorly understood. Findings Here, we show that human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4 protein expression at maternal centrioles. Real-time quantitative reverse transcriptase (qRT-PCR analysis of these cells revealed an increase of PLK4 mRNA levels compared to control cells. Importantly, the ability of the HPV-16 E7 oncoprotein to induce centriole multiplication was found to correlate with its ability to activate the PLK4 promoter and to up-regulate PLK4 mRNA. Conclusions These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. Our findings encourage further experiments to test transcriptional inhibitors or small molecules targeting PLK4 to prevent centriole abnormalities, mitotic infidelity and malignant progression in HPV-associated neoplasms and other tumors in which PLK4 regulation is disrupted.

Estudio del 'tener' según Gabriel Marcel y Leonardo Polo

OpenAIRE

Urabayen, J. (Julia)

2003-01-01

Estudio del idener» según Gabriel Marcel y Leonardo Polo.- El objetivo de este trabajo es estudiar el pensamiento de Gabriel Marcel y Leonardo Polo acerca de un rasgo esencial del ser humano, el tener, y la visión del hombre que se obtiene desde esta característica. Polo considera que existe una jerarquía en el tener, que puede adoptar tres formas: el tener corpóreo, el tener cognoscitivo y el tener habitual. Marcel establece una diferencia entre ser y tener, y vincula el tener...

Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

International Nuclear Information System (INIS)

Ward, Alejandra; Morettin, Alan; Shum, David; Hudson, John W

2011-01-01

Hepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC. We used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western blot analysis to examine epigenetic changes for the Polo-like kinases (Plks) during the development of hepatocellular carcinoma (HCC) in Plk4 heterozygous mice and murine embryonic fibroblasts (MEFs). Here we report that the promoter methylation of Plk4 CpG islands increases with age, was more prevalent in males and that Plk4 epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in Plk4 mutant mice. Interestingly, the opposite occurs with another Plk family member, Plk1 which was typically hypermethylated in normal liver tissue but became hypomethylated and upregulated in liver tumours. Furthermore, upon alcohol exposure murine embryonic fibroblasts exhibited increased Plk4 hypermethylation and downregulation along with increased centrosome numbers and multinucleation. These results suggest that aberrant Plk methylation is correlated with the development of HCC in mice

Ten days of simulated live high:train low altitude training increases Hbmass in elite water polo players.

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Garvican-Lewis, Laura A; Clark, Sally A; Polglaze, Ted; McFadden, Greg; Gore, Christopher J

2013-12-01

Water polo requires high aerobic power to meet the demands of match play. Live high:train low (LHTL) may enhance aerobic capacity at sea level. Before the Olympics, the Australian women's water polo team utilised LHTL in an attempt to enhance aerobic fitness. Over 6 months, 11 players completed three normobaric LHTL exposures (block 1:11 days at 3000 m; block 2+3:9 days at 2500 m, 11 days normoxia, 10 days at 2800 m). Haemoglobin mass (Hbmass) was measured through carbon monoxide-rebreathing. Before each block, the relationship between Hbmass and water polo-specific aerobic fitness was investigated using the Multistage Shuttle Swim Test (MSST). Effect size statistics were adopted with likely, highly likely and almost certainly results being >75%, >95%, >99%, respectively. A Pearson product moment correlation was used to characterise the association between pooled data of Hbmass and MSST. Hbmass (mean ± SD, pre 721 ± 66 g) likely increased after block 1 and almost certainly after block 2+3 (% change; 90% confidence limits: block 1: 3.7%; 1.3-6.2%, block 2+3: 4.5%; 3.8-5.1%) and the net effect was almost certainly higher after block 2+3 than before block 1 (pre) by 8.5%; 7.3-9.7%. There was a very large correlation between Hbmass (g/kg) and MSST score (r=0.73). LHTL exposures of <2 weeks induced approximately 4% increase in Hbmass of water polo players. Extra Hbmass may increase aerobic power, but since match performance is nuanced by many factors it is impossible to ascertain whether the increased Hbmass contributed to Australia's Bronze medal.

Megakaryocyte polyploidization is associated with decreased expression of polo-like kinase (PLK).

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Yagi, M; Roth, G J

2006-09-01

During differentiation, megakaryocytes (MK), the bone marrow precursors of circulating blood platelets, undergo polyploidization, repeated rounds of DNA replication without cell division. Mature normal MK may contain a DNA content of up to 128N, in contrast to normal diploid (2N) cells. The extent of polyploidy may influence the number of platelets produced by the MK. Therefore, understanding the molecular mechanisms regulating polyploidization could identify events involved in controlling both cell division and thrombopoiesis. We investigated the expression of several proteins involved in mitosis in cultured mouse MK, and tested the effect of expression on polyploidization. Western blot and immunofluorescent analyses were used to assess expression of cell cycle proteins in cultured MK. Populations of polyploidizing MK were separated on the basis of DNA content by flow cytometry. The gene encoding mouse polo-like kinase 1 (PLK-1) was introduced into MK by retroviral transduction, and its effects measured by flow cytometry. Polyploid mouse MK expressed lower levels of two proteins, p55CDC and PLK-1, whose activity is necessary for cell cycle progression and completion of mitosis. Comparison of sorted 2N/4N and polyploid MK indicated that PLK-1 expression was absent in polyploid MK, while expression of other cell cycle proteins was similar in both populations. Forced expression of PLK-1 during MK differentiation was associated with decreased polyploidization. These experiments suggest that PLK-1 is an important regulator of polyploidization in differentiating MK.

Relationship among maximal grip, throwing velocity and anthropometric parameters in elite water polo players.

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Ferragut, C; Vila, H; Abraldes, J A; Argudo, F; Rodriguez, N; Alcaraz, P E

2011-03-01

As independent aspects, body size, body composition, and physiological performance of elite athletes have aroused the interest of sports scientists but, unfortunately, studies that combine these aspects are scarcely avalaible in water polo. The aim of the present study was to: 1) to develop an anthropometric profile of highly skilled male Water Polo players, and 2) to identify significant relationships between these features and overhead throwing velocity in highly skilled male water polo players. Thirteen male water polo players, with a mean age of 26.10±4.82, were recruited from the Spanish Water Polo team and an anthropometric assessment on all of them was carried out. Throwing velocity was evaluated in three different situations from the 5 m-penalty line on the center of the water polo goal: A) throwing without a defender nor a goalkeeper; B) throwing with a goalkeeper only, and C) 3) armfuls running shot with goalkeeper. Maximal handgrip was also tested. Biacromial breadth shows a significative correlation with hand grip in water polo players (r=0.792; P=0.001) and also correlates with Throwing velocity (r=0.716; P<0.001). Biepicondylar femur breadth correlates significatively with hand grip (r=0.727; P<0.05) and also with throwing velocity in "throwing with goalkeeper" situation (r=0.664; P<0.05). Hand grip shows a significant correlation with throwing velocity in "throwing with goalkeeper" situation (r=0.603; P<0.05). In conclusion, body mass aspects are not related with throwing velocity in highly skilled Water Polo players. Maximal hand grip is related with throwing velocity in "throwing with goalkeeper" situation. More investigations about water polo are necessary.

Marco Polo, Nicknamed the Million, and His “Book on the Diversity of the World”

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A.N. Garkavets

2017-09-01

Full Text Available Objective: To highlight the most urgent problems related to the person of Marco Polo and his works, written in collaboration with Rustichano (commonly known as Rustichello of Pisa. Research materials: the work of Marco Polo, with attention drawn to its general characteristics and scientific value. Materials are used which describe the history of the Polo family and the biography of Marco Polo the traveler. This work explores the routes of Polo’s travels, his career success in China and his documentary information about the country in the era of the Mongol Yuan Dynasty. We explore his language proficiency, in particular regard to the “Tatar” language in light of the source for the “Tatar” Lord Prayer in edition of Marco Polo in a German translation of Jerome Megizer; the return-route from China to Ilkhanate of the Hulaguides; the introduction of paper money in Mongol Iran at that time; Marco’s return to Venice and his acquaintance with the novelist, Rustichano of Pisa, while in Genoese captivity; versions of their joint writing on the East; Rustichano and scribes’ additions to the memoirs of Marco; the debated date of the will of Marco Polo and the mystery of two gold items listed in the inventory of his property, which are identified as two of Gaykhatu’s golden paizas; Marco Polo’s connections to the discovery of America by Christopher Columbus and Amerigo Vespucci; fake maps of China, Japan, Sakhalin, the Aleutian Islands, Chukotka, Alaska and much of the North American West, attributed to Marco Polo. Results and novelty of the research: We have confirmed the hypothesis about the origin of the generic nickname Million, received by Polos, and its connection to the estate of the Venetian family, Vilione / Milione. We have identified the source of the “Tatar” Lord Prayer in the German edition of Marco Polo. We have raised the question of the participation of Polo in the printing of paper money by Gaykhatu. We have proved the

RELATIONSHIPS BETWEEN HEART RATE AND PHYSIOLOGICAL PARAMETERS OF PERFORMANCE IN TOP-LEVEL WATER POLO PLAYERS

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O. Galy

2014-07-01

Full Text Available The aim of this study was to measure the heart rate (HR response of eight elite water polo players during the four 7-min quarters of the game and to check for relationships with the physiological parameters of performance ( ·VO2max, Th1vent, Th2vent. Each athlete performed a ·VO2max treadmill test and played a water polo game wearing a heart rate monitor. The game fatigue index was calculated as the ratio of the fourth-quarter HR to the first-quarter HR: HR4/HR1. The results showed a slight decrease in fourth-quarter HR compared with the first quarter, with the mean four-quarter HR equal to 79.9 ± 4.2% of HRmax. Stepwise multiple regression analysis showed ·VO2max to be the main explanatory factor of game intensity, i.e. game HR expressed in %HRreserve (R=0.88, P<0.01. We observed that higher aerobic capacity resulted in higher game intensity. We also observed a decrease in the playing intensity in the fourth quarter compared with the first, likely due to very high game involvement. We concluded that high aerobic capacity seems necessary to ensure high game intensity in water polo. This suggests that coaches should encourage their athletes to reach a minimum level of ·VO2max and that HR monitoring could be of great interest in the control of water polo training sessions.

Throwing velocities, anthropometric characteristics, and efficacy indices of women's European water polo subchampions.

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Alcaraz, Pedro E; Abraldes, J Arturo; Ferragut, Carmen; Rodríguez, Nuria; Argudo, Francisco M; Vila, Helena

2011-11-01

Water polo is a team sport characterized by a high-intensity, intermittent activity, where technical and tactical aspect are of a great importance. For that reason, the main aim of this study was to define the anthropometrical characteristics, maximum isometric grip strength, training and competition throwing velocities, and the efficacy indices in female high-level water polo players. A second purpose was to examine the differences between the throwing velocities in training vs. European championships in the water polo female national team. Ten elite trained female water polo players participated in this study. Before the competitive phase of their season, the following measures were taken: standard anthropometry, static and dynamic training throwing velocities, and hand-grip dynamometry. In the competitive phase, efficacy indices, average and maximum throwing velocities from all the participants were also determined. Significant differences (p ≤ 0.05) were found between different training situations and different competitive throwing velocities. We concluded that elite female water polo players modify their throwing velocity depending if the throw is performed during training or competitive situation.

QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo-Like Kinase 1.

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Comelli, Nieves C; Duchowicz, Pablo R; Castro, Eduardo A

2014-10-01

The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (-logIC50) was predicted by QSAR modeling. Multivariate linear regression (MLR) was employed to model the relationship between 0D and 3D molecular descriptors and biological activities of molecules using the replacement method (MR) as variable selection tool. The 136 compounds were separated into several training and test sets. Two splitting approaches, distribution of biological data and structural diversity, and the statistical experimental design procedure D-optimal distance were applied to the dataset. The significance of the training set models was confirmed by statistically higher values of the internal leave one out cross-validated coefficient of determination (Q2) and external predictive coefficient of determination for the test set (Rtest2). The model developed from a training set, obtained with the D-optimal distance protocol and using 3D descriptor space along with activity values, separated chemical features that allowed to distinguish high and low pIC50 values reasonably well. Then, we verified that such model was sufficient to reliably and accurately predict the activity of external diverse structures. The model robustness was properly characterized by means of standard procedures and their applicability domain (AD) was analyzed by leverage method. Copyright © 2014 Elsevier B.V. All rights reserved.

serologic evidence of equine h7 influenza virus in polo horses

African Journals Online (AJOL)

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disease signs in horses, the infection produced by equine-2 viruses is typically ... 1992; FAOSTAT, 2008) and majority are use for playing the game of polo. Polo is a ... Seven samples. (17.5%) had antibodies levels of 5,120-20,480 and only one .... Adeyefa, C. A. O., McCauley, J. W., Danefi, A. I., Kalejaiye, O.A.,. Bakare, A.

Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac Progenitor Cells.

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Mochizuki, Michika; Lorenz, Vera; Ivanek, Robert; Della Verde, Giacomo; Gaudiello, Emanuele; Marsano, Anna; Pfister, Otmar; Kuster, Gabriela M

2017-10-24

Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (<2 hours). Ninety-four genes were differentially regulated on laminin versus fibronectin, consisting of mostly downregulated genes that were enriched for Yes-associated protein (YAP) conserved signature and TEA domain family member 1 (TEAD1)-related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2 ( Plk2 ). Plk2 expression depended on YAP stability and was enhanced in CPCs transfected with a nuclear-targeted mutant YAP. Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

El Pseudo-Hiepes es Bernardo Polo

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Jordan, William B.

2009-12-01

Full Text Available Nearly fifteen years ago, the author proposed the name Pseudo-Hiepes to refer to a then anonymous painter whom certain Italian art historians had called the Master of the Lombard Fruit Bowl. At the time, he argued for an Aragonese origin in the later part of the century. A signed work has finally been discovered and is published here. The artist was indeed from Zaragoza, and his name is Bernardo Polo.

Hace unos quince años, el autor propuso el apodo Pseudo-Hiepes para identificar al pintor anónimo a quien algunos entendidos italianos habían bautizado como Maestro del Frutero lombardo. En aquel entonces, argumentó que debía tratarse de un artista aragonés, de la segunda mitad de siglo. Por fin ha aparecido una obra firmada que se presenta aquí. Efectivamente, el artista era zaragozano y su nombre es Bernardo Polo.

Strength, Endurance, Throwing Velocity and in-Water Jump Performance of Elite German Water Polo Players

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Zinner Christoph

2015-03-01

Full Text Available The purpose of this study was threefold: 1 to assess the eggbeater kick and throwing performance using a number of water polo specific tests, 2 to explore the relation between the eggbeater kick and throwing performance, and 3 to investigate the relation between the eggbeater kick in the water and strength tests performed in a controlled laboratory setting in elite water polo players. Fifteen male water polo players of the German National Team completed dynamic and isometric strength tests for muscle groups (adductor, abductor, abdominal, pectoralis frequently used during water polo. After these laboratory strength tests, six water polo specific in-water tests were conducted. The eggbeater kick assessed leg endurance and agility, maximal throwing velocity and jump height. A 400 m test and a sprint test examined aerobic and anaerobic performance. The strongest correlation was found between jump height and arm length (p < 0.001, r = 0.89. The laboratory diagnostics of important muscles showed positive correlations with the results of the in-water tests (p < 0.05, r = 0.52-0.70. Muscular strength of the adductor, abdominal and pectoralis muscles was positively related to in-water endurance agility as assessed by the eggbeater kick (p < 0.05; r = 0.53-0.66. Findings from the current study emphasize the need to assess indices of water polo performance both in and out of the water as well as the relation among these parameters to best assess the complex profile of water polo players.

Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation.

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Conde, Carlos; Osswald, Mariana; Barbosa, João; Moutinho-Santos, Tatiana; Pinheiro, Diana; Guimarães, Sofia; Matos, Irina; Maiato, Helder; Sunkel, Claudio E

2013-06-12

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.

Comparison of anthropometric parameters among Iranian and Spanish water polo players

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Pooya Nekooei

2016-06-01

Full Text Available The purpose of this study was to compare the anthropometric parameters between Iranian and Spanish water polo national team players. Material and Methods ― The research was conducted in the physiological laboratory of Isfahan Azad University. Participants who participate in this study were 44 male national water polo players (22 Iranian and 22 Spanish, age 22±2 years old (Mean±SD. For the aim of this study twenty anthropometric parameters that was more important for water polo was measured and analysis. All the parameters were measured base on the international standard of anthropometric parameters (International Society for the Advancement of Kinanthropometry – ISAK. For analysis data, normal distribution of the data was proved by Kolmogorov-Smirnov test and then comparison between two groups was done by t-test. Results ― The results showed a significant difference in seven anthropometric parameters contain body fat percentage (P=0.031, biliocristal breadth (P<0.001, wrist breadth (P<0.001, chest girth (P=0.021, mid-thigh girth (P=0.019, palm length (P<0.001 and height (P=0.032. Conclusion ― Spanish players with relatively higher underlying levels of anthropometric parameters compare to Iranian water polo players had stronger ability to control the ball with the bigger palm and bigger wrist breadth, also they had stronger ability to do water vertical jump, cause of higher value of biliocristal breadth and mid-thigh girth and also stronger throwing the ball because of bigger muscle on their chest part of their body. However, Base on this study, having longer hands, more muscular body than fat and taller stature is an advantage for the players because it is considered to be a useful parameter in water polo.

The founder of the church of Saint George at Pološko

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Pavlović Dragana

2015-01-01

Full Text Available The paper seeks to establish who was the founder of the church of Saint George at Pološko and revise the conclusions of previous researchers regarding this issue. According to the opinion commonly adopted in the scholarly literature, Jovan Dragušin, a cousin of King Dušan, had merely undertaken the construction of church at Pološko, whereas his mother was responsible for the completion of construction and painting of frescoes in the church. Through an analysis of written and visual sources the conclusion is reached that the sole person responsible for the construction and painting of the church at Pološko was the nun Maria, the mother of Jovan Dragušin. [Projekat Ministarstva nauke Republike Srbije, br. 177036: Srpska srednjovekovna umetnost i njen evropski kontekst

Polo pony injuries: player-owner reported risk, perception, mitigation and risk factors.

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Inness, C M; Morgan, K L

2015-07-01

Polo, one of the world's oldest sports, is unique in merging human skill and balance with animal agility and performance in a contact sport. These modern-day 'centaurs' offer medical, dental and veterinary scientists an unrivalled, if quirky, opportunity to collaborate. Collection of epidemiological data on injuries to UK polo riders and ponies is the first step. To measure the reported risk and risk factors for injuries to UK polo ponies, their perception and mitigation by player-owners. A retrospective cohort design and telephone interviews were used. Data on equine injuries, preseason training and risk perception were collected from a random sample of player-owners using a structured questionnaire. Injuries were defined as requiring veterinary treatment. Frequencies were represented as percentages and 95% confidence intervals (CIs). Risk factors for injuries were identified by univariable and multivariable analyses. The cumulative incidence of player-owner-reported injury was 10.6% (95% CI 8.4-12.7). Tendon injuries were most common (4.3%; 95% CI 2.9-5.7), followed by wounds and splints. The only risk factor was stabling all season (odds ratio 4.79; 95% CI 1.46-15.73). Tendon injuries were perceived as the major risk and hard ground the most important risk factor. Risk mitigation practices were bandaging before exercise (45.7%; 95% CI 34.8-56.5), checking tendons (84.0%; 95% CI 76.0-91.9), cold hosing (40.7%; 95% CI 30.0-51.4), bandaging (38.3%; 95% CI 27.7-48.9) and using clays and coolants after exercise (24.7%; 15.3-34.1). Cuts and wounds were considered most frequent by only 2.5% (95% CI 0.0-3.6) of players but were the second most common injury, accounting for 21.6% of veterinary treatments. Splints accounted for 12.5% of injuries. The risk of injury to polo ponies is similar to that in the general horse population; musculoskeletal injuries, particularly tendon injuries, are most common, followed by wounds and splints. The association between stabling and

Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents [version 1; referees: 4 approved

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Jung-Eun Park

2017-06-01

Full Text Available Although significant levels of side effects are often associated with their use, microtubule-directed agents that primarily target fast-growing mitotic cells have been considered to be some of the most effective anti-cancer therapeutics. With the hope of developing new-generation anti-mitotic agents with reduced side effects and enhanced tumor specificity, researchers have targeted various proteins whose functions are critically required for mitotic progression. As one of the highly attractive mitotic targets, polo-like kinase 1 (Plk1 has been the subject of an extensive effort for anti-cancer drug discovery. To date, a variety of anti-Plk1 agents have been developed, and several of them are presently in clinical trials. Here, we will discuss the current status of generating anti-Plk1 agents as well as future strategies for designing and developing more efficacious anti-Plk1 therapeutics.

Monitoring and assessment of regional air quality in China using space observations (Marco Polo)

NARCIS (Netherlands)

Ronald, A. van der; Timmermans, R.; Bai, J.; Zhang, Q.; Wal, L. van der

2013-01-01

In this paper we will present the FP7-project 'MarcoPolo'. The main objective of MarcoPolo is to improve air quality monitoring, modelling and forecasting over China using satellite data. During the project a new emission inventory will be constructed by combining Chinese and European expertise. It

A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1.

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Davide Danovi

Full Text Available Glioblastoma multiforme (GBM is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS cells and genetically normal neural stem (NS cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101 as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1 (phospho T210, with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364 phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF(-/-, or p53(-/-, as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value.

Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.

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Watanabe, Nobumoto; Sekine, Tomomi; Takagi, Masatoshi; Iwasaki, Jun-ichi; Imamoto, Naoko; Kawasaki, Hisashi; Osada, Hiroyuki

2009-01-23

Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase.

The Oxidative Stress Response in Elite Water Polo Players: Effects of Genetic Background.

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Vecchio, Mercurio; Currò, Monica; Trimarchi, Fabio; Naccari, Sergio; Caccamo, Daniela; Ientile, Riccardo; Barreca, Davide; Di Mauro, Debora

2017-01-01

Acute exercise is known to induce oxidative stress. Here we assessed the effects of gene polymorphisms SOD2 A16V, CAT -844 G>A, and GPx-1 rs1800668 C>T on oxidative stress markers in 28 elite water polo male players prior to and after a routinely programmed friendly match. The mean plasma concentrations of derivatives of reactive oxygen metabolites (dROMs), as well as lactic dehydrogenase (LDH) activity, creatine kinase (CK) activity, CK-MB, and myoglobin, were significantly increased after exercise, while blood antioxidant potential (BAP) and total free thiols were significantly decreased, compared with those measured before exercise. Advanced oxidation protein products (AOPP) were also increased after exercise but not significantly. We observed that water polo players having either AV16 or VV16 SOD genotype exhibited a significant increase of postexercise AOPP, LDH, CK, and myoglobin plasma levels in comparison with wild-type athletes. Water polo players having either CAT -844 GA or GPx1 CT genotype showed a significant increase of postexercise dROMs plasma levels and, respectively, GPx and CAT enzyme activities in comparison with wild-type subjects. These preliminary results suggest that the screening for gene variants of antioxidant enzymes could be useful to assess individual susceptibility to oxidative stress and muscle damage in water polo players.

The Oxidative Stress Response in Elite Water Polo Players: Effects of Genetic Background

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Mercurio Vecchio

2017-01-01

Full Text Available Acute exercise is known to induce oxidative stress. Here we assessed the effects of gene polymorphisms SOD2 A16V, CAT −844 G>A, and GPx-1 rs1800668 C>T on oxidative stress markers in 28 elite water polo male players prior to and after a routinely programmed friendly match. The mean plasma concentrations of derivatives of reactive oxygen metabolites (dROMs, as well as lactic dehydrogenase (LDH activity, creatine kinase (CK activity, CK-MB, and myoglobin, were significantly increased after exercise, while blood antioxidant potential (BAP and total free thiols were significantly decreased, compared with those measured before exercise. Advanced oxidation protein products (AOPP were also increased after exercise but not significantly. We observed that water polo players having either AV16 or VV16 SOD genotype exhibited a significant increase of postexercise AOPP, LDH, CK, and myoglobin plasma levels in comparison with wild-type athletes. Water polo players having either CAT −844 GA or GPx1 CT genotype showed a significant increase of postexercise dROMs plasma levels and, respectively, GPx and CAT enzyme activities in comparison with wild-type subjects. These preliminary results suggest that the screening for gene variants of antioxidant enzymes could be useful to assess individual susceptibility to oxidative stress and muscle damage in water polo players.

The Polo-Like Kinase 1 (PLK1 inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia.

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Alessia Casolaro

Full Text Available CD56 is expressed in 15-20% of acute myeloid leukaemias (AML and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8, generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+ monoblastic AML (M5a. The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1 has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively. Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.

Human-like object tracking and gaze estimation with PKD android.

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Wijayasinghe, Indika B; Miller, Haylie L; Das, Sumit K; Bugnariu, Nicoleta L; Popa, Dan O

2016-05-01

As the use of robots increases for tasks that require human-robot interactions, it is vital that robots exhibit and understand human-like cues for effective communication. In this paper, we describe the implementation of object tracking capability on Philip K. Dick (PKD) android and a gaze tracking algorithm, both of which further robot capabilities with regard to human communication. PKD's ability to track objects with human-like head postures is achieved with visual feedback from a Kinect system and an eye camera. The goal of object tracking with human-like gestures is twofold : to facilitate better human-robot interactions and to enable PKD as a human gaze emulator for future studies. The gaze tracking system employs a mobile eye tracking system (ETG; SensoMotoric Instruments) and a motion capture system (Cortex; Motion Analysis Corp.) for tracking the head orientations. Objects to be tracked are displayed by a virtual reality system, the Computer Assisted Rehabilitation Environment (CAREN; MotekForce Link). The gaze tracking algorithm converts eye tracking data and head orientations to gaze information facilitating two objectives: to evaluate the performance of the object tracking system for PKD and to use the gaze information to predict the intentions of the user, enabling the robot to understand physical cues by humans.

Human-like object tracking and gaze estimation with PKD android

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Wijayasinghe, Indika B.; Miller, Haylie L.; Das, Sumit K.; Bugnariu, Nicoleta L.; Popa, Dan O.

2016-05-01

As the use of robots increases for tasks that require human-robot interactions, it is vital that robots exhibit and understand human-like cues for effective communication. In this paper, we describe the implementation of object tracking capability on Philip K. Dick (PKD) android and a gaze tracking algorithm, both of which further robot capabilities with regard to human communication. PKD's ability to track objects with human-like head postures is achieved with visual feedback from a Kinect system and an eye camera. The goal of object tracking with human-like gestures is twofold: to facilitate better human-robot interactions and to enable PKD as a human gaze emulator for future studies. The gaze tracking system employs a mobile eye tracking system (ETG; SensoMotoric Instruments) and a motion capture system (Cortex; Motion Analysis Corp.) for tracking the head orientations. Objects to be tracked are displayed by a virtual reality system, the Computer Assisted Rehabilitation Environment (CAREN; MotekForce Link). The gaze tracking algorithm converts eye tracking data and head orientations to gaze information facilitating two objectives: to evaluate the performance of the object tracking system for PKD and to use the gaze information to predict the intentions of the user, enabling the robot to understand physical cues by humans.

Male Hypogonadism and Germ Cell Loss Caused by a Mutation in Polo-Like Kinase 4

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Harris, Rebecca M.; Weiss, Jeffrey

2011-01-01

The genetic etiologies of male infertility remain largely unknown. To identify genes potentially involved in spermatogenesis and male infertility, we performed genome-wide mutagenesis in mice with N-ethyl-N-nitrosourea and identified a line with dominant hypogonadism and patchy germ cell loss. Genomic mapping and DNA sequence analysis identified a novel heterozygous missense mutation in the kinase domain of Polo-like kinase 4 (Plk4), altering an isoleucine to asparagine at residue 242 (I242N). Genetic complementation studies using a gene trap line with disruption in the Plk4 locus confirmed that the putative Plk4 missense mutation was causative. Plk4 is known to be involved in centriole formation and cell cycle progression. However, a specific role in mammalian spermatogenesis has not been examined. PLK4 was highly expressed in the testes both pre- and postnatally. In the adult, PLK4 expression was first detected in stage VIII pachytene spermatocytes and was present through step 16 elongated spermatids. Because the homozygous Plk4I242N/I242N mutation was embryonic lethal, all analyses were performed using the heterozygous Plk4+/I242N mice. Testis size was reduced by 17%, and histology revealed discrete regions of germ cell loss, leaving only Sertoli cells in these defective tubules. Testis cord formation (embryonic day 13.5) was normal. Testis histology was also normal at postnatal day (P)1, but germ cell loss was detected at P10 and subsequent ages. We conclude that the I242N heterozygous mutation in PLK4 is causative for patchy germ cell loss beginning at P10, suggesting a role for PLK4 during the initiation of spermatogenesis. PMID:21791561

ASSOCIATION BETWEEN MORPHOLOGICAL DIMENSIONS OF WATER POLO PLAYERS AND PLAY PERFORMANCE INDICATORS

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Dragan Milanović

2013-07-01

Full Text Available The goal of the paper is to determine relevance of certain morphological parameters, understood as the dimensions of morphological status of water polo players, in relation to their game performance in the phases of defence and attack. The sample of subjects embraced 104 (aged 17–19 yrs top-quality water polo players, members of junior selections from eight water polo clubs, who participated in the Adriatic League competition. The total variable sample consisted of the predictor variables (10 and two criterion variables based on the expert evaluations of the subjects' play in attack and defence. The associations between the predictor variables and play performance grades were established using regression analysis. The obtained results suggest the quantity of subcutaneous fat directly affects quality of playing in the phase of defence, meaning that the players with larger quantities of subcutaneous fat perform poorly in polyvalent defensive actions and demonstrate a low level of agility, both resulting in less effective play in defence. Although the quantity of subcutaneous fat has been recognized as the factor affecting play quality in attack as well, we obtained that it has smaller effect than in the case of defence. The probable cause of the afore-mentioned may be found in water polo players with a relatively greater amount of fatty tissue (hole sets, who are still highly efficient in attack tasks performance. Their situation-related efficiency is manifested in better positioning and position keeping, as well as in larger number of forced exclusions of the opponents, which contributes comprehen¬sively to attack efficiency.

Physiological Responses of Water-Polo Players Under Different Tactical Strategie

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Petros G. Botonis, Argyris G. Toubekis

2015-01-01

Full Text Available The aim of this study was to investigate the effect of defense tactical strategy on physiological responses characterizing playing intensity in water-polo game. In the first part of the study, fourteen players were assigned to defending (n = 7 and offending (n = 7 groups and participated in nine 4-min plays applying three different defending systems: press, static-zone and zone-press, in front of the defense court of one goalpost. In the second part, 18 players participated in nine different real full court water-polo games consisting of 3X15min of live-time playing periods. Both in defense court plays and real games, the three defense systems were played in a counterbalanced order and heart rate (HR was continuously recorded. Additionally, in defense court plays, blood lactate concentration (La was measured at the end of each 4-min period. Mean HR within defense court plays was higher in press (153 ± 10 beats.min-1 than in static-zone (140 ± 11 beats.min-1 and zone-press (143 ± 16 beats.min-1, p 0.05. Defenders and offenders showed similar HR and La responses across the tactical modes. In conclusion, defense tactical strategies affect physiological responses within a part of the game but do not affect the overall playing intensity of a real water-polo game. Tactical strategies similarly affect offenders and defenders.

THE RELATIONS OF MORPHOLOGIC CHARACTERISTICS AND MOTOR ABILITIES OF JOUNG WATER POLO PLAYERS

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Dragan Toskić

2013-07-01

Full Text Available The aim of our research was to determine the connection between morphologic characteristics and motor abilities of young water polo players. The sample of participants for this research can be defined as the population of water polo swimmers (N=60 aged 16 to 18, who were only included in the study under the condition that they have taken part in the water polo training process for a period of at least four years. In order to evaluate morphological characteristics of the participants we used 20 anthro¬po¬me¬tric variables (IBP to evaluated longitudinal and transversal dimenions, mass and body voluminosity and subcutaneous fatty tissue. In this study, the measurings of the sig¬ni¬ficant motor dimensions were carried by means of the following measuring instruments which the authors (Gredelj, Hošek, Metikoš, Momirović, 1975 had previously evaluated with the help of physiological mechanisms: the integration factor, based on the me¬cha¬nism for movement structure (MSK, the synergistic automatism and tonus regulation factor (SRT; the factor for excitation intensity regulation (RIE; the excitation duration re¬gulation factor (RTE. The relations between morphological and motor dimensions we¬re determined using a canonical correlation analysis. A correlation analysis was carried out and it indicated a very high correlation between dimesions morphological cha¬ra¬cte¬ri¬stics and motor abilities of young water polo players.

Neuromuscular and technical abilities related to age in water-polo players.

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De Siati, Fabio; Laffaye, Guillaume; Gatta, Giorgio; Dello Iacono, Antonio; Ardigò, Luca Paolo; Padulo, Johnny

2016-08-01

Testing is one of the important tasks in any multi-step sport programme. In most ball games, coaches assess motor, physical and technical skills on a regular basis in early stages of talent identification in order to further athletes' development. The purpose of the study was to investigate anthropometric variables and vertical jump heights as a free throw effectiveness predictor in water-polo players of different age groups. Two hundred and thirty-six young (10-18 years) male water-polo players partitioned into three age groups underwent anthropometric variables' measures and squat- and countermovement-jump tests, and performed water-polo free throws. Anthropometric variables, vertical jump heights and throw speed - as a proxy for free throw effectiveness - resulted different over age groups. Particularly, throw speed changed from 9.28 to 13.70 m · s(-1) (+48%) from younger to older players. A multiple-regression model indicated that body height, squat-jump height and throw time together explain 52% of variance of throw speed. In conclusion, tall height, high lower limb power and throwing quickness appeared to be relevant determinants for effective free throws. Such indications can help coaches during talent identification and development processes, even by means of novel training strategies. Further research is needed over different maturity statuses.

Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

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Douglas, Pauline; Ye, Ruiqiong; Morrice, Nicholas; Britton, Sébastien; Trinkle-Mulcahy, Laura; Lees-Miller, Susan P

2015-08-01

Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Targeting Echinococcus multilocularis stem cells by inhibition of the Polo-like kinase EmPlk1.

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Andreas Schubert

2014-06-01

Full Text Available Alveolar echinococcosis (AE is a life-threatening disease caused by larvae of the fox-tapeworm Echinococcus multilocularis. Crucial to AE pathology is continuous infiltrative growth of the parasite's metacestode stage, which is driven by a population of somatic stem cells, called germinative cells. Current anti-AE chemotherapy using benzimidazoles is ineffective in eliminating the germinative cell population, thus leading to remission of parasite growth upon therapy discontinuation.We herein describe the characterization of EmPlk1, encoded by the gene emplk1, which displays significant homologies to members of the Plk1 sub-family of Polo-like kinases that regulate mitosis in eukaryotic cells. We demonstrate germinative cell-specific expression of emplk1 by RT-PCR, transcriptomics, and in situ hybridization. We also show that EmPlk1 can induce germinal vesicle breakdown when heterologously expressed in Xenopus oocytes, indicating that it is an active kinase. This activity was significantly suppressed in presence of BI 2536, a Plk1 inhibitor that has been tested in clinical trials against cancer. Addition of BI 2536 at concentrations as low as 20 nM significantly blocked the formation of metacestode vesicles from cultivated Echinococcus germinative cells. Furthermore, low concentrations of BI 2536 eliminated the germinative cell population from mature metacestode vesicles in vitro, yielding parasite tissue that was no longer capable of proliferation.We conclude that BI 2536 effectively inactivates E. multilocularis germinative cells in parasite larvae in vitro by direct inhibition of EmPlk1, thus inducing mitotic arrest and germinative cell killing. Since germinative cells are decisive for parasite proliferation and metastasis formation within the host, BI 2536 and related compounds are very promising compounds to complement benzimidazoles in AE chemotherapy.

Abundance, distribution and conservation status of Siberian ibex, Marco Polo and Blue sheep in Karakoram-Pamir mountain area

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Babar Khan

2016-07-01

Full Text Available This study was carried out to investigate abundance, distribution, structure and conservation status of three major ungulate species viz., Capra sibirica, Pseudois nayaur and Ovis ammon polii, in the Karakoram-Pamir mountain area between China and Pakistan. Results showed that the entire study area had a scattered but worthwhile population of Siberian ibex, Blue sheep and Marco Polo sheep, except Khunjerab Pass, Koksil-Pateshek and Barkhun areas of Khunjerab National Park (KNP. Large groups of Blue sheep were sighted in Shimshal and Barkhun valleys (KNP but it did not show up in the Muztagh part of Taxkorgan Nature Reserve (TNR in China. Despite scarcity of natural vegetation and extreme climate, estimated abundance of ibex and Marco Polo sheep was not different from that in Protected Areas of Nepal, China, and India, except for Blue sheep. Marco Polo sheep, Blue sheep and Snow leopard roam across international borders among China, Pakistan and other adjacent countries. Illegal hunting and poaching, removal of natural vegetation for fodder and firewood, and over grazing of pastures by livestock were main habitat issues whereas, border fencing for security reasons, has been a major impediment restricting free movement of the wildlife across international borders. A science based conservation and development strategy is proposed to restore viable wildlife populations and maintain ecological flows of Karakoram Pamir Mountains to benefit both the wild species and the local human communities.

Cdk1 Phosphorylates Drosophila Sas-4 to Recruit Polo to Daughter Centrioles and Convert Them to Centrosomes.

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Novak, Zsofia A; Wainman, Alan; Gartenmann, Lisa; Raff, Jordan W

2016-06-20

Centrosomes and cilia are organized by a centriole pair comprising an older mother and a younger daughter. Centriole numbers are tightly regulated, and daughter centrioles (which assemble in S phase) cannot themselves duplicate or organize centrosomes until they have passed through mitosis. It is unclear how this mitotic "centriole conversion" is regulated, but it requires Plk1/Polo kinase. Here we show that in flies, Cdk1 phosphorylates the conserved centriole protein Sas-4 during mitosis. This creates a Polo-docking site that helps recruit Polo to daughter centrioles and is required for the subsequent recruitment of Asterless (Asl), a protein essential for centriole duplication and mitotic centrosome assembly. Point mutations in Sas-4 that prevent Cdk1 phosphorylation or Polo docking do not block centriole disengagement during mitosis, but block efficient centriole conversion and lead to embryonic lethality. These observations can explain why daughter centrioles have to pass through mitosis before they can duplicate and organize a centrosome. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Repeated Sprint Ability in Elite Water Polo Players and Swimmers and its Relationship to Aerobic and Anaerobic Performance

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Yoav Meckel

2013-12-01

Full Text Available The purpose of this study was to determine indices of swimming repeated sprint ability (RSA in 19 elite water polo players compared to 16 elite swimmers during a repeated sprint swimming test (RST, and to examine the relationships between these indices and aerobic and anaerobic performance capabilities in both groups. Indices of RSA were determined by the ideal sprint time (IS, the total sprint time (TS, and the performance decrement (PD recorded during an 8 x 15-m swimming RST. Single long - (800-m and short-(25-m distance swim tests were used to determined indices of aerobic and anaerobic swimming capabilities, respectively. The water polo players exhibited lower RSA swimming indices, as well as lower scores in the single short and long swim distances, compared to the swimmers. Significant relationships were found between the 25- m swim results and the IS and the TS, but not the PD of both the swimmers and the water polo players. No significant relationships were found between the 800-m swim results and any of the RSA indices in either the swimmers or the water polo players. No significant relationships were found between the 25-m and the 800-m swim results in either the swimmers or the water polo players. The results indicate that swimmers posses better RSA as well as higher anaerobic and aerobic capabilities, as reflected by the single short- and long-distance swim tests, compared to water polo players. The results also indicate that, as for running and cycling, repeated sprint swim performance is strongly related to single sprint performance.

Caenorhabditis elegans polo-like kinase PLK-1 is required for merging parental genomes into a single nucleus.

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Rahman, Mohammad M; Munzig, Mandy; Kaneshiro, Kiyomi; Lee, Brandon; Strome, Susan; Müller-Reichert, Thomas; Cohen-Fix, Orna

2015-12-15

Before the first zygotic division, the nuclear envelopes of the maternal and paternal pronuclei disassemble, allowing both sets of chromosomes to be incorporated into a single nucleus in daughter cells after mitosis. We found that in Caenorhabditis elegans, partial inactivation of the polo-like kinase PLK-1 causes the formation of two nuclei, containing either the maternal or paternal chromosomes, in each daughter cell. These two nuclei gave rise to paired nuclei in all subsequent cell divisions. The paired-nuclei phenotype was caused by a defect in forming a gap in the nuclear envelopes at the interface between the two pronuclei during the first mitotic division. This was accompanied by defects in chromosome congression and alignment of the maternal and paternal metaphase plates relative to each other. Perturbing chromosome congression by other means also resulted in failure to disassemble the nuclear envelope between the two pronuclei. Our data further show that PLK-1 is needed for nuclear envelope breakdown during early embryogenesis. We propose that during the first zygotic division, PLK-1-dependent chromosome congression and metaphase plate alignment are necessary for the disassembly of the nuclear envelope between the two pronuclei, ultimately allowing intermingling of the maternal and paternal chromosomes. © 2015 Rahman et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Posture and isokinetic shoulder strength in female water polo players

African Journals Online (AJOL)

Background: Being overhead athletes, water polo players can present with muscular imbalances of the shoulder, between the internal rotators (IR) and external rotators (ER), leading to changes in posture and an increased risk of injury. Objectives: To assess posture and isokinetic shoulder strength of female club-level ...

Water polo throwing velocity and kinematics: differences between competitive levels in male players.

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Melchiorri, G; Viero, V; Triossi, T; De Sanctis, D; Padua, E; Salvati, A; Galvani, C; Bonifazi, M; Del Bianco, R; Tancredi, V

2015-11-01

In water polo, throwing is one of the most important and frequently used technical skills for the player. There is no scientific literature that provides information about differences in throwing between elite and sub-elite water polo players. The aim of our study was to study differences in throwing velocities and kinematic variables in elite and sub-elite level male water polo players. We considered the variables under standardized conditions during a typical motion, the five-meter shot (penalty). Thirty-four athletes from the Men's First Division Water Polo Championship and forty-two players participating in the National Fourth Division League, took part in the study. Video analysis measures were taken with high-speed digital cameras and the videos were analyzed offline with Dartfish 5.0 Pro. No correlation was found between body mass, height and throwing velocity. Elite players had higher values ​for ball speed (22.8±2.4 m/s for elite team and 18.4±1.7 m/s for sub-elite team; P=0.002) and greater elbow angle (157.5±10.3 degree for elite team versus 146.7±8.9 degree for sub-elite team; P=0.002). In elite team the throwing time was lower (165.6±22.2 and 188.6±23.9 ms, respectively; P=0.05) and the shoulder angle was smaller (115.1±10.3 and 123.8±12.4 degree, respectively; P=0.03) than in sub-elite team. Head height was significantly greater in elite players (elite players 71.1±8.7 cm, sub-elite players 65.6±6.2 cm; P=0.03). Differences in kinematic characteristics between elite and sub-elite players were showed. Differences in elbow and shoulder action must be considered both in training and injury prevention.

Avaliação eletrocardiográfica de equinos após exercício de polo (baixo handicap Electrocardiographic evaluation of horses after polo exercise

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Camila A.O. Bello

2012-12-01

Full Text Available A eletrocardiografia pode ser usada para quantificar o treinamento e o desempenho atlético. Pode ainda avaliar a função cardíaca sob efeito do exercício identificando a influência de anomalias cardíacas, assim como os efeitos deletérios do esforço frente à função cardíaca. Considerando a complexidade do esforço físico inerente a cavalos em competições de polo, juntamente com a carência de relatos na literatura sobre a demanda cardíaca resultante. O objetivo deste estudo foi o de identificar e avaliar eletrocardiograficamente os efeitos cardíacos do exercício de polo em equinos de forma a subsidiar dados para a compreensão da demanda fisiológica cardíaca desta modalidade. Foram avaliados 27 equinos praticante de polo em repouso e entre cinco e dez minutos após o exercício. Os resultados obtidos demonstraram que as alterações observadas na duração e amplitude da onda P e duração do intervalo PR e QT foram consideradas fisiológicas em resposta ao aumento da frequência cardíaca. A onda P difásica encontrada em repouso representou hipertrofia atrial e quando bífida representou diferentes pontos de ativação do nó sinoatrial. Como esperado o complexo QRS não sofreu alterações consideráveis entre os dois momentos. O supradesnível do segmento ST e as variações da onda T observadas após o exercício poderiam representar efeito adverso ao miocárdio, entretanto estudos analisando múltiplos fatores são necessários para confirmar esta associação e definir sua real causa. O aumento do QTc sugeriu fadiga miocárdica leve representando alta demanda cardíaca para esta modalidade. O escore cardíaco demonstrou que estes animais estavam dentro do padrão de adaptação cardíaca para um cavalo atleta. A rápida recuperação cardíaca demonstrou bom condicionamento atlético. O marca-passo atrial mutável foi um achado normal encontrado nos equinos de polo. Foi observada baixa incidência de alterações no

Analysis of the electrodynamics of subcable current distribution in the superconducting POLO coil cable

International Nuclear Information System (INIS)

Sihler, C.; Heller, R.; Maurer, W.; Ulbricht, A.; Wuechner, F.

1995-10-01

Unexpected ramp rate limitations (RRL) found in superconducting magnets during the development of magnet systems can be attributed to a current imbalance amongst the cabled strands which leads to a lower than expected quench current. In superconducting magnets the current distribution in the cable during ramping depends mainly on the electromagnetic properties of the system. A detailed analysis of principle causes for RRL phenomena was performed with a model for one half of the POLO coil considering the complete inductance matrix of the cable and the fact that all turns are mutually coupled. The main results of these calculations are that unequal contact resistances can not be responsible for RRL phenomena in coils with parameters comparable to those of the POLO coil and that already minor geometrical disturbances in the cable structure can lead to major and lasting imbalances in the current distribution of cables with insulated and non-insulated strands. During the POLO experiment the half-coil model was employed to get a better understanding of the measured compensated subcable voltages during quench. The good agreement of the calculated and measured results demonstrates the validity of the model for RRL analyses. (orig.)

A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells

NARCIS (Netherlands)

C. Buecker (Christa); H.H. Chen; J.M. Polo (Jose); L. Daheron (Laurence); L. Bu (Lei); T.S. Barakat (Tahsin Stefan); P. Okwieka (Patricia); A. Porter (Andrew); J.H. Gribnau (Joost); K. Hochedlinger (Konrad); N. Geijsen (Niels)

2010-01-01

textabstractMurine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human

Polo-like kinase phosphorylation determines Caenorhabditis elegans centrosome size and density by biasing SPD-5 toward an assembly-competent conformation

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Oliver Wueseke

2016-10-01

Full Text Available Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM. In Caenorhabditis elegans embryos, the mitotic PCM expands by Polo-like kinase 1 (PLK-1 phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-54A could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased. In vitro, purified SPD-54A self-assembled into functional supramolecular scaffolds over long time scales, suggesting that phosphorylation only controls the rate of SPD-5 scaffold assembly. Furthermore, the SPD-5 scaffold, once assembled, remained intact and supported microtubule nucleation in the absence of PLK-1 activity in vivo. We conclude that PLK-1 is required for rapid assembly of the PCM scaffold but not for scaffold maintenance or function. Based on this idea, we developed a theoretical model that adequately predicted PCM growth rates in different mutant conditions in vivo. We propose that PLK-1 phosphorylation-dependent conversion of SPD-5 into an assembly-competent form underlies PCM formation in vivo and that the rate of this conversion determines final PCM size and density.

Large-scale label-free comparative proteomics analysis of polo-like kinase 1 inhibition via the small-molecule inhibitor BI 6727 (Volasertib) in BRAF(V600E) mutant melanoma cells.

Science.gov (United States)

Cholewa, Brian D; Pellitteri-Hahn, Molly C; Scarlett, Cameron O; Ahmad, Nihal

2014-11-07

Polo-like kinase 1 (Plk1) is a serine/threonine kinase that plays a key role during the cell cycle by regulating mitotic entry, progression, and exit. Plk1 is overexpressed in a variety of human cancers and is essential to sustained oncogenic proliferation, thus making Plk1 an attractive therapeutic target. However, the clinical efficacy of Plk1 inhibition has not emulated the preclinical success, stressing an urgent need for a better understanding of Plk1 signaling. This study addresses that need by utilizing a quantitative proteomics strategy to compare the proteome of BRAF(V600E) mutant melanoma cells following treatment with the Plk1-specific inhibitor BI 6727. Employing label-free nano-LC-MS/MS technology on a Q-exactive followed by SIEVE processing, we identified more than 20 proteins of interest, many of which have not been previously associated with Plk1 signaling. Here we report the down-regulation of multiple metabolic proteins with an associated decrease in cellular metabolism, as assessed by lactate and NAD levels. Furthermore, we have also identified the down-regulation of multiple proteasomal subunits, resulting in a significant decrease in 20S proteasome activity. Additionally, we have identified a novel association between Plk1 and p53 through heterogeneous ribonucleoprotein C1/C2 (hnRNPC), thus providing valuable insight into Plk1's role in cancer cell survival.

Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

International Nuclear Information System (INIS)

Inoue-Toyoda, Maki; Kato, Kohsuke; Nagata, Kyosuke; Yoshikawa, Hiroyuki

2015-01-01

Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX

Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

International Nuclear Information System (INIS)

Harris, Peter S; Foreman, Nicholas K; Vibhakar, Rajeev; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Donson, Andrew M; Knipstein, Jeffrey; Dubuc, Adrian; Taylor, Michael D; Handler, Michael H

2012-01-01

Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation

Kaasaeg vajab pragmaatikuid / Alejandro Zaera-Polo ; intervjueerinud Triin Ojari, Veronika Valk, Toomas Tammis

Index Scriptorium Estoniae

Zaera-Polo, Alejandro

2012-01-01

Eesti Kunstiakadeemia arhitektuuriteaduskonna välisesinejate loengusarjas esinenud hispaania arhitekt Alejandro Zaera-Polo, kes 2012. aastast juhib Princetoni ülikooli arhitektuurikooli, räägib endast, arhitektuuriharidusest, linnaplaneerimisest, hoone väliskesta (envelope) poliitilisusest

Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.

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David J Huggins

2010-08-01

Full Text Available The Polo-Like Kinase 1 (PLK1 acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD. The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors.

APPLICATION OF THE BATTERY OF TESTS IN EVALUATION OF PSYCHOLOGICAL, SOCIOLOGICAL AND ANTHROPOMOTOR STATUS OF THE WATER POLO PLAYERS

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Dragan Krivokapić

2009-11-01

Full Text Available A huge international success of the Montenegrin national water polo team incre- ased the interest rate for this sport among the young people in our country. Announced construction of at least five pools in Podgorica, as well as reconstruction of already exi- sting ones in Niksic and some of the coastal cities will offer a new perspective for the de- velopment of this sport in Montenegro. Water Polo World League Super Final which is, according to announcements, to be held at the pools in Podgorica will probably enhance the interest in this sport even more. Due to the reasons mentioned above, the intensifying of the expert selection is more popular than ever. This paper lists some of the tests for the evaluation of psychological, sociological and anthropomotor status of younger age categories that are adequate in the process of systematic selection for doing water polo

Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans.

Science.gov (United States)

Martino, Lisa; Morchoisne-Bolhy, Stéphanie; Cheerambathur, Dhanya K; Van Hove, Lucie; Dumont, Julien; Joly, Nicolas; Desai, Arshad; Doye, Valérie; Pintard, Lionel

2017-10-23

In animal cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how they coordinate their activity to trigger this event is unclear. Here, we show that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK-1) is recruited to the nuclear pore complexes, just prior to NEBD, through its Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear envelope (NE) is required for efficient NEBD. We identify the central channel nucleoporins NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62 as the critical factors anchoring PLK-1 to the NE in C. elegans. In particular, NPP-1, NPP-4, and NPP-11 primed at multiple Polo-docking sites by Cdk1 and PLK-1 itself physically interact with the PLK-1 PBD. We conclude that nucleoporins play an unanticipated regulatory role in NEBD, by recruiting PLK-1 to the NE thereby facilitating phosphorylation of critical downstream targets. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of polo-like kinase 1 leads to the suppression of osteosarcoma cell growth in vitro and in vivo.

Science.gov (United States)

Liu, Xianzhe; Choy, Edwin; Harmon, David; Yang, Shuhua; Yang, Cao; Mankin, Henry; Hornicek, Francis J; Duan, Zhenfeng

2011-06-01

Osteosarcoma is the most common type of primary bone cancer in children and adolescents. Treatment options for osteosarcoma may include surgery, chemotherapy, and radiotherapy. Unfortunately, many patients eventually relapse, resulting in an unsatisfactory outcome. The serine/threonine-specific polo-like kinase 1 (PLK1) is a kinase that plays an important role in mitosis and the maintenance of genomic stability. PLK1 has been found to be highly expressed in the malignant cells of osteosarcoma. Here, we describe the in-vitro and in-vivo effects of BI 2536, a small-molecule inhibitor of PLK1, which through inhibiting PLK1 enzymatic activity, causes mitotic arrest and eventually induces cancer cell apoptosis. In this study, we show that the PLK1 inhibitor, BI 2536, inhibits proliferation and induces apoptosis in two-dimensional and three-dimensional cultures of osteosarcoma cell lines, KHOS and U-2OS. A proliferation assay performed both in two-dimensional and three-dimensional culture showed that the growth of both cell lines was inhibited by BI 2536. Cell cycle analysis showed that the cells treated with BI 2536 were mainly arrested in the G2/M phase. Immunofluorescence and western blotting analysis confirmed that the administration of BI 2536 led to significant decrease of PLK1 and Mcl-1 protein expression levels in dose-dependent and time-dependent manners. Furthermore, BI 2536-induced apoptosis in the osteosarcoma cell lines was shown by poly (ADP-ribose) polymerase cleavage and caspase assay. Finally, in mouse osteosarcoma xenografts, BI 2536-treated mice had significantly smaller tumors compared with the control mice. These findings offer evidence of the potential role for targeting PLK1 in osteosarcoma therapy.

Mars Atmosphere and Regolith COllector/PrOcessor for Lander Ops (MARCO POLO) Atmospheric Processing Module

Data.gov (United States)

National Aeronautics and Space Administration — The multi-NASA center Mars Atmosphere and Regolith COllector/PrOcessor for Lander Operations (MARCO POLO) project was established to build and demonstrate a...

Impaired c-Fos and polo-like kinase 2 induction in the limbic system of fear-conditioned α-synuclein transgenic mice.

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Heinrich Schell

Full Text Available α-Synuclein (αSYN is genetically and neuropathologically linked to a spectrum of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and related disorders. Cognitive impairment is recapitulated in several αSYN transgenic mouse lines. However, the mechanisms of dysfunction in affected neurons are largely unknown. Here we measured neuronal activity induced gene products in the limbic system of αSYN transgenic mice upon fear conditioning (FC. Induction of the synaptic plasticity marker c-Fos was significantly reduced in the amygdala and hippocampus of (Thy1-h[A30P]αSYN transgenic mice in an age-dependent manner. Similarly, the neuronal activity inducible polo-like kinase 2 (Plk2 that can phosphorylate αSYN at the pathological site serine-129 was up-regulated in both brain regions upon FC. Plk2 inductions were also significantly impaired in aged (Thy1-h[A30P]αSYN transgenic mice, both in the amygdala and hippocampus. Plk2 inductions in the amygdala after FC were paralleled by a small but significant increase in the number of neuronal cell bodies immunopositive for serine-129 phosphorylated αSYN in young but not aged (Thy1-h[A30P]αSYN transgenic mice. In addition, we observed in the aged hippocampus a distinct type of apparently unmodified transgenic αSYN profiles resembling synaptic accumulations of αSYN. Thus, the cognitive decline observed in aged αSYN transgenic mice might be due to impairment of neurotransmission and synaptic plasticity in the limbic system by distinct αSYN species.

Throwing velocity and kinematics in elite male water polo players.

Science.gov (United States)

Melchiorri, G; Padua, E; Padulo, J; D'Ottavio, S; Campagna, S; Bonifazi, M

2011-12-01

Fifty-three members of the Italian Men Water Polo Team were filmed using two synchronized cameras, while they were shooting a goal. Considering the differences in body mass, height, training strategies and the technical-tactical features of the players, the aims of this study were to employ video-analysis techniques in order to investigate selected kinematic parameters in water polo throwing, and to provide comprehensive quantitative information on the throwing movement in relation to the different team player positions. Video analysis was used to estimate the elbow angle at release, the shoulder angle at follow through, the back and head height at ball release, trunk rotation angle and ball velocity at release. Ball release velocities ranged from 21.0 to 29.8 m/s (average value 25.3±1.4 m/s), for field players. Goal keepers show the lowest team values (average 21.7±0.3 m/s). Similar to previous study results, ball release was typically reached just prior to the elbow approaching full extension (151.6±3.6°), and the follow through shoulder angle was 143±5.9°. No significant statistical difference was recorded between injured and non-injured athletes. No positive association was demonstrated between physical characteristics (body mass and height) and ball velocity.

Activation of a Neospora caninum EGFR-Like Kinase Facilitates Intracellular Parasite Proliferation

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Xiaoxia Jin

2017-10-01

Full Text Available The Apicomplexan parasite Neospora caninum, an obligate intracellular protozoan, causes serious diseases in a number of mammalian species, especially in cattle. Infection with N. caninum is associated with abortions in both dairy and beef cattle worldwide which have a major economic impact on the cattle industry. However, the mechanism by which N. caninum proliferates within host cells is poorly understood. Epidermal growth factor receptor (EGFR is a protein kinase ubiquitously expressed, present on cell surfaces in numerous species, which has been confirmed to be essential in signal transduction involved in cell growth, proliferation, survival, and many other intracellular processes. However, the presence of EGFR in N. caninum and its role in N. caninum proliferation remain unclear. In the present study, we identified a putative EGFR-like kinase in N. caninum, which could be activated in tachyzoites by infection or treatment with rNcMIC3 [containing four epidermal growth factor (EGF domains] or human EGF. Blockade of EGFR-like in tachyzoites by AG1478 significantly reduced parasite proliferation in host cells. Our data suggested that the activation of tachyzoite EGFR-like might facilitate the intracellular proliferation of N. caninum.

Perceived Benefits of Human Sexuality Peer Facilitators

Science.gov (United States)

Butler, Scott M.; Hartzell, Rose M.; Sherwood, Catherine M.

2008-01-01

Peer education, facilitation, and counseling programs are commonly utilized in primary and secondary prevention programs within colleges and universities. In addition, peer-based human sexuality discussions have been used as an adjunct to traditional human sexuality pedagogic programs over the last 20 years. Whereas ample evidence suggests that…

CRESCIMENTO ECONÔMICO NO SEMIÁRIDO BRASILEIRO: O CASO DO POLO FRUTÍCOLA PETROLINA/JUAZEIRO

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Guilherme José Ferreira Araújo

2013-07-01

Full Text Available O Polo Frutícola Petrolina (PE / Juazeiro (BA, localizado no Semiárido brasileiro depois de receber investimentos do Estado para o desenvolvimento da sua atividade agrícola passou por uma significativa transformação do seu espaço agrário. Os investimentos em técnicas de irrigação favoreceram os produtores a cultivar manga e uva e expandir sua rede comercial para a Europa, Estados Unidos e Japão. O polo é um centro de atração populacional consolidado, exercendo a função de líder na região concentrando os principais serviços, além de ser o ponto de escoamento da produção agrícola local. Em virtude do desenvolvimento na agricultura, diversas empresas agrícolas, cooperativas e associações se instalaram na região, favorecendo o surgimento de novos serviços voltados para agricultura irrigada. Associado ao desenvolvimento agrícola surgiu exigências voltadas para proteção ambiental, favorecendo uma reestruturação do espaço agrário local. Este artigo tem como objetivo apresentar os vetores de impulso do crescimento econômico no Polo Frutícola Petrolina/Juazeiro, abordando as principais transformações no seu espaço. A metodologia consistiu em levantamento bibliográfico e visitas em campo, com realização de entrevistas nos órgãos públicos, privados e com os produtores agrícolas. A região em análise configura-se como um dos polos mais dinâmicos do Sertão pernambucano e baiano, destacando-se pela pelas altas taxas de exportação de manga e uva. O crescimento de sua atividade econômica contribuiu para intensificação do capital empresarial, mudanças nos hábitos de produção e a reconfiguração na hierarquia regional.

ANÁLISE DA CIDADE BAIXA COMO POLO CRIATIVO POTENCIAL

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Lisiane Quadrado Closs

Full Text Available RESUMO A Economia Criativa vem recebendo atenção crescente, podendo contribuir para um desenvolvimento centrado nas pessoas e como insumo para a criação de empregos e inovação, favorecendo a inclusão social, a diversidade cultural e a sustentabilidade. Para ampliar sua discussão no Brasil, este trabalho tem por objetivo analisar as potencialidades e os limites para um território localizado no bairro Cidade Baixa, em Porto Alegre, constituir-se como polo criativo. Entre os aspectos favoráveis destacam-se: a localização, o patrimônio histórico e o ambiente que reúne arte e cultura, bares, restaurante e casas de espetáculos, tornando-o atrativo para o turismo; a aceitação da diversidade; a concentração de empreendimentos criativos e o interesse de moradores e empreendedores no seu desenvolvimento como espaço criativo. Entre as limitações estão: as disputas entre moradores, proprietários de bares e promotores de eventos; a falta de comunicação; a ausência de laços fortes e de articulação entre atores ligados à economia criativa em prol de objetivos comuns; o risco de supervalorização de imóveis na região e de afastamento de artistas e estudantes para outros bairros, descaracterizando o seu tecido constituinte. Como principais contribuições deste estudo, alerta-se para: (a a incorporação acrítica da noção de economia criativa por instituições públicas e privadas, reproduzindo modelos internacionais; (b o predomínio do interesse em ganhos econômicos em detrimento da preservação de aspectos históricos e culturais do bairro; (c a desarticulação entre os atores do território, o que amplia conflitos e compromete a construção de uma proposta integrada para a constituição de um polo criativo; e (d o uso do conceito de território criativo para uma compreensão do espaço mais profunda do que a de polos criativos, que enfatiza elementos objetivos e convergentes, deixando de explorar contradições e

O polo de apoio presencial como espaço de gestão e autonomia na EAD. As contingências na Gestão da EAD

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Simone do Nascimento da Costa

2017-02-01

Full Text Available Este artigo revela os resultados de pesquisa sobre três polos de apoio presencial ligados a modalidade a distância, considerando os processos de gestão e autonomia no contexto em que atuam. Trata-se de dois momentos de análise, respectivamente relacionados à estruturação dos polos, a partir de diretrizes preestabelecidas e da discussão sobre a realidade cultural e contingencial existente neste espaço; e, por fim à utilização da técnica da entrevista semiestruturada para a análise do processo de gestão e autonomia existente nos polos pesquisados. Para a aplicação da pesquisa foram realizadas entrevistas com os coordenadores dos respectivos polos (dois localizados no Estado de São Paulo e um no Estado do Paraná, sendo dois destes polos de ordem privada e o outro de ordem pública. Como resultado, obtém-se que apesar das diretrizes preestabelecidas, os polos possuem um modelo contingencial e, portanto, cultural de adaptação à realidade em que se instalam, compreendendo uma gestão voltada a adequações e readequações diante de um contexto em constante desenvolvimento. Quanto à autonomia revela-se a existência de trâmites não negociáveis relacionados às bases legais que os regulamentam, contudo, estabelecidos estes parâmetros, a autonomia se determina pela tomada de decisão deste gestor diante da realidade em que se instala.

Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

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Douglas W McMillin

Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

A key centriole assembly interaction interface between human PLK4 and STIL appears to not be conserved in flies

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Matthew A. Cottee

2017-03-01

Full Text Available A small number of proteins form a conserved pathway of centriole duplication. In humans and flies, the binding of PLK4/Sak to STIL/Ana2 initiates daughter centriole assembly. In humans, this interaction is mediated by an interaction between the Polo-Box-3 (PB3 domain of PLK4 and the coiled-coil domain of STIL (HsCCD. We showed previously that the Drosophila Ana2 coiled-coil domain (DmCCD is essential for centriole assembly, but it forms a tight parallel tetramer in vitro that likely precludes an interaction with PB3. Here, we show that the isolated HsCCD and HsPB3 domains form a mixture of homo-multimers in vitro, but these readily dissociate when mixed to form the previously described 1:1 HsCCD:HsPB3 complex. In contrast, although Drosophila PB3 (DmPB3 adopts a canonical polo-box fold, it does not detectably interact with DmCCD in vitro. Thus, surprisingly, a key centriole assembly interaction interface appears to differ between humans and flies.

Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

Science.gov (United States)

Wang, Hui; Tian, Chan; Fan, Xue-Yu; Chen, Li-Na; Lv, Yan; Sun, Jing; Zhao, Yang-Jing; Zhang, Lu-bin; Wang, Jing; Shi, Qi; Gao, Chen; Chen, Cao; Shao, Qi-Xiang; Dong, Xiao-Ping

2015-05-01

Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Reliability of a Functional Agility Test for Water Polo

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Tucher Guilherme

2014-07-01

Full Text Available Few functional agility tests for water polo take into consideration its specific characteristics. The preliminary objective of this study was to evaluate the reliability of an agility test for water polo players. Fifteen players (16.3 ± 1.8 years old with a minimum of two years of competitive experience were evaluated. A Functional Test for Agility Performance (FTAP was designed to represent the context of this sport. Several trials were performed to familiarize the athlete with the movement. Two experienced coaches measured three repetitions of the FTAP. Descriptive statistics, repeated measures analysis of variance (ANOVA, 95% limit of agreement (LOA, intraclass correlation coefficient (ICC and standard error of measurements (SEM were used for data analysis. It was considered that certain criteria of reliability measures were met. There was no significant difference between the repetitions, which may be explained by an effect of the evaluator, the ability of the players or fatigue (p > 0.05. The ICC average from evaluators was high (0.88. The SEM varied between 0.13 s and 0.49 s. The CV average considering each individual was near 6-7%. These values depended on the condition of measurement. As the FTAP contains some characteristics that create a degree of unpredictability, the same athlete may reach different performance results, increasing variability. An adjustment in the sample, familiarization and careful selection of subjects help to improve this situation and enhance the reliability of the indicators.

Using a cellular model to explore human-facilitated spread of risk of EAB in Minnesota

Science.gov (United States)

Anantha Prasad; Louis Iverson; Matthew Peters; Steve. Matthews

2011-01-01

The Emerald Ash Borer has made inroads to Minnesota in the past two years, killing ash trees. We use our spatially explicit cell based model called EAB-SHIFT to calculate the risk of infestation owing to flight characteristics and short distance movement of the insect (insect flight model, IFM), and the human facilitated agents like roads, campgrounds etc. (insect ride...

Temporal and SUMO-specific SUMOylation contribute to the dynamics of Polo-like kinase 1 (PLK1) and spindle integrity during mouse oocyte meiosis.

Science.gov (United States)

Feitosa, Weber Beringui; Hwang, KeumSil; Morris, Patricia L

2018-02-15

During mammalian meiosis, Polo-like kinase 1 (PLK1) is essential during cell cycle progression. In oocyte maturation, PLK1 expression is well characterized but timing of posttranslational modifications regulating its activity and subcellular localization are less clear. Small ubiquitin-related modifier (SUMO) posttranslational modifier proteins have been detected in mammalian gametes but their precise function during gametogenesis is largely unknown. In the present paper we report for mouse oocytes that both PLK1 and phosphorylated PLK1 undergo SUMOylation in meiosis II (MII) oocytes using immunocytochemistry, immunoprecipitation and in vitro SUMOylation assays. At MII, PLK1 is phosphorylated at threonine-210 and serine-137. MII oocyte PLK1 and phosphorylated PLK1 undergo SUMOylation by SUMO-1, -2 and -3 as shown by individual in vitro assays. Using these assays, forms of phosphorylated PLK1 normalized to PLK1 increased significantly and correlated with SUMOylated PLK1 levels. During meiotic progression and maturation, SUMO-1-SUMOylation of PLK1 is involved in spindle formation whereas SUMO-2/3-SUMOylation may regulate PLK1 activity at kinetochore-spindle attachment sites. Microtubule integrity is required for PLK1 localization with SUMO-1 but not with SUMO-2/3. Inhibition of SUMOylation disrupts proper meiotic bipolar spindle organization and spindle-kinetochore attachment. The data show that both temporal and SUMO-specific-SUMOylation play important roles in orchestrating functional dynamics of PLK1 during mouse oocyte meiosis, including subcellular compartmentalization. Copyright © 2018 Elsevier Inc. All rights reserved.

Origen y establecimiento de un polo de crecimiento en Colombia, relato de la industria siderúrgica integrada

Directory of Open Access Journals (Sweden)

Juan Sebastián Lara R.

2013-03-01

Full Text Available Rev.esc.adm.neg Los polos de crecimiento como concepto o teoría, continúan una evolución singular, siendo su implementación en Colombia poco estudiada. En este artículo, se aborda su aplicabilidad partiendo del acontecimiento de la creación de la Empresa Siderúrgica Nacional de Paz del Río, aclarando los efectos sociales, económicos y culturales que produjo. De manera que se provee una revisión histórica y teórica sobre el polo de crecimiento, contrastando sus beneficios y desventajas con el objeto de provocar reflexiones, que en la actualidad puedan asentar un ideario estratégico para el impulso de las regiones del país, donde el desarrollo económico y empresarial es limitado.

Effects of 4 Weeks of β-Alanine Supplementation on Swim-Performance Parameters in Water Polo Players.

Science.gov (United States)

Brisola, Gabriel Motta Pinheiro; Milioni, Fabio; Papoti, Marcelo; Zagatto, Alessandro Moura

2017-08-01

In water polo, several high-intensity efforts are performed, leading to the fatigue process due to accumulation of hydrogen ions, and thus β-alanine supplementation could be an efficient strategy to increase the intramuscular acid buffer. Purpose To investigate whether 4 wk of β-alanine supplementation enhances parameters related to water polo performance. Methods Twenty-two highly trained male water polo players of national level were randomly assigned to receive 28 d of either β-alanine or a placebo (4.8 g/d of the supplement in the first 10 d and 6.4 g/d in the final 18 d). The participants performed 30-s maximal tethered swimming (30TS), 200-m swimming (P200m), and 30-s crossbar jumps (30CJ) before and after the supplementation period. Results The β-alanine group presented significant increases in 30TS for mean force (P = .04; Δ = 30.5% ± 40.4%) and integral of force (P = .05; Δ = 28.0% ± 38.0%), as well as P200m (P = .05; Δ = -2.2% ± 2.6%), while the placebo group did not significantly differ for mean force (P = .13; Δ = 24.1% ± 33.7%), integral of force (P = .12; Δ = 24.3% ± 35.1%), or P200m (P = .10; Δ = -1.6% ± 3.8%). However, there was no significant group effect for any variable, and the magnitude-based-inference analysis showed unclear outcomes between groups (Cohen d ± 95%CL mean force = 0.16 ± 0.83, integral of force = 0.12 ± 0.84, and P200m = 0.05 ± 0.30). For 30CJ the results were similar, with improvements in both groups (placebo, Δ = 14.9% ± 14.1%; β-alanine, Δ = 16.9% ± 18.5%) but with no significant interaction effect between groups and an unclear effect (0.14 ± 0.75). Conclusion Four weeks of β-alanine supplementation does not substantially improve performance of 30TS, P200m, or 30CJ in highly trained water polo athletes compared with a control group.

Deep Space Gateway Facilitates Exploration of Planetary Crusts: A Human/Robotic Exploration Design Reference Campaign to the Lunar Orientale Basin

Science.gov (United States)

Head, J. W.; Pieters, C. M.; Scott, D. R.

2018-02-01

We outline an Orientale Basin Human/Robotic Architecture that can be facilitated by a Deep Space Gateway International Science Operations Center (DSG-ISOC) (like McMurdo/Antarctica) to address fundamental scientific problems about the Moon and Mars.

The Functional Test for Agility Performance is a Reliable Quick Decision-Making Test for Skilled Water Polo Players

Directory of Open Access Journals (Sweden)

Tucher Guilherme

2015-06-01

Full Text Available The reliability of the Functional Test for Agility Performance has only been evaluated in water polo players in a small group of novice athletes. Thus, the aim of this study was to evaluate the reliability of the Functional Test for Agility Performance in skilled water polo players. Forty-two athletes (17.81 ± 3.24 years old with a minimum of 5 years of competitive experience (7.05 ± 2.84 years and playing at the national or international level were evaluated. The Functional Test for Agility Performance is characterized as a specific open decision-making test where a tested player moves as quickly as possible in accordance to a pass made by another player. The time spent in the test was measured by two experienced coaches. Descriptive statistics, repeated measures analysis of variance (ANOVA, 95% limit of agreement (LOA, intraclass correlation coefficient (ICC and standard error of measurements (SEM were used for data analysis. Athletes completed the Functional Test for Agility Performance in 4.15 0.47 s. The ICC value was 0.87 (95% IC = 0.80-0.92. The SEM varied between 0.24 and 0.38 s. The LOA was 1.20 s and the CV average considering each individual trial was 6%. The Functional Test for Agility Performance was shown to be a reliable quick decision-making test for skilled water polo players.

Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

Science.gov (United States)

Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

2015-12-01

Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis.

Science.gov (United States)

Douglas, Pauline; Ye, Ruiqiong; Trinkle-Mulcahy, Laura; Neal, Jessica A; De Wever, Veerle; Morrice, Nick A; Meek, Katheryn; Lees-Miller, Susan P

2014-06-25

The protein kinase activity of the DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and its autophosphorylation are critical for DBS (DNA double-strand break) repair via NHEJ (non-homologous end-joining). Recent studies have shown that depletion or inactivation of DNA-PKcs kinase activity also results in mitotic defects. DNA-PKcs is autophosphorylated on Ser2056, Thr2647 and Thr2609 in mitosis and phosphorylated DNA-PKcs localize to centrosomes, mitotic spindles and the midbody. DNA-PKcs also interacts with PP6 (protein phosphatase 6), and PP6 has been shown to dephosphorylate Aurora A kinase in mitosis. Here we report that DNA-PKcs is phosphorylated on Ser3205 and Thr3950 in mitosis. Phosphorylation of Thr3950 is DNA-PK-dependent, whereas phosphorylation of Ser3205 requires PLK1 (polo-like kinase 1). Moreover, PLK1 phosphorylates DNA-PKcs on Ser3205 in vitro and interacts with DNA-PKcs in mitosis. In addition, PP6 dephosphorylates DNA-PKcs at Ser3205 in mitosis and after IR (ionizing radiation). DNA-PKcs also phosphorylates Chk2 on Thr68 in mitosis and both phosphorylation of Chk2 and autophosphorylation of DNA-PKcs in mitosis occur in the apparent absence of Ku and DNA damage. Our findings provide mechanistic insight into the roles of DNA-PKcs and PP6 in mitosis and suggest that DNA-PKcs' role in mitosis may be mechanistically distinct from its well-established role in NHEJ.

Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

International Nuclear Information System (INIS)

Fitzgerald, Kent; Bergeron, Marcelle; Willits, Christopher; Bowers, Simeon; Aubele, Danielle L.; Goldbach, Erich; Tonn, George; Ness, Daniel; Olaharski, Andrew

2013-01-01

Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646 decreased

Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

Energy Technology Data Exchange (ETDEWEB)

Fitzgerald, Kent, E-mail: Kent.fitzgerald@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bergeron, Marcelle, E-mail: Marcelle.bergeron@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Willits, Christopher, E-mail: Chris.willits@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bowers, Simeon, E-mail: Simeon.bowers@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Aubele, Danielle L., E-mail: Danielle.aubele@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Goldbach, Erich, E-mail: Erich.goldbach@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Tonn, George, E-mail: George.tonn@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Ness, Daniel, E-mail: Dan.ness@elan.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Olaharski, Andrew, E-mail: andrew.olaharski@agios.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States)

2013-05-15

Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646

Položaj nacionalnih i vjerskih manjina u Bosni i Hercegovini

OpenAIRE

Kukić, Slavo

2002-01-01

Autor analizira rezultate empirijskog istraživanja “Položaj nacionalnih i vjerskih manjina u Bosni i Hercegovini”. Istraživanje je pokazalo da se u svoje predratne domove najsporije vraćaju građani srpske nacionalnosti. Spremnost na povratak iskazuje preko sedamdeset posto građana BiH. Što se tiče ljudskih prava, preko polovice stanovništva smatra da su u BiH ugrožena temeljna ljudska prava. Autor smatra da je rat doveo do velikih demografskih pokreta stanovništva te je utjecao na radikalno p...

TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans

Science.gov (United States)

Washington, A. Valance; Gibot, Sébastien; Acevedo, Ismael; Gattis, James; Quigley, Laura; Feltz, Robert; De La Mota, Alina; Schubert, Rebecca L.; Gomez-Rodriguez, Julio; Cheng, Jun; Dutra, Amalia; Pak, Evgenia; Chertov, Oleg; Rivera, Linette; Morales, Jessica; Lubkowski, Jacek; Hunter, Robert; Schwartzberg, Pamela L.; McVicar, Daniel W.

2009-01-01

Triggering receptor expressed on myeloid cells–like (TREM-like) transcript-1 (TLT-1), a type 1 single Ig domain orphan receptor specific to platelet and megakaryocyte α-granules, relocates to the platelet surface upon platelet stimulation. We found here that patients diagnosed with sepsis, in contrast to healthy individuals, had substantial levels of soluble TLT-1 (sTLT-1) in their plasma that correlated with the presence of disseminated intravascular coagulation. sTLT-1 bound to fibrinogen and augmented platelet aggregation in vitro. Furthermore, the cytoplasmic domain of TLT-1 could also bind ezrin/radixin/moesin family proteins, suggesting its ability to link fibrinogen to the platelet cytoskeleton. Accordingly, platelets of Treml1–/– mice failed to aggregate efficiently, extending tail-bleeding times. Lipopolysaccharide-treated Treml1–/– mice developed higher plasma levels of TNF and D-dimers than wild-type mice and were more likely to succumb during challenge. Finally, Treml1–/– mice were predisposed to hemorrhage associated with localized inflammatory lesions. Taken together, our findings suggest that TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. Therefore, therapeutic modulation of TLT-1–mediated effects may provide clinical benefit to patients with hypercoagulatory conditions, including those associated with inflammation. PMID:19436112

Towards Prognostic Profiling of Non-Small Cell Lung Cancer: New Perspectives on the Relevance of Polo-Like Kinase 1 Expression, the TP53 Mutation Status and Hypoxia

Science.gov (United States)

Van den Bossche, Jolien; Deben, Christophe; Op de Beeck, Ken; Deschoolmeester, Vanessa; Hermans, Christophe; De Pauw, Ines; Jacobs, Julie; Van Schil, Paul; Vermorken, Jan Baptist; Pauwels, Patrick; Peeters, Marc; Lardon, Filip; Wouters, An

2017-01-01

Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area. While several studies reported Plk1 overexpression in a broad range of human malignancies, inconsistent results were published regarding the clinical significance hereof. A prognostic panel, consisting of Plk1 and additional biomarkers that are related to the Plk1 pathway, might further improve prediction of patient prognosis. Methods: In this study, we evaluated for the first time the prognostic value of Plk1 mRNA and protein expression in combination with the TP53 mutation status (next generation sequencing), induction of apoptotic cell death (immunohistochemistry for cleaved caspase 3) and hypoxia (immunohistochemistry for carbonic anhydrase IX (CA IX)) in 98 NSCLC adenocarcinoma patients. Results: Both Plk1 mRNA and protein expression and CA IX protein levels were upregulated in the majority of tumor samples. Plk1 mRNA and protein expression levels were higher in TP53 mutant samples, suggesting that Plk1 overexpression is, at least partially, the result of loss of functional p53 (<0.05). Interestingly, the outcome of patients with both Plk1 mRNA and CA IX protein overexpression, who also harbored a TP53 mutation, was much worse than that of patients with aberrant expression of only one of the three markers (p=0.001). Conclusion: The combined evaluation of Plk1 mRNA expression, CA IX protein expression and TP53 mutations shows promise as a prognostic panel in NSCLC patients. Moreover

La autotrascendencia del sentido en Heidegger, según Apel y Polo

OpenAIRE

Ortiz-de-Landázuri, C. (Carlos)

2003-01-01

Martin Heidegger planteó la pregunta acerca de la autotrascendencia del sentido en contraste con sus anteriores análisis autodestructivos del sentido del ser. Según Apel y Polo, Heidegger llevó a cabo una transformación semiotica o un giro sapiencial en el modo de concebir la filosofia, con capacidad de autotranscender los límites semióticos y gnoscológicos que ellos mismos habían detectado anteriormente en su proyecto programático a favor de la metafísica. El artículo trata de mostrar a este...

The influence of game duration and playing position on intensity of exercise during match-play in elite water polo players.

Science.gov (United States)

Platanou, T; Geladas, N

2006-11-01

In this study, we assessed exercise intensity in 20 water polo games of different duration. The hypothesis that right wing players perform at a higher intensity than back and forward central players was also tested. Thirty water polo players, equally split between three field positions, participated in the study. Initially, their performance-related physiological capabilities were evaluated. Subsequently, during water polo games of short (4 x 7-min periods) or long duration (4 x 9-min periods), heart rate was monitored continuously and blood lactate concentration was measured at the end of each period. Activity patterns were also recorded using a video camera. Mean heart rate over the entire game was 156 +/- 18 beats x min(-1). Overall exercise intensity fluctuated around a value corresponding to the lactate threshold (4.03 +/- 0.96 mmol x l(-1), 86 +/- 5% of peak heart rate) and decreased (P game time (4.22 +/- 1.8 and 3.47 +/- 1.9 mmol x l(-1) in the second and fourth quarter, respectively). During the last 6 min, heart rate was higher (P games of short duration (156 +/- 3 beats x min(-1)) than in games of long duration (152 +/- 8 beats x min(-1)). Video analysis showed that the percentage of time spent in low-intensity activities (i.e. "out of game") was lower (23 vs. 26%), whereas that in high-intensity activities (i.e. "sprinting crawl") was higher (21 vs. 19%), in games of short compared with long duration. No difference was observed among players of various field positions in any of the variables examined. Thus during match-play, games of long duration produced significantly lower heart rate responses than games of short duration, and the physiological response exhibited by the players was not affected by field position. The water polo authorities should consider these results before changing game duration and coaches should prepare their athletes accordingly.

MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1

International Nuclear Information System (INIS)

Liu, Jing; Lu, Kai-Hua; Liu, Zhi-Li; Sun, Ming; De, Wei; Wang, Zhao-Xia

2012-01-01

Polo-like kinase 1 (PLK1) is highly expressed in many human cancers and regulates critical steps in mitotic progression. Previously, we have reported that PLK1 was overexpressed in non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms are not well understood. By using microRNA (miR) target prediction algorithms, we identified miR-100 that might potentially bind the 3’-untranslated region of PLK1 transcripts. The purpose of this study was to investigate the roles of miR-100 and its association with PLK1 in NSCLC development. Taqman real-time quantitative RT-PCR assay was performed to detect miR-100 expression 10 NSCLC tissues and corresponding nontumor tissues. Additionally, the expression of miR-100 in 110 NSCLC tissues and its correlation with clinicopathological factors or prognosis of patients was analyzed. Finally, the effects of miR-100 expression on growth, apoptosis and cell cycle of NSCLC cells by posttranscriptionally regulating PLK1 expression were determined. MiR-100 was significantly downregulated in NSCLC tissues, and low miR-100 expression was found to be closely correlated with higher clinical stage, advanced tumor classification and lymph node metastasis of patients. The overall survival of NSCLC patients with low miR-100 was significantly lower than that of those patients with high miR-100, and univariate and multivariate analyses indicated that low miR-100 expression might be a poor prognostic factor. Also, miR-100 mimics could lead to growth inhibition, G 2 /M cell cycle arrest and apoptosis enhancement in NSCLC cells. Meanwhile, miR-100 mimics could significantly inhibit PLK1 mRNA and protein expression and reduce the luciferase activity of a PLK1 3’ untranslated region-based reporter construct in A549 cells. Furthermore, small interfering RNA (siRNA)-mediated PLK1 downregulation could mimic the effects of miR-100 mimics while PLK1 overexpression could partially rescue the phenotypical changes of NSCLC cells induced by

Human neutrophils facilitate tumor cell transendothelial migration.

LENUS (Irish Health Repository)

Wu, Q D

2012-02-03

Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

Estudios sobre la libertad en la filosofía de Leonardo Polo

OpenAIRE

Zorroza, M.I. (María Idoya); González-Gonocchio, D. (David)

2012-01-01

Como los trabajos dejan de manifiesto, la filosofía de la libertad de Polo no es pura especulación trascendental, abstracta y alejada de lo empírico. Por el contrario, la libertad inclina a la consideración de todas las dimensiones de lo humano. Es de agradecer que los participantes del congreso hayan abordado temas tan distintos: pedagogía, psicología, epistemología, filosofía de la eco­nomía, de la ciencia, de la historia, del arte, de la cultura, etc. Hemos intentado que el orden de los tr...

Cross-sensory facilitation reveals neural interactions between visual and tactile motion in humans

Directory of Open Access Journals (Sweden)

Monica eGori

2011-04-01

Full Text Available Many recent studies show that the human brain integrates information across the different senses and that stimuli of one sensory modality can enhance the perception of other modalities. Here we study the processes that mediate cross-modal facilitation and summation between visual and tactile motion. We find that while summation produced a generic, non-specific improvement of thresholds, probably reflecting higher-order interaction of decision signals, facilitation reveals a strong, direction-specific interaction, which we believe reflects sensory interactions. We measured visual and tactile velocity discrimination thresholds over a wide range of base velocities and conditions. Thresholds for both visual and tactile stimuli showed the characteristic dipper function, with the minimum thresholds occurring at a given pedestal speed. When visual and tactile coherent stimuli were combined (summation condition the thresholds for these multi-sensory stimuli also showed a dipper function with the minimum thresholds occurring in a similar range to that for unisensory signals. However, the improvement of multisensory thresholds was weak and not directionally specific, well predicted by the maximum likelihood estimation model (agreeing with previous research. A different technique (facilitation did, however, reveal direction-specific enhancement. Adding a non-informative pedestal motion stimulus in one sensory modality (vision or touch selectively lowered thresholds in the other, by the same amount as pedestals in the same modality. Facilitation did not occur for neutral stimuli like sounds (that would also have reduced temporal uncertainty, nor for motion in opposite direction, even in blocked trials where the subjects knew that the motion was in the opposite direction showing that the facilitation was not under subject control. Cross-sensory facilitation is strong evidence for functionally relevant cross-sensory integration at early levels of sensory

Automovimiento y crecimiento como característica de la vida según Leonardo Polo

OpenAIRE

Sanguineti, J.J. (Juan José)

2009-01-01

Este artículo analiza las caracterizaciones de la vida como autopoiesis, autoorganización, sistema complejo organizado, en términos de la visión de Polo de la vida como praxis orgánica. Se consideran especialmente las notas del automovimiento y el crecimiento. El viviente puede entenderse a la luz de la concausalidad como sustancia "más que hilemórfica" en cuanto la forma viviente incorpora el movimiento de un modo intrínseco.

Facilitators and barriers in the humanization of childbirth practice in Japan

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Goulet Lise

2010-05-01

Full Text Available Abstract Background Humanizing birth means considering women's values, beliefs, and feelings and respecting their dignity and autonomy during the birthing process. Reducing over-medicalized childbirths, empowering women and the use of evidence-based maternity practice are strategies that promote humanized birth. Nevertheless, the territory of birth and its socio-cultural values and beliefs concerning child bearing can deeply affect birthing practices. The present study aims to explore the Japanese child birthing experience in different birth settings where the humanization of childbirth has been indentified among the priority goals of the institutions concerned, and also to explore the obstacles and facilitators encountered in the practice of humanized birth in those centres. Methods A qualitative field research design was used in this study. Forty four individuals and nine institutions were recruited. Data was collected through observation, field notes, focus groups, informal and semi-structured interviews. A qualitative content analysis was performed. Results All the settings had implemented strategies aimed at reducing caesarean sections, and keeping childbirth as natural as possible. The barriers and facilitators encountered in the practice of humanized birth were categorized into four main groups: rules and strategies, physical structure, contingency factors, and individual factors. The most important barriers identified in humanized birth care were the institutional rules and strategies that restricted the presence of a birth companion. The main facilitators were women's own cultural values and beliefs in a natural birth, and institutional strategies designed to prevent unnecessary medical interventions. Conclusions The Japanese birthing institutions which have identified as part of their mission to instate humanized birth have, as a whole, been successful in improving care. However, barriers remain to achieving the ultimate goal

P1 and N170 components distinguish human-like and animal-like makeup stimuli.

Science.gov (United States)

Luo, Shuwei; Luo, Wenbo; He, Weiqi; Chen, Xu; Luo, Yuejia

2013-06-19

This study used event-related potentials to investigate the sensitivity of P1 and N170 components to human-like and animal-like makeup stimuli, which were derived from pictures of Peking opera characters. As predicted, human-like makeup stimuli elicited larger P1 and N170 amplitudes than did animal-like makeup stimuli. Interestingly, a right hemisphere advantage was observed for human-like but not for animal-like makeup stimuli. Dipole source analyses of 130-200-ms window showed that the bilateral fusiform face area may contribute to the differential sensitivity of the N170 component in response to human-like and animal-like makeup stimuli. The present study suggests that the amplitudes of both the P1 and the N170 are sensitive for the mouth component of face-like stimuli.

Avaliação eletrocardiográfica de equinos após exercício de polo (baixo handicap

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Camila A.O. Bello

2012-12-01

Full Text Available A eletrocardiografia pode ser usada para quantificar o treinamento e o desempenho atlético. Pode ainda avaliar a função cardíaca sob efeito do exercício identificando a influência de anomalias cardíacas, assim como os efeitos deletérios do esforço frente à função cardíaca. Considerando a complexidade do esforço físico inerente a cavalos em competições de polo, juntamente com a carência de relatos na literatura sobre a demanda cardíaca resultante. O objetivo deste estudo foi o de identificar e avaliar eletrocardiograficamente os efeitos cardíacos do exercício de polo em equinos de forma a subsidiar dados para a compreensão da demanda fisiológica cardíaca desta modalidade. Foram avaliados 27 equinos praticante de polo em repouso e entre cinco e dez minutos após o exercício. Os resultados obtidos demonstraram que as alterações observadas na duração e amplitude da onda P e duração do intervalo PR e QT foram consideradas fisiológicas em resposta ao aumento da frequência cardíaca. A onda P difásica encontrada em repouso representou hipertrofia atrial e quando bífida representou diferentes pontos de ativação do nó sinoatrial. Como esperado o complexo QRS não sofreu alterações consideráveis entre os dois momentos. O supradesnível do segmento ST e as variações da onda T observadas após o exercício poderiam representar efeito adverso ao miocárdio, entretanto estudos analisando múltiplos fatores são necessários para confirmar esta associação e definir sua real causa. O aumento do QTc sugeriu fadiga miocárdica leve representando alta demanda cardíaca para esta modalidade. O escore cardíaco demonstrou que estes animais estavam dentro do padrão de adaptação cardíaca para um cavalo atleta. A rápida recuperação cardíaca demonstrou bom condicionamento atlético. O marca-passo atrial mutável foi um achado normal encontrado nos equinos de polo. Foi observada baixa incidência de alterações no

An ontology for human-like interaction systems

OpenAIRE

Albacete García, Esperanza

2016-01-01

This report proposes and describes the development of a Ph.D. Thesis aimed at building an ontological knowledge model supporting Human-Like Interaction systems. The main function of such knowledge model in a human-like interaction system is to unify the representation of each concept, relating it to the appropriate terms, as well as to other concepts with which it shares semantic relations. When developing human-like interactive systems, the inclusion of an ontological module can be valuab...

Human conglutinin-like protein

DEFF Research Database (Denmark)

Jensenius, J C; Thiel, S; Baatrup, G

1985-01-01

The presence in human plasma of a molecule homologous to bovine conglutinin is indicated by the results of biological and immunochemical analysis. The human conglutinin-like protein shows calcium-dependent binding to complement-treated solid phase IgG and immunological cross-reaction with chicken...... anti-bovine conglutinin. The binding of the human protein to complement-treated IgG was inhibited by N-acetyl-D-glucosamine but not by other sugars. Analysis by SDS-PAGE and Western blotting showed reaction of anti-conglutinin with molecules of similar mobility to the monomer and hexamer of bovine...

Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

Science.gov (United States)

Hampson, Robert E.; Song, Dong; Robinson, Brian S.; Fetterhoff, Dustin; Dakos, Alexander S.; Roeder, Brent M.; She, Xiwei; Wicks, Robert T.; Witcher, Mark R.; Couture, Daniel E.; Laxton, Adrian W.; Munger-Clary, Heidi; Popli, Gautam; Sollman, Myriam J.; Whitlow, Christopher T.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

2018-06-01

Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient’s own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

Oxygen uptake in water polo, comparison and agreement in cycle ergometer and eggbeater kick: A pilot study

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Ligia Ignêz Engelmann

Full Text Available Abstract The aim of this study was to compare and verify the agreement of maximal oxygen uptake (VO2 max values obtained from tests on land and in water. Twelve recreational water polo players (30.5 ± 7.7 years; 79.2 ± 7.2 kg body mass; 179.1 ± 5.9 cm height were assessed in two phases: (1 in laboratory with maximal test on a cycle ergometer and (2 in a swimming pool with maximal test in eggbeater kick. Maximum values obtained in the two tests (respectively, cycle ergometer, and eggbeater kick: VO2 max = 40.2 ± 2.7 ml.kg-1.min-1 and 38.4 ± 5.7 ml.kg-1.min-1; RER = 1.17 ± 0.08 and 1.19 ± 0.12; HR max = 181.4 ± 11.7 bpm and 179 ± 11.7 bpm; IEP = 20 and 20 did not show significant differences. According to the Bland-Altman analyses, there were acceptable limits of agreement between the two tests (land and water. Therefore, it can be concluded that the eggbeater kick test is a specific and valid protocol to asses VO2 max in water polo players.

A experiência com gás natural/GLP no polo gesseiro do Araripe, PE

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M. A. C. Oliveira

2014-06-01

Full Text Available Gipsita, sulfato de cálcio dihidratado (CaSO4.2H2O, encontrada no Polo Gesseiro do Araripe, Pernambuco, é considerada a de melhor qualidade no mundo, com teor de pureza variando de 88% a 98%, contendo 79% de sulfato de cálcio e 21% de água de cristalização. Quando desidratada até a perda de 1,5 moléculas de água, constitui-se num hemidrato estável, denominado gesso, cujas características são a capacidade de rehidratação (reação exotérmica, o fenômeno de pega e o retorno à estrutura cristalina. O polo fornece 95% do gesso consumido no Brasil. As reservas são estimadas em 1,2 bilhões de toneladas, quinto volume do mundo. Os fornos do Polo podem ser de contato direto ou indireto entre os gases de combustão e o minério, e quanto ao tipo de funcionamento, batelada ou contínuo. No indireto, os gases aquecem uma superfície metálica que transfere o calor usando lenha ou óleo BPF, já que o contato dos mesmos com a gipsita não é recomendável, podendo ocorrer mistura do material, acarretando alteração das propriedades do gesso. No direto, o gás flui no interior de um cilindro metálico, permitindo maior eficiência na troca térmica. A utilização de gás natural traz vantagens como eficiência da troca térmica, maior volume de processamento e preservação do ecossistema, por ser pouco poluente. Sua combustão é limpa, isenta de fuligem e outros materiais que possam prejudicar o meio ambiente com baixos teores de nitrogênio, dióxido de carbono, água e compostos de enxofre. O gás natural chegou ao Araripe em março de 2011, numa experiência piloto, com expectativa de um salto de qualidade e de volume na produção local. Mais limpo e eficiente, poderá oferecer a segurança energética necessária para que o setor atenda melhor uma demanda crescente, evitando o desmatamento da região que usa a lenha como combustível.

El encomendero Polo de Ondegardo y los mitimaes del valle de Cochabamba: los interrogatorios contra los indios de Paria y Tapacarí

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Villarías Robles, Juan J. R.

1998-12-01

Full Text Available Not available.

Los autores ofrecen una nueva transcripción de dos interrogatorios judiciales relacionados con Polo de Ondegardo (ca. 1520-1575 y la situación en el valle de Cochabamba (Bolivia en el siglo XVI. Los dos documentos ayudan a entender el concepto que tenía Polo de Ondegardo sobre los mitimaes en el imperio inca. También ilustran sobre el importante papel económico que podía llegar a tener esta categoría social en el orden incaico. Los mitimaes no perdían por ello necesariamente la vinculación con sus grupos étnicos de origen, contrariamente a la idea más extendida sobre los llamados “mitimaes del Inca” que se encuentra en la bibliografía.

El Estado y la política de los polos turísticos de desarrollo: el caso de Cancún, México

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Octavio Castillo Pavón

2014-12-01

Full Text Available RESUMEN A cuarenta años de su creación, el polo de desarrollo turístico de Cancún no sólo es el paradigma del éxito económico del turismo, como base de la actividad productiva de la Riviera Maya y del estado de Quintana Roo en su conjunto, sino que es la muestra más clara del impacto que este tipo de actividades, desarticuladas de la realidad económica y social de las regiones en las que se enclavan, tienen en las condiciones de segregación socio-espacial de centros de población cuyo origen está en el impulso de políticas públicas dirigidas, fundamentalmente, a crear nuevas condiciones de acumulación por encima de las necesidades sociales de la población. El presente documento ubica la experiencia de los polos de desarrollo turístico, impulsados en México a partir de la década de los años 70 del siglo pasado, en el marco de las manifestaciones socio-económicas, culturales y, particularmente, espaciales registradas en el país en el último tercio del siglo XX. En particular se analiza el proceso de creación y surgimiento de la ciudad de Cancún como Polo de Desarrollo Turístico Integralmente Planeado, haciendo énfasis en las principales características de su proceso de urbanización y en los resultados socio-territoriales de su creación.

'Wild league' in water polo: An exploration of recreational sports event visit motivation

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Sindik Joško

2016-01-01

Full Text Available Scope of this study was to identify motivational factors related to specific recreational sport event: 'Wild league' in water polo, which takes place in Dubrovnik, have very long tradition. First goal of the study is to determine the relationship between motivational factors related to this event, as well as with socio-demographic variables. Second goal is to determine the differences in motivational factors, according to several independent variables, mainly related to the previous experiences with sports and touristic destination. The cross-sectional study is conducted. The sample of 125 participants was examined, using the Questionnaire on sports event. All participants were Croatian citizens, excluding those who are born, and currently live in Dubrovnik. Major sports tourism motives of the potential tourists in this sporting event, were obtained. In general, the importance of the benefits of sports and tourist destination prevailed, as compared with their limitations, which appeared as an important factor only in participants who didn't visited Dubrovnik yet. At the participants, pull factors, i.e. advanced sports and travel motives slightly dominated over push motives, but statistically significant only in females, who expressed more sophisticated pulling tourist motives, such as the acquisition of knowledge about the destination. Correlations indicate that previous interest in sport, particularly in water polo and Wild League, are moderate positively associated with pushing motives. Moreover, previous recreationally engaging in sports, as well as destination-related origin, appeared as the important factors for having more emphasized pull motives for visiting this sport event. Level of the education did not appear as important factor in differentiating main type of motives in target population. Results provide initial information about the possibility of profiling potential tourists who could be motivated to visit the destination by this

Into the 21st Century with the Istituto Geografico Polare "Silvio Zavatti" and its journal "Il Polo"

Science.gov (United States)

Casarini, M.

2013-12-01

By Maria Pia Casarini We are now nearing the 70th anniversary of the foundation of this unique institution, established in the city of Fermo in the Marche region of Italy by the late Prof. Silvio Zavatti (d. 1985), a true polar enthusiast working before the time when Italy had any official interest in the polar regions. The Institute has the largest and most comprehensive polar library in Italy; a polar museum with Inuit artifacts and relics of expeditions by the Duke of Abruzzi and Umberto Nobile; and it has published a quarterly journal, "Il Polo", since 1945. Given the increasing official role of Italy in both Arctic and Antarctic research, and the increasing interest of Italian institutions and individuals in the rapidly developing problems of Arctic development, governance and environmental protection, the Institute aims to play an increased role in assisting Italian polar efforts through its resources and scholarship. For instance, the Institute is a member of the Arctic Table at the Italian Foreign Ministry by which Italy's role as an observer in the Arctic Council is mapped. The journal "Il Polo" has become bilingual and is becoming a global polar journal with survey papers by distinguished polar leaders. We are linked with PEI (Polar Educators International), which spreads knowledge of the polar regions in schools.

Understanding and changing human behaviour--antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour.

Science.gov (United States)

Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

2014-05-01

This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the 'stages of change model', including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to 'global good', so-called 'social marketing', to improve 'welfare of the individual and society' is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement 'antibiotic mainstreaming' as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society.

Work, Gender and Public Policies: A Women's Experience Study on Polo Naval of Rio Grande

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Claudia Socoowski de Anello e Silva

2016-10-01

Full Text Available This work is the product of reflections from the dissertation project on gender and employment. The aim of this study is to examine in what way the occupation of jobs generated in the Polo Naval of Rio Grande-RS by women. For to understand this hiring dynamics, the starting point is the conceptualization of the categories work and gender in social and legal perspectives to arrive in the discussion of public policies guided by these categories. The following will be describe the scenario that will give factual support for empirical research with the partial discussion of the data already collected.

Polo gastronómico Tomás Jofré

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Regina G. Schlüter

2008-01-01

Full Text Available El turismo gastronómico está adquiriendo cada vez mayor importancia en el mundo, independientemente de si se trata de un país desarrollado o no. En Argentina este tipo de turismo cuenta con una larga tradición, en particular referida al enoturismo que se refleja en la Fiesta Nacional de la Vendimia que se lleva a cabo desde 1936 en la provincia de Mendoza. Hacia fines del siglo XX un plan nacional de turismo hace referencias explícitas a las rutas alimentarias y a partir de allí, desde el sector privado, surgen iniciativas para desarrollar destinos en función de su gastronomía. Una de estas iniciativas se relaciona con la transformación de un pequeño pueblo en un polo gastronómico de gran atracción. En este artículo se presentan los resultados de un estudio que se hizo en el mismo para determinar el perfil de los visitantes y las motivaciones que tienen las personas para desplazarse hacia Tomás Jofré los días domingos.

Understanding and changing human behaviour—antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour

Science.gov (United States)

Tamhankar, Ashok J.

2014-01-01

This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the ‘stages of change model’, including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to ‘global good’, so-called ‘social marketing’, to improve ‘welfare of the individual and society’ is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement ‘antibiotic mainstreaming’ as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society. PMID:24735112

Higher iron bioavailability of a human-like collagen iron complex.

Science.gov (United States)

Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Talent identification and early development of elite water-polo players: a 2-year follow-up study.

Science.gov (United States)

Falk, Bareket; Lidor, Ronnie; Lander, Yael; Lang, Benny

2004-04-01

The processes of talent detection and early development are critical in any sport programme. However, not much is known about the appropriate strategies to be implemented during these processes, and little scientific inquiry has been conducted in this area. The aim of this study was to identify variables of swimming, ball handling and physical ability, as well as game intelligence, which could assist in the selection process of young water-polo players. Twenty-four players aged 14-15 years underwent a battery of tests three times during a 2-year period, before selection to the junior national team. The tests included: freestyle swim for 50, 100, 200 and 400 m, 100-m breast-stroke, 100-m 'butterfly' (with breast-stroke leg motion), 50-m dribbling, throwing at the goal, throw for distance in the water, vertical 'jump' from the water, and evaluation of game intelligence by two coaches. A comparison of those players eventually selected to the team and those not selected demonstrated that, 2 years before selection, selected players were already superior on most of the swim tasks (with the exception of breast-stroke and 50-m freestyle), as well as dribbling and game intelligence. This superiority was maintained throughout the 2 years. Two-way tabulation revealed that, based on baseline scores, the prediction for 67% of the players was in agreement with the final selection to the junior national team. We recommend that fewer swim events be used in the process of selecting young water-polo players, and that greater emphasis should be placed on evaluation of game intelligence.

Avaliação ecocardiográfica de equinos após exercício de polo

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Camila A.O. Bello

2012-11-01

Full Text Available Considerando a complexidade do esforço físico inerente a cavalos em competições de polo e da carência de relatos na literatura sobre os efeitos cardíacos resultantes de um chukker, associado ainda a dinâmica do peso, o objetivo deste estudo foi de avaliar por meio da ecocardiografia, 27 equinos atletas de polo, submetidos à partida treino, em repouso e após o exercício. Os resultados demonstraram que esta modalidade alterou diversos índices ecocardiográfico no período de cinco a dez minutos do término de um chukker. Foram eles, estruturais com: redução da espessura do septo interventricular e parede livre do ventrículo esquerdo e aumento do diâmetro interno do ventrículo esquerdo em sístole, e funcionais como: aumento do débito cardíaco e frequência cardíaca, enquanto que o volume sistólico, a fração de encurtamento e a fração de ejeção reduziram. A perda de peso corporal não foi significativa, portanto não foi associado às alterações ecocardiográficas. Estes resultados sugeriram que a demanda cardíaca foi alta, indicando a importância de um acompanhamento físico e treinamento cardiovascular específico para esta modalidade.

When Humanoid Robots Become Human-Like Interaction Partners: Corepresentation of Robotic Actions

Science.gov (United States)

Stenzel, Anna; Chinellato, Eris; Bou, Maria A. Tirado; del Pobil, Angel P.; Lappe, Markus; Liepelt, Roman

2012-01-01

In human-human interactions, corepresenting a partner's actions is crucial to successfully adjust and coordinate actions with others. Current research suggests that action corepresentation is restricted to interactions between human agents facilitating social interaction with conspecifics. In this study, we investigated whether action…

Polo kinase Cdc5 is a central regulator of meiosis I

Science.gov (United States)

Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-sha; Elkin, Sheryl K.; Amon, Angelika

2013-01-01

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

Seguridad, inseguridad y no seguridad en los polos: una agenda inexistente para dos regiones convenientemente olvidadas...

OpenAIRE

María Cristina Rosas

2002-01-01

El presente artículo se centra en dos de las regiones más ignoradas en la geopolítica inter-nacional: los polos. En este trabajo, la autora pone énfasis en la importancia estratégica deesta zona, las diferencias entre el Ártico y la Antártica y los problemas que reviste, en términossoberanos, para Canadá y Australia cada una de estas regiones. Asimismo, se analizan las gran-des problemáticas relacionadas con su trascendencia internacional como escenarios geo-político-militar-económicos de cap...

Seguridad, inseguridad y no seguridad en los polos: una agenda inexistente para dos regiones convenientemente olvidadas...

Directory of Open Access Journals (Sweden)

María Cristina Rosas

2002-01-01

Full Text Available El presente artículo se centra en dos de las regiones más ignoradas en la geopolítica inter-nacional: los polos. En este trabajo, la autora pone énfasis en la importancia estratégica deesta zona, las diferencias entre el Ártico y la Antártica y los problemas que reviste, en términossoberanos, para Canadá y Australia cada una de estas regiones. Asimismo, se analizan las gran-des problemáticas relacionadas con su trascendencia internacional como escenarios geo-político-militar-económicos de capital importancia.

MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome.

Science.gov (United States)

Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J

2017-06-01

One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Remember like humans

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Ning An

2017-02-01

Full Text Available Visual tracking is a challenging computer vision task due to the significant observation changes of the target. By contrast, the tracking task is relatively easy for humans. In this article, we propose a tracker inspired by the cognitive psychological memory mechanism, which decomposes the tracking task into sensory memory register, short-term memory tracker, and long-term memory tracker like humans. The sensory memory register captures information with three-dimensional perception; the short-term memory tracker builds the highly plastic observation model via memory rehearsal; the long-term memory tracker builds the highly stable observation model via memory encoding and retrieval. With the cooperative models, the tracker can easily handle various tracking scenarios. In addition, an appearance-shape learning method is proposed to update the two-dimensional appearance model and three-dimensional shape model appropriately. Extensive experimental results on a large-scale benchmark data set demonstrate that the proposed method outperforms the state-of-the-art two-dimensional and three-dimensional trackers in terms of efficiency, accuracy, and robustness.

Tutorial Facilitation in the Humanities Based on the Tenets of Carl Rogers

Science.gov (United States)

Heim, Caroline

2012-01-01

This article introduces a model for group facilitation in the humanities based on Carl Rogers' model for group psychotherapy. Certain aspects of Carl Rogers' reflective learning strategies are reappraised and principles, specific only to psychotherapy, are introduced. Five of Rogers' axioms are applied to the tutorial discussion model: a…

Chapecó (SC), para além de polo regional, uma cidade média no oeste catarinense

OpenAIRE

Cristiane Gretzler

2011-01-01

Uma das primeiras cidades criadas no impulso colonizador do Oeste Catarinense, Chapecó, durante vários anos foi à sede administrativa de vasto território, situação que conferiu à cidade uma centralidade que se manifesta ainda hoje. O processo de urbanização brasileira provocou mudanças na estrutura das diferentes cidades, independente de seu porte, suscitando novas análises e interpretações. As metrópoles assumiram novos papéis em escala mundial e, muitas cidades polo regionais, acabam criand...

Enrique Santos Discépolo o el arte de la inversión

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Dulce María Dalbosco

2013-06-01

Full Text Available El objetivo de este artículo es abordar la presencia de lo grotesco y de sus códigos en la obra tanguera de Enrique Santos Discépolo. En ella hallamos algunos textos que invierten los tópicos de ciertos motivos estereotipados del tango, mecanismo que da lugar a auténticas acuarelas grotescas. En esta ocasión nos interesa descifrar los artilugios utilizados por el autor para producir tal efecto, con el fin de comprender, en última instancia, cuál es su concepción de lo grotesco. Atenderemos tanto a las composiciones que pertenecen a lo que la crítica ha denominado “vertiente grotesca” (Conde 2003, Gobello 2004 como a la presencia de rasgos o de recursos de lo grotesco presentes en otros tangos de su autoría.

Sobrecarga de trabalho e adoecimento no Polo Industrial de Manaus

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Gerusa Menezes de Carvalho

2011-12-01

Full Text Available O avanço de doenças como LER/DORT traz como imperativo analisar asnovas formas de organização de trabalho e sua relação com o adoecimento. A pesquisa que fundamenta este artigo buscou compreender o processo de adoecimento no trabalho no Polo Industrial de Manaus (PIM, partindo da fundamentação teórica da Psicodinâmica do Trabalho, que estuda os processos intersubjetivos mobilizados no trabalhar e os destinos possíveis do sofrimento. Utilizou-se a metodologia qualitativa, tendo como instrumento de coleta de dados uma entrevista individual semiestruturada. Participaram cinco trabalhadores de indústrias do PIM, afastados por doença, membros de uma associação para lesionados no trabalho. Os resultados indicam que a organização de trabalho no PIM é marcada por sobrecarga, pressão e outros elementos patogênicos, relacionados às novas formas de gestão, associadas ao modo de acumulação flexível do capital, que contribuem para o agravamento do sofrimento e para a proliferação das novas patologias sociais do trabalho.

POLOS, EIXOS E ZONAS: CIDADES E ORDENAMENTO TERRITORIAL NA AMAZÔNIA

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Saint-Clair Cordeiro da Trindade Júnior

2016-07-01

Full Text Available Uma fase de rápida ocupação do território foi inaugurada a partir da década de 1960 na Amazônia. A presença de empresários, especuladores e migrantes, mediados por ações intencionais do Estado, definiu uma nova forma de ocupação territorial para a região. As estratégias de ação se basearam em pelo menos três tipos principais de ordenamento do território. Não obstante a continuidade existente entre eles, expressam-se em diferentes geometrias do desenvolvimento: os pontos (polos de crescimento, as linhas (eixos de integração e as zonas (zoneamento ecológico-ecomico. Considerando esses diferentes arranjos territoriais, o artigo busca considerar o papel assumido pelas cidades em cada uma dessas estratégias de desenvolvimento regional, de forma a mostrar mudanças e continuidades que se fazem presentes na história regional recentente da Amazônia

Concentra??o nas exporta??es de eletroeletr?nicos do Polo Industrial de Manaus: aspectos quantitativos e percep??es institucionais

OpenAIRE

Lopes, Vitor Cesar Pican?o

2012-01-01

Esta disserta??o tem como objetivo principal analisar a evolu??o da concentra??o das exporta??es do Subsetor de Eletroeletr?nicos do Polo Industrial de Manais - PIM, verificando as poss?veis implica??es de tal fen?meno em termos de afeta??o no ?mbito comercial do mesmo. Os dados da pesquisa compreendem dois n?veis: dados secund?rios de com?rcio exterior, provenientes dos sistemas de acompanhamento e controle do fluxo de exporta??es do Minist?rio da Ind?stria e Com?rcio MDIC e Superint...

Impact of Human like Cues on Human Trust in Machines: Brain Imaging and Modeling Studies for Human-Machine Interactions

Science.gov (United States)

2018-01-05

opponent had some human-likeness. In particular, the research shows that activity in the left parietal region correlating with a human players future ...human-likeness. In particular, our research shows that activity in the left parietal region correlating with a human player’s future behavior can be...this work. - Emotional Conversational Agent: The 4th Korean Flagship AI Project, from December 2016 to December 2020, about US$14,000,000 (Principal

Quality of life after multiple trauma: validation and population norm of the Polytrauma Outcome (POLO) chart.

Science.gov (United States)

Lefering, R; Tecic, T; Schmidt, Y; Pirente, N; Bouillon, B; Neugebauer, E

2012-08-01

Due to an increasing number of survivors after multiple injuries in Western countries, the health-related quality of life (QoL) is considered to be an important outcome parameter. Up to now, measuring instruments used in this field lacked validity and comparability. Within 6 years, our working group developed a new modular instrument, called the Polytrauma Outcome (POLO) chart. This study documents the validation of the trauma-specific module specifically designed for trauma patients, the Trauma Outcome Profile (TOP). A total of 172 multiply injured patients (mean Injury Severity Score [ISS] 26.7) recruited from eight trauma centres participating in the German Trauma Registry were compared with 166 marginally injured patients (mean ISS 3.9). The mean follow-up was 24.2 and 26.4 months, respectively. The validation questionnaires used were the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), Impact of Event Scale-Revised (IES-R), Social Support Questionnaire (F-SOZU-K-22), Barthel Index of Activities of Daily Living (ADL) and the Short Form Health Survey (SF-36). The internal consistency of the different dimensions of QoL assessed with the TOP was good. Factor analysis provides evidence of the construct validity of the questionnaire. Correlation with external measures gives evidence of criterion validity for the various dimensions of QoL and similar exceedance of proposed cut-off points within TOP and external measures is verified. The TOP module is a reliable and valid instrument to assess health-related QoL in patients with multiple injuries. It can be used stand-alone or as part of the POLO chart together with the Glasgow Outcome Scale (GOS), the EuroQoL and the SF-36 as a regular systematic follow-up instrument.

Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment

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Xie, Maorong; Xuan, Baoqin; Shan, Jiaoyu; Pan, Deng; Sun, Yamei; Shan, Zhao; Zhang, Jinping; Yu, Dong

2014-01-01

ABSTRACT Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we

Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice

OpenAIRE

Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

2005-01-01

Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear con...

Transcriptional profiling of adult neural stem-like cells from the human brain.

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Cecilie Jonsgar Sandberg

Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

Human-like Walking with Compliant Legs

NARCIS (Netherlands)

Visser, L.C.; de Geus, Wouter; Stramigioli, Stefano; Carloni, Raffaella

2011-01-01

This work presents a novel approach to robotic bipedal walking. Based on the bipedal spring-mass model, which is known to closely describe human-like walking behavior, a robot has been designed that approaches the ideal model as closely as possible. The compliance of the springs is controllable by

As práticas de gestão de pessoas nas empresas de economia de comunhão: estudo de caso no Polo Spartaco

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Maria Célia Vieira Ladain

Full Text Available Para que uma firma seja considerada empresa de economia de comunhão (EEdC, ela deve seguir princípios específicos, fundamentados nos valores da cultura da partilha, expressos na Carta de Princípios da Empresa de Economia de Comunhão (EdC. Este estudo teve por objetivo verificar se as empresas do Polo Spartaco coadunam os princípios expostos nessa carta, na prática cotidiana da gestão de pessoas, por meio de um estudo de caso descritivo, com abordagem qualiquantitativa, utilizando-se de entrevistas semiestruturadas com os gestores, aplicação de questionário aos funcionários, observação direta e evidências documentais. Os resultados apontam que as práticas de gestão de pessoas das empresas vinculadas ao Polo Spartaco, de fato, coadunam o discurso expresso na Carta de Princípios da EdC. Observou-se que suas práticas de gestão de pessoas, ainda que de forma pouco estruturada, são bem-sucedidas para gerar produtividade, engajamento, participação e consolidação de valores.

Human-like brain hemispheric dominance in birdsong learning.

Science.gov (United States)

Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

2012-07-31

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

Stable panoramic views facilitate snap-shot like memories for spatial reorientation in homing pigeons.

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Tommaso Pecchia

Full Text Available Following spatial disorientation, animals can reorient themselves by relying on geometric cues (metric and sense specified both by the macroscopic surface layout of an enclosed space and prominent visual landmarks in arrays. Whether spatial reorientation in arrays of landmarks is based on explicit representation of the geometric cues is a matter of debate. Here we trained homing pigeons (Columba livia to locate a food-reward in a rectangular array of four identical or differently coloured pipes provided with four openings, only one of which allowed the birds to have access to the reward. Pigeons were trained either with a stable or a variable position of the opening on pipes, so that they could view the array either from the same or a variable perspective. Explicit mapping of configural geometry would predict successful reorientation irrespective of access condition. In contrast, we found that a stable view of the array facilitated spatial learning in homing pigeons, likely through the formation of snapshot-like memories.

Target cell cyclophilins facilitate human papillomavirus type 16 infection.

Science.gov (United States)

Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

2009-07-01

Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

Target cell cyclophilins facilitate human papillomavirus type 16 infection.

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Malgorzata Bienkowska-Haba

2009-07-01

Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

Trabecular evidence for a human-like gait in Australopithecus africanus.

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Meir M Barak

Full Text Available Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb.

The Archive's Weight: Notables daños de no guardar a los indios sus fueros (1571 by Lawyer Polo de Ondegardo

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Oscar Martin Aguierrez

2018-01-01

Full Text Available The notion of Archive is central to know how the colonial logic marks the ways of appropriating America. The Archive is the beginning and the mandate (Derrida, 1997. It organizes, orders and institutes what the gods and men command. It imposes a dynamic in which the texts delimites a readers communities and excludes others comunities. In this articule, Notables daños de no guardar a los indios sus fueros (1571 of Polo of Ondegardo is presented catched into the networks of the Archive. This manuscript contributes to the consolidation of imperial policies introduced by Felipe II and delimits an inside and an outside of Archive. American nature and geographic space, the political system and the economic organization of the Incas, the past, the myth, all that enters into the Archive thanks to the writing. The writing becomes them in manipulable objects and it make them circulates like a secret. Meanwhile, on the outside of Archive, the bodies suffer the violence of a pacification political project that finishes with the death of Tupac Amaru I in the public square of Lima.

Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts

Science.gov (United States)

Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

2016-01-01

Abstract Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes. A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students’ satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students’ satisfaction. Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01). This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was

An Abbreviated Protocol for In Vitro Generation of Functional Human Embryonic Stem Cell-Derived Beta-Like Cells

DEFF Research Database (Denmark)

Massumi, Mohammad; Pourasgari, Farzaneh; Nalla, Amarnadh

2016-01-01

developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems......The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have...... positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux...

A Liberation Health Approach to Examining Challenges and Facilitators of Peer-to-Peer Human Milk Sharing.

Science.gov (United States)

McCloskey, Rebecca J; Karandikar, Sharvari

2018-04-01

Human milk sharing between peers is a common and growing practice. Although human milk has been unequivocally established as the ideal food source for infants, much stigma surrounds the practice of human milk sharing. Furthermore, there is little research examining peer-to-peer human milk sharing. Research Aim: We used the liberation health social work model to examine the experiences of mothers who have received donated human milk from a peer. Research questions were as follows: (a) What challenges do recipient mothers experience in peer-to-peer human milk sharing? (b) What supports do recipient mothers identify in peer-to-peer human milk sharing? Researchers conducted in-depth interviews with mothers ( N = 20) in the United States and Canada who were recipients of peer-to-peer human milk sharing. Researchers independently reviewed transcripts and completed open, axial, and selective coding. The authors discussed conflicts in theme identification until agreement was reached. Challenges to peer-to-peer human milk sharing were (a) substantial effort required to secure human milk; (b) institutional barriers; (c) milk bank specific barriers; and (d) lack of societal awareness and acceptance of human milk sharing. Facilitators included (a) informed decision making and transparency and (b) support from healthcare professionals. Despite risks and barriers, participants continued to pursue peer-to-peer human milk sharing. Informed by a liberation health framework, healthcare professionals-rather than universally discouraging human milk sharing between peers-should facilitate open dialogue with parents about the pros and cons of this practice and about screening recommendations to promote safety and mitigate risk.

Alteraciones del polo posterior en la miopía degenerativa Alterations of the posterior pole in degenerative myopia patients

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Suzel Ivón Lapido Polanco

2012-12-01

Full Text Available La miopía degenerativa constituye una de las causas fundamentales de pérdida de la visión. Esto está relacionado con las alteraciones del polo posterior, que afectan la retina neurosensorial, el epitelio pigmentario de la retina y las capas más internas de la coroides. Su curso lento y progresivo demanda una exploración integral, con seguimiento en el tiempo y constituye un reto para el oftalmólogo. Se realizó una revisión de artículos publicados e indexados en la base de datos de PubMed que se refirieran a las características clínicas del fondo de ojo en pacientes con miopía degenerativa, para describir las principales alteraciones del polo posterior del globo ocular en esta entidad. Se encontró entre las lesiones típicas de la alta miopía, al estafiloma posterior como un signo patognomónico de la enfermedad, asociado a la atrofia coriorretiniana en parches o difusa, así como las estrías de laca y las hemorragias maculares secundarias a ellas o provenientes de membranas neovasculares coroideas. La tomografía de coherencia óptica ha permitido un diagnóstico más preciso de otras lesiones maculares como la foveosquisis, el agujero macular y, más recientemente, la mácula en domo. Los cambios degenerativos del polo posterior parecen guardar relación unos con otros pero la patogenia no ha sido bien esclarecida a pesar de los avances tecnológicos.Degenerative myopia is one of the main causes of visual impairment. This is related to disorders in the posterior pole, affecting the neurosensorial retina, the retinal pigmented epithelium and the inner choroidal layers. The slow and progressive course of this condition demands comprehensive assessment and long follow-up, which is a challenging task for ophthalmologists. A review of the articles indexed in PubMed regarding the clinical characteristics of the fundus in patients with degenerative myopia was made to describe the main disorders of the posterior pole of the eyeball

Systems Analysis of Human Visuo-Myoelectric Control Facilitated by Anodal Transcranial Direct Current Stimulation in Healthy Humans

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Vinh Kha

2018-04-01

Full Text Available Induction of neuroplasticity by transcranial direct current stimulation (tDCS applied to the primary motor cortex facilitates motor learning of the upper extremities in healthy humans. The impact of tDCS on lower limb functions has not been studied extensively so far. In this study, we applied a system identification approach to investigate the impact of anodal transcranial direct current stimulation of the leg area of the motor cortex via the human visuo-myoelectric controller. The visuo-myoelectric reaching task (VMT involves ballistic muscle contraction after a visual cue. We applied a black box approach using a linear ARX (Auto-regressive with eXogenous input model for a visuomotor myoelectric reaching task. We found that a 20th order finite impulse response (FIR model captured the TARGET (single input—CURSOR (single output dynamics during a VMT. The 20th order FIR model was investigated based on gain/phase margin analysis, which showed a significant (p < 0.01 effect of anodal tDCS on the gain margin of the VMT system. Also, response latency and the corticomuscular coherence (CMC time delay were affected (p < 0.05 by anodal tDCS when compared to sham tDCS. Furthermore, gray box simulation results from a Simplified Spinal-Like Controller (SSLC model demonstrated that the input-output function for motor evoked potentials (MEP played an essential role in increasing muscle activation levels and response time improvement post-tDCS when compared to pre-tDCS baseline performance. This computational approach can be used to simulate the behavior of the neuromuscular controller during VMT to elucidate the effects of adjuvant treatment with tDCS.

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons.

Science.gov (United States)

Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M; Campbell, Michael S; Barrell, Daniel; Martin, Kyle J; Mulley, John F; Ravi, Vydianathan; Lee, Alison P; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E G; Sun, Yi; Hertel, Jana; Beam, Michael J; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H; Litman, Gary W; Litman, Ronda T; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F; Wang, Han; Taylor, John S; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M J; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T; Venkatesh, Byrappa; Holland, Peter W H; Guiguen, Yann; Bobe, Julien; Shubin, Neil H; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H

2016-04-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

Better decision making in complex, dynamic tasks training with human-facilitated interactive learning environments

CERN Document Server

Qudrat-Ullah, Hassan

2015-01-01

This book describes interactive learning environments (ILEs) and their underlying concepts. It explains how ILEs can be used to improve the decision-making process and how these improvements can be empirically verified. The objective of this book is to enhance our understanding of and to gain insights into the process by which human facilitated ILEs are effectively designed and used in improving users’ decision making in complex, dynamic tasks. This book is divided into four major parts. Part I serves as an introduction to the importance and complexity of decision making in dynamic tasks. Part II provides background material, drawing upon relevant literature, for the development of an integrated process model on the effectiveness of human facilitated ILEs in improving decision making in dynamic tasks. Part III focuses on the design, development, and application of FishBankILE in laboratory experiments to gather empirical evidence for the validity of the process model. Finally, part IV presents a comprehensi...

Effect of Technological Treatments on Human-Like Leptin Level in Bovine Milk for Human Consumption.

Science.gov (United States)

Magistrelli, Damiano; Rosi, Fabia

2014-07-23

In this experiment, raw milk and commercially available full-cream UHT milk, semi-skimmed UHT milk, skimmed UHT milk, full-cream pasteurized milk, semi-skimmed pasteurized milk and infant formulas for babies between 6 and 12 months of age were analyzed by RIA, with a method using an antibody directed against human leptin and human leptin as reference standard. Raw milk and full-cream UHT milk did not differ for human-like leptin. Leptin content of full-cream pasteurized milk was not different to that of full-cream UHT milk, but it was 14% lower ( p raw milk. Human-like leptin level of semi-skimmed UHT milk was not different to that of semi-skimmed pasteurized milk, but it was 30% lower ( p pasteurized milks. In skimmed UHT milk, leptin was 40% lower ( p milk. Leptin was correlated ( p milks. Results suggest that the heat treatment (pasteurization or UHT) is not a modifier of human-like leptin content of edible commercial bovine milks, whereas the skimming process significantly reduces milk leptin level.

Knowledge and attitudes about sports-related dental injuries and mouthguard use in young athletes in four different contact sports-water polo, karate, taekwondo and handball.

Science.gov (United States)

Galic, Tea; Kuncic, Domagoj; Poklepovic Pericic, Tina; Galic, Ivan; Mihanovic, Frane; Bozic, Josko; Herceg, Mark

2018-03-11

The increasing popularity of participating in sports activities among children and adolescents has increased the risk of sports-related orofacial and dental injuries. Therefore, it is important to establish efficient preventive strategies regarding sports-related dental trauma. The aim of this study was to evaluate the occurrence of sports-related dental injuries in young athletes and to compare the frequency of such injuries between high-risk and medium-risk sports, along with assessing athletes' attitudes and habits regarding mouthguard use. A total of 229 young athletes from four different sports (water polo (n = 59), karate (n = 58), taekwondo (n = 57) and handball (n = 55)) participated in this study. A standardized questionnaire about the frequency of orofacial and dental injuries was used. Questions were also asked about athletes' habits related to mouthguard use. Mean age of the participants was 12.9 ± 3.2 years, and the average time of playing experience was 4.8 ± 3.1 years. Orofacial injury had been experienced by 58 athletes (25.3%), while 31 athletes (13.5%) suffered dental injury. Higher rate of dental injuries was observed in water polo (18.6%), karate (17.2%) and handball (21.8%) than in taekwondo (3.5%) (P = .035). Most participants were aware of mouthguards for dental trauma prevention and considered them efficient for preventing dental injuries during sports activities, but only 94 (41%) used them. There was a statistically significant difference in the use of mouthguards between taekwondo (73.7%) and karate (70.7%) players compared to handball (14.5%) and water polo players (5.1%) (P art sport. Therefore, the classification of sports according to the risk of dental trauma should be reconsidered. It would be beneficial to make wearing a mouthguard mandatory in all high-risk sports, as well as in those with medium-risk for dental injuries. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GESTÃO AMBIENTAL DE ATIVIDADES RURAIS NO POLO DE AGRICULTURA NATURAL DE IPEÚNA, SP

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Luiz Carlos Demattê Filho

2014-12-01

verificadas, como segue: Ecologia da paisagem (0,87, Qualidade da atmosfera (0,78, Qualidade da água (0,91, Qualidade do solo (0,85, Valores socioculturais (0,83, Valores econômicos (0,88 e Gestão e administração (1,00. Todos os indicadores apresentaram índices de desempenho superiores ao nível de conformidade preconizado no sistema de indicadores APOIA-NovoRural. Com estas características de desempenho ambiental, o Polo de Agricultura Natural de Ipeúna representa um empreendimento rural com excelente índice integrado de sustentabilidade (0,87, justificando sua posição de destaque como unidade de experimentação e pesquisa, transferência de tecnologia, e modelo de produção agrícola natural e orgânica.

Geographic Layers as Landscape Drivers for the Marco Polo Argali Habitat in the Southeastern Pamir Mountains of Tajikistan

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Eric Ariel L. Salas

2015-10-01

Full Text Available We described in this report the essential geographic layers used as landscape drivers for the Marco Polo Argali habitat in the eastern Tajik Pamirs. Using remote sensing techniques and geographic information systems (GIS, individual layers were generated in order to acquire more information on argali patterns and habitat suitability and to make the dataset available online. We introduced an improved object-based image analysis in our mapping of the vegetation cover by utilizing spectral, topographic, and texture variables. We exhausted every Landsat image band and texture feature combination to select the best pairing of band-texture components. For vegetation class alone, the producer’s accuracy was 90.8% and the user’s accuracy was 91.6%.

Evidence that the periaqueductal gray matter mediates the facilitation of panic-like reactions in neonatally-isolated adult rats.

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Jeyce Willig Quintino-dos-Santos

Full Text Available Plenty of evidence suggests that childhood separation anxiety (CSA predisposes the subject to adult-onset panic disorder (PD. As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG. Accordingly, here we examined whether the neonatal social isolation (NSI, a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM and forced-swimming test (FST respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2 until weaning (PN21 allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26 whilst siblings (sham-isolated rats, SHAM, n = 27 and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18 remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60 and subjected to sessions of intracranial stimulation (PN65, EPM (PN66 and FST (PN67-PN68. Groups were compared by Fisher's exact test (stimulation sites, likelihood ratio chi-square tests (stimulus-response threshold curves and Bonferroni's post hoc t-tests (EPM and FST, for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate

Understanding and changing human behaviour—antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour

OpenAIRE

Stålsby Lundborg, Cecilia; Tamhankar, Ashok J.

2014-01-01

This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factor...

Human-like motion planning model for driving in signalized intersections

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Yanlei Gu

2017-10-01

Full Text Available Highly automated and fully autonomous vehicles are much more likely to be accepted if they react in the same way as human drivers do, especially in a hybrid traffic situation, which allows autonomous vehicles and human-driven vehicles to share the same road. This paper proposes a human-like motion planning model to represent how human drivers assess environments and operate vehicles in signalized intersections. The developed model consists of a pedestrian intention detection model, gap detection model, and vehicle control model. These three submodels are individually responsible for situation assessment, decision making, and action, and also depend on each other in the process of motion planning. In addition, these submodels are constructed and learned on the basis of human drivers' data collected from real traffic environments. To verify the effectiveness of the proposed motion planning model, we compared the proposed model with actual human driver and pedestrian data. The experimental results showed that our proposed model and actual human driver behaviors are highly similar with respect to gap acceptance in intersections.

Glucose enhancement of human memory: a comprehensive research review of the glucose memory facilitation effect.

Science.gov (United States)

Smith, Michael A; Riby, Leigh M; Eekelen, J Anke M van; Foster, Jonathan K

2011-01-01

The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the 'glucose memory facilitation effect'. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

ANÁLISE DAS AÇÕES DO POLO DE EXCELÊNCIA EM FLORESTAS PARA A INOVAÇÃO E SUA CONTRIBUIÇÃO PARA A O SETOR FLORESTAL EM MINAS GERAIS

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Mariana Luísa da Costa Lage

2016-06-01

Full Text Available A inovação tecnológica assume destaque por manifestar-se como a mais importante força do crescimento econômico. O objetivo deste estudo foi compreender as ações realizadas pelo Polo de Excelência em Florestas em busca da inovação no setor florestal de Minas Gerais. A teoria utilizada discorre sobre o Sistema de Inovação e a Hélice Tríplice, como fundamento para a articulação entre governo, universidade e setor privado na promoção da inovação. Trata-se de uma pesquisa descritiva realizada por meio de análise documental, observação e entrevistas semiestruturadas. Utilizou-se o modelo de processo de inovação de Bessant e Tidd (2009 para analisar em que níveis se concentravam as ações na busca pela inovação. Os resultados da pesquisa apontam que Polo de Excelência em Florestas desenvolveu, entre 2007 e 2013, essencialmente, projetos que buscam gerar inovação, em estágio primário, e quatro deles em estágio de seleção da inovação, em estágio secundário. Destaca-se o projeto Sistema de Informação Florestal, responsável pela criação do Centro de Inteligência Florestal (CIFlorestas, da Biblioteca Virtual Florestal e do Bureau de Inteligência Florestal, como resultados dos esforços do Polo em se tornar referência no setor florestal. 

The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons

Science.gov (United States)

Braasch, Ingo; Gehrke, Andrew R.; Smith, Jeramiah J.; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M.; Campbell, Michael S.; Barrell, Daniel; Martin, Kyle J.; Mulley, John F.; Ravi, Vydianathan; Lee, Alison P.; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E. G.; Sun, Yi; Hertel, Jana; Beam, Michael J.; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H.; Litman, Gary W.; Litman, Ronda T.; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F.; Wang, Han; Taylor, John S.; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M. J.; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A.; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T.; Venkatesh, Byrappa; Holland, Peter W. H.; Guiguen, Yann; Bobe, Julien; Shubin, Neil H.; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H.

2016-01-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before the teleost genome duplication (TGD). The slowly evolving gar genome conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization, and development (e.g., Hox, ParaHox, and miRNA genes). Numerous conserved non-coding elements (CNEs, often cis-regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles of such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses revealed that the sum of expression domains and levels from duplicated teleost genes often approximate patterns and levels of gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes, and the function of human regulatory sequences. PMID:26950095

Kinesiology-Based Robot Foot Design for Human-Like Walking

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SangJoo Kwon

2012-12-01

Full Text Available Compared with the conventional flat foot, the flexible foot is advantageous in implementing human-like walking and much reduces energy consumption. In this paper, from an anatomical and kinesiological point of view, a flexible foot with toes and heels is investigated for a bipedal robot and three critical design parameters for walking stability are drawn, which include stiffness of toes and heels, frontal toe position, and ankle joint position. In addition, a human-like walking trajectory compatible with the flexible foot is proposed by mimicking a human walking pattern. First of all, the zero moment point (ZMP trajectory continuously moves forward without stopping, even in the single support phase. Secondly, the centre of mass (CoM trajectory includes vertical motion similar to that seen in human beings. Thirdly, the ankle trajectory follows the rotational motion of a human foot while being lifted from and landing on the ground. Through the simulation study, it is shown that the suggested design parameters can be applied as useful indices for the mechanical design of biped feet; interestingly, the vertical motion of the centre of mass tends to compensate for the transient response in the initial walking step.

Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

Science.gov (United States)

Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina

2018-02-27

Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

Drug repositioning for enzyme modulator based on human metabolite-likeness.

Science.gov (United States)

Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

2017-05-31

Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for

Parallel workflow tools to facilitate human brain MRI post-processing

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Zaixu eCui

2015-05-01

Full Text Available Multi-modal magnetic resonance imaging (MRI techniques are widely applied in human brain studies. To obtain specific brain measures of interest from MRI datasets, a number of complex image post-processing steps are typically required. Parallel workflow tools have recently been developed, concatenating individual processing steps and enabling fully automated processing of raw MRI data to obtain the final results. These workflow tools are also designed to make optimal use of available computational resources and to support the parallel processing of different subjects or of independent processing steps for a single subject. Automated, parallel MRI post-processing tools can greatly facilitate relevant brain investigations and are being increasingly applied. In this review, we briefly summarize these parallel workflow tools and discuss relevant issues.

Effect of Technological Treatments on Human-Like Leptin Level in Bovine Milk for Human Consumption

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Damiano Magistrelli

2014-07-01

Full Text Available In this experiment, raw milk and commercially available full-cream UHT milk, semi-skimmed UHT milk, skimmed UHT milk, full-cream pasteurized milk, semi-skimmed pasteurized milk and infant formulas for babies between 6 and 12 months of age were analyzed by RIA, with a method using an antibody directed against human leptin and human leptin as reference standard. Raw milk and full-cream UHT milk did not differ for human-like leptin. Leptin content of full-cream pasteurized milk was not different to that of full-cream UHT milk, but it was 14% lower (p < 0.05 than that observed in raw milk. Human-like leptin level of semi-skimmed UHT milk was not different to that of semi-skimmed pasteurized milk, but it was 30% lower (p < 0.0001 than those of full-cream UHT and full-cream pasteurized milks. In skimmed UHT milk, leptin was 40% lower (p < 0.0001 than in full-cream UHT milk. Leptin was correlated (p < 0.001 with lipid content. Leptin level of infant formulas was not different to that of skimmed milks. Results suggest that the heat treatment (pasteurization or UHT is not a modifier of human-like leptin content of edible commercial bovine milks, whereas the skimming process significantly reduces milk leptin level.

Human-like Compliance for Dexterous Robot Hands

Science.gov (United States)

Jau, Bruno M.

1995-01-01

This paper describes the Active Electromechanical Compliance (AEC) system that was developed for the Jau-JPL anthropomorphic robot. The AEC system imitates the functionality of the human muscle's secondary function, which is to control the joint's stiffness: AEC is implemented through servo controlling the joint drive train's stiffness. The control strategy, controlling compliant joints in teleoperation, is described. It enables automatic hybrid position and force control through utilizing sensory feedback from joint and compliance sensors. This compliant control strategy is adaptable for autonomous robot control as well. Active compliance enables dual arm manipulations, human-like soft grasping by the robot hand, and opens the way to many new robotics applications.

Integrating Human Factors Engineering and Information Processing Approaches to Facilitate Evaluations in Criminal Justice Technology Research.

Science.gov (United States)

Salvemini, Anthony V; Piza, Eric L; Carter, Jeremy G; Grommon, Eric L; Merritt, Nancy

2015-06-01

Evaluations are routinely conducted by government agencies and research organizations to assess the effectiveness of technology in criminal justice. Interdisciplinary research methods are salient to this effort. Technology evaluations are faced with a number of challenges including (1) the need to facilitate effective communication between social science researchers, technology specialists, and practitioners, (2) the need to better understand procedural and contextual aspects of a given technology, and (3) the need to generate findings that can be readily used for decision making and policy recommendations. Process and outcome evaluations of technology can be enhanced by integrating concepts from human factors engineering and information processing. This systemic approach, which focuses on the interaction between humans, technology, and information, enables researchers to better assess how a given technology is used in practice. Examples are drawn from complex technologies currently deployed within the criminal justice system where traditional evaluations have primarily focused on outcome metrics. Although this evidence-based approach has significant value, it is vulnerable to fully account for human and structural complexities that compose technology operations. Guiding principles for technology evaluations are described for identifying and defining key study metrics, facilitating communication within an interdisciplinary research team, and for understanding the interaction between users, technology, and information. The approach posited here can also enable researchers to better assess factors that may facilitate or degrade the operational impact of the technology and answer fundamental questions concerning whether the technology works as intended, at what level, and cost. © The Author(s) 2015.

Cognitive Factors Affecting Freeze-like Behavior in Humans.

Science.gov (United States)

Alban, Michael W; Pocknell, Victoria

2017-01-01

Contemporary research on survival-related defensive behaviors has identified physiological markers of freeze/flight/fight. Our research focused on cognitive factors associated with freeze-like behavior in humans. Study 1 tested if an explicit decision to freeze is associated with the psychophysiological state of freezing. Heart rate deceleration occurred when participants chose to freeze. Study 2 varied the efficacy of freezing relative to other defense options and found "freeze" was responsive to variations in the perceived effectiveness of alternative actions. Study 3 tested if individual differences in motivational orientation affect preference for a "freeze" option when the efficacy of options is held constant. A trend in the predicted direction suggested that naturally occurring cognitions led loss-avoiders to select "freeze" more often than reward-seekers. In combination, our attention to the cognitive factors affecting freeze-like behavior in humans represents a preliminary step in addressing an important but neglected research area.

WATER POLO GAME-RELATED STATISTICS IN WOMEN'S INTERNATIONAL CHAMPIONSHIPS: DIFFERENCES AND DISCRIMINATORY POWER

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Yolanda Escalante

2012-09-01

Full Text Available The aims of this study were (i to compare women's water polo game-related statistics by match outcome (winning and losing teams and phase (preliminary, classificatory, and semi-final/bronze medal/gold medal, and (ii identify characteristics that discriminate performances for each phase. The game-related statistics of the 124 women's matches played in five International Championships (World and European Championships were analyzed. Differences between winning and losing teams in each phase were determined using the chi-squared. A discriminant analysis was then performed according to context in each of the three phases. It was found that the game-related statistics differentiate the winning from the losing teams in each phase of an international championship. The differentiating variables were both offensive (centre goals, power-play goals, counterattack goal, assists, offensive fouls, steals, blocked shots, and won sprints and defensive (goalkeeper-blocked shots, goalkeeper-blocked inferiority shots, and goalkeeper-blocked 5-m shots. The discriminant analysis showed the game-related statistics to discriminate performance in all phases: preliminary, classificatory, and final phases (92%, 90%, and 83%, respectively. Two variables were discriminatory by match outcome (winning or losing teams in all three phases: goals and goalkeeper-blocked shots

Discriminatory power of water polo game-related statistics at the 2008 Olympic Games.

Science.gov (United States)

Escalante, Yolanda; Saavedra, Jose M; Mansilla, Mirella; Tella, Victor

2011-02-01

The aims of this study were (1) to compare water polo game-related statistics by context (winning and losing teams) and sex (men and women), and (2) to identify characteristics discriminating the performances for each sex. The game-related statistics of the 64 matches (44 men's and 20 women's) played in the final phase of the Olympic Games held in Beijing in 2008 were analysed. Unpaired t-tests compared winners and losers and men and women, and confidence intervals and effect sizes of the differences were calculated. The results were subjected to a discriminant analysis to identify the differentiating game-related statistics of the winning and losing teams. The results showed the differences between winning and losing men's teams to be in both defence and offence, whereas in women's teams they were only in offence. In men's games, passing (assists), aggressive play (exclusions), centre position effectiveness (centre shots), and goalkeeper defence (goalkeeper-blocked 5-m shots) predominated, whereas in women's games the play was more dynamic (possessions). The variable that most discriminated performance in men was goalkeeper-blocked shots, and in women shooting effectiveness (shots). These results should help coaches when planning training and competition.

Human finger-prick induced pluripotent stem cells facilitate the development of stem cell banking.

Science.gov (United States)

Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A; Loh, Yuin-Han

2014-05-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a "do-it-yourself" basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.

TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis.

Science.gov (United States)

Rueda, Analiz; Sifuentes, Cecilia; Gilman, Robert H; Gutiérrez, Andrés H; Piña, Ruby; Chile, Nancy; Carrasco, Sebastián; Larson, Sandra; Mayta, Holger; Verástegui, Manuela; Rodriguez, Silvia; Gutiérrez-Correa, Marcel; García, Héctor H; Sheen, Patricia; Zimic, Mirko

2011-12-01

Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva. Although the mechanism of infection is not completely understood, it is likely driven by proteolytic activity that degrades the intestinal wall to facilitate oncosphere penetration and further infection. We analyzed the publicly available T. solium EST/DNA library and identified two contigs comprising a full-length cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium cDNA sequence included a proteolytic trypsin-like-domain in the C-terminal region, and a thrombospondin type-1 adherence-domain in the N-terminal region. Both the trypsin-like and adherence domains were expressed independently as recombinant proteins in bacterial systems. TsAg5 showed marginal trypsin-like activity and high sequence similarity to Ag5. The purified antigens were tested in a Western immunoblot assay to diagnose human neurocysticercosis. The sensitivity of the trypsin-like-domain was 96.36% in patients infected with extraparenchymal cysts, 75.44% in patients infected with multiple cysts, and 39.62% in patients with a single cyst. Specificity was 76.70%. The thrombospondin type-1 adherence-domain was not specific for neurocysticercosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Las principales políticas públicas de Formación Docente desde las voces de los actores. El caso de los Polos de Desarrollo (2000-2001

Directory of Open Access Journals (Sweden)

Luis Porta

2017-11-01

Full Text Available En la historia reciente de la formación docente de nuestro país han sucedido diversos procesos que pretendieron generar y construir proyectos de formación diferenciados y con alto recupero pedagógico. En este artículo expondremos, las principales políticas públicas para el sector de la formación docente no universitario que a nuestro criterio merecen ser destacadas y recuperadas. Consideramos que el Magisterio de Educación Básica (MEB, el Programa de Transformación de la Formación Docente (PTFD, el Proyecto Polos de Desarrollo, el Programa de Renovación Pedagógica y la creación del Instituto Nacional de Formación Docente (INFOD, vertebran el esqueleto de políticas públicas más importante desde la restitución democrática en materia de formación docente y cuyas huellas hoy se reconocen sedimentadas de maneras diversas en las instituciones y en el subsistema formador argentino. Recuperaremos particularmente el proyecto “Polos de Desarrollo (2000-2001” a partir de los testimonios de los propios actores y de referentes del campo de la formación docente.

Engineered human broncho-epithelial tissue-like assemblies

Science.gov (United States)

Goodwin, Thomas J. (Inventor)

2012-01-01

Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

Formation and characterization of iron-binding phosphorylated human-like collagen as a potential iron supplement

International Nuclear Information System (INIS)

Deng, Jianjun; Chen, Fei; Fan, Daidi; Zhu, Chenhui; Ma, Xiaoxuan; Xue, Wenjiao

2013-01-01

Iron incorporated into food can induce precipitation and unwanted interaction with other components in food. Iron-binding proteins represent a possibility to avoid these problems and other side effects, as the iron is protected. However, there are several technical problems associated with protein–iron complex formation. In this paper, the iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared under physiological conditions through phosphorylated modification. One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. Spectroscopy analysis, differential scanning calorimetry (DSC) and equilibrium dialysis techniques were employed to investigate the characteristics of the Fe-G6P-HLC. The binding sites (n b ) and apparent association constant (K app ) between iron and phosphorylated HLC were measured at n b = 23.7 and log K app = 4.57, respectively. The amount of iron (Fe 2+ sulfate) binding to phosphorylated HLC was found to be a function of pH and phosphate content. In addition, the solubility and thermal stability of HLC were not significantly affected. The results should facilitate the utilization of HLC as a bioactive iron supplement in the food and medical industry and provide an important theoretical evidence for the application of HLC chelates. - Highlights: • The iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared. • One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. • The binding properties could be modulated through alterations in pH and phosphate content presented in HLC. • A novel strategy for preparing iron-binding proteins was provided

Comparação tecnológica, mineralógica e química da Formação Corumbataí em dois polos cerâmicos distintos visando sua aplicação na indústria de revestimentos cerâmicos

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S. R. Christofoletti

2015-12-01

Full Text Available Resumo No presente trabalho foram estudadas as variações tecnológicas, químicas, mineralógicas e cerâmicas da Formação Corumbataí em três seções geológicas de dois polos cerâmicos distintos no estado de S. Paulo, Tambaú/Porto Ferreira (T/PF e Santa Gertrudes (SG, com intuito de entender as variações que ocorrem nestas matérias primas buscando a diversificação de produtos. Para estudar estas variações, a metodologia empregada constou do levantamento de seções geológicas, análise mineralógica por difração de raios X na sua constituição total e menor que 2 μm, caracterização geoquímica para identificação dos principais elementos por ICP OES/MS e caracterização cerâmica para revestimento. Os resultados mineralógicos e químicos encontrados refletiram diretamente nos característicos cerâmicos obtidos. O sódio, elemento fundente encontrado principalmente no feldspato sódico, é mais abundante nas seções do Polo SG do que nas seções do PoloT/PF; este elemento age durante a sinterização em conjunto com o K das illitas, porém no Polo T/PF o conteúdo de feldspato potássico é maior que em SG; sendo assim, o K disponível pode ser menor. Além dos argilominerais do grupo illita, presente em todas as amostras, foram identificados argilominerais do grupo das esmectitas e caulinitas. De acordo com os resultados dos ensaios cerâmicos, as amostras das seções P-4 e P-11 do Polo T/PF foram classificadas dentro do grupo de absorção de água como BIII (poroso, sendo sua aplicação mais usual na produção de revestimentos com alta porosidade, azulejos e pastilhas, ou na formulação de revestimento pelo processo via seca e via úmida. Já nas amostras da seção P-19 do Polo SG, os resultados obtidos enquadraram-se dentro do grupo BIb, BIIb e BIII possibilitando sua aplicação, principalmente no caso do BIb e BIIb, na produção de revestimento pelo processo via seca ou na composição de massas para a

In vitro human periodontal ligament-like tissue formation with porous poly-L-lactide matrix

International Nuclear Information System (INIS)

Liao, Wen; Okada, Masahiro; Sakamoto, Fumito; Okita, Naoya; Inami, Kaoru; Nishiura, Aki; Hashimoto, Yoshiya; Matsumoto, Naoyuki

2013-01-01

This study aimed to establish an in vitro human periodontal ligament-like tissue (HPdLLT) by three-dimensional culturing of human periodontal ligament fibroblasts (HPdLFs) in a porous poly-L-lactide (PLLA) matrix modified hydrophilically with ammonia solution. After ammonia modification, the surface roughness and culture-medium-soaking-up ability of the PLLA matrix increased, whereas the contact angle of water drops decreased. The thickness, porosity, and pore size of the PLLA matrix were 400 ± 50 μm, 83.3%, and 75–150 μm, respectively. HPdLFs (1 × 10 5 cells) were seeded on the modified PLLA matrix and centrifuged to facilitate seeding into its interior and cultured for 14 days. Scanning electron microscope (SEM) observation, proliferation assay, picrosirius-red staining, and real-time polymerase chain reaction (RT-PCR) for type-1 collagen (COL1), periodontal ligament associated protein-1 (PLAP-1), fibroblast growth factor-2 (FGF-2), and alkaline phosphatase (ALP) mRNA were conducted on days 1, 3, 7, and 14. HPdLFs were observed entirely from the surface to the rear side of the matrix. Cell proliferation analysis, SEM observation, and picrosirius-red staining showed both progressive growth of 3D-cultured HPdLFs and extracellular matrix maturation by the secretion of COL1 and type 3 collagen (COL3) from days 1 to 14. Expressions of COL1, PLAP-1, and FGF-2 mRNA suggested the formation of cellular components and supplementation of extracellular components. Expressions of ALP, COL1, and PLAP-1 mRNA suggested the osteogenic potential of the HPdLLT. The results indicated in vitro HPdLLT formation, and it could be used in future periodontal ligament tissue engineering to achieve optimal periodontal regeneration. - Highlights: • First report on ammonia treated PLLA matrix for in vitro human periodontal ligament-like tissue generation. • Good combination of matrix thickness, pore size, and porosity. • Biodegradable PLLA is also possible to be used in vivo

In vitro human periodontal ligament-like tissue formation with porous poly-L-lactide matrix

Energy Technology Data Exchange (ETDEWEB)

Liao, Wen [Graduate School of Dentistry, Department of Orthodontics, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan); Okada, Masahiro [Department of Biomaterials, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan); Sakamoto, Fumito; Okita, Naoya [Graduate School of Dentistry, Department of Orthodontics, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan); Inami, Kaoru; Nishiura, Aki [Department of Orthodontics, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan); Hashimoto, Yoshiya, E-mail: yoshiya@cc.osaka-dent.ac.jp [Department of Biomaterials, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan); Matsumoto, Naoyuki [Department of Orthodontics, Osaka Dental University, 8-1 Kuzuha-hanazono-cho, Hirakata-shi, Osaka-fu 573-1121 (Japan)

2013-08-01

This study aimed to establish an in vitro human periodontal ligament-like tissue (HPdLLT) by three-dimensional culturing of human periodontal ligament fibroblasts (HPdLFs) in a porous poly-L-lactide (PLLA) matrix modified hydrophilically with ammonia solution. After ammonia modification, the surface roughness and culture-medium-soaking-up ability of the PLLA matrix increased, whereas the contact angle of water drops decreased. The thickness, porosity, and pore size of the PLLA matrix were 400 ± 50 μm, 83.3%, and 75–150 μm, respectively. HPdLFs (1 × 10{sup 5} cells) were seeded on the modified PLLA matrix and centrifuged to facilitate seeding into its interior and cultured for 14 days. Scanning electron microscope (SEM) observation, proliferation assay, picrosirius-red staining, and real-time polymerase chain reaction (RT-PCR) for type-1 collagen (COL1), periodontal ligament associated protein-1 (PLAP-1), fibroblast growth factor-2 (FGF-2), and alkaline phosphatase (ALP) mRNA were conducted on days 1, 3, 7, and 14. HPdLFs were observed entirely from the surface to the rear side of the matrix. Cell proliferation analysis, SEM observation, and picrosirius-red staining showed both progressive growth of 3D-cultured HPdLFs and extracellular matrix maturation by the secretion of COL1 and type 3 collagen (COL3) from days 1 to 14. Expressions of COL1, PLAP-1, and FGF-2 mRNA suggested the formation of cellular components and supplementation of extracellular components. Expressions of ALP, COL1, and PLAP-1 mRNA suggested the osteogenic potential of the HPdLLT. The results indicated in vitro HPdLLT formation, and it could be used in future periodontal ligament tissue engineering to achieve optimal periodontal regeneration. - Highlights: • First report on ammonia treated PLLA matrix for in vitro human periodontal ligament-like tissue generation. • Good combination of matrix thickness, pore size, and porosity. • Biodegradable PLLA is also possible to be used in vivo.

Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

Science.gov (United States)

He, YingYing; Lawlor, Nathan T

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

Facilitation Processes and Skills Supporting EcoCity Development

Directory of Open Access Journals (Sweden)

Carmen Antuña-Rozado

2018-03-01

Full Text Available Ecocities can provide solutions for the improvement of human settlements around the world and the living conditions therein, but in the authors’ experience, only as long as they are able to address the following questions correctly: How to formulate an ecocity concept that, considering issues of general concern, can be at the same time adapted to different local conditions? What are the instruments supporting the development and implementation of ecocity solutions? VTT’s EcoCity concept for sustainable community and neighbourhood regeneration and development has been designed in response to the first question. Likewise, specific methodologies and effective facilitation processes and skills have been developed in response to the second question. Since the methodologies have been discussed in a previous scientific article, the present one focuses on the facilitation processes and skills, and also on other related, fundamental aspects like participation, adaptation, capacity building, etc. Facilitation processes supporting EcoCity development require matching “hard” and “soft” skills in a fluid way. The main findings are discussed with the help of two case studies: one in Medellín (Colombia, and the other one in Zambia.

Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study.

Science.gov (United States)

Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

2016-02-01

Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This

Human-Like Room Segmentation for Domestic Cleaning Robots

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David Fleer

2017-11-01

Full Text Available Autonomous mobile robots have recently become a popular solution for automating cleaning tasks. In one application, the robot cleans a floor space by traversing and covering it completely. While fulfilling its task, such a robot may create a map of its surroundings. For domestic indoor environments, these maps often consist of rooms connected by passageways. Segmenting the map into these rooms has several uses, such as hierarchical planning of cleaning runs by the robot, or the definition of cleaning plans by the user. Especially in the latter application, the robot-generated room segmentation should match the human understanding of rooms. Here, we present a novel method that solves this problem for the graph of a topo-metric map: first, a classifier identifies those graph edges that cross a border between rooms. This classifier utilizes data from multiple robot sensors, such as obstacle measurements and camera images. Next, we attempt to segment the map at these room–border edges using graph clustering. By training the classifier on user-annotated data, this produces a human-like room segmentation. We optimize and test our method on numerous realistic maps generated by our cleaning-robot prototype and its simulated version. Overall, we find that our method produces more human-like room segmentations compared to mere graph clustering. However, unusual room borders that differ from the training data remain a challenge.

Pitch then power: limitations to acceleration in quadrupeds

OpenAIRE

Williams, Sarah B.; Tan, Huiling; Usherwood, James R.; Wilson, Alan M.

2009-01-01

Rapid acceleration and deceleration are vital for survival in many predator and prey animals and are important attributes of animal and human athletes. Adaptations for acceleration and deceleration are therefore likely to experience strong selective pressures?both natural and artificial. Here, we explore the mechanical and physiological constraints to acceleration. We examined two elite athletes bred and trained for acceleration performance (polo ponies and racing greyhounds), when performing...

Audiovisual integration facilitates monkeys' short-term memory.

Science.gov (United States)

Bigelow, James; Poremba, Amy

2016-07-01

Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.

The Motivation for Visiting Recreational Sports Event “Wild League” in Water Polo

Directory of Open Access Journals (Sweden)

Joško Sindik

2017-03-01

Full Text Available The “Wild League” is a recreational sports event, which takes place in Dubrovnik and has an extremely long tradition. The sport that is played in this competition is water polo. A study was conducted in order to identify motivational factors related to this amateur sport. The study had two main goals: to determine basic psychometric properties (construct validity and reliability of the adjusted Questionnaire on sports events (QSE, as well as to determine the differences in motivational factors, according to several independent variables. A sample of 125 participants were examined in this study, using the QSE. All participants were Croatian citizens, and the study did not include those who are born (and currently live in Dubrovnik. The results revealed three-component principal components’ structure, with reliable principal components that represent pushing motives, pulling motives and the limitations. Moreover, previous visiting Dubrovnik and the level of education did not appear as important independent variables to differentiate any sport tourists’ motives. Pushing motives are highly emphasized in males, participants who were actively engaged in sports, or those with Dubrovnik’s heritage. This clearly define some profile of tourist who may be attracted to visit the destination, motivated with “Wild League” event.

A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome.

Science.gov (United States)

Miyamoto, T; Bando, Y; Koh, E; Tsujimura, A; Miyagawa, Y; Iijima, M; Namiki, M; Shiina, M; Ogata, K; Matsumoto, N; Sengoku, K

2016-01-01

About 15% of couples wishing to have children are infertile; approximately half these cases involve a male factor. Polo-like kinase 4 (PLK-4) is a member of the polo protein family and a key regulator of centriole duplication. Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss. Mutational analysis of 81 patients with azoospermia and Sertoli cell-only syndrome (SCOS) identified one man with a heterozygous 13-bp deletion in the Ser/Thr kinase domain of PLK4. Division of centrioles occurred in wild-type PLK4-transfected cells, but was hampered in PLK-4-mutant transfectants, which also showed abnormal nuclei. Thus, this PLK4 mutation might be a cause of human SCOS and nonobstructive azoospermia. © 2015 American Society of Andrology and European Academy of Andrology.

Dynamic perceptions of human-likeness while interacting with a social robot

NARCIS (Netherlands)

Ruijten, P.A.M.; Cuijpers, R.H.

2017-01-01

In human-robot interaction research, much attention is given to the development of socially assistive robots that can have natural interactions with their users. One crucial aspect of such natural interactions is that the robot is perceived as human-like. Much research already exists that

Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

International Nuclear Information System (INIS)

Ramasharma, K.; Li, C.H.

1987-01-01

Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

Science.gov (United States)

Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

2017-04-01

Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

Formation and characterization of iron-binding phosphorylated human-like collagen as a potential iron supplement

Energy Technology Data Exchange (ETDEWEB)

Deng, Jianjun; Chen, Fei; Fan, Daidi, E-mail: fandaidi@nwu.edu.cn; Zhu, Chenhui; Ma, Xiaoxuan; Xue, Wenjiao

2013-10-01

Iron incorporated into food can induce precipitation and unwanted interaction with other components in food. Iron-binding proteins represent a possibility to avoid these problems and other side effects, as the iron is protected. However, there are several technical problems associated with protein–iron complex formation. In this paper, the iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared under physiological conditions through phosphorylated modification. One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. Spectroscopy analysis, differential scanning calorimetry (DSC) and equilibrium dialysis techniques were employed to investigate the characteristics of the Fe-G6P-HLC. The binding sites (n{sub b}) and apparent association constant (K{sub app}) between iron and phosphorylated HLC were measured at n{sub b} = 23.7 and log K{sub app} = 4.57, respectively. The amount of iron (Fe{sup 2+} sulfate) binding to phosphorylated HLC was found to be a function of pH and phosphate content. In addition, the solubility and thermal stability of HLC were not significantly affected. The results should facilitate the utilization of HLC as a bioactive iron supplement in the food and medical industry and provide an important theoretical evidence for the application of HLC chelates. - Highlights: • The iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared. • One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. • The binding properties could be modulated through alterations in pH and phosphate content presented in HLC. • A novel strategy for preparing iron-binding proteins was provided.

Dominant control region of the human β- like globin gene cluster

NARCIS (Netherlands)

Blom van Assendelft, Margaretha van

1989-01-01

The structure and regulation of the human β -like globin gene cluster has been studied extensively. Genetic disorders connected with this gene cluster are responsible for human diseases associated with high levels of morbidity and mortality, such as β-thalassaemia and sickle cell anaemia. The work

The human likeness dimension of the "uncanny valley hypothesis": behavioral and functional MRI findings.

Science.gov (United States)

Cheetham, Marcus; Suter, Pascal; Jäncke, Lutz

2011-01-01

The uncanny valley hypothesis (Mori, 1970) predicts differential experience of negative and positive affect as a function of human likeness. Affective experience of humanlike robots and computer-generated characters (avatars) dominates "uncanny" research, but findings are inconsistent. Importantly, it is unknown how objects are actually perceived along the hypothesis' dimension of human likeness (DOH), defined in terms of human physical similarity. To examine whether the DOH can also be defined in terms of effects of categorical perception (CP), stimuli from morph continua with controlled differences in physical human likeness between avatar and human faces as endpoints were presented. Two behavioral studies found a sharp category boundary along the DOH and enhanced visual discrimination (i.e., CP) of fine-grained differences between pairs of faces at the category boundary. Discrimination was better for face pairs presenting category change in the human-to-avatar than avatar-to-human direction along the DOH. To investigate brain representation of physical change and category change along the DOH, an event-related functional magnetic resonance imaging study used the same stimuli in a pair-repetition priming paradigm. Bilateral mid-fusiform areas and a different right mid-fusiform area were sensitive to physical change within the human and avatar categories, respectively, whereas entirely different regions were sensitive to the human-to-avatar (caudate head, putamen, thalamus, red nucleus) and avatar-to-human (hippocampus, amygdala, mid-insula) direction of category change. These findings show that Mori's DOH definition does not reflect subjective perception of human likeness and suggest that future "uncanny" studies consider CP and the DOH's category structure in guiding experience of non-human objects.

The human likeness dimension of the "uncanny valley hypothesis": behavioural and functional MRI findings.

Directory of Open Access Journals (Sweden)

Marcus eCheetham

2011-11-01

Full Text Available The uncanny valley hypothesis (Mori, 1970 predicts differential experience of negative and positive affect as a function of human likeness. Affective experience of realistic humanlike robots and computer-generated characters (avatars dominates uncanny research, but findings are inconsistent. How objects are actually perceived along the hypothesis’ dimension of human likeness (DOH, defined only in terms of human physical similarity, is unknown. To examine whether the DOH can be defined also in terms of effects of categorical perception (CP, stimuli from morph continua with controlled differences in physical human likeness between avatar and human faces as endpoints were presented. Two behavioural studies found a sharp category boundary along the DOH and enhanced visual discrimination (i.e. CP of fine-grained differences between face pairs at the category boundary. Discrimination was better for face pairs that presented category change in the human-to-avatar than avatar-to-human direction along DOH. To investigate brain representation of physical and category change within the uncanny valley hypothesis’ framework, an event-related fMRI study used the same stimuli in a paired repetition-priming paradigm. Bilateral mid-fusiform areas and a different right mid-fusiform area were sensitive to physical change within the human and avatar categories, respectively, whereas entirely different regions were sensitive to the human-to-avatar (caudate head, putamen, thalamus, red nucleus and avatar-to-human (hippocampus, amygdala, mid-insula direction of category change. Our findings show that Mori's DOH definition does not reflect subjective perception of human likeness and suggest that future uncanny studies consider CP and the DOH category structure in guiding experience of nonhuman objects.

Cells isolated from human periapical cysts express mesenchymal stem cell-like properties.

Science.gov (United States)

Marrelli, Massimo; Paduano, Francesco; Tatullo, Marco

2013-01-01

We provide a detailed description of mesenchymal stem cells (MSCs) isolated from human periapical cysts, which we have termed hPCy-MSCs. These cells have a fibroblast-like shape and adhere to tissue culture plastic surfaces. hPCy-MSCs possess high proliferative potential and self-renewal capacity properties. We characterised the immunophenotype of hPCy-MSCs (CD73(+), CD90(+), CD105(+), CD13(+), CD29(+), CD44(+), CD45(-), STRO-1(+), CD146(+)) by flow cytometry and immunofluorescence. hPCy-MSCs possess the potential to differentiate into osteoblast- and adipocyte-like cells in vitro. Multi-potentiality was evaluated with culture-specific staining and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis for osteo/odontogenic and adipogenic markers. This is the first report to indicate that human periapical cysts contain cells with MSC-like properties. Taken together, our findings indicate that human periapical cysts could be a rich source of MSCs.

Generation of Functional Beta-Like Cells from Human Exocrine Pancreas.

Directory of Open Access Journals (Sweden)

Maria J Lima

Full Text Available Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

Science.gov (United States)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Establishment of functional acinar-like cultures from human salivary glands.

Science.gov (United States)

Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

2015-02-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. © International & American Associations for Dental Research 2014.

Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

Energy Technology Data Exchange (ETDEWEB)

Kan, Lijuan [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Thayer, Patrick [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Fan, Huimin [Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai (China); Ledford, Benjamin; Chen, Miao [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Goldstein, Aaron [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Cao, Guohua [School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); He, Jia-Qiang, E-mail: jiahe@vt.edu [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States)

2016-09-10

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

Facilitative root interactions in intercrops

DEFF Research Database (Denmark)

Hauggaard-Nielsen, H.; Jensen, E.S.

2005-01-01

of root architecture, exudation of growth stimulating substances, and biofumigation. Facilitative root interactions are most likely to be of importance in nutrient poor soils and in low-input agroecosystems due to critical interspecific competition for plant growth factors. However, studies from more...... nitrogen transfer between legumes and non-leguminous plants, exploitation of the soil via mycorrhizal fungi and soil-plant processes which alter the mobilisation of plant growth resources such as through exudation of amino acids, extra-cellular enzymes, acidification, competition-induced modification......Facilitation takes place when plants ameliorate the environment of their neighbours, and increase their growth and survival. Facilitation occurs in natural ecosystems as well as in agroecosystems. We discuss examples of facilitative root interactions in intercropped agroecosystems; including...

Bioelectronic tongue using heterodimeric human taste receptor for the discrimination of sweeteners with human-like performance.

Science.gov (United States)

Song, Hyun Seok; Jin, Hye Jun; Ahn, Sae Ryun; Kim, Daesan; Lee, Sang Hun; Kim, Un-Kyung; Simons, Christopher T; Hong, Seunghun; Park, Tai Hyun

2014-10-28

The sense of taste helps humans to obtain information and form a picture of the world by recognizing chemicals in their environments. Over the past decade, large advances have been made in understanding the mechanisms of taste detection and mimicking its capability using artificial sensor devices. However, the detection capability of previous artificial taste sensors has been far inferior to that of animal tongues, in terms of its sensitivity and selectivity. Herein, we developed a bioelectronic tongue using heterodimeric human sweet taste receptors for the detection and discrimination of sweeteners with human-like performance, where single-walled carbon nanotube field-effect transistors were functionalized with nanovesicles containing human sweet taste receptors and used to detect the binding of sweeteners to the taste receptors. The receptors are heterodimeric G-protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member 2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have multiple binding sites and allow a human tongue-like broad selectivity for the detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a powerful tool for the detection of sweeteners as an alternative to labor-intensive and time-consuming cell-based assays and the sensory evaluation panels used in the food and beverage industry. Furthermore, this study also allows the artificial sensor to exam the functional activity of dimeric GPCRs.

Consequences of evolution: is rhinosinusitis, like otitis media, a unique disease of humans?

Science.gov (United States)

Bluestone, Charles D; Pagano, Anthony S; Swarts, J Douglas; Laitman, Jeffrey T

2012-12-01

We hypothesize that if otitis media is most likely primarily a human disease due to consequences of evolution, rhinosinusitis may also be limited to humans for similar reasons. If otitis media, with its associated hearing loss, occurred in animals in the wild, they probably would have been culled out by predation. Similarly, if rhinosinusitis occurred regularly in animals, they likely would have suffered from severely decreased olfactory abilities, crucial for predator avoidance, and presumably would likewise have been selected against evolutionarily. Thus, both otitis media and rhinosinusitis-common conditions particularly in infants and young children-appear to be essentially human conditions. Their manifestation in our species is likely due to our unique evolutionary trajectory and may be a consequence of adaptations, including adaptations to bipedalism and speech, loss of prognathism, and immunologic and environmental factors.

Asteroid electrostatic instrumentation and modelling

Energy Technology Data Exchange (ETDEWEB)

Aplin, K L; Bowles, N E; Urbak, E [Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH (United Kingdom); Keane, D; Sawyer, E C, E-mail: k.aplin1@physics.ox.ac.uk [RAL Space, R25, Harwell Oxford, Didcot OX11 0QX (United Kingdom)

2011-06-23

Asteroid surface material is expected to become photoelectrically charged, and is likely to be transported through electrostatic levitation. Understanding any movement of the surface material is relevant to proposed space missions to return samples to Earth for detailed isotopic analysis. Motivated by preparations for the Marco Polo sample return mission, we present electrostatic modelling for a real asteroid, Itokawa, for which detailed shape information is available, and verify that charging effects are likely to be significant at the terminator and at the edges of shadow regions for the Marco Polo baseline asteroid, 1999JU3. We also describe the Asteroid Charge Experiment electric field instrumentation intended for Marco Polo. Finally, we find that the differing asteroid and spacecraft potentials on landing could perturb sample collection for the short landing time of 20min that is currently planned.

Human-like robots as platforms for electroactive polymers (EAP)

Science.gov (United States)

Bar-Cohen, Yoseph

2008-03-01

Human-like robots, which have been a science fiction for many years, are increasingly becoming an engineering reality thanks to many technology advances in recent years. Humans have always sought to imitate the human appearance, functions and intelligence and as the capability progresses they may become our household appliance or even companion. Biomimetic technologies are increasingly becoming common tools to support the development of such robots. As artificial muscles, electroactive polymers (EAP) are offering important actuation capability for making such machines lifelike. The current limitations of EAP are hampering the possibilities that can be adapted in such robots but progress is continually being made. As opposed to other human made machines and devices, this technology raises various questions and concerns that need to be addressed. These include the need to prevent accidents, deliberate harm, or their use in crimes. In this paper the state-of-the-art and the challenges will be reviewed.

Differentiation of human multipotent dermal fibroblasts into islet-like cell clusters

Directory of Open Access Journals (Sweden)

Liu Wei

2010-06-01

Full Text Available Abstract Background We have previously obtained a clonal population of cells from human foreskin that is able to differentiate into mesodermal, ectodermal and endodermal progenies. It is of great interest to know whether these cells could be further differentiated into functional insulin-producing cells. Results Sixty-one single-cell-derived dermal fibroblast clones were established from human foreskin by limiting dilution culture. Of these, two clones could be differentiated into neuron-, adipocyte- or hepatocyte-like cells under certain culture conditions. In addition, those two clones were able to differentiate into islet-like clusters under pancreatic induction. Insulin, glucagon and somatostatin were detectable at the mRNA and protein levels after induction. Moreover, the islet-like clusters could release insulin in response to glucose in vitro. Conclusions This is the first study to demonstrate that dermal fibroblasts can differentiate into insulin-producing cells without genetic manipulation. This may offer a safer cell source for future stem cell-based therapies.

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

Science.gov (United States)

Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

2017-06-01

In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells. Copyright © 2017 Endocrine Society

Occurrence and structural characterization of versican-like proteoglycan in human vitreous.

Science.gov (United States)

Theocharis, Achilleas D; Papageorgakopoulou, Nickoletta; Feretis, Elias; Theocharis, Dimitrios A

2002-12-01

Human vitreous gel is a special type of extracellular matrix, in which interpenetrating networks of collagen fibrils and hyaluronan are found. In this study, we report that apart from significant amounts of collagen, hyaluronan and sialylated glycoproteins, it was found that the human vitreous gel also contained low amounts of versican-like proteoglycan. The concentration of versican-like proteoglycan in the whole vitreous is 0.06 mg protein/ml of vitreous gel and represents a small percentage (about 5%) of the total protein content. The versican-like proteoglycan has a molecular mass of 380 kDa, as estimated by gel chromatography. Its core protein is substituted by chondroitin sulphate side chains (average molecular weight 37 kDa), in which 6-sulphated disaccharides predominated. According to the physicochemical data, the number of chondroitin sulphate chains is likely to be 5-7 per molecule. These proteoglycan monomers form large aggregates with endogenous hyaluronan. Versican, which is able to bind lectins via its C-terminal region, may bridge or interconnect various constituents of the extracellular matrix via its terminal domains in order to stabilize large supramolecular complexes at the vitreous, contributing towards the integrity and specific properties of the tissue.

Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas

DEFF Research Database (Denmark)

Dezso, Katalin; Halász, Judit; Bisgaard, Hanne Cathrine

2008-01-01

Delta-like protein (DLK) is a membrane protein with mostly unknown function. It is expressed by several embryonic tissues among others by the hepatoblasts of rodent and human fetal livers. We have investigated in the present study if this protein is expressed in human hepatoblastomas. The presenc...

Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.

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Ben Hudjetz

2012-01-01

Full Text Available Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics. Interplay of human- (PB2 627K and avian-like (PB2 627E influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission. Here, we have identified human importin-α isoforms (α1 and α7 as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of α1 and α7 to viral ribonucleoprotein complexes (vRNPs without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in α1 and α7 downregulated human lung cells. Mice lacking α7 were less susceptible to human- but not avian-like influenza virus infection. Thus, α1 and α7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.

Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels

International Nuclear Information System (INIS)

Zhang, Jingjing; Ma, Xiaoxuan; Fan, Daidi; Zhu, Chenhui; Deng, Jianjun; Hui, Junfeng; Ma, Pei

2014-01-01

Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H and E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair. - Highlights: • Human-like collagen was used with hyaluronic acid to prepare soft tissue filling meterials. • 1,4-Butanediol diglycidyl ether (BDDE) was introduced to treat the hydrogels. • The addition of human-like collagen could improve the biological properties of hydrogels

Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jingjing; Ma, Xiaoxuan, E-mail: xiaoxuanma@163.com; Fan, Daidi, E-mail: fandaidi@nwu.edu.cn; Zhu, Chenhui; Deng, Jianjun; Hui, Junfeng; Ma, Pei

2014-10-01

Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H and E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair. - Highlights: • Human-like collagen was used with hyaluronic acid to prepare soft tissue filling meterials. • 1,4-Butanediol diglycidyl ether (BDDE) was introduced to treat the hydrogels. • The addition of human-like collagen could improve the biological properties of hydrogels.

From Teaching to Facilitation

DEFF Research Database (Denmark)

de Graaff, Erik

2013-01-01

A shift from teaching to learning is characteristic of the introduction of Problem Based Learning (PBL) in an existing school. As a consequence the teaching staff has to be trained in skills like facilitating group work and writing cases. Most importantly a change in thinking about teaching...

In Vivo-Like Culture Conditions in a Bioreactor Facilitate Improved Tissue Quality in Corneal Storage.

Science.gov (United States)

Schmid, Richard; Tarau, Ioana-Sandra; Rossi, Angela; Leonhardt, Stefan; Schwarz, Thomas; Schuerlein, Sebastian; Lotz, Christian; Hansmann, Jan

2018-01-01

The cornea is the most-transplanted tissue worldwide. However, the availability and quality of grafts are limited due to the current methods of corneal storage. In this study, a dynamic bioreactor system is employed to enable the control of intraocular pressure and the culture at the air-liquid interface. Thereby, in vivo-like storage conditions are achieved. Different media combinations for endothelium and epithelium are tested in standard and dynamic conditions to enhance the viability of the tissue. In contrast to culture conditions used in eye banks, the combination of the bioreactor and biochrom medium 1 allows to preserve the corneal endothelium and the epithelium. Assessment of transparency, swelling, and the trans-epithelial-electrical-resistance (TEER) strengthens the impact of the in vivo-like tissue culture. For example, compared to corneas stored under static conditions, significantly lower optical densities and significantly higher TEER values were measured (p-value <0.05). Furthermore, healing of epithelial defects is enabled in the bioreactor, characterized by re-epithelialization and initiated stromal regeneration. Based on the obtained results, an easy-to-use 3D-printed bioreactor composed of only two parts was derived to translate the technology from the laboratory to the eye banks. This optimized bioreactor facilitates noninvasive microscopic monitoring. The improved storage conditions ameliorate the quality of corneal grafts and the storage time in the eye banks to increase availability and reduce re-grafting. © 2017 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Instructional Design, Facilitation, and Perceived Learning Outcomes: An Exploratory Case Study of a Human Trafficking MOOC for Attitudinal Change

Science.gov (United States)

Watson, Sunnie Lee; Loizzo, Jamie; Watson, William R.; Mueller, Chad; Lim, Jieun; Ertmer, Peggy A.

2016-01-01

This exploratory case study describes the design and facilitation of a massive open online course (MOOC) for attitudinal change regarding human trafficking. It examines the course from the learners', instructor's, and instructional designer's perspectives. Two interviews with the instructor and instructional designer were conducted, and data from…

Human likeness: cognitive and affective factors affecting adoption of robot-assisted learning systems

Science.gov (United States)

Yoo, Hosun; Kwon, Ohbyung; Lee, Namyeon

2016-07-01

With advances in robot technology, interest in robotic e-learning systems has increased. In some laboratories, experiments are being conducted with humanoid robots as artificial tutors because of their likeness to humans, the rich possibilities of using this type of media, and the multimodal interaction capabilities of these robots. The robot-assisted learning system, a special type of e-learning system, aims to increase the learner's concentration, pleasure, and learning performance dramatically. However, very few empirical studies have examined the effect on learning performance of incorporating humanoid robot technology into e-learning systems or people's willingness to accept or adopt robot-assisted learning systems. In particular, human likeness, the essential characteristic of humanoid robots as compared with conventional e-learning systems, has not been discussed in a theoretical context. Hence, the purpose of this study is to propose a theoretical model to explain the process of adoption of robot-assisted learning systems. In the proposed model, human likeness is conceptualized as a combination of media richness, multimodal interaction capabilities, and para-social relationships; these factors are considered as possible determinants of the degree to which human cognition and affection are related to the adoption of robot-assisted learning systems.

Embryonic stem cell-like cells derived from adult human testis

NARCIS (Netherlands)

Mizrak, S. C.; Chikhovskaya, J. V.; Sadri-Ardekani, H.; van Daalen, S.; Korver, C. M.; Hovingh, S. E.; Roepers-Gajadien, H. L.; Raya, A.; Fluiter, K.; de Reijke, Th M.; de la Rosette, J. J. M. C. H.; Knegt, A. C.; Belmonte, J. C.; van der Veen, F.; de rooij, D. G.; Repping, S.; van Pelt, A. M. M.

2010-01-01

Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the

La vocazione territoriale tra approccio sistemico e situazionista: analisi di una collaborazione culture driven tra aziende del made in Italy attraverso il caso del Contratto di Rete Polo Alta Moda Area Vestina / The territorial vocation between the “systemic” approach and the “situationist” approach: analysis of a culture-driven collaboration between Made-in-Italy firms. The case of the network contract of “Polo Alta Moda Area Vestina

Directory of Open Access Journals (Sweden)

Elena Cedrola

2014-06-01

Full Text Available Il presente lavoro si propone di mostrare come una collaborazione culture driven tra aziende del made in Italy possa innescare un processo virtuoso capace di alimentare la competitività d’impresa. Nello specifico, intende verificare la validità di una nuova chiave di lettura dei processi di governance del territorio, detta situazionista, che affianca la concezione prevalente in letteratura, definita unitaria o sistemica. Il punto di discrepanza principale tra le due visioni sembra essere quello della vocazione territoriale. Pur riconoscendo entrambe la presenza di interessi condivisi tra gli attori, la visione situazionista non riconosce alla vocazione la funzione “razionalizzante” riscontrabile nell’approccio sistemico. A seguito di una sintetica review della letteratura sui temi del territorio come cultura condivisa, sulla dimensione reticolare territoriale ed extraterritoriale e sul contratto di rete, verrà introdotto lo studio di un contratto di rete stipulato l’8 giugno 2010 tra le aziende che costituiscono il Polo Alta Moda Area Vestina. Attraverso le evidenze emerse da alcune interviste in profondità, sarà indagato il ruolo dell’azienda Brioni nella duplice veste di key player del territorio e di impresa capofila del contratto di rete analizzato e saranno esaminati gli altri attori che compongono il Polo Alta Moda. Le interviste realizzate hanno coinvolto i manager dell’impresa capofila del contratto di rete, il vice presidente Confindustria Pescara e presidente della Sezione Unificata Sistema Moda Chieti Pescara e il direttore delle fondazioni partecipanti al contratto.   This case study aims to validate how a culture-driven collaboration between firms could trigger the competitiveness of a Country, starting from a specific territorial culture. Specifically, it intends to investigate the validity of a new interpretation of the territorial governance processes, named “situationist”, that supports the prevailing

Role of Genetic Background in Cardiovascular Risk Markers Changes in Water Polo Players.

Science.gov (United States)

Di Mauro, Debora; Currò, Monica; Trimarchi, Fabio; Vecchio, Mercurio; Rizzo, Giuseppina; Barreca, Davide; Visalli, Giuseppa; Ientile, Riccardo; Caccamo, Daniela

2018-05-01

Methylene-tetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms have been associated with hyperhomocysteinemia and oxidative stress increase, that are established cardiovascular risk factors. Given that intense physical activity may increase the susceptibility to adverse cardiovascular outcomes, here we investigated the effects of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms on cardiovascular risk markers in twenty-eight male water polo elite players. The mean plasma levels of homocysteine (Hcy) and advanced oxidation protein products (AOPP) were above reference limits in resting conditions, and increased after competition. Moreover, a positive correlation was found between Hcy and AOPP concentrations, and also between their variations (ratio post-exercise/pre-exercise values) and the variations of lactic dehydrogenase (LDH) and creatine kinase (CK) activities, known as muscle damage markers. The highest Hcy and AOPP values were found in subjects having either MTHFR CT/AC or TT/AA, and PON1 QR192 genotype, respectively. After exercise, Hcy concentrations significantly increased in CT/AC or TT/AA subjects than in athletes having other MTHFR genotypes. A training-induced increase in plasma levels of LDH and CK activities, as well as myoglobin concentrations, was also observed, even if significant differences were found only for CK activity in athletes with MTHFR CT/AC or TT/AA athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Human-Like Behavior of Robot Arms: General Considerations and the Handwriting Task-Part I: Mathematical Description of Human-Like Motion: Distributed Positioning and Virtual Fatigue

NARCIS (Netherlands)

Potkonjak, V.; Tzafestas, S.; Kostic, D.; Djordjevic, G.

2001-01-01

This two-part paper is concerned with the analysis and achievement of human-like behavior by robot arms (manipulators). The analysis involves three issues: (i) the resolution of the inverse kinematics problem of redundant robots, (ii) the separation of the end-effector's motion into two components,

Billion-scale production of hepatocyte-like cells from human induced pluripotent stem cells.

Science.gov (United States)

Yamashita, Tomoki; Takayama, Kazuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki

2018-02-19

Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells are expected to be utilized in drug screening and regenerative medicine. However, hepatocyte-like cells have not been fully used in such applications because it is difficult to produce such cells on a large scale. In this study, we tried to establish a method to mass produce hepatocyte-like cells using a three-dimensional (3D) cell culture bioreactor called the Rotary Cell Culture System (RCCS). RCCS enabled us to obtain homogenous hepatocyte-like cells on a billion scale (>10 9  cells). The gene expression levels of some hepatocyte markers (alpha-1 antitrypsin, cytochrome (CYP) 1A2, CYP2D6, and hepatocyte nuclear factor 4alpha) were higher in 3D-cultured hepatocyte-like cells than in 2D-cultured hepatocyte-like cells. This result suggests that RCCS could provide more suitable conditions for hepatocyte maturation than the conventional 2D cell culture conditions. In addition, more than 90% of hepatocyte-like cells were positive for albumin and could uptake low-density lipoprotein in the culture medium. We succeeded in the large-scale production of homogenous and functional hepatocyte-like cells from human iPS cells. This technology will be useful in drug screening and regenerative medicine, which require enormous numbers of hepatocyte-like cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Huh-7 cell line as an alternative cultural model for the production of human like erythropoietin (EPO

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Kausar Humera

2011-11-01

Full Text Available Abstract Background and Aims Erythropoietin (EPO is a glycoprotein hormone which is required to regulate the production of red blood cells. Deficiency of EPO is known to cause anemia in chronically infected renal patients and they require regular blood transfusion. Availability of recombinant EPO has eliminated the need for blood transfusion and now it is extensively used for the treatment of anemia. Glycosylation of erythropoietin is essential for its secretion, stability, protein conformation and biological activity. However, maintenance of human like glycosylation pattern during manufacturing of EPO is a major challenge in biotechnology. Currently, Chinese hamster ovary (CHO cell line is used for the commercial production of erythropoietin but this cell line does not maintain glycosylation resembling human system. With the trend to eliminate non-human constituent from biopharmaceutical products, as a preliminary approach, we have investigated the potential of human hepatoma cell line (Huh-7 to produce recombinant EPO. Materials and methods Initially, the secretory signal and Kozak sequences was added before the EPO mature protein sequence using overlap extension PCR technique. PCR-amplified cDNA fragments of EPO was inserted into mammalian expression vector under the control of the cytomegalovirus (CMV promoter and transiently expressed in CHO and Huh-7 cell lines. After RT-PCR analysis, ELISA and Western blotting was performed to verify the immunochemical properties of secreted EPO. Results Addition of secretory signal and Kozak sequence facilitated the extra-cellular secretion and enhanced the expression of EPO protein. Significant expression (P Conclusion Huh-7 cell line has a great potential to produce glycosylated EPO, suggesting the use of this cell line to produce glycoproteins of the therapeutic importance resembling to the natural human system.

Monoclonal antibodies directed to human insulin-like growth factor I (IGF I)

International Nuclear Information System (INIS)

Laubli, U.K.; Baier, W.; Celio, M.R.; Binz, H.; Humbel, R.E.

1982-01-01

Mouse hybridomas secreting antibodies to human insulin-like growth factor I (IGF I) were produced by fusion of spleen cells of hyperimmunised mice with FO mouse-myeloma cells. Eight clones producing antibodies against human IGF I have been isolated, two of which have been characterised. One was used in a radioimmunoassay, the other for immunopurification of IGF. (Auth.)

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

DEFF Research Database (Denmark)

Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

2012-01-01

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.

Science.gov (United States)

d'Hennezel, Eva; Abubucker, Sahar; Murphy, Leon O; Cullen, Thomas W

2017-01-01

Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact

HGVA: the Human Genome Variation Archive

OpenAIRE

Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

2017-01-01

Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

Utilization of Human-Like Pelvic Rotation for Running Robot

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Takuya eOtani

2015-07-01

Full Text Available The spring loaded inverted pendulum (SLIP is used to model human running. It is based on a characteristic feature of human running, in which the linear-spring-like motion of the standing leg is produced by the joint stiffness of the knee and ankle. Although this model is widely used in robotics, it does not include human-like pelvic motion. In this study, we show that the pelvis actually contributes to the increase in jumping force and absorption of landing impact. On the basis of this finding, we propose a new model, SLIP2 (spring loaded inverted pendulum with pelvis, to improve running in humanoid robots. The model is composed of a body mass, a pelvis, and leg springs, and, it can control its springs while running by use of pelvic movement in the frontal plane. To achieve running motions, we developed a running control system that includes a pelvic oscillation controller to attain control over jumping power and a landing placement controller to adjust the running speed. We also developed a new running robot by using the SLIP2 model and performed hopping and running experiments to evaluate the model. The developed robot could accomplish hopping motions only by pelvic movement. The results also established that the difference between the pelvic rotational phase and the oscillation phase of the vertical mass displacement affects the jumping force. In addition, the robot demonstrated the ability to run with a foot placement controller depending on the reference running speed.

Differential bacterial capture and transport preferences facilitate co-growth on dietary xylan in the human gut

DEFF Research Database (Denmark)

Leth, Maria Louise; Ejby, Morten; Workman, Christopher

2018-01-01

Metabolism of dietary glycans is pivotal in shaping the human gut microbiota. However, the mechanisms that promote competition for glycans among gut commensals remain unclear. Roseburia intestinalis, an abundant butyrate-producing Firmicute, is a key degrader of the major dietary fibre xylan...... of capture and transport preferences as a possible strategy to facilitate co-growth on abundant dietary fibres and may offer a unique route to manipulate the microbiota based on glycan transport preferences in therapeutic interventions to boost distinct taxa....

Isolated corneal papilloma-like lesion associated with human papilloma virus type 6.

Science.gov (United States)

Park, Choul Yong; Kim, Eo-Jin; Choi, Jong Sun; Chuck, Roy S

2011-05-01

To report a case of a corneal papilloma-like lesion associated with human papilloma virus type 6. A 48-year-old woman presented with a 2-year history of ocular discomfort and gradual visual deterioration in her right eye. Ophthalmic examination revealed an elevated, semitranslucent, well-defined vascularized mass approximately 4 × 2.5 mm in size localized to the right cornea. The surface of the mass appeared smooth and many small, shallow, and irregular elevations were noted. An excisional biopsy was performed. The underlying cornea was markedly thinned, and fine ramifying vasculature was also noted on the exposed corneal stroma. Typical koilocytic change was observed on the histopathologic examination. Polymerase chain reaction revealed the existence of human papilloma virus type 6 DNA. Here we describe a case of an isolated corneal papilloma-like lesion. Although the corneal extension of the limbal or the conjunctival papillomas has been commonly observed, an isolated corneal papilloma-like lesion with underlying stromal destruction has only rarely been reported.

Prevalence of chronic autoimmune thyroiditis in the urban area neighboring a petrochemical complex and a control area in Sao Paulo, Brazil Prevalência de tireoidite de Hashimoto na população vicinal ao Pólo Petroquímico de Capuava (área Polo e área controle (São Bernardo Campo na região metropolitana da grande São Paulo, Brasil

Directory of Open Access Journals (Sweden)

Rosalinda Y. A. Camargo

2006-08-01

Full Text Available PURPOSE: To evaluate the prevalence of chronic autoimmune thyroiditis in 2 urban areas of metropolitan São Paulo (Brazil: Polo Area neighboring a large petrochemical complex and São Bernardo Campo Area (control area. SUBJECTS AND METHODS: Subjects were randomly included from the adult population (20 to 70 years of age of both genders (women 80%, men 20% who voluntarily agreed to participate. From the Polo Area, in the vicinity of a large petrochemical industrial complex, 409 subjects were included; from the control area (São Bernardo Campo Area 420 individuals were included. All subjects were clinically examined, and a detailed record of past thyroid illness and medications was obtained. Ultrasonographic studies were performed using a portable GE Medical Systems apparatus. Blood samples were obtained for free T4, serum TSH, and serum anti-thyroid peroxidase autoantibodies. Urine specimens were collected in Monovette syringes for assaying iodine content. Salt samples were collected at households, and the iodine content was measured. RESULTS: Chronic autoimmune thyroiditis was diagnosed both echographically (marked hypoechogenicity and immunologically (presence of autoantibodies against thyroid peroxidase. In the Polo Area, 15.6% of the examined population had chronic autoimmune thyroiditis, and in the control area (São Bernardo Campo Area, 19.5% of the population had evidence of chronic autoimmune thyroiditis (P > 0.057, not significant. The prevalence of hypothyroidism was 4.9% in the Polo Area and 8.3% in the São Bernardo Campo Area (P = 0.0461 significant. Taking the 2 populations together, 6.6% had hypothyroidism (about one third of these patients were on L-T4 treatment. The mean thyroid volume was 11.2 mL. Domestic salt had a normal concentration of iodine (35.5 + 6.61 mg/kg. Urinary excretion of iodine was above 300 µg Iodine/L in 58.5% of the total population. CONCLUSION: The high iodine intake (above 300 µg Iodine/L of urine that

Retinoic acid combined with spermatogonial stem cell conditions facilitate the generation of mouse germ-like cells

DEFF Research Database (Denmark)

Dong, Guoyi; Shang, Zhouchun; Liu, Longqi

2017-01-01

Spermatogenic lineage has been directly generated in spermatogonial stem cell (SSC) conditions from human pluripotent stem cells (PSCs). However, it remains unknown whether mouse embryonic stem cells (ESCs) can directly differentiate into advanced male germ cell lineage in the same conditions. Here......, we showed rather low efficiency of germ-like cell generation from mouse ESCs in SSC conditions. Interestingly, addition of retinoic acid (RA) into SSC conditions enabled efficient differentiation of mouse ESCs into germ-like cells, as shown by the activation of spermatogenesis-associated genes...... such as Mvh, Dazl, Prdm14, Stella, Scp1, Scp3, Stra8 and Rec8. In contrast, for cells cultured in control medium, the activation of the above genes barely occurred. In addition, RA with SSC conditions yielded colonies of Acrosin-expressing cells and the positive ratio reached a peak at day 6. Our work thus...

Repeated imitation makes human vocalizations more word-like.

Science.gov (United States)

Edmiston, Pierce; Perlman, Marcus; Lupyan, Gary

2018-03-14

People have long pondered the evolution of language and the origin of words. Here, we investigate how conventional spoken words might emerge from imitations of environmental sounds. Does the repeated imitation of an environmental sound gradually give rise to more word-like forms? In what ways do these forms resemble the original sounds that motivated them (i.e. exhibit iconicity)? Participants played a version of the children's game 'Telephone'. The first generation of participants imitated recognizable environmental sounds (e.g. glass breaking, water splashing). Subsequent generations imitated the previous generation of imitations for a maximum of eight generations. The results showed that the imitations became more stable and word-like, and later imitations were easier to learn as category labels. At the same time, even after eight generations, both spoken imitations and their written transcriptions could be matched above chance to the category of environmental sound that motivated them. These results show how repeated imitation can create progressively more word-like forms while continuing to retain a resemblance to the original sound that motivated them, and speak to the possible role of human vocal imitation in explaining the origins of at least some spoken words. © 2018 The Author(s).

Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

Science.gov (United States)

Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

2016-01-19

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2

NARCIS (Netherlands)

Crellin, Natasha K.; Trifari, Sara; Kaplan, Charles D.; Satoh-Takayama, Naoko; Di Santo, James P.; Spits, Hergen

2010-01-01

Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express

The Silk Road, Marco Polo, a Bible and its proteome: a detective story.

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Toniolo, Lucia; D'Amato, Alfonsina; Saccenti, Riccardo; Gulotta, Davide; Righetti, Pier Giorgio

2012-06-18

Around the end of XIII century (at the time of young Marco Polo's first trip to China at the court of Khubilai Khan in Khan Baliq) a pocket Bible was delivered by a Franciscan friar to the Mogul Emperor, in the framework of the evangelization program of the Far East. Four centuries later, in 1685, this Bible was rediscovered by the Jesuit Philippe Couplet in the house of a rich Chinese in Nanchin and donated to Cosimo III, Grand Duke of Tuscany. This Bible was recently "unearthed" in the Biblioteca Medicea Laurenziana in Florence, wrapped up in a precious yellow silk cloth, in a rather ruined state. After two years of restoration, the Bible will return to China in 2012 for a celebration of its >700years of life and of its remarkable return trip on the Silk Road. On account of the thinness of the parchment (barely 80μm thickness, the size of each foil being 16.5×11cm) it was widely held that the pages were produced from foetal lambskins. On tiny fragments of the margins of a foil, after several unsuccessful attempts at digesting the vellum, we were able to obtain a tryptic peptide mixture, which, upon mass spectrometry analysis, yielded the identity of 8 unique proteins, belonging to the genus Bos taurus, thus confirming the origin of the vellum from calfskins rather than from foetal lambskins. Our results prove that it is possible to obtain reliable protein extraction and IDs from ancient parchment documents. Copyright © 2012 Elsevier B.V. All rights reserved.

Interaction between M-like protein and macrophage thioredoxin facilitates antiphagocytosis for Streptococcus equi ssp. zooepidemicus.

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Zhe Ma

Full Text Available Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, S.z is one of the common pathogens that can cause septicemia, meningitis, and mammitis in domesticated species. M-like protein (SzP is an important virulence factor of S. zooepidemicus and contributes to bacterial infection and antiphagocytosis. The interaction between SzP of S. zooepidemicus and porcine thioredoxin (TRX was identified by the yeast two-hybrid and further confirmed by co-immunoprecipitation. SzP interacted with both reduced and the oxidized forms of TRX without inhibiting TRX activity. Membrane anchored SzP was able to recruit TRX to the surface, which would facilitate the antiphagocytosis of the bacteria. Further experiments revealed that TRX regulated the alternative complement pathway by inhibiting C3 convertase activity and associating with factor H (FH. TRX alone inhibited C3 cleavage and C3a production, and the inhibitory effect was additive when FH was also present. TRX inhibited C3 deposition on the bacterial surface when it was recruited by SzP. These new findings indicated that S. zooepidemicus used SzP to recruit TRX and regulated the alternative complement pathways to evade the host immune phagocytosis.

Interaction between M-Like Protein and Macrophage Thioredoxin Facilitates Antiphagocytosis for Streptococcus equi ssp. zooepidemicus

Science.gov (United States)

Ma, Zhe; Zhang, Hui; Zheng, Junxi; Li, Yue; Yi, Li; Fan, Hongjie; Lu, Chengping

2012-01-01

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, S.z) is one of the common pathogens that can cause septicemia, meningitis, and mammitis in domesticated species. M-like protein (SzP) is an important virulence factor of S. zooepidemicus and contributes to bacterial infection and antiphagocytosis. The interaction between SzP of S. zooepidemicus and porcine thioredoxin (TRX) was identified by the yeast two-hybrid and further confirmed by co-immunoprecipitation. SzP interacted with both reduced and the oxidized forms of TRX without inhibiting TRX activity. Membrane anchored SzP was able to recruit TRX to the surface, which would facilitate the antiphagocytosis of the bacteria. Further experiments revealed that TRX regulated the alternative complement pathway by inhibiting C3 convertase activity and associating with factor H (FH). TRX alone inhibited C3 cleavage and C3a production, and the inhibitory effect was additive when FH was also present. TRX inhibited C3 deposition on the bacterial surface when it was recruited by SzP. These new findings indicated that S. zooepidemicus used SzP to recruit TRX and regulated the alternative complement pathways to evade the host immune phagocytosis. PMID:22384152

Human Dental Pulp-Derived Cells Produce Bone-Like Tissue and Exhibit Bone Cell-Like Responsiveness to Mechanical Loading

DEFF Research Database (Denmark)

Kraft, David Christian Evar; Melsen, Birte; Bindslev, Dorthe Arenholt

2010-01-01

and characterize cell lines from human 3rd molar dental pulp tissue to determine whether human dental pulp-derived cells (DPCs) are osteogenic and responsive to mechanical loading by pulsating fluid flow (PFF) in vitro. Methods: Human DPCs used for this study were characterized by measuring proliferation....... We also assessed bone formation by DPCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Results: We found that DPCs are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. Implantation of DPCs resulted...... remodeling in vivo, and therefore provide a promising new tool for regenerative dentistry, for example mineralized tissue engineering to restore bone defects in relation to periodontitis, periimplantatis and orofacial surgery. Experiments in progress have proven that DPCSs are also useful for assessing...

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

Science.gov (United States)

Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

International Nuclear Information System (INIS)

Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

2011-01-01

Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study.

Science.gov (United States)

Korchounov, Alexei; Ziemann, Ulf

2011-08-01

Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory.

Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

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Shumei Man

2008-01-01

Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

DIFFERENCES BETWEEN YOUNG (13-14 YEARS OF AGE WATER POLO PLAYERS SELECTED AND NOT SELECTED TO THE NATIONAL TEAM

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Igor Štirn

2010-09-01

Full Text Available Young water polo players at age 13 to 14 years were examined once a year in a four- year period using three morphological and eight specific skill tests: body height and mass, vital capacity, swimming at distances 5, 25 and 200 meters, swimming 4x5 meters with changing directions, ball dribbling, vertical jump and reach, vertical eggbeater kick and velocity of a throw at the goal. From the sum of 139 players tested, a group of 73 non-selected and of 66 selected players to the national team (U16, wider selection were formed and checked for differences. Differences in all observed variables (except body mass were found between the groups (P<0.05. One significant discriminant function was revealed (canonical R = 0.52 and the accounted variance was 100 %, P = 0.000. The variables that most differentiated the groups were swimming tests at distances of 25 and 200 meters, followed by vertical-egg beater kick and throwing velocity, while morphological variables differentiated the groups least.

A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

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Kampf Caroline

2012-09-01

Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

Formation and characterization of iron-binding phosphorylated human-like collagen as a potential iron supplement.

Science.gov (United States)

Deng, Jianjun; Chen, Fei; Fan, Daidi; Zhu, Chenhui; Ma, Xiaoxuan; Xue, Wenjiao

2013-10-01

Iron incorporated into food can induce precipitation and unwanted interaction with other components in food. Iron-binding proteins represent a possibility to avoid these problems and other side effects, as the iron is protected. However, there are several technical problems associated with protein-iron complex formation. In this paper, the iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared under physiological conditions through phosphorylated modification. One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. Spectroscopy analysis, differential scanning calorimetry (DSC) and equilibrium dialysis techniques were employed to investigate the characteristics of the Fe-G6P-HLC. The binding sites (nb) and apparent association constant (Kapp) between iron and phosphorylated HLC were measured at nb=23.7 and log Kapp=4.57, respectively. The amount of iron (Fe(2+) sulfate) binding to phosphorylated HLC was found to be a function of pH and phosphate content. In addition, the solubility and thermal stability of HLC were not significantly affected. The results should facilitate the utilization of HLC as a bioactive iron supplement in the food and medical industry and provide an important theoretical evidence for the application of HLC chelates. © 2013.

Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.

Science.gov (United States)

Zhang, Xi; Wang, Qifan; Wu, Jianping; Wang, Jiawei; Shi, Yigong; Liu, Minhao

2018-04-10

Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery. Copyright © 2018 the Author(s). Published by PNAS.

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

NARCIS (Netherlands)

W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R.D.H. de Boer (Remco); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef

1997-01-01

textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds

How Facilitation May Interfere with Ecological Speciation

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P. Liancourt

2012-01-01

Full Text Available Compared to the vast literature linking competitive interactions and speciation, attempts to understand the role of facilitation for evolutionary diversification remain scarce. Yet, community ecologists now recognize the importance of positive interactions within plant communities. Here, we examine how facilitation may interfere with the mechanisms of ecological speciation. We argue that facilitation is likely to (1 maintain gene flow among incipient species by enabling cooccurrence of adapted and maladapted forms in marginal habitats and (2 increase fitness of introgressed forms and limit reinforcement in secondary contact zones. Alternatively, we present how facilitation may favour colonization of marginal habitats and thus enhance local adaptation and ecological speciation. Therefore, facilitation may impede or pave the way for ecological speciation. Using a simple spatially and genetically explicit modelling framework, we illustrate and propose some first testable ideas about how, when, and where facilitation may act as a cohesive force for ecological speciation. These hypotheses and the modelling framework proposed should stimulate further empirical and theoretical research examining the role of both competitive and positive interactions in the formation of incipient species.

Molecular-level characterization of elastin-like constructs and human aortic elastin

DEFF Research Database (Denmark)

Heinz, Andrea; Schräder, Christoph U; Baud, Stéphanie

2014-01-01

This study aimed to characterize the structures of two elastin-like constructs, one composed of a cross-linked elastin-like polypeptide and the other one of cross-linked tropoelastin, and native aortic elastin. The structures of the insoluble materials and human aortic elastin were investigated...... quantification revealed that the cross-linking degree of the two in vitro cross-linked materials was significantly lower than that of native elastin. Molecular dynamics simulations were performed, based on molecular species identified in the samples, to follow the formation of elastin cross-links. The results...... provide evidence for the significance of the GVGTP hinge region of domain 23 for the formation of elastin cross-links. Overall, this work provides important insight into structural similarities and differences between elastin-like constructs and native elastin. Furthermore, it represents a step toward...

Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity.

Science.gov (United States)

Zhu, Kang; Shan, Zelin; Zhang, Lu; Wen, Wenyu

2016-07-06

In Drosophila neuroblasts (NBs), the asymmetrical localization and segregation of the cell-fate determinant Numb are regulated by its adaptor Partner of Numb (Pon) and the cell-cycle kinase Polo. Polo phosphorylates the Pon localization domain, thus leading to its basal distribution together with Numb, albeit through an unclear mechanism. Here, we find that Cdk1 phosphorylates Pon at Thr63, thus creating a docking site for the Polo-box domain (PBD) of Polo-like kinase 1 (Plk1). The crystal structure of the Plk1 PBD/phospho-Pon complex reveals that two phospho-Pon bound PBDs associate to form a dimer of dimers. We provide evidence that phospho-Pon binding-induced PBD dimerization relieves the autoinhibition of Plk1. Moreover, we demonstrate that the priming Cdk1 phosphorylation of Pon is important for sequential Plk1 phosphorylation. Our results not only provide structural insight into how phosphoprotein binding activates Plk1 but also suggest that binding to different phosphoproteins might mediate the fine-tuning of Plk1 activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of Unanticipated Alkylation at the N(π) Position of a Histidyl Residue Under Mitsunobu Conditions and Synthesis of Orthogonally Protected Histidine Analogues

Science.gov (United States)

Qian, Wenjian; Liu, Fa; Burke, Terrence R.

2011-01-01

We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in phosphothreonine-containing peptides can impart high binding affinity against the polo box domain of polo like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies. PMID:21950469

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

NARCIS (Netherlands)

W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R. de Boer (Renske); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef (W.)

1997-01-01

textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His- ProNH2) in the middle aminoacid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the

Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

Science.gov (United States)

Nagasawa, Miho; Mitsui, Shouhei; En, Shiori; Ohtani, Nobuyo; Ohta, Mitsuaki; Sakuma, Yasuo; Onaka, Tatsushi; Mogi, Kazutaka; Kikusui, Takefumi

2015-04-17

Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment. Copyright © 2015, American Association for the Advancement of Science.

Facilitated uptake of a bioactive metabolite of maritime pine bark extract (pycnogenol into human erythrocytes.

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Max Kurlbaum

Full Text Available Many plant secondary metabolites exhibit some degree of biological activity in humans. It is a common observation that individual plant-derived compounds in vivo are present in the nanomolar concentration range at which they usually fail to display measurable activity in vitro. While it is debatable that compounds detected in plasma are not the key effectors of bioactivity, an alternative hypothesis may take into consideration that measurable concentrations also reside in compartments other than plasma. We analysed the binding of constituents and the metabolite δ-(3,4-dihydroxy-phenyl-γ-valerolactone (M1, that had been previously detected in plasma samples of human consumers of pine bark extract Pycnogenol, to human erythrocytes. We found that caffeic acid, taxifolin, and ferulic acid passively bind to red blood cells, but only the bioactive metabolite M1 revealed pronounced accumulation. The partitioning of M1 into erythrocytes was significantly diminished at higher concentrations of M1 and in the presence of glucose, suggesting a facilitated transport of M1 via GLUT-1 transporter. This concept was further supported by structural similarities between the natural substrate α-D-glucose and the S-isomer of M1. After cellular uptake, M1 underwent further metabolism by conjugation with glutathione. We present strong indication for a transporter-mediated accumulation of a flavonoid metabolite in human erythrocytes and subsequent formation of a novel glutathione adduct. The physiologic role of the adduct remains to be elucidated.

Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir

International Nuclear Information System (INIS)

Santiago, Francisco; Oguma, Junya; Brown, Anthony M.C.; Laurence, Jeffrey

2012-01-01

Highlights: ► First demonstration of direct role for noncanonical Wnt in osteoclast differentiation. ► Demonstration of Ryk as a Wnt5a/b receptor in inhibition of canonical Wnt signaling. ► Modulation of noncanonical Wnt signaling by a clinically important drug, ritonavir. ► Establishes a mechanism for an important clinical problem: HIV-associated bone loss. -- Abstract: Wnt proteins that signal via the canonical Wnt/β-catenin pathway directly regulate osteoblast differentiation. In contrast, most studies of Wnt-related effects on osteoclasts involve indirect changes. While investigating bone mineral density loss in the setting of human immunodeficiency virus (HIV) infection and its treatment with the protease inhibitor ritonavir (RTV), we observed that RTV decreased nuclear localization of β-catenin, critical to canonical Wnt signaling, in primary human and murine osteoclast precursors. This occurred in parallel with upregulation of Wnt5a and Wnt5b transcripts. These Wnts typically stimulate noncanonical Wnt signaling, and this can antagonize the canonical Wnt pathway in many cell types, dependent upon Wnt receptor usage. We now document RTV-mediated upregulation of Wnt5a/b protein in osteoclast precursors. Recombinant Wnt5b and retrovirus-mediated expression of Wnt5a enhanced osteoclast differentiation from human and murine monocytic precursors, processes facilitated by RTV. In contrast, canonical Wnt signaling mediated by Wnt3a suppressed osteoclastogenesis. Both RTV and Wnt5b inhibited canonical, β-catenin/T cell factor-based Wnt reporter activation in osteoclast precursors. RTV- and Wnt5-induced osteoclast differentiation were dependent upon the receptor-like tyrosine kinase Ryk, suggesting that Ryk may act as a Wnt5a/b receptor in this context. This is the first demonstration of a direct role for Wnt signaling pathways and Ryk in regulation of osteoclast differentiation, and its modulation by a clinically important drug, ritonavir. These studies

Inducing homeostatic-like plasticity in human motor cortex through converging corticocortical inputs

DEFF Research Database (Denmark)

Pötter-Nerger, Monika; Fischer, Sarah; Mastroeni, Claudia

2009-01-01

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1(HAND)) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression......TMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1(HAND) via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve...... and left M1(HAND) to induce spike-time-dependent plasticity in sensory-to-motor inputs to left M1(HAND). We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PAS(N20+2ms)) or an LTD-like decrease (PAS(N20-5ms...

Innovación y desarrollo territorial en aglomeraciones industriales periféricas: el caso del Polo Petroquímico de Bahía Blanca (Argentina

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Cincunegui, Carmen

2012-02-01

Full Text Available Since the 1980s, under a post-fordism scenery an “imagery” has been developed that represents regions as carriers of an opportunity for being more flexible and innovative than large national units. It has been emphasized also that foreign investments have an impact on innovation initiatives when an articulated social, economic and institutional context open to novelty and change exists. Regions, therefore, abandoned their position as “objects” of development to become “subjects” in charge of their own territorial development process. Under this new perspective, this article presents results of a study on innovation and territorial development in peripheral industrial agglomerations. This research analyses in the case of Bahía Blanca’s Petrochemical Pole. Investigates whether large enterprises activities have promoted territory’s competitiveness by pushing the advantages of proximity and located interaction.

Bajo un escenario postfordista, se ha desarrollado desde la década de 1980 un “imaginario” que presenta a las regiones como portadoras de la oportunidad de actuar en forma más flexible e innovadora que las grandes unidades nacionales. Se ha enfatizado también el impacto de las inversiones extranjeras para el surgimiento de iniciativas innovadoras, siempre que exista un entorno social, económico e institucional articulado y receptivo a la novedad y al cambio. Así las regiones abandonan su pretérita situación de “objetos” de desarrollo para colocarse como “sujetos” encargados de reemprender su proceso de desarrollo territorial. Considerando este nuevo enfoque, el artículo expone los resultados de una investigación sobre innovación y desarrollo territorial en aglomeraciones industriales periféricas y analiza, para el caso del Polo Petroquímico de Bahía Blanca, si la actuación de las grandes empresas del Polo ha propiciado la competitividad del territorio al impulsar las ventajas de la proximidad

Epidemiology of Sepsis-like Illness in Young Infants Major Role of Enterovirus and Human Parechovirus

NARCIS (Netherlands)

de Jong, Eveline P.; van den Beuken, Monique G. A.; van Elzakker, Erika P. M.; Wolthers, Katja C.; Sprij, Arwen J.; Lopriore, Enrico; Walther, Frans J.; Brus, Frank

2018-01-01

Background: Sepsis-like illness is a main cause for hospital admission in young infants. Our aim was to investigate incidence, epidemiology and clinical characteristics of enterovirus (EV) and human parechovirus (HPeV) infections in young infants with sepsis-like illness. Methods: This is a

Polo-like kinase 1 inhibits DNA damage response during mitosis.

Science.gov (United States)

Benada, Jan; Burdová, Kamila; Lidak, Tomáš; von Morgen, Patrick; Macurek, Libor

2015-01-01

In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are required for homologous recombination and non-homologous end joining, respectively. Whereas mechanisms of DDR are relatively well understood in interphase cells, comparatively less is known about organization of DDR during mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage. Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows spatiotemporally controlled suppression of 53BP1 function during mitosis.

Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress.

Science.gov (United States)

Kraft, David Christian Evar; Bindslev, Dorth Arenholt; Melsen, Birte; Klein-Nulend, Jenneke

2011-02-01

For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular response via loading-induced flow of interstitial fluid. After surgical removal of ectopically impacted third molars, human dental pulp tissue is an easily accessible and interesting source of cells for mineralized tissue engineering. The aim of this study was to determine whether human dental pulp-derived cells (DPC) are responsive to mechanical loading by pulsating fluid flow (PFF) upon stimulation of mineralization in vitro. Human DPC were incubated with or without mineralization medium containing differentiation factors for 3 weeks. Cells were subjected to 1-h PFF (0.7 ± 0.3 Pa, 5 Hz) and the response was quantified by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and gene expression of cyclooxygenase (COX)-1 and COX-2. We found that DPC are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. PFF stimulated NO and PGE₂ production, and up-regulated COX-2 but not COX-1 gene expression. In DPC cultured under mineralizing conditions, the PFF-induced NO, but not PGE₂, production was significantly enhanced. These data suggest that human DPC, like osteogenic cells, acquire responsiveness to pulsating fluid shear stress in mineralizing conditions. Thus DPC might be able to perform bone-like functions during mineralized tissue remodeling in vivo, and therefore provide a promising new tool for mineralized tissue engineering to restore, for example, maxillofacial defects.

In vitro myogenesis induced by human recombinant elastin-like proteins.

Science.gov (United States)

D'Andrea, Paola; Scaini, Denis; Ulloa Severino, Luisa; Borelli, Violetta; Passamonti, Sabina; Lorenzon, Paola; Bandiera, Antonella

2015-10-01

Mammalian adult skeletal muscle has a limited ability to regenerate after injury, usage or trauma. A promising strategy for successful regenerative technology is the engineering of bio interfaces that mimic the characteristics of the extracellular matrix. Human elastin-like polypeptides (HELPs) have been synthesized as biomimetic materials that maintain some peculiar properties of the native protein. We developed a novel Human Elastin Like Polypeptide obtained by fusing the elastin-like backbone to a domain present in the α2 chain of type IV collagen, containing two RGD motives. We employed this peptide as adhesion substrate for C2C12 myoblasts and compared its effects to those induced by two other polypeptides of the HELP series. Myoblast adhered to all HELPs coatings, where they assumed morphology and cytoarchitecture that depended on the polypeptide structure. Adhesion to HELPs stimulated at a different extent cell proliferation and differentiation, the expression of Myosin Heavy Chain and the fusion of aligned fibers into multinucleated myotubes. Adhesion substrates significantly altered myotubes stiffness, measured by Atomic Force Microscopy, and differently affected the cells Ca(2+) handling capacity and the maturation of excitation-contraction coupling machinery, evaluated by Ca(2+) imaging. Overall, our findings indicate that the properties of HELP biopolymers can be exploited for dissecting the molecular connections underlying myogenic differentiation and for designing novel substrates for skeletal muscle regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Facilitation as a teaching strategy : experiences of facilitators

Directory of Open Access Journals (Sweden)

E Lekalakala-Mokgele

2006-09-01

Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

Th1 and Th2-like protein balance in human inflammatory radicular cysts and periapical granulomas.

Science.gov (United States)

de Carvalho Fraga, Carlos Alberto; Alves, Lucas Rodrigues; de Sousa, Adriana Alkmim; de Jesus, Sabrina Ferreira; Vilela, Daniel Nogueira; Pereira, Camila Santos; Batista Domingos, Patrícia Luciana; Viana, Agostinho Gonçalves; Jham, Bruno Correia; Batista de Paula, Alfredo Maurício; Sena Guimarães, André Luiz

2013-04-01

Chronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. Archived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. Our study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies. Copyright © 2013 American Association of Endodontists. All rights reserved.

Barriers and Facilitators to Engagement and Retention in Care among Transgender Women Living with Human Immunodeficiency Virus

Science.gov (United States)

Sevelius, Jae M.; Patouhas, Enzo; Keatley, JoAnne G.; Johnson, Mallory O.

2014-01-01

Background Transgender women have 49 times the odds of human immunodeficiency virus (HIV) infection compared to other groups, yet they are disproportionately underserved by current treatment efforts. Purpose To examine culturally unique barriers and facilitators to engagement and retention in HIV care and strengthen efforts to mitigate health disparities, guided by the Models of Gender Affirmation and Health Care Empowerment. Methods Through 20 interviews and 5 focus groups (n=38), transgender women living with HIV discussed their experiences and life contexts of engagement in and adherence to HIV care and treatment. Results Our participants faced substantial challenges to adhering to HIV care and treatment, including avoidance of healthcare due to stigma and past negative experiences, prioritization of hormone therapy, and concerns about adverse interactions between antiretroviral treatment for HIV and hormone therapy. Receiving culturally competent, transgender-sensitive healthcare was a powerful facilitator of healthcare empowerment. Conclusions Recommendations are offered to inform intervention research and guide providers, emphasizing gender affirming HIV care that integrates transition-related healthcare needs. PMID:24317955

MACC1 facilitates chemoresistance and cancer stem cell‑like properties of colon cancer cells through the PI3K/AKT signaling pathway.

Science.gov (United States)

Wang, Jiankai; Wang, Wenjuan; Cai, Hongyi; Du, Binbin; Zhang, Lijuan; Ma, Wen; Hu, Yongguo; Feng, Shifang; Miao, Guoying

2017-12-01

With regards to colon cancer, resistance to 5‑fluorouracil (5‑FU)‑based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis‑associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC‑like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5‑FU; subsequently, CSC‑like properties and 5‑FU sensitivity were investigated. Within 5‑FU‑resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3‑kinase/protein kinase B signaling pathway may be associated with 5‑FU resistance and CSC‑like properties via MACC1.

MACC1 facilitates chemoresistance and cancer stem cell-like properties of colon cancer cells through the PI3K/AKT signaling pathway

Science.gov (United States)

Wang, Jiankai; Wang, Wenjuan; Cai, Hongyi; Du, Binbin; Zhang, Lijuan; Ma, Wen; Hu, Yongguo; Feng, Shifang; Miao, Guoying

2017-01-01

With regards to colon cancer, resistance to 5-fluorouracil (5-FU)-based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis-associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC-like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5-FU; subsequently, CSC-like properties and 5-FU sensitivity were investigated. Within 5-FU-resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3-kinase/protein kinase B signaling pathway may be associated with 5-FU resistance and CSC-like properties via MACC1. PMID:28990068

Zoneamento ambiental do polo de desenvolvimento agroindustrial do Alto Piranhas, Estado da Paraíba

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J. S. Almeida

2015-12-01

Full Text Available Este trabalho teve como objetivo zonear os níveis de deterioração ambiental na paisagem entre os anos de 2001 e 2012, adotando os critérios da ecodinâmica nos municípios que compõe o polo de desenvolvimento agroindustrial do Alto Piranhas. Foram realizadas análises envolvendo a dinâmica da paisagem e da vulnerabilidade ambiental. A metodologia utilizada na pesquisa foi baseada em localizações pontuais, que inclui o processo de selecionar e combinar, através de procedimento de álgebra de mapas disponíveis em um SIG, cada variável geográfica contém diferenciação espacial e a combinação entre elas promove a subdivisão do espaço geográfico em regiões equiproblemáticas. Tomando-se por base as superposições dos mapas geológico, geomorfológico e pedológico foi efetuado o mapa de zoneamento ambiental, com informações que permitiram identificar as condições do meio natural e suas aptidões. Esses fatores foram comparados entre si, conforme a importância atribuída a elas. Os resultados indicaram que as áreas centrais concentram as classes com maiores riscos ambientais, como as instáveis (risco ambiental entre 60 e 80%, e as de instabilidade emergente (risco maior que 80. Já nas áreas distribuídas em toda a área de estudo encontra-se as áreas com risco ambiental entre 40 e 60% (instabilidade moderada. Com base na análise, percebe-se que a área de estudo possui um tênue equilíbrio por estar localizado em ambiente semiárido que pode ser rompido com facilidade com a intensificação das atividades agroindustriais.Environmental zoning polo agro industry development of Alto Piranhas, Paraíba StateAbstract: This study aimed to zone the levels of environmental deterioration in the landscape between the years 2001 and 2012, adopting the criteria of ecodynamics municipalities that make up the hub of agro-industrial development of the Alto Piranhas. Analyzes involving the dynamics of landscape and environmental

Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS facilitates surface expression of GluR2-containing AMPA receptors.

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Hyunjeong Yang

Full Text Available Some ubiquitin-like (UBL domain-containing proteins are known to play roles in receptor trafficking. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs undergo constitutive cycling between the intracellular compartment and the cell surface in the central nervous system. However, the function of UBL domain-containing proteins in the recycling of the AMPARs to the synaptic surface has not yet been reported.Here, we report that the Transmembrane and ubiquitin-like domain-containing 1 (Tmub1 protein, formerly known as the Hepatocyte Odd Protein Shuttling (HOPS protein, which is abundantly expressed in the brain and which exists in a synaptosomal membrane fraction, facilitates the recycling of the AMPAR subunit GluR2 to the cell surface. Neurons transfected with Tmub1/HOPS-RNAi plasmids showed a significant reduction in the AMPAR current as compared to their control neurons. Consistently, the synaptic surface expression of GluR2, but not of GluR1, was significantly decreased in the neurons transfected with the Tmub1/HOPS-RNAi and increased in the neurons overexpressing EGFP-Tmub1/HOPS. The altered surface expression of GluR2 was speculated to be due to the altered surface-recycling of the internalized GluR2 in our recycling assay. Eventually, we found that GluR2 and glutamate receptor interacting protein (GRIP were coimmunoprecipitated by the anti-Tmub1/HOPS antibody from the mouse brain. Taken together, these observations show that the Tmub1/HOPS plays a role in regulating basal synaptic transmission; it contributes to maintain the synaptic surface number of the GluR2-containing AMPARs by facilitating the recycling of GluR2 to the plasma membrane.

Facilitating Learning at Conferences

DEFF Research Database (Denmark)

Ravn, Ib; Elsborg, Steen

2011-01-01

The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...... and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes...

Human Trafficking: A Security Challenge in Nigeria. | Tor-Anyiin ...

African Journals Online (AJOL)

This paper examines human trafficking, which is today rated as the third world organized crime after drugs and arms. The concept of the trade, which crosses internal and international borders, has also been discussed. The factors that facilitate the trade like poverty, personal and social are equally identified and discussed.

Anxiolytic-Like Actions of Fatty Acids Identified in Human Amniotic Fluid

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Rosa Isela García-Ríos

2013-01-01

Full Text Available Eight fatty acids (C12–C18 were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic-like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic-like effects. Although a trend toward a dose-response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p. in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic-like effects, suggesting similar actions during intrauterine development.

Genome engineering in human cells.

Science.gov (United States)

Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

2014-01-01

Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

Generating human-like movements on an anthropomorphic robot using an interior point method

Science.gov (United States)

Costa e Silva, E.; Araújo, J. P.; Machado, D.; Costa, M. F.; Erlhagen, W.; Bicho, E.

2013-10-01

In previous work we have presented a model for generating human-like arm and hand movements on an anthropomorphic robot involved in human-robot collaboration tasks. This model was inspired by the Posture-Based Motion-Planning Model of human movements. Numerical results and simulations for reach-to-grasp movements with two different grip types have been presented previously. In this paper we extend our model in order to address the generation of more complex movement sequences which are challenged by scenarios cluttered with obstacles. The numerical results were obtained using the IPOPT solver, which was integrated in our MATLAB simulator of an anthropomorphic robot.

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

Science.gov (United States)

Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

2017-05-01

Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amygdala Lesions Reduce Anxiety-like Behavior in a Human Benzodiazepine-Sensitive Approach-Avoidance Conflict Test.

Science.gov (United States)

Korn, Christoph W; Vunder, Johanna; Miró, Júlia; Fuentemilla, Lluís; Hurlemann, Rene; Bach, Dominik R

2017-10-01

Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation. In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions. Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report. Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

Science.gov (United States)

Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

2017-05-01

Extracellular matrix (ECM) is crucial to many aspects of vascular morphogenesis and maintenance of vasculature function. Currently the recapitulation of angiogenic ECM microenvironment is still challenging, due mainly to its diverse components and complex organization. Here we investigate the angiogenic potential of human lung fibroblast-derived matrix (hFDM) in creating a three-dimensional (3D) vascular construct. hFDM was obtained via decellularization of in vitro cultured human lung fibroblasts and analyzed via immunofluorescence staining and ELISA, which detect multiple ECM macromolecules and angiogenic growth factors (GFs). Human umbilical vein endothelial cells (HUVECs) morphology was more elongated and better proliferative on hFDM than on gelatin-coated substrate. To prepare 3D construct, hFDM is collected, quantitatively analyzed, and incorporated in collagen hydrogel (Col) with HUVECs. Capillary-like structure (CLS) formation at 7day was significantly better with the groups containing higher doses of hFDM compared to the Col group (control). Moreover, the group (Col/hFDM/GFs) with both hFDM and angiogenic GFs (VEGF, bFGF, SDF-1) showed the synergistic activity on CLS formation and found much larger capillary lumen diameters with time. Further analysis of hFDM via angiogenesis antibody array kit reveals abundant biochemical cues, such as angiogenesis-related cytokines, GFs, and proteolytic enzymes. Significantly up-regulated expression of VE-cadherin and ECM-specific integrin subunits was also noticed in Col/hFDM/GFs. In addition, transplantation of Col/hFMD/GFs with HUVECs in skin wound model presents more effective re-epithelialization, many regenerated hair follicles, better transplanted cells viability, and advanced neovascularization. We believe that current system is a very promising platform for 3D vasculature construction in vitro and for cell delivery toward therapeutic applications in vivo. Functional 3D vasculature construction in vitro is still

DNA-mediated strand displacement facilitates sensitive electronic detection of antibodies in human serums.

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Dou, Baoting; Yang, Jianmei; Shi, Kai; Yuan, Ruo; Xiang, Yun

2016-09-15

We describe here the development of a sensitive and convenient electronic sensor for the detection of antibodies in human serums. The sensor is constructed by self-assembly formation of a mixed monolayer containing the small molecule epitope conjugated double stranded DNA probes on gold electrode. The target antibody binds the epitope on the dsDNA probe and lowers the melting temperature of the duplex, which facilitates the displacement of the antibody-linked strand of the duplex probe by an invading methylene blue-tagged single stranded DNA (MB-ssDNA) through the strand displacement reaction and leads to the capture of many MB-ssDNA on the sensor surface. Subsequent electrochemical oxidation of the methylene blue labels results in amplified current response for sensitive monitoring of the antibodies. The antibody assay conditions are optimized and the sensor exhibits a linear range between 1.0 and 25.0nM with a detection limit of 0.67nM for the target antibody. The sensor is also selective and can be employed to detect the target antibodies in human serum samples. With the advantages of using small molecule epitope as the antibody recognition element over traditional antigen, the versatile manipulability of the DNA probes and the unique properties of the electrochemical transduction technique, the developed sensor thus hold great potential for simple and sensitive detection of different antibodies and other proteins in real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Yeast prions and human prion-like proteins: sequence features and prediction methods.

Science.gov (United States)

Cascarina, Sean M; Ross, Eric D

2014-06-01

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis. This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms.

Flowing like a river: facilitation in practice development and the evolution of critical-creative companionship

Directory of Open Access Journals (Sweden)

Angie Titchen

2018-05-01

Full Text Available Beginnings: Using a river landscape metaphor, the purpose of this paper is to locate critical creativity in the evolution of practice development in the UK and show how it can be facilitated through critical-creative companionship. Critical creativity is a new landscape for practice development that has evolved through three decades of a deepening understanding of: the philosophical foundations of practice development (bedrocks; paradigms (landscapes; projects/studies (gardens; and practice development/research roles, relationships and skills (gardeners. As a practice development practitioner, facilitator and researcher, I have helped shape the course of the river, peaking with the slow-burn, yet intense, co-creation of critical creativity. Panorama, flow and transformation: A panoramic view of the river is offered as it changes over time. This view includes the river’s changes of flow and direction, powered by different philosophical and theoretical influences and resultant transformations in practice development practice/research and facilitation. Unfolding: I telescope in on the critical creativity landscape, showing how it is a synthesis of previous influences and how the critical companionship of my earlier work flowed gently into critical-creative companionship. I show broad-brush how critical-creative companions help people to use the philosophical, theoretical and methodological mandalas of critical creativity, not only in their practice development, but also in their own being and becoming critical-creative companions. Conclusion and implications for practice development and inquiry: Critical-creative companions help people to work in the gardens of critical creativity to embody and live what might seem difficult, complex and mysterious. Becoming a critical-creative companion takes time. It requires a scholarly approach to practice and the development of enabling facilitation skills and experiential and theoretical understanding

SCM, a novel M-like protein from Streptococcus canis, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration.

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Fulde, Marcus; Rohde, Manfred; Hitzmann, Angela; Preissner, Klaus T; Nitsche-Schmitz, D Patric; Nerlich, Andreas; Chhatwal, Gursharan Singh; Bergmann, Simone

2011-03-15

Streptococcus canis is an important zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. In the present paper we report the binding of human plasminogen to S. canis and the recruitment of proteolytically active plasmin on its surface. The binding receptor for plasminogen was identified as a novel M-like protein designated SCM (S. canis M-like protein). SPR (surface plasmon resonance) analyses, radioactive dot-blot analyses and heterologous expression on the surface of Streptococcus gordonii confirmed the plasminogen-binding capability of SCM. The binding domain was located within the N-terminus of SCM, which specifically bound to the C-terminal part of plasminogen (mini-plasminogen) comprising kringle domain 5 and the catalytic domain. In the presence of urokinase, SCM mediated plasminogen activation on the bacterial surface that was inhibited by serine protease inhibitors and lysine amino acid analogues. Surface-bound plasmin effectively degraded purified fibrinogen as well as fibrin clots, resulting in the dissolution of fibrin thrombi. Electron microscopic illustration and time-lapse imaging demonstrated bacterial transmigration through fibrinous thrombi. The present study has led, for the first time, to the identification of SCM as a novel receptor for (mini)-plasminogen mediating the fibrinolytic activity of S. canis.

Formation of human hepatocyte-like cells with different cellular phenotypes by human umbilical cord blood-derived cells in the human-rat chimeras

International Nuclear Information System (INIS)

Sun, Yan; Xiao, Dong; Zhang, Ruo-Shuang; Cui, Guang-Hui; Wang, Xin-Hua; Chen, Xi-Gu

2007-01-01

We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a noninjury human-rat xenograft small animal model, in which the in utero transplantation of low-density mononuclear cells (MNCs) from human umbilical cord blood (hUCB) into fetal rats at 9-11 days of gestation led to the formation of human hepatocyte-like cells (hHLCs) with different cellular phenotypes, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), cytokeratin 19 (CK19), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and albumin (Alb), and with some animals exhibiting levels as high as 10.7% of donor-derived human cells in the recipient liver. More interestingly, donor-derived human cells stained positively for CD34 and CD45 in the liver of 2-month-old rat. Human hepatic differentiation appeared to partially follow the process of hepatic ontogeny, as evidenced by the expression of AFP gene at an early stage and albumin gene at a later stage. Human hepatocytes generated in this model retained functional properties of normal hepatocytes. In this xenogeneic system, the engrafted donor-derived human cells persisted in the recipient liver for at least 6 months after birth. Taken together, these findings suggest that the donor-derived human cells with different cellular phenotypes are found in the recipient liver and hHLCs hold biological activity. This humanized small animal model, which offers an in vivo environment more closely resembling the situations in human, provides an invaluable approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future

N-terminally truncated forms of human cathepsin F accumulate in aggresome-like inclusions.

Science.gov (United States)

Jerič, Barbara; Dolenc, Iztok; Mihelič, Marko; Klarić, Martina; Zavašnik-Bergant, Tina; Gunčar, Gregor; Turk, Boris; Turk, Vito; Stoka, Veronika

2013-10-01

The contribution of individual cysteine cathepsins as positive mediators of programmed cell death is dependent on several factors, such as the type of stimuli, intensity and duration of the stimulus, and cell type involved. Of the eleven human cysteine cathepsins, cathepsin F is the only cathepsin that exhibits an extended N-terminal proregion, which contains a cystatin-like domain. We predicted that the wild-type human cathepsin F contains three natively disordered regions within the enzyme's propeptide and various amino acid stretches with high fibrillation propensity. Wild-type human cathepsin F and its N-terminally truncated forms, Ala(20)-Asp(484) (Δ(19)CatF), Pro(126)-Asp(484) (Δ(125)CatF), and Met(147)-Asp(484) (Δ(146)CatF) were cloned into the pcDNA3 vector and overexpressed in HEK 293T cells. Wild-type human cathepsin F displayed a clear vesicular labeling and colocalized with the LAMP2 protein, a lysosomal marker. However, all three N-terminally truncated forms of human cathepsin F were recovered as insoluble proteins, suggesting that the deletion of at least the signal peptides (Δ(19)CatF), results in protein aggregation. Noteworthy, they concentrated large perinuclear-juxtanuclear aggregates that accumulated within aggresome-like inclusions. These inclusions showed p62-positive immunoreactivity and were colocalized with the autophagy marker LC3B, but not with the LAMP2 protein. In addition, an approximately 2-3 fold increase in DEVDase activity was not sufficient to induce apoptotic cell death. These results suggested the clearance of the N-terminally truncated forms of human cathepsin F via the autophagy pathway, underlying its protective and prosurvival mechanisms. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

A Killer Immunoglobulin - Like Receptor Gene - Content Haplotype and A Cognate Human Leukocyte Antigen Ligand are Associated with Autism

OpenAIRE

Torres, Anthony; Westover, Jonna; Benson, Michael; Johnson, Randall; Dykes, Annelise

2016-01-01

The killing activity of natural killer cells is largely regulated by the binding of class I human leukocyte antigen cognate ligands to killer cell immunoglobulin - like receptor proteins. The killer cell immunoglobulin - like receptor gene - complex contains genes that activate and others that inhibit the killing state of natural killer cells depending on the binding of specific human leukocyte antigen cognate ligands. It has been suggested in previous publications that activating human leuko...

Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells

International Nuclear Information System (INIS)

Wu Hualin; Lin ChiIou; Huang Yuanli; Chen, Pin-Shern; Kuo, Cheng-Hsiang; Chen, Mei-Shing; Wu, G.C.-C.; Shi, G.-Y.; Yang, H.-Y.; Lee Hsinyu

2008-01-01

Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation

The choice of facilitators in medical tourism.

Science.gov (United States)

Gan, Lydia L; Frederick, James R

2018-01-01

The study identified which of the four facilitators (themselves, agents, insurers, or doctors) consumers are most likely to use when they travel for various medical procedures. A survey conducted between 2011 and 2014 yielded 964 responses. The multinomial logistic regression results showed that being 51-64 years old was positively related to going on their own or using agents to arrange for knee replacements. Having a high school education or less was positively linked to using both agents and insurers to facilitate knee replacements, whereas having a bachelor's degree was negatively associated with going on their own for stem cell therapy.

Potencial de implementação da certificação florestal no polo moveleiro de Ubá Potential of implementing forest certification for Uba furniture center

Directory of Open Access Journals (Sweden)

Ricardo Ribeiro Alves

2009-04-01

Full Text Available O trabalho objetivou avaliar o potencial de implementação da certificação florestal no polo moveleiro de Ubá, MG. Delimitaram-se, como objeto de estudo no polo, somente empresas ligadas à exportação, consideradas as potencialmente interessadas nessa certificação. Elaborou-se um questionário para buscar informações de seus produtos principais, incluindo composição, matéria-prima, fornecedores e mercado. Verificou-se que a maioria dessas empresas atendia principalmente ao mercado interno e suas exportações eram ocasionais. A matéria-prima utilizada, em geral, era de painéis reconstituídos, já certificados por muitos dos seus fornecedores. Em torno de 85% das empresas pesquisadas já atendiam plena ou parcialmente à política de porcentagens do FSC, vigente atualmente. Conclui-se que a certificação florestal pode ser considerada viável, visto que muitas das empresas já adquirem matéria-prima certificada, além do fato de que suas exportações têm aumentado, atingindo, assim, um mercado que exigirá essa certificação em breve.This work aimed to evaluate the potential of implementing forest certification in the furniture center region of Ubá, MG. Only export companies, considered potentially interested in this type of certification,were selected for this study. A questionnaire was elaborated to obtain information on their main products, including composition, raw material, suppliers and market. The majority of these companies supplied the domestic market and exportation was an occasional activity. The raw material used was, in general, reconstituted panels that had been previously certified by its suppliers. Around 85% of the companies studied fully or partially met the currently effective FSC percentage policy. It was concluded that forest certification can be considered viable, since many of the companies already acquire certified raw material. Besides, their export activities has increased, soon reaching a market

Evidence that a functional fertilin-like ADAM plays a role in human sperm-oolemmal interactions.

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Bronson, R A; Fusi, F M; Calzi, F; Doldi, N; Ferrari, A

1999-05-01

Fertilin is a protein initially identified in guinea pig spermatozoa; it is the prototype of a larger family of conserved, proteins designated as a disintegrin and a metalloproteinase (ADAM). These heterodimers which consist of alpha and beta subunits, containing metalloproteinase-like and disintegrin-like domains, appear to play a role in mammalian fertilization. Peptides derived from the disintegrin domains of two ADAMs, fertilin and cyritestin, interfere with gamete adhesion and sperm-egg membrane fusion in non-human species. It has been suggested that fertilin-beta binds to an oolemmal integrin, and it is proposed that the tripeptide FEE (Phe-Glu-Glu) is the integrin recognition sequence in human fertilin-beta. We evaluated whether fertilin beta plays a role in human fertilization by studying the effects of a linear octapeptide containing the FEE sequence, SFEECDLP, and a scrambled octapeptide with the same amino acids, SFPCEDEL, on the incorporation of human spermatozoa by human zona-free eggs. The effects of G4120, a potent RGD-containing (Arg-Gly-Asp) thioether-bridged cyclic peptide which blocks both fibronectin and vitronectin receptors, and the relationship between FEE- and RGD-receptor interactions on sperm-egg interactions were also studied. The FEE-containing peptide, but not the scrampled peptide, inhibited sperm adhesion to oocytes and their penetration, over the range 1-5 microM. The inhibition induced by SFEECDLP was reversible and occurred only in the presence of peptide itself. The G4120 peptide exhibited 10-fold less inhibitory effects on sperm adhesion and penetration than did SFEECDLP. When combined, SFEECDLP and G4120 exhibited strong inhibition of both adhesion and penetration at concentrations that individually had been ineffective, suggesting co-operation between the two receptor-ligand interactions during fertilization. We propose that a fertilin-like molecule is functionally active on human spermatozoa and that its interaction with an

Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

DEFF Research Database (Denmark)

Brandt, Claus; Pedersen, Maria; Rinnov, Anders

2014-01-01

, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. CONCLUSION: Plasma fstl3 is increased in obese subjects......BACKGROUND: Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. OBJECTIVE: To elucidate the association between...... plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. STUDY DESIGN: Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS...

Acceptance and Attitudes Toward a Human-like Socially Assistive Robot by Older Adults.

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Louie, Wing-Yue Geoffrey; McColl, Derek; Nejat, Goldie

2014-01-01

Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person-centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications.

Ubiquitin-Like Protein from Human Placental Extract Exhibits Collagenase Activity

Science.gov (United States)

De, Debashree; Datta Chakraborty, Piyali; Mitra, Jyotirmoy; Sharma, Kanika; Mandal, Somnath; Das, Aneesha; Chakrabarti, Saikat; Bhattacharyya, Debasish

2013-01-01

An aqueous extract of human placenta exhibits strong gelatinase/collagenase activity in zymography. 2-D gel electrophoresis of the extract with gelatin zymography in the second dimension displayed a single spot, identified as ubiquitin-like component upon MALDI/TOF MS/MS analysis. Immunoblot indicated presence of ubiquitin and absence of collagenase in the extract. Collagenase activity of the ubiquitin-like component was confirmed from the change in solubility of collagen in aqueous buffer, degradation of collagen by size-exclusion HPLC and atomic force microscopy. Quantification with DQ-gelatin showed that the extract contains 0.04 U/ml of collagenase activity that was inhibited up to 95% by ubiquitin antibody. Ubiquitin from bovine erythrocytes demonstrated mild collagenase activity. Bioinformatics studies suggest that placental ubiquitin and collagenase follow structurally divergent evolution. This thermostable intrinsic collagenase activity of placental extract might have wide physiological relevance in degrading and remodeling collagen as it is used as a drug for wound healing and pelvic inflammatory diseases. PMID:23555718

Work System Assessment to Facilitate the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use: A Case Study Using a Human Factors Engineering Approach.

Science.gov (United States)

Xie, Anping; Woods-Hill, Charlotte Z; King, Anne F; Enos-Graves, Heather; Ascenzi, Judy; Gurses, Ayse P; Klaus, Sybil A; Fackler, James C; Milstone, Aaron M

2017-11-20

Work system assessments can facilitate successful implementation of quality improvement programs. Using a human factors engineering approach, we conducted a work system assessment to facilitate the dissemination of a quality improvement program for optimizing blood culture use in pediatric intensive care units at 2 hospitals. Semistructured face-to-face interviews were conducted with clinicians from Johns Hopkins All Children's Hospital and University of Virginia Medical Center. Interview data were analyzed using qualitative content analysis. Blood culture-ordering practices are influenced by various work system factors, including people, tasks, tools and technologies, the physical environment, organizational conditions, and the external environment. A clinical decision-support tool could facilitate implementation by (1) standardizing blood culture-ordering practices, (2) ensuring that prescribing clinicians review the patient's condition before ordering a blood culture, (3) facilitating critical thinking, and (4) empowering nurses to communicate with physicians and advocate for adherence to blood culture-ordering guidelines. The success of interventions for optimizing blood culture use relies heavily on the local context. A work system analysis using a human factors engineering approach can identify key areas to be addressed for the successful dissemination of quality improvement interventions. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity.

Science.gov (United States)

Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

2016-04-01

Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

Intermittent Access to Ethanol Drinking Facilitates the Transition to Excessive Drinking After Chronic Intermittent Ethanol Vapor Exposure.

Science.gov (United States)

Kimbrough, Adam; Kim, Sarah; Cole, Maury; Brennan, Molly; George, Olivier

2017-08-01

Alcohol binge drinking in humans is thought to increase the risk for alcohol use disorder (AUD). Unclear is whether drinking patterns (e.g., bingelike or stable drinking) differentially affect the transition to compulsive-like drinking in dependent individuals. We examined whether chronic bingelike drinking facilitates the transition to compulsive-like drinking in rats. Male Wistar rats were given 5 months of intermittent access to ethanol (EtOH) (IAE) or continuous access to EtOH (CAE) in a 2-bottle choice paradigm. Then, rats were given chronic intermittent EtOH (CIE) vapor exposure. Escalation of EtOH intake and compulsive-like responding for EtOH, using a progressive-ratio schedule of reinforcement and quinine-adulterated EtOH, were measured. IAE rats escalated EtOH drinking after 2 weeks of 2-bottle choice, whereas CAE rats exhibited stable EtOH drinking for 5 months. After 8 weeks of CIE, both IAE + CIE and CAE + CIE rats escalated their EtOH intake. However, IAE rats escalated their EtOH intake weeks sooner than CAE rats and exhibited greater EtOH intake. No differences in compulsive-like responding were found between IAE + CIE and CAE + CIE rats. However, both IAE + CIE and CAE + CIE rats showed strong compulsive-like responding compared with rats without prior IAE or CAE. Chronic EtOH drinking at stable or escalated levels for several months is associated with more compulsive-like responding for EtOH in rats that are exposed to CIE compared with rats without a prior history of EtOH drinking. Moreover, IAE facilitated the transition to compulsive-like responding for EtOH after CIE exposure, reflected by the escalation of EtOH intake. These results suggest that IAE may facilitate the transition to AUD. This study indicates that despite a moderate level of EtOH drinking, the IAE animal model is highly relevant to early stages of alcohol abuse and suggests that it may be associated with neuroadaptations that produce a faster transition to

Dressed for Sex: Red as a Female Sexual Signal in Humans

Science.gov (United States)

Elliot, Andrew J.; Pazda, Adam D.

2012-01-01

Background In many non-human primate species, a display of red by a female serves as a sexual signal to attract male conspecifics. Red is associated with sex and romance in humans, and women convey their sexual interest to men through a variety of verbal, postural, and behavioral means. In the present research, we investigate whether female red ornamentation in non-human primates has a human analog, whereby women use a behavioral display of red to signal their sexual interest to men. Methodology/Principal Findings Three studies tested the hypothesis that women use red clothing to communicate sexual interest to men in profile pictures on dating websites. In Study 1, women who imagined being interested in casual sex were more likely to display red (but not other colors) on their anticipated web profile picture. In Study 2, women who indicated interest in casual sex were more likely to prominently display red (but not other colors) on their actual web profile picture. In Study 3, women on a website dedicated to facilitating casual sexual relationships were more likely to prominently exhibit red (but not other colors) than women on a website dedicated to facilitating marital relationships. Conclusions/Significance These results establish a provocative parallel between women and non-human female primates in red signal coloration in the mating game. This research shows, for the first time, a functional use of color in women's sexual self-presentation, and highlights the need to extend research on color beyond physics, physiology, and preference to psychological functioning. PMID:22514643

Dressed for sex: red as a female sexual signal in humans.

Directory of Open Access Journals (Sweden)

Andrew J Elliot

Full Text Available BACKGROUND: In many non-human primate species, a display of red by a female serves as a sexual signal to attract male conspecifics. Red is associated with sex and romance in humans, and women convey their sexual interest to men through a variety of verbal, postural, and behavioral means. In the present research, we investigate whether female red ornamentation in non-human primates has a human analog, whereby women use a behavioral display of red to signal their sexual interest to men. METHODOLOGY/PRINCIPAL FINDINGS: Three studies tested the hypothesis that women use red clothing to communicate sexual interest to men in profile pictures on dating websites. In Study 1, women who imagined being interested in casual sex were more likely to display red (but not other colors on their anticipated web profile picture. In Study 2, women who indicated interest in casual sex were more likely to prominently display red (but not other colors on their actual web profile picture. In Study 3, women on a website dedicated to facilitating casual sexual relationships were more likely to prominently exhibit red (but not other colors than women on a website dedicated to facilitating marital relationships. CONCLUSIONS/SIGNIFICANCE: These results establish a provocative parallel between women and non-human female primates in red signal coloration in the mating game. This research shows, for the first time, a functional use of color in women's sexual self-presentation, and highlights the need to extend research on color beyond physics, physiology, and preference to psychological functioning.

Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

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Ho, Lin; Hsu, Shan-Hui

2018-04-01

3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be

Composite cell sheet for periodontal regeneration: crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration.

Science.gov (United States)

Zhang, Hao; Liu, Shiyu; Zhu, Bin; Xu, Qiu; Ding, Yin; Jin, Yan

2016-11-14

Tissue-engineering strategies based on mesenchymal stem cells (MSCs) and cell sheets have been widely used for periodontal tissue regeneration. However, given the complexity in periodontal structure, the regeneration methods using a single species of MSC could not fulfill the requirement for periodontal regeneration. We researched the interaction between the periodontal ligament stem cells (PDLSCs) and jaw bone marrow-derived mesenchymal stem cells (JBMMSCs), and constructed a composite cell sheet comprising both of the above MSCs to regenerate complex periodontium-like structures in nude mice. Our results show that by co-culturing PDLSCs and JBMMSCs, the expressions of bone and extracellular matrix (ECM)-related genes and proteins were significantly improved in both MSCs. Further investigations showed that, compared to the cell sheet using PDLSCs or JBMMSCs, the composite stem cell sheet (CSCS), which comprises these two MSCs, expressed higher levels of bone- and ECM-related genes and proteins, and generated a composite structure more similar to the native periodontal tissue physiologically in vivo. In conclusion, our results demonstrate that the crosstalk between PDLSCs and JBMMSCs in cell sheets facilitate regeneration of complex periodontium-like structures, providing a promising new strategy for physiological and functional regeneration of periodontal tissue.

Molecular and structural characterization of fluorescent human parvovirus B19 virus-like particles

International Nuclear Information System (INIS)

Gilbert, Leona; Toivola, Jouni; White, Daniel; Ihalainen, Teemu; Smith, Wesley; Lindholm, Laura; Vuento, Matti; Oker-Blom, Christian

2005-01-01

Although sharing a T = 1 icosahedral symmetry with other members of the Parvoviridae family, it has been suggested that the fivefold channel of the human parvovirus B19 VP2 capsids is closed at its outside end. To investigate the possibility of placing a relatively large protein moiety at this site of B19, fluorescent virus-like particles (fVLPs) of B19 were developed. The enhanced green fluorescent protein (EGFP) was inserted at the N-terminus of the structural protein VP2 and assembly of fVLPs from this fusion protein was obtained. Electron microscopy revealed that these fluorescent protein complexes were very similar in size when compared to wild-type B19 virus. Further, fluorescence correlation spectroscopy showed that an average of nine EGFP domains were associated with these virus-like structures. Atomic force microscopy and immunoprecipitation studies showed that EGFP was displayed on the surface of these fVLPs. Confocal imaging indicated that these chimeric complexes were targeted to late endosomes when expressed in insect cells. The fVLPs were able to efficiently enter cancer cells and traffic to the nucleus via the microtubulus network. Finally, immunoglobulins present in human parvovirus B19 acute and past-immunity serum samples were able to detect antigenic epitopes present in these fVLPs. In summary, we have developed fluorescent virus-like nanoparticles displaying a large heterologous entity that should be of help to elucidate the mechanisms of infection and pathogenesis of human parvovirus B19. In addition, these B19 nanoparticles serve as a model in the development of targetable vehicles designed for delivery of biomolecules

Bioactivity of a modified human Glucagon-like peptide-1.

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Fangfang Xu

Full Text Available Diabetes has become the third largest cause of death in humans worldwide. Therefore, effective treatment for this disease remains a critical issue. Glucagon-like peptide-1 (GLP-1 plays an important role in glucose homeostasis, and therefore represents a promising candidate to use for the treatment of diabetes. Native GLP-1, however, is quickly degraded in in the circulatory system; which limits its clinical application. In the present study, a chemically-synthesized, modified analogue of human GLP-1 (mGLP-1 was designed. Our analyses indicated that, relative to native GLP-1, mGLP-1 is more resistant to trypsin and pancreatin degradation. mGLP-1 promotes mouse pancreatic β-cell proliferation by up-regulating the expression level of cyclin E, CDK2, Bcl-2 and down-regulating Bax, p21, and stimulates insulin secretion. An oral glucose tolerance test indicated that mGLP-1 significantly improved glucose tolerance in mice. Intraperitoneal injections of mGLP-1 into streptozotocin (STZ-induced type 2 diabetic mice significantly reduced blood sugar levels and stimulated insulin secretion. Oral gavages of mGLP-1 in diabetic mice did not result in significant hypoglycemic activity.

Human rather than ape-like orbital morphology allows much greater lateral visual field expansion with eye abduction

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Denion, Eric; Hitier, Martin; Levieil, Eric; Mouriaux, Frédéric

2015-01-01

While convergent, the human orbit differs from that of non-human apes in that its lateral orbital margin is significantly more rearward. This rearward position does not obstruct the additional visual field gained through eye motion. This additional visual field is therefore considered to be wider in humans than in non-human apes. A mathematical model was designed to quantify this difference. The mathematical model is based on published computed tomography data in the human neuro-ocular plane (NOP) and on additional anatomical data from 100 human skulls and 120 non-human ape skulls (30 gibbons; 30 chimpanzees / bonobos; 30 orangutans; 30 gorillas). It is used to calculate temporal visual field eccentricity values in the NOP first in the primary position of gaze then for any eyeball rotation value in abduction up to 45° and any lateral orbital margin position between 85° and 115° relative to the sagittal plane. By varying the lateral orbital margin position, the human orbit can be made “non-human ape-like”. In the Pan-like orbit, the orbital margin position (98.7°) was closest to the human orbit (107.1°). This modest 8.4° difference resulted in a large 21.1° difference in maximum lateral visual field eccentricity with eyeball abduction (Pan-like: 115°; human: 136.1°). PMID:26190625

An Abbreviated Protocol for In Vitro Generation of Functional Human Embryonic Stem Cell-Derived Beta-Like Cells.

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Mohammad Massumi

Full Text Available The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs. We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems. The activation of FGF and Retinoic Acid along with the inhibition of BMP, SHH and TGF-beta led to the generation of 75% NKX6.1+/NGN3+ Endocrine Progenitors. The inhibition of Notch and tyrosine kinase receptor AXL, and the treatment with Exendin-4 and T3 in the final stage resulted in 35% mono-hormonal insulin positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux analyses using Seahorse demonstrated that the ES-DBCs could efficiently metabolize glucose and generate intracellular signals to trigger insulin secretion. In conclusion, targeting selected signaling pathways for 25-30 days was sufficient to generate ES-DBCs in vitro. The ability of ES-DBCs to secrete insulin in response to glucose renders them a promising model for the in vitro screening of drugs, small molecules or genes that may have potential to influence beta-cell function.

Conciliatory gestures promote forgiveness and reduce anger in humans.

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McCullough, Michael E; Pedersen, Eric J; Tabak, Benjamin A; Carter, Evan C

2014-07-29

Conflict is an inevitable component of social life, and natural selection has exerted strong effects on many organisms to facilitate victory in conflict and to deter conspecifics from imposing harms upon them. Like many species, humans likely possess cognitive systems whose function is to motivate revenge as a means of deterring individuals who have harmed them from harming them again in the future. However, many social relationships often retain value even after conflicts have occurred between interactants, so natural selection has very likely also endowed humans with cognitive systems whose function is to motivate reconciliation with transgressors whom they perceive as valuable and nonthreatening, notwithstanding their harmful prior actions. In a longitudinal study with 337 participants who had recently been harmed by a relationship partner, we found that conciliatory gestures (e.g., apologies, offers of compensation) were associated with increases in victims' perceptions of their transgressors' relationship value and reductions in perceptions of their transgressors' exploitation risk. In addition, conciliatory gestures appeared to accelerate forgiveness and reduce reactive anger via their intermediate effects on relationship value and exploitation risk. These results strongly suggest that conciliatory gestures facilitate forgiveness and reduce anger by modifying victims' perceptions of their transgressors' value as relationship partners and likelihood of recidivism.

Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests

DEFF Research Database (Denmark)

Andreasen, Jesper T; Redrobe, John P; Nielsen, Elsebet Ø

2012-01-01

Emerging evidence points to an involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. Nicotine improves symptoms of depression in humans and shows antidepressant-like effects in rodents. Monoamine release is facilitated by nAChR stimulation, and nicotine-evoked serotonin (5...

Avaliação do potencial de aproveitamento energético dos resíduos de madeira e derivados gerados em fábricas do polo moveleiro de Ubá - MG

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Rogério Machado Pinto Farage

2013-03-01

Full Text Available http://dx.doi.org/10.5902/198050988454O presente estudo avaliou o potencial de reaproveitamento energético dos resíduos de madeira e seus derivados gerados no Polo Moveleiro de Ubá, MG. Painéis reconstituídos de MDF (medium density fiberboard, aglomerado e compensado foram caracterizados e classificados, identificando assim as oportunidades e possíveis limitações quanto à sua utilização. Por meio de diagnóstico realizado em 11 fábricas de móveis, verificou-se que os resíduos de madeira compreendem mais de 90 % do total dos resíduos sólidos gerados. Além da grande quantidade gerada, não foi identificada nenhuma ação integrada entre as fábricas do Polo para o adequado gerenciamento dos resíduos, negligenciando seus riscos ambientais e sanitários, bem como seu potencial energético. Contudo, os teores de umidade e poder calorífico dos resíduos demonstraram potencial para o seu reaproveitamento energético através da produção de briquetes. Os gases gerados em ensaios de combustão dos resíduos não apresentaram substâncias ou compostos tóxicos acima dos limites preconizados pelas normas ambientais, verificando, neste aspecto, um bom desempenho ambiental para o aproveitamento destes resíduos conforme proposto pelo presente estudo. Entretanto, as cinzas dos resíduos de aglomerado BP (baixa pressão e FF (finish foil apresentaram elevadas concentrações de cromo, enquadrando-se como Classe I (perigosos, segundo a ABNT/NBR 10004/2004.

Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes.

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Lipomi, Darren J; Vosgueritchian, Michael; Tee, Benjamin C-K; Hellstrom, Sondra L; Lee, Jennifer A; Fox, Courtney H; Bao, Zhenan

2011-10-23

Transparent, elastic conductors are essential components of electronic and optoelectronic devices that facilitate human interaction and biofeedback, such as interactive electronics, implantable medical devices and robotic systems with human-like sensing capabilities. The availability of conducting thin films with these properties could lead to the development of skin-like sensors that stretch reversibly, sense pressure (not just touch), bend into hairpin turns, integrate with collapsible, stretchable and mechanically robust displays and solar cells, and also wrap around non-planar and biological surfaces such as skin and organs, without wrinkling. We report transparent, conducting spray-deposited films of single-walled carbon nanotubes that can be rendered stretchable by applying strain along each axis, and then releasing this strain. This process produces spring-like structures in the nanotubes that accommodate strains of up to 150% and demonstrate conductivities as high as 2,200 S cm(-1) in the stretched state. We also use the nanotube films as electrodes in arrays of transparent, stretchable capacitors, which behave as pressure and strain sensors.

Localization of rDNA in small, nucleolus-like structures in human diplotene oocyte nuclei

Energy Technology Data Exchange (ETDEWEB)

Wolgemuth-Jarashow, D.J.; Jagiello, G.M.; Henderson, A.S.

1977-01-01

Small, nucleolus-like structures were demonstrated in the nuclei of human diplotene oocytes. At least some of these bodies were shown to be true micronucleoli by virtue of their ability to bind rRNA during RNA-DNA hybridization in situ.

Questions on unusual Mimivirus-like structures observed in human cells [version 1; referees: 2 approved

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Elena Angela Lusi

2017-03-01

Full Text Available Background: Mimiviruses or giant viruses that infect amoebas have the ability to retain the Gram stain, which is usually used to colour bacteria. There is some evidence suggesting that Mimiviruses can also infect human cells. Guided by these premises, we performed a routine Gram stain on a variety of human specimens to see if we could detect the same Gram positive blue granules that identify Mimiviruses in the amoebas. Methods: We analysed 24 different human specimens (liver, brain, kidney, lymph node and ovary using Gram stain histochemistry, electron microscopy immunogold, high resolution mass spectrometry and protein identification. Results: We detected in the human cells Gram positive granules that were distinct from bacteria. The fine blue granules displayed the same pattern of the Gram positive granules that diagnose Mimiviruses in the cytoplasm of the amoebas. Electron microscopy confirmed the presence of human Mimiviruses-like structures and mass spectrometry identified histone H4 peptides, which had the same footprints as giant viruses. However, some differences were noted: the Mimivirus-like structures identified in the human cells were ubiquitous and manifested a distinct mammalian retroviral antigenicity. Conclusions: Our main hypotheses are that the structures could be either giant viruses having a retroviral antigenicity or ancestral cellular components having a viral origin. However, other possible alternatives have been proposed to explain the nature and function of the newly identified structures.

Interactive Learning in SME-University Collaborations: A Conceptual Framework for Facilitating Interaction

DEFF Research Database (Denmark)

Filip, Diane

2013-01-01

. The facilitation process focuses on interactive learning and is divided into phases, which makes it easier for SMEs to progressive engage in innovation projects with researchers. In-depth interviews with the facilitators of the programme were conducted and focused on barriers to collaboration, human interaction......, and lessons learned. From the facilitators’ perspective, a conceptual model capturing the main actor’s activities in each phase paralleled with an illustration of the narrowed gap from the human interaction is presented in the paper. The main findings addressed the issues of human-based and system......-based barriers. One of the lessons learned is the importance of human interaction of narrowing the perceived gap by mitigating the human-based barriers, and to some extent also system-based barriers. The case presented in this paper has managerial and innovation policy implications....

Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles

International Nuclear Information System (INIS)

Teimoori, Salma; Seesuay, Watee; Jittavisutthikul, Surasak; Chaisri, Urai; Sookrung, Nitat; Densumite, Jaslan; Saelim, Nawannaporn; Chulanetra, Monrat; Maneewatch, Santi; Chaicumpa, Wanpen

2016-01-01

A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials. - Highlights: • Cell penetrable human scFvs (transbodies) to Ebolavirus (EBOV) VP40 were produced. • The transbodies inhibited egress of EBOV-like particles (VLPs) from human hepatocytes. • They interacted with VP40 CTD basic residues important for plasma membrane binding. • And hence interfere with viral matrix assembly and viral progeny budding. • This is the first report on human antibodies that target intracellular EBOV VP40.

Identification of Interstitial Cajal-like cells in the Human Thoracic Duct

DEFF Research Database (Denmark)

Bødtkjer, Donna Marie Briggs; Rumessen, Jüri; Baandrup, Ulrik

2013-01-01

were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c......-kit with vimentin or CD34 was observed in some cells. Electron microscopy analysis confirmed ICLCs as a major cell type of the human TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina, intermediate filaments and specific junctions to SMCs. ICLCs were ultrastructurally differentiable from other......Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques...

Cytocompatibility and biologic characteristics of synthetic scaffold materials of rabbit acellular vascular matrix combining with human-like collagen I.

Science.gov (United States)

Liu, Xuqian; Wang, Jie; Dong, Fusheng; Song, Peng; Tian, Songbo; Li, Hexiang; Hou, Yali

2017-10-01

Scaffold material provides a three-dimensional growing environment for seed cells in the research field of tissue engineering. In the present study, rabbit arterial blood vessel cells were chemically removed with trypsin and Triton X-100 to prepare rabbit acellular vascular matrix scaffold material. Observation by He&Masson staining revealed that no cellular components or nuclei existed in the vascular intima and media after decellularization. Human-like collagen I was combined with acellular vascular matrix by freeze-drying to prepare an acellular vascular matrix-0.25% human-like collagen I scaffold to compensate for the extracellular matrix loss during the decellularization process. We next performed a series of experiments to test the water absorbing quality, biomechanics, pressure resistance, cytotoxicity, and ultra-micro structure of the acellular vascular matrix composite material and natural rabbit artery and found that the acellular vascular matrix-0.25% human-like collagen I material behaved similarly to natural rabbit artery. In conclusion, the acellular vascular matrix-0.25% human-like collagen I composite material provides a new approach and lays the foundation for novel scaffold material research into tissue engineering of blood vessels.

Adult maturational processes and the facilitating environment.

Science.gov (United States)

Acklin, M W

1986-09-01

The psychoanalytic theory of religion has been seriously limited in its development, largely owing to Freud's emphasis on religion's neurotic elements and an overemphasis on the infantile origins of religious development. This paper offers a conceptual framework and advances the thesis, based on contemporary psychoanalytic, developmental theory, that 1) Erikson's concept of epigenesis has applicability across the life span; 2) that beyond-the-self identity is constituent to human maturation and self-completion; 3) that successful adult maturation requires a mirroring-facilitating environment; and 4) that religious values, meanings, images, and communities play an essential role-as-elements of the facilitating environment of later life.

You Look Human, But Act Like a Machine: Agent Appearance and Behavior Modulate Different Aspects of Human-Robot Interaction.

Science.gov (United States)

Abubshait, Abdulaziz; Wiese, Eva

2017-01-01

Gaze following occurs automatically in social interactions, but the degree to which gaze is followed depends on whether an agent is perceived to have a mind, making its behavior socially more relevant for the interaction. Mind perception also modulates the attitudes we have toward others, and determines the degree of empathy, prosociality, and morality invested in social interactions. Seeing mind in others is not exclusive to human agents, but mind can also be ascribed to non-human agents like robots, as long as their appearance and/or behavior allows them to be perceived as intentional beings. Previous studies have shown that human appearance and reliable behavior induce mind perception to robot agents, and positively affect attitudes and performance in human-robot interaction. What has not been investigated so far is whether different triggers of mind perception have an independent or interactive effect on attitudes and performance in human-robot interaction. We examine this question by manipulating agent appearance (human vs. robot) and behavior (reliable vs. random) within the same paradigm and examine how congruent (human/reliable vs. robot/random) versus incongruent (human/random vs. robot/reliable) combinations of these triggers affect performance (i.e., gaze following) and attitudes (i.e., agent ratings) in human-robot interaction. The results show that both appearance and behavior affect human-robot interaction but that the two triggers seem to operate in isolation, with appearance more strongly impacting attitudes, and behavior more strongly affecting performance. The implications of these findings for human-robot interaction are discussed.

Development and the evolvability of human limbs.

Science.gov (United States)

Young, Nathan M; Wagner, Günter P; Hallgrímsson, Benedikt

2010-02-23

The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.

Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

Science.gov (United States)

Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

2018-02-01

Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success. Testes from 15 adult gender dysphoria patients (mean ± standard deviation age 35 ± 9.3 years) showing spermatogonial arrest became available for this study after sex-reassignment surgery. In vitro primary testicular somatic cell cultures were generated to explore the self-organizing ability of testicular somatic cells to form testis cords over a 2-week period. Morphological phenotype, protein marker expression and temporal dynamics of cell reassembly were analyzed. Cell suspensions obtained by two-step enzymatic digestion were plated onto glass coverslips in 24-well plates. To obtain adherent somatic cells, the supernatant was discarded on Day 2. The culture of the attached cell population was continued. Reassembly into cord-like structures was analyzed daily by microscopic observations. Endpoints were qualitative changes in morphology. Cell types were characterized by phase-contrast microscopy and immunohistochemistry. Dynamics of cord formation were recorded by time-lapse microscopy. Primary adult human testicular cells underwent sequential morphological changes including compaction and reaggregation resulting in round or elongated cord-like structures. Time-lapse video recordings within the first 4 days of culture revealed highly dynamic processes of migration and coalescence of reaggregated cells. The cellular movements were mediated by peritubular cells. Immunohistochemical analysis showed that both SRY-related high mobility box 9-positive Sertoli and α-smooth muscle actin-positive peritubular myoid cells

Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK) inhibitors.

Science.gov (United States)

Sato, Yoshiyuki; Onozaki, Yu; Sugimoto, Tetsuya; Kurihara, Hideki; Kamijo, Kaori; Kadowaki, Chie; Tsujino, Toshiaki; Watanabe, Akiko; Otsuki, Sachie; Mitsuya, Morihiro; Iida, Masato; Haze, Kyosuke; Machida, Takumitsu; Nakatsuru, Yoko; Komatani, Hideya; Kotani, Hidehito; Iwasawa, Yoshikazu

2009-08-15

A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model.

Lipoestructura y relleno del polo superior de la mama frente a implantes Structural fat graft and lipofilling of mammary upper pole versus mammary implants

Directory of Open Access Journals (Sweden)

J.M. Cervilla Lozano

2012-09-01

Full Text Available La lipoestructura mamaria ofrece nuevas alternativas de tratamiento en la cirugía estética de aumento mamario, cumpliendo en algunos casos las expectativas esperadas y en otros no. Analizamos este hecho en 4 tipos de aplicación de lipoestructura mamaria que hemos venido realizando en los últimos años, centrándonos en un aspecto importante de esta cirugía que es el relleno del polo superior de la mama. Los tipos de aplicación empleados son: aumento mamario simple mediante lipoestructura en comparación con implantes; pexia más lipoestructura frente a pexia más implantes mamarios; reconstrucción de mama tuberosa mediante lipoestructura o implantes y finalmente, relleno periprotésico mediante lipoestructura en mamas sometidas a cirugía de aumento mamario con implantes. En definitiva, podríamos resumir este trabajo en una frase diciendo que la lipoestructura mamaria, a nuestro juicio, no sirve si lo que prima es conseguir el relleno del polo superior de la mama, siendo en este caso de elección la colocación de implantes mamarios. No obstante, en alguno de los casos señalados no solo es una alternativa, sino que obtiene resultados superiores a los logrados sólamente con implantes.The mammary structural fat graft offers news treatment options in breast augmentation cosmetic surgery, but it sometimes meets expectations and sometimes doesn´t. We analyze 4 different types of lipostructure mammary applications that we have been using in the last years, focused in an important aspect of this surgery as it´s the filling of the upper mammary pole. These applications are: mammary augmentation by simple structural fat compared with the use of mammary implants; structural fat graft and mastopexy versus implants and mastopexy; tuberous breast reconstruction using structural fat graft or implants and finally, periprosthetic filling in breast augmentation with mammary implants using structural fat graft. In short, we could summarize this paper

Treatment of dwarfism with recombinant human insulin-like growth factor-1.

Science.gov (United States)

Ranke, Michael B; Wölfle, Joachim; Schnabel, Dirk; Bettendorf, Markus

2009-10-01

The growth hormone-IGF (insulin-like growth factor) system plays a central role in hormonal growth regulation. Recombinant human (rh) growth hormone (GH) has been available since the late 1980s for replacement therapy in GH-deficient patients and for the stimulation of growth in patients with short stature of various causes. Growth promotion by GH occurs in part indirectly through the induction of IGF-1 synthesis. In primary disturbances of IGF-1 production, short stature can only be treated with recombinant human IGF-1 (rhIGF-1). rhIGF-1 was recently approved for this indication but can also be used to treat other conditions. Selective review of the literature on IGF-1 therapy, based on a PubMed search. In children with severe primary IGF-1 deficiency (a rare condition whose prevalence is less than 1:10,000), the prognosis for final height is very poor (ca. 130 cm), and IGF-1 therapy is the appropriate form of pathophysiologically based treatment. There is no alternative treatment at present. The subcutaneous administration of IGF-1 twice daily in doses of 80 to 120 microg/kg accelerates growth and increases final height by 12 to 15 cm, according to current data. There is, however, a risk of hypoglycemia, as IGF-1 has an insulin-like effect. As treatment with IGF-1 is complex, this new medication should only be prescribed, for the time being, by experienced pediatric endocrinologists and diabetologists.

Human-like collagen/nano-hydroxyapatite scaffolds for the culture of chondrocytes

Energy Technology Data Exchange (ETDEWEB)

Jia, Liping; Duan, Zhiguang [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Mi, Yu; Hui, Junfeng [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Chang, Le [School of Chemical Engineering, Northwest University, Xi' an, Shaanxi 710069 (China)

2013-03-01

Three dimensional (3D) biodegradable porous scaffolds play a key role in cartilage tissue repair. Freeze-drying and cross-linking techniques were used to fabricate a 3D composite scaffold that combined the excellent biological characteristics of human-like collagen (HLC) and the outstanding mechanical properties of nano-hydroxyapatite (nHA). The scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and compression tests, using Relive Registered-Sign Artificial Bone (RAB) scaffolds as a control. HLC/nHA scaffolds displayed homogeneous interconnected macroporous structure and could withstand a compression stress of 2.67 {+-} 0.37 MPa, which was higher than that of the control group. Rabbit chondrocytes were seeded on the composite porous scaffolds and cultured for 21 days. Cell/scaffold constructs were examined using SEM, histological procedures, and biochemical assays for cell proliferation and the production of glycosaminoglycans (GAGs). The results indicated that HLC/nHA porous scaffolds were capable of encouraging cell adhesion, homogeneous distribution and abundant GAG synthesis, and maintaining natural chondrocyte morphology compared to RAB scaffolds. In conclusion, the presented data warrants the further exploration of HLC/nHA scaffolds as a potential biomimetic platform for chondrocytes in cartilage tissue engineering. - Highlights: Black-Right-Pointing-Pointer Human-like collagen was first used to prepare cartilage tissue engineering scaffold. Black-Right-Pointing-Pointer Genipin, a natural biological cross-linking agent, was introduced to treat scaffold. Black-Right-Pointing-Pointer We chose market product as a control.

Forensic toxicology in drug-facilitated sexual assault.

Science.gov (United States)

Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

2013-09-01

The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

A genome-wide RNAi screen to dissect centriole duplication and centrosome maturation in Drosophila.

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Jeroen Dobbelaere

2008-09-01

Full Text Available Centrosomes comprise a pair of centrioles surrounded by an amorphous pericentriolar material (PCM. Here, we have performed a microscopy-based genome-wide RNA interference (RNAi screen in Drosophila cells to identify proteins required for centriole duplication and mitotic PCM recruitment. We analysed 92% of the Drosophila genome (13,059 genes and identified 32 genes involved in centrosome function. An extensive series of secondary screens classified these genes into four categories: (1 nine are required for centriole duplication, (2 11 are required for centrosome maturation, (3 nine are required for both functions, and (4 three genes regulate centrosome separation. These 32 hits include several new centrosomal components, some of which have human homologs. In addition, we find that the individual depletion of only two proteins, Polo and Centrosomin (Cnn can completely block centrosome maturation. Cnn is phosphorylated during mitosis in a Polo-dependent manner, suggesting that the Polo-dependent phosphorylation of Cnn initiates centrosome maturation in flies.

Acer negundo invasion along a successional gradient: early direct facilitation by native pioneers and late indirect facilitation by conspecifics.

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Saccone, Patrick; Pagès, Jean-Philippe; Girel, Jacky; Brun, Jean-Jacques; Michalet, Richard

2010-08-01

*Here, we analysed the role of direct and indirect plant interactions in the invasion process of Acer negundo along a natural successional gradient in the Middle Rhone floodplain (France). We addressed two questions: What are the responses of the invasive Acer seedlings to native communities' effects along the successional gradient? What are the effects of the invasive Acer adult trees on the native communities? *In the three communities (Salix, Acer and Fraxinus stands) we transplanted juveniles of the invasive and juveniles of the natives within the forest and in experimental gaps, and with and without the herb layer. We also quantified changes in understory functional composition, light, nitrogen and moisture among treatments. *Acer seedlings were directly facilitated for survival in the Salix and Acer communities and indirectly facilitated for growth by adult Acer through the reduction of the abundance of highly competitive herbaceous competitors. *We conclude that direct facilitation by the tree canopy of the native pioneer Salix is very likely the main biotic process that induced colonization of the invasive Acer in the floodplain and that indirect facilitation by adult conspecifics contributed to population establishment.

Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

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Govindarajan Kunde R

2011-05-01

Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates.

Science.gov (United States)

Hodge, L D; Barrett, J M; Welter, D A

1995-04-01

There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G-specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell.

Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells

DEFF Research Database (Denmark)

Wanscher, Anne Sofie Molsted; Williamson, Michael; Ebersole, Tasja Wainani

2015-01-01

on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins...... and the final protein yields were between 1 and 12mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2.......Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge...

Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells.

Science.gov (United States)

Wanscher, Anne Sofie Molsted; Williamson, Michael; Ebersole, Tasja Wainani; Streicher, Werner; Wikström, Mats; Cazzamali, Giuseppe

2015-04-01

Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins such as full-length human IGFBPs, still remains a challenge. Here we present a mammalian HEK293 expression method suitable for over-expression of secretory full-length human IGFBP-1 to -7. Protein purification of full-length human IGFBP-1, -2, -3 and -5 was conducted using a two-step chromatography procedure and the final protein yields were between 1 and 12mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2. Copyright © 2014 Elsevier Inc. All rights reserved.

Human blood-brain barrier insulin-like growth factor receptor

International Nuclear Information System (INIS)

Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

1988-01-01

Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125 I-IGF-1, 125 I-IGF-2, and 125 I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

Full Genome Characterization of Novel DS-1-Like G8P[8] Rotavirus Strains that Have Emerged in Thailand: Reassortment of Bovine and Human Rotavirus Gene Segments in Emerging DS-1-Like Intergenogroup Reassortant Strains.

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Ratana Tacharoenmuang

Full Text Available The emergence and rapid spread of unusual DS-1-like intergenogroup reassortant rotavirus strains have been recently reported in Asia, Australia, and Europe. During rotavirus surveillance in Thailand in 2013-2014, novel DS-1-like intergenogroup reassortant strains having G8P[8] genotypes (i.e., strains KKL-17, PCB-79, PCB-84, PCB-85, PCB-103, SKT-107, SWL-12, NP-130, PCB-656, SKT-457, SSKT-269, and SSL-55 were identified in stool samples from hospitalized children with severe diarrhea. In this study, we determined and characterized the complete genomes of these 12 strains (seven strains, KKL-17, PCB-79, PCB-84, PCB-85, PCB-103, SKT-107, and SWL-12, found in 2013 (2013 strains, and five, NP-130, PCB-656, SKT-457, SSKT-269, and SSL-55, in 2014 (2014 strains. On full genomic analysis, all 12 strains showed a unique genotype constellation comprising a mixture of genogroup 1 and 2 genes: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. With the exception of the G genotype, the unique genotype constellation of the 12 strains (P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 was found to be shared with DS-1-like intergenogroup reassortant strains. On phylogenetic analysis, six of the 11 genes of the 2013 strains (VP4, VP2, VP3, NSP1, NSP3, and NSP5 appeared to have originated from DS-1-like intergenogroup reassortant strains, while the remaining four (VP7, VP6, VP1, and NSP2 and one (NSP4 gene appeared to be of bovine and human origin, respectively. Thus, the 2013 strains appeared to be reassortant strains as to DS-1-like intergenogroup reassortant, bovine, bovine-like human, and/or human rotaviruses. On the other hand, five of the 11 genes of the 2014 strains (VP4, VP2, VP3, NSP1, and NSP3 appeared to have originated from DS-1-like intergenogroup reassortant strains, while three (VP7, VP1, and NSP2 and one (NSP4 were assumed to be of bovine and human origin, respectively. Notably, the remaining two genes, VP6 and NSP5, of the 2014 strains appeared to have originated from locally

Facilitated Articulation of Implicit Knowledge in Textile Design

DEFF Research Database (Denmark)

Bang, Anne Louise

2009-01-01

This is a report from an ongoing research project and as such it is work in progress. The paper proposes an exploratory approach in order to enable end-users to contribute with their experiences of emotional values of fabrics in use. It is suggested that the textile designer with her repertoire...... of (experiential, implicit and tacit) textile design knowledge should facilitate the articulation process. The paper specifically draws on a series of workshops conducted within the collaborating company inviting all employees to participate. The series of workshops were based on a game-like setting and introduced...... - being a textile designer herself, who functioned as the facilitator. This paper uses two examples from the series of workshops to exemplify a facilitated articulation of implicit knowledge in textile design. From the examples the following themes are synthesised as being important for articulation...

Empirical evaluation of a forecasting model for successful facilitation ...

African Journals Online (AJOL)

During 2000 the annual Facilitator Customer Satisfaction Survey was ... the forecasting model is successful concerning the CSI value and a high positive linear ... namely that of human behaviour to incorporate other influences than just the ...

Creation and Staging of Android Theatre “Sayonara”towards Developing Highly Human-Like Robots

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Takenobu Chikaraishi

2017-11-01

Full Text Available Even after long-term exposures, androids with a strikingly human-like appearance evoke unnatural feelings. The behavior that would induce human-like feelings after long exposures is difficult to determine, and it often depends on the cultural background of the observers. Therefore, in this study, we generate an acting performance system for the android, in which an android and a human interact in a stage play in the real world. We adopt the theatrical theory called Contemporary Colloquial Theatre Theory to give the android natural behaviors so that audiences can comfortably observe it even after long-minute exposure. A stage play is created and shown in various locations, and the audiences are requested to report their impressions of the stage and their cultural and psychological backgrounds in a self-evaluating questionnaire. Overall analysis indicates that the audience had positive feelings, in terms of attractiveness, towards the android on the stage even after 20 min of exposure. The singularly high acceptance of the android by Japanese audiences seems to be correlated with a high animism tendency, rather than to empathy. We also discuss how the stage play approach is limited and could be extended to contribute to realization of human–robot interaction in the real world.

Design of a Vitronectin-Based Recombinant Protein as a Defined Substrate for Differentiation of Human Pluripotent Stem Cells into Hepatocyte-Like Cells.

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Masato Nagaoka

Full Text Available Maintenance and differentiation of human pluripotent stem cells (hPSCs usually requires culture on a substrate for cell adhesion. A commonly used substratum is Matrigel purified from Engelbreth-Holm-Swarm sarcoma cells, and consists of a complex mixture of extracellular matrix proteins, proteoglycans, and growth factors. Several studies have successfully induced differentiation of hepatocyte-like cells from hPSCs. However, most of these studies have used Matrigel as a cell adhesion substrate, which is not a defined culture condition. In an attempt to generate a substratum that supports undifferentiated properties and differentiation into hepatic lineage cells, we designed novel substrates consisting of vitronectin fragments fused to the IgG Fc domain. hPSCs adhered to these substrates via interactions between integrins and the RGD (Arg-Gly-Asp motif, and the cells maintained their undifferentiated phenotypes. Using a previously established differentiation protocol, hPSCs were efficiently differentiated into mesendodermal and hepatic lineage cells on a vitronectin fragment-containing substrate. We found that full-length vitronectin did not support stable cell adhesion during the specification stage. Furthermore, the vitronectin fragment with the minimal RGD-containing domain was sufficient for differentiation of human induced pluripotent stem cells into hepatic lineage cells under completely defined conditions that facilitate the clinical application of cells differentiated from hPSCs.

Expression and function of NOD-like receptors by human term gestation-associated tissues.

Science.gov (United States)

Bryant, Aled H; Bevan, Ryan J; Spencer-Harty, Samantha; Scott, Louis M; Jones, Ruth H; Thornton, Catherine A

2017-10-01

Nucleotide-binding oligomerization domain (NOD)-like receptors or NOD-like receptors (NLRs) have been implicated in several disease pathologies associated with inflammation. Since local and systemic inflammation is a hallmark of both term and preterm labour, a role for NLRs at the materno-fetal interface has been postulated. Gene expression and immunolocalisation of NLR family members in human placenta, choriodecidua, and amnion were examined. Tissue explants were used to examine the response to activators of NOD1 (Tri-DAP), NOD2 (MDP) and NLRP3 (nigericin). Cell/tissue-free supernatants were examined for the production of interleukin (IL)-1β, IL-6, IL-8 and IL-10 using specific ELISAs. Expression of transcripts for NOD1, NOD2, NLRP3, NLRC4, NLRX1, NLRP1 and NAIP and protein expression of NOD1, NOD2 and NLRP3 were a broad feature of all term gestation-associated tissues. Production of cytokines was increased significantly in response to all ligands in placenta and choriodecidua, except for MDP-induced IL-10. Similarly, there was a significant in the amnion except for MDP induced IL-1β and IL-10 response to either agonist. IL-1β production was dependent on caspase-1 regardless of agonist used or tissue examined. Term human gestation-associated tissues express functional NLRs which likely play a role in both sterile and pathogen-driven inflammatory responses at the materno-fetal interface. Copyright © 2017 Elsevier Ltd. All rights reserved.

Argumentation: A Methodology to Facilitate Critical Thinking.

Science.gov (United States)

Makhene, Agnes

2017-06-20

Caring is a difficult nursing activity that involves a complex nature of a human being in need of complex decision-making and problem solving through the critical thinking process. It is mandatory that critical thinking is facilitated in general and in nursing education particularly in order to render care in diverse multicultural patient care settings. This paper aims to describe how argumentation can be used to facilitate critical thinking in learners. A qualitative, exploratory and descriptive design that is contextual was used. Purposive sampling method was used to draw a sample and Miles and Huberman methodology of qualitative analysis was used to analyse data. Lincoln and Guba's strategies were employed to ensure trustworthiness, while Dhai and McQuoid-Mason's principles of ethical consideration were used. Following data analysis the findings were integrated within literature which culminated into the formulation of guidelines that can be followed when using argumentation as a methodology to facilitate critical thinking.

Oxygen uptake during Wingate tests for arms and legs in swimmers and water polo players

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Colantonio Emilson

2003-01-01

Full Text Available OBJECTIVE: The aim of the present study is to compare the values of the maximal oxygen uptake (O2 max during two consecutive bouts in Wingate tests for arms and legs in swimmers (S and water polo players (WP. METHODS: Sample - seven national level athletes (4 S and 3 WP, age 17,90 ± 2,14 years, body mass 71,41 ± 6,84 kg, height 176,65 ± 7,02 cm, % body fat 13,23 ± 4,18. Two Wingate bouts with 30 sec each with 3 min interval between them, for arms and legs in alternated days. Oxygen uptake: breath-by-breath using the gas analysis system K4 b² Cosmed. Statistical analysis: Wilcoxon test for dependent variables and Kolmogorov-Smirnov test for independent variables. RESULTS: The mean values found at the O2 peak (PO2, mean power (MP and peak power (PP for each bout of the Wingate test, for arms and legs. For Arms: PO2 = 55.16 ± 5.72 ml.kg-1.min-1, MP = 5.28 ± 0.59 watts.kg-1 and PP = 6.71 ± 0.88 watts.kg-1 got in the first bout (1st Arms and PO2 = 60.12 ± 6.10 ml.kg-1.min-1, MP = 5.03 ± 0.40 watts.kg-1 and PP = 6.25 ± 0.51 watts.kg-1, got in the second bout (2nd Arms. For legs: PO2 = 55.66 ± 6.85 ml.kg-1.min-1, MP = 4.75 ± 1.79 watts.kg-1 and PP = 7.44 ± 1.96 watts.kg-1 got in the first bout (1st Legs and PO2 = 62.09 ± 5.99 ml.kg-1.min-1, MP = 4.28 ± 1.47 watts.kg-1 and PP = 6.68 ± 1.63 watts.kg-1 got in the second bout (2nd Legs. DISCUSSION AND CONCLUSION: All variables studied did not present significant difference among arms and legs, as much the first as the second bout for arms for PO2 (p < 0.05. There was no difference between the PM mean values of the first and the second bout. But the mean of the second bout of legs was significant smaller than the first bout (p < 0.05. For the PP variable there was no difference among the mean values to the first and second bout as much for arms as for legs. It looks like to exist larger magnitude to O2 adjustment for arms than legs, that could be associated to specific demands to which S

Semantic Coherence Facilitates Distributional Learning.

Science.gov (United States)

Ouyang, Long; Boroditsky, Lera; Frank, Michael C

2017-04-01

Computational models have shown that purely statistical knowledge about words' linguistic contexts is sufficient to learn many properties of words, including syntactic and semantic category. For example, models can infer that "postman" and "mailman" are semantically similar because they have quantitatively similar patterns of association with other words (e.g., they both tend to occur with words like "deliver," "truck," "package"). In contrast to these computational results, artificial language learning experiments suggest that distributional statistics alone do not facilitate learning of linguistic categories. However, experiments in this paradigm expose participants to entirely novel words, whereas real language learners encounter input that contains some known words that are semantically organized. In three experiments, we show that (a) the presence of familiar semantic reference points facilitates distributional learning and (b) this effect crucially depends both on the presence of known words and the adherence of these known words to some semantic organization. Copyright © 2016 Cognitive Science Society, Inc.

Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer.

Science.gov (United States)

Peng, Liu-Sheng; Mao, Fang-Yuan; Zhao, Yong-Liang; Wang, Ting-Ting; Chen, Na; Zhang, Jin-Yu; Cheng, Ping; Li, Wen-Hua; Lv, Yi-Pin; Teng, Yong-Sheng; Guo, Gang; Luo, Ping; Chen, Weisan; Zou, Quan-Ming; Zhuang, Yuan

2016-08-23

CD3+CD56+ natural killer T (NKT)-like cells are a group of CD3+ T cells sharing characteristics of NK and T cells and constitute a major component of host anti-tumor immune response in human cancer. However, the nature, function and clinical relevance of CD3+CD56+ NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3+CD56+NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3+CD56+ NKT-like cells were positively correlated with poor survival and disease progression. Most CD3+CD56+NKT-like cells in GC tumors were CD45RA-CD27+/- central/effector-memory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3+CD56+ NKT-like cells had impaired effector function as shown by decreased IFN-γ, TNF-α, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3+CD56+ NKT-like cells. Collectively, our data indicate that decreased tumor-infiltrating CD3+CD56+ NKT-like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC.

The Influences of Arm Resist Motion on a CAR Crash Test Using Hybrid III Dummy with Human-Like Arm

Science.gov (United States)

Kim, Yongchul; Youm, Youngil; Bae, Hanil; Choi, Hyeonki

Safety of the occupant during the crash is very essential design element. Many researches have been investigated in reducing the fatal injury of occupant. They are focusing on the development of a dummy in order to obtain the real human-like motion. However, they have not considered the arm resist motion during the car accident. In this study, we would like to suggest the importance of the reactive force of the arm in a car crash. The influences of reactive force acting on the human upper extremity were investigated using the impedance experimental method with lumped mass model of hand system and a Hybrid III dummy with human-like arm. Impedance parameters (e.g. inertia, spring constant and damping coefficient) of the elbow joint in maximum activation level were measured by free oscillation test using single axis robot. The results showed that without seat belt, the reactive force of human arm reduced the head, chest, and femur injury, and the flexion moment of the neck is higher than that of the conventional dummy.

Two different mechanisms associated with ripple-like oscillations (100-250 Hz) in the human epileptic subiculum in vitro

Science.gov (United States)

Alvarado-Rojas, C; Huberfeld, G; Baulac, M; Clemenceau, S; Charpier, S; Miles, R; Menendez de la Prida, L; Le Van Quyen, M

2015-01-01

Transient high-frequency oscillations (150-600 Hz) in local field potential generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of high-frequency oscillations (HFO) has been controversial. Here, we searched for HFOs in slices of the subiculum prepared from human hippocampal tissue resected for treatment of pharmacoresistant epilepsy. HFOs occurred spontaneously in extracellular field potentials during interictal discharges (IID) and also during pharmacologically induced preictal discharges (PID) preceding ictal-like events. While most of these events might be considered pathological since they invaded the fast ripple band (>250 Hz), others were spectrally similar to physiological ripples (150-250 Hz). Do similar cellular mechanisms underly IID-ripples and PID-ripples? Are ripple-like oscillations a valid proxy of epileptogenesis in human TLE? With combined intra- or juxta-cellular and extracellular recordings, we showed that, despite overlapping spectral components, ripple-like IID and PID oscillations were associated with different cellular and synaptic mechanisms. IID-ripples were associated with rhythmic GABAergic and glutamatergic synaptic potentials with moderate neuronal firing. In contrast, PID-ripples were associated with depolarizing synaptic inputs frequently reaching the threshold for bursting in most cells. Thus ripple-like oscillations (100-250 Hz) in the human epileptic hippocampus are associated with different mechanisms for synchrony reflecting distinct dynamic changes in inhibition and excitation during interictal and pre-ictal states. PMID:25448920

Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

Directory of Open Access Journals (Sweden)

Juan Roberto Rodriguez-Madoz

Full Text Available The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272 improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

Science.gov (United States)

Rodriguez-Madoz, Juan Roberto; San Jose-Eneriz, Edurne; Rabal, Obdulia; Zapata-Linares, Natalia; Miranda, Estibaliz; Rodriguez, Saray; Porciuncula, Angelo; Vilas-Zornoza, Amaia; Garate, Leire; Segura, Victor; Guruceaga, Elizabeth; Agirre, Xabier; Oyarzabal, Julen; Prosper, Felipe

2017-01-01

The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

3D electrical image in area contaminated by hydrocarbons at the Cubatao, Brazil, industrial pole; Imageamento eletrico 3D em area contaminada por hidrocarbonetono no polo industrial de Cubatao - SP, Brasil

Energy Technology Data Exchange (ETDEWEB)

Baessa, Marcus Paulus Martins [Centro de Pesquisas e Desenvolvimento Leopoldo Americo Miguez de Mello, CENPES, Rio de Janeiro, RJ (Brazil)], E-mail: marcus.baessa@petrobras.br; Oliva, Andresa; Kiang, Chang Hung [Universidade Estadual Paulista, UNESP, Rio Claro, SP (Brazil)], E-mails: aoliva@rc.unesp.br, chang@rc.unesp.br

2010-12-15

This work presents the results of geophysical surveys performed over an oil contaminated site in the Polo Industrial de Cubatao - Sao Paulo. The aim is to characterize geoelectrical signatures associated to hydrocarbon presence in order to delimit and calculate the volume of the contaminated area. For this study were used Vertical Electrical Sounding (VES) and 3D Electrical Imaging for characterization of geology and geoelectrical response of the contaminant. The results showed that the hydrocarbon presence is associated to conductive anomalies due to products from biodegradation. The conductive anomalies are disseminated over the area, totalizing 1365.3 m3 volume. This volume, however, corresponds only to the residual phase contaminants, since it was not possible to map free-phase hydrocarbons. (author)

Recognition of Histo-Blood Group Antigen-Like Carbohydrates in Lettuce by Human GII.4 Norovirus.

Science.gov (United States)

Gao, Xiang; Esseili, Malak A; Lu, Zhongyan; Saif, Linda J; Wang, Qiuhong

2016-05-15

Human norovirus (HuNoV) genogroup II genotype 4 (GII.4) strains account for about 80% of the gastroenteritis outbreaks in the United States. Contaminated food is a major transmission vehicle for this virus. In humans, pigs, and oysters, histo-blood group antigens (HBGAs) act as attachment factors for HuNoVs. In lettuce, although the virus-like particles (VLPs) of a GII.4 HuNoV were found to bind to cell wall carbohydrates, the exact binding site has not been investigated. Here, we show the presence of HBGA-like carbohydrates in the cell wall of lettuce. The digestion of lettuce leaves with cell wall-degrading enzymes exposed more binding sites and significantly increased the level of binding of GII.4 HuNoV VLPs. Competition assays showed that both the HBGA monoclonal antibody, recognizing the H type, and plant lectins, recognizing α-l-fucose in the H type, effectively inhibited VLP binding to lettuce tissues. Lettuce cell wall components were isolated and their NoV VLP binding characteristics were tested by enzyme-linked immunosorbent assays. The binding was inhibited by pretreatment of the lettuce cell wall materials with α-1,2-fucosidase. Collectively, our results indicate that H-type HBGA-like carbohydrates exist in lettuce tissues and that GII.4 HuNoV VLPs can bind the exposed fucose moiety, possibly in the hemicellulose component of the cell wall. Salad crops and fruits are increasingly recognized as vehicles for human norovirus (HuNoV) transmission. A recent study showed that HuNoVs specifically bind to the carbohydrates of the lettuce cell wall. Histo-blood group antigens (HBGAs) are carbohydrates and are known as the attachment factors for HuNoV infection in humans. In this study, we show the presence of HBGA-like carbohydrates in lettuce, to which HuNoVs specifically bind. These results suggest that specifically bound HuNoVs cannot be removed by simple washing, which may allow viral transmission to consumers. Our findings provide new information needed

A radioreceptor-assay of a methionine-enkephalin-like substance in human CSF

International Nuclear Information System (INIS)

Furui, Tomoo; Kageyama, Naoki; Haga, Tatsuya; Ichiyama, Arata; Fukushima, Masanori.

1980-01-01

The purpose of this study was to establish a radioreceptor-assay system of the met-enkephalin-like substance in human CSF. A particulate fraction was prepared from rat brain essentially according to the method of Pasternak and used as a receptor. In order to obtain the most sensitive radioreceptor-assay, displacement curves by met-enkephalin were compared with each other using three kinds of radiolabeled ligand: 3 H-met-enkephalin, 3 H-naloxone and 3 H-dihydromorphine. When 3 H-dihydromorphine was used as the radiolabeled ligand, the concentration of met-enkephalin required to inhibit 50% of specific binding (IC 50 ) was the lowest. The addition of 1 mM EDTA and 2 mM Mg was found to decrease further the IC 50 and enhance the binding. Thus the radioreceptor-assay of the metenkephalin-like substance in CSF was carried out using 3 H-dihydromorphine as the radiolabeled ligand in the presence of 1 mM EDTA and 2 mM Mg. The sensitivity of the assay ranged from about 1 to 100 pmoles of met-enkephalin. The isolation of met-enkephalin from CSF was performed by a Sephadex G 10 gel filtration followed by a SP-Sephadex (H + ) column chromatography. Sodium and non-specific inhibitor (s) of the specific binding of 3 H-dihydromorphine were removed from CSF by the chromatography. The overall recovery of met-enkephalin was about 60%. Human CSF was obtained from 8 patients hospitalized for neurosurgical study and therapy. All assays were duplicated. The met-enkephalin-like substance levels were 3.3 +- 2.1 (mean +- S.D., n=8) pmoles/ml and ranged from 0.7 to 6.7 pmoles of the met-enkephalin equivalents. (J.P.N.)

Leadership Development Through Peer-Facilitated Simulation in Nursing Education.

Science.gov (United States)

Brown, Karen M; Rode, Jennifer L

2018-01-01

Baccalaureate nursing graduates must possess leadership skills, yet few opportunities exist to cultivate leadership abilities in a clinical environment. Peer-facilitated learning may increase the leadership skills of competence, self-confidence, self-reflection, and role modeling. Facilitating human patient simulation provides opportunities to develop leadership skills. With faculty supervision, senior baccalaureate students led small-group simulation experiences with sophomore and junior peers and then conducted subsequent debriefings. Quantitative and qualitative descriptive data allowed evaluation of students' satisfaction with this teaching innovation and whether the experience affected students' desire to take on leadership roles. Students expressed satisfaction with the peer-facilitated simulation experience and confidence in mastering the content while developing necessary skills for practice. Peer-facilitated simulation provides an opportunity for leadership development and learning. Study results can inform the development of nursing curricula to best develop the leadership skills of nursing students. [J Nurs Educ. 2018;57(1):53-57.]. Copyright 2018, SLACK Incorporated.

Modulation of Hematopoietic Lineage Specification Impacts TREM2 Expression in Microglia-Like Cells Derived From Human Stem Cells.

Science.gov (United States)

Amos, Peter J; Fung, Susan; Case, Amanda; Kifelew, Jerusalem; Osnis, Leah; Smith, Carole L; Green, Kevin; Naydenov, Alipi; Aloi, Macarena; Hubbard, Jesse J; Ramakrishnan, Aravind; Garden, Gwenn A; Jayadev, Suman

2017-01-01

Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines. Our approach is based on recent studies demonstrating that microglia originate from primitive yolk sac mesoderm distinct from peripheral macrophages that arise during definitive hematopoiesis. We hypothesized that functional microglia could be derived from human stem cells by employing BMP-4 mesodermal specification followed by exposure to microglia-relevant cytokines, M-CSF, GM-CSF, IL-34, and TGF-β. Using immunofluorescence microscopy, flow cytometry, and reverse transcription polymerase chain reaction, we observed cells with microglia morphology expressing a repertoire of markers associated with microglia: Iba1, CX3CR1, CD11b, TREM2, HexB, and P2RY12. These microglia-like cells maintain myeloid functional phenotypes including Aβ peptide phagocytosis and induction of pro-inflammatory gene expression in response to lipopolysaccharide stimulation. Addition of small molecules BIO and SB431542, previously demonstrated to drive definitive hematopoiesis, resulted in decreased surface expression of TREM2. Together, these data suggest that mesodermal lineage specification followed by cytokine exposure produces microglia-like cells in vitro from human pluripotent stem cells and that this phenotype can be modulated by factors influencing hematopoietic lineage in vitro.

Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors

OpenAIRE

Wu, Shwu-Yuan; Zhou, Tianyuan; Chiang, Cheng-Ming

2003-01-01

Mediator is a general cofactor implicated in the functions of many transcriptional activators. Although Mediator with different protein compositions has been isolated, it remains unclear how Mediator facilitates activator-dependent transcription, independent of its general stimulation of basal transcription. To define the mechanisms of Mediator function, we isolated two forms of human Mediator complexes (Mediator-P.5 and Mediator-P.85) and demonstrated that Mediator-P.5 clearly functions by e...

PCDD/F and dioxin-like PCB in human blood and milk from German mothers

Energy Technology Data Exchange (ETDEWEB)

Wittsiepe, J.; Schrey, P.; Lemm, F.; Wilhelm, M. [Ruhr-Univ. Bochum, Abt. fuer Hygiene, Sozial- und Umweltmedizin (Germany); Fuerst, P. [Chemisches Landes- und Staatliches Veterinaeruntersuchungsamt, Muenster (Germany); Kraft, M. [Ministerium fuer Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Duesseldorf (Germany); Eberwein, G. [Landesumweltamt Nordrhein-Westfalen, Essen (Germany); Winneke, G. [Medizinisches Inst. fuer Umwelthygiene an der Heinrich-Heine Univ. Duesseldorf (Germany)

2004-09-15

Human biomonitoring of polychlorinated dibenzo-p-dioxins and dibenzofuranes (PCDD/F) and polychlorinated biphenyls (PCB) is done by analyzing both blood and milk samples. With reference to calculation of Toxicity Equivalents (TEq) as published by the World Health Organization (WHO) in 1998 determination of 17 PCDD/F congeners together with 4 non- and 8 mono-ortho PCB congeners is the preferred method. In contrast to data on PCDD/F only little is known on background levels of dioxin-like PCB in human blood or milk samples. In the present study we report on PCDD/F and PCB levels in human blood samples of pregnant women living in an industrialized area of Germany and of human milk samples from the same women taken in the first weeks after birth. The investigations demonstrate the current background levels found in Germany, make a contribution for the assessment of preand postnatal exposure of infants and show correlations between the two matrices.

Advancing knowledge on practice change: linking facilitation to the senses framework.

Science.gov (United States)

Cooper, Julie; Meyer, Julienne; Holman, Cheryl

2013-06-01

To explore the facilitating factors that enabled staff on a rehabilitation ward for older people engage in change activities. The importance of facilitation in practice change is widely acknowledged; however, little nursing research has taken place in relation to its nature. Following identification in the early phases of an action research study that learned helplessness states and the use of socially structured defence techniques were preventing staff on a rehabilitation ward for older people from engaging in practice development, some change was achieved. What facilitated this to take place needed to be explored. An action research approach was used. Data gained from 13 in-depth interviews with staff and managers together with three years of researcher field notes were analysed using thematic analysis. The continuous presence and neutrality of the researcher who worked together with staff on their issues of concern using a flexible ward-based approach, combined with giving staff the opportunity to explore what it was like for them working in this area, were considered key in helping staff to engage with change. Analysis of findings suggests that the senses framework presents a theoretical approach to facilitation that can help staff move out of learned helplessness states and reduce the need for the use of socially structured defence techniques. This study identifies a facilitation approach that enabled staff to engage with practice change. Although carried out in the UK, its findings have wider relevance through the application of a theoretical perspective for practice change facilitation that has not before been considered in this literature, and which is likely to be of interest to those involved in practice change internationally. © 2013 Blackwell Publishing Ltd.

Rho kinase inhibitor Y-27632 promotes the differentiation of human bone marrow mesenchymal stem cells into keratinocyte-like cells in xeno-free conditioned medium.

Science.gov (United States)

Li, Zhenzhen; Han, Shichao; Wang, Xingqin; Han, Fu; Zhu, Xiongxiang; Zheng, Zhao; Wang, Hongtao; Zhou, Qin; Wang, Yunchuan; Su, Linlin; Shi, Jihong; Tang, Chaowu; Hu, Dahai

2015-03-11

Bone marrow mesenchymal stem cells (BMSCs), which have the ability to self-renew and to differentiate into multiple cell types, have recently become a novel strategy for cell-based therapies. The differentiation of BMSCs into keratinocytes may be beneficial for patients with burns, disease, or trauma. However, the currently available cells are exposed to animal materials during their cultivation and induction. These xeno-contaminations severely limit their clinical outcomes. Previous studies have shown that the Rho kinase (ROCK) inhibitor Y-27632 can promote induction efficiency and regulate the self-renewal and differentiation of stem cells. In the present study, we attempted to establish a xeno-free system for the differentiation of BMSCs into keratinocytes and to investigate whether Y-27632 can facilitate this differentiation. BMSCs isolated from patients were cultured by using a xeno-free system and characterised by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. Human primary keratinocytes were also isolated from patients. Then, the morphology, population doubling time, and β-galactosidase staining level of these cells were evaluated in the presence or absence of Y-27632 to determine the effects of Y-27632 on the state of the keratinocytes. Keratinocyte-like cells (KLCs) were detected at different time points by immunocytofluorescence analysis. Moreover, the efficiency of BMSC differentiation under different conditions was measured by quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. The ROCK inhibitor Y-27632 promoted the proliferation and lifespan of human primary keratinocytes. In addition, we showed that keratinocyte-specific markers could be detected in BMSCs cultured in a xeno-free system using keratinocyte-conditioned medium (KCM) independent of the presence of Y-27632. However, the efficiency of the differentiation of BMSCs into KLCs was significantly higher in the presence of Y

A model of human motor sequence learning explains facilitation and interference effects based on spike-timing dependent plasticity.

Directory of Open Access Journals (Sweden)

Quan Wang

2017-08-01

Full Text Available The ability to learn sequential behaviors is a fundamental property of our brains. Yet a long stream of studies including recent experiments investigating motor sequence learning in adult human subjects have produced a number of puzzling and seemingly contradictory results. In particular, when subjects have to learn multiple action sequences, learning is sometimes impaired by proactive and retroactive interference effects. In other situations, however, learning is accelerated as reflected in facilitation and transfer effects. At present it is unclear what the underlying neural mechanism are that give rise to these diverse findings. Here we show that a recently developed recurrent neural network model readily reproduces this diverse set of findings. The self-organizing recurrent neural network (SORN model is a network of recurrently connected threshold units that combines a simplified form of spike-timing dependent plasticity (STDP with homeostatic plasticity mechanisms ensuring network stability, namely intrinsic plasticity (IP and synaptic normalization (SN. When trained on sequence learning tasks modeled after recent experiments we find that it reproduces the full range of interference, facilitation, and transfer effects. We show how these effects are rooted in the network's changing internal representation of the different sequences across learning and how they depend on an interaction of training schedule and task similarity. Furthermore, since learning in the model is based on fundamental neuronal plasticity mechanisms, the model reveals how these plasticity mechanisms are ultimately responsible for the network's sequence learning abilities. In particular, we find that all three plasticity mechanisms are essential for the network to learn effective internal models of the different training sequences. This ability to form effective internal models is also the basis for the observed interference and facilitation effects. This suggests that

Effect of intermittent feedback control on robustness of human-like postural control system

Science.gov (United States)

Tanabe, Hiroko; Fujii, Keisuke; Suzuki, Yasuyuki; Kouzaki, Motoki

2016-03-01

Humans have to acquire postural robustness to maintain stability against internal and external perturbations. Human standing has been recently modelled using an intermittent feedback control. However, the causality inside of the closed-loop postural control system associated with the neural control strategy is still unknown. Here, we examined the effect of intermittent feedback control on postural robustness and of changes in active/passive components on joint coordinative structure. We implemented computer simulation of a quadruple inverted pendulum that is mechanically close to human tiptoe standing. We simulated three pairs of joint viscoelasticity and three choices of neural control strategies for each joint: intermittent, continuous, or passive control. We examined postural robustness for each parameter set by analysing the region of active feedback gain. We found intermittent control at the hip joint was necessary for model stabilisation and model parameters affected the robustness of the pendulum. Joint sways of the pendulum model were partially smaller than or similar to those of experimental data. In conclusion, intermittent feedback control was necessary for the stabilisation of the quadruple inverted pendulum. Also, postural robustness of human-like multi-link standing would be achieved by both passive joint viscoelasticity and neural joint control strategies.

Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

Science.gov (United States)

Takayama, Kazuo; Mizuguchi, Hiroyuki

2017-02-01

Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells

Directory of Open Access Journals (Sweden)

Yukari Komuta

2016-06-01

Full Text Available Direct reprogramming is a promising, simple and low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells. Recently, peripheral blood mononuclear cells (PBMCs have attracted considerable attention as a somatic cell source for reprogramming. As a cell source, PBMCs have an advantage over dermal fibroblasts with respect to the ease of collecting tissues. Based on our studies involving generation of photosensitive photoreceptor cells from human iris cells and human dermal fibroblasts by transduction of photoreceptor-related transcription factors via retrovirus vectors, we transduced these transcription factors into PBMCs via Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced cells, most of which are crucial to photoreceptor functions. In functional studies, a light-induced inward current was detected in some CRX-transduced cells. Moreover, by modification of the culture conditions including additional transduction of RAX1 and NEUROD1, we found a greater variety of retinal disease-related genes than that observed in CRX-transduced PBMCs. These data suggest that CRX acts as a master control gene for reprogramming PBMCs into photoreceptor-like cells and that our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.

Facilitating job retention for chronically ill employees: perspectives of line managers and human resource managers.

Science.gov (United States)

Haafkens, Joke A; Kopnina, Helen; Meerman, Martha G M; van Dijk, Frank J H

2011-05-17

Chronic diseases are a leading contributor to work disability and job loss in Europe. Recent EU policies aim to improve job retention among chronically ill employees. Disability and occupational health researchers argue that this requires a coordinated and pro-active approach at the workplace by occupational health professionals, line managers (LMs) and human resource managers (HRM). Little is known about the perspectives of LMs an HRM on what is needed to facilitate job retention among chronically ill employees. The aim of this qualitative study was to explore and compare the perspectives of Dutch LMs and HRM on this issue. Concept mapping methodology was used to elicit and map statements (ideas) from 10 LMs and 17 HRM about what is needed to ensure continued employment for chronically ill employees. Study participants were recruited through a higher education and an occupational health services organization. Participants generated 35 statements. Each group (LMs and HRM) sorted these statements into six thematic clusters. LMs and HRM identified four similar clusters: LMs and HRM must be knowledgeable about the impact of chronic disease on the employee; employees must accept responsibility for work retention; work adaptations must be implemented; and clear company policy. Thematic clusters identified only by LMs were: good manager/employee cooperation and knowledge transfer within the company. Unique clusters identified by HRM were: company culture and organizational support. There were both similarities and differences between the views of LMs and HRM on what may facilitate job retention for chronically ill employees. LMs perceived manager/employee cooperation as the most important mechanism for enabling continued employment for these employees. HRM perceived organizational policy and culture as the most important mechanism. The findings provide information about topics that occupational health researchers and planners should address in developing job retention

Facilitating job retention for chronically ill employees: perspectives of line managers and human resource managers

Directory of Open Access Journals (Sweden)

Meerman Martha GM

2011-05-01

Full Text Available Abstract Background Chronic diseases are a leading contributor to work disability and job loss in Europe. Recent EU policies aim to improve job retention among chronically ill employees. Disability and occupational health researchers argue that this requires a coordinated and pro-active approach at the workplace by occupational health professionals, line managers (LMs and human resource managers (HRM. Little is known about the perspectives of LMs an HRM on what is needed to facilitate job retention among chronically ill employees. The aim of this qualitative study was to explore and compare the perspectives of Dutch LMs and HRM on this issue. Methods Concept mapping methodology was used to elicit and map statements (ideas from 10 LMs and 17 HRM about what is needed to ensure continued employment for chronically ill employees. Study participants were recruited through a higher education and an occupational health services organization. Results Participants generated 35 statements. Each group (LMs and HRM sorted these statements into six thematic clusters. LMs and HRM identified four similar clusters: LMs and HRM must be knowledgeable about the impact of chronic disease on the employee; employees must accept responsibility for work retention; work adaptations must be implemented; and clear company policy. Thematic clusters identified only by LMs were: good manager/employee cooperation and knowledge transfer within the company. Unique clusters identified by HRM were: company culture and organizational support. Conclusions There were both similarities and differences between the views of LMs and HRM on what may facilitate job retention for chronically ill employees. LMs perceived manager/employee cooperation as the most important mechanism for enabling continued employment for these employees. HRM perceived organizational policy and culture as the most important mechanism. The findings provide information about topics that occupational health

Possible additional exposure to dioxin and dioxin-like compounds from waste incineration. Biomonitoring using human milk and animal samples

Energy Technology Data Exchange (ETDEWEB)

Sampaio, C.; M. Fatima Reis; J. Pereira Miguel [Inst. of Preventive Medicine, Univ. of Lisbon (Portugal); Murk, A. [Wageningen Univ., Dept. of Toxicology (Netherlands)

2004-09-15

In the ambit of an Environmental Health Survey Program relative to a MSW facility, which has been operating near to Lisbon since 1999 a biomonitoring study using human breast milk has been performed. Specific aims of this study were: (1) determine whether living in the vicinity of the incinerator increases dioxin maternal body burden and accordingly perinatal (intra-uterus and lactacional) exposure; (2) to investigate the possibility of increased human exposure to dioxins and dioxin-like compounds via locally produced food items from animal origin. Therefore, levels of dioxins and dioxin-like compounds have been determined in human milk samples collected in the vicinity of the incinerator and in a control area, for comparison. From the same areas, cow and sheep milk and eggs from free-range chickens have also been collected to get an indication of possible local additional exposure to air-borne dioxins via the food chain. Analyses of TCDD-equivalents (TEQs) were mainly performed with a reporter gene assay for dioxin-like activity, the DR-CALUX bioassay (Dioxin Responsive Chemical Activated LUciferase gene eXpression).To determine congeners profile, some human milk samples have also been analysed for PCDD/Fs and relevant dioxin-like PCBs, by using high-resolution gas chromatography and high-resolution mass spectrometry (HRGC/HRMS). Both the Ethics Committees of the Faculty of Medicine, University of Lisbon, and of the Maternity Dr. Alfredo da Costa have approved the study protocol.

Identification of human synenkephalin-like immunoreactivity in phaechromacytoma tissue using a novel carboxy-terminal radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Corder, R; Gaillard, R C; Rossier, J

1987-12-04

An antiserum raised against the synthetic tyrosinylated carboxy-terminal sequence of synenephalin (Tyr-Glu-Glu-Ser-His-Leu-Leu-Ala) has been used to chromatographically characterize the human synenkephalin-like immunoreactivity extracted from 3 adrenal medullary phaechromocytomas. Gel filtration chromatography identified in each tumor a single peak of 8kDa which on subsequent ion-exchange chromatography had the elution characteristics of an acidic polypeptide. These results are compatible with the human-synenkephalin sequence predicted from cDNA studies, and indicate that this is the authentic peptide. 17 refs.

The predominant mechanism of intercellular calcium wave propagation changes during long-term culture of human osteoblast-like cells

DEFF Research Database (Denmark)

Henriksen, Zanne; Hiken, Jeffrey F; Steinberg, Thomas H

2006-01-01

cells still responded to addition of ATP, but P2Y desensitization did not inhibit ICW propagation. Our data indicate that the relative role of P2Y-mediated and gap junction-mediated ICW changes during osteoblast differentiation in vitro. In less differentiated cells, P2Y-mediated ICW predominate......Intercellular calcium waves (ICW) are calcium transients that spread from cell to cell in response to different stimuli. We previously demonstrated that human osteoblast-like cells in culture propagate ICW in response to mechanical stimulation by two mechanisms. One mechanism involves autocrine...... activation of P2Y receptors, and the other requires gap junctional communication. In the current work we ask whether long-term culture of osteoblast-like cells affects the propagation of ICW by these two mechanisms. Human osteoblast-like cells were isolated from bone marrow. Mechanically induced ICW were...

Interfaces entre modelo produtivo e divisão do trabalho flexível: a visão do trabalhador sobre a terceirização no polo naval de Rio Grande

Directory of Open Access Journals (Sweden)

Eder Dion de Paula Costa

2016-07-01

Full Text Available O objetivo deste trabalho é trazer uma reflexão sobre a pesquisa empírica realizada no Polo Naval de Rio Grande acerca do modelo flexível de organização produtiva e seu impacto nos processos de sociabilidade da classe trabalhadora. A perspectiva que se pretende mostrar é a do trabalhador terceirizado dentro da organização da produção e da divisão do trabalho, ambos flexíveis. O presente artigo é produto de reflexões a partir do projeto de dissertação de mestrado da segunda autora sobre a invisibilidade social causada pela terceirização elaborado para o Programa de Pós-graduação em Sociologia da Universidade Federal de Pelotas.

The human Vδ2+ T-cell compartment comprises distinct innate-like Vγ9+ and adaptive Vγ9- subsets.

Science.gov (United States)

Davey, Martin S; Willcox, Carrie R; Hunter, Stuart; Kasatskaya, Sofya A; Remmerswaal, Ester B M; Salim, Mahboob; Mohammed, Fiyaz; Bemelman, Frederike J; Chudakov, Dmitriy M; Oo, Ye H; Willcox, Benjamin E

2018-05-02

Vδ2 + T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the Vδ2 + compartment comprises both innate-like and adaptive subsets. Vγ9 + Vδ2 + T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9 - Vδ2 + T-cell subset that typically has a CD27 hi CCR7 + CD28 + IL-7Rα + naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27 lo CD45RA + CX 3 CR1 + granzymeA/B + effector phenotype. Consistent with a function in solid tissue immunosurveillance, we detect human intrahepatic Vγ9 - Vδ2 + T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human γδ T-cell subsets by delineating the Vδ2 + T-cell compartment into innate-like (Vγ9 + ) and adaptive (Vγ9 - ) subsets, which have distinct functions in microbial immunosurveillance.

A complex small RNA repertoire is generated by a plant/fungal-like machinery and effected by a metazoan-like Argonaute in the single-cell human parasite Toxoplasma gondii.

Directory of Open Access Journals (Sweden)

Laurence Braun

2010-05-01

Full Text Available In RNA silencing, small RNAs produced by the RNase-III Dicer guide Argonaute-like proteins as part of RNA-induced silencing complexes (RISC to regulate gene expression transcriptionally or post-transcriptionally. Here, we have characterized the RNA silencing machinery and exhaustive small RNAome of Toxoplasma gondii, member of the Apicomplexa, a phylum of animal- and human-infecting parasites that cause extensive health and economic damages to human populations worldwide. Remarkably, the small RNA-generating machinery of Toxoplasma is phylogenetically and functionally related to that of plants and fungi, and accounts for an exceptionally diverse array of small RNAs. This array includes conspicuous populations of repeat-associated small interfering RNA (siRNA, which, as in plants, likely generate and maintain heterochromatin at DNA repeats and satellites. Toxoplasma small RNAs also include many microRNAs with clear metazoan-like features whose accumulation is sometimes extremely high and dynamic, an unexpected finding given that Toxoplasma is a unicellular protist. Both plant-like heterochromatic small RNAs and metazoan-like microRNAs bind to a single Argonaute protein, Tg-AGO. Toxoplasma miRNAs co-sediment with polyribosomes, and thus, are likely to act as translational regulators, consistent with the lack of catalytic residues in Tg-AGO. Mass spectrometric analyses of the Tg-AGO protein complex revealed a common set of virtually all known RISC components so far characterized in human and Drosophila, as well as novel proteins involved in RNA metabolism. In agreement with its loading with heterochromatic small RNAs, Tg-AGO also associates substoichiometrically with components of known chromatin-repressing complexes. Thus, a puzzling patchwork of silencing processor and effector proteins from plant, fungal and metazoan origin accounts for the production and action of an unsuspected variety of small RNAs in the single-cell parasite Toxoplasma and

Uptake of human papillomavirus (HPV) vaccination in Hong Kong: Facilitators and barriers among adolescent girls and their parents.

Science.gov (United States)

Yuen, Winnie Wing Yan; Lee, Albert; Chan, Paul K S; Tran, Lynn; Sayko, Erica

2018-01-01

The present study is aimed at assessing the feasibility of delivering the HPV (human papillomavirus) vaccine to girls through a school-based program in Hong Kong, as well as to examine the facilitators and barriers associated with their participation. We approached 1,229 eligible girls aged 9 to 14 at eight schools in Hong Kong to join the program and then delivered the bivalent HPV vaccine at 0 and 6 months over the course of one school year. The students and their parents completed separate questionnaires to indicate their decision on whether or not to participate, and to assess their knowledge of cervical cancer and the HPV vaccine. The overall vaccine uptake was 81.4% (1,000/1,229) for the first dose and 80.8% (993/1,229) for the second dose. Parents and students were given separate questionnaires and asked whether or not they would like to participate in the vaccination program. 87.1% (1,010/1,160) of parents and 84.9% (974/1,147) of students indicated that they would join the program. The reasons associated with parents' decision not to vaccinate their daughters primarily included concerns around side effects and safety. Multivariate regression analysis showed that parents who thought that the vaccine would protect their daughter from getting cervical cancer (OR = 3.16, 95% CI = 1.39-7.15, p parents who had never heard of the vaccine (OR = .15, 95% CI = .03-.71, p vaccine (OR = .39, 95% CI = .19-.81, p HPV vaccine with high uptake rate in a school setting is feasible in Hong Kong. Engaging key stakeholders including school administrators, teachers and community physicians, and providing relevant information on safety and vaccine effectiveness to parents were important to the success of the program.

Practice Facilitators' and Leaders' Perspectives on a Facilitated Quality Improvement Program.

Science.gov (United States)

McHugh, Megan; Brown, Tiffany; Liss, David T; Walunas, Theresa L; Persell, Stephen D

2018-04-01

Practice facilitation is a promising approach to helping practices implement quality improvements. Our purpose was to describe practice facilitators' and practice leaders' perspectives on implementation of a practice facilitator-supported quality improvement program and describe where their perspectives aligned and diverged. We conducted interviews with practice leaders and practice facilitators who participated in a program that included 35 improvement strategies aimed at the ABCS of heart health (aspirin use in high-risk individuals, blood pressure control, cholesterol management, and smoking cessation). Rapid qualitative analysis was used to collect, organize, and analyze the data. We interviewed 17 of the 33 eligible practice leaders, and the 10 practice facilitators assigned to those practices. Practice leaders and practice facilitators both reported value in the program's ability to bring needed, high-quality resources to practices. Practice leaders appreciated being able to set the schedule for facilitation and select among the 35 interventions. According to practice facilitators, however, relying on practice leaders to set the pace of the intervention resulted in a lower level of program intensity than intended. Practice leaders preferred targeted assistance, particularly electronic health record documentation guidance and linkages to state smoking cessation programs. Practice facilitators reported that the easiest interventions were those that did not alter care practices. The dual perspectives of practice leaders and practice facilitators provide a more holistic picture of enablers and barriers to program implementation. There may be greater opportunities to assist small practices through simple, targeted practice facilitator-supported efforts rather than larger, comprehensive quality improvement projects. © 2018 Annals of Family Medicine, Inc.

Lysozyme's lectin-like characteristics facilitates its immune defense function

KAUST Repository

Zhang, Ruiyan

2017-06-06

Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

Lysozyme's lectin-like characteristics facilitates its immune defense function

KAUST Repository

Zhang, Ruiyan; Wu, Lisha; Eckert, Thomas; Burg-Roderfeld, Monika; Rojas-Macias, Miguel A.; Lü tteke, Thomas; Krylov, Vadim B.; Argunov, Dmitry A.; Datta, Aritreyee; Markart, Philipp; Guenther, Andreas; Norden, Bengt; Schauer, Roland; Bhunia, Anirban; Enani, Mushira Abdelaziz; Billeter, Martin; Scheidig, Axel J.; Nifantiev, Nikolay E.; Siebert, Hans-Christian

2017-01-01

Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach.

Science.gov (United States)

Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-03-01

Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices. Published by Elsevier Inc.

Two insulin-like growth factor I messenger RNAs are expressed in human liver

International Nuclear Information System (INIS)

Rotwein, P.

1986-01-01

Through use of a synthetic radiolabelled oligonucleotide probe, human insulin-like growth factor I (IGF-I) cDNA clones were isolated from a liver library. Two types of cDNAs were defined by restriction enzyme analysis and DNA sequencing. Both encode IGF-I precursors of either 195 or 153 amino acids. The two predicted protein precursors are identical from their amino terminus to a lysine residue 16 codons beyond the IGF-I sequence, and then they diverge. Both cDNAs predict additional unique carboxyl-terminal extension peptides. Since there is only one IGF-I gene in the human genome, the finding of two different cDNAs suggests that alternative RNA processing plays a role in IGF-I gene expression. The functions of the different extension peptides remain to be elucidates

Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

Science.gov (United States)

Mathapati, Santosh; Siller, Richard; Impellizzeri, Agata A R; Lycke, Max; Vegheim, Karianne; Almaas, Runar; Sullivan, Gareth J

2016-08-17

Hepatocyte-like cells (HLCs) generated in vitro from human pluripotent stem cells (hPSCs) provide an invaluable resource for basic research, regenerative medicine, drug screening, toxicology, and modeling of liver disease and development. This unit describes a small-molecule-driven protocol for in vitro differentiation of hPSCs into HLCs without the use of growth factors. hPSCs are coaxed through a developmentally relevant route via the primitive streak to definitive endoderm (DE) using the small molecule CHIR99021 (a Wnt agonist), replacing the conventional growth factors Wnt3A and activin A. The small-molecule-derived DE is then differentiated to hepatoblast-like cells in the presence of dimethyl sulfoxide. The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Variable Thumb Moment Arm Modeling and Thumb-Tip Force Production of a Human-Like Robotic Hand.

Science.gov (United States)

Niehues, Taylor D; Deshpande, Ashish D

2017-10-01

The anatomically correct testbed (ACT) hand mechanically simulates the musculoskeletal structure of the fingers and thumb of the human hand. In this work, we analyze the muscle moment arms (MAs) and thumb-tip force vectors in the ACT thumb in order to compare the ACT thumb's mechanical structure to the human thumb. Motion data are used to determine joint angle-dependent MA models, and thumb-tip three-dimensional (3D) force vectors are experimentally analyzed when forces are applied to individual muscles. Results are presented for both a nominal ACT thumb model designed to match human MAs and an adjusted model that more closely replicates human-like thumb-tip forces. The results confirm that the ACT thumb is capable of faithfully representing human musculoskeletal structure and muscle functionality. Using the ACT hand as a physical simulation platform allows us to gain a better understanding of the underlying biomechanical and neuromuscular properties of the human hand to ultimately inform the design and control of robotic and prosthetic hands.

Documents for Recommended Toxicity Equivalency Factors for Human Health Risk Assessments of Dioxin and Dioxin-Like Compounds

Science.gov (United States)

This document describes the U.S. Environmental Protection Agency’s (U.S. EPA’s) updated approach for evaluating the human health risks from exposures to environmental media containing dioxin-like compounds (DLCs).

A controllable tactile device for human-like tissue realization using smart magneto-rheological fluids: fabrication and modeling

Science.gov (United States)

Cha, Seung-Woo; Kang, Seok-Rae; Hwang, Yong-Hoon; Oh, Jong-Seok; Choi, Seung-Bok

2018-06-01

This paper proposes a new tactile device to realize the force of human-like organs using the viscoelastic property by combing a smart magneto-rheological (MR) fluid with a sponge (MR sponge in short). The effectiveness of the sensor is validated through the comparison of the force obtained through measurement and the proposed prediction model. As the first step, a conventional standard linear solid model is adopted to independently investigate the force characteristics of MR fluid and sponge. Force is measured using a 3-axis robot with a force sensor to obtain certain properties of MR fluid and sponge. In addition, to show that the proposed MR sponge can realize the force of human-like tissues, experiments are performed using three specimens, i.e., porcine heart, lung, and liver. Subsequently, a quasi-static model for predicting the field-dependent force of the MR sponge is formulated using empirical values. It is demonstrated through comparison that the proposed force model can accurately predict the force of the specimens without significant error. In addition, a psychophysical test is carried out by ordinary subjects to validate the effectiveness of the proposed tactile device. Results show that the MR sponge tactile device can easily produce various levels of the force of human-like tissues, such as the liver and lung of the porcine, by controlling input current.

African Journal of Cross-Cultural Psychology and Sport Facilitation ...

African Journals Online (AJOL)

Focus and Scope. The African Journal of Cross-Cultural Psychology and Sport Facilitation is a professional journal of the Association of Psychology in Sport and Human Behaviour. It publishes a wide variety of original articles and reports relevant to cultural and sport behaviour, theoretical propositions, research outcomes ...

Encapsulation of probiotic Bifidobacterium longum BIOMA 5920 with alginate-human-like collagen and evaluation of survival in simulated gastrointestinal conditions.

Science.gov (United States)

Su, Ran; Zhu, Xiao-Li; Fan, Dai-Di; Mi, Yu; Yang, Chan-Yuan; Jia, Xin

2011-12-01

Alginate (ALg)-human-like collagen (HLC) microspheres were prepared by the technology of electrostatic droplet generation in order to develop a biocompatible vehicle for probiotic bacteria. Microparticles were spherical with mean particle size of 400μm. The encapsulation efficiency (EE) of ALg-HLC microspheres could reach 92-99.2%. Water-soluble and fibrous human-like collagen is combined with sodium alginate through intermolecular hydrogen bonding and electrostatic force which were investigated by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), thus the matrix of ALg-HLC was very stable. Bifidobacterium longum BIOMA 5920, as a kind of probiotic bacteria, was encapsulated with alginate-human-like collagen to survive and function in simulated gastrointestinal juice. Microparticles were very easy to degradation in simulated intestinal juices. After incubation in simulated gastric (pH 2.0, 2h), the encapsulated B. longum BIOMA 5920 numbers were 4.81 ± 0.38 log cfu/g. Copyright © 2011 Elsevier B.V. All rights reserved.

Influenza A Virus with a Human-Like N2 Gene Is Circulating in Pigs

DEFF Research Database (Denmark)

Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

2013-01-01

A novel reassortant influenza A virus, H1avN2hu, has been found in Danish swine. The virus contains an H1 gene similar to the hemagglutinin (HA) gene of H1N1 avian-like swine viruses and an N2 gene most closely related to the neuraminidase (NA) gene of human H3N2 viruses from the mid-1990s....

Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

Directory of Open Access Journals (Sweden)

Maucksch C

2012-01-01

Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

Science.gov (United States)

Benes, L; Kappus, C; McGregor, G P; Bertalanffy, H; Mennel, H D; Hagner, S

2004-02-01

Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

Subcortical structures in humans can be facilitated by transcranial direct current stimulation

NARCIS (Netherlands)

Nonnekes, Johan Hendrik; Arrogi, Anass; Munneke, Moniek; van Asseldonk, Edwin H.F.; Oude Nijhuis, Lars; Geurts, Alexander; Weerdesteyn, Vivian

2014-01-01

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability via application of a weak direct current. Interestingly, it was demonstrated in cats that tDCS can facilitate subcortical structures as well (Bolzonii et al., J

Derivation of Stromal (Skeletal and Mesenchymal) Stem-Like Cells from Human Embryonic Stem Cells

Science.gov (United States)

Harkness, Linda; Abdallah, Basem M.; Elsafadi, Mona; Al-Nbaheen, May S.; Aldahmash, Abdullah; Kassem, Moustapha

2012-01-01

Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESCs) is a prerequisite for their use in clinical applications. However, there is no standard protocol for differentiating hESCs into osteoblastic cells. The aim of this study was to identify the emergence of a human stromal (mesenchymal and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESCs in a feeder-free environment using serum replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day developmental period, the hEBs demonstrated increasing enrichment for cells expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and CD166 as revealed by immunohistochemical staining and flow cytometry (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs using bone morphogenic protein 2 (BMP2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold, revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These tissues were of human origin and there was no evidence of differentiation to nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated tissue containing glandular, fibrous and muscle-like tissue elements. Conversely, implantation of undifferentiated hESCs resulted in the formation of a teratoma containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study demonstrates that hMSC-like cells can be obtained from hESCs and they can be induced to form skeletal tissues in vivo when combined with HA/TCP. These findings are relevant for tissue engineering and suggest that differentiated hEBs can provide an unlimited source for

Development of Scientific Thinking Facilitated by Reflective Self-Assessment in a Communication-Intensive Food Science and Human Nutrition Course

Science.gov (United States)

Hendrich, Suzanne; Licklider, Barbara; Thompson, Katherine; Thompson, Janette; Haynes, Cynthia; Wiersema, Jan

2018-01-01

A one-credit seminar on controversies in food science and human nutrition was a platform to introduce students to learning frameworks for thinking-like-a-scientist. We hypothesized that explicitly engaging students in thinking about their thinking abilities within these frameworks would enhance their self-perception of scientific thinking, an…

beta. -endorphin-like and. alpha. -MSH-like immunoreactivities in human milk

Energy Technology Data Exchange (ETDEWEB)

Ferrando, T.; Rainero, I.; De Gennaro, T.; Oggero, R.; Mostert, M.; Dattola, P.; Pinessi, L. (Univ. of Turin (Italy))

1990-01-01

We measured with radioimmunoassay the {beta}-endorphin-like and {alpha}-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean {beta}-endorphin concentrations ({plus minus} SD) were 16.6 {plus minus} 6.7 fmol/ml in milk and 9.9 {plus minus} 4.1 fmol/ml in plasma. {alpha}-MSH concentrations were 39.4 {plus minus} 15.5 pg/ml in milk and 18.2 {plus minus} 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.

Isolation and characterization of the human parathyroid hormone-like peptide gene

International Nuclear Information System (INIS)

Mangin, M.; Ikeda, K.; Dreyer, B.E.; Broadus, A.E.

1989-01-01

A parathyroid hormone-like peptide (PTH-LP) has recently been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The peptide appears to be encoded by a single-copy gene that gives rise to multiple mRNAs that are heterogeneous at both their 5' and their 3' ends. Alternative RNA splicing is responsible for the 3' heterogeneity and results in mRNAs encoding three different peptides, each with a unique C terminus. The authors have isolated and characterized the human PTHLP gene. The gene is a complex transcriptional unit spanning more than 12 kilobases of DNA and containing six exons. Two 5' exons encode distinct 5' untranslated regions and are separated by a putative promoter element, indicating that the gene either has two promoters or is alternatively spliced from a single promoter upstream of the first exon. The middle portion of the PTHLP gene, comprising exons 2-4, has an organizational pattern of introns and exons identical to that of the parathyroid hormone gene, consistent with a common ancestral origin of these two genes. Exon 4 of the PTHLP gene encodes the region common to all three peptides and the C terminus of the shortest peptide, and exons 5 and 6 encode the unique C termini of the other two peptides. Northern analysis of mRNAs from four human tumors of different histological types reveals the preferential use of 3' splicing patterns of individual tumors

CD146 positive human dental pulp stem cells promote regeneration of dentin/pulp-like structures.

Science.gov (United States)

Matsui, Mikiko; Kobayashi, Tomoko; Tsutsui, Takeo W

2018-04-01

CD146 and STRO-1 are endothelial biomarkers that are co-expressed on the cellular membranes of blood vessels within human dental pulp tissue. This study characterized the percentage of dentin-like structures produced by CD146-positive (CD146 + ) human dental pulp stem cells (DPSCs), compared with their CD146-negative (CD146 - ) counterparts. DPSC populations were enriched using magnetic-activated cell sorting (MACS), yielding CD146 + and CD146 - cells, as well as mixtures composed of 25% CD146 + cells and 75% CD146 - cells (CD146 +/- ). Cell growth assays indicated that CD146 + cells exhibit an approximate 3-4 h difference in doubling time, compared with CD146 - cells. Cell cycle distributions were determined by flow cytometry analysis. The low percentage of CD146 + cells' DNA content in G 0 /G 1 phase were compared with CD146 - and non-separated cells. In contrast to CD146 - and non-separated cells, prompt mineralization was observed in CD146 + cells. Subsequently, qRT-PCR revealed high mRNA expression of CD146 and Alkaline phosphatase in mineralization-induced CD146 + cells. CD146 + cells were also observed high adipogenic ability by Oil red O staining. Histological examinations revealed an increased area of dentin/pulp-like structures in transplanted CD146 + cells, compared with CD146 - and CD146 +/- cells. Immunohistochemical studies detected dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP), as well as human mitochondria, in transplanted DPSCs. Co-expression of CD146 and GFP indicated that CD146 was expressed in transplanted CD146 + cells. CD146 + cells may promote mineralization and generate dentin/pulp-like structures, suggesting a role in self-renewal of stem cells and dental pulp regenerative therapy.

Customized Body Mapping to Facilitate the Ergonomic Design of Sportswear.

Science.gov (United States)

Cao, Mingliang; Li, Yi; Guo, Yueping; Yao, Lei; Pan, Zhigeng

2016-01-01

A successful high-performance sportswear design that considers human factors should result in a significant increase in thermal comfort and reduce energy loss. The authors describe a body-mapping approach that facilitates the effective ergonomic design of sportswear. Their general framework can be customized based on the functional requirements of various sports and sportswear, the desired combination and selection of mapping areas for the human body, and customized quantitative data distribution of target physiological indicators.

Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells.

Science.gov (United States)

Hsieh, Ching-Lin; Tseng, Andrew; He, Hongxuan; Kuo, Chih-Jung; Wang, Xuannian; Chang, Yung-Fu

2017-01-01

Leptospira immunoglobulin-like protein B (LigB), a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM). Human tropoelastin (HTE), the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N). Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first β-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38) by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis.

Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

Directory of Open Access Journals (Sweden)

Ching-Lin Hsieh

2017-05-01

Full Text Available Leptospira immunoglobulin-like protein B (LigB, a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM. Human tropoelastin (HTE, the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N. Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first β-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38 by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis.

Derivation of Stromal (Skeletal, Mesenchymal) Stem-like cells from Human Embryonic Stem Cells

DEFF Research Database (Denmark)

Mahmood, Amer; Harkness, Linda; Abdallah, Basem

2012-01-01

EBs using BMP2 (bone morphogenic protein 2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold......Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESC) is a pre-requisite for their use in clinical applications. However, there is no standard protocol for differentiating hESC into osteoblastic cells. The aim of this study was to identify the emergence of a human...... stromal (mesenchymal, skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESC in a feeder-free environment using serum replacement and as suspension aggregates (embryoid...

Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis

NARCIS (Netherlands)

Gomes Fernandes, Maria; He, Nannan; Wang, Fang; Van Iperen, Liesbeth; Eguizabal, Cristina; Matorras, Roberto; Roelen, Bernard A J; Chuva de Sousa Lopes, Susana M

2018-01-01

STUDY QUESTION: What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? SUMMARY ANSWER: PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during

ZFP521 regulates murine hematopoietic stem cell function and facilitates MLL-AF9 leukemogenesis in mouse and human cells.

Science.gov (United States)

Garrison, Brian S; Rybak, Adrian P; Beerman, Isabel; Heesters, Balthasar; Mercier, Francois E; Scadden, David T; Bryder, David; Baron, Roland; Rossi, Derrick J

2017-08-03

The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521 / Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis whose function in HSC biology remains elusive. Competitive serial transplantation assays using Zfp521 -deficient mice revealed that ZFP521 regulates HSC self-renewal and differentiation. In contrast, ectopic expression of ZFP521 in HSCs led to a robust maintenance of progenitor activity in vitro. Transcriptional analysis of human acute myeloid leukemia (AML) patient samples revealed that ZNF521 is highly and specifically upregulated in AMLs with MLL translocations. Using an MLL-AF9 murine leukemia model and serial transplantation studies, we show that ZFP521 is not required for leukemogenesis, although its absence leads to a significant delay in leukemia onset. Furthermore, knockdown of ZNF521 reduced proliferation in human leukemia cell lines possessing MLL-AF9 translocations. Taken together, these results identify ZNF521/ZFP521 as a critical regulator of HSC function, which facilitates MLL-AF9-mediated leukemic disease in mice.

Barriers and facilitators of mental health screening in pregnancy.

Science.gov (United States)

Kingston, Dawn; Austin, Marie-Paule; Heaman, Maureen; McDonald, Sheila; Lasiuk, Gerri; Sword, Wendy; Giallo, Rebecca; Hegadoren, Kathy; Vermeyden, Lydia; van Zanten, Sander Veldhuyzen; Kingston, Joshua; Jarema, Karly; Biringer, Anne

2015-11-01

Access to mental health services during pregnancy is most commonly mobilized through formal mental health screening. However, few studies to date have identified barriers and facilitators that affect pregnant women's responses to mental health screening. The objective was to identify barriers and facilitators that influence pregnant women's responses to the screening process and factors associated with their identification. This multi-site, cross-sectional survey recruited pregnant women >16 years of age who spoke/read English in Alberta, Canada. Main outcomes were barriers and facilitators of mental health screening. Descriptive statistics were generated to identify the most common barriers and facilitators and multivariable logistic regression models were conducted to determine factors associated with barriers and facilitators. Study participation rate was 92% (460/500). Women's most common barriers were: significant others normalizing their emotional difficulties; desiring to handle mental health problems on their own; preferring to discuss feelings with significant others; and not knowing what emotions were 'normal'. Women who identified these barriers were more likely not to have been treated previously for mental illness, were primiparous, and could not be completely honest with their provider. Main facilitators were provider characteristics (sensitive, interested), reassurance that mental healthcare is a part of routine prenatal care, hearing that other women have emotional problems during pregnancy and knowing that help was available. The sample comprised largely Caucasian, well-educated, and partnered women, which limits generalizability of the findings. Personal and stigma-related barriers influence pregnant women's responses to mental health screening. Efforts to minimize barriers and enhance facilitators should be explored as potential strategies for optimizing prenatal mental health screening. Copyright © 2015 Elsevier B.V. All rights reserved.

Our Preferences: Why We Like What We Like

Science.gov (United States)

Grammer, Karl; Oberzaucher, Elisabeth

Humans tend to judge and sort their social and non-social environment permanently into a few basic categories: 'likes' and 'don't likes'. Indeed we have developed general preferences for our social and non-social environment. These preferences can be subsumed under the term 'evolutionary aesthetics' (Voland & Grammer 2003). Indeed humans and animals have evolved preferences for mates, food, habitats, odors, and objects. Those stimuli that promoted reproductive success are bound to evoke positive emotional responses, and humans develop an obsession-like attitude towards aesthetics and beauty. Although we are 'all legally equal', people are often treated differently according to their physical appearance. This differential treatment by others starts early in life. Three-month-old children gaze longer at attractive faces than at unattractive faces. From these results, Langlois et al. (1990) conclude that beauty standards are not learned, but that there is an innate beauty detector. Attractive children receive less punishment than unattractive children for the same types of misbehavior. Differential treatment goes on at school, college, and even university (Baugh & Parry 1991). In this part of our lives attractiveness is coupled to academic achievements - attractive students receive better grades. Even when we apply for jobs, appearance may dominate qualification (Collins & Zebrowitz 1995). This differential treatment reaches its peak perhaps in jurisdiction, where attractiveness can lead to better treatment and lighter sentences. However, this is only the case if attractiveness did not play a role in the crime (Hateld & Sprecher 1986). We even believe that attractive people are better - 'what is beautiful is good' is a common standard in our thinking, according to Dion et al. (1972). The question then arises: Where does this obsessive preoccupation with beauty and attractiveness come from?We will outline here the thesis that human mate selection criteria, which have

Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

International Nuclear Information System (INIS)

Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

2011-01-01

Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators

NARCIS (Netherlands)

Rachmawati, D.; Bontkes, H.J.; Verstege, M.I.; Muris, J.; von Blomberg, B.M.E.; Scheper, R.J.; van Hoogstraten, I.M.W.

2013-01-01

Background Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4. Objectives Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

Science.gov (United States)

Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

2015-01-01

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

Science.gov (United States)

Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

2017-05-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

Science.gov (United States)

Fu, Qinqin; Yuan, Y Adam

2013-03-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses

OpenAIRE

Kanno, Shin-ichiro; Kuzuoka, Hiroyuki; Sasao, Shigeru; Hong, Zehui; Lan, Li; Nakajima, Satoshi; Yasui, Akira

2007-01-01

DNA damage causes genome instability and cell death, but many of the cellular responses to DNA damage still remain elusive. We here report a human protein, PALF (PNK and APTX-like FHA protein), with an FHA (forkhead-associated) domain and novel zinc-finger-like CYR (cysteine–tyrosine–arginine) motifs that are involved in responses to DNA damage. We found that the CYR motif is widely distributed among DNA repair proteins of higher eukaryotes, and that PALF, as well as a Drosophila protein with...

A novel anti-tumor inhibitor identified by virtual screen with PLK1 structure and zebrafish assay.

Directory of Open Access Journals (Sweden)

Jing Lu

Full Text Available Polo-like kinase 1 (PLK1, one of the key regulators of mitosis, is a target for cancer therapy due to its abnormally high activity in several tumors. Plk1 is highly conserved and shares a nearly identical 3-D structure between zebrafish and humans. The initial 10 mitoses of zebrafish embryonic cleavages occur every∼30 minutes, and therefore provide a rapid assay to evaluate mitosis inhibitors including those targeting Plk1. To increase efficiency and specificity, we first performed a computational virtual screen of∼60000 compounds against the human Plk1 3-D structure docked to both its kinase and Polo box domain. 370 candidates with the top free-energy scores were subjected to zebrafish assay and 3 were shown to inhibit cell division. Compared to general screen for compounds inhibiting zebrafish embryonic cleavage, computation increased the efficiency by 11 folds. One of the 3 compounds, named I2, was further demonstrated to effectively inhibit multiple tumor cell proliferation in vitro and PC3 prostate cancer growth in Xenograft mouse model in vivo. Furthermore, I2 inhibited Plk1 enzyme activity in a dose dependent manner. The IC50 values of I2 in these assays are compatible to those of ON-01910, a Plk1 inhibitor currently in Phase III clinic trials. Our studies demonstrate that zebrafish assays coupled with computational screening significantly improves the efficiency of identifying specific regulators of biological targets. The PLK1 inhibitor I2, and its analogs, may have potential in cancer therapeutics.

Complete sequences of glucagon-like peptide-1 from human and pig small intestine

DEFF Research Database (Denmark)

Orskov, C; Bersani, M; Johnsen, A H

1989-01-01

intestine of the proglucagon precursor were determined by pairs of basic amino acid residues flanking the two peptides. Earlier studies have shown that synthetic glucagon-like peptide-1 (GLP-1) synthesized according to the proposed structure (proglucagon 71-108 or because residue 108 is Gly, 72-107 amide......) had no physiological effects, whereas a truncated from of GLP-1, corresponding to proglucagon 78-107 amide, strongly stimulated insulin secretion and depressed glucagon secretion. To determine the amino acid sequence of the naturally occurring peptide we isolated GLP-1 from human small intestine...

Effect of Tris-acetate buffer on endotoxin removal from human-like collagen used biomaterials

International Nuclear Information System (INIS)

Zhang, Huizhi; Fan, Daidi; Deng, Jianjun; Zhu, Chenghui; Hui, Junfeng; Ma, Xiaoxuan

2014-01-01

Protein preparation, which has active ingredients designated for the use of biomaterials and therapeutical protein, is obtained by genetic engineering, but products of genetic engineering are often contaminated by endotoxins. Because endotoxin is a ubiquitous and potent proinflammatory agent, endotoxin removal or depletion from protein is essential for researching any biomaterials. In this study, we have used Tris-acetate (TA) buffer of neutral pH value to evaluate endotoxins absorbed on the Pierce high-capacity endotoxin removal resin. The effects of TA buffer on pH, ionic strength, incubation time as well as human-like collagen (HLC) concentration on eliminating endotoxins are investigated. In the present experiments, we design an optimal method for TA buffer to remove endotoxin from recombinant collagen and use a chromogenic tachypleus amebocyte lysate (TAL) test kit to measure the endotoxin level of HLC. The present results show that, the endotoxins of HLC is dropped to 8.3 EU/ml at 25 mM TA buffer (pH 7.8) with 150 mM NaCl when setting incubation time at 6 h, and HLC recovery is about 96%. Under this experimental condition, it is proved to exhibit high efficiencies of both endotoxin removal and collagen recovery. The structure of treated HLC was explored by Transmission Electron Microscopy (TEM), demonstrating that the property and structure of HLC treated by TA buffer are maintained. Compared to the most widely used endotoxin removal method, Triton X-114 extraction, using TA buffer can obtain the non-toxic HLC without extra treatment for removing the toxic substances in Triton X-114. In addition, the present study aims at establishing a foundation for further work in laboratory animal science and providing a foundation for medical grade biomaterials. - Graphical abstract: The processes of endotoxins adsorbed from HLC. - Highlights: • TA buffer is a mild buffer system for endotoxins removal of HLC. • TA buffer may facilitate endotoxins adsorbed on the

A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.

Science.gov (United States)

Spandorfer, Philip R; Mace, Sharon E; Okada, Pamela J; Simon, Harold K; Allen, Coburn H; Spiro, David M; Friend, Keith; Harb, George; Lebel, Francois

2012-11-01

Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children. This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration. The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire. 148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration

Identification and purification of human induced pluripotent stem cell-derived atrial-like cardiomyocytes based on sarcolipin expression.

Directory of Open Access Journals (Sweden)

Rebecca Josowitz

Full Text Available The use of human stem cell-derived cardiomyocytes to study atrial biology and disease has been restricted by the lack of a reliable method for stem cell-derived atrial cell labeling and purification. The goal of this study was to generate an atrial-specific reporter construct to identify and purify human stem cell-derived atrial-like cardiomyocytes. We have created a bacterial artificial chromosome (BAC reporter construct in which fluorescence is driven by expression of the atrial-specific gene sarcolipin (SLN. When purified using flow cytometry, cells with high fluorescence specifically express atrial genes and display functional calcium handling and electrophysiological properties consistent with atrial cardiomyocytes. Our data indicate that SLN can be used as a marker to successfully monitor and isolate hiPSC-derived atrial-like cardiomyocytes. These purified cells may find many applications, including in the study of atrial-specific pathologies and chamber-specific lineage development.

Mode of action of dioxin-like versus non-dioxin-like PCBs

Energy Technology Data Exchange (ETDEWEB)

Schoeters, G. [VITO (Flemish Institute for Technological Research), Dept. of Environemental Toxicology (Belgium)]|[Antwerp Univ. (Belgium); Birnbaum, L. [United States Environmental Protection Agency, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory (United States)

2004-09-15

Exposure of humans to polychlorinated biphenyls has been associated with different adverse effects such as immune impairment, changes in hormone levels, reproductive and neuropsychological changes and cancer. It is difficult to attribute the observed effects to either dioxin-like, non-dioxin-like PCBs or to both. All known human exposures are mixed, comprising dioxin and non-dioxin like PCB congeners as well as dioxins and furans. The purpose of this work was to evaluate, based on mechanistic data available in the open literature, whether non-dioxin like PCBs (NDL-PCBs) themselves may pose specific health risks. It is clear that dioxin and NDL-PCBs differ in the spectrum of metabolizing enzymes they induce, but the mechanistic links to health of these biochemical changes remain unclear at the moment. NDL-PCBs also cause immunotoxicity and tumor promotion via different mechanisms than do dioxin-like PCBs. We focus on neurotoxicity which has been associated with developmental exposure to PCBs and which is considered as one of the most sensitive adverse health effects.

Sensibilidade à secagem da matéria-prima cerâmica da Formação Corumbataí na região do Polo Cerâmico de Santa Gertrudes, SP

Directory of Open Access Journals (Sweden)

A. A. Azzi

2015-06-01

Full Text Available As argilas provenientes da Formação Corumbataí são atualmente a principal fonte de matéria-prima para as indústrias do Polo Cerâmico de Santa Gertrudes. 73% das indústrias desse polo que utilizam o processo de secagem via seca são hoje alvo de crescente pressão dos órgãos de controle ambiental devido à emissão de partículas (poeira associado ao processo de secagem da matéria-prima. Neste trabalho, foram realizados quatro diferentes testes de secagem em três tipos de matéria-prima (D, I e M da Formação Corumbataí, com umidades naturais iniciais de 8%, 18% e 19%, respectivamente, para poder avaliar a sensibilidade à secagem. Dentre os testes analisados neste trabalho estão o processo natural de secagem ao sol, secagem ao vento, secagem ao sol combinado a uma corrente de vento, e secagem ao sol com matéria-prima previamente umedecida em água corrente. Os testes foram ainda correlacionados à análise termogravimétrica. A análise por difração de raios X, juntamente com as análises química e petrográfica mostrou que as amostras D, I e M contêm predominantemente filossilicatos 2:1 como illitas (25-30% e esmectitas (15-25%, e em menor quantidade caulinita (0-15% e clorita (0-5%. Os resultados dos experimentos de secagem associados à mineralogia mostram que entre 100 °C e 200 °C nos gráficos de termogravimetria pode indicar de modo rápido a sensibilidade à secagem que o material apresenta, uma vez que a maior perda de umidade obtida nesta faixa indica a maior quantidade de minerais do grupo das esmectitas, que por sua vez conferem ao material menor sensibilidade à secagem. Além disso, os procedimentos de secagem natural sugerem que secar separadamente a matéria-prima pode resultar em maior eficiência do processo de secagem.

Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

Science.gov (United States)

Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

2013-05-01

Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

Science.gov (United States)

Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

International Nuclear Information System (INIS)

Tong, Meng; Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R.

2013-01-01

The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

Energy Technology Data Exchange (ETDEWEB)

Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

2013-04-15

The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

Studi Eksperimental Pengaruh Penambahan Disturbance Body Terhadap Karakteristik Aliran Yang Melintasi Sebuah Silinder Sirkular Yang Tersusun Secara Tandem Dalam Saluran Sempit ”Studi Kasus Untuk Disturbance Body Berulir Dan Polos Dengan Rasio Diameter D

Directory of Open Access Journals (Sweden)

Pratista Hariyanto

2012-09-01

Full Text Available Penelitian ini bertujuan untuk mempelajari aliran yang melintasi silinder sirkular yang tersusun tandem yang ditempatkan pada saluran sempit. Adapun penelitian ini juga berusaha untuk mereduksi gaya hambat yang terjadi dengan menggunakan sebuah disturbance body yang memiliki rasio yang d/D=0.1dengan kondisi permukaan polos dan berulir dengan rasio jarap gap L/D = 2.0. Penelitian ini dilakukan secara eksperimental dengan cara meletakkan silinder sirkular (D= 37.5mm dalam sebuah terowongan udara saluran sempit berpenampang bujur sangkar (h=125mm dengan bilangan Reynolds sebesar 1.16x102 (berdasarkan diameter hidrolis saluran dan kecepatan freestream. Tekanan diukur dengan pressure tap yang terpasang pada permukaan silinder sirkular dan pada test section terowongan angin (inlet dan outlet. Sedangkan profil kecepatan aliran didapatkan dengan menggunakan pitot static tube yang dipasang dibelakang silinder sirkular.

Human immunodeficiency virus-like particles activate multiple types of immune cells

International Nuclear Information System (INIS)

Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

2007-01-01

The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

Induced vibrations facilitate traversal of cluttered obstacles

Science.gov (United States)

Thoms, George; Yu, Siyuan; Kang, Yucheng; Li, Chen

When negotiating cluttered terrains such as grass-like beams, cockroaches and legged robots with rounded body shapes most often rolled their bodies to traverse narrow gaps between beams. Recent locomotion energy landscape modeling suggests that this locomotor pathway overcomes the lowest potential energy barriers. Here, we tested the hypothesis that body vibrations induced by intermittent leg-ground contact facilitate obstacle traversal by allowing exploration of locomotion energy landscape to find this lowest barrier pathway. To mimic a cockroach / legged robot pushing against two adjacent blades of grass, we developed an automated robotic system to move an ellipsoidal body into two adjacent beams, and varied body vibrations by controlling an oscillation actuator. A novel gyroscope mechanism allowed the body to freely rotate in response to interaction with the beams, and an IMU and cameras recorded the motion of the body and beams. We discovered that body vibrations facilitated body rolling, significantly increasing traversal probability and reducing traversal time (P locomotor pathways in complex 3-D terrains.

The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19

Energy Technology Data Exchange (ETDEWEB)

Wasco, W.; Tanzi, R.E. (Harvard Medical School, Boston, MA (United States)); Brook, J.D. (Center for Medical Genetics, Nottingham (United Kingdom))

1993-01-01

We have recently isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid [beta] protein precursor (APP; 16). This 653-amino-acid amyloid precursor-like protein (APLP) is similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are particularly strong in three distinct regions of the proteins where the identities are 47, 54, and 56% (16). All three of these regions are also conserved in the Drosophila APP-like gene, APPL (11). Notably, 12 cysteine residues and a N -glyco-sylation site are conserved in the extracellular portion of APLP and APP, and a clathrin-binding domain is conserved in the cytoplasmic domain. The cytoplasmic domain is also conserved in a partial CDNA reported to encode an APP-like gene in rat testes (17), These data suggest that APLP and APP are members of a highly conserved gene family. A panel of DNAs from 31 human-rodent somatic cell lines of known karyotype was digested with EcoR1. These DNAs were then probed with the human APLP cDNA clone and the hybridization pattern was consistent with the assignment of the APLP locus to chromosome 19. 17 refs., 1 fig.

Corticospinal inhibition of transmission in propriospinal-like neurones during human walking

DEFF Research Database (Denmark)

Iglesias, Caroline; Nielsen, Jens Bo; Marchand-Pauvert, Véronique

2008-01-01

It is crucial for human walking that muscles acting at different joints are optimally coordinated in relation to each other. This is ensured by interaction between spinal neuronal networks, sensory feedback and supraspinal control. Here we investigated the cortical control of spinal excitation from...... ankle dorsiflexor afferents to quadriceps motoneurones mediated by propriospinal-like interneurones. During walking and tonic contraction of ankle dorsiflexors and knee extensors while standing [at matched electromyography (EMG) levels], the effect of common peroneal nerve (CPN) stimulation...... was enhanced during walking, and when CPN stimulation was combined with FN or TMS, the resulting H-reflexes and MEPs were inhibited. The CPQ-reflex was also depressed when CPN stimulation was combined with subthreshold TMS. The peripheral (in CPN and FN) and corticospinal volleys may activate inhibitory non...

Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

Energy Technology Data Exchange (ETDEWEB)

Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

2011-10-28

Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

Parenteral nutrition facilitates activation of coagulation but not of fibrinolysis during human endotoxemia

NARCIS (Netherlands)

van der Poll, T.; Levi, M. [=Marcel M.; Braxton, C. C.; Coyle, S. M.; Roth, M.; ten Cate, J. W.; Lowry, S. F.

1998-01-01

Venous thrombosis and bacterial infections are common complications of parenteral nutrition. To test the hypothesis that infection facilitates activation of coagulation during parenteral nutrition, healthy subjects were intravenously injected with endotoxin (2 ng/kg) after they had received either 1

A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.

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Jean-Philippe Coppé

2010-02-01

Full Text Available Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP, which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen, do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3% oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.

Constructive anthropomorphism: a functional evolutionary approach to the study of human-like cognitive mechanisms in animals.

Science.gov (United States)

Arbilly, Michal; Lotem, Arnon

2017-10-25

Anthropomorphism, the attribution of human cognitive processes and emotional states to animals, is commonly viewed as non-scientific and potentially misleading. This is mainly because apparent similarity to humans can usually be explained by alternative, simpler mechanisms in animals, and because there is no explanatory power in analogies to human phenomena when these phenomena are not well understood. Yet, because it is also difficult to preclude real similarity and continuity in the evolution of humans' and animals' cognitive abilities, it may not be productive to completely ignore our understanding of human behaviour when thinking about animals. Here we propose that in applying a functional approach to the evolution of cognitive mechanisms, human cognition may be used to broaden our theoretical thinking and to generate testable hypotheses. Our goal is not to 'elevate' animals, but rather to find the minimal set of mechanistic principles that may explain 'advanced' cognitive abilities in humans, and consider under what conditions these mechanisms were likely to enhance fitness and to evolve in animals. We illustrate this approach, from relatively simple emotional states, to more advanced mechanisms, involved in planning and decision-making, episodic memory, metacognition, theory of mind, and consciousness. © 2017 The Author(s).

Enabling Facilitation of Mass Customization via Partnering in the Construction Industry

DEFF Research Database (Denmark)

Ditlev Bohnstedt, Kristian

2014-01-01

containing information on the realization processes and the integration of customers likely to answer the question of which procurement or contract form that would best accommodate the facilitation of near-mass customization performance. To test this, a one-way ANOVA comparison was used, and it was found...

Learning facilitating leadership

DEFF Research Database (Denmark)

Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

2016-01-01

This paper explains how engineering students at a Danish university acquired the necessary skills to become emergent facilitators of organisational development. The implications of this approach are discussed and related to relevant viewpoints and findings in the literature. The methodology deplo....... By connecting the literature, the authors’ and engineering students’ reflections on facilitator skills, this paper adds value to existing academic and practical discussions on learning facilitating leadership....

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

Science.gov (United States)

Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

2017-01-01

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

Structure of the thioredoxin-fold domain of human phosducin-like protein 2

International Nuclear Information System (INIS)

Lou, Xiaochu; Bao, Rui; Zhou, Cong-Zhao; Chen, Yuxing

2009-01-01

The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Human phosducin-like protein 2 (hPDCL2) has been identified as belonging to subgroup II of the phosducin (Pdc) family. The members of this family share an N-terminal helix domain and a C-terminal thioredoxin-fold (Trx-fold) domain. The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Comparative structural analysis revealed the structural basis of their putative functional divergence

Stabilization of Transfected Cells Expressing Low-Incidence Blood Group Antigens: Novel Methods Facilitating Their Use as Reagent-Cells.

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Cecilia González

Full Text Available The identification of erythrocyte antibodies in the serum of patients rely on panels of human red blood cells (RBCs, which coexpress many antigens and are not easily available for low-incidence blood group phenotypes. These problems have been addressed by generating cell lines expressing unique blood group antigens, which may be used as an alternative to human RBCs. However, the use of cell lines implies several drawbacks, like the requirement of cell culture facilities and the high cost of cryopreservation. The application of cell stabilization methods could facilitate their use as reagent cells in clinical laboratories.We generated stably-transfected cells expressing low-incidence blood group antigens (Dia and Lua. High-expresser clones were used to assess the effect of TransFix® treatment and lyophilization as cell preservation methods. Cells were kept at 4°C and cell morphology, membrane permeability and antigenic properties were evaluated at several time-points after treatment.TransFix® addition to cell suspensions allows cell stabilization and proper antigen detection for at least 120 days, despite an increase in membrane permeability and a reduction in antigen expression levels. Lyophilized cells showed minor morphological changes and antigen expression levels were rather conserved at days 1, 15 and 120, indicating a high stability of the freeze-dried product. These stabilized cells have been proved to react specifically with human sera containing alloantibodies.Both stabilization methods allow long-term preservation of the transfected cells antigenic properties and may facilitate their distribution and use as reagent-cells expressing low-incidence antigens, overcoming the limited availability of such rare RBCs.

Effect of calcium ions on structure and stability of the C1q-like domain of otolin-1 from human and zebrafish.

Science.gov (United States)

Hołubowicz, Rafał; Wojtas, Magdalena; Taube, Michał; Kozak, Maciej; Ożyhar, Andrzej; Dobryszycki, Piotr

2017-12-01

Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. It provides an organic scaffold for otoliths in fish and otoconia in land vertebrates. In this study, the expression and purification procedure of C1q-like domain of otolin-1 from human and zebrafish was developed. The structure and stability of the proteins were investigated. The results of sedimentation velocity analytical ultracentrifugation and small-angle X-ray scattering indicated that the C1q-like domain of otolin-1 forms stable trimers in solution in the presence of calcium ions. It was also observed that calcium ions influenced the secondary structure of the proteins. C1q-like domains were stabilized by the calcium ions. The human variant was especially affected by the calcium ions. The results indicate the importance of the C1q-like domain for the assembly of the organic matrix of otoliths and otoconia. © 2017 Federation of European Biochemical Societies.

Barriers and facilitators to primary care or human immunodeficiency virus clinics providing methadone or buprenorphine for the management of opioid dependence.

Science.gov (United States)

Turner, Barbara J; Laine, Christine; Lin, Yi-Ting; Lynch, Kevin

Federal initiatives aim to increase office-based treatment of opioid dependence, but, to our knowledge, factors associated with willingness to deliver this care have not been defined. The objective of this study was to describe clinics' willingness to provide methadone hydrochloride or buprenorphine hydrochloride for opioid dependence. The design of the study was a survey conducted in New York State. Two hundred sixty-one directors of primary care and/or human immunodeficiency virus specialty clinics (response rate, 61.1%) that serve Medicaid enrollees were questioned. Outcomes were willingness to provide methadone and buprenorphine. Predictors included clinic characteristics, attitudes about drug users and their treatment, and reported barriers and facilitators to treatment. Clinics were more willing to provide buprenorphine than methadone treatment (59.8% vs 32.6%; P methadone. Willingness was positively associated with continuing medical education credits for training, but negatively associated with greater concern about medication abuse. Immediate telephone access to an addiction expert was associated with willingness to provide buprenorphine (AOR, 2.08; 95% CI, 1.15-3.76). Greater willingness to provide methadone was associated with a belief that methadone-treated patients should be seen along with other patients (AOR, 6.20; 95% CI, 1.78-21.64), methadone program affiliation (AOR, 4.76; 95% CI, 1.64-13.82), and having more patients with chronic pain in the clinic (AOR, 2.80; 95% CI, 1.44-5.44). These clinics serving Medicaid enrollees were more receptive to buprenorphine than methadone treatment. Willingness to provide this care was greater in clinics offering human immunodeficiency virus services, treating more chronic pain, or affiliated with methadone programs. Accessible addiction experts and continuing medical education for training may facilitate adoption of this care.

Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium

DEFF Research Database (Denmark)

Pedersen, G; Andresen, Lars; Matthiessen, M W

2005-01-01

Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colo...... in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway....

Group Ia afferents likely contribute to short-latency interlimb reflexes in the human biceps femoris muscle

DEFF Research Database (Denmark)

Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

2017-01-01

amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion: Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...... neurons in humans, with primary contributions from group Ia muscle spindle afferents....

Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry.

Science.gov (United States)

Bienkowska-Haba, Malgorzata; Williams, Carlyn; Kim, Seong Man; Garcea, Robert L; Sapp, Martin

2012-09-01

Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.

Interdependency and phosphorylation of KIF4 and condensin I are essential for organization of chromosome scaffold.

Directory of Open Access Journals (Sweden)

Rawin Poonperm

Full Text Available Kinesin family member 4 (KIF4 and condensins I and II are essential chromosomal proteins for chromosome organization by locating primarily to the chromosome scaffold. However, the mechanism of how KIF4 and condensins localize to the chromosome scaffold is poorly understood. Here, we demonstrate a close relationship between the chromosome localization of KIF4 and condensin I, but not condensin II, and show that KIF4 and condensin I assist each other for stable scaffold formation by forming a stable complex. Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo-like kinase 1 (Plk1 is important for KIF4 and condensin I localization to the chromosome. Aurora B activity facilitates the targeting of KIF4 and condensin I to the chromosome, whereas Plk1 activity promotes the dissociation of these proteins from the chromosome. Thus, the interdependency between KIF4 and condensin I, and their phosphorylation states play important roles in chromosome scaffold organization during mitosis.

Interdependency and phosphorylation of KIF4 and condensin I are essential for organization of chromosome scaffold.

Science.gov (United States)

Poonperm, Rawin; Takata, Hideaki; Uchiyama, Susumu; Fukui, Kiichi

2017-01-01

Kinesin family member 4 (KIF4) and condensins I and II are essential chromosomal proteins for chromosome organization by locating primarily to the chromosome scaffold. However, the mechanism of how KIF4 and condensins localize to the chromosome scaffold is poorly understood. Here, we demonstrate a close relationship between the chromosome localization of KIF4 and condensin I, but not condensin II, and show that KIF4 and condensin I assist each other for stable scaffold formation by forming a stable complex. Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo-like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome. Aurora B activity facilitates the targeting of KIF4 and condensin I to the chromosome, whereas Plk1 activity promotes the dissociation of these proteins from the chromosome. Thus, the interdependency between KIF4 and condensin I, and their phosphorylation states play important roles in chromosome scaffold organization during mitosis.

Characteristics and critical success factors for implementing problem-based learning in a human resource-constrained country.

Science.gov (United States)

Giva, Karen R N; Duma, Sinegugu E

2015-08-31

Problem-based learning (PBL) was introduced in Malawi in 2002 in order to improve the nursing education system and respond to the acute nursing human resources shortage. However, its implementation has been very slow throughout the country. The objectives of the study were to explore and describe the goals that were identified by the college to facilitate the implementation of PBL, the resources of the organisation that facilitated the implementation of PBL, the factors related to sources of students that facilitated the implementation of PBL, and the influence of the external system of the organisation on facilitating the implementation of PBL, and to identify critical success factors that could guide the implementation of PBL in nursing education in Malawi. This is an ethnographic, exploratory and descriptive qualitative case study. Purposive sampling was employed to select the nursing college, participants and documents for review.Three data collection methods, including semi-structured interviews, participant observation and document reviews, were used to collect data. The four steps of thematic analysis were used to analyse data from all three sources. Four themes and related subthemes emerged from the triangulated data sources. The first three themes and their subthemes are related to the characteristics related to successful implementation of PBL in a human resource-constrained nursing college, whilst the last theme is related to critical success factors that contribute to successful implementation of PBL in a human resource-constrained country like Malawi. This article shows that implementation of PBL is possible in a human resource-constrained country if there is political commitment and support.

Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax®23 are serotype specific and facilitate opsonophagocytosis.

Science.gov (United States)

Smith, Kenneth; Muther, Jennifer J; Duke, Angie L; McKee, Emily; Zheng, Nai-Ying; Wilson, Patrick C; James, Judith A

2013-05-01

B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23. Copyright © 2012 Elsevier GmbH. All rights reserved.

Facilitating practical knowledge by using ECT

Directory of Open Access Journals (Sweden)

Rita Jentoft

2009-11-01

Full Text Available Practical skills constitute essential knowledge in occupational therapy. The knowledge is situation- and experience-based, generated from within the situation. In a particular program for educating Palestinian Occupational Therapists in Gaza, facilitating such knowledge proved to be difficult. Due to travel restrictions and an unstable political situation, teachers and students were separated. Educational communication technology (ECT like videoconferences, internet and videos became new and necessary tools. This article is based on results from an action research project which followed the process of using flexible forms of learning and developing an internet based learning programme named Ergonet. The learning process of the students using it was examined with the aim of answering the following research question: How can flexible forms of learning be developed and used to facilitate practical knowledge in Occupational Therapy education? The development and implementation of Ergonet as a supporting device in students’ learning of practical skills is described through the experience of the teachers involved. The results indicate how rote-learning and lack of reflective and critical thinking, firmly established among Palestinian students, have been challenged and changed by the didactic use of Ergonet.

Expression and characterization of human group C rotavirus virus-like particles in insect cells

International Nuclear Information System (INIS)

Clark, Kristina B.; Lin, S.-C.; Humphrey, Charles; Foytich, Kimberly; Esona, Mathew; Wang Yuhuan; Liu, Merry; Jiang Baoming

2009-01-01

Group C rotavirus (GpC RV) is a causative agent of acute gastroenteritis in children and adults. We expressed the three major capsid proteins VP2, VP6 and VP7 of human GpC RV in baculovirus and demonstrated the self-assembly of VP2/6/7 or VP6/7 virus-like particles (VLPs) in insect cells. We examined a number of parameters, including the kinetics of protein synthesis in different cell lines and media, to optimize the most favorable conditions for the synthesis of recombinant viral proteins and the production of VLPs in Sf9 cells. Hyperimmune serum to VP2/6/7 and VP6/7 VLPs recognized individual recombinant proteins of human GpC RV by Western blot analysis. This serum also showed specific reactivities with the corresponding GpC VLPs but not GpA RV by using immune electron microscopy (IEM) and enzyme immunoassay (EIA). The ability to produce an unlimited amount of GpC RV antigen and the availability of high quality antibody will allow us to develop sensitive and specific diagnostic assays to better determine the epidemiology and disease burden of GpC RV in humans.

Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes.

Directory of Open Access Journals (Sweden)

Kuo Ching Chao

Full Text Available BACKGROUND: There is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs, which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets. METHODOLOGY AND PRINCIPAL FINDINGS: HUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic beta-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2 in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin

Facilitating Shared Understandings of Risk

DEFF Research Database (Denmark)

Mitchell, Robb

This thesis contributes an identification of a key mechanism and its constituent qualities, for facilitating shared understandings of risk. Globalisation and the pace of technological change increases the uncertainties of decision making within many design and innovation practices. Accordingly......, the focus of participatory workshops has expanded towards addressing broader questions of strategy, business models and other organizational and inter-organisational issues. To develop effective partnerships across the boundaries separating companies, I argue that is necessary for those involved to gain...... or proxy for absent others, 4) an incomplete comic with which children could contribute sketched ideas to a design process 5) a table top tool kits for discussing business relationship issues and 5) a number of bespoke interactive sculpture-like artifacts for provoking insights concerning business dilemmas...

Social Bots: Human-Like by Means of Human Control?

Science.gov (United States)

Grimme, Christian; Preuss, Mike; Adam, Lena; Trautmann, Heike

2017-12-01

Social bots are currently regarded an influential but also somewhat mysterious factor in public discourse and opinion making. They are considered to be capable of massively distributing propaganda in social and online media, and their application is even suspected to be partly responsible for recent election results. Astonishingly, the term social bot is not well defined and different scientific disciplines use divergent definitions. This work starts with a balanced definition attempt, before providing an overview of how social bots actually work (taking the example of Twitter) and what their current technical limitations are. Despite recent research progress in Deep Learning and Big Data, there are many activities bots cannot handle well. We then discuss how bot capabilities can be extended and controlled by integrating humans into the process and reason that this is currently the most promising way to realize meaningful interactions with other humans. This finally leads to the conclusion that hybridization is a challenge for current detection mechanisms and has to be handled with more sophisticated approaches to identify political propaganda distributed with social bots.

A Spatial Cognitive Map and a Human-Like Memory Model Dedicated to Pedestrian Navigation in Virtual Urban Environments

Science.gov (United States)

Thomas, Romain; Donikian, Stéphane

Many articles dealing with agent navigation in an urban environment involve the use of various heuristics. Among them, one is prevalent: the search of the shortest path between two points. This strategy impairs the realism of the resulting behaviour. Indeed, psychological studies state that such a navigation behaviour is conditioned by the knowledge the subject has of its environment. Furthermore, the path a city dweller can follow may be influenced by many factors like his daily habits, or the path simplicity in term of minimum of direction changes. It appeared interesting to us to investigate how to mimic human navigation behavior with an autonomous agent. The solution we propose relies on an architecture based on a generic model of informed environment, a spatial cognitive map model merged with a human-like memory model, representing the agent's temporal knowledge of the environment, it gained along its experiences of navigation.

What makes a successful species? Traits facilitating survival in altered tropical forests.

Science.gov (United States)

Hirschfeld, Mareike; Rödel, Mark-Oliver

2017-06-28

Ongoing conversion, disturbance and fragmentation of tropical forests stress this ecosystem and cause the decline or disappearance of many species. Particular traits have been identified which indicate an increasing extinction risk of a species, but traits facilitating survival in altered habitats have mostly been neglected. Here we search for traits that make a species tolerant to disturbances, thus independent of pristine forests. We identify the fauna that have an increasing effect on the ecosystem and its functioning in our human-dominated landscapes. We use a unique set of published data on the occurrences of 243 frog species in pristine and altered forests throughout the tropics. We established a forest dependency index with four levels, based on these occurrence data and applied Random Forest classification and binomial Generalized Linear Models to test whether species life history traits, ecological traits or range size influence the likelihood of a species to persist in disturbed habitats. Our results revealed that indirect developing species exhibiting a large range size and wide elevational distribution, being independent of streams, and inhabiting the leaf litter, cope best with modifications of their natural habitats. The traits identified in our study will likely persist in altered tropical forest systems and are comparable to those generally recognized for a low species extinction risk. Hence our findings will help to predict future frog communities in our human-dominated world.

Pals in power armor: attribution of human-like emotions to video game characters in an ingroup/outgroup situation.

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Besmann, Anna; Rios, Kimberly

2012-08-01

Previous research has demonstrated the tendency for humans to anthropomorphize computers-that is, to react to computers as social actors, despite knowing that the computers are mere machines. In the present research, we examined the attribution of both primary (non-uniquely human) and secondary (human-like) emotions to ingroup (teammate) and outgroup (opponent) computer-controlled characters in a video game. We found that participants perceived the teammate character as experiencing more secondary emotions than the opponent character, but that they perceived the teammate and opponent character as experiencing equal levels of primary emotions. Thus, participants anthropomorphized the ingroup character to a greater extent than the outgroup character. These results imply that computers' "emotions" are treated with a similar ingroup/outgroup social regard as the emotions of actual humans.

Genome editing: a robust technology for human stem cells.

Science.gov (United States)

Chandrasekaran, Arun Pandian; Song, Minjung; Ramakrishna, Suresh

2017-09-01

Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human disease models. Zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system are powerful tools for editing DNA at specific loci. Here, we discuss recent technological advances in genome editing with site-specific nucleases in human stem cells.

Facilitating Group Decision-Making: Facilitator's Subjective Theories on Group Coordination

Directory of Open Access Journals (Sweden)

Michaela Kolbe

2008-10-01

Full Text Available A key feature of group facilitation is motivating and coordinating people to perform their joint work. This paper focuses on group coordination which is a prerequisite to group effectiveness, especially in complex tasks. Decision-making in groups is a complex task that consequently needs to be coordinated by explicit rather than implicit coordination mechanisms. Based on the embedded definition that explicit coordination does not just happen but is purposely executed by individuals, we argue that individual coordination intentions and mechanisms should be taken into account. Thus far, the subjective perspective of coordination has been neglected in coordination theory, which is understandable given the difficulties in defining and measuring subjective aspects of group facilitation. We therefore conducted focused interviews with eight experts who either worked as senior managers or as experienced group facilitators and analysed their approaches to group coordination using methods of content analysis. Results show that these experts possess sophisticated mental representations of their coordination behaviour. These subjective coordination theories can be organised in terms of coordination schemes in which coordination-releasing situations are facilitated by special coordination mechanisms that, in turn, lead to the perception of specific consequences. We discuss the importance of these subjective coordination theories for effectively facilitating group decision-making and minimising process losses. URN: urn:nbn:de:0114-fqs0901287

Activation of Phosphatidylinositol-Linked Dopamine Receptors Induces a Facilitation of Glutamate-Mediated Synaptic Transmission in the Lateral Entorhinal Cortex.

Directory of Open Access Journals (Sweden)

Iulia Glovaci

Full Text Available The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores. Whole-cell patch-clamp recordings of glutamate-mediated evoked excitatory postsynaptic currents were obtained from pyramidal and fan cells. Activation of D1-like receptors using SKF38393, SKF83959, or 1 µM dopamine induced a reversible facilitation of EPSCs which was abolished by loading cells with either the phospholipase C inhibitor U-73122 or the Ca2+ chelator BAPTA. Neither the L-type voltage-gated Ca2+ channel blocker nifedipine, nor the L/N-type channel blocker cilnidipine, blocked the facilitation of synaptic currents. However, the facilitation was blocked by blocking Ca2+ release from internal stores via inositol 1,4,5-trisphosphate (InsP3 receptors or ryanodine receptors. Follow-up studies demonstrated that inhibiting CaMKII activity with KN-93 failed to block the facilitation, but that application of the protein kinase C inhibitor PKC(19-36 completely blocked the dopamine-induced facilitation. Overall, in addition to our previous report indicating a role for the cAMP-PKA pathway in dopamine-induced facilitation of synaptic transmission, we demonstrate here that the dopaminergic facilitation of synaptic responses in layer II entorhinal neurons also relies on a signaling cascade dependent on PI-linked D1 receptors, PLC, release of Ca2+ from internal stores, and PKC activation which is

I Reach Faster When I See You Look: Gaze Effects in Human-Human and Human-Robot Face-to-Face Cooperation.

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Boucher, Jean-David; Pattacini, Ugo; Lelong, Amelie; Bailly, Gerrard; Elisei, Frederic; Fagel, Sascha; Dominey, Peter Ford; Ventre-Dominey, Jocelyne

2012-01-01

Human-human interaction in natural environments relies on a variety of perceptual cues. Humanoid robots are becoming increasingly refined in their sensorimotor capabilities, and thus should now be able to manipulate and exploit these social cues in cooperation with their human partners. Previous studies have demonstrated that people follow human and robot gaze, and that it can help them to cope with spatially ambiguous language. Our goal is to extend these findings into the domain of action, to determine how human and robot gaze can influence the speed and accuracy of human action. We report on results from a human-human cooperation experiment demonstrating that an agent's vision of her/his partner's gaze can significantly improve that agent's performance in a cooperative task. We then implement a heuristic capability to generate such gaze cues by a humanoid robot that engages in the same cooperative interaction. The subsequent human-robot experiments demonstrate that a human agent can indeed exploit the predictive gaze of their robot partner in a cooperative task. This allows us to render the humanoid robot more human-like in its ability to communicate with humans. The long term objectives of the work are thus to identify social cooperation cues, and to validate their pertinence through implementation in a cooperative robot. The current research provides the robot with the capability to produce appropriate speech and gaze cues in the context of human-robot cooperation tasks. Gaze is manipulated in three conditions: Full gaze (coordinated eye and head), eyes hidden with sunglasses, and head fixed. We demonstrate the pertinence of these cues in terms of statistical measures of action times for humans in the context of a cooperative task, as gaze significantly facilitates cooperation as measured by human response times.

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

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Martínez, Isidoro; Oliveros, Juan C.; Cuesta, Isabel; de la Barrera, Jorge; Ausina, Vicente; Casals, Cristina; de Lorenzo, Alba; García, Ernesto; García-Fojeda, Belén; Garmendia, Junkal; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortín, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos-Sevillano, Elisa; Regueiro, Verónica; Rodriguez-Frandsen, Ariel; Solís, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.

2017-01-01

Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here. PMID:28298903

Proprioceptive neuromuscular facilitation in HTLV-I-associated myelopathy/tropical spastic paraparesis

Directory of Open Access Journals (Sweden)

Vera Lúcia Santos de Britto

2014-01-01

Full Text Available Introduction: Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP can impact the independence and motricity of patients. The aims of this study were to estimate the effects of physiotherapy on the functionality of patients with HAM/TSP during the stable phase of the disease using proprioceptive neuromuscular facilitation (PNF and to compare two methods of treatment delivery. Methods: Fourteen patients with human T cell lymphotropic virus type I (HTLV-I were randomly allocated into two groups. In group I (seven patients, PNF was applied by the therapist, facilitating the functional activities of rolling, sitting and standing, walking and climbing and descending stairs. In group II (seven patients, PNF was self-administered using an elastic tube, and the same activities were facilitated. Experiments were conducted for 1h twice per week for 12 weeks. Low-back pain, a modified Ashworth scale, the functional independence measure (FIM and the timed up and go test (TUG were assessed before and after the interventions. Results: In the within-group evaluation, low-back pain was significantly reduced in both groups, the FIM improved in group II, and the results of the TUG improved in group I. In the inter-group analysis, only the tone was lower in group II than in group I. Conclusions: Both PNF protocols were effective in treating patients with HAM/TSP.

Renal expression of Toll-like receptor 2 and 4 : Dynamics in human allograft injury and comparison to rodents

NARCIS (Netherlands)

Stribos, Elisabeth G. D.; van Werkhoven, Maaike B.; Poppelaars, Felix; van Goor, Harry; Olinga, Peter; van Son, Willem J.; Damman, Jeffrey; Seelen, Marcus

Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated

Renal expression of Toll-like receptor 2 and 4: dynamics in human allograft injury and comparison to rodents

NARCIS (Netherlands)

Stribos, Elisabeth G. D.; van Werkhoven, Maaike B.; Poppelaars, Felix; van Goor, Harry; Olinga, Peter; van Son, Willem J.; Damman, Jeffrey; Seelen, Marc A.

2015-01-01

Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated

Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

DEFF Research Database (Denmark)

Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F

2001-01-01

While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

Determination of the levels of dioxin and dioxin-like compounds in the Australian population by analysis of pooled human breast milk

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Harden, F.; Mueller, J.F.; Toms, L.M.L.; Moore, M. [National Research Centre for Environmental Toxicology, The Univ. of Queensland, Brisbane (Australia); Burniston, D.; Symons, R. [AGAL, Sydney (Australia); Ahokas, J. [RMIT, Melbourne (Australia); Fuerst, P. [State Lab. of NRW, Muenster (Germany); Paepke, O. [ERGO Forschungsgesellschaft, Hamburg (Germany)

2004-09-15

Dioxin-like compounds are ubiquitously distributed and humans are exposed to them via various sources but primarily through food. They can be detected in air, water, soil, sediment and biota. These compounds are lipid soluble, poorly eliminated and thus can accumulate in human adipose tissue. They can cross the placenta and are also transferred to breast milk during the lactation process. Therefore infants are exposed ante and postnatally. Since PCDD/PCDF concentration in blood and human milk are very similar when concentrations are expressed on a lipid basis, human milk provides a good monitoring tool of exposure for a given population in a given area. Previously the WHO has co-ordinated international studies on dioxin-like compounds in breast milk. These were conducted in 1987/88, 1992/93 and 2001. In summary, these studies demonstrated that levels of dioxins in breast milk are relatively high in industrialised countries when compared to non-industrialised countries that PCDD/PCDFs were higher in human milk from mothers with their first child and that the levels decrease over a given lactation period. The present study aims to examine the levels of these compounds in primiparae women throughout Australia.

Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

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Deacon, Naomi L; McEvoy, R Doug; Stadler, Daniel L; Catcheside, Peter G

2017-09-01

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO 2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO 2 and 3.0 ± 0.2% O 2 ) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO 2 , O 2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea. NEW & NOTEWORTHY Both arousal state and concomitant CO 2 levels are known modulators of the effects of intermittent hypoxia on

Interaction of human osteoblast-like Saos-2 cells with stainless steel coated by silicalite-1 films

Czech Academy of Sciences Publication Activity Database

Jirka, Ivan; Vandrovcová, Marta; Plšek, Jan; Bouša, Milan; Brabec, Libor; Dragounová, Helena; Bačáková, Lucie

2017-01-01

Roč. 76, JUL 2017 (2017), s. 775-781 ISSN 0928-4931 R&D Projects: GA ČR(CZ) GA16-02681S Institutional support: RVO:61388955 ; RVO:67985823 Keywords : silicalite-1 film * biocompatibility * human osteoblast-like Saos-2 cells Subject RIV: CF - Physical ; Theoretical Chemistry; EI - Biotechnology ; Bionics (FGU-C) OBOR OECD: Physical chemistry; Biomaterials (as related to medical implants, devices, sensors) (FGU-C)

Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation.

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Misme-Aucouturier, Barbara; Albassier, Marjorie; Alvarez-Rueda, Nidia; Le Pape, Patrice

2017-01-01

A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at an in vitro cellular scale, Candida and human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32 Candida albicans and non-albicans (C. glabrata, C. tropicalis, C. parapsilosis, C. dubliniensis, C. lusitaniae, C. krusei, and C. kefyr) clinical isolates, we showed that Candida spp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to the Candida species. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response against Candida spp. Higher proportions of neutrophils and elevated CD4 + /CD8 + T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence of Candida could result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4 lo CD8 hi doubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence. Copyright © 2016 Misme-Aucouturier et al.

Containers, facilitators, innovators?

DEFF Research Database (Denmark)

Makkonen, Teemu; Merisalo, Maria; Inkinen, Tommi

2018-01-01

: are they containers, facilitators or innovators? This is investigated here through empirical material derived from 27 interviews with top departmental management in three Finnish cities (Helsinki, Espoo and Vantaa). The results show that local city governments (LCGs) consider cities as facilitators of innovation...

CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases.

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Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

2011-12-01

CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

Shoes alter the spring-like function of the human foot during running

Science.gov (United States)

Kelly, Luke A.; Lichtwark, Glen A.; Farris, Dominic J.; Cresswell, Andrew

2016-01-01

The capacity to store and return energy in legs and feet that behave like springs is crucial to human running economy. Recent comparisons of shod and barefoot running have led to suggestions that modern running shoes may actually impede leg and foot-spring function by reducing the contributions from the leg and foot musculature. Here we examined the effect of running shoes on foot longitudinal arch (LA) motion and activation of the intrinsic foot muscles. Participants ran on a force-instrumented treadmill with and without running shoes. We recorded foot kinematics and muscle activation of the intrinsic foot muscles using intramuscular electromyography. In contrast to previous assertions, we observed an increase in both the peak (flexor digitorum brevis +60%) and total stance muscle activation (flexor digitorum brevis +70% and abductor hallucis +53%) of the intrinsic foot muscles when running with shoes. Increased intrinsic muscle activation corresponded with a reduction in LA compression (−25%). We confirm that running shoes do indeed influence the mechanical function of the foot. However, our findings suggest that these mechanical adjustments are likely to have occurred as a result of increased neuromuscular output, rather than impaired control as previously speculated. We propose a theoretical model for foot–shoe interaction to explain these novel findings. PMID:27307512

Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

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Elçin, Ayşe Eser; Parmaksiz, Mahmut; Dogan, Arin; Seker, Sukran; Durkut, Serap; Dalva, Klara; Elçin, Yaşar Murat, E-mail: elcinmurat@gmail.com

2017-03-15

Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety of inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and interpretation

HOLA: Human-like Orthogonal Network Layout.

Science.gov (United States)

Kieffer, Steve; Dwyer, Tim; Marriott, Kim; Wybrow, Michael

2016-01-01

Over the last 50 years a wide variety of automatic network layout algorithms have been developed. Some are fast heuristic techniques suitable for networks with hundreds of thousands of nodes while others are multi-stage frameworks for higher-quality layout of smaller networks. However, despite decades of research currently no algorithm produces layout of comparable quality to that of a human. We give a new "human-centred" methodology for automatic network layout algorithm design that is intended to overcome this deficiency. User studies are first used to identify the aesthetic criteria algorithms should encode, then an algorithm is developed that is informed by these criteria and finally, a follow-up study evaluates the algorithm output. We have used this new methodology to develop an automatic orthogonal network layout method, HOLA, that achieves measurably better (by user study) layout than the best available orthogonal layout algorithm and which produces layouts of comparable quality to those produced by hand.

Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms

International Nuclear Information System (INIS)

Haselbacher, G.K.; Schwab, M.E.; Pasi, A.; Humbel, R.E.

1985-01-01

Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain

From Annotated Multimodal Corpora to Simulated Human-Like Behaviors

DEFF Research Database (Denmark)

Rehm, Matthias; André, Elisabeth

2008-01-01

Multimodal corpora prove useful at different stages of the development process of embodied conversational agents. Insights into human-human communicative behaviors can be drawn from such corpora. Rules for planning and generating such behavior in agents can be derived from this information....... And even the evaluation of human-agent interactions can rely on corpus data from human-human communication. In this paper, we exemplify how corpora can be exploited at the different development steps, starting with the question of how corpora are annotated and on what level of granularity. The corpus data...

Robot Faces that Follow Gaze Facilitate Attentional Engagement and Increase Their Likeability.

Science.gov (United States)

Willemse, Cesco; Marchesi, Serena; Wykowska, Agnieszka

2018-01-01

Gaze behavior of humanoid robots is an efficient mechanism for cueing our spatial orienting, but less is known about the cognitive-affective consequences of robots responding to human directional cues. Here, we examined how the extent to which a humanoid robot (iCub) avatar directed its gaze to the same objects as our participants affected engagement with the robot, subsequent gaze-cueing, and subjective ratings of the robot's characteristic traits. In a gaze-contingent eyetracking task, participants were asked to indicate a preference for one of two objects with their gaze while an iCub avatar was presented between the object photographs. In one condition, the iCub then shifted its gaze toward the object chosen by a participant in 80% of the trials (joint condition) and in the other condition it looked at the opposite object 80% of the time (disjoint condition). Based on the literature in human-human social cognition, we took the speed with which the participants looked back at the robot as a measure of facilitated reorienting and robot-preference, and found these return saccade onset times to be quicker in the joint condition than in the disjoint condition. As indicated by results from a subsequent gaze-cueing tasks, the gaze-following behavior of the robot had little effect on how our participants responded to gaze cues. Nevertheless, subjective reports suggested that our participants preferred the iCub following participants' gaze to the one with a disjoint attention behavior, rated it as more human-like and as more likeable. Taken together, our findings show a preference for robots who follow our gaze. Importantly, such subtle differences in gaze behavior are sufficient to influence our perception of humanoid agents, which clearly provides hints about the design of behavioral characteristics of humanoid robots in more naturalistic settings.

An exploration of person-centred concepts in human services: A thematic analysis of the literature.

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Waters, Rebecca A; Buchanan, Angus

2017-10-01

Being 'person-centred' in the delivery of health and human services has become synonymous with quality care, and it is a core feature of policy reform in Australia and other Western countries. This research aimed to identify the uses, definitions and characteristics of the term 'person-centred' in the ageing, mental health and disability literature. A thematic analysis identified seven common core themes of person-centredness: honouring the person, being in relationship, facilitating participation and engagement, social inclusion/citizenship, experiencing compassionate love, being strengths/capacity focussed, and organisational characteristics. These suggest a set of higher-order experiences for people that are translated differently in different human services. There is no common definition of what it means to be person-centred, despite being a core feature of contemporary health and human service policy, and this suggests that its inclusion facilitates further misunderstanding and misinterpretation. A common understanding and policy conceptualisation of person-centredness is likely to support quality outcomes in service delivery especially where organisations work across human service groups. Further research into the application and service expressions of being 'person-centred' in context is necessary. Copyright © 2017 Elsevier B.V. All rights reserved.

Connecting today's climates to future climate analogs to facilitate movement of species under climate change.

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Littlefield, Caitlin E; McRae, Brad H; Michalak, Julia L; Lawler, Joshua J; Carroll, Carlos

2017-12-01

Increasing connectivity is an important strategy for facilitating species range shifts and maintaining biodiversity in the face of climate change. To date, however, few researchers have included future climate projections in efforts to prioritize areas for increasing connectivity. We identified key areas likely to facilitate climate-induced species' movement across western North America. Using historical climate data sets and future climate projections, we mapped potential species' movement routes that link current climate conditions to analogous climate conditions in the future (i.e., future climate analogs) with a novel moving-window analysis based on electrical circuit theory. In addition to tracing shifting climates, the approach accounted for landscape permeability and empirically derived species' dispersal capabilities. We compared connectivity maps generated with our climate-change-informed approach with maps of connectivity based solely on the degree of human modification of the landscape. Including future climate projections in connectivity models substantially shifted and constrained priority areas for movement to a smaller proportion of the landscape than when climate projections were not considered. Potential movement, measured as current flow, decreased in all ecoregions when climate projections were included, particularly when dispersal was limited, which made climate analogs inaccessible. Many areas emerged as important for connectivity only when climate change was modeled in 2 time steps rather than in a single time step. Our results illustrate that movement routes needed to track changing climatic conditions may differ from those that connect present-day landscapes. Incorporating future climate projections into connectivity modeling is an important step toward facilitating successful species movement and population persistence in a changing climate. © 2017 Society for Conservation Biology.

Novos lugares para aprender: o google nos polos de apoio presencial do sistema Universidade Aberta do Brasil

Directory of Open Access Journals (Sweden)

Dilce Eclai de Vargas Gil Vicente

2016-06-01

Full Text Available Este artigo apresenta a experiência do Polo Universitário Santo Antônio na formação continuada de professores e acadêmicos, que se apropriaram dos aplicativos Google para inovação e inclusão das tecnologias digitais na educação presencial e a distância. Esta ação se justifica para atender as demandas da sociedade, onde as informações, a cada dia, estão mais presentes nas nuvens. As demandas por espaços de aprendizagem, que ultrapassem as paredes da escola e que possibilitem aprender de forma colaborativa, são urgentes. A formação Google para Educação aconteceu no ano de 2015, sendo utilizada a metodologia da pesquisa-ação, que possibilitou contato com os cursistas durante quatro meses, com atividades planejadas e executadas semanalmente. Foram utilizados Moran (2015 e Behar (2013, entre outros, como preceito teórico. Encontramos resultados positivos evidenciados em vários aspectos. Primeiro pela criação de contas institucionais; segundo pelos depoimentos dos cursistas publicados na internet, indicando que a grande maioria dos participantes do curso qualificou sua prática docente, pois passou a utilizar os aplicativos do Google na sala de aula. Outro resultado positivo ficou evidenciado no acompanhamento de escola, em que todo o corpo docente realizou a formação sobre os aplicativos Google e, atualmente, adota o Classroom como ambiente de aprendizagem com os estudantes e também como instrumento de gestão, por meio de diferentes registros que mantém o grupo informado. Outra evidência de resultado positivo foi o número de concluintes do curso, em 2015, onde 90 cursistas completaram o curso e socializaram seu Classroom no Seminário de encerramento do curso. Os resultados positivos inspiraram outros professores, pois, em 2016, 80 novos cursistas iniciaram outra edição do curso.

Facilitating complex shape drawing in Williams syndrome and typical development.

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Hudson, Kerry D; Farran, Emily K

2013-07-01

Individuals with Williams syndrome (WS) produce drawings that are disorganised, likely due to an inability to replicate numerous spatial relations between parts. This study attempted to circumvent these drawing deficits in WS when copying complex combinations of one, two and three shapes. Drawing decisions were reduced by introducing a number of facilitators, for example, by using distinct colours and including facilitatory cues on the response sheet. Overall, facilitation improved drawing in the WS group to a comparable level of accuracy as typically developing participants (matched for non-verbal ability). Drawing accuracy was greatest in both groups when planning demands (e.g. starting location, line lengths and changes in direction) were reduced by use of coloured figures and providing easily distinguished and clearly grouped facilitatory cues to form each shape. This study provides the first encouraging evidence to suggest that drawing of complex shapes in WS can be facilitated; individuals with WS might be receptive to remediation programmes for drawing and handwriting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diversity of the tetracycline resistance gene tet(M) and identification of Tn916- and Tn5801-like (Tn6014) transposons in Staphylococcus aureus from humans and animals

DEFF Research Database (Denmark)

de Vries, Lisbeth Elvira; Christensen, H.; Skov, R. L.

2009-01-01

To analyse the sequence diversity of the tetracycline resistance gene tet(M) in Staphylococcus aureus from humans and animals and to determine mobile elements associated with tet(M) in S. aureus. In total, 205 tetracycline-resistant isolates were screened for tet(M) by PCR. tet(M) genes were...... sequenced and compared with tet(M) deposited in GenBank. Based on phylogenetic analysis isolates were screened for Tn916- and Tn5801-like xis/int genes, and transposons were confirmed by linking PCR. spa typing was performed and selected isolates were used as donors in a filter mating experiment. Forty......-one isolates (21.3%, 60.7%, 2.6% and 4.4% of the human, pig, poultry and cattle isolates, respectively) were tet(M) positive. tet(M) was located on Tn5801-like and Tn916-like transposons in humans and on a specific Tn916-like element in animals. Human isolates were of different spa types (t034, t008, t037, t...

Facilitators and constraints at each stage of the migration decision process.

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Kley, Stefanie

2017-10-01

Behavioural models of migration emphasize the importance of migration decision-making for the explanation of subsequent behaviour. But empirical migration research regularly finds considerable gaps between those who intend to migrate and those who actually realize their intention. This paper applies the Theory of Planned Behaviour, enriched by the Rubicon model, to test specific hypotheses about distinct effects of facilitators and constraints on specific stages of migration decision-making and behaviour. The data come from a tailor-made panel survey based on random samples of people drawn from two German cities in 2006-07. The results show that in conventional models the effects of facilitators and constraints on migration decision-making are likely to be underestimated. Splitting the process of migration decision-making into a pre-decisional and a pre-actional phase helps to avoid bias in the estimated effects of facilitators and constraints on both migration decision-making and migration behaviour.

The first imported human case of Yersinia pseudotuberculosis serotype O1 septicemia presents with acute appendicitis-like syndrome in Taiwan

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Chung-Hsu Lai

2014-09-01

Full Text Available Human nonplague yersiniosis occurs more commonly in temperate regions than in tropical or subtropical regions. In Taiwan, which is located in a subtropical region of Southeast Asia, only environmental isolates and human infection of Yersinia enterocolitica were reported, but a human case of Y. pseudotuberculosis infection had not been identified. We report the first person with Y. pseudotuberculosis serotype O1 septicemia who presented with acute appendicitis-like syndrome and who was probably contracted the infection via ingestion of raw foods in a barbecue restaurant in Japan.

A Review of Domestic Dogs' ("Canis Familiaris") Human-Like Behaviors: Or Why Behavior Analysts Should Stop Worrying and Love Their Dogs

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